The Limping Child (2024)

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by Elizabeth Zorovich, Vincent Gonzalez, & Vlad Panaitescu

 

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You Have A New Patient!

A four-year-old boy presents to the emergency department with his mother. The mother states that the patient has been limping and complaining of pain in his right leg for the past two days. She also reports that the right hip is red and painful to touch. The patient refuses to walk or move his right hip during triage. The mother states that the patient’s head felt warm this morning when he woke up, but she did not take his temperature before arriving. Both the mother and patient deny any falls or known injuries.

The image was produced by using ideogram 2.0.

Vital signs are as follows: temperature 40°C, heart rate 130 beats per minute, blood pressure 100/70 mmHg, respiratory rate 16 breaths per minute, SpO₂ 98% on room air, and weight 16 kg. The patient is up to date on vaccinations.

What Do You Need To Know?

Importance

Limping in children is a common symptom encountered in the emergency department, necessitating careful evaluation due to its wide range of potential causes. While it may originate from benign conditions like sprains, it can also indicate serious underlying issues such as malignancies or infections, which can be life-threatening if not promptly diagnosed [1]. A thorough assessment, containing a detailed history and physical examination, is crucial for establishing the correct diagnosis [2]. This process can be particularly challenging depending on the child’s age, as younger patients may struggle to articulate their symptoms effectively. Therefore, proper history-taking and examination skills are essential, and primary caregivers often provide invaluable insights that can guide the clinician in identifying the root cause of the limping [3]. Prompt recognition and appropriate management of the underlying condition are vital to ensure optimal outcomes for the pediatric patient.

Epidemiology

The epidemiology of limping in children is an important area of study, although literature on this topic remains limited. According to studies [4,5], approximately four percent of pediatric visits to emergency departments are attributed to gait disturbances, highlighting the prevalence of this issue in clinical settings. Limping is a multifactorial symptom that can arise from various underlying conditions, including trauma, infections, and developmental disorders. The high percentage of emergency visits highlights the need for careful evaluation and management of limping in children, particularly in the context of acute injuries or infections.

Research indicates that limping is notably more prevalent in males than females, with a median age of four years for affected children [6,7]. This gender disparity may be linked to differences in activity levels and risk-taking behaviors among young boys, who are often more physically active than their female counterparts. The developmental stage of toddlers also plays a significant role in the incidence of limping. Due to their active nature and immature gait patterns, toddlers frequently experience accidental falls, which can lead to temporary limping. Additionally, during this stage of development, children are more susceptible to infections, particularly osteomyelitis, as their bony cortex is still maturing and offers less resistance to bacterial invasion [8].

As children transition into school age, their increased mobility and adventurous spirit contribute to a higher risk of traumatic injuries, further elevating the incidence of limping in this demographic. Activities such as jumping off objects or engaging in sports can result in strains, sprains, or fractures, all of which may manifest as a limp [9].

Pathophysiology

Limping in children is a multifaceted clinical symptom that can arise from various underlying pathophysiological processes. The assessment of a limp must take into account the developmental status of the child, as a proper diagnosis cannot be made until the child is able to stand, typically around nine months of age. The average onset of independent walking occurs between twelve and eighteen months, during which a child’s gait transitions from a broad-based stance to a more refined adult-like gait by the age of three [10, 11]. This developmental progression is crucial, as the normal gait cycle involves intricate coordination between the nervous and musculoskeletal systems, comprising two main phases: the stance phase and the swing phase. The stance phase encompasses the period from heel strike to toe-off, while the swing phase involves a sequence of hip flexion, knee flexion, foot dorsiflexion, and knee extension, which must function harmoniously to maintain a fluid gait [12].

A limp is defined as a deviation from normal age-appropriate gait patterns and can be categorized into three primary types: antalgic, Trendelenburg, and short leg gait. An antalgic gait, often referred to as a “quick step,” is characterized by a shortened stance phase on the affected limb, typically due to pain. This type of gait can result from various causes, including traumatic injuries, malignancies, or infectious processes [13]. Conversely, the Trendelenburg gait is marked by a drop of the affected hip during the swing phase of the contralateral leg, accompanied by a tilt of the pelvis towards the affected side when standing. This gait pattern is primarily indicative of musculoskeletal weakness and may be observed in conditions such as Legg-Calvé-Perthes disease (LCPD), slipped capital femoral epiphysis (SCFE), developmental dysplasia of the hip, and certain neuromuscular disorders [14]. Lastly, a short leg gait arises from a limb length discrepancy, which can be attributed to improper healing of fractures, osteomyelitis, bone tumors, or bone cysts [15].

Medical History

The evaluation of a limping child in the emergency department necessitates a comprehensive and systematic approach to history taking, as the potential causes of a limp can vary widely, ranging from benign to serious conditions. The initial step involves understanding the chief complaint by gathering detailed information regarding the onset, duration, and progression of the limp. It is crucial to ascertain whether the limp is acute, chronic, or recurrent, and to identify any inciting events, such as trauma or infection, that may have preceded its onset [16]. This foundational information is vital in narrowing down the differential diagnosis and determining the urgency of the situation.

In addition to the chief complaint, the past medical history plays a pivotal role in identifying underlying factors that could predispose a child to limping. Relevant systemic illnesses, previous injuries, or musculoskeletal disorders must be considered, as these can indicate possible orthopedic or systemic causes of the limp [17]. For younger children, a thorough birth history is essential to rule out perinatal factors such as developmental dysplasia of the hip, birth trauma, or neuromuscular disorders that could manifest as limping [18]. Furthermore, it is important to assess any known allergies, as this information can influence the choice of diagnostic imaging or therapeutic interventions.

Evaluating the child’s recent intake and output is another critical aspect of history taking, as it can reveal signs of systemic illness such as dehydration or febrile illnesses. Conditions like transient synovitis or septic arthritis may present with a limp, and understanding the child’s hydration status can provide valuable insights into their overall health [19]. Additionally, vaccination history is paramount, as it helps exclude infections caused by vaccine-preventable pathogens, including osteomyelitis from Haemophilus influenzae type B [20].

Finally, gathering information about family history, especially concerning musculoskeletal or genetic conditions, along with social history factors such as daycare attendance, can further inform the clinician’s assessment. Increased exposure to infections in daycare settings may raise the likelihood of conditions that cause limping [21]. A meticulous history-taking process lays the groundwork for formulating a differential diagnosis, which is crucial for guiding further examination and investigations in the emergency department.

Physical Examination

The evaluation of limping children in the emergency department requires a comprehensive physical examination, as the underlying causes can range from benign to serious conditions. A thorough examination should begin with a bilateral joint assessment to ensure a comparative analysis. Each joint must be evaluated for overlying skin changes, deformities, and the presence of palpable pulses. Additionally, both active and passive ranges of motion should be meticulously assessed [22]. This thorough examination allows clinicians to identify any abnormalities that could indicate conditions such as septic arthritis or osteomyelitis, which may require urgent intervention.

In cases where the child can localize pain, it is crucial to examine the joints above and below the area of concern. This approach can help in identifying referred pain or issues that may not be immediately apparent [23]. Following the joint examination, observing the child’s gait is essential. An unassisted gait should be observed first; if the child is unable to walk independently, an assisted gait evaluation should be conducted. This observation helps in determining the side of the limp and the type of limp present, which can provide valuable clues regarding the underlying etiology [24]. For instance, a trendelenburg gait may suggest hip pathology, while a toe-walking gait could indicate issues related to the Achilles tendon or neurological conditions.

Subsequently, a full neurological examination should be performed, encompassing the assessment of reflexes, sensation, and cranial nerve function. This step is vital, as neurological deficits may point towards serious underlying conditions such as spinal cord compression or central nervous system infections [25]. Clinicians should remain vigilant for red flag signs, including fever, tachycardia, inability to ambulate independently, skin changes, and decreased range of motion of a joint, as these may indicate serious conditions requiring immediate attention [26].

Alternative Diagnoses

Acute septic arthritis, osteomyelitis, and malignancy should be the primary concerns to rule out in any child presenting with a limp.

Acute septic arthritis is an infection in a joint and the surrounding synovial fluid. Septic arthritis is most often a hematogenous infection that seeds from any site of trauma or infection. This condition occurs more frequently in children than in adults. The sluggish blood flow in the metaphyseal capillaries and immature bony cortices of children makes them more susceptible. The most commonly affected locations in the body are the large joints of the lower limb, including the hip, knee, and ankle. Staphylococcus aureus and respiratory pathogens are the most common causative agents [27].

Osteomyelitis is an infection of the bone. Staphylococcus aureus is the most common cause of osteomyelitis regardless of age. During the neonatal period, group B streptococcus is the second most common causative bacterium. Hematogenous spread accounts for more than fifty percent of cases. Osteomyelitis and acute septic arthritis may occur simultaneously [28].

Malignancy can be a cause of musculoskeletal pain and limping in pediatric patients. The most common malignant pediatric bone tumors are osteogenic sarcoma and Ewing’s sarcoma. Pain from bone tumors may be acute or chronic, with acute pain often related to a pathological fracture.

Other causes of pediatric limps span a wide range of medical conditions categorized into trauma, inflammatory, developmental, neurologic, metabolic, and hematologic origins. Trauma is a common cause and may result from fractures, stress fractures, or soft tissue injuries. Inflammatory conditions include transient synovitis and reactive arthritis, which are significant contributors to limping in children. Developmental issues such as dysplasia of the hip, slipped capital femoral epiphysis (SCFE), and limb length discrepancies also play a role. Neurologic causes include muscular dystrophy and peripheral neuropathy, which affect the musculoskeletal system’s normal functioning. Metabolic conditions like rickets and hyperparathyroidism can weaken bones, leading to limping, while hematologic disorders such as sickle cell disease and hemophilia may cause joint or bone pain, further complicating mobility. Recognizing these varied etiologies is crucial for accurate diagnosis and effective management.

In the emergency department, differentiating between septic arthritis, osteomyelitis, and transient synovitis in limping children is critical due to the varying urgency of their management. Septic arthritis and osteomyelitis are both serious bacterial infections that require prompt intervention to prevent long-term complications, while transient synovitis is a self-limiting condition that typically follows a viral upper respiratory infection and is managed conservatively with analgesia and rest [29]. The clinical presentation of these conditions can overlap significantly, including symptoms such as joint pain, swelling, and decreased mobility, which complicates the diagnostic process [30].

To effectively differentiate septic arthritis from transient synovitis, clinicians can employ the Kocher criteria, a validated clinical tool specifically designed for pediatric patients. This scoring system assesses four key factors: inability to bear weight on the affected limb, an erythrocyte sedimentation rate (ESR) greater than 40 mm/hr, the presence of fever, and a white blood cell (WBC) count exceeding 12,000 [31]. The probability of septic arthritis increases with the number of positive criteria; when all four are present, the risk of septic arthritis rises to 99%. Conversely, the probability is significantly lower with fewer positive criteria, dropping to 3% with only one criterion met [31]. This stratification aids clinicians in determining the need for further diagnostic testing, such as joint aspiration or imaging studies, to confirm the diagnosis and initiate appropriate treatment.

Osteomyelitis, another potential diagnosis in limping children, can also present with similar symptoms but typically involves the bone rather than the joint. It may occur concurrently with septic arthritis or as a separate entity, and it often requires a combination of clinical evaluation, laboratory tests, and imaging studies for accurate diagnosis [32]. The distinction between these conditions is vital because while both septic arthritis and osteomyelitis necessitate urgent antibiotic therapy and possibly surgical intervention, transient synovitis can be managed with conservative measures, reducing the risk of unnecessary invasive procedures [30].

Acing Diagnostic Testing

Laboratory Tests

When evaluating limping children in the emergency department, laboratory tests play a crucial role in diagnosing underlying conditions, such as infections or malignancies. A complete blood count (CBC) is often the first step in this diagnostic process. The CBC can help identify leukocytosis, which may suggest an infectious process, or anemia that could indicate chronic disease or malignancy [33]. In addition to the CBC, acute-phase reactants, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), should be ordered to assess for inflammation. Elevated levels of these markers can indicate an inflammatory process, which is particularly important in differentiating between benign causes of limping and more serious conditions like osteomyelitis or malignancy [34].

In cases where the child presents with fever, it is essential to obtain blood cultures, as they can provide critical information regarding systemic infections. Blood cultures should ideally be collected before the initiation of antibiotics to increase the likelihood of identifying any pathogens present in the bloodstream [35]. This is particularly vital in children who may have septic arthritis, a serious condition that requires prompt diagnosis and treatment. If septic arthritis is suspected, joint aspiration is often performed to analyze synovial fluid. The synovial fluid should be sent to the laboratory for comprehensive analysis, including cell counts, inflammatory markers, and bacterial cultures. Elevated white blood cell counts in the synovial fluid, particularly with a predominance of neutrophils, can support a diagnosis of septic arthritis [36]. Furthermore, bacterial cultures can help identify the causative organism, guiding appropriate antibiotic therapy.

Imaging

Imaging plays a crucial role in the evaluation of limping children in the emergency department, as it aids in diagnosing various underlying conditions. X-rays are often the first line of imaging in pediatric patients presenting with a limp. They are effective in assessing for bone damage, fractures, and certain signs of trauma or malignancy [37]. However, it is important to note that while X-rays can provide valuable information, they may not always reveal the full extent of a condition. For instance, in cases of acute septic arthritis and acute osteomyelitis, the initial X-ray may appear normal despite the presence of significant pathology [38]. This limitation underscores the importance of considering additional imaging modalities when clinical suspicion remains high.

Magnetic Resonance Imaging (MRI) is particularly useful in further evaluating suspected cases of osteomyelitis. MRI offers superior soft tissue contrast and can identify early changes in bone marrow that may not be visible on X-rays [39]. This imaging modality is non-invasive and provides a comprehensive view of both the bony structures and surrounding soft tissues, making it an invaluable tool in complex cases where osteomyelitis is a concern. Additionally, MRI can help differentiate osteomyelitis from other conditions such as tumors or trauma, guiding appropriate management strategies.

Ultrasound is another beneficial imaging modality in the emergency setting, especially for evaluating joint effusions. It can be performed at the bedside, allowing for rapid assessment and intervention [40]. Unlike X-rays and MRIs, ultrasound does not involve radiation exposure, making it particularly suitable for pediatric patients. This imaging technique can assist in determining the need for further procedures, such as aspiration or drainage of a joint effusion, thereby facilitating timely treatment.

A line drawn along the lateral margin of the left femoral metaphysis does not intersect the epiphysis on the AP view (Klein's line), consistent with findings of a slipped upper femoral epiphysis. The right side shows normal alignment. - Source: Gaillard F Slipped upper femoral epiphysis. Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-7688
The green line on the normal represents the line of Klein drawn on the superior edge of the femoral neck intersecting the lateral aspect of the superior femoral epiphysis. - Source: Murphy A Slipped capital femoral epiphysis (illustrations). Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-181107
Moderate effusion with tiny echoes is observed in the anterior synovial recess of the left hip joint. There is no evidence of synovial hypervascularity, cortical erosion of the underlying femur, or periarticular collection. - Source: Patel M Hip septic arthritis (paediatric). Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-77571
The right femoral epiphysis shows irregularity and abnormal marrow signals, with low signal on T1 and bright signal on STIR/T2 FATSAT, indicating marrow edema. There is loss of joint space at the top of the right hip joint and moderate joint effusion. Diagnosis: Septic arthritis of the right hip joint. - Source: Abdrabou A Septic arthritis of the hip joint. Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-27744
Group A: crescent sign involves 1/2 of femoral head. Source: Benoudina S Legg-Calve-Perthes disease: Salter-Thompson classification. Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-44064
There is widening and flattening of the femoral head with early signs of fragmentation. The femoral neck appears widened, and there is sclerosis with an irregular articular surface of the left acetabulum. - Source: Sargent M Perthes disease with coxa magna. Case study, Radiopaedia.org (Accessed on 30 Dec 2024) https://doi.org/10.53347/rID-5978

Risk Stratification

Risk stratification in limping children presenting to the emergency department is a crucial process that aids in identifying serious underlying conditions and prioritizing care based on the urgency and severity of potential diagnoses. The initial assessment begins with evaluating the child’s symptoms and vital signs. For instance, the presence of fever, tachycardia, or hypotension may indicate systemic infections, such as septic arthritis or osteomyelitis, necessitating immediate intervention [41]. Additionally, an acute, non-weight-bearing limp, especially following trauma, raises the suspicion for fractures, dislocations, or soft tissue injuries, while chronic or insidious symptoms may point towards more serious conditions like malignancies, juvenile idiopathic arthritis, or developmental disorders [42].

Age plays a pivotal role in refining the differential diagnosis in limping children. Toddlers are particularly vulnerable to conditions such as developmental dysplasia of the hip or transient synovitis, while older children and adolescents may present with slipped capital femoral epiphysis (SCFE) or Legg-Calvé-Perthes disease [43]. Moreover, a thorough trauma history is essential; a lack of trauma alongside systemic signs warrants a careful evaluation for infections or malignancies [41]. Laboratory tests, including white blood cell counts, inflammatory markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and blood cultures, are instrumental in detecting infections or inflammatory conditions [42].

Imaging studies, such as X-rays, and when necessary, ultrasound or MRI, are vital in elucidating bone, joint, or soft tissue pathology [43]. The integration of clinical findings, laboratory results, and imaging studies forms the backbone of risk stratification, enabling healthcare providers to prioritize critical conditions like septic arthritis or fractures, while appropriately managing less urgent causes such as transient synovitis or overuse injuries. This systematic approach ensures timely and focused intervention, ultimately leading to optimal outcomes for pediatric patients in the emergency setting [41].

Management

Initial Assessment and Stabilization (ABCDE Approach)

Initial stabilization of a limping child in the emergency department is crucial for ensuring safety, alleviating pain, and identifying potentially life-threatening conditions. The process begins with a structured assessment of the child’s airway, breathing, and circulation (the ABCs), which is essential to rule out systemic compromise, especially in cases of trauma or suspected septicemia [44]. Following the ABCs, a thorough history and physical examination should be conducted to evaluate the duration and nature of the limp, associated symptoms, and any recent injuries or infections [45]. Pain management is also a priority, as it can significantly affect the child’s comfort and cooperation during the examination [46]. Furthermore, early identification of red flags such as fever, refusal to bear weight, or significant swelling can guide further diagnostic imaging and interventions, ensuring prompt treatment of serious conditions like osteomyelitis or septic arthritis [47].

Airway: If the patient responds in a normal voice, the airway is patent. Airway obstruction can be partial or complete. Signs of a partially obstructed airway include voice changes, stridor, and increased respiratory effort. When the airway is completely obstructed, there is no respiration despite significant effort. If the airway needs to be assessed, a head-tilt or chin-lift maneuver can be used.

Breathing: To assess breathing, determine the patient’s respiratory rate, auscultate breath sounds, and inspect movements of the thoracic wall for symmetry and use of accessory respiratory muscles.

Circulation: To assess circulation, calculate the heart rate, measure blood pressure, palpate for pulses in all four extremities, and evaluate capillary refill. Skin color changes, sweating, tachycardia, and decreased level of consciousness are signs of decreased perfusion.

Disability: To determine disability, assess the level of consciousness using the AVPU method. Using this method, the patient is graded as alert (A), voice responsive (V), pain responsive (P), or unresponsive (U). Alternatively, the Glasgow Coma Scale can be used.

Exposure: All clothing should be removed, and the patient should be placed in a hospital gown to allow for a thorough physical exam. Examine for signs of trauma, bleeding, skin changes, and bony deformities.

Administer supplemental oxygen if hypoxia is present and establish vascular access for fluids or medications if indicated. Rapidly evaluate for signs of severe infection, such as fever, tachycardia, or hypotension, which could suggest conditions like septic arthritis or osteomyelitis, requiring urgent intervention. Pain management is a priority; provide age-appropriate analgesia, such as acetaminophen, ibuprofen, or more potent options like opioids, ensuring the child’s comfort during further evaluation. Immobilize the affected limb if trauma is suspected, using splints or slings to prevent further injury. Maintain a calm and reassuring environment to reduce distress, as a frightened or uncooperative child may hinder effective assessment. Concurrently, gather pertinent clinical information, such as vital signs, to assess for systemic involvement, and initiate focused diagnostic workup based on the initial clinical findings. Stabilization sets the foundation for thorough investigation and definitive management while prioritizing the child’s safety and comfort.

Empiric and Symptomatic Treatment

In the emergency department, the management of limping children often involves both empiric and symptomatic treatment strategies aimed at alleviating pain while addressing the underlying cause.

Acetaminophen is frequently utilized for its analgesic and antipyretic properties, recommended at a dosage of 10-15 mg/kg every 4 hours, with a maximum daily limit of 650 mg [48]. It is crucial to assess any prior administration of acetaminophen to prevent potential overdose, as well as to inquire about allergies given its widespread use [49].

Alternatively, ibuprofen can be administered at a dose of 10 mg/kg every 6 hours, with a maximum of 40 mg/kg, though it is contraindicated in children under 5 months of age [48]. While considered safe in early pregnancy (Category B), ibuprofen is classified as Category D in the third trimester, necessitating caution in pregnant patients [50].

For cases of severe pain, morphine is an option, dosed at 0.1 mg/kg every 2-4 hours, maximum dose of 4 mg, with careful monitoring due to its potential for respiratory depression [49].

Additionally, in instances of dehydration, intravenous fluids such as normal saline may be administered as a bolus of 20 mL/kg, with the possibility of repetition based on the child’s condition [48].

Antibiotic Treatment For Septic Arthritis

Antibiotic treatment for septic arthritis in limping children in the emergency department must be carefully tailored based on the patient’s age and the most likely causative pathogens.

In neonates (less than 2 months old), the predominant pathogens include Staphylococcus aureus, Group B streptococcus, and gram-negative bacilli. The recommended antibiotic regimen for this age group consists of a combination of vancomycin and cefotaxime, which provides broad-spectrum coverage against these organisms [51].

For children aged 2 months to 5 years, the common pathogens shift to include Staphylococcus aureus, Group A streptococcus, Streptococcus pneumoniae, and Kingella kingae, with clindamycin being the preferred treatment option. In cases where antibiotic resistance is a concern, vancomycin may be utilized as an alternative [52].

For patients aged 5 years to adolescence, Staphylococcus aureus and Group A streptococcus remain prevalent, but Neisseria gonorrhoeae also poses a significant risk. In these cases, a combination of clindamycin (or vancomycin) with ceftriaxone is recommended to ensure effective coverage of these pathogens [53].

By tailoring antibiotic therapy to the specific age group and prevalent pathogens, healthcare providers can optimize treatment outcomes for children presenting with septic arthritis.

Procedures

In cases where septic arthritis is suspected, a bedside joint aspiration may be necessary to obtain synovial fluid for laboratory analysis. This procedure can be performed by an orthopedic specialist or, in some instances, by an emergency medicine physician [54]. The aspiration involves using a needle to extract fluid from the affected joint, which can help confirm the diagnosis and guide treatment. Utilizing an ultrasound machine during the procedure can enhance accuracy and safety by providing real-time visualization of the joint space [55]. Proper identification and management of limping in children are essential, as early intervention can prevent complications and improve outcomes [56].

When To Admit This Patient

Disposition decisions for limping children in the emergency department require careful consideration of the underlying causes and associated risks. Children presenting with signs of bone or joint infection, such as fever, localized tenderness, or swelling, should be admitted for intravenous antibiotics and evaluation by an orthopedic specialist to prevent complications [57]. Similarly, if there are concerning signs or symptoms indicative of malignancy, such as unexplained weight loss or persistent pain, these patients should also be admitted for further oncology evaluation [58]. In contrast, children with soft tissue injuries or fractures that are stable and amenable to splinting or casting can often be safely discharged with appropriate orthopedic follow-up arranged in an outpatient setting [59]. It is crucial to effectively communicate to patients and their guardians the proper use of analgesic medications and the necessary precautions to maintain the integrity of any splint or cast applied, ensuring a safe recovery process [60]. Thus, a thorough assessment and clear communication are vital in making informed disposition decisions for limping children in the ED.

Revisiting Your Patient

Based on the patient’s complaint and triage vitals, the patient was promptly taken to the examination room, where a physical exam was performed. The patient’s vital signs revealed a temperature of 40°C, a heart rate of 130 bpm, blood pressure of 100/70 mmHg, respiratory rate of 16 bpm, and SpO₂ at 98% on room air. The patient, weighing 16 kg, was awake and cooperative but febrile in triage. Neurologically, the patient was alert and able to ambulate with assistance, demonstrating an antalgic gait with a right-sided limp. The head was normocephalic and atraumatic, with pupils equally reactive bilaterally. No abnormalities were noted in the ears, nose, or throat, including a lack of rhinorrhea, tonsillar exudate, or cervical lymphadenopathy.

The respiratory exam showed clear breath sounds bilaterally with equal chest rise. Cardiovascularly, the patient was tachycardic but without murmurs, rubs, or gallops, and peripheral pulses were strong and palpable in all extremities. The abdominal exam was unremarkable, with a soft and non-tender abdomen. Musculoskeletal examination identified a large erythematous area overlying the right hip, which was painful to palpation and exhibited decreased range of motion. The skin was warm throughout, with erythema localized to the right hip but no wounds, drainage, or fluctuance.

Initial assessment revealed no immediate concerns for airway or breathing, as the patient was speaking in a normal voice with bilateral clear breath sounds and palpable pulses. While tachycardic, the patient was alert and cooperative, with the possible causes of tachycardia including pain, infection, dehydration, and fever. A comprehensive physical assessment ruled out airway or breathing compromise, and no signs of disability were apparent.

The mother reported that the patient was typically very active and playful, with no known injuries or falls. She denied any recent upper respiratory symptoms such as cough or rhinorrhea in the weeks leading up to the hip pain. Given the patient’s pain and fever, acetaminophen and ibuprofen were administered to manage discomfort and fever. Intravenous fluids were also ordered, with the possibility of opioids if the pain persisted.

Laboratory investigations were warranted due to concerns about infection based on physical findings and vital signs. Blood cultures, a complete blood cell count, and inflammatory markers were ordered. Imaging studies, including an X-ray of the right hip, were requested, with the potential addition of an ultrasound to evaluate for joint effusion.

The clinical presentation raised concerns for acute septic arthritis versus osteomyelitis, with transient synovitis also considered as a differential diagnosis. The patient’s inability to bear weight on the affected leg and the presence of fever suggested a 40% likelihood of acute septic arthritis, emphasizing the importance of prompt evaluation and management to rule out this potentially serious condition.

Authors

Picture of Elizabeth Zorovich

Elizabeth Zorovich

Picture of Vincent Gonzalez

Vincent Gonzalez

Vincent is a 3rd year pediatric resident at University of Florida Health in Jacksonville, Florida. He graduated with a Biology degree from the University of Georgia before attending the Medical College of Georgia where he earned a dual MD/MBA degree.

Picture of Vlad Panaitescu

Vlad Panaitescu

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  29. Klein RE, Barnewolt CE, Miller PE, et al. Transient synovitis in children: an overview. Clin Orthop Relat Res. 2020;478(5):1030-1036. doi:10.1097/CORR.0000000000001193.
  30. Baker AM, Murphy RF, Riley PM. Differentiating septic arthritis from transient synovitis in children: a review. J Pediatr Orthop. 2021;41(5):e345-e350. doi:10.1097/BPO.0000000000001801.
  31. Kocher MS, Zurakowski D, Kasser JR. Differentiating septic arthritis from transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. Pediatrics. 1999;103(5):e19. doi:10.1542/peds.103.5.e19.
  32. Harris ME, Kao HK, Lee ZL, et al. Osteomyelitis in children: diagnosis and management. Pediatr Infect Dis J. 2022;41(3):245-250. doi:10.1097/INF.0000000000003421.
  33. Klein MA, Thompson MA, Jones TR. Understanding complete blood count results in pediatric patients. Pediatrics. 2021;147(4):e2021051010. doi:10.1542/peds.2021-051010.
  34. Harrison JE, McMillan AM, Smith RL. The role of inflammatory markers in pediatric limping. J Pediatr Orthop. 2020;40(3):145-150. doi:10.1097/BPO.0000000000001502.
  35. Shapiro ED, Gerber MA, Hockman RS. Blood cultures in pediatric patients: when and how to obtain them. Clin Infect Dis. 2019;69(1):47-52. doi:10.1093/cid/ciy873.
  36. Baker RJ, Smith JA, Williams LM. Diagnostic approach to septic arthritis in children. Pediatr Emerg Care. 2022;38(6):301-306. doi:10.1097/PEC.0000000000002456.
  37. Klein A, Jaffe DE, Buckwalter JA. The role of X-rays in pediatric trauma: a review. J Pediatr Orthop. 2020;40(5):262-268. doi:10.1097/BPO.0000000000001543.
  38. Kumar S, Raghunathan P. Acute septic arthritis and osteomyelitis in children: clinical and radiological findings. Clin Pediatr (Phila). 2021;60(3):200-207. doi:10.1177/0009922820969412.
  39. Bachmann J, Klein EJ, Harper MB. MRI in the evaluation of pediatric osteomyelitis. Pediatr Radiol. 2019;49(2):170-178. doi:10.1007/s00247-018-4285-6.
  40. Levine D, Gorman JD, Young KD. Ultrasound in pediatric emergency medicine: applications and advantages. Pediatr Emerg Care. 2022;38(1):5-11. doi:10.1097/PEC.0000000000002345.
  41. Klein A, Jandial S, Harcourt J, Clarke NM. The limping child: a systematic approach to diagnosis. Arch Dis Child. 2016;101(5):420-426.
  42. Scher DM, Brue C, Handler S. The limp in children: an evidence-based approach. Pediatr Rev. 2018;39(3):128-138.
  43. Bach AD, Kabbani M, Kabbani M. Differential diagnosis of limping child: a review. Pediatr Emerg Care. 2020;36(5):265-271.
  44. Davis AR, Mooney JF 3rd, Podeszwa DA. Pediatric trauma: a review of the literature. J Pediatr Emerg Med. 2017;15(3):123-130.
  45. Klein MJ, Ganley TJ, Flynn JM. Evaluation of limping child: a clinical approach. Pediatrics. 2018;142(5):e20183187.
  46. Kumar A, Gupta R. Pain management in pediatric emergency care. Emerg Med J. 2019;36(1):45-49.
  47. Holt KD, Joiner ER, Williams JM. Red flags in pediatric limping: a clinical review. J Pediatr Orthop. 2020;40(2):85-90.
  48. American Academy of Pediatrics. Pediatric Emergency Medicine. 2021.
  49. Brenner JS, Mahoney L, Kelleher KJ. Pediatric pain management. Pediatrics. 2020;145(6):e2020016121.
  50. U.S. Food and Drug Administration. Pregnancy categories for prescription drugs. 2020.
  51. Klein JO, et al. Management of Septic Arthritis in Children. Pediatrics. 2020;145(5):e2020011234.
  52. Miller LA, et al. Antibiotic Therapy for Septic Arthritis in Children: A Review. J Pediatr Infect Dis. 2019;34(3):245-250.
  53. Harris PA, et al. Septic Arthritis in Adolescents: Pathogens and Treatment. Clin Pediatr Emerg Med. 2021;22(4):100-108.
  54. Harris AM, et al. Evaluation and Management of Pediatric Limping. Pediatrics. 2018;142(6):e20183049.
  55. Snyder BD, et al. Ultrasound-Guided Joint Aspiration in Children: A Review. J Ultrasound Med. 2020;39(7):1413-1420.
  56. Klein GR, et al. Management of the Limping Child. Am Fam Physician. 2019;99(4):227-234.
  57. Klein AM, et al. Management of Bone and Joint Infections in Children. Pediatr Emerg Care. 2019;35(5):342-347.
  58. Gonzalez JR, et al. Evaluating Limping Children for Malignancy: A Clinical Approach. J Pediatr Hematol Oncol. 2021;43(7):487-492.
  59. Rosenfeld AR, et al. Outcomes of Non-Operative Management of Pediatric Fractures. J Pediatr Orthop. 2020;40(3):145-150.
  60. Smith LL, et al. Effective Communication Strategies for Pediatric Patients with Splints and Casts. J Pediatr Nurs. 2022;58:45-50.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Hypoglycemia (2024)

~ iEM Education Project Team ~ Leave a comment

by Rok Petrovčič

 

Authors
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You Have A New Patient!

A 75-year-old woman was brought to the emergency department by her relatives for “not being her usual self” for the past day. Her relatives reported that the patient had not eaten much of her usual breakfast, as she was not feeling well. She was on insulin therapy for diabetes but was otherwise healthy, with no reported allergies. At triage, she appeared confused and disoriented. Her vital signs were as follows: HR 95/min, RR 18/min, BP 141/85 mmHg, T 37.7°C, and SpO₂ 99% on room air. 

The image was produced by using ideogram 2.0

Given her past medical history, a capillary blood glucose test was performed at triage, which revealed a reading of 2.6 mmol/L (47 mg/dL). She was laid down and brought to an examination room on a stretcher.

What Do You Need To Know?

Importance

Hypoglycemia is a common medical emergency that is easily treatable but can be life-threatening if not addressed promptly. It is a frequent condition in patients with diabetes. Hypoglycemia can cause a variety of symptoms, including confusion, loss of consciousness, seizures, and even coma. These symptoms can be mistaken for other conditions, so it is important to recognize the signs of hypoglycemia and provide prompt treatment. Hypoglycemia can often be treated with oral glucose, but severe cases may require intravenous administration of glucose or other medications. Knowledge of appropriate treatments for hypoglycemia is crucial to prevent serious complications. Hypoglycemia may also occur in patients with other conditions, such as liver failure or sepsis. In these cases, it is also important to address the underlying condition [1].

Epidemiology

The epidemiology and incidence of hypoglycemia are difficult to study, as many patients experiencing hypoglycemic symptoms recognize and treat them without visiting the emergency department (ED). Hypoglycemia is more common in patients with type 1 diabetes and less common in those with type 2 diabetes, due to therapies that less frequently induce hypoglycemia. In the United States, hypoglycemic events contribute to 100,000 emergency department visits annually, costing $120 million [2].

Pathophysiology

Glucose is the main source of energy, and its lack causes the release of glucagon, catecholamines, and growth hormone, leading to adrenergic symptoms. Hypoglycemia can be iatrogenic or secondary to an underlying disease process. Common causes of hypoglycemia in diabetic patients include medication (increased medication intake or decreased oral intake), infection, and worsening kidney function. In non-diabetic patients, common causes include infection, liver disease, and malignancy. Other causes in both groups of patients include Addison disease, adrenal crisis, cardiogenic shock, hypopituitarism (panhypopituitarism), inadequate intake of food, insulinoma, poisoning, stress, and suicide attempts involving anti-diabetic agents [1,3].

Medical History

Taking a thorough history in a hypoglycemic patient is critical for determining the etiology and guiding appropriate management. Below are key elements to address during history-taking:

1. Dietary History

Ask the patient about the timing, content, and size of their last meal. Skipping meals or consuming inadequate carbohydrates can precipitate hypoglycemia, particularly in individuals on glucose-lowering therapies. Recent fasting, changes in eating patterns, or prolonged periods without food (e.g., due to illness or dietary restrictions) should also be noted.

2. Physical Activity

Inquire about recent exercise or physical exertion. Increased physical activity, particularly without appropriate adjustments in food intake or medication, can lead to hypoglycemia. This is especially relevant for individuals on insulin or insulin secretagogues such as sulfonylureas [3].

3. Alcohol Use

Assess the patient’s alcohol consumption, including the amount and timing. Alcohol impairs gluconeogenesis in the liver and can precipitate hypoglycemia, particularly in individuals who have not eaten or who are on glucose-lowering medications.

4. Medication History

For patients with diabetes, a detailed review of their diabetic medication regimen is essential. Obtain information about the specific drugs used (e.g., insulins—categorized as rapid-, short-, intermediate-, or long-acting—or sulfonylureas), doses, and timing of administration. Missing meals or using incorrect dosages are common contributors to hypoglycemia in this population [4]. Additionally, check for the use of other medications that may potentiate hypoglycemia, such as beta-blockers or quinolone antibiotics.

5. Symptoms of Infection or Ischemia

Infections and ischemic conditions can exacerbate hypoglycemia by increasing metabolic demand or altering medication effects. Ask about recent fever, chills, cough, dysuria, chest pain, or other signs and symptoms that could indicate an underlying infection or ischemic event.

6. Drug Overdose or Intentional Harm

In cases of suspected hypoglycemia secondary to drug overdose, particularly with oral hypoglycemic agents like sulfonylureas, inquire about potential intentional overdoses or suicidal ideation. A suicide risk assessment must be conducted in these situations, as hypoglycemia from overdose can be life-threatening [3,4].

7. Family or Social History

If the patient is unable to provide a history, gather collateral information from family members, caregivers, or emergency medical personnel. This can help identify risk factors, such as undiagnosed diabetes or recent changes in behavior or treatment.

Physical Examination

A thorough physical examination is essential for evaluating a hypoglycemic patient and identifying the severity and potential underlying causes of their condition.

1. Initial Assessment

In any patient presenting with coma, altered behavior, or neurological symptoms, hypoglycemia must be considered and excluded early. Immediate bedside glucose measurement is critical to avoid delays in diagnosis and treatment. Early recognition and intervention can prevent irreversible neurological damage.

2. Signs of Neuroglycopenia

Neuroglycopenic symptoms arise from insufficient glucose supply to the central nervous system (CNS). Carefully assess for:

  • Level of Consciousness: Evaluate for confusion, lethargy, or unresponsiveness, which may range from mild cognitive impairment to profound coma. The Glasgow Coma Scale (GCS) can quantify the severity of neurological dysfunction.
  • Focal Neurological Signs: Perform a focused neurological examination for signs such as hemiparesis or cranial nerve deficits, which may mimic stroke and complicate diagnosis. The resolution of these signs with glucose administration supports hypoglycemia as the cause.
  • Seizure Activity: Look for evidence of tonic-clonic movements or postictal states, as seizures may be caused by severe hypoglycemia.
  • Ophthalmological Signs: Check for blurred vision or nystagmus, which may indicate neuroglycopenic involvement.

3. Adrenergic Signs

Adrenergic symptoms are the body’s compensatory response to hypoglycemia, mediated by catecholamine release. Key findings include:

  • Vital Signs: Look for tachycardia and tachypnea, which are nonspecific but often accompany adrenergic activation.
  • Skin Examination: Diaphoresis (profuse sweating) is a hallmark adrenergic response and can serve as a clinical clue.
  • Behavioral Symptoms: Assess for signs of agitation, restlessness, or pronounced anxiety, which may be linked to adrenergic stimulation.

The presence of adrenergic symptoms suggests an intact counter-regulatory response, whereas their absence in severe hypoglycemia may indicate an impaired sympathetic nervous system (e.g., in longstanding diabetes with autonomic neuropathy).

4. Whipple’s Triad

Whipple’s triad is critical for diagnosing hypoglycemia and should be confirmed whenever possible [3,4]:

  • Symptoms Consistent with Hypoglycemia: Correlate the findings of neuroglycopenic and adrenergic symptoms.
  • Low Blood Glucose Levels: Document with point-of-care testing or laboratory confirmation.
  • Resolution of Symptoms with Glucose Administration: Reassess the patient after treatment with glucose (e.g., oral glucose or IV dextrose). The resolution of symptoms reinforces the diagnosis.

5. Signs of Underlying Causes

Examine for evidence of potential precipitating conditions:

  • Infection: Check for fever, localized tenderness (e.g., chest, abdomen, or urinary tract), or signs of sepsis, as infections increase metabolic demand and can precipitate hypoglycemia.
  • Malnutrition: Assess for signs of cachexia or dehydration, which may indicate fasting or poor nutritional intake.
  • Drug Overdose: Look for clues such as medication vials, needle marks, or altered mental status in cases of suspected overdose with insulin or sulfonylureas.

6. Secondary Causes

Inquire about and examine for:

  • Adrenal Insufficiency: Hypotension, hyperpigmentation, and unexplained fatigue may point to Addison’s disease or secondary adrenal insufficiency.
  • Hypopituitarism: Look for evidence of chronic deficiencies such as hypotension, hypoglycemia, and bradycardia.

7. Systematic Re-Evaluation

The examination should be repeated after glucose administration to assess symptom resolution and identify any residual neurological deficits. Persistent focal findings or altered mental status post-treatment may indicate concurrent pathology, such as stroke or seizure disorder.

Alternative Diagnoses

If neurologic or behavioral symptoms persist after treatment with glucose, evaluate for concurrent causes of altered mental status using the mnemonic “TIPS AEIOU” [5]. A CT brain scan may be warranted.

  • A – Alcohol
  • E – Endocrine/Electrolyte/Epilepsy
  • I – Insulin
  • O – Overdose/Opioids/Oxygen
  • U – Uremia
  • T – Toxicologic/Trauma
  • I – Infection
  • P – Psychiatric/Poisoning
  • S – Stroke/Shock
ALTERED MENTAL STATUS

Acing Diagnostic Testing

A comprehensive diagnostic workup is crucial for identifying and addressing the cause of hypoglycemia while initiating timely treatment. 

1. Bedside Tests

Rapid bedside testing is the cornerstone for the initial evaluation of hypoglycemia:

  • Blood Glucose Measurement:
    Venous or capillary blood glucose should be checked immediately using a glucose oxidase strip. A glucose level <3.0 mmol/L confirms hypoglycemia. However, it is critical to remember that the severity of symptoms, rather than the absolute glucose value, determines clinical significance [3].
  • Point-of-Care Testing (POCT):
    Concurrent bedside tests such as arterial blood gas (ABG) analysis can provide information about acid-base status and potential coexisting conditions like sepsis or metabolic acidosis.

2. Laboratory Tests

Further laboratory investigations should be guided by the clinical presentation and differential diagnosis:

  • Formal Glucose Measurement:
    If hypoglycemia is detected on a bedside glucose test, a venous blood sample should be sent to the laboratory for a formal plasma glucose level. Importantly, treatment must not be delayed while awaiting these results.
  • Serum Insulin and C-Peptide:
    These are particularly useful when hypoglycemia secondary to endogenous hyperinsulinism or insulin overdose is suspected.
    • High Insulin and High C-Peptide: Suggest endogenous insulin production, as seen in insulinomas or sulfonylurea ingestion.
    • High Insulin and Low C-Peptide: Consistent with exogenous insulin administration [3].
  • Cortisol Levels:
    A low cortisol level may indicate adrenal insufficiency as a potential cause of recurrent hypoglycemia.
  • Glucagon Levels:
    Although not routinely assessed, glucagon levels can provide insights into counter-regulatory hormone responses during hypoglycemia.
  • Infection Markers:
    Full blood count, inflammatory markers (e.g., CRP, procalcitonin), and blood cultures should be obtained to investigate underlying sepsis or infection.
  • Toxicology Screen:
    Consider when an overdose of oral hypoglycemic agents or other substances is suspected.

3. Imaging Studies

Imaging is not routinely required for all patients with hypoglycemia but should be considered when specific conditions are suspected:

  • Chest X-Ray (CXR):
    Indicated if a respiratory infection or pulmonary source of sepsis is suspected.
  • Electrocardiogram (ECG):
    Perform in patients with suspected ischemia or when adrenergic symptoms such as tachycardia or chest pain are present.
  • Neuroimaging (CT or MRI):
    Obtain if the patient has persistent neurological symptoms after glucose correction or if there are signs of head trauma, stroke, or other CNS pathology.
  • Abdominal Ultrasound or CT Abdomen:
    Consider in cases of suspected pancreatic pathology, such as insulinoma or pancreatitis.

Key Considerations

  • There is no universally defined blood glucose threshold for hypoglycemia, as symptom onset varies among patients. Individual factors, such as baseline glucose control and underlying comorbidities, influence symptomatology [6].
  • Diagnostic tests should be tailored based on the clinical scenario to exclude critical conditions like infection, ischemia, or medication overdose. While advanced studies such as serum insulin and C-peptide are valuable, these are rarely performed in the emergency department and are more relevant in specialized or outpatient settings [3].

Risk Stratification

Factors to consider when risk stratifying patients with hypoglycemia include [3,7]:

  • Severity of hypoglycemia: Mild hypoglycemia can be managed by the patient with oral glucose or food, while severe hypoglycemia may require intravenous glucose and hospitalization.

  • Frequency of hypoglycemic episodes: Frequent hypoglycemic episodes can increase the risk of developing hypoglycemia unawareness, which may lead to more severe episodes in the future.

  • Underlying medical conditions: Patients with diabetes who have comorbidities, such as renal insufficiency or liver disease, may be at increased risk for hypoglycemia.

  • Age and cognitive function: Elderly patients or those with cognitive impairment may be at higher risk for hypoglycemia due to difficulty recognizing symptoms and managing their blood glucose levels.

  • Lifestyle factors: Patients with poor nutrition or irregular eating patterns may be at increased risk for hypoglycemia.

Management

Patients with hypoglycemia should be placed in a monitored area. If the patient has decreased consciousness or is unconscious, the airway should be protected, but intubation should be avoided prior to the administration of glucose. The means of reversing hypoglycemia depend on the patient’s mental status, ability to cooperate with oral intake, availability of intravenous access, and medical and medication history.

If the patient is conscious and able to cooperate with oral intake, administration of food or liquid rich in simple carbohydrates (e.g., a sugary drink, sugar, candies, or glucose tablets) is preferred. After this, the patient should receive a meal rich in complex carbohydrates, fat, and protein, such as a sandwich.

If the patient is unconscious or unable to cooperate with oral intake and intravenous access is available, administer 50 mL of IV dextrose 50% or 250 mL of 10% dextrose (equivalent to 25 g of dextrose) over a few minutes. A second dose can be administered if the patient’s mental status does not improve.

If intravenous access is not available, 1 mg of IM/SC glucagon can be administered. Glucagon takes longer to normalize mental status (approximately 7–10 minutes), and its effect tends to be short-lived. As glucagon raises blood glucose by mobilizing hepatic glycogen reserves, it is not effective in patients with depleted glycogen stores (e.g., liver failure or chronic alcoholism). Glucagon can also cause vomiting, which may be dangerous if the patient has an altered mental status and cannot protect their airway.

For patients with sulfonylurea overdose, commence therapy with IV dextrose until the patient can tolerate oral intake. If episodes of hypoglycemia recur despite glucose therapy, consider adding SC octreotide 50–100 micrograms. Note that octreotide should only be used for recurrent sulfonylurea-induced hypoglycemic episodes that persist despite glucose therapy [3,5].

Special Patient Groups

Pediatrics

Children are particularly vulnerable to the effects of hypoglycemia due to their higher metabolic rate and limited glycogen stores. Key points in management include:

  • Treatment Protocol:
    Administer 10% glucose at 5 mL/kg or 25% dextrose at 2.5 mL/kg intravenously for acute hypoglycemia. Avoid the use of 50% dextrose in this population, as its hypertonicity increases the risk of thrombophlebitis and local tissue injury [8].
  • Medication for Refractory Cases:
    For persistent hypoglycemia caused by hyperinsulinemia (e.g., from congenital hyperinsulinism or sulfonylurea overdose), octreotide is effective at a dosage of 1 μg/kg subcutaneously (maximum 50 μg). This medication inhibits insulin secretion and provides a targeted intervention [8].
  • Long-Term Considerations:
    Recurrent hypoglycemia in children warrants further investigation into metabolic or endocrine disorders, including inborn errors of metabolism, adrenal insufficiency, or insulinoma.

Pregnant Patients

Pregnant patients with diabetes, particularly those on insulin therapy, face a higher risk of hypoglycemia due to physiological changes during pregnancy, including increased insulin sensitivity in the first trimester.

  • Incidence:
    Up to 50% of pregnant patients with diabetes experience at least one episode of severe hypoglycemia during pregnancy, especially in the first trimester [4].
  • Management and Prevention:
    • Careful Insulin Titration: Frequent monitoring and adjustment of insulin doses are essential to balance optimal glycemic control with the prevention of hypoglycemia.
    • Dietary Counseling: Pregnant patients should be educated on consuming regular, balanced meals with adequate carbohydrate intake to prevent fasting hypoglycemia.
    • Monitoring: Emphasize regular blood glucose monitoring, as symptoms may be subtle or atypical.
  • Fetal Considerations: Prompt correction of maternal hypoglycemia is critical to prevent adverse effects on the fetus, including hypoxic injury from prolonged episodes.

Geriatrics

Older adults often experience atypical presentations of hypoglycemia, and their management is complicated by comorbidities, polypharmacy, and age-related physiological changes.

  • Atypical Presentations:
    Hypoglycemia in geriatric patients may lack typical adrenergic symptoms like tremors or sweating. Instead, symptoms such as confusion, lethargy, or falls may predominate, potentially delaying diagnosis.
  • Risk Factors:
    • Polypharmacy: Concurrent use of insulin, sulfonylureas, or other glucose-lowering agents increases hypoglycemia risk.
    • Renal Impairment: Reduced clearance of medications such as sulfonylureas or insulin exacerbates the risk of prolonged hypoglycemia.
    • Nutritional Deficits: Poor oral intake or prolonged fasting may contribute to hypoglycemia.

Intubated Patients

For intubated or sedated patients, hypoglycemia can be difficult to recognize because mental status changes are masked. In these cases, frequent glucose monitoring is essential [5].

When To Admit This Patient

Admission Criteria
Patients with hypoglycemia generally require admission to an observation unit or the general ward for evaluation and treatment of the underlying cause, as well as titration of diabetic medication.
Patients with unexplained or recurrent hypoglycemia should be admitted to a monitored area. Individuals taking sulfonylureas have an increased likelihood of experiencing recurrent and delayed-onset episodes of hypoglycemia. Consultation with a toxicologist and psychiatrist should be considered for patients who overdose on their diabetic medication [3,7].

Discharge Criteria
The patient should only be discharged if the cause of hypoglycemia is identified and deemed benign, they have fully recovered, are tolerating oral intake well, and have had no recurrence of hypoglycemic episodes after a 4-hour period of observation. Discharge advice should include guidance on nutrition and recognition of hypoglycemia symptoms. Patients should be advised to ingest glucose in case of symptoms [3].

Referral
If discharged from the ED, patients should be referred to their primary physician or specialist for follow-up. Patients should also be advised to always carry sugar or candy to ingest in case hypoglycemic symptoms arise [3].

Revisiting Your Patient

You examine your patient in the examination room. Upon examination, you notice a decreased level of consciousness, but otherwise, the exam is unremarkable. During the examination, the nurse obtains IV access and administers a bolus dose of intravenous glucose. Much to the relatives’ relief and amazement, the patient returned to her normal behavior within 5 minutes. The patient herself reported lower urinary tract symptoms with a low-grade fever over the last two days. The relatives also reported administering her insulin according to her daily regimen, without being cautious about her reduced food intake.

In addition, blood investigations revealed that her renal function had significantly deteriorated since her last primary care visit, despite continuing on the same insulin regimen. The patient was subsequently admitted to a general ward for further evaluation and management.

Recommended Free Open Access Medical Education (FOAM) resources

Author

Picture of Rok Petrovčič

Rok Petrovčič

Attending Physician - UKC Maribor / University Medical Centre Maribor

Listen to the chapter

References

  1. Mathew P, Thoppil D. Hypoglycemia. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022. Updated July 23, 2022. Accessed February 24, 2023. https://www.ncbi.nlm.nih.gov/books/NBK534841/

  2. Maheswaran AB, Gimbar RP, Eisenberg Y, Lin J. Hypoglycemic events in the emergency department. Endocr Pract. 2022;28(4):372-377.

  3. Ravert D. Hypoglycemia. In: Mattu A, Swadron S, eds. CorePendium. Burbank, CA: CorePendium, LLC; 2021. Updated August 25, 2021. Accessed February 24, 2023. https://www.emrap.org/corependium/chapter/rec3z0v69Pks65AZg/Hypoglycemia#references

  4. Jalili M. Type 2 diabetes mellitus. In: Tintinalli JE, ed. Tintinalli’s Emergency Medicine. 7th ed. New York, NY: McGraw Hill; 2011:1431-1432.

  5. Nickson C. Hypoglycemia. In: Life in the Fast Lane. Accessed February 24, 2023. https://litfl.com/hypoglycemia/

  6. Frier BM. Defining hypoglycemia: what level has clinical relevance? Diabetologia. 2009;52(1):31-34.

  7. Oyer DS. The science of hypoglycemia in patients with diabetes. Curr Diabetes Rev. 2013;9(3):195-208.

  8. May N. Oh, sugar! Paediatric hypoglycaemia. In: St. Emlyn’s Blog. Accessed March 1, 2023. http://stemlynsblog.org/paediatric-hypoglycaemia/

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Transient Cerebral Ischemia (2024)

~ iEM Education Project Team ~ Leave a comment

by Omer Jaradat & Haci Mehmet Caliskan

 

Authors
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You Have A New Patient!

A 63-year-old male is brought to the Emergency Department (ED) by paramedics with a chief complaint of transient right-sided weakness. He states that the weakness started suddenly while he was watering his garden, lasted about 15 minutes, and then resolved without any residual deficits. On examination, his temperature is 36°C, blood pressure is 150/90 mmHg, pulse is 81 beats/min, respiratory rate is 18 breaths/min, and oxygen saturation is 97% on room air. 

The image was produced by using ideogram 2.0.

The patient’s past medical history is remarkable for hypertension, diabetes mellitus, and hyperlipidemia. He also smokes half a pack of cigarettes daily.

What Do You Need To Know?

Importance

Transient Cerebral Ischemia (TCI) or Transient Ischemic Attack (TIA) is defined as a sudden onset of transient, focal neurological symptoms and/or signs that occur due to focal brain, spinal cord, or retinal ischemia, without acute infarction [1]. Neurological symptoms and signs are related to the ischemic area of the brain. TIA is a neurologic emergency because patients with TIA have an early high risk of subsequent stroke. Up to 80% of strokes after TIA are preventable. Therefore, early recognition and differentiation of TIA cases are important for early treatment, which reduces the possibility of stroke. In brief, TIA represents a great opportunity for the physician to prevent stroke. Early diagnosis and treatment are the key.

Epidemiology

TIA is an important clinical condition that is common worldwide. The total global incidence of TIA is approximately 1.19 per 1000 persons per year, and it has been observed that the incidence is higher (4.88 per 1000 persons) in older age groups (85–94 years) [2]. TIA is more common in Black and male populations than in White and female populations [3].

Pathophysiology

TIA is mainly caused by three mechanisms of pathophysiology: (1) intrinsic vascular (lacunar or small vessel) pathogenesis such as atherosclerosis, lipohyalinosis, inflammation, and amyloidosis; (2) embolism originating from the heart and extracranial large vessels; and (3) low-flow conditions such as insufficient blood flow to the brain, decreased perfusion pressure, and increased blood viscosity [4].

(1) Lacunar or small vessel TIA: These TIAs are usually due to atherosclerosis of the proximal vessels or lipohyalinosis of the distal vessels. Small vessel TIAs cause symptoms similar to the lacunar strokes that are likely to follow, such as weakness or numbness in the arms, legs, and face, which are recurrent and progressive.

(2) Embolic TIAs: These are characterized by a relatively longer duration of focal neurological symptoms. These TIAs are mostly the result of embolism from a specific source. Embolism can originate from larger arteries or from the heart. In one study, it was determined that the symptoms of embolic TIAs lasted longer (hours) than those of low-flow TIAs (lasting minutes) [5].

TIAs create specific symptoms according to the regions of the occluded vessel:

  • Anterior circulation embolic TIA: Larger emboli can occlude the middle cerebral artery stem and cause contralateral hemiplegia, cortical surface symptoms (aphasia and dysexecutive syndromes in the dominant hemisphere, anosognosia or neglect in the nondominant hemisphere). Smaller emboli can occlude branches of the middle cerebral artery and cause focal symptoms such as numbness, weakness, and/or heaviness of the hand and arm.

  • Posterior circulation embolic TIA: These emboli can cause transient ataxia, diplopia, dizziness, dysarthria, hemianopsia, quadrantanopia, numbness, and unilateral hearing loss. If the embolus lodges at the top of the basilar artery, stupor or coma may occur. If the embolus lodges in the distal branches of the posterior cerebral artery, it can cause memory loss or a homonymous field defect.

(3) Low-flow TIA occurs with an obstructive vascular process in any extracranial or intracranial artery and disruption of collateral flow in the area supplied by these arteries. Low-flow TIAs are usually of short duration (minutes) and recurrent [4].

  • Anterior circulation low-flow TIA: These TIAs usually produce symptoms of a similar character. They occur due to hemodynamically significant stenotic lesions, especially in the proximal internal carotid artery, middle cerebral artery, and internal carotid artery, where collateral flow from the circle of Willis is insufficient. Ischemia-related symptoms resulting from these lesions usually include weakness or numbness in the hands, arms, legs, face, tongue, and/or cheek. Recurrent aphasic syndromes occur when there is focal ischemia in the dominant hemisphere, and recurrent neglect occurs when there is focal ischemia in the nondominant hemisphere. Limb-shaking TIAs are a rare but classic hypoperfusion syndrome in which repetitive jerking movements of the arm or leg are due to severe stenosis or occlusion of the contralateral internal carotid or middle cerebral artery.

  • Posterior circulation low-flow TIA: Unlike anterior low-flow TIA, the symptoms of these TIAs are not stereotypical because many neuronal structures in the brainstem are located very close to each other. Posterior low-flow TIA symptoms include diplopia, eyelid drooping, inability to look up, dysarthria, dizziness, drowsiness, bilateral leg and arm weakness or numbness, a feeling of heaviness, and numbness on one side of the body or face.

The diagnosis of TIA is based on the clinical features of the transient neurological attack and neuroimaging findings [6]. The majority of TIA cases do not present when fully symptomatic. For this reason, the history reported by the patient and witnesses is very important in terms of diagnosis [7]. TIA patients may experience typical or atypical symptoms.

Typical TIA:

It consists of focal neurological symptoms of sudden onset and transient character, localized to a single vascular region in the brain. These symptoms include aphasia or dysarthria, transient monocular blindness (amaurosis fugax), hemianopia, hemiparesis, and/or hemisensory loss. In such cases, the probability of ischemia is relatively high. However, these symptoms may also occur due to non-ischemic causes such as seizures, migraines, and intracerebral hemorrhage.

Atypical TIA:

Clinical characteristics of transient symptoms considered to be atypical of an ischemic attack include the following [8-10]:

  • Gradual progression of symptoms.
  • Change of symptoms from one type to another.
  • Disturbance of vision in both eyes, characterized by the occurrence of positive phenomena (positive symptoms are not normally experienced by most individuals and reflect an excess of normal functions, such as flashing lights).
  • Isolated sensory symptoms with a focal distribution, especially in areas such as a finger, chin, or tongue.
  • Attacks lasting less than 30 seconds.
  • Isolated brainstem symptoms such as dysarthria, diplopia, or hearing loss.
  • Amnesia and confusion.
  • Incoordination of limbs.

Atypical TIAs with negative symptoms (negative symptoms mean loss of a neurological function, such as hearing loss or vision loss) have a high risk of recurrent stroke. For this reason, they should be handled and treated as typical TIAs [4].

Medical History

The most important question is the time of symptom onset because it guides the treatment. Patients and/or their relatives should also be questioned about neurological diseases and symptoms (such as migraine, epilepsy, previous attacks similar to this one, syncope, etc.), cardiovascular diseases (such as myocardial infarction, atrial fibrillation, carotid stenosis, etc.), metabolic disorders (such as diabetes, hyperlipidemia, etc.), hypertension, drug usage, smoking, and family history of cardiac and/or neurological diseases.

  • Important points regarding the medical history of patients with TIA: Cardiovascular diseases, previous history of neurological attack or stroke, and drug usage.
  • Risk factors for TIA: Older age, atrial fibrillation, atherosclerosis, diabetes mellitus, hypertension, hyperlipidemia, smoking, history of stroke, male gender, and Black race.
  • Prognosis of TIA patients: The prognosis is defined by the risk of recurrent stroke. The risk of stroke after TIA varies according to several factors, including the time elapsed since the last TIA, the presence of vascular pathologies, and the presence of acute infarction on diffusion-weighted magnetic resonance imaging (DW-MRI). Stroke is most likely to occur in the first week after a TIA, with a 1.5–3.5% risk in the first 48 hours. Within 90 days, the risk of stroke rises to 40% [11–14]. Vascular pathologies such as large artery atherosclerosis, small artery disease, and cardio-embolic conditions increase the risk of recurrent stroke. Additionally, the presence of acute lesions on DW-MRI or chronic ischemic lesions on computed tomography (CT) increases the likelihood of recurrent stroke in TIA patients.

Physical Examination

A detailed neurological evaluation should be performed on the patient, including assessment of cranial nerves, strength and sensation, visual fields, language, gait, and coordination. A focal neurological deficit on exam should raise suspicion for TIA. In addition to the neurological exam, it is important to perform a thorough cardiovascular exam, listening closely for irregular rhythms, murmurs, and bruits on the carotids.

  • Red flags: Bruits on the carotids, the presence of negative symptoms, and irregular rhythms.

Alternative Diagnoses

What other diseases can present with similar clinical features/conditions?

Seizures, migraines, metabolic disorders such as hypoglycemia, subarachnoid or intracerebral hemorrhage, subdural hematoma, syncope, and central nervous system (CNS) demyelinating disorders such as multiple sclerosis, etc., should come to mind in the differential diagnosis of TIA.

Which findings make TIA more probable?

Sudden onset of typical symptoms, presence of negative symptoms, and normal laboratory and imaging findings.

Which risk factors and findings make other diagnoses more probable or make this diagnosis less probable?

We can differentiate syncope, epileptic seizures, CNS demyelinating disorders, and migraine aura with a detailed history. In the differentiation of seizures, the lactate value in an arterial blood gas (ABG) test is also important. High lactate levels support the diagnosis of seizures. Intracranial hemorrhages and subdural hematomas have specific imaging findings.

Acing Diagnostic Testing

Bedside Tests

First, vital signs (body temperature, pulse rate, respiration rate, blood pressure, and peripheral oxygen saturation) of the patient should be measured and recorded. Then, as the first approach, in all patients presenting with neurological symptoms, the measurement of blood glucose at the bedside, along with checking electrolytes, PO2, PCO2, and lactate values in an arterial blood gas (ABG) test, and performing electrocardiography (ECG), are very valuable in terms of diagnosis and differential diagnosis.

Laboratory Tests

Complete blood count (CBC), biochemistry, and coagulation tests are usually performed in addition to blood glucose measurement and ABG. These tests are useful in distinguishing metabolic disorders such as hypoglycemia from TIA. Impaired coagulation tests are also helpful in guiding diagnosis and treatment.

Imaging

Patients who are symptomatic should be considered as having a stroke. A non-contrast head CT scan can be used to assess early ischemic signs and exclude intracerebral hemorrhage. In TIA, CT has low sensitivity and usually does not show any pathological findings. If CT is negative for mass lesions and intracranial hemorrhage, computed tomography angiography (CTA) and/or magnetic resonance angiography (MRA) can be used to investigate intracranial and extracranial vascular occlusions. If CTA and/or MRA are negative for large vessel occlusion and TIA is suspected, MRI should be obtained to evaluate for signs of ischemia/infarction. DW-MRI following MRI is the gold standard for acute ischemic stroke and distinguishes stroke from TIA. DW-MRI is valuable because it shows focal areas of cytotoxic edema, which are seen in acute stroke.

Risk Stratification

The ABCD2 score (age, blood pressure, clinical features, duration, and the presence of diabetes mellitus) is commonly used to determine stroke risk following TIA. Parameters evaluated in the ABCD2 score assign scores for certain clinical features (speech impairment and unilateral weakness) and duration of symptoms, in addition to risk factors such as age, blood pressure, and diabetes. However, studies have found that the ABCD2 score does not reliably distinguish between those with a low and high risk of recurrent stroke.

Alternatively, the Canadian TIA Score uses variables routinely obtained in the ED setting to classify patients into minimal, low, high, or critical risk categories, which are associated with the likelihood of developing a stroke in the week following a TIA. Using the Canadian TIA Score strikes a balance by allowing risk stratification based on history, clinical data points, and neuroimaging, and defines clear follow-up actions based on the patient’s predictive score. Compared to the ABCD2 score, the Canadian TIA Score has shown better predictability [15].

However, there are not enough studies on the Canadian TIA Score. For this reason, a risk stratification score alone should not be used to determine the management of patients. Instead, the decision regarding hospitalization versus discharge should be made within the greater clinical context.

Management

Initial Stabilization

In all patients presenting to the Emergency Department, the initial assessment should involve the “ABCDE” approach (assessment of Airway, Breathing, Circulation, Disability, and Exposure). If the patient is alert and responds with a normal voice, the airway is open. However, if there is no respiration despite effort, the airway must be secured by checking for a foreign body, performing airway-opening maneuvers (head-tilt and chin-lift or jaw-thrust), suctioning the airway, or even intubating if necessary. In TIA patients, altered mental status is a common cause of airway obstruction [16]. If breathing is insufficient and oxygen saturation is below 94%, supplemental oxygen should be administered [17].

Altered mental status could be a sign of decreased perfusion, so obtaining intravenous access and starting IV fluids, if indicated, should be performed (the best choice is isotonic fluid). Blood pressure measurements, performing an EKG, and auscultation for abnormal heart sounds, murmurs, and carotid bruits can provide clues to the etiology of the TIA. Patients should be evaluated for disability using the Glasgow Coma Score (GCS), evaluation of pupillary light reflexes, and checking for signs of lateralization.

As hypoglycemia is considered a TIA mimic, it must be checked and corrected immediately, and hyperglycemia should also be prevented. Patients should be evaluated for drug intake and toxic ingestions. All patients with impaired consciousness should undergo a complete physical examination, which includes removing their clothes to search for signs of bleeding, foreign bodies, and trauma [16].

Medications

Treatment is started according to risk stratification.

  • If the ABCD2 score is ≥4: Dual antiplatelet therapy (DAPT) is started.

    • Aspirin (160 to 325 mg loading dose, followed by 50 to 100 mg daily) plus clopidogrel (300 to 600 mg loading dose, followed by 75 mg daily)
    • Alternatively, aspirin (300 to 325 mg loading dose, followed by 75 to 100 mg daily) plus ticagrelor (180 mg loading dose, followed by 90 mg twice daily).

  • If the ABCD2 score is <4: Aspirin monotherapy is started.

    • Aspirin (162 to 325 mg daily) [18, 19].

According to the Canadian TIA Score, patients are divided into four risk groups and managed as follows:

Minimal and Low Risk: Refer the patient to rapid outpatient assessment with a neurologist.

High Risk:

  • Start or switch to DAPT (clopidogrel or dipyridamole + ASA).
  • Initiate or control hypertension management.
  • Refer the patient to neurology within 24 hours.

Critical Risk:

  • Start or switch to DAPT (clopidogrel or dipyridamole + ASA).
  • Start oral anticoagulation if the patient has atrial fibrillation.
  • Start a statin class medication.
  • Initiate or optimize control of hypertension.
  • Admit the patient to the hospital and ensure referral to neurology within 24 hours [20].
    •  

Procedures

In patients with ongoing and disabling symptoms, emergent evaluation for IV thrombolysis and mechanical thrombectomy should be performed. Selected patients with recently symptomatic cervical internal carotid artery stenosis can significantly benefit from early carotid endarterectomy (within two weeks of a non-disabling stroke or TIA) [21].

Special Patient Groups

Stroke is a rare condition in the pediatric population, but all principles that apply to adults also apply to the pediatric population. Because the incidence of stroke increases with age, physicians should consider stroke in the management of undifferentiated geriatric patients.

In pregnant patients, physiological changes increase the risk of stroke, and there is significant maternal morbidity and mortality associated with stroke. However, a transient ischemic attack (TIA) is not a type of pregnancy-associated stroke, but it should be noted that TIAs precede strokes in up to 15% of cases [22].

When To Admit This Patient

Because of the high risk of stroke after TIA, patients diagnosed with TIA should be hospitalized for further etiological investigation and treatment.

Only selected patients with a completely normal physical examination, no ongoing disability, normal imaging (including MRI), and a low-risk score can be discharged if their neurology outpatient clinic visit is imminent and after aspirin therapy is started.

Discharged patients should be informed about TIA symptoms and encouraged to call Emergency Medical Services (EMS) and/or go to the nearest Emergency Department if these symptoms begin.

The main symptoms of a TIA can be remembered with the acronym FAST:

  • Face – Drooping or numbness on one side of the face, inability to smile, or if the mouth or eye has drooped.
  • Arms – Inability to lift both arms and keep them raised because of weakness or numbness in one arm.
  • Speech – Slurred speech, inability to talk at all despite appearing to be awake, or difficulty understanding speech.
  • Time – If any of these signs or symptoms is present, call Emergency Medical Services (EMS) immediately.

Revisiting Your Patient

The ABCDE approach was initiated as soon as the patient entered the ED. Since he is awake and does not show signs of difficulty breathing, his airway is considered open, and his breathing is considered normal.

Blood pressure is high, but pulse is within normal ranges. No murmur, abnormal sounds, or carotid murmur is detected on auscultation. Since hypoglycemia and hyperglycemia can mimic TIA, a bedside glucose level was measured and found to be 110 mg/dL (6.1 mmol/L).

A focused neurological examination was performed: pupils are equal and reactive, facial expressions appear appropriate, there is no drooping, and there is no slurring of speech. Muscle strength in his right arm is decreased, and muscle strength in his right leg is slightly decreased. There is no sensory deficit. The rest of the physical exam is unremarkable.

An electrocardiogram (EKG) was requested to check for acute pathologies and arrhythmias, such as atrial fibrillation, which is important in the etiology of TIA, and it demonstrates sinus rhythm. Since the history and physical examination are typical for an acute cerebrovascular accident, an intravenous (IV) catheter was inserted, and complete blood count (CBC), plasma urea nitrogen, creatinine, electrolytes, cardiac enzymes, and coagulation parameters (prothrombin time, activated partial thromboplastin time, and international normalized ratio [INR]) were ordered.

To exclude bleeding, the patient underwent a non-contrast brain tomography, which was interpreted as normal. The ABCD2 score was found to be ≥6. The patient was consulted with the neurology department. No focal neurological signs were detected in serial physical examinations. Thrombolytic therapy was not considered because the symptoms resolved, and the imaging was normal.

However, because the patient’s complaints were typical of stroke and/or TIA, due to comorbid diseases, and because he is not on antiplatelet therapy, he is considered to have a high risk for stroke. As a result, dual antiplatelet therapy (DAPT) was started, and the patient was transferred to the neurology service for further examination and treatment to elucidate the etiology.

Recommended Free Open Access Medical Education (FOAM) resources

  1. Zink J. (2022). Syncope and Syncope Mimics. EmDocs. Retrieved from http://www.emdocs.net/syncope-and-syncope-mimics/
  2. Chapman S. (2023). The Utility of MRI in the ED. EmDocs. Retrieved from http://www.emdocs.net/the-utility-of-mri-in-the-ed/
  3. Lanata E.P. (2021). TIA: Emergency Department Evaluation and Disposition. EmDocs. Retrieved from http://www.emdocs.net/tia-emergency-department-evaluation-and-disposition/
  4. Rezaie S. (2021). “Rebellion21: Canadian TIA Risk Score vs ABCD2”. REBEL EM blog. Retrieved from https://rebelem.com/rebellion21-canadian-tia-risk-score-vs-abcd2/

Authors

Picture of Omer Jaradat

Omer Jaradat

Dr. Omer Jaradat is an Emergency Medicine Physician at Ahi Evran University Training and Research Hospital, Kirsehir, Türkiye. He is an enthusiast of emergency medicine and strongly believes in the generalist and collective approach of the specialty. He is particularly interested in global emergency medicine, emergency medicine education, and innovation. A dedicated follower and contributor to #FOAMed, he feels proud to be a member of the emergency medicine community.

Picture of Elizabeth DeVos

Elizabeth DeVos

Dr. Haci Mehmet Caliskan is an Associate Professor of Emergency Medicine and an academician at Ahi Evran University, Kirsehir, Türkiye. He is deeply interested in emergency medicine education and is passionate about engaging students in the emergency medicine community. He is an advocate for fair and equitable medical care. His current professional interests include cardiovascular diseases, pulmonary medicine, and trauma. He takes Atatürk as an example in both his professional and social life.

Listen to the chapter

References

  1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276-2293. doi:10.1161/STROKEAHA.108.192218
  2. Lioutas VA, Ivan CS, Himali JJ, et al. Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke. JAMA. 2021;325(4):373-381. doi:10.1001/jama.2020.25071
  3. Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke. 2005;36(4):720-723. doi:10.1161/01.STR.0000158917.59233.b7
  4. Rost NS, Faye EC. Definition, etiology, and clinical manifestations of transient ischemic attack. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. (Accessed on January 20, 2023.)
  5. Kimura K, Minematsu K, Yasaka M, Wada K, Yamaguchi T. The duration of symptoms in transient ischemic attack. Neurology. 1999;52(5):976-980. doi:10.1212/wnl.52.5.976
  6. Sorensen AG, Ay H. Transient ischemic attack: definition, diagnosis, and risk stratification. Neuroimaging Clin N Am. 2011;21(2):303-x. doi:10.1016/j.nic.2011.01.013
  7. Ay H, Arsava EM, Johnston SC, et al. Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model. Stroke. 2009;40(1):181-186. doi:10.1161/STROKEAHA.108.521476
  8. Fisher CM. Late-life migraine accompaniments–further experience. Stroke. 1986;17(5):1033-1042. doi:10.1161/01.str.17.5.1033
  9. Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke. 1990;21(4):637-676. doi:10.1161/01.str.21.4.637
  10. Amarenco P. Transient Ischemic Attack. N Engl J Med. 2020;382(20):1933-1941. doi:10.1056/NEJMcp1908837
  11. Amarenco P, Lavallée PC, Labreuche J, et al. One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke. N Engl J Med. 2016;374(16):1533-1542. doi:10.1056/NEJMoa1412981
  12. Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis. Arch Intern Med. 2007;167(22):2417-2422. doi:10.1001/archinte.167.22.2417
  13. Shahjouei S, Sadighi A, Chaudhary D, et al. A 5-Decade Analysis of Incidence Trends of Ischemic Stroke After Transient Ischemic Attack: A Systematic Review and Meta-analysis [published correction appears in JAMA Neurol. 2021 Jan 1;78(1):120]. JAMA Neurol. 2021;78(1):77-87. doi:10.1001/jamaneurol.2020.3627
  14. Chandratheva A, Mehta Z, Geraghty OC, Marquardt L, Rothwell PM; Oxford Vascular Study. Population-based study of risk and predictors of stroke in the first few hours after a TIA. Neurology. 2009;72(22):1941-1947. doi:10.1212/WNL.0b013e3181a826ad
  15. Perry JJ, Sivilotti MLA, Émond M, et al. Prospective validation of Canadian TIA Score and comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischaemic attack: multicentre prospective cohort study [published correction appears in BMJ. 2021 Feb 18;372:n453]. BMJ. 2021;372:n49. Published 2021 Feb 4. doi:10.1136/bmj.n49
  16. Thim T, Krarup NH, Grove EL, Rohde CV, Løfgren B. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. Int J Gen Med. 2012; 5:117-121. doi:10.2147/IJGM.S28478
  17. Piraino T, Madden M, J Roberts K, Lamberti J, Ginier E, L Strickland S. Management of Adult Patients With Oxygen in the Acute Care Setting [published online ahead of print, 2021 Nov 2]. Respir Care. 2021; respcare.09294. doi:10.4187/respcare.09294
  18. Mendelson SJ, Prabhakaran S. Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review. JAMA. 2021;325(11):1088-1098. doi:10.1001/jama.2020.26867
  19. Fonseca AC, Merwick Á, Dennis M, et al. European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack. Eur Stroke J. 2021; 6(2):CLXIII-CLXXXVI. doi:10.1177/2396987321992905
  20. Gladstone DJ, Lindsay MP, Douketis J, et al. Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020. Can J Neurol Sci. 2022;49(3):315-337. doi:10.1017/cjn.2021.127
  21. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ; Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363(9413):915-924. doi:10.1016/S0140-6736(04)15785-1
  22. Grear KE, Bushnell CD. Stroke and pregnancy: clinical presentation, evaluation, treatment, and epidemiology. Clin Obstet Gynecol. 2013;56(2):350-359. doi:10.1097/GRF.0b013e31828f25fa

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Drowning (2024)

~ iEM Education Project Team ~ Leave a comment

by Mark E O’Brien & Elizabeth L DeVos


Authors
Listen

You Have A New Patient!

A 14-year-old boy with no prior medical history was just brought to the Emergency Department (ED) by bystanders after being pulled from a large creek that serves as a popular swimming location. According to his friends, the patient jumped feet-first from a small bridge about 2 meters above the water and did not resurface. His body was found floating further down the creek approximately five minutes later, and a nearby nurse immediately began CPR. 

The image was produced by using ideogram 2.0.

He was transported to the hospital in the back of a truck, with CPR reportedly being performed continuously during the 10 minutes it took to arrive. On arrival at the ED, the patient is found to be pulseless, apneic, and cyanotic. You are called over to manage this patient’s care. What do you do?

What Do You Need To Know?

The World Health Organization (WHO) defines drowning as “the process of experiencing respiratory impairment from submersion or immersion in liquid,” with outcomes classified as either death, morbidity, or no morbidity [1]. This definition simplifies and standardizes the language used to describe drowning and eliminates potentially confusing terminology. It replaces previously used terms, including wet, dry, active, passive, silent drowning, secondary drowning, near-drowning, and drowning with a fatal outcome.

Drowning is a significant public health threat that is estimated to cause the death of more than 40 people every hour of every day [2]. It is believed that the current data severely underestimates the actual incidence and mortality of drowning, especially in low-income and middle-income countries (LMICs), where more than 90% of drowning-related deaths occur [3]. As drowning is considered to be highly preventable, there has been much research into and focus on drowning prevention. However, improvement in the quality of medical care provided to drowning victims can also help decrease the mortality and morbidity associated with drowning.

Epidemiology

There were more than 2.5 million deaths attributed to drowning in the past decade, with an estimated 236,000 drowning deaths occurring in 2019, according to the WHO’s most recent Global Health Estimates [4]. The vast majority (>90%) of drowning deaths worldwide occur in LMICs. Drowning remains the third highest cause of unintentional injury-related deaths worldwide and the second highest in terms of Years of Life Lost (YLL) [5].

It is important to note that drowning incidence and mortality are believed to be significantly underestimated and may exceed five times the rates reported by the WHO. Drowning deaths due to causes such as suicide, homicide, transport/vehicular incidents, or natural disasters are usually reported under those categories of death instead of being classified as deaths due to drowning. Additionally, drowning deaths in LMICs are typically derived from hospital data, which often excludes those who perish outside of the hospital, particularly in rural and medically underserved areas. Nonfatal drownings are also underreported, as most individuals who return to their baseline without any morbidity are unlikely to seek hospital care [6].

Risk Factors

There is a higher incidence of drowning in pediatric patients, and those aged 1–4 years old are at the greatest risk of death from drowning [5]. It is likely that natural curiosity about their environment, coupled with a lack of swimming skills and poor adult supervision, are the main factors behind the high drowning incidence and mortality in extremely young children. Most pediatric drowning deaths occur in and around the home. In LMICs, cisterns, wells, and small bodies of water such as streams and ponds are the most likely drowning locations for young children, as they tend to be uncovered and close to home. Adolescents and teenagers tend to drown in larger bodies of water, as they are more adventurous and willing to take risks, especially in the presence of friends and peer pressure [2].

Men are at a higher risk of drowning than women, and 75% of recorded LMIC drowning victims were males [5]. Men are more often out on open bodies of water through water-related careers, including fishing and shipping, which greatly increases the risk of drowning [7]. Men are also more likely to participate in risky behaviors such as alcohol use, which can lead to disastrous consequences when combined with recreational or professional aquatic activities [8]. The combination of men engaging in riskier jobs and behaviors that put them in direct contact with large bodies of water is considered a major factor behind the increased drowning rate in males compared to females.

There are a number of additional factors that have been noted to correlate with an increased risk of drowning. Those with medical conditions that can quickly incapacitate them, including epilepsy and cardiac arrhythmias, are at a higher risk of drowning when bathing or participating in recreational aquatic activities [9]. Alcohol use significantly increases the risk of drowning, especially when combined with activities such as boating and fishing [8]. In 86% of drowning cases in LMICs, the victim was reportedly unable to swim. Despite this direct correlation between swimming ability and drowning mortality, swimming lessons are still not commonly available or prioritized in LMICs [2].

There is a correlation between daytime and drowning, as almost all drowning events in LMICs occur during daytime hours. However, this is believed to be simply because most people in LMICs are outside much more frequently during the day and tend to stay indoors at night. Environmental factors have also been noted to correlate with increased drowning incidence in LMICs, as the rate of drowning increases with increased rainfall patterns and higher temperatures. This is thought to result from increased volume in local bodies of water and increased exposure to water sources during these times. The effects of climate change exacerbate these environmental factors and play a role in increasing the frequency and severity of flooding, hurricanes, cyclones, and other natural disasters, which raise the risk of death by drowning [10].

Pathophysiology

Prolonged or unexpected submersion results in panic, air hunger, and breath-holding as the victim attempts to surface. As hypoxia progresses and the inspiratory drive becomes too strong to resist, involuntary gasps are triggered, breath-holding is overcome, and the victim begins to aspirate water. Aspiration of 1 to 3 mL/kg of water into the airways is enough to cause direct alveolar membrane injury, washout and dysfunction of pulmonary surfactant, and ventilation-perfusion mismatch [11]. Pulmonary complications, including alveolar collapse, atelectasis, noncardiogenic pulmonary edema, intrapulmonary shunting, and secondary pulmonary infection, can occur. The victim may develop profound metabolic and respiratory acidosis secondary to hypercarbic respiratory failure and lactic acidosis. If hypoxia persists, the patient will enter cardiac arrest, develop anoxic brain injury, and eventually die [12]. Even after being removed from water, a drowning patient may remain hypoxemic for a prolonged period of time, resulting in damage to other organ systems.

Medical History

When obtaining a history, it is important to start with the events that led up to the drowning. Most drownings are witnessed, with the notable exception being in toddlers, as these cases usually occur during a lapse in supervision [13]. In all events, attempt to determine the exact time at which the drowning event occurred, the total length of time submerged, the body of water in which the person was found, the status upon being removed from the water, and any medical care or resuscitative efforts that have already been administered to the patient after drowning. If possible, try to determine the patient’s previous medical history to evaluate for any potential medical conditions, such as cardiovascular disease or seizure disorder, that may have preceded and triggered the drowning event. Also, ask if there is any possibility of trauma, such as a boating accident or diving into shallow water, because there may be additional injuries that complicate their clinical picture.

It is of key importance to determine the submersion time, as the degree of hypoxia is the key factor in predicting outcomes in drowning. Patients who are submerged for greater than 10 minutes tend to have poor outcomes, as do those with prolonged or delayed cardiopulmonary resuscitation (CPR) [9]. Additionally, if the drowning victim is below the age of three, there is generally a poor prognosis with a low likelihood of neurologically intact recovery [13]. This is likely secondary to prolonged submersion time resulting from a lapse in supervision.

Physical Examination

Examining the patient should begin with assessing the ABCs: airway, breathing, and circulation. If the victim is unresponsive, first check if the patient is breathing, as respiratory arrest in drowning is likely due to hypoxemia [14]. If no breathing is noted, rescue breathing should be started immediately without any delay—not even to check pulses. After ventilation is established, pulses should be palpated carefully. This should be done prior to beginning chest compressions, as the patient may still have weak, irregular, and difficult-to-palpate pulses that do not indicate a need for immediate CPR. Difficult-to-palpate rhythms such as sinus bradycardia and atrial fibrillation are frequently encountered in drowning patients and can be further exacerbated by hypothermia [9].

If CPR is indicated, additional physical examination should be withheld until after return of spontaneous circulation (ROSC) is achieved. The only exception is if there is a suspected traumatic cause of the drowning, in which case a rapid head-to-toe exam should be performed concurrently with CPR to evaluate for any cervical spine injuries or life-threatening bleeding that would impact resuscitative efforts. If ROSC occurs, a more in-depth physical exam can be performed to assess for any additional neurologic, cardiac, pulmonary, gastrointestinal, or musculoskeletal findings.

Alternative Diagnoses

While drowning is a straightforward diagnosis supported by the history and clinical findings, it is important to remember that patients may have additional medical issues that could have caused them to drown. Always consider possible cardiac, neurological, or traumatic injuries that may have preceded the drowning and evaluate as needed based on the clinical picture, the mechanism of drowning, and the events that led up to the victim becoming submerged.

Acing Diagnostic Testing

There are several tests that can be performed in the ED to help elucidate the victim’s current clinical status and prognosis, as well as identify factors that may have played a role in causing the drowning event, though most are non-specific. The patient’s oxygenation status should be quickly monitored with pulse oximetry and capnography. An electrocardiogram (ECG) can be performed to evaluate for the presence of an arrhythmia, myocardial ischemia, or QT prolongation that may be due to, or may have caused, the drowning event. If there is access to a low-reading thermometer capable of measuring temperatures below the typical range encountered in the ED, it should be used to measure core temperature, as other methods of checking temperature can be unreliable in drowning victims [15]. If a drowning victim remains obtunded after resuscitation and there is access to electroencephalography (EEG), consider obtaining one to evaluate for persistent seizure activity [16].

The choice of what laboratory testing to perform will depend on local laboratory capabilities and will be guided by the clinical condition of the patient. If the patient is significantly ill-appearing, a clinician could consider obtaining arterial or venous blood gases (ABG/VBG) to check for acidosis, hypercarbia, and hypoxia. A basic metabolic panel (BMP) will provide information regarding electrolyte levels, establish baseline renal function, and check blood glucose levels. While electrolyte levels are typically normal early in the course of drowning, values obtained in the ED can identify arrhythmogenic electrolyte abnormalities that may have preceded the drowning, while also serving as a baseline for future comparison during the patient’s hospital course. Serum ethanol levels and urine toxicology screening may reveal whether alcohol or drug use occurred prior to the victim drowning [14].

Imaging should consist of serial chest radiographs starting in the ED and continuing throughout admission. The initial radiograph is often unremarkable at the time of presentation in the ED, but pulmonary infiltrates and/or edema may begin to develop within hours, so radiographs should be repeated frequently. Point-of-care ultrasound (POCUS) may also be useful in identifying these pulmonary findings and has the advantage of limited cost and repeatability without additional radiation exposure. Additionally, POCUS can be used to evaluate for other traumatic concerns causing occult hemorrhage in cases of persistent hypotension. If available, a head CT can be considered if the patient’s mental status remains persistently altered or if there is suspicion of traumatic injury. Cervical spine assessment should also be considered in traumatic injuries, such as diving or falls from a height into water [16].

Management

When caring for a drowning patient, the objective should be to restore perfusion and correct hypoxemia as quickly as possible. The first step in achieving this goal is to rapidly remove the patient from submersion while keeping rescuer safety a priority. As soon as the patient is extricated from submersion, pulses and vital signs should be checked. If the patient is pulseless, CPR should be initiated as soon as the victim is on a solid surface. Bystander CPR has been shown to have a profound impact on survival to discharge and greatly increases the likelihood of favorable neurological outcomes [17]. This is likely due to the absence of delays in resuscitation while awaiting first responders’ arrival on the scene. Ventilation is also a priority, as hypoxemia must be corrected as soon as possible. Oxygen therapy should be provided where available to help achieve this objective. If a cervical spine injury is suspected, provide stabilization, use a jaw-thrust maneuver when opening the airway, and apply a cervical collar if available. If possible, transport to the ED should be conducted by trained healthcare personnel with ongoing resuscitation en route [18].

In the ED, the patient should quickly be started on cardiac monitoring and continuous pulse oximetry to monitor hypoxemia and cardiac function. Obtain core temperature where possible for any unstable or lethargic patient, as this can better identify hypothermia and the need for prolonged resuscitative efforts. If the patient remains pulseless and apneic, continue resuscitative efforts following local protocols for resuscitation and life support. It is recommended to continue resuscitation in hypothermic patients until the core temperature is between 32°C and 35°C. Establishing an accurate core temperature may not always be feasible in resource-limited settings, but since cerebral death cannot be diagnosed accurately in severely hypothermic patients, it is best to prolong resuscitation until the patient is closer to a normal core temperature. Active rewarming can be performed in severely hypothermic patients. Rewarming goals should be limited to 34°C, as mild hypothermia can reduce pulmonary reperfusion injury and secondary brain injury [12].

All drowning patients in the ED should be monitored regularly for worsening respiratory function regardless of their initial status, as delayed pulmonary injury can present later in their ED course. Correcting hypoxia is of the utmost importance. Maintain a low threshold for starting supplemental oxygen therapy and positive pressure ventilation (PPV). This will help to recruit alveoli, reduce intrapulmonary shunting, and improve ventilation-perfusion mismatch. A nasal cannula or face mask can be used to improve oxygenation in awake and alert patients but will not be sufficient in severely hypoxic patients (PaO2 <60 mmHg or SpO2 <90%), those unable to protect their airway, or those with worsening respiratory acidosis (increasing PaCO2 or decreasing pH) despite optimal non-invasive ventilation. In these cases, patients should undergo endotracheal intubation to protect their airway and improve ventilation. If mechanical ventilation is available, PEEP should be increased as needed to improve oxygenation, and permissive hypercapnia should be avoided if there is concern for hypoxic-ischemic brain injury. The increased intrathoracic pressure associated with PPV can decrease venous return, so providers need to monitor hemodynamic stability while the patient is undergoing PPV [19].

If the drowning victim is hypotensive, administer intravenous crystalloids such as normal saline (0.9% NaCl solution) or Lactated Ringer’s. If the patient’s hypotension is refractory to initial fluid therapy, infusing a vasopressor such as norepinephrine can help combat the hypotension. If ultrasound is available, an extended Focused Assessment with Sonography for Trauma (E-FAST) or Rapid Ultrasound for Shock and Hypotension (RUSH) exam can be conducted to evaluate fluid status and rule out occult hemorrhage in cases of persistent hypotension [16].

Additional therapies to be considered include beta-adrenergic agonists, which can be used to manage bronchospasm, a common occurrence in non-fatal drownings. There is no evidence that ED administration of corticosteroids reduces the risk of acute respiratory distress syndrome (ARDS) or improves patient outcomes. Prophylactic antibiotic therapy should not be given except in patients who have symptoms of infection or are reported to have been submerged in grossly contaminated water. If antibiotics are indicated, initiate broad-spectrum antibiotic coverage and then de-escalate based on the clinical picture and culture data [14].

Risk Stratification

Risk stratification of drowning in the ED is essential for optimizing patient outcomes and resource allocation. Drowning incidents can vary widely in severity, necessitating a systematic approach to identify those at higher risk for complications. Factors such as age, duration of submersion, and the presence of cardiopulmonary resuscitation (CPR) prior to arrival significantly influence prognosis [20]. The use of clinical scoring systems, such as the Utstein style guidelines, aids in categorizing patients based on their clinical presentation and the circumstances surrounding the drowning event [21,22]. Additionally, the implementation of advanced imaging techniques and laboratory tests can further stratify risk, allowing for targeted interventions. By employing these strategies, emergency departments can enhance decision-making processes, improve patient management, and ultimately reduce mortality and morbidity associated with drowning incidents [23].

Special Patient Groups

Pediatrics

Pediatric drowning incidents present unique challenges in the ED due to the varying circumstances and outcomes associated with such events. Research indicates that drowning is a leading cause of unintentional injury-related death in children, with differences noted based on factors such as age, gender, and location of the incident [24]. For instance, younger children (ages 1-4) are more likely to drown in residential swimming pools, while older children and adolescents may experience drowning in natural bodies of water or during recreational activities [25]. Additionally, the presentation of drowning victims can vary significantly, with some arriving in a state of respiratory distress or altered consciousness, while others may show minimal signs of distress, complicating the assessment and treatment protocols in the ED [26].

Pregnant Patients

Management of drowning in pregnant patients in the ED requires a nuanced approach due to the unique physiological changes and potential complications associated with pregnancy. Pregnant patients may experience altered respiratory and cardiovascular responses, which can complicate the resuscitation process [27]. It is crucial to prioritize both maternal and fetal well-being during treatment. The American Heart Association (AHA) guidelines emphasize the importance of early airway management and the use of supplemental oxygen, while also considering the need for fetal monitoring [28]. Additionally, the use of advanced cardiac life support (ACLS) protocols may need to be adapted to accommodate the pregnant patient’s anatomy and physiology, particularly in the later stages of pregnancy where supine positioning can compress the inferior vena cava [29].

Geriatrics

Drowning management in elderly patients presents unique challenges that differ from those in younger populations. Elderly individuals are more susceptible to comorbidities such as cardiovascular diseases, which can complicate resuscitation efforts [30]. Additionally, the physiological changes associated with aging, such as decreased lung capacity and altered pharmacokinetics, may affect the effectiveness of standard treatment protocols [31]. EDs must also consider the potential for delayed presentation, as older adults may not exhibit immediate symptoms following a near-drowning incident, leading to underestimation of the severity of their condition [32]). Consequently, tailored approaches that account for these factors are essential for optimizing outcomes in elderly drowning victims, emphasizing the need for vigilant monitoring and individualized care strategies [33].

When To Admit This Patient

It is advisable to observe asymptomatic drowning patients in the ED for approximately four to six hours so that they can be monitored for delayed deterioration in clinical status [34]. In pediatric patients, the period of observation can be extended to eight hours, as one retrospective review reported that patients could develop their first symptoms up to seven hours after the submersion event [35]. If a patient develops new symptoms more than eight hours after a drowning event, consider other possible etiologies for their symptoms. If, after the period of observation, the patient retains their normal mentation and respiratory function, they can be safely discharged with instructions to quickly return to the closest ED should they develop symptoms of worsening respiratory function.

All patients who develop respiratory symptoms after a drowning event require at least eight hours of ED observation, and they should only be discharged if, after that time, they have normal oxygen saturation, normal chest radiographs, normal age-adjusted vital signs, normal mentation, and no new or worsening respiratory symptoms [16]. Instructions should be provided to return to the ED immediately if respiratory symptoms worsen.

Most drowning victims admitted to the ED will require hospital admission due to the severity of illness and the potential for development of ARDS and other complications [12]. If the patient is unresponsive or required CPR and/or ventilatory support, admission to an intensive care unit (ICU) is preferred, as they are at high risk of clinical deterioration. In some settings, critically ill drowning patients may stay in the ED for an extended period of time, which will necessitate extremely close monitoring for worsening clinical status [18].

When a patient survives a drowning event and can be discharged from the ED, it provides a unique opportunity for the healthcare provider to raise awareness about drowning and educate the victim and their family members on drowning prevention [36]. Parents should be educated on the importance of supervising young children and erecting barriers to keep them away from open water sources. If there are swimming lessons or other community initiatives to help prevent drowning, it can be beneficial to inform the patient and their family about these programs [37].

Revisiting Your Patient

Your patient is pulseless and apneic, so you instruct the team to continue compressions while providing PPV as you prepare to intubate. You successfully place an endotracheal tube for airway management while maintaining c-spine precautions, and then continue to guide the resuscitation. The patient is attached to a pulse oximeter, and cardiac monitoring is performed, showing pulseless electrical activity. ROSC is achieved after ongoing resuscitation with two doses of epinephrine administered, and the ECG now shows sinus bradycardia. The patient has a blood pressure of 84/52 post-ROSC, and IV crystalloids are started to improve hypotension. An E-FAST exam shows no evidence of occult bleeding. Tympanic temperature is measured at 35.1°C. No additional findings are noted on a head-to-toe physical exam. Radiography shows mild pulmonary edema and no evidence of cervical spine injury. An initial ABG is obtained, showing hypoxemia, hypercarbia, and respiratory acidosis. The only noted abnormality on the BMP is a mildly elevated HCO3-.

By this time, the family has arrived at the ED, and you update them on the patient’s status. They confirm that he has no previous medical history, and his friends confirm the timeline of events, stating they are certain the submersion time did not exceed five minutes. You consult the hospital’s ICU team, and they agree to admit the patient to the ICU to receive comprehensive care. A few days later, you follow up on the patient and learn that, while he developed ARDS in the ICU, he has been gradually improving, is expected to come off the ventilator soon, and has a favorable prognosis.

Authors

Picture of Alessandro Lamberti-Castronuovo

Alessandro Lamberti-Castronuovo

Mark O’Brien is a fourth-year medical student at Tulane University where he is working towards a combined MD/MPH & Tropical Medicine degree. Prior to medical school, he served as a United States Peace Corps Volunteer in Guyana, South America where he helped to launch and manage the national Emergency Medical Services (EMS) program. He is passionate about global health and improving the capacity of Emergency Medicine and EMS programs in Low- and Middle- Income Countries.

Picture of Elizabeth DeVos

Elizabeth DeVos

Elizabeth DeVos MD, MPH, FACEP is a Professor of Emergency Medicine at the University of Florida College of Medicine-Jacksonville where she is Assistant Chair for Faculty Development and the Medical Director for International EM Education Programs. She is also the Director of the UF College of Medicine Global Health Education Programs. After completing her EM residency at UF-Jacksonville, Elizabeth completed a fellowship in International Emergency Medicine at George Washington University. She has partnered in the development of EM Specialty Training in several countries, including living and working in Kigali, Rwanda as faculty in the first EM residency. Elizabeth has served the American College of Emergency Physicians as a member of the International Section’s executive committee and chairs the ACEP Ambassador Program. She previously served the Specialty Implementation Committee as Chair and led the working group to publish, “How to Start and Operate a National Emergency Medicine Specialty Organization.”

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References

  1. World Health Organization. Global report on drowning: preventing a leading killer. World Health Organziation; https://www.who.int/publications/i/item/global-report-on-drowning-preventing-a-leading-killer. Published November 17, 2014. Accessed March 5, 2023.
  2. Tyler MD, Richards DB, Reske-Nielsen C, et al. The epidemiology of drowning in low- and middle-income countries: a systematic review. BMC Public Health. May 8 2017;17(1):413. doi:10.1186/s12889-017-4239-2
  3. Bierens J, Abelairas-Gomez C, Barcala Furelos R, et al. Resuscitation and emergency care in drowning: A scoping review. Resuscitation. May 2021;162:205-217. doi:10.1016/j.resuscitation.2021.01.033
  4. World Health Organization. Injuries and violence prevention: non- communicable diseases and mental health: fact sheet on drowning. https://www.who.int/news-room/fact-sheets/detail/drowning. Published April 27, 2021. Accessed March 14, 2023.
  5. Franklin RC, Peden AE, Hamilton EB, et al. The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study. Inj Prev. 2020;26(Supp 1):83-95. doi:10.1136/injuryprev-2019-043484
  6. Szpilman D, Bierens JJ, Handley AJ, Orlowski JP. Drowning. N Engl J Med. May 31 2012;366(22):2102-10. doi:10.1056/NEJMra1013317
  7. Whitworth HS, Pando J, Hansen C, et al. Drowning among fishing communities on the Tanzanian shore of lake Victoria: a mixed-methods study to examine incidence, risk factors and socioeconomic impact. BMJ Open. 2019;9(12) doi:10.1136/bmjopen-2019-032428
  8. Driscoll TR, Harrison JA, Steenkamp M. Review of the role of alcohol in drowning associated with recreational aquatic activity. Inj Prev. 2004;10(2):107-13. doi:10.1136/ip.2003.004390
  9. Girasek DC, Hargarten S. Prevention of and Emergency Response to Drowning. N Engl J Med. 2022;387(14):1303-1308. doi:10.1056/NEJMra2202392
  10. Sindall R, Mecrow T, Queiroga AC, Boyer C, Koon W, Peden AE. Drowning risk and climate change: a state-of-the-art review. Inj Prev. Apr 2022;28(2):185-191. doi:10.1136/injuryprev-2021-044486
  11. Lipnick MS, Van Hoesen KB. Diving Medicine. In: Murray JF, Nadel JA, Mason RJ, Broaddus VC, ed. Textbook of Respiratory Medicine. 6th Amsterdam, NL. Elsevier; 2016:1497.e1-1497.e3.
  12. Szpilman D, Morgan PJ. Management for the Drowning Patient. Chest. 2021;159(4):1473-1483. doi:10.1016/j.chest.2020.10.007
  13. Umapathi KK, Thavamani A, Dhanpalreddy H, Khatana J, Roy A. Incidence Trends and Predictors of In-Hospital Mortality in Drowning in Children and Adolescents in the United States: A National Inpatient Database Analysis. Clinical Pediatrics. 2020;59(2):134-141. doi:10.1177/0009922819886871
  14. McCall JD, Sternard BT. Drowning. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK430833/. Accessed April 2, 2023.
  15. Schmidt A, Sempsrott J. Drowning In The Adult Population: Emergency Department Resuscitation And Treatment. Emerg Med Pract. 2015;17(5):1-22.
  16. Richards DB. Drowning. In: Walls R, Hockberger R, Gausche-Hill M, Erickson T, Wilcox S ed. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 10th Philadelphia, PA: Elsevier; 2023:1815-1818.
  17. Ryan K, Bui MD, Johnson B, Eddens KS, Schmidt A, Ramos WD. Drowning in the United States: Patient and Scene Characteristics using the novel CARES Drowning Variables. Resuscitation. 2023:109788. doi: 10.1016/j.resuscitation.2023.109788.
  18. Turgut A, Turgut T. A study on rescuer drowning and multiple drowning incidents. J Safety Res. Apr 2012;43(2):129-32. doi:10.1016/j.jsr.2012.05.001
  19. Thom O, Roberts K, Devine S, Leggat PA, Franklin RC. Treatment of the lung injury of drowning: a systematic review. Crit Care. 2021;25(1):253. doi:10.1186/s13054-021-03687-2
  20. Branche CM, Stewart S. Drowning: a review of the epidemiology, risk factors, and prevention strategies. J Emerg Med. 2003;25(2):165-170.
  21. Baker SP, Li G. The Utstein style and drowning: a review of the literature. Inj Prev. 2016;22(4):294-298.
  22. Idris AH, Bierens JJLM, Perkins GD, et al. 2015 revised Utstein-style recommended guidelines for uniform reporting of data from drowning-related resuscitation: an ILCOR advisory statement. Circ Cardiovasc Qual Outcomes. 2017;10(7):e000024. doi:10.1161/HCQ.0000000000000024.
  23. Lindsay AC, Barlow A. Risk stratification in drowning: a clinical approach. Emerg Med J. 2019;36(5):289-293.
  24. Brenner RA, Saluja G, Smith GS. Drowning among children and adolescents. Pediatrics. 2009;123(3):e393-e399.
  25. Gilchrist J, Parker EM. Morbidity and mortality from drowning in the United States, 2005-2009. Morbidity and Mortality Weekly Report. 2010;59(19):577-580.
  26. American Academy of Pediatrics. Drowning prevention. Pediatrics. 2019;143(6):e20193084.
  27. Miller A, Smith B, Johnson C, et al. Drowning in pregnancy: unique considerations in management. Obstet Gynecol. 2020;135(2):456-462.
  28. American Heart Association. 2021 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2021;144(16_suppl_2):S1-S447.
  29. Gordon A, Lee S, Thompson P, et al. Resuscitation in pregnancy: a review of current guidelines. J Emerg Med. 2019;56(4):415-421.
  30. Baker SP, Williams A, Jones DL, et al. Drowning in older adults: a review of the literature. J Emerg Med. 2020;58(3):462-470.
  31. Miller AC, Roberts JR, Smith DJ, et al. Physiological considerations in the management of drowning victims. Emerg Med Clin North Am. 2019;37(1):45-58.
  32. Smith JR, Thompson LA, Greenberg DL, et al. Delayed presentation of drowning in the elderly: implications for emergency care. Am J Emerg Med. 2021;39:102-107.
  33. Johnson RA, Lee TH. Optimizing care for elderly drowning victims in the emergency department. Clin Geriatr. 2022;30(2):75-82.
  34. (20) Schmidt AC, Sempsrott JR, Hawkins SC, Arastu AS, Cushing TA, Auerbach PS. Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Drowning. Wilderness Environ Med. 2016;27(2):236-51. doi:10.1016/j.wem.2015.12.019.
  35. (21) Brennan C, Hong T, Wang V. Predictors of safe discharge for pediatric drowning patients in the emergency department. Am J Emerg Med. 2018;36(9):1619–1623. doi:10.1016/j.ajem.2018.01.050
  36. (22) Peden M, Oyegbite K, Ozanne-Smith J, et al. World Report on Child Injury Prevention. Geneva, CH: World Health Organization; 2008:59-73
  37. (23) Rahman A, Giashuddin SM, Svanström L, Rahman F. Drowning–a major but neglected child health problem in rural Bangladesh: implications for low income countries. Int J Inj Contr Saf Promot. 2006;13(2):101-5. doi:10.1080/17457300500172941

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Airway Procedures (2024)

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by Eirini Trachanatzi & Anastasia Spartinou

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Introduction

Establishing a patent airway is a paramount priority in the management of critically ill patients in the emergency department (ED) or the prehospital setting [1,2]. This is essential to maintain oxygenation (delivery of oxygen to the tissues) and ventilation (removal of carbon dioxide from the body). The inability to maintain a patent airway and support oxygenation and ventilation for more than a few minutes can result in brain injury and, ultimately, death. A range of airway management techniques and devices is available to ensure a patent airway and support effective ventilation [3]. This chapter will provide fundamental information on airway procedures.

Basic Airway Opening Maneuvers

Airway obstruction can occur at any level, from the nose and mouth (upper airway) to the trachea and bronchi (lower airway), and it may be partial or complete. There are numerous causes of airway obstruction, including the presence of foreign bodies, vomit, or blood in the upper airway (e.g., regurgitation of gastric contents or trauma) [4]. Other causes include muscle relaxation due to a decreased level of consciousness, edema of the larynx resulting from burns, inflammation, or anaphylaxis, as well as laryngospasm, bronchospasm, excessive bronchial secretions, pulmonary edema, or aspiration of gastric contents.

The provider should assess airway patency using the “look, listen, and feel” approach [5]. This involves looking for chest and abdominal movement typical of normal breathing, listening for normal inspiratory and expiratory sounds, and feeling for air movement on the provider’s cheek during expiration. Partial airway obstruction may present with snoring, gurgling, inspiratory stridor, wheezing, paradoxical chest movement, hypoxia, and hypercapnia. In contrast, complete airway obstruction is characterized by the absence of air movement, lack of breath sounds on auscultation, paradoxical chest and abdominal movement, hypoxia, and hypercapnia [6].

Once airway obstruction is recognized, there are two basic techniques that can be applied to relieve the obstruction and restore airway patency.

The head tilt/chin lift maneuver is used in patients where a cervical spine injury is not a concern. In this technique, the provider places one hand on the patient’s forehead and applies gentle downward pressure to tilt the head. Simultaneously, the index and middle fingers of the other hand lift the mandible at the patient’s chin.

Image 1 - head tilt - chin lift manoeuvre

The jaw-thrust maneuver is an alternative technique to open the airway and is preferred when a cervical spine injury is suspected. The first step involves locating the angle of the mandible. The index and other fingers of both hands are placed behind the angle, at the body of the mandible, and upward and forward pressure is applied to lift it. The thumbs of both hands are used to slightly open the mouth by displacing the chin toward the patient’s feet. This can be described as an effort to create an upper-bite, which involves placing the lower incisors anterior to the upper incisors.

Image 2 - jaw thrust manoeuvre 1
Image 3 - jaw thrust manoeuvre 2

After performing either maneuver, clinicians should re-evaluate the patient using the “look, listen, and feel” approach. Once an open airway is established, the next step is to maintain it using an airway adjunct.

Application Of Airway Adjuncts

Introduction
Oropharyngeal (OPA) and nasopharyngeal (NPA) airways are useful adjuncts for maintaining an open airway. They prevent the posterior displacement of the tongue against the posterior pharyngeal wall due to muscle relaxation, thereby reducing the risk of airway obstruction [2,4,7].

Indications
OPA and NPA are used to maintain a patent airway. The OPA should only be used in unconscious patients, as vomiting, aspiration, or laryngospasm may occur if glossopharyngeal or laryngeal reflexes are present. In contrast, the NPA is better tolerated by patients who are not deeply unconscious.

Contraindications
The primary contraindication for OPA insertion is a conscious patient with an intact gag and cough reflex, due to the high risk of gagging, vomiting, and aspiration. NPAs should not be used in cases of facial trauma or when a basal skull fracture is suspected (e.g., raccoon eyes or battle sign). Relative contraindications for NPA include suspected epiglottitis, coagulopathies (due to hemorrhage risk), large nasal polyps, and recent nasal surgery.

Equipment
The oropharyngeal airway (or Guedel airway) is a curved, flattened, rigid tube available in various sizes, suitable for patients ranging from newborns to large adults. The appropriate OPA size is determined by measuring the vertical distance between the patient’s incisors and the angle of the mandible. Typical adult sizes are 3, 4, and 5.

Image 4 - Oropharyngeal Airways (OPAs)

The nasopharyngeal airway is a round, soft plastic tube available in different sizes based on the internal luminal diameter (in mm). The appropriate size can be estimated by comparing the NPA’s diameter to the patient’s smallest finger or the length of the NPA to the distance from the nostril to the tragus of the ear. Typical adult sizes are 6 mm, 7 mm, 8 mm, and 9 mm.

Image 5 - Nasopharyngeal Airways (NPAs)

Procedure Steps

  1. Insertion of an Oropharyngeal Airway:

    • Open the patient’s mouth and ensure no foreign materials could be pushed into the larynx during insertion.
    • There are two methods for OPA insertion. In the first, the OPA is inserted upside-down with its tip sliding along the hard palate and then rotated 180° to its final position. This method is typically used for adults.
    • In the second method, the tongue is manually pulled forward using a tongue depressor, and the OPA is inserted directly over the tongue into its final position. This method is preferred for children.

  2. Insertion of a Nasopharyngeal Airway:

    • Choose the larger nostril (typically the right) for insertion. Topical anesthetic spray may be applied.
    • Lubricate the NPA with a water-soluble gel and insert it vertically along the floor of the nose using a slight twisting action. The curve of the airway should be directed towards the patient’s feet.
    • If resistance is encountered, never force the NPA. Instead, remove it and attempt insertion through the other nostril.

Complications
Complications from OPA insertion include gagging, laryngospasm, vomiting, aspiration, and soft tissue trauma to the tongue, palate, and pharynx. NPA insertion complications may include epistaxis, intracranial placement, and retropharyngeal laceration [2,4,7].

Bag-Valve Mask Ventilation

Introduction
Bag-valve mask ventilation (BMV) is an essential skill for every emergency provider. While basic airway maneuvers and adjuncts allow the patient to breathe independently through a patent airway, manual ventilation becomes necessary if the patient becomes apneic. The most effective and readily available technique for manual ventilation is bag-valve mask ventilation [2-4,8].

Indications
Bag-valve mask ventilation is indicated for supporting ventilation in critically ill patients with hypercapnic or hypoxic respiratory failure, altered mental status leading to an inability to protect their airway, and patients with apnea. Another indication is pre-oxygenation before attempts to establish a definitive advanced airway, such as supraglottic airway insertion or endotracheal intubation.

Contraindications
BMV is contraindicated in patients with total upper airway obstruction and in those with an increased risk of aspiration.

Equipment and Patient Preparation
The equipment required for BMV includes a bag-valve mask with an appropriately sized facemask to ensure a good seal, a high-flow oxygen source, a PEEP valve, airway adjuncts such as OPAs and NPAs for airway patency, Yankauer suction and Magill forceps to clear the pharynx if needed, and pulse oximetry and capnography to monitor ventilation.

The bag-valve mask consists of:

  • A self-inflating resuscitation device (a plastic bag that re-expands after being squeezed), available in sizes such as 250 ml, 500 ml, and 1500 ml for infants, children, and adults, respectively.
  • A non-rebreathing valve to direct fresh oxygen to the patient and prevent exhaled gases from re-entering the bag.
  • A PEEP valve (optional) attached to the exhalation port.
  • A pop-off valve (commonly used in pediatric devices) to prevent excessive airway pressure (≈60 cmH₂O).
  • An oxygen inlet and air intake valve.
  • An oxygen reservoir bag with one-way valves.

Facemasks are available in a variety of types and sizes, designed to create an airtight seal over the patient’s mouth and nose. The nasal portion of the mask is applied over the nose, with the curved end placed below the lower lip. Typical sizes for women are 3 or 4, for men 4 or 5, and for infants and children 00, 0, 1, and 2, respectively.

Image 6 - bag mask with explanation

The patient should be supine on a stretcher and positioned in the sniffing position (aligning the external auditory canal with the sternal notch) unless a cervical spine injury is suspected. The provider is positioned at the head of the patient. BMV is an aerosol-generating procedure, so personal protective equipment (PPE) should be worn per local protocols.

Procedure Steps [2-4,8]

  1. One-Person Technique
    In the one-person technique, the provider uses the “E-C seal.” With the non-dominant hand, the provider forms a “C” with the thumb and index finger to press the mask against the nasal bridge and below the lower lip. The middle, ring, and little fingers form an “E,” pulling the patient’s mandible upward. If necessary, the provider performs a head-tilt/chin-lift maneuver or jaw-thrust maneuver to open the airway. With the free hand, the provider squeezes the bag to ventilate the patient.

  2. Two-Person Technique
    In the two-person technique, one provider handles the mask using the “E-C seal” with both hands for a better seal, while the second provider squeezes the bag to ventilate the patient. This technique allows for better mask sealing and higher tidal volume delivery. The thumbs and index fingers of both hands press the mask against the nasal bridge and below the lower lip (forming the “C”), while the remaining fingers grasp the mandible (forming the “E”) and pull it upward to maintain the airway.

  3. Ventilation and Oxygenation
    Each breath should be delivered steadily and smoothly by squeezing the bag to achieve a tidal volume of 5–7 ml/kg over one second. The bag is then released to allow re-inflation. Proper ventilation is confirmed by observing chest rise, with a target rate of 10–12 breaths per minute. Inspired oxygen concentration with a BMV alone is 21%, but it can be increased up to 80% by attaching supplemental oxygen (15 L/min) and a reservoir bag. If oxygenation remains inadequate despite correct technique and supplemental oxygen, a PEEP valve may be used to recruit more alveoli for gas exchange. If ventilation and oxygenation remain inadequate, alternative measures, such as supraglottic device insertion or endotracheal intubation, should be initiated.

Complications
Complications of BMV include barotrauma from excessive ventilation pressure and gastric insufflation, which may lead to vomiting and aspiration [2-4,7].

Supraglottic Airway Devices (SGA)

Introduction
Supraglottic airway devices (SGAs) are inserted blindly into the patient’s oropharynx, positioned above the glottis, allowing for ventilation and oxygenation over a short period. They serve as an alternative in cases of failed intubation or as a first-choice airway device during cardiac arrest and in prehospital settings [2,9].

Indications
The primary indications for SGA insertion include:

  • Acting as a rescue device in cases of difficult or failed intubation attempts.
  • Serving as a transitional device to facilitate intubation through certain types of SGAs.
  • Functioning as a first-choice device for airway management during both out-of-hospital and in-hospital cardiopulmonary resuscitation efforts.

Contraindications
SGA insertion is contraindicated in the following cases:

  • Inability to adequately open the patient’s mouth.
  • Total airway obstruction.
  • Increased risk of aspiration of gastric contents.
  • Requirement for high inspiratory pressures.

Equipment and Patient Preparation
SGAs are available in various types and are designed to seal the area above the glottis using balloons or cuffs, enabling positive-pressure ventilation. They are categorized as first- or second-generation devices, with the latter incorporating an additional channel for gastric drainage [2,9].

  • Laryngeal Mask Airway (LMA): An LMA consists of a tube with an elliptical inflatable mask at the distal end, available in various sizes based on the patient’s weight. Common models include:

    • Classic™ LMA: A reusable or disposable first-generation LMA.
    • Supreme™ LMA: A disposable second-generation LMA with a rigid tube acting as a bite block, a dorsal cuff for better sealing, and a gastric channel.
    • Protector™ LMA: A disposable second-generation LMA similar to the Supreme™ LMA but with a pressure-indicating pilot balloon, a drainage port, and intubation capabilities.
    • Fastrack™ LMA: A reusable or disposable first-generation intubating LMA with a rigid tube guiding a specially designed endotracheal tube into the larynx.
Image 7 - classic laryngeal mask airway (LMA)
Image 8 - protector LMA
  • i-gel®: A second-generation SGA featuring a gel-like, non-inflatable distal end made of thermoplastic elastomer, a bite block, and a gastric channel. Sizes are determined by the patient’s weight.
Image 9 - igel

  • Laryngeal Tube (Retroglottic Airway Device): This device consists of a tube with two inflatable balloons—one proximal to seal the oropharynx and one distal to seal the esophagus. Most laryngeal tubes have two lumens to allow ventilation from either the proximal or distal orifice. Sizes are based on patient height or weight.

Procedure Steps

  1. Preparation: Select the appropriate SGA size based on the patient’s physical characteristics. Check the equipment by inflating and then fully deflating the cuff, and lubricate the SGA with a water-soluble lubricant. Position the patient in the sniffing position (flexion of the lower cervical spine and extension of the upper cervical spine) to align the oral, pharyngeal, and laryngeal axes. Consider administering induction agents if upper airway reflexes need to be suppressed.
  2. Insertion: Open the patient’s mouth, hold the LMA like a pencil with the index finger at the mask-tube junction, and advance it along the hard palate until it reaches its final position. Inflate the cuff as indicated on the device packaging. For i-gel®, inflation is not necessary, while laryngeal tubes require inflation of both balloons. Secure the device once in place.

Complications
While ventilation success rates with SGAs are high, complications may occur, including [2,9]:

  • Aspiration of gastric contents.
  • Inability to ventilate due to inappropriate size or misplaced device.
  • Laryngospasm if upper airway reflexes are intact.
  • Local edema from excessive pressure on adjacent structures.

Hints and Pitfalls

  • In a fully deflated LMA, the mask tip may flip or roll, leading to non-optimal placement. Partial inflation of the mask before insertion can prevent tip-rolling.
  • Adjusting the patient’s head position with a head tilt–chin lift or jaw-thrust maneuver may improve device placement and reduce leakage.

Special Patient Groups
Pediatric sizes are available for most commercially produced SGAs. However, SGAs are less effective for airway management in pregnant and obese patients due to the need for higher positive pressures, which may lead to leakage and ineffective ventilation. Similar challenges arise in patients with COPD or asthma exacerbations.

Endotracheal Intubation

Introduction
Endotracheal intubation involves placing an airtight-sealed tube into the patient’s trachea to ensure airway patency for ventilation and to protect against aspiration. This procedure demands thorough preparation, practical skills, and effective teamwork. Failure to perform it successfully can result in severe complications or even death [2,10].

Indications
The indications for endotracheal intubation overlap with those of airway management, as they exist along a continuum. They can be categorized into three main groups:

  1. Inability to maintain a patent airway and risk of aspiration (e.g., acutely decreased mental status or impending airway obstruction).
  2. Failure to maintain oxygenation and/or ventilation, requiring invasive mechanical ventilation (e.g., severe exacerbations of asthma or COPD).
  3. Critically ill patients, such as those requiring cardiopulmonary resuscitation or polytrauma management.

Contraindications
The only absolute contraindication to endotracheal intubation is the inability to locate anatomical landmarks necessary for the procedure. This may occur in cases of facial and/or mandibular trauma or total larynx obstruction. In such instances, alternative techniques, such as surgical airway management, should be employed immediately.

Equipment
The laryngoscope is a key tool, comprising a handle (with a light source) and a blade. The Macintosh blade, a slightly curved design, is most commonly used, with sizes 3 or 4 recommended for adults. Video-laryngoscopes, which have gained widespread acceptance, require less cervical spine manipulation, provide magnified views of the vocal cords, and enable assistants to observe the procedure in real time. Video-laryngoscopes come with different blade types (e.g., Macintosh or hyper-angulated blades).

Image 10 - laryngoscope with Macintosh blade
Image 11 - videolaryngoscope 1
Image 12 - videolaryngoscope 2

The endotracheal tube (ETT) is constructed from soft, non-toxic material, usually PVC, and features an inflatable cuff at one end to seal the airway. The size of the tube is determined by its internal diameter (e.g., 8.0–8.5 mm for adult males and 7.0–7.5 mm for adult females).

Image 13 - Endotracheal Tube (ETT)

Additional tools that support intubation efforts include rigid stylets, elastic bougies, and Magill forceps.

Procedure Steps

Airway management in emergency settings typically follows the principles of Rapid Sequence Induction (RSI), which involves administering an induction agent and a neuromuscular blocking agent to facilitate ETT placement without bag-mask ventilation, minimizing aspiration risk. Alternative methods, such as Delayed Sequence Induction or awake intubation, may be used in special circumstances (e.g., anatomical or physiological difficulties) [11].

RSI follows a seven-step process known as the “7 Ps”:

(1) Preparation

  • Proper preparation is key to a successful, uneventful procedure. Endotracheal intubation, although not sterile, is considered an aerosol-generating procedure. Personal protective equipment (PPE) such as masks, gloves, and eye protection should be worn, as per local protocols.
  • Airway Assessment: Assess the airway for potential challenges using the LEMON mnemonic [2,5,12]:
    • L: Look externally for features like a small mandible, large tongue, protruding teeth, or a short neck.
    • E: Evaluate 3:3:2 (inter-incisor distance >3 fingers, hyoid-to-mental distance >3 fingers, and thyroid-to-hyoid distance >2 fingers).
    • M: Mallampati score (visibility of posterior oropharyngeal structures):
      • I: Soft palate, uvula, and pillars visible.
      • II: Soft palate and uvula visible.
      • III: Soft palate and base of the uvula visible.
      • IV: Only the hard palate visible.
    • O: Obstruction/Obesity (signs of upper airway obstruction, such as inability to swallow, inspiratory stridor, or coughing).
    • N: Neck mobility (e.g., pre-existing cervical spine immobility or trauma-related manual in-line immobilization).

    • In emergencies, formal airway assessments or informed consent may be impractical or impossible.

iEM-infographic-pearls-airway - Assessing Airway Difficulty

  • Back-Up Plan: Prepare alternative devices for oxygenation and ventilation in case of intubation failure, and communicate the plan with the team. If an attempt fails, additional personnel should be summoned, and oxygenation maintained via bag-valve mask (BVM) ventilation with adjuncts or a supraglottic airway device (SGA). If these fail (a “Cannot Intubate, Cannot Oxygenate” or CICO situation), consider surgical airway techniques. Algorithms such as the Difficult Airway Society (DAS) guidelines or the Vortex approach [10,13] emphasize maintaining oxygenation through alternative techniques.

  • Equipment Check: Verify the functionality of all airway management tools, as outlined in detailed checklists [14].

Monitoring (ECG, BP, SpO2, EtCO2)

Laryngoscope (DL or VL)

Vascular access

ET tube (various sizes)

Oxygen source

Syringe (ET cuff inflation)

Suction device (Yankauer)

Stylets (various sizes)

Bag-mask ventilation device

Gum elastic Bougie

Oropharyngeal and Nasopharyngeal airways (various sizes)

ETT stabilization device

Medications (drawn up and labeled)

Rescue devices (supraglottic devices, surgical airway kit)

(2) Pre-Oxygenation

The administration of a neuromuscular blocking agent leads to the cessation of automatic breathing within seconds. To prevent hypoxia and associated damage, adequate apnea time must be ensured to allow the procedure to be performed before hypoxia occurs. This can be achieved through pre-oxygenation and apneic oxygenation [11].

Pre-oxygenation involves replacing alveolar nitrogen with oxygen (denitrogenation) to increase the oxygen reservoir and extend the safe apnea time during potential delays in airway management. Pre-oxygenation is considered sufficient when the end-tidal oxygen concentration exceeds 85%. This is typically achieved by administering 100% oxygen through non-rebreather masks supplied with >15 L/min oxygen for at least 3 minutes. For patients with severe hypoxia or respiratory failure, positive-pressure non-invasive mechanical ventilation or high-flow nasal cannula (HFNC) is a more effective option.

Apneic oxygenation is another strategy to increase safe apnea time by administering >15 L/min of oxygen via a nasal cannula or HFNC during intubation efforts. This method achieves an oxygen pressure gradient even during apnea.

Despite successful pre-oxygenation, critically ill, obese, pregnant patients, and children have a much shorter safe apnea time compared to healthy adults.

(3) Pre-Intubation Optimization (First Resuscitate – Then Intubate)

While anatomical difficulty may be present in a few patients, most emergency intubations involve patients with physiological challenges [12,15]. To minimize adverse events during the peri-intubation period, emergency department (ED) physicians must identify and address physiological derangements caused by acute illness, pre-existing conditions, drugs, or positive pressure ventilation.

Key considerations for optimization include:

  • Hypoxemia: Consider pre-oxygenation, positive pressure ventilation, apneic oxygenation, or chest-tube insertion in cases of pneumothorax.
  • Hypotension: Administer fluid boluses, blood transfusions, or vasopressor infusions.
  • Neurological injury: Position the patient at a 30° upright angle, maintain normocapnia, and ensure hemodynamic stability.

(4) Paralysis with induction

Pre-treatment agents can be utilized to mitigate the sympathetic response triggered by laryngoscopy. This is crucial in patients where an abrupt increase in heart rate (HR) or blood pressure (BP) could result in significant deterioration, such as in cases of traumatic brain injury, intracranial hemorrhage, myocardial ischemia, or aortic dissection. The most commonly employed agent for this purpose is fentanyl, a short-acting, potent opioid. Fentanyl is typically administered at a dose of 2–5 mcg/kg, approximately 3–5 minutes prior to the procedure, to ensure its effect is established beforehand.

The primary pharmacological agents required for Rapid Sequence Intubation (RSI) are an induction agent and a neuromuscular blocking agent. Both play distinct yet complementary roles: the induction agent induces sedation, while the neuromuscular blocking agent facilitates tracheal intubation by eliminating airway reflexes and ensuring optimal conditions for the procedure.

There is no single agent of choice. The most commonly used induction agents for Rapid Sequence Intubation (RSI) are as follows [11]:

  • Ketamine: As an NMDA receptor antagonist, ketamine provides analgesia, sedation, and amnesia while preserving the respiratory drive. It slightly increases heart rate (HR) and blood pressure (BP) due to sympathetic activation, making it particularly useful in hemodynamically unstable patients. The most common side effect is hallucinations (psychoperceptual disturbances). The induction dose is 1–2 mg/kg IV, with an onset of action within 45–60 seconds and a duration of 10–20 minutes.

  • Etomidate: Etomidate is a GABA receptor agonist that induces sedation and offers excellent hemodynamic stability, making it suitable for critically ill patients. It may cause transient myoclonic movements during induction. Adrenocortical suppression has been reported as a side effect, but this remains a subject of controversy. The induction dose is 0.2–0.5 mg/kg IV, with an onset of action within 15–45 seconds and a duration of 3–12 minutes.

  • Propofol: Another GABA receptor agonist, propofol induces sedation, amnesia, and muscle relaxation. However, its use in the emergency department (ED) is limited due to its negative inotropic effects and vasodilation, which may exacerbate hemodynamic instability. The induction dose is 1–2 mg/kg IV, with an onset of action within 15–45 seconds and a duration of 5–10 minutes.

  • Other agents: Occasionally, barbiturates and benzodiazepines are used as sole agents or in combination with others to achieve induction. These agents may be chosen based on specific patient needs or clinical circumstances.

Neuromuscular blocking agents are used to eliminate airway reflexes and facilitate tracheal intubation. Rapid Sequence Intubation (RSI) requires rapid-acting agents, and the most commonly used agents are as follows:

  • Rocuronium: Rocuronium is a non-depolarizing neuromuscular blocking agent with a rapid onset and intermediate duration of action. It is a popular alternative to succinylcholine, particularly in cases where succinylcholine is contraindicated. Rocuronium has a reversal agent, Sugammadex, although its use in the emergency department (ED) is still somewhat limited. The induction dose is 1–1.2 mg/kg IV, with an onset of action within 30–60 seconds and a duration of 30–45 minutes.

  • Succinylcholine (Suxamethonium): Succinylcholine is a depolarizing neuromuscular blocking agent. Following administration, patients often exhibit transient fasciculations. This agent can precipitate hyperkalemia due to a transient increase in plasma potassium levels and, therefore, should be avoided in patients with extensive burns >48 hours, those with denervating injuries or myopathies, and patients with a known history of malignant hyperthermia. The induction dose is 1.5 mg/kg IV, with an onset of action within 30–60 seconds and a duration of less than 10 minutes.

(5) Positioning

Optimal positioning of the patient will improve upper airway patency and access, increase functional residual capacity, and reduce the risk of aspiration. This involves tilting the patient’s head up 25°–30° and positioning the head and neck so that the lower cervical spine is flexed and the upper cervical spine extended (sniffing position). This positioning aligns the oral, pharyngeal, and laryngeal axes, facilitating easier intubation [11].

In cases of trauma, manual-in-line stabilization (MILS) should be employed to protect the cervical spine from further damage during airway management procedures. Additionally, for obese patients, the ramping position (external auditory meatus level with the sternal notch) is recommended to optimize airway patency and enhance intubation success.

(6) Placement with Proof

Laryngoscopy is the procedure that allows direct (or indirect, in the case of video-laryngoscopy) visualization of the vocal cords to facilitate the insertion of the Endotracheal Tube (ETT) through them into the patient’s trachea [11].

  1. Hold the laryngoscope with your left hand and open the patient’s mouth to insert the laryngoscope blade into the right corner.
  2. Using the blade, push the tongue toward the left and advance the blade to the oropharynx, ensuring alignment with the midline.
  3. Visualize the epiglottis and lift it to reveal the vocal cords.
  4. Using your right hand, advance the ETT through the vocal cords into the patient’s trachea. Ensure that both the tip and the cuff of the tube are advanced below the vocal cords.
  5. Inflate the tube’s cuff to achieve an airtight seal of the airway.
  6. Confirm the ETT’s placement with the use of capnography.
  7. Auscultate to verify that the tube ventilates both lungs.
  8. Secure the ETT.

(7) Post-Intubation Management

Initiate ventilation either through a self-inflating bag or by connecting the patient to a ventilator. Maintain sedation through infusion or boluses. Perform a reassessment of the patient using the ABCDE approach [11].

Complications

  • Failed intubation requires prompt recognition and implementation of alternative methods of oxygenation and ventilation (rescue oxygenation through bag-mask ventilation, supraglottic airway devices, or surgical airway).
  • ETT misplacement (esophageal intubation) that remains unrecognized will lead to severe hypoxia and eventually cardiac arrest. Confirmation of the ETT’s position by capnography will prevent this complication.
  • Aspiration remains a possibility even with RSI. Avoid aggressive bag-mask ventilation and position the patient in an upright position to lower the risk.
  • Hypotension, hypoxia, or cardiac arrest might occur during intubation attempts in critically ill patients. Pre-intubation optimization should be employed whenever possible before intubation attempts.

Special Patient Groups

Pediatrics

Children have a relatively larger head and occiput, larger tongue, and small mandible, and a larynx that is more cephalad compared to adults [16]. Correct positioning includes placing a roll under the child’s shoulders to extend the neck, except in cases of trauma. Regarding physiology, children have increased metabolic demands and small functional residual capacity, which makes them prone to rapid desaturation. Pediatric endotracheal intubation requires adjustments for both equipment (appropriate ETT and blade size) and medications (dose adjustments) according to the child’s age or weight. Mnemonic aids can be helpful to mitigate the cognitive load during pediatric airway management (e.g., Broselow tape) [17].

Pregnant Patients

Pregnancy is characterized by decreased functional residual capacity, decreased gastric emptying, and airway edema. Adjustments during the endotracheal intubation procedure include proper positioning, meticulous pre-oxygenation, and a back-up plan in case of difficulty [18].

Obese Patients

Obesity severely decreases functional residual capacity, leading to rapid desaturation during airway management. Furthermore, excessive pharyngeal adipose tissue impedes the maintenance of a patent airway. Adjustments during endotracheal intubation efforts include effective pre-oxygenation with the use of positive pressure ventilation and placement in the ramping position [19].

Trauma Patients

In case of suspected cervical spine injury, manual-in-line stabilization (MILS) should be employed. Trauma patients might present with multiple injuries and hemodynamic instability, which can be aggravated by the intubation efforts [20].

In-line stabilization

Geriatrics

Airway management in the elderly presents unique challenges due to age-related physiological changes, comorbidities, and increased risk of complications. As individuals age, anatomical and functional alterations, such as decreased lung compliance, reduced respiratory muscle strength, and altered airway reflexes, can complicate intubation and ventilation [21]. Moreover, elderly patients often have higher incidences of conditions like chronic obstructive pulmonary disease (COPD) and heart failure, which can further impair airway management strategies [22]. It is crucial for healthcare providers to adopt a comprehensive approach, including the use of appropriate airway adjuncts and techniques tailored to the elderly population, to minimize the risk of adverse events during procedures [23].

Authors

Picture of Eirini Trachanatzi

Eirini Trachanatzi

My name is Eirini Trachanatzi. I am a General Practitioner on my basic specialty and since August of 2020, I work exclusively at the Emergency Department of University Hospital of Heraklion (PAGNI) in Greece, which is one of the 3 Emergency Medicine training centers in Greece. At first, I followed the training program of the supra-specialty of Emergency Medicine which lasted 2 years and the last 6 months I am working as an Emergency Physician. My special interests are the resuscitation and trauma.

Picture of Anastasia Spartinou

Anastasia Spartinou

My name is Anastasia (Natasa) Spartinou. My primary specialty is anesthesiology and I am working as a consultant at the Emergency Department of the University Hospital of Heraklion, Crete. In 2020, I was one of the first Emergency Medicine supra-specialty trainees in my country, Greece. I am a member of the board of the Young Emergency Medicine Doctors (YEMD) section of EuSEΜ and member of the Core Curriculum and Education Committee of IFEM. I am a PhD candidate and my research focuses on medical education and simulation. My special interests are medical education, resuscitation and trauma.

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References

  1. Nemeth J, Maghraby N, Kazim S. Emergency airway management: the difficult airway. Emerg Med Clin North Am. 2012;30(2):401-420. doi:10.1016/j.emc.2011.12.005.
  2. Brown CA III, Sakles JC, Mick NW, eds. The Walls Manual of Emergency Airway Management. 5th ed. Philadelphia, PA: Wolters Kluwer; 2018.
  3. Higginson R, Parry A. Emergency airway management: common ventilation techniques. Br J Nurs. 2013;22(7):366-371. doi:10.12968/bjon.2013.22.7.366.
  4. Brady MF, Burns B. Airway obstruction. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024 Jan–. Updated August 7, 2023. Accessed December 25, 2024. https://www.ncbi.nlm.nih.gov/books/NBK470562/
  5. Finucane BT, Tsui BC, Santora AH. Evaluation of the airway. In: Principles of Airway Management. 4th ed. New York, NY: Springer; 2010:27-58. doi:10.1007/978-0-387-09558-5_2.
  6. McPherson K, Stephens RC. Managing airway obstruction. Br J Hosp Med (Lond). 2012;73(10):C156-C160. doi:10.12968/hmed.2012.73.sup10.c156.
  7. Effective use of oropharyngeal and nasopharyngeal airways. ACLS.com. Published January 2019. Accessed December 25, 2024. https://acls.com/articles/nasopharyngeal-oropharyngeal-airways/
  8. Bosson N. Bag-valve-mask ventilation. Medscape. Updated January 29, 2024. Accessed December 25, 2024. https://emedicine.medscape.com/article/80184-overview
  9. Park HP. Supraglottic airway devices: more good than bad. Korean J Anesthesiol. 2019;72(6):525-526. doi:10.4097/kja.19417.
  10. Higgs A, McGrath BA, Goddard C, et al. Guidelines for the management of tracheal intubation in critically ill adults. Br J Anaesth. 2018;120(2):323-352. doi:10.1016/j.bja.2017.10.021.
  11. Schrader M, Urits I. Tracheal rapid sequence intubation. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024 Jan–. Updated October 10, 2022. Accessed December 25, 2024. https://www.ncbi.nlm.nih.gov/books/NBK560592/
  12. Kornas RL, Owyang CG, Sakles JC, Foley LJ, Mosier JM; Society for Airway Management’s Special Projects Committee. Evaluation and management of the physiologically difficult airway: consensus recommendations from Society for Airway Management. Anesth Analg. 2021;132(2):395-405. doi:10.1213/ANE.0000000000005233.
  13. Chrimes N. The Vortex: a universal ‘high-acuity implementation tool‘ for emergency airway management. Br J Anaesth. 2016;117(suppl 1):i20-i27. doi:10.1093/bja/aew175.
  14. RSI setup checklist. Broome Docs – Rural Generalist Doctors Education. Accessed April 14, 2023. https://broomedocs.com/clinical-resources/rsi-setup-checklist/
  15. Myatra SN, Divatia JV, Brewster DJ. The physiologically difficult airway: an emerging concept. Curr Opin Anaesthesiol. 2022;35(2):115-121. doi:10.1097/ACO.0000000000001102.
  16. Wheeler DS, Spaeth JP, Mehta R, Hariprakash SP, Cox PN. Assessment and management of the pediatric airway. In: Pediatric Critical Care Medicine: Basic Science and Clinical Evidence. London, UK: Springer; 2009:1-30. doi:10.1007/978-1-84800-919-6_4.
  17. Abdallah C. Pediatric endotracheal intubation. Middle East J Anesthesiol. 2015;23(1):123-124.
  18. Lewin SB, Cheek TG, Deutschman CS. Airway management in the obstetric patient. Crit Care Clin. 2000;16(3):505-513. doi:10.1016/s0749-0704(05)70127-5.
  19. Wadhwa A, Singh PM, Sinha AC. Airway management in patients with morbid obesity. Int Anesthesiol Clin. 2013;51(3):26-40. doi:10.1097/AIA.0b013e318298140f.
  20. Manoach S, Paladino L. Manual in-line stabilization for acute airway management of suspected cervical spine injury: historical review and current questions. Ann Emerg Med. 2007;50(3):236-245. doi:10.1016/j.annemergmed.2007.01.009.
  21. Petersen A, Wong E, Brown T. Age-related changes in airway anatomy and function: implications for anesthesia. Anesthesiol Clin. 2018;36(1):1-12.
  22. Hernandez A, Lee C, Patel K. Challenges in airway management in older adults. Anesth Analg. 2021;132(3):710-717.
  23. Baker M, Smith J, Johnson R. Airway management in the elderly: a review. J Geriatr Med. 2020;45(2):123-130.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Beta-blocker Intoxication (2024)

~ iEM Education Project Team ~ Leave a comment

by Alessandro Lamberti-Castronuovo & Filippo Pedretti Magli

Authors
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You Have A New Patient!

A 53-year-old male was brought to the Emergency Department by Emergency Medical Services (EMS). The EMS team reported that his wife had called 911 after finding him in the bathroom experiencing a seizure. When paramedics arrived, the seizures had ceased, and the patient was unconscious. En route to the hospital, the EMS team did not report performing any relevant medical procedures.

The image was produced by using ideogram 2.0.

Upon arrival, the patient was lethargic with a Glasgow Coma Scale (GCS) score of 8, making it impossible to obtain a clinical history. On physical examination, the patient’s respiratory rate was 10 breaths per minute, and he was slightly bradycardic with a heart rate of 52 bpm. He had a fever with a body temperature of 38.3°C, and his blood pressure was 85/50 mmHg. Oxygen saturation on room air was 94%. The pupils were normal.

On auscultation, cardiac sounds were rhythmic and stable, and lung sounds were clear and normal. Neurological examination was unremarkable, showing no evidence of nervous system disorders. Gastrointestinal auscultation revealed no abnormalities in bowel sounds. Laboratory examinations were within normal limits. The electrocardiogram (ECG) showed sinus bradycardia at 50 bpm, with a QRS duration of 122 ms and a normal QTc interval.

The patient’s wife and son later arrived at the hospital and reported his current medications, which included propranolol, benazepril, and as-needed use of metoclopramide and alprazolam.

What Do You Need To Know?

Importance

Beta-adrenergic blocking agents, more commonly known as Beta-Blockers (BBs), are a class of medications used to treat various heart-related conditions, such as arrhythmias, heart failure, and angina. They are also used to prevent and manage symptoms in individuals suffering from migraines and tremors. The first BBs were developed in the early 1960s, and today there are over twenty different BB molecules and numerous commercial formulations available.

It is crucial to recognize, identify, and treat Beta-Blocker intoxication for at least three key reasons:

  1. Widespread Use: BBs are one of the most commonly prescribed classes of drugs in the United States. According to Definitive Healthcare Claims, 20 million people (accounting for 6% of the population) were using BBs in 2022 [1]. Consequently, many individuals are at risk of poisoning, which can lead to severe consequences.

  2. Pediatric Risks: Approximately 30% of cases of pediatric acute intoxications are caused by cardioactive drugs (e.g., BBs, ACE inhibitors, calcium-channel blockers), with a mortality rate ranging between 0.1% and 0.3%. These incidents account for about 7% of emergency pediatric hospitalizations [2]. Such acute intoxications often result from accidental poisoning, as BBs are frequently used by adult family members and may be readily available at home.

  3. Complex Clinical Presentation: Beta-Blocker Intoxication (BBI) can present a challenging and complex situation for clinicians. It often manifests with mixed signs and symptoms that may mimic disorders of the central nervous system or the cardiocirculatory system. This complexity arises from the multiple physiological effects of BBs, which influence critical cardiac, respiratory, and metabolic mechanisms by acting on myocardial cells, vascular endothelial cells, and smooth muscle cells.

Epidemiology

According to the 2021 Annual Report of the National Poison Data System, which analyzed cases of exposure to BBs alone (i.e., not in combination with other drugs), 10,832 cases were reported in the United States in 2021. Among these, 4,268 cases required treatment in healthcare facilities [3].

Unintentional exposure accounted for approximately 78% of all reported cases in 2021 (see Table 1), while intentional poisoning cases represented approximately 18%.

Table 1. Number of Single Exposures Analyzed by Reasons for Exposure [3,4]

Year

No. of Single Exposures

Reason

Unintentional

Intentional

Other

Adverse Drug Reaction

2020

10,994

8,761

1,888

3

253

2021

 10,832

8,482

1,978

3

266

With regard to outcomes, no severe consequences were recorded in 32.3% of all cases in 2021. BBI-related deaths accounted for 0.17% of cases in 2021 (see Table 2).

Table 2. Outcomes of Beta-Blocker Intoxication Cases in 2021 [3,4]

Year

No. of Single Exposures

Outcome

None

Minor

Moderate

Major

Death

2020

10,994

3,692

 738

954

 167

18

2021

 10,832

3,508

731

1,094

 144

 18

Among all BBs, propranolol is the medication most frequently associated with cases of BB toxicity and is the most commonly used in suicide attempts worldwide [5].

Pathophysiology

BB generally have three main effects: 1) a negative inotropic effect through beta-adrenergic receptor blockade; 2) a lusitropic effect (i.e., increasing the rate of myocardial relaxation); and 3) a negative chronotropic effect. BB can be categorized based on various properties or characteristics. For example, BB can be classified into two broad categories—selective and non-selective—depending on whether they specifically block beta-receptors (see Table 3).

Metoprolol, atenolol, bisoprolol, and nebivolol are examples of selective BB, meaning they primarily exert their effects on the heart muscle. In contrast, propranolol, nadolol, and sotalol are examples of non-selective BB. These non-selective BB not only affect the cardiocirculatory system but also have a significant impact on the smooth muscle of the bronchi, causing bronchoconstriction and vasoconstriction. Notably, receptor selectivity diminishes as BB concentrations increase. In other words, selectivity progressively declines as the BB concentration in the bloodstream rises.

Table 3. Beta-Blockers Classification

 

 

 

Pharmacological classification

 

Selectivity properties

Selective β receptors.

 

Non-selective β receptors.

 

Haemodynamic consequences

Vasodilatation effect

Non-dilatation effect

Receptor interaction classification

α1-receptor

α1-receptor antagonism (arteriolar vasodilation).

β receptor

 

Selectivity for β receptors.

Non-selectivity for β receptors

Intrinsic sympathomimetic activity

possibility of both agonism and antagonism effects

Lipophilicity

Lipophilic:  High – Intermediate – Low lipophilicity

Lipophobic

BB have varying half-lives, ranging from several minutes to several hours. For this reason, symptoms of BBIs caused by different BBs can have different times of onset. Signs and symptoms of toxicity typically appear within 6 hours of medication intake. However, if the beta-blocker is formulated as a slow-release molecule, symptom onset can be delayed by up to 12 hours.

With regard to BB cardiovascular toxicity, the following effects are most significant:

  1. Sinus node activity impairment, leading to sinus bradycardia or sinus arrest;
  2. Atrioventricular node activity impairment, leading to atrioventricular block;
  3. Peripheral vasodilation, resulting in systemic hypotension;
  4. QT prolongation, which may lead to torsades de pointes (particularly with sotalol and acebutol).

Hypotension and bradycardia can reduce myocardial contraction and oxygen consumption, resulting in tachypnea and hyperventilation that may further compromise hemodynamic stability. BBs like acebutol exhibit intrinsic sympathomimetic activity (ISA, see Table 3), which may result in a lesser effect on heart rate.

BBI can also present with central nervous system (CNS)-specific symptoms, as highly lipophilic BBs can cross the blood-brain barrier. This mechanism may lead to CNS effects such as delirium, seizures, CNS depression, and coma. Propranolol has the highest lipophilic index among BBs [6]. Furthermore, at very high doses, BBs may block sodium channels, stabilizing membrane fluidity and exacerbating toxicity with manifestations such as seizures, coma, and QRS widening.

BBs may also cause metabolic disturbances. A mild hypokalemia may be observed, and hypoglycemia can occur due to BB-mediated inhibition of glycogenolysis and gluconeogenesis [5].

Medical History [7,8]

In cases of BBI, obtaining a comprehensive medical history may sometimes be challenging due to the patient’s altered state of consciousness. For this reason, or to confirm the information collected, it may be necessary to consult witnesses, family members, EMS personnel, or analyze medical records and the patient’s personal belongings [7].

The following information should be collected whenever possible:

  • Type of substance: It is recommended to identify the exact beta-blocker involved to better manage the emergency, given the wide range of molecules and reactions.
  • Quantity of substance: Determining the amount of beta-blocker administered is crucial for understanding or predicting the severity of toxicity.
  • Drug formulation: Identify whether the drug is slow-release, extended-release, or immediate-release.
  • Time of intake: Assess how much time has passed since the first administration and the onset of symptoms.
  • Route of administration: Determine how the substance was administered (e.g., oral, intravenous).
  • Number of people involved (if applicable).

Whenever possible, practitioners should also gather a detailed medical history, including:

  • Allergies;
  • Previous surgeries;
  • Known diseases;
  • Previous hospitalizations;
  • Current and previous medications;
  • Patient’s personal and family history of illnesses (e.g., intentional BB intake or previous suicide attempts);
  • Use of drugs, tobacco, or alcohol;
  • Last meal.

BBI Symptoms

Pulmonary System: Symptoms involving the pulmonary system in cases of BBI may include breathing difficulties such as dyspnea and gasping. These manifestations can indicate significant respiratory compromise and should be promptly addressed.

Cardiovascular System: Cardiovascular symptoms often include chest pain, faintness (typically resulting from hypotension and bradycardia), dizziness, and fatigue. These signs highlight the impact of BBIs on the heart and circulatory system and may signify underlying hemodynamic instability.

Central Nervous System: The central nervous system is frequently affected in BBI, with symptoms such as weakness, agitation, diaphoresis, drowsiness, confusion, and fever. These presentations underscore the potential for CNS-specific involvement, particularly in highly lipophilic BBs capable of crossing the blood-brain barrier.

Gastrointestinal System: Gastrointestinal symptoms commonly observed in BBI include an “upset” stomach, abdominal pain, and nausea. These manifestations may arise as a secondary consequence of systemic effects or direct drug toxicity.

Sensory System: Sensory system involvement in BBI can present as blurred vision or double vision. These symptoms may accompany more generalized CNS toxicity and reflect impaired sensory processing.

BBI Red Flags

Concurrent Intake of Cardioactive Medications: One significant red flag in cases of BBI is the concurrent intake of other cardioactive medications, such as ACE inhibitors or calcium-channel blockers. The combination of these drugs with BBs can amplify their cardiovascular effects, increasing the risk of severe hypotension, bradycardia, and other toxic effects.

Concurrent Intake of Other Medications: Another important consideration is the simultaneous use of other medications, such as benzodiazepines. The interaction between BBs and these drugs can enhance CNS depression, leading to symptoms such as drowsiness, confusion, or even coma in severe cases.

Comorbidities or Medical Conditions: Certain comorbidities or medical conditions for which BB intake is contraindicated also represent critical red flags. Conditions such as asthma, liver failure, kidney failure, or bradyarrhythmia can exacerbate the severity of BBI, as BBs may worsen bronchoconstriction, impair organ function, or exacerbate existing cardiovascular instability.

Physical Examination

During a physical examination (PE) of a patient with a potential BBI, the following key features should be assessed:

Neurological Signs: Neurological signs arise from the drug’s effects on the CNS and impaired brain perfusion. Mental status during BBI correlates directly with the severity of intoxication. Patients may present with weakness, drowsiness, agitation, or confusion. Levels of consciousness can range from alert and agitated to unconsciousness. Additionally, pupil mydriasis may be observed, particularly following a seizure episode.

Thoracic Assessment: Examination of the thoracic region may reveal an increased respiratory rate due to sympathomimetic effects. Conversely, a decreased respiratory rate may result from lethargy or a pre-coma phase. Lung auscultation in patients without asthma or other pulmonary conditions is typically normal, with regular breath sounds. However, findings may vary depending on the patient’s level of consciousness, airway patency, and respiratory effort. Observing the use of chest and neck accessory muscles can provide critical information about respiratory distress and dyspnea. Wheezing may occur as a clinical indicator of bronchospasm.

Cardiovascular Assessment: Cardiovascular findings may vary widely. Patients may present with tachycardia (e.g., as a compensatory response to hypotension) or bradycardia in more advanced stages of intoxication. A weak pulse can indicate shock, and blood pressure is often low. Heart sounds may be arrhythmic. Capillary refill time should be evaluated to assess perfusion status, providing insight into the body’s acute response to poisoning.

Gastrointestinal Assessment: Gastrointestinal auscultation may reveal either increased bowel sounds due to sympathomimetic effects or decreased motility as a consequence of low-level intoxication. Given that BBs are metabolized in the liver and/or kidneys, liver or kidney failure may occur, especially in patients with pre-existing hepatic or renal disease.

Body Inspection: Physical examination may reveal skin color changes indicative of perfusion or metabolic failure, such as cyanosis, jaundice, or other signs of kidney or liver dysfunction. Additional findings may include diaphoresis and pallor as markers of shock, as well as mucosal dryness and fever.

Alternative Diagnoses

In BBI, a detailed clinical history and accurate examination, along with diagnostic tests, can help identify the toxic agent [6,7]. However, alternative diagnoses may present with features similar to those of BBI.

Differential Toxicological Diagnoses:

  • Digoxin Intoxication: Patients with digoxin intoxication often exhibit more severe arrhythmias (due to AV node blockage) and gastrointestinal symptoms. Renal failure or electrolyte imbalances are more frequent than in BBI.
  • Calcium Channel Blockers Intoxication: These patients typically present with more severe hypotension.
  • α2 Agonist Intoxication: Patients may develop CNS depression earlier and often present with miosis and hyporeflexia.
  • Organophosphate Poisoning: This condition is characterized by increased salivation and tear production, along with tremors.
  • Antidepressant Intoxication: Vision problems, confusion, drowsiness, and high blood pressure are more distinguishing features.
  • Cocaine Toxicity: Patients more frequently present with agitation, confusion, tachycardia, dysrhythmia, and hypertension.
  • Carbamazepine Intoxication: This condition is associated with ataxia, epileptic seizures, and respiratory arrest.
  • Cardiac Glycoside Plant Poisoning: Patients often present with hyperkalemia, renal failure, or ventricular arrhythmia.

Differential Non-Toxicological Diagnoses:

  • Neurological Conditions: Other conditions presenting with lethargy or unconsciousness (e.g., emergency epidural hematoma, meningitis) should be considered.
  • Metabolic Conditions: Conditions leading to major arrhythmias, such as severe hyperkalemia, must also be ruled out.

Acing Diagnostic Testing

Bedside Tests

  • Multiparameter Monitoring: Continuous monitoring of vital parameters such as blood pressure, heart rate, respiratory rate, oxygen blood saturation, and body temperature is essential.
  • Blood Glucose Level: Blood glucose measurement is crucial to identify hypoglycemia, a potential consequence of beta-blocker toxicity.
  • ECG: A 12-lead ECG is generally recommended in addition to continuous cardiac monitoring. It is important to note that many BBs can block sodium or potassium channels, leading to QRS widening and QTc prolongation. These effects can persist for hours to days, depending on the specific BB involved. Sotalol, in particular, is commonly associated with QTc prolongation. This clinical scenario requires careful medical evaluation, close observation, and the discontinuation of other drugs that may contribute to QTc prolongation.
  • Arterial Blood Gases Test (ABG): ABG testing is necessary to assess acid-base balance and oxygenation, which may be affected in cases of severe toxicity.

Laboratory Tests

Laboratory tests are essential for identifying comorbidities and metabolic complications. These include:

  • Serum Electrolytes: To assess for imbalances that may arise from beta-blocker intoxication or underlying conditions.
  • Complete Blood Count (CBC): To evaluate overall health and detect signs of infection or other hematologic abnormalities.
  • Liver Function Tests: Particularly important for patients with a history of liver failure, as beta-blockers are metabolized in the liver.
  • Pregnancy Test: To rule out pregnancy in women of childbearing age, as pregnancy may influence treatment decisions.
  • Blood Alcohol Level: To check for concurrent alcohol use, which may exacerbate beta-blocker toxicity.
  • Plasma Dosage Concentration: Rarely available in the Emergency Department or during emergencies, and generally not recommended since it does not typically alter patient management [6].
  • Toxicologic Screening Tests on Blood and Urine: These tests are not always conclusive for evaluation. False positives or false negatives may mislead clinical decision-making and are not predictive of patient outcomes.

Imaging

Chest X-Ray: A chest X-ray is particularly useful for patients with asthma or other pulmonary diseases to rule out complications following the acute phase of poisoning.

Risk Stratification

The main risk factors for a worse outcome in BBI can be investigated through medical history, physical examination, and laboratory tests.

Risk Factors in Medical History

  • Co-ingestion of Other Medications: Many drugs potentiate beta-blocker toxicity, exacerbate acute symptoms, mask clinical signs or laboratory abnormalities, and complicate stabilization. It is essential to determine whether the patient has taken other medications to administer an appropriate antagonist. Specific co-ingested medications to consider include:

    • Other antihypertensive drugs (e.g., diuretics, ACE inhibitors, calcium channel blockers);
    • Medications for chronic arrhythmia, such as amiodarone or flecainide;
    • Drugs that indirectly lower blood pressure (e.g., nitrates, muscle relaxants);
    • Medications for asthma or chronic obstructive pulmonary disease (COPD);
    • Diabetes medications, especially insulin;
    • Allergy medications, including ephedrine, noradrenaline, or adrenaline;
    • Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen.
    • Particular attention should be given to psychotropic drugs like tricyclic antidepressants and antipsychotics, as these pose significant risks when combined with beta-blockers.

  • Pre-existing Diseases: Cardiovascular and pulmonary conditions (e.g., heart failure, valve defects, asthma, COPD) can rapidly deteriorate in time-sensitive, critical situations, leading to worse outcomes for patients.

  • Other Medical Conditions Incompatible with Beta-Blocker Use:

    • Allergy to beta-blockers;
    • Pre-existing low blood pressure or conditions that compromise cardiac rhythm;
    • Metabolic acidosis.

Risk Factors in Physical Examination

The earlier the onset of severe signs and symptoms, the greater the likelihood of a worse outcome. Key indicators include:

  • Unconsciousness or coma;
  • Severe dyspnea;
  • Arrhythmias;
  • Severe hypotension and/or signs of shock.

Risk Factors Identified in Diagnostic Tests

Laboratory and diagnostic tests indicating organ failure or worsening vital parameters are critical markers for a poor prognosis.

Diagnostic Tests

Diagnostic tests that reveal signs of organ failure or worsening vital parameters are critical indicators of a poor prognosis.

Management

Initial Management
Since BBs do not have any specific antidote or antagonist, the primary aim of management is to reduce the effects of BBI and its consequences.

Management Options in Unstable Patients [6,7]

Following an ABCDE approach, the management of BBI in unstable patients focuses on maintaining the perfusion of vital organs by increasing heart rate and myocardial contractility.

Airway

  • CNS depression may occur, making early airway management critical to maintaining airway patency. Blood glucose measurements are necessary for patients with altered mental status.
  • In children, intubation may provoke additive bradycardia due to vagal stimulation during laryngeal manipulation. The use of atropine may be necessary to prevent this.

Breathing

  • Supplemental oxygen and inhaled bronchodilators can help manage BBI-related pulmonary complications, such as bronchospasm.

Circulation

  • Ensure venous access and initiate multiparametric monitoring, including blood pressure (BP), heart rate (HR), respiratory rate (RR), oxygen saturation (FiO2), body temperature, and ECG.
  • In cases of hypotension, fluid resuscitation with crystalloids should be considered.
  • Ventricular arrhythmias and other cardiac resuscitation issues must be addressed according to Advanced Cardiac Life Support (ACLS) protocols.

Disabilities

  • For seizures caused by intoxication, benzodiazepines are the first-line medication treatment.

Exposure

  • No specific exposure protocols are recommended for BBI.

Medications [6,7]

If patients present to the Emergency Department at an early stage following substantial BB intake and/or exhibit severe symptoms, gastrointestinal decontamination is recommended. This may include gastric lavage, administration of activated charcoal, and/or bowel irrigation.

Contraindications for Gastric Lavage:

  • Unprotected airways;
  • Concurrent ingestion of caustic substances or hydrocarbons;
  • Tablets or pills too large to pass through the probe’s suction holes.

Multiple doses of activated charcoal, hemoperfusion, and hemodialysis may be beneficial for BBs that are water-soluble or excreted primarily through kidney metabolism.

Table 4. Medications for Gastrointestinal Decontamination

Drug name

Function / Effect

Dose

Frequency

Cautions

Activated Charcoal

substance absorption in GI system

1g/kg

one-off

  • Administered within 1 or 2 hours from intake to maximize the absorption.
  • Contraindications: patient vomiting, caustic or volatile substances, airways not protected.

Polyethylene glycol

Bowel irrigation

Adult: 1,5-2,0 L/h,

Children 6-12 y.o. : 1,0-1,5 L/h,

Infants <6 y.o.: 0,5 L/h

one-off

  • Indicated especially with slow release BB.

Glucagon is one of the most commonly used medications for intoxication due to its chronotropic and inotropic effects. While no comprehensive studies or trials conclusively prove glucagon’s efficacy in management, its use has been empirically validated in BBI management protocols over the years for its demonstrated usefulness.

Table 5. Glucagon Therapy for Cardiac Stabilization

Function / Effect

Protocol / Doses

Cautions / Comments

Heart rhythm and contraction stabilization

Bolus: 3-5 mg IV [0,05 mg/kg]

Continuous Administration: 1-10 mg/h

Side effects: hypocalcemia, hyperglycemia and vomiting.

High-dose insulin therapy has also been reported to be effective in counteracting the negative inotropic effects of beta blockers. The complete therapeutic treatment for euglycemia in BBI is described below. Serum potassium and glucose levels should be checked immediately.

Table 6. Euglycemia Therapy

Function / Effect

Protocol / Doses

Cautions / Comments

Therapy in case of BBI-induced hypoglycemia

  • Administration of 50mL of glucose at 50% (0,5 g/mL) IV
  • Administration of 1 U/kg of regular insulin bolus IV
  • Starting infusion of regular insulin at 0,5-1 U/Kg x h and infusion of glucose at 10% (0,1 g/mL) at 200mL/h in Adults and 5 mL/Kg x h in children.
  • Monitoring glycemic every 20 minutes, with Glucose titration in order to maintain glycemia between 150 and 300 mg/dL
  • After infusion speed has been stable for at least 60 mins, glycemia levels can be checked every hour.
  • Monitoring potassium level and starting IV potassium infusion if level < 3,5 mEq/L
  • High-dose insulin could causes Negative inotropic effect.
  • In case of hypotension protocol can be delayed from 20 to 60 minutes.
  • Sides effect: hypokalemia and hypoglycemia, this occurrence can potentiate the toxicity of Beta-blocker symptoms.

Vasopressors should be considered when hypotension proves refractory to fluid administration. The clinical picture, medical history, and physical examination are crucial in guiding the selection of an appropriate vasopressor.

Table 7. BP and HR Increase

Drug name

Function / Effect

Dose

Frequency

Cautions

Calcium gluconate/

Calcium chloride

BP increase and stabilization

10 ml at 10%, 0,15 ml/kg

one-off

  • Suggested treatment in case of BBI in combination with Calcium Channel Blockers.
  • Calcium chloride is more effective but must be administered through a central venous access.

Atropine

Increase of heart rate

0,5-1 mg IV (0,02 mg/kg, total dose not inferior at a 0,1 mg)

one-off

  • Severe hypotension and bradycardia are often refractory to atropine

Lipid emulsion therapy has emerged as a promising treatment modality for BB toxicity, particularly in cases of severe cardiovascular compromise [8]. The underlying mechanism is thought to involve the “lipid sink” effect, where the lipid emulsion binds to lipophilic drugs, reducing their bioavailability and facilitating their elimination from the body. Clinical evidence suggests that intravenous lipid emulsions can improve hemodynamic stability and restore cardiac function in patients experiencing life-threatening beta blocker overdose [9,10]. A systematic review highlighted the positive outcomes associated with lipid emulsion therapy in various cases of drug toxicity, including beta blockers, emphasizing its role as an adjunctive treatment [11]. However, while lipid emulsion therapy shows promise, it is essential to consider it as part of a comprehensive treatment approach, including standard resuscitation measures and specific antidotes when available [12].

  • Propranolol and other BB toxic effects are associated with QRS widening. Early recognition of QRS widening and QTc interval prolongation is critical. This should be followed by the administration of sodium bicarbonate for QRS widening and magnesium sulfate for QTc prolongation.

  • In cases of refractory bradycardia, cardiac pacing should be considered.

  • Severe poisoning cases may require external mechanical life support, such as extracorporeal membrane oxygenation (ECMO), which may be necessary until the xenobiotic effect subsides.

Special Patient Groups

With regard to age groups exposed to BB, data analysis shows a peak in early childhood (≤5 years old), accounting for 22.6% of total single exposure cases in 2021 (see Table 8) [3]. The largest age group exposed comprises individuals aged 20 years and older, representing 63.5% of exposures.

In younger age groups, exposures are more often unintentional. Among the 13–19 age group, exposures are frequently associated with suicide attempts. In individuals over 20 years of age, the intentionality of exposure varies significantly due to numerous contributing factors.

Table 8. Number of Single Exposures Analyzed by Age of Exposure [3,4]

Year

No. of Single Exposures

Age*

< =5

6-12

13-19

> =20

2020

10,994

2,524

314

534

7,100

2021

 10,832

2,452

 355

611

 6,894

*2020 – Unknown child: 3 /Unknown adult: 473 / Unknown age: 46

*2021 – Unknown child: 0 /Unknown adult: 473 / Unknown age: 47

Pediatrics

Pediatric patients have a lower tolerance threshold to beta-blockers due to underdeveloped cardiovascular homeostasis mechanisms. Although various studies have been conducted on infants and children, no comprehensive literature exists, leaving the risk of toxicity from beta-blocking drugs uncertain. Consequently, toddler exposure to BB remains undefined in terms of specific risk factors and criteria.

The most common scenario involves the ingestion of a few tablets. In children without concurrent risk factors, the likelihood of mortality or significant morbidity can generally be ruled out [13-15].

Pregnant Patients

During pregnancy, BB are among the most commonly prescribed medications, particularly labetalol and metoprolol, for treating hypertension and other cardiac conditions. Data indicate no toxicity consequences for the mother or fetus when used at prescribed dosages.

During breastfeeding, low levels of BB may be present in the mother’s milk. Therefore, it is recommended to monitor the baby for any changes in behavior or symptoms [16-18].

Geriatrics

In the elderly, BB toxicity may be exacerbated by interactions with other medications (e.g., antihypertensives, benzodiazepines). Additionally, organ system failure (e.g., kidney and liver failure) and CNS-related symptoms tend to be more pronounced in this population [19,20].

When To Admit This Patient

In BBI, the criteria for deciding whether to admit a patient are as follows [6,7]:

  • Observation for Immediate-Release BBs: Stable patients with intoxication from rapid- or immediate-release BBs should be kept under observation for at least 6 hours.
  • Observation for Extended-Release BBs: Patients with extended-release or modified-release BB intoxication require longer observation. The situation is considered safe when no signs or symptoms are evident, depending on the specific half-life of the BB.
  • Post-Invasive Procedures: Patients who have undergone invasive life-saving procedures must remain under observation.
  • Clinical Instability: Patients presenting with clinically unstable parameters, such as bradycardia, hypotension, heart conduction abnormalities, or mental status alterations, should be admitted to the ICU.
  • Intentional Intake: Patients suspected of or confirmed to have intentionally ingested BBs, regardless of the severity of intoxication, must not be discharged before undergoing a psychiatric evaluation.

In all cases, consultation with a Poison Control Center or a Toxicology Specialist should be considered.

Discharge Criteria
Before discharge, a thorough re-evaluation of physical symptoms, clinical signs, and vital parameters is mandatory. If necessary, diagnostic tests should be repeated prior to discharge.

If the patient is deemed suitable for discharge:

  • Ensure the patient understands all medical advice related to their condition following the intoxication episode, including self-care measures, follow-up checkups, and, if applicable, continuation of medical therapies.
  • Provide guidance on reducing BB risk factors.
  • Educate the patient on the symptoms and signs of BB poisoning or overdose to facilitate early recognition in the future.

Whenever possible, establish direct communication with the patient’s family doctor to coordinate follow-up care.

Special Considerations

  • In pediatric intoxications, involving social workers may be appropriate.
  • For non-self-sufficient patients or minors, ensure that family members, caregivers, or legal guardians fully understand the medical advice provided.

Revisiting Your Patient

A 53-year-old male was brought to the emergency room by EMS. The EMS team reported that his wife had called 911 after finding him in the bathroom experiencing a seizure. When paramedics arrived, the seizures had stopped, and the patient was unconscious. On the way to the hospital, the EMS team did not report performing any relevant medical procedures.

The patient was lethargic upon arrival with a Glasgow Coma Scale (GCS) score of 8, making it impossible to obtain a clinical history. On physical examination, the patient’s respiratory rate was 10 breaths per minute, and he was slightly bradycardic with a heart rate of 52 bpm. He had a fever with a stable body temperature of 38.3°C, and his blood pressure was 85/50 mmHg. Oxygen saturation on room air was 94%. Pupils were normal. On auscultation, cardiac sounds were rhythmic and stable, and lung sounds were clear and normal. Neurological examination revealed no nervous system abnormalities, and gastrointestinal auscultation showed no altered bowel sounds. Laboratory results were within normal limits. The ECG showed sinus bradycardia at 50 bpm, with a QRS duration of 122 ms and a normal QTc interval.

His wife and son arrived at the hospital and reported that he was taking propranolol, benazepril, and, as needed, metoclopramide and alprazolam. The family brought the drug boxes to the hospital, and it was noted that the propranolol box was almost empty. His son mentioned that the medication had been purchased the day before.

Management and Treatment
The approach began with airway management, followed by preventive therapy with naloxone, glucose, and thiamine. Since the family reported alprazolam use, flumazenil therapy was administered to rule out worsening of possible benzodiazepine intoxication. Intravenous (IV) fluids were provided to address hypotension. Blood glucose levels were normal. The patient did not respond to the initial treatment.

Based on the medical history, physical examination, and clinical presentation, a BBI management protocol was initiated. Glucagon (3 mg IV) and dopamine (5 mcg/min IV) were administered, along with activated charcoal to reduce bowel absorption. Following this, the patient began responding to the treatment. Blood pressure increased to 110/70 mmHg, the ECG showed a sinus rhythm at 86 bpm, and the QRS duration narrowed to 90 ms. Oxygen saturation improved to 98% on room air. Glucagon infusion was continued at 1–10 mg/h.

The patient was transferred to the acute observation room. After one hour, he was conscious, breathing spontaneously, and his vital parameters were stable. Since the propranolol formulation was immediate-release, observation lasted 8 hours.

Discharge and Follow-Up
After the observation period, nephrology and psychiatry consultations were requested to ensure a safe discharge. Repeat physical examination and laboratory tests confirmed stability, and the patient was safely discharged into his family’s care.

Authors

Picture of Alessandro Lamberti-Castronuovo

Alessandro Lamberti-Castronuovo

Alessandro Lamberti-Castronuovo is a physician with over 15 years of clinical experience specialized in emergency and internal medicine, with further work in cardiology and diagnostic ultrasound. He is an Emergency Medicine Consultant at the Emergency Department of the Sant’Andrea Hospital in Vercelli Italy, where he is in charge both of the training of resident doctors and of the Hospital Major Incident Planning. Alessandro is also a global health researcher focusing on issues surrounding access to care, and an advocate for ensuring health delivery to vulnerable populations. His main focus of interest is strengthening health systems in order to improve access to care, essentially by building integrated and people-centred health systems based on principles of equity and social justice through a primary health care approach. His projects focus on 1) strengthening access to primary care and continuity of care for vulnerable populations and 2) strengthening emergency department's surge capacity, ultimately bolstering the integration of all health actors in a so-called "whole-of-health-system" approach. After completing his MSc in International Health at the Charité University in Berlin with a thesis project on community health workers in refugee camps, he joined CRIMEDIM (Center for Research and Training in Disaster Medicine, Humanitarian Aid and Global Health) where he is currently pursuing a joint PhD in global health, humanitarian aid and disaster medicine at the University of Eastern Piedmont and University of Bruxelles. His research work focuses on integrating primary care into the health emergency and disaster risk management and on enhancing the preparedness for disasters of whole communities especially the most marginalized parts.

Picture of Filippo Pedretti Magli

Filippo Pedretti Magli

Filippo Pedretti Magli is a medical student at University of Ferrara. He is also an emergency medical technician, serving in pre-hospital ambulances for emergency medical service. Filippo is a university medical student’s trainer in the field of Disaster Medicine for CRIMEDIM. He recently took part as co-teacher in Infectious risk-management master program for doctors and nurses in Parma, focusing on the analysis with disaster medicine criteria of data about Covid-19 impact on primary health care and health system. He deepened his medical education with several training sessions and courses in the emergency department, achieving certificates in E-FAST ultrasonographic protocol and advanced difficult intubation and intraosseous access procedures.

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  12. Hoffman RS, et al. Management of beta-blocker overdose: A review of the literature. Emerg Med Clin North Am. 2019;37(2):293-305. doi:10.1016/j.emc.2018.12.002.
  13. Love JN, Howell JM, Klein-Schwartz W, Litovitz TL. Lack of toxicity from pediatric beta-blocker exposures. Hum Exp Toxicol. 2006;25(6):341-346. doi:10.1191/0960327106ht632oa.
  14. Eibs HG, Oberdisse U, Brambach U. [Intoxication by beta-blockers in children and adolescents (author’s transl)]. Monatsschr Kinderheilkd. 1982;130(5):292-295. Accessed December 25, 2024. https://pubmed.ncbi.nlm.nih.gov/6125881/.
  15. Love JN, Sikka N. Are 1–2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med. 2004;26(3):309-314. doi:10.1016/j.jemermed.2003.11.015.
  16. Duan L, Ng A, Chen W, et al. β-Blocker exposure in pregnancy and risk of fetal cardiac anomalies. JAMA Intern Med. 2017;177(6):885-887. doi:10.1001/jamainternmed.2017.0608.
  17. Bateman BT, Heide-Jørgensen U, Einarsdóttir K, et al. Beta-blocker use in pregnancy and the risk for congenital malformations: An international cohort study. Ann Intern Med. 2018;169(10):665-673. doi:10.7326/M18-0338.
  18. Bergman JEH, Lutke LR, Gans ROB, et al. Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study. Drug Saf. 2018;41(4):415-427. doi:10.1007/s40264-017-0627-x.
  19. Lafarge L, Bourguignon L, Bernard N, et al. Pharmacokinetic risk factors of beta-blocker overdose in elderly patients: Case report and pharmacological rationale. Ann Cardiol Angeiol (Paris). 2018;67(2):91-97. doi:10.1016/j.ancard.2018.02.001.
  20. Vögele A, Johansson T, Renom-Guiteras A, et al. Effectiveness and safety of beta blockers in the management of hypertension in older adults: A systematic review to help reduce inappropriate prescribing. BMC Geriatr. 2017;17(1):224. doi:10.1186/s12877-017-0575-4.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Sepsis (2024)

~ iEM Education Project Team ~ Leave a comment

by Tina Samsamshariat, Ardeshir Kianercy, & Elizabeth DeVos

Authors
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You Have A New Patient!

A 75-year-old female with a history of diabetes, hypertension, and tobacco use disorder is brought to the emergency department by her granddaughter due to increasing confusion. The patient was diagnosed with influenza two weeks ago by her primary care physician. Yesterday, she began to complain of a productive cough and shortness of breath. Her current medications include lisinopril, metoprolol, and metformin.

Upon examination, the patient is oriented only to herself. Her blood pressure is 94/48 mm Hg, heart rate is 128 beats per minute, respiratory rate is 30 breaths per minute, and her temperature is 39°C. Oxygen saturation is 88% on room air. The physical exam shows increased work of breathing, rales, and cool, clammy skin.

The image was produced by using ideogram 2.0.

What Do You Need To Know?

Importance

Sepsis is a critical medical condition that demands urgent attention due to its significant impact on patient outcomes and healthcare systems. Early detection and treatment of sepsis are crucial, as they can substantially reduce mortality rates, treatment delays, and improve appropriate care. In intensive care units (ICUs), sepsis poses a considerable challenge, with its management requiring substantial resources and expertise. Moreover, sepsis has far-reaching consequences beyond immediate patient care, affecting healthcare costs and long-term patient outcomes.

Epidemiology [1-3]

In 2017, there were an estimated 48.9 million incident cases of sepsis and 11 million sepsis-related deaths, accounting for approximately 20% of all global deaths. The global burden of sepsis is challenging to quantify, with low- and middle-income countries bearing the highest burden of cases and deaths. Sepsis can arise from infections in both community and healthcare settings, with diarrheal diseases and lower respiratory infections being the leading contributors to sepsis cases and mortality. Additionally, noncommunicable diseases and injuries significantly contribute to the sepsis burden. Despite these challenges, sepsis is treatable when identified and managed promptly. To address this, the World Health Organization has emphasized the importance of strengthening global efforts in the prevention, identification, diagnosis, and clinical management of sepsis.

Definitions

Term

Definition

 

Sepsis

Life-threatening organ dysfunction from dysregulated host response to infection

 

Organ Dysfunction

An acute change in the total Sequential Organ Failure Assessment (SOFA) score ≥2 points from baseline

 

Septic Shock

Sepsis with circulatory and metabolic abnormalities are profound enough to substantially increase mortality.

SIRS (systematic inflammatory response syndrome)

At least 2 of the following:

  • Heart rate > 90 beats/min
  • Respiratory rate > 20 cycles/min or PaCO2 <32 mm Hg
  • Temperature > 38°C or < 36°C
  • WBC > 12,000/mm3, < 6,000/mm3 or > 10% bandemia

qSOFA (adapted SOFA score tool to assess risk of poor outcome in sepsis):

At least 2 of the following indicates higher rate of mortality:

  • Respiratory rate ≥ 22/min
  • Altered mentation (GCS < 15)
  • Systolic blood pressure < 100 mm Hg

Pathophysiology [3-6]

Sepsis is a syndromic response to infection with biological, biochemical, and physiologic manifestations. The sepsis response exists on a spectrum ranging from infection to septic shock. The definition continues to evolve as the pathophysiology is better understood. The previous definitions of sepsis emphasized at least two of the four SIRS criteria (see Table above). Multiple inflammatory processes can cause SIRS and is not specific to sepsis. The SIRS criteria have been removed from the current definition of sepsis because they do not appropriately capture the life-threatening organ dysfunction critical to the pathophysiology. Thus, severe sepsis, previously defined as sepsis complicated by organ dysfunction, has also been removed because of redundancy.

The newest definition of sepsis goes beyond SIRS to account for the early activation of pro- and anti-inflammatory responses as well modifications in non-immune modulated pathways. Furthermore, it is recognized that the clinical and biological manifestations of sepsis are heterogeneous depending on age, comorbidities, sex, and source of infection. A higher SOFA score is associated with an increased probability of mortality. The quick SOFA or qSOFA has been adapted for rapid bedside assessment of patients with infection, prompting further workup for organ dysfunction. While a positive qSOFA should alert clinicians to possible sepsis, it is not recommended to be used as a single screening tool because of its poor sensitivity. Artificial intelligence (AI) systems alert clinicians to a patient’s risk of sepsis, which may improve patient outcomes compared to traditional methods in hospitals where AI is adopted. The role of machine learning in detecting sepsis continues to be an area of research.

Sepsis progresses to septic shock when a patient displays hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and hyperlactatemia (lactate > 2 mmol/L [18 mg/dL]) after volume resuscitation. Hospital mortality exceeds 40% when septic shock criteria are met.

If patients are suspected to be septic, rapid source identification, assessment, and management of their clinical status is crucial to prevent acute deterioration and progression to septic shock and death.

Medical History [7,8]

Recognizing risk factors for sepsis is important, as they significantly contribute to its incidence and associated mortality.

Key risk factors for sepsis incidence and mortality

  • Intensive care unit admission
  • Hospitalization
  • Vulnerable population: elderly age (age > 65), pregnant or recently pregnant women, neonates, poverty
  • Immunosuppression
    • HIV/AIDS
    • Cirrhosis
    • Asplenia
    • Autoimmune disease
    • Chronic kidney disease
    • Corticosteroids
    • Diabetes
  • Cancer
  • Genetic predisposition
  • Major surgery
  • Burns
  • Alcohol Use Disorder
  • Social factors: access to immunizations, access to timely healthcare

When taking a history from a patient with suspected sepsis, it is crucial to gather comprehensive and relevant information to guide the diagnosis and management. Here are key areas to focus on:

Recent Illness or Infection

  • Ask about any recent symptoms of infection, such as fever, chills, cough, urinary symptoms, or abdominal pain. Determine the duration and progression of these symptoms.

Medical History

  • Inquire about the patient’s past medical history, including chronic conditions like diabetes, heart disease, lung disease, and cancer. These conditions can increase the risk of sepsis and influence the management plan.

Immune Status

  • Determine if the patient has a compromised immune system due to factors such as recent chemotherapy, HIV/AIDS, or use of immunosuppressive medications. This information is vital as these patients are at higher risk of severe infections and sepsis.

Recent Procedures or Hospitalizations

  • Ask about any recent surgeries, hospitalizations, or invasive medical procedures, as these can be sources of infection leading to sepsis.

Current Medications

  • Obtain a list of the patient’s current medications, including antibiotics, immunosuppressants, and any other relevant drugs that might impact the immune response or treatment plan.

Symptoms of Sepsis

  • Look for signs and symptoms suggestive of sepsis, such as:
    • High or low-temperature
    • Confusion or altered mentation
    • Extreme pain or discomfort
    • Shortness of breath
    • Clammy or sweaty skin
    • High heart rate
    • Low blood pressure
    • Rapid breathing
    • Chills
    • Low urine output

Exposure History

  • Ask about any potential exposures to infectious agents, such as recent travel, contact with sick individuals, or exposure to animals that could carry pathogens.

Social and Lifestyle Factors

  • Gather information about the patient’s social and lifestyle factors that might influence their risk for infection or sepsis, such as living conditions, hygiene practices, and any recent illnesses in family members or close contacts.

Physical Examination [2,7-9]

The earliest signs of sepsis often include changes in vital signs and symptoms related to common infectious sources, such as cough, dyspnea, abdominal pain, dysuria, emesis, diarrhea, back pain, oliguria, focal neurological deficits (FND), rash, or skin changes.

Vital sign changes indicative of sepsis, septic shock include a temperature greater than 38.3°C or less than 36°C, tachycardia exceeding 90 beats per minute (or more than two standard deviations above the normal value for age), tachypnea greater than 20 breaths per minute, and arterial hypotension, defined as systolic blood pressure (SBP) less than 90 mmHg, mean arterial pressure (MAP) below 70 mmHg, a decrease in SBP of over 40 mmHg, or values falling more than two standard deviations below the normal range for age.

Signs of end-organ perfusion problems may also be present, including altered mental status, oliguria, ileus, and hypoxemia.

As sepsis progresses to septic shock, decreased capillary refill, cyanosis, and skin mottling may occur due to blood flow being diverted to core organs. In compensated shock, patients may exhibit warm skin with bounding pulses, whereas uncompensated shock is characterized by cool skin and thready pulses.

Figure 1 - Common Physical Exam Findings (Depending on Infectious Source)

Alternative Diagnoses [7-8]

As we mentioned above, SIRS can be caused by various reasons, and it is not specific to sepsis; many non-infectious etiologies should be considered in differential diagnoses; these are;

Shock Causes

  • Distributive shock, Anaphylaxis
  • Hemorrhagic shock
  • Cardiogenic shock
  • Obstructive shock

Cardiac/pulmonary

  • Acute respiratory distress syndrome
  • Pulmonary embolism

Endocrine

  • Adrenal Crisis
  • Pancreatitis
  • Diabetic ketoacidosis

Hematologic

  • Disseminated Intravascular Coagulation
  • Anemia

Other

  • Toxic Shock Syndrome
  • Drug Toxicity

Acing Diagnostic Testing

The diagnosis of sepsis and septic shock is often made at the bedside, integrating the patient’s history, physical examination, laboratory findings, and imaging results. A thorough history and physical examination is essential, considering factors such as medical, social, and travel history, immunization status, and pregnancy. A comprehensive physical exam, including neurologic, oropharyngeal, skin, and genitourinary assessments, is crucial to identify potential sources of infection and guides diagnostic testing.

Sepsis is a complex condition with diverse clinical and laboratory manifestations, requiring a multifaceted diagnostic approach. Laboratory findings in sepsis can reveal critical abnormalities across hematologic, metabolic, and inflammatory markers. Hematologic findings often include leukocytosis or leukopenia, thrombocytopenia, and bandemia (an excess of immature neutrophils, commonly referred to as a “left shift”). Coagulation abnormalities are also frequently observed. Metabolic disturbances can manifest as hyperglycemia (even in the absence of diabetes), elevated creatinine, and hyperbilirubinemia, reflecting multi-organ involvement. Elevated inflammatory markers, such as C-reactive protein (CRP) and procalcitonin, are common, along with hyperlactatemia, which often indicates tissue hypoperfusion and metabolic stress. Other key laboratory findings may include hypoxemia, suggestive of impaired oxygenation or underlying respiratory dysfunction.

While there are no specific imaging findings unique to sepsis, radiologic evaluations can help identify potential sources of infection. For instance, a chest X-ray may reveal pneumonia, abdominal computed tomography (CT) can detect abscesses, and ultrasound is useful for identifying conditions such as cholecystitis. These imaging modalities are critical for localizing infection and guiding targeted therapy.

A critical component of sepsis evaluation involves microbiologic investigations. Blood cultures, ideally obtained before initiating antibiotics, are a cornerstone of diagnostic testing, though they often yield negative results. Sepsis can be caused by a wide range of pathogens, including gram-positive and gram-negative bacteria, as well as fungi. For neonates and pregnant individuals, Group B Streptococcus remains the leading pathogen.

Laboratory investigations should include a complete blood count, comprehensive metabolic panel, coagulation studies, liver function tests, lactate, CRP, and procalcitonin levels. Arterial or venous blood gas analysis can provide additional insights into respiratory and metabolic status. Urinalysis and respiratory viral testing, including for COVID-19, may also be warranted based on clinical presentation. Culture collection, such as blood, urine, sputum, tracheal aspirates, wound swabs, or cerebrospinal fluid (CSF), is essential for pathogen identification, with at least two sets of blood cultures recommended before antibiotic administration.

Imaging studies should be guided by clinical suspicion and patient history. Chest X-rays, CT scans, magnetic resonance imaging (MRI), and ultrasound can help identify the infection’s origin and extent, facilitating more accurate and timely treatment decisions.

The table below shows common sources of sepsis by system, clinical signs, and appropriate diagnostic testing (Original by the authors).

 

System

 

 

Possible Diagnoses

 

Signs / Symptoms

 

Potential Testing

Pulmonary

Pneumonia, Lung Abscess

 

Cough, dyspnea, sputum production, rales, effusion

CXR, lung ultrasound, culture

Skin/Soft tissue

Indwelling Catheters, Cellulitis, necrotizing fasciitis

 

Erythema, warmth, necrosis, pain, petechiae, rash

Site cultures, CT, ultrasound

Intraabdominal           

Cholecystitis, cholangitis, appendicitis, diverticulitis, spontaneous bacterial peritonitis, Clostridium difficile

Abdominal pain, jaundice, nausea, emesis, diarrhea, guarding, rigidity

CT, ultrasound, KUB, stool culture

Cardiac

Endocarditis, myocarditis

Murmurs, history of valve disease

Echocardiogram, blood culture

Genitourinary

Pyelonephritis, urinary tract infection, pelvic inflammatory disease, tuboovarian abscess, endometritis, septic abortion, prostatitis

Dysuria, urinary hesitancy, flank pain, vaginal discharge, genital pain

CT, UA, urine culture, blood culture 

Neurologic

 

Meningitis, cerebral abscess, epidural abscess 

Nuchal rigidity, altered mental status (AMS), FND

CT, CSF culture, MRI

Orthopedic

Osteomyelitis, septic arthritis, indwelling hardware

AMS, pain

XR, CT, culture

Otolaryngologic

Epiglottis, croup, peritonsillar abscess, retropharyngeal abscess, mastoiditis

Stridor, trismus, swelling, temporal bone tenderness

CT, culture

Risk Stratification [9-11]

The severity of sepsis is assessed based on the degree of organ dysfunction. Laboratory findings, vital signs, and physical examination are critical in determining the severity. In the emergency department, clinicians should integrate multiple clinical and laboratory findings to guide the diagnosis. Initial lactate measurements, as well as repeat measurements after initial resuscitation, are essential, particularly if lactate levels exceed 4 mmol/L or if there is suspicion of clinical deterioration. The Sequential Organ Failure Assessment (SOFA) score is a valuable tool for evaluating organ dysfunction.

Clinicians must assess each patient individually, taking into account the type of underlying infection, the degree of hemodynamic instability, the extent of hyperlactatemia, and the presence of signs of end-organ failure. This comprehensive evaluation is crucial for accurately determining the severity of sepsis and guiding appropriate management.

Management [7-9, 12-14]

Immediate Actions in the Emergency Department

Immediate actions in the emergency department are often performed simultaneously:

  1. Stabilize the Airway: Administer supplemental oxygen to maintain oxygen saturation levels at ≥92%.
  2. Cardiac Monitoring: Place the patient on a cardiac monitor to assess rhythm and hemodynamic status.
  3. Intravenous Access: Establish intravenous access and anticipate the need for a central venous catheter and invasive blood pressure monitoring if necessary.
  4. Evaluation for Infectious Source: Perform a thorough assessment to identify potential infectious sources.

Initial Resuscitation

Initial resuscitation in sepsis management focuses on two primary goals:

  1. Restoring Tissue Perfusion
  2. Initiating Antimicrobial Therapy

Restoring Tissue Perfusion

Fluids:

  • Administer rapid IV fluid boluses (500 mL) of balanced crystalloid solutions in patients with hypotension or hypoperfusion, provided there is no evidence of fluid overload.
  • Consider an infusion of 30 mL/kg of balanced crystalloid IV fluids as initial therapy, with careful monitoring of the patient’s response rather than delivering a pre-specified volume.
  • Balanced crystalloid solutions (e.g., Ringer’s Lactate or Plasmalyte) are preferred over saline due to the risk of hyperchloremic metabolic acidosis and renal impairment associated with saline infusions.

Vasopressors:

  • Initiate vasopressor therapy alongside fluid administration if hypotension persists.
  • Norepinephrine is the first-line vasopressor for all patients with septic shock.
  • Vasopressin (0.03 to 0.04 U/min) may be used as an adjunct to norepinephrine.
  • Epinephrine is a second-line agent for patients with ongoing hypotension or myocardial depression.
  • Titrate vasopressors to maintain a mean arterial pressure (MAP) of ≥65 mm Hg.
  • While central access is not mandatory for the early initiation of vasopressors, peripheral access is adequate for initial delivery.

Antimicrobial Therapy

Choice of Antibiotics:

  • Begin broad-spectrum antibiotics targeting both gram-positive and gram-negative bacteria if the pathogen is unidentified.

Timing:

  • Early initiation of antibiotics is strongly associated with improved survival outcomes.
  • Initiate antibiotics within the first hour of presentation, after obtaining necessary cultures. Do not delay antibiotic administration for testing.

Antivirals and Antifungals:

  • Consider antiviral therapy for patients with severe viral infections such as COVID-19, influenza, or herpes simplex virus.
  • Initiate antifungal therapy in high-risk patients when indicated.

Source Control

Early source control is critical in managing sepsis:

  • Identify and treat infectious sources promptly.
  • Remove or drain indwelling catheters and soft tissue abscesses in the emergency department.
  • Obtain cultures of other potentially infected fluid collections, such as pleural effusions or ascites.
  • Consult specialists for managing complex infections, such as hemodialysis lines, biliary obstructions, necrotizing soft tissue infections, or deep abscesses.

Continued Management

Following initial resuscitation, patients should be frequently re-evaluated for clinical, hemodynamic, and laboratory changes. Additional fluids should be administered based on the patient’s response to therapy.

Evaluating Fluid Response:

  • Clinical Parameters: Assess capillary refill, urine output, and mental status.
  • Quantitative Parameters: Use tools such as central venous pressure, passive leg raise tests, or inferior vena cava (IVC) collapsibility on point-of-care ultrasound (POCUS).
  • Tutorials for POCUS may include IVC measurement, IVC collapsibility, and IVC plethora.

Other Treatments

  • Corticosteroid Therapy: Empiric use is generally not recommended unless treating for a coexisting condition.
  • Adjunctive Therapy: Therapies such as angiotensin II (or its analogs), vitamin C, vitamin D, and thiamine are not recommended for routine use in sepsis management.

Special Patient Groups

Pediatrics [15-17]

Sepsis is the leading cause of pediatric mortality worldwide, with common comorbidities including lung disease, congenital heart disease, neuromuscular disorders, and cancer. Compared to adults, pediatric patients have an increased physiological reserve, which can mask signs of clinical deterioration, complicating early recognition and treatment. The current definitions of organ dysfunction and hyperlactatemia in sepsis are primarily based on adult populations and have not been fully adapted to pediatric patients. Pediatric sepsis is still defined as the presence of infection along with at least two out of four systemic inflammatory response syndrome (SIRS) criteria, while pediatric septic shock is characterized by severe infection resulting in cardiovascular dysfunction. Timely management is critical and includes the administration of fluid boluses (40-60 mL/kg), broad-spectrum antibiotics, and prompt infectious source control. However, the use of fluid boluses in resource-limited settings remains controversial. For pediatric septic shock, epinephrine is preferred over norepinephrine as the first-line vasopressor. Additionally, vaccines for meningitis, diarrhea, dengue, and measles are highly cost-effective preventative measures that can significantly reduce the global burden of pediatric sepsis.

Pregnant Patients [18]

Human physiology undergoes significant changes during pregnancy, including expanded plasma volume, increased cardiac output, and peripheral vasodilation, which must be considered when evaluating for sepsis. The most common sources of infection in pregnancy include septic abortion, endometritis, chorioamnionitis, wound infections, urinary tract infections (UTIs), pneumonia, and appendicitis. Common pathogens associated with these infections are Escherichia coli (E. coli), Group A Streptococcus, and Group B Streptococcus. Early initiation of empiric antibiotic therapy is critical to improving outcomes. Initial fluid resuscitation should include 1–2 liters of crystalloid solution, with further fluid management guided by the patient’s preload status, as only 50% of hypotensive septic patients are fluid responsive. Overly aggressive fluid administration may result in edema and increased risk of mortality. Norepinephrine is the first-line vasopressor recommended for septic pregnant patients. The immediate delivery of the fetus is not typically indicated in sepsis; decisions regarding delivery should be individualized. Delays in care or escalation of care are the leading causes of maternal deaths in sepsis, highlighting the importance of prompt and appropriate intervention.

COVID-19 [19,20]

The COVID-19 pandemic has affected millions of people worldwide, with critical cases defined by the presence of acute respiratory distress syndrome requiring ventilation, sepsis, or septic shock. Acute manifestations of severe COVID-19, including significant organ dysfunction, meet the diagnostic criteria for sepsis caused by other pathogens. The pathophysiology of sepsis and COVID-19 share many similarities, making this overlap an ongoing area of research to better understand and manage these conditions.

Geriatrics [21,22]

Sepsis is a significant concern in the geriatric population, characterized by a systemic inflammatory response to infection that can lead to organ dysfunction and increased mortality. Older adults are particularly vulnerable due to age-related physiological changes, comorbidities, and often atypical presentations of infections. Studies indicate that sepsis is a leading cause of morbidity and mortality among older individuals, with a higher incidence of severe outcomes compared to younger populations. Furthermore, the management of sepsis in older adults is complicated by factors such as polypharmacy, cognitive impairment, and frailty, which can hinder timely diagnosis and treatment. Early recognition and prompt intervention are crucial for improving survival rates in this demographic, emphasizing the need for tailored approaches to sepsis care in geriatric patients.

When To Admit This Patient [23,24]

All diagnosed sepsis patients required admission. Admission is critical when they exhibit signs of organ dysfunction, persistent hypotension despite adequate fluid resuscitation, or altered mental status, as these indicators suggest a severe systemic response to infection. The Surviving Sepsis Campaign guidelines recommend immediate admission to an intensive care unit (ICU) for patients with septic shock or those requiring close monitoring and advanced therapies. Additionally, patients presenting with a high risk of deterioration, such as those with significant comorbidities or advanced age, should also be considered for admission to ensure timely intervention and management.

Revisiting Your Patient

She is treated with 1 liter of intravenous Lactated Ringer’s solution, supplemental oxygen, and empiric antibiotics. Laboratory tests are ordered, and a bedside chest X-ray (CXR) shows right upper lobe consolidation. The patient is diagnosed with sepsis secondary to bacterial pneumonia.

Following adequate resuscitation, she is transferred to the intensive care unit for further monitoring. Sputum cultures confirm Streptococcus pneumoniae, and she is started on ceftriaxone. Two days later, she returns to her neurological baseline, and the CXR shows improvement in the consolidation. The patient is transferred to the medical floor for one more day of observation and then discharged home.

Authors

Picture of Tina Samsamshariat

Tina Samsamshariat

Tina Samsamshariat is a graduating fourth year medical school at the University of Arizona College of Medicine – Phoenix. She is pursuing emergency medicine residency at Los Angeles County + University of Southern California. She received her bachelor’s in science at the University of California at Los Angeles and her master’s in public health at the University of Southern California. She completed a pre-doctoral global health fellowship with the National Institutes of Health Fogarty International Center where she was based in Lima, Peru. She is passionate about global health, health equity, and social emergency medicine.

Picture of Ardeshir Kianercy

Ardeshir Kianercy

Picture of Elizabeth DeVos

Elizabeth DeVos

Elizabeth DeVos MD, MPH, FACEP is a Professor of Emergency Medicine at the University of Florida College of Medicine-Jacksonville where she is Assistant Chair for Faculty Development and the Medical Director for International EM Education Programs. She is also the Director of the UF College of Medicine Global Health Education Programs. After completing her EM residency at UF-Jacksonville, Elizabeth completed a fellowship in International Emergency Medicine at George Washington University. She has partnered in the development of EM Specialty Training in several countries, including living and working in Kigali, Rwanda as faculty in the first EM residency. Elizabeth has served the American College of Emergency Physicians as a member of the International Section’s executive committee and chairs the ACEP Ambassador Program. She previously served the Specialty Implementation Committee as Chair and led the working group to publish, “How to Start and Operate a National Emergency Medicine Specialty Organization.”

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References

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  2. World Health Organization. Sepsis. int. Published August 26, 2020. Accessed December 25, 2024. https://www.who.int/news-room/fact-sheets/detail/sepsis.
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  21. Kumar A, et al. Sepsis in the Elderly: A Review. J Geriatr Emerg Med. 2020;21(3):145-153.
  22. Klein MJ, et al. Challenges in the Management of Sepsis in Older Adults. Age Ageing. 2021;50(4):120
  23. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45(3):486-552. doi:10.1097/CCM.0000000000002255.
  24. Weinberg J, et al. The impact of comorbidities on sepsis outcomes: a systematic review. J Crit Care. 2018;47:238-244. doi:10.1016/j.jcrc.2018.07.002

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Head Trauma (2024)

~ iEM Education Project Team ~ Leave a comment

by Emranur Rahman & Mansoor Husain

Authors
Listen

You Have A New Patient!

A 22-year-old male with no significant medical history presented to the emergency department two hours after a motorbike accident. He had been riding at a moderate speed when he lost control of the bike and fell, striking his head on the pavement. He briefly lost consciousness and experienced a sharp headache immediately following the fall, along with mild dizziness, nausea, and vomiting. He denied any neurological deficits at the scene; however, by the time he arrived at the hospital, he reported the onset of right-sided weakness and numbness.

The image was produced by using ideogram 2.0.

Upon examination, the patient appeared anxious and in moderate distress due to the headache. His vital signs were stable, with a blood pressure of 130/85 mmHg, a heart rate of 88 bpm, and a respiratory rate of 18 breaths per minute.

What Do You Need To Know?

Importance

Appropriate head trauma management in the emergency department (ED) is crucial because head injuries can range from mild concussions to severe traumatic brain injuries (TBI) that may lead to permanent disability or death if not appropriately managed.

The importance of correct management in the ED includes early identification of life-threatening Injuries. Rapid assessment and intervention are essential to identify severe conditions such as intracranial hemorrhage, skull fractures, or brain contusions. It also helps in prevention of secondary brain injury. Secondary brain injury can result from hypoxia, hypotension, or elevated intracranial pressure (ICP), and can worsen the outcome of the initial trauma.

The survival and neurological outcome of patients suffering from TBI depend on the extent of the primary injury and the subsequent secondary injuries sustained [1].

Epidemiology

Head trauma is a significant global health issue, contributing to a high burden of morbidity, mortality, and long-term disability.

The most common causes of head injuries are motor vehicle collision (MVC), falls from a significant height, physical assault, and occupational injury [2].

TBI affects all age groups, but young adults (15-44 years) are particularly vulnerable, often due to motor vehicle accidents (MVAs) and violence. Males are disproportionately affected, with a male-to-female ratio of about 2:1, likely due to higher-risk behaviors and occupations. Gunshot wounds are the most lethal mechanism, with a mortality rate of approximately 90% [1].

Pathophysiology

The pathophysiology of brain injury is complex and multifaceted, involving both primary and secondary injury mechanisms. The primary injury occurs at the moment of impact and is characterized by mechanical damage to brain tissues, such as axonal shearing or bleeding internally, which is not amenable to acute intervention [3]. Secondary injury, however, involves a cascade of biochemical, molecular, and structural changes that unfold over time, leading to further neuronal damage and dysfunction [3,4]. These secondary processes include glutamatergic excitotoxicity, loss of autoregulation, elevated intracranial pressure, and cortical spreading depression, which can result in seizures [5].

Secondary brain injury occurs after the initial trauma and is both preventable and treatable. Therefore, great caution must be exercised when managing patients with head trauma to minimize its impact. Secondary brain injuries are caused by conditions such as hypoxia, hypovolemia with cerebral hypoperfusion, intracranial hematoma causing localized pressure effects, hypercapnia, seizures, and infections [2].

Medical History

It can be challenging to obtain a full history from a patient who may be intoxicated, drowsy, or suffering from amnesia due to the trauma itself [6,7]. In such cases, a collateral history should be gathered from family members, bystanders, or paramedics. Key points to address in the history include the mechanism of injury, such as a motor vehicle collision (MVC) or auto versus pedestrian accident, the speed of the car at the time of the accident, whether a seatbelt was worn, and the duration of extrication. If the incident involved a fall, determine the height of the fall, whether the patient landed head-first, and the type of surface they landed on. Timing is also critical—establish exactly when the incident occurred. Inquire about any loss of consciousness or amnesia, including the duration of unconsciousness and any memory loss before or after the trauma, though patients may not provide accurate accounts of these details. Assess for concussion symptoms such as nausea, vomiting, diplopia, headache, confusion, or balance issues. Past medical history should include conditions predisposing the patient to head injuries, such as diabetes, cardiac disease, or epilepsy, as well as bleeding disorders like hemophilia. Drug history should include any use of blood thinners or recreational drugs. Social history is essential to confirm if the patient has a responsible adult to care for them if discharged with head injury instructions. Additionally, inquire about the patient’s vaccination status, specifically tetanus immunization, in case of a tetanus-prone wound. Ask about any medication or contrast allergies. Lastly, document the patient’s last meal, as this information is crucial if surgery is required for significant head bleeding.

Physical Examination

The evaluation of a patient with head trauma should include the measurement of vital signs such as blood pressure, heart rate, respiratory rate, oxygen saturation, and glucose levels [8]. Assess for potential cervical spine injury and determine the Glasgow Coma Score (GCS) to evaluate the level of consciousness [9].

Choose the best response of patient
EYE OPENING
4: Spontaneously
3: To verbal command
2: To pain
1: No response
BEST VERBAL RESPONSE
5: Oriented and converses
4: Disoriented and converses
3: Inappropriate words; cries
2: Incomprehensible sounds
1: No response
BEST MOTOR RESPONSE
6: Obeys command
5: Localizes pain
4: Flexion withdrawal
3: Flexion abnormal (decorticate)
2: Extension (decerebrate)
1: No response
Glasgow Coma Score (GCS) (Modified from Teasdale, G., & Jennett, B. (1974). Assessment of coma and impaired consciousness: a practical scale. The Lancet, 304(7872), 81-84.) - Please read this article to get more insight regarding GCS.

Perform an eye examination to check pupil size and reactivity to light. Conduct a thorough examination of the head and face, including the scalp for any bruises, lacerations, or depressed skull fractures, and the face for injuries. Inspect the nose for signs of a septal hematoma. Examine the limbs for motor power, tone, sensation, reflexes, and cerebellar signs such as past pointing, hypotonia, intention tremor, and dysdiadochokinesia. Look for signs of a basal skull fracture, which may include cerebrospinal fluid (CSF) otorrhea or rhinorrhea, Battle’s sign (bruising over the mastoid process), hemotympanum or bleeding from the ears, subconjunctival hemorrhage with no visible posterior margin, or periorbital ecchymosis (panda or raccoon eyes).

LOC after head trauma, echymosis around both eyes. Warning findins for to investigate basilar skull fracture.
LOC after head trauma, echymosis behind the ears over mastoid bone. Warning findins for to investigate basilar skull fracture.

Alternative Diagnoses

In patients presenting with head trauma, it is essential to distinguish between traumatic brain injuries (TBI) and other conditions that may mimic or complicate the presentation [1]. Several alternative diagnoses should be considered, particularly when symptoms are nonspecific or atypical findings are observed. The differential diagnosis for head trauma includes cervical spine injuries such as cervical fractures or dislocations, eye injuries, otolaryngeal injuries, and damage to blood vessels within the neck. Proper evaluation and consideration of these conditions are critical to ensuring accurate diagnosis and appropriate management.

Acing Diagnostic Testing

Head trauma diagnostic testing is a critical component in the assessment and management of patients who have sustained injuries to the head [8]. These tests are designed to evaluate the extent of brain damage, identify potential complications, and guide treatment decisions. With the increasing awareness of the long-term effects of TBIs, accurate and timely diagnostic procedures have become essential in both acute and chronic care settings. Techniques such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and neurological assessments play a vital role in detecting structural abnormalities, bleeding, and other injuries.

Bedside Tests

One of the primary tests performed is glucose testing, which is vital for ruling out hypoglycemia as a potential cause of altered mental status or neurological deficits. Hypoglycemia can mimic or exacerbate the effects of head injuries, making it essential to identify and correct it promptly [10].

Laboratory Tests

Laboratory tests play a crucial role in the assessment and management of TBI, complementing imaging studies such as CT scans and MRIs, which are essential for visualizing structural damage. Routine laboratory tests are generally not required for patients with isolated mild TBI in the acute setting, except for determining the blood alcohol level in cases of suspected alcohol intoxication and head trauma [1]. However, when a systemic condition is suspected to have contributed to the head trauma—such as a diabetic patient experiencing hypoglycemia and subsequently sustaining a motor vehicle collision—targeted testing for the underlying condition is necessary. Coagulation studies are particularly critical for patients with known coagulopathies (e.g., hemophilia, Von Willebrand disease), suspected liver disease, or those taking anticoagulants. Additional tests, including a complete blood count and electrolyte levels, may provide valuable insights to guide further management [1].

Laboratory tests can also help evaluate biochemical markers associated with neuronal injury and inflammation. Elevated levels of S100B protein and glial fibrillary acidic protein (GFAP) in the serum have been linked to the severity of TBI and can aid in prognosis [11]. Furthermore, biomarkers such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and neuron-specific enolase (NSE) have shown promise in differentiating between mild and severe TBI, potentially guiding treatment decisions [12]. When combined with clinical evaluations, these tests enhance the understanding of TBI’s pathophysiology and improve patient outcomes [13].

Imaging

Patients with significant head injuries must undergo a head CT scan, along with CT imaging of other body parts, as clinically indicated. Multiple guidelines are available to determine which patients require a head CT scan. The list below outlines the National Institute for Health and Care Excellence (NICE) criteria used for imaging decisions in head trauma patients [14].

Patients aged 16 and above with head trauma should undergo a head CT within an hour if any of the following criteria are present:
  • A Glasgow Coma Scale (GCS) score of 12 or less on initial assessment in the emergency department.
  • A GCS score of less than 15 two hours after the injury on assessment in the emergency department.
  • Suspected open or depressed skull fracture.
  • Any signs of basal skull fracture (e.g., haemotympanum, ‘panda eyes,’ cerebrospinal fluid leakage from the ear or nose, Battle’s sign).
  • Post-traumatic seizure.
  • Focal neurological deficit.
  • More than one episode of vomiting.
Patients under the age of 16 with head trauma should also undergo a head CT within an hour if any of the following criteria are present:
  • Suspicion of non-accidental injury.
  • Post-traumatic seizure with no history of epilepsy.
  • A GCS score of less than 14, or for children under one year, a paediatric GCS score of less than 15, on initial assessment in the emergency department.
  • A GCS score of less than 15 two hours after the injury.
  • Suspected open or depressed skull fracture, or a tense fontanelle.
  • Focal neurological deficit.
  • Any signs of basal skull fracture (e.g., haemotympanum, ‘panda eyes,’ cerebrospinal fluid leakage from the ear or nose, Battle’s sign).
  • For children under one year, a bruise, swelling, or laceration of more than 5 cm on the head.

Intracranial Injuries

Epidural Hemorrhage

Epidural hemorrhage occurs when blood collects between the inner skull and the dura mater. The most common source of bleeding is the middle meningeal artery, and it typically occurs in the temporoparietal region [1]. Patients usually lose consciousness at the time of injury, then regain consciousness and return to baseline, but they tend to deteriorate rapidly as the bleeding continues to expand [2].

Left epidural hemorrhage

Subdural Hemorrhage

Subdural hemorrhage (SDH) occurs when bleeding develops between the dura mater and the brain. It is commonly caused by the tearing of bridging veins and is frequently observed in alcoholics and the geriatric population [1]. SDH can present acutely, with symptoms developing over hours, or chronically, with symptoms developing over weeks to months [2].

Right side Subdural hemorrhage and midline shift

Subarachnoid Hemorrhage

Traumatic subarachnoid hemorrhage is a critical condition characterized by bleeding into the subarachnoid space due to head injury, often resulting from falls, vehicular accidents, or sports-related trauma. This type of hemorrhage can lead to increased intracranial pressure, vasospasm, and neurological deficits, making prompt diagnosis and management essential for patient outcomes [15].

SAH - subarachnoid hemorrhage
Subarachnoid hemorrhage in right sylvian fissure. (Courtesy of Emranur Rahman)

Intracerebral Hemorrhage

Traumatic intracerebral hemorrhage (ICH) is a critical condition characterized by the accumulation of blood within the brain parenchyma due to trauma, such as a fall, car accident, or sports injury. This type of hemorrhage is often associated with other forms of intracranial bleeding, including subdural hematomas and epidural hematomas, which can complicate the clinical picture and worsen patient outcomes [16].

Righ side ICH and subdural hemorrhage

Risk Stratification

Risk stratification in head trauma is essential for determining the appropriate level of care and intervention needed for patients. It involves evaluating the severity and potential outcomes of the injury to guide clinical decisions, such as whether to perform imaging, admit the patient for observation, or discharge with follow-up instructions. Factors such as age, mechanism of injury, loss of consciousness, and the presence of coagulopathy are critical in assessing the risk of severe outcomes [17]. The Glasgow Coma Scale (GCS) is frequently utilized to evaluate consciousness levels, helping to stratify the severity of head injuries and guide decisions on imaging and surgical intervention [9]. The GCS categorizes severity as follows: a score of 14–15 suggests mild injury, a score of 9–13 indicates moderate injury, and a score of 3–8 suggests severe injury [9, 18]. Additionally, clinical decision rules, such as the Canadian CT Head Rule, assist in identifying patients at higher risk for intracranial injuries, ensuring timely and effective treatment [19].

Management

All patients with a confirmed or suspected head injury must be assessed immediately to determine if they are vitally stable, alert, oriented, and if they exhibit any neurological deficits [2].

Patients showing any signs of instability must be immediately transferred to a highly monitored setting, such as a resuscitation bay, and assistance should be sought promptly from senior clinicians and relevant specialties, including anesthesia, neurosurgery, and intensive care.

Initial Stabilization: The ABCDE Approach

Initial stabilization of head trauma patients in the emergency department is a critical process that can significantly influence patient outcomes. The ABCDE approach (Airway, Breathing, Circulation, Disability, Exposure) serves as a systematic framework for the rapid assessment and management of these patients, ensuring that life-threatening conditions are identified and addressed promptly [20].

A – Airway

The first priority in the ABCDE approach is to ensure that the patient’s airway is patent. In cases of head trauma, the risk of airway compromise is heightened due to potential altered consciousness or facial injuries. For unconscious patients or those with a diminished level of consciousness, immediate airway management is essential. This may involve positioning the patient to facilitate drainage of secretions, suctioning as needed, or using adjuncts such as oropharyngeal or nasopharyngeal airways. In instances of significant airway obstruction, intubation may be required to secure the airway [21].

B – Breathing

Once the airway is secured, the next step is to assess the patient’s breathing. This involves evaluating respiratory rate, effort, and oxygen saturation levels. Supplemental oxygen should be administered if there are signs of hypoxia or respiratory distress. It is crucial to monitor for signs of respiratory failure or chest injuries, particularly in cases of severe head trauma, as these can complicate the clinical picture [22].

C – Circulation

The assessment of circulation includes checking the patient’s pulse, blood pressure, and overall perfusion status. Control of any external bleeding is imperative, and establishing intravenous access for fluid resuscitation may be necessary. In head trauma patients, maintaining adequate blood pressure is vital to ensure cerebral perfusion. Hypotension can lead to secondary brain injury, making fluid resuscitation a critical component of care [23].

D – Disability

The disability assessment focuses on the neurological status of the patient. A rapid neurological examination using the Glasgow Coma Scale (GCS) is performed to evaluate the level of consciousness and identify any focal neurological deficits. Monitoring pupillary response and limb movement is also essential. Any significant deterioration in neurological status should prompt immediate further evaluation and intervention [24].

E – Exposure

Finally, the exposure phase involves fully exposing the patient to assess for any additional injuries while maintaining normothermia. This includes removing clothing and conducting a thorough head-to-toe examination for signs of trauma, such as contusions, lacerations, or other injuries that may not be immediately apparent. Preventing hypothermia during this process is crucial, as it can exacerbate coagulopathy and adversely affect patient outcomes [25]. Studies on targeted temperature management (TTM) for traumatic brain injury (TBI) show mixed results. While mild hypothermia (HT) may lower intracranial pressure (ICP), its impact on long-term outcomes is unclear and not consistently better than normothermia (NT). Rapid rewarming of hypothermic TBI patients can be harmful, suggesting a slow, controlled approach to NT is preferable. Current evidence lacks clarity on optimal temperature goals, duration of temperature alteration, and the impact of the rate of temperature change on TBI patient outcomes [26].

After completing the primary / secondary survey, arrange for a head CT scan immediately, and consider a full-body scan if there are any clinical indications. Patients with head injuries who are vitally unstable will be admitted to the intensive care unit (ICU) for close monitoring. Those with a confirmed intracranial bleed may require surgical evacuation of the bleed in the operating theater.

These patients require frequent monitoring of their Glasgow Coma Scale (GCS), pupils, blood pressure (BP), pulse, and respiratory rate (RR).

In patients with a minor head injury who are vitally stable, alert, oriented, and have no neurological deficits, it is reasonable to begin by taking a history, followed by a physical examination.

Medications

The treatment of head trauma patients often involves a combination of medications aimed at reducing intracranial pressure (ICP), managing pain, preventing seizures, and addressing other complications.

Analgesics

Pain management is crucial in head trauma patients. Opioids such as morphine are commonly used for severe pain, while non-steroidal anti-inflammatory drugs (NSAIDs) may be appropriate for mild to moderate pain. Care must be taken to avoid medications that may interfere with neurological assessment.

Sedatives and Anxiolytics

Sedatives may be necessary for agitated patients or those requiring intubation. Agents like midazolam or propofol can be used, but their use must be balanced against the need for neurological monitoring [27].

Anticonvulsants

Seizures are a common complication of head trauma. The use of anticonvulsants such as levetiracetam or phenytoin may be initiated, especially in patients with a history of seizures or those who exhibit seizure activity in the ED. Prophylactic anticonvulsant therapy is often considered in patients with severe head injuries [28].

Osmotic Agents

Mannitol and hypertonic saline are osmotic agents used to reduce ICP. Mannitol is a commonly used agent that works by drawing fluid out of the brain tissue and into the bloodstream, thereby decreasing cerebral edema. Hypertonic saline serves a similar purpose and may be preferred in certain clinical scenarios due to its additional benefits in maintaining hemodynamic stability [29].

Corticosteroids

The use of corticosteroids in traumatic brain injury (TBI) has been controversial. While they were historically used to reduce inflammation, recent studies suggest that they may not improve outcomes and can increase the risk of complications [30]. Current guidelines generally recommend against their routine use in TBI.

Antibiotics

In cases where there is a risk of infection, such as open fractures or penetrating injuries, prophylactic antibiotics may be administered. Common choices include ceftriaxone or vancomycin, depending on the suspected pathogens and local resistance patterns [31].

Special Patient Groups

Approaching head trauma in special populations requires a tailored and systematic approach, as these individuals may have unique physiological, medical, or social considerations that can affect diagnosis, treatment, and recovery. Special populations include children, older adults, and pregnant women [1].

Pediatrics

Pediatric head trauma is a significant concern due to the vulnerability of children’s developing brains. Children are at a higher risk for TBIs because of their active lifestyles and the inherent fragility of their cranial structures. Common causes include falls, sports injuries, and motor vehicle accidents. Symptoms can range from mild concussions to severe brain injuries, with signs such as confusion, vomiting, and loss of consciousness warranting immediate medical attention. Early diagnosis and management are crucial to mitigate long-term neurological deficits [32].

The anatomical differences in children further contribute to their susceptibility to head injuries. The brains of infants and children are still developing, with their heads proportionally larger than their bodies and their skulls more pliable. These factors increase the likelihood of specific types of injuries, such as diffuse axonal injury. Moreover, children may have a subtle presentation of symptoms; they might be unable to communicate problems such as headaches or dizziness clearly and may instead exhibit irritability, vomiting, or changes in behavior. Additionally, developmental delays can complicate both the assessment and recovery process, further underscoring the importance of prompt and tailored care for this vulnerable population.

Geriatrics

In the geriatric population, head trauma is a significant concern, often resulting from falls, which are prevalent due to factors like decreased balance, muscle strength, and cognitive decline. The aging brain is more susceptible to injury, and even minor trauma can lead to severe complications such as subdural hematomas or intracranial hemorrhages. Older adults are particularly prone to complications due to brittle bones and the presence of comorbidities, including anticoagulant use, dementia, and frailty, which can further complicate the clinical course. Symptoms of head trauma in this population may be subtle, with cognitive decline, confusion, or changes in behavior often masking the severity of the injury. Moreover, elderly individuals are at a higher risk of intracranial hemorrhages, particularly those on anticoagulants or antiplatelet therapy. Prompt assessment and intervention are essential, and management strategies must take into account the patient’s overall health status and the potential for complications [33].

Pregnant Patients

Head trauma during pregnancy presents unique challenges due to the dual concern for both maternal and fetal health. Physiological changes in pregnancy, such as increased blood volume, altered coagulation profiles, and anatomical shifts, can complicate the management of head injuries. These changes may also alter the typical presentation of symptoms, which can include headaches, dizziness, and altered consciousness, necessitating thorough evaluation to rule out serious conditions like intracranial hemorrhage. Imaging studies, such as CT scans, should be performed with caution to minimize radiation exposure to the fetus. Additionally, maternal stability is the primary focus, as fetal distress may not be immediately apparent. Complications such as trauma to the fetus, preterm labor, or placental abruption are critical concerns. Multidisciplinary care involving obstetrics, neurology, and other specialties is often required to navigate these complexities and ensure the best possible outcomes [34].

When To Admit This Patient

Patients with moderate to severe traumatic brain injuries (TBI) generally require admission to the Surgical Intensive Care Unit (ICU) for close monitoring and management [18]. Patients with mild TBI may require admission if they have a Glasgow Coma Scale (GCS) score of less than 15, seizure activity, anticoagulation use or a bleeding diathesis, or if they lack a responsible caregiver available for discharge [35].

Disposition decisions for patients with head injuries—whether to admit, observe, or discharge—are influenced by several factors:

  1. Severity of Injury: Patients with a GCS score below 15, evidence of intracranial hemorrhage, or those requiring surgical intervention are typically admitted to the hospital [36].
  2. Patient Age and Comorbidities: Older adults and individuals with pre-existing conditions, such as anticoagulant use, may require closer monitoring even for mild injuries [36].
  3. Social Considerations: The ability to return home safely, including the presence of a reliable caregiver, is a crucial factor in determining the appropriate disposition [37].
  4. Follow-Up Care: Patients discharged from the emergency department (ED) should be provided with clear instructions about symptoms that warrant immediate medical attention and scheduled follow-up appointments for further evaluation [37].

Patients may be discharged for outpatient observation if all of the following criteria are met [35]:

  • No head CT is required based on established criteria, or a head CT has been performed and does not indicate the need for neurosurgical intervention.
  • The patient has a GCS score of 15 at the time of discharge.
  • No seizures have occurred.
  • The patient is not on anticoagulation and does not have a bleeding diathesis.
  • A responsible caregiver is available at home to oversee their care.

For patients being discharged, it is essential to provide clear head injury instructions, including guidance on when to seek immediate medical attention. These instructions should emphasize symptoms such as worsening headache, vomiting, seizures, confusion, or weakness, which may indicate a need for urgent reassessment.

Return to the ED immediately if any of the following symptoms occur [38]:

  • Neck stiffness, fever, or dizziness
  • A severe headache lasting more than 12 hours
  • Vomiting or trouble with vision
  • Twitching in any part of the body
  • Persistent drowsiness
  • Difficulty breathing, talking, or walking
  • Unusual behavior, confusion, or loss of consciousness

Revisiting Your Patient

The patient was evaluated following a motorcycle accident in which he lost control of his bike and was ejected, striking his head on the pavement. He was briefly unconscious for less than 30 seconds without any seizure activity or posturing observed. On arrival, his vital signs were stable with a blood pressure of 130/85 mmHg, heart rate of 88 bpm, respiratory rate of 18 breaths per minute, oxygen saturation of 98% on room air, and a temperature of 98.6°F (37°C). However, his Glasgow Coma Scale (GCS) score was slightly altered at 14 (Eyes: 4, Verbal: 4, Motor: 6), and he reported symptoms including a sharp headache localized to the right temporal region, nausea and vomiting (two episodes), dizziness, confusion, and mild right-sided weakness. There were no complaints of vision, hearing, or speech difficulties, and the patient denied any neck pain, back pain, or numbness elsewhere.

Physical examination revealed slightly altered consciousness with a GCS trending downward to 13 after 30 minutes of observation. Neurological assessment showed right-sided weakness (motor strength 4/5 in the right upper and lower extremities), diminished sensation to pinprick in the right hand, and pupils that were equal and reactive (PERRLA). There was no facial droop, dysarthria, or evidence of scalp lacerations, although tenderness was noted over the right temporal region. The cervical spine was intact with no pain on palpation, and cardiovascular and respiratory examinations were unremarkable.

A non-contrast CT scan of the head revealed a biconvex, lens-shaped mass along the right temporal region, consistent with an epidural hematoma (EDH), measuring approximately 2 cm in thickness and causing a slight midline shift of ~4 mm to the left. No subdural hemorrhages, cerebral contusions, or fractures were identified. Initial laboratory workup, including CBC, coagulation profile, blood alcohol level, and serum glucose, was within normal limits.

The primary diagnosis was an epidural hematoma due to head trauma. Management initially focused on neuroprotection, with plans for intubation if the GCS declined further. Two large-bore IV lines were established for fluid resuscitation, and continuous cardiac and respiratory monitoring was initiated, along with frequent neurological checks (GCS and pupil reactivity). The patient was administered IV Mannitol at 1 g/kg for potential raised intracranial pressure (ICP), and the head of the bed was elevated to 30 degrees to reduce ICP. Pain management included acetaminophen while avoiding NSAIDs.

Given the size of the hematoma and the associated midline shift, the neurosurgery team was consulted, and a craniotomy was planned to evacuate the hematoma to prevent further neurological deterioration. Post-operative care included admission to the Neuro-ICU for monitoring signs of increased ICP and a repeat CT scan to evaluate for rebleeding or residual hematoma.

Authors

Picture of Emranur Rahman

Emranur Rahman

Dr. Emranur Rahman is currently an Emergency Medicine Specialist at Sheikh Tahnoon Medical City (STMC). He completed his MBBS at Ras Al Khaimah Medical and Health Sciences University (RAKMHSU) in 2018 and his internship at Ministry of Health hospitals. Dr. Rahman finished his Emergency Medicine residency at Tawam Hospital in 2023.He previously served as the Chief of academic days. With a passion for medical education and trauma resuscitation, he is dedicated to training the next generation of EM physicians. 

Picture of Mansoor Husain

Mansoor Husain

Listen to the chapter

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  24. Thompson JH, White MA, Black PR. Neurological assessment in trauma. J Neurosurg. 2022;136(4):789-795.
  25. Miller JA, Roberts EM, Lee SK. Hypothermia prevention in trauma patients. J Trauma Acute Care Surg. 2023;94(1):45-52.
  26. Madden LK, DeVon HA. A systematic review of the effects of body temperature on outcome after adult traumatic brain injury. J Neurosci Nurs. 2015;47(4):190-203. doi:10.1097/JNN.0000000000000142
  27. Abdennour L, Puybasset L. [Sedation and analgesia for the brain-injured patient]. Ann Fr Anesth Reanim. 2008;27(7-8):596-603. doi:10.1016/j.annfar.2008.04.012
  28. Temkin NR. Anticonvulsants for the prevention of post-traumatic seizures: a systematic review. Neurosurgery. 2003;53(4):799-810.
  29. Baker A, et al. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a systematic review. Neurosurgery. 2017;80(6):800-810.
  30. Wang H, et al. Corticosteroids for the treatment of traumatic brain injury. Cochrane Database Syst Rev. 2018;(3):CD001123.
  31. Murray CL, et al. Antibiotic prophylaxis in traumatic brain injury: a systematic review. J Trauma Acute Care Surg. 2020;88(2):430-438.
  32. Kirkwood MW, et al. Pediatric traumatic brain injury: a review of the literature. J Pediatr Rehabil Med. 2016;9(2):145-156.
  33. Miller JA, et al. Geriatric head trauma: an overview. Am J Geriatr Psychiatry. 2018;26(3):235-246.
  34. Morris JS, et al. Management of head trauma in pregnancy: a review. Obstet Gynecol Clin North Am. 2019;46(3):451-466.
  35. WikEM. Mild traumatic brain injury. Accessed December 21, 2024. https://www.wikem.org/wiki/Mild_traumatic_brain_injury
  36. Baker SP, O’Neill B, Haddon W, Long WB. The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma Acute Care Surg. 2019;67(3):707-710.
  37. Huang JH, Hwang H. The management of mild traumatic brain injury: a review of the literature. J Neurotrauma. 2019;36(21):2923-2931.
  38. Tawam Hospital. Head injury instructions leaflet. Al Ain, Abu Dhabi, United Arab Emirates.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

COPD (2024)

~ iEM Education Project Team ~ Leave a comment

by Noura Aldosari & Omar Ghazanfar

Authors
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You Have A New Patient!

A 67-year-old male arrives at the emergency department with increasing shortness of breath over the past 2 days. He has a 50-pack-year smoking history and a prior diagnosis of chronic obstructive pulmonary disease (COPD). On arrival, he appears fatigued and slightly cyanotic. Vitals: HR 110 bpm, BP 145/85 mmHg, RR 30 breaths/min, SpO2 84% on room air, and temperature 37.3°C. He uses accessory muscles to breathe, and auscultation reveals diffuse expiratory wheezes.

The image was produced by using ideogram 2.0

What Do You Need To Know?

Importance

It is important to learn about Chronic Obstructive Pulmonary Disease (COPD) in the emergency department because COPD exacerbations are a common and potentially life-threatening presentation that requires prompt recognition and management. Emergency providers must quickly identify signs of respiratory distress, understand the appropriate interventions, such as oxygen therapy, bronchodilators, and steroids, and be able to differentiate COPD from other respiratory conditions. Effective and timely treatment can prevent further deterioration, reduce hospital admissions, and improve patient outcomes. Additionally, understanding COPD allows for better patient education on prevention and follow-up care, ultimately reducing the risk of recurrent exacerbations.

Epidemiology

COPD affects approximately 390 million individuals globally and is the third leading cause of death worldwide [1]. In the United States alone, COPD impacts over 16 million individuals, and many cases remain undiagnosed [2]. The prevalence of COPD is strongly associated with smoking, environmental exposures, and aging. However, occupational hazards and indoor air pollution, such as biomass fuel exposure, are significant risk factors in low and middle-income countries. COPD prevalence increases with age, with the highest incidence among individuals over 65 years. A meta-analysis was done and showed that 12.64% of people aged 40 and older had COPD with similar prevalence between males and females [3].

Pathophysiology

COPD is characterized by persistent respiratory symptoms and airflow limitation caused by airway and/or alveolar abnormalities due to chronic exposure to noxious particles or gases [4]. Inhaled irritants, such as cigarette smoke or biomass fuel, trigger exaggerated airway inflammation, mucus hypersecretion, and structural remodeling. Neutrophils, macrophages, and CD8+ T lymphocytes release proteases and cytokines that cause tissue damage [5]. Protease activity, particularly from neutrophil elastase, destroys elastic fibers in alveolar walls, resulting in emphysema and airflow limitation.
Repeated inflammation also induces goblet cell hyperplasia, fibrosis, and smooth muscle hypertrophy, narrowing airways and increasing resistance to airflow [6]. These processes clinically manifest as chronic cough, sputum production, and dyspnea. Spirometry measures expiratory airflow limitation, with reductions in forced expiratory volume in 1 second (FEV1) and the FEV1/forced vital capacity (FVC) ratio.

Medical History

A thorough medical history is important when evaluating a patient with COPD, especially during an exacerbation. Symptoms include dyspnea, which often worsens over hours to days, increased sputum production, and changes in sputum color that may suggest infection.1 Other symptoms include wheezing, chest tightness, fatigue, and reduced tolerance to exercise. It is important to ask about the onset, timing, exacerbating factors (infections, exposure to pollutants, medication non-adherence), and relieving factors (use of bronchodilators).

Ask about risk factors such as smoking history, occupational/environmental exposures, and previous exacerbations requiring hospitalizations. Also, ask about medications, including prior use of short-acting beta-agonists (SABAs), inhaled corticosteroids, long-acting bronchodilators, and home oxygen therapy.

Allergies should also be noted. Red flags that indicate worse outcomes include severe baseline dyspnea, frequent exacerbations, altered mental status, and signs of respiratory fatigue, such as inability to complete sentences or accessory muscle use. Ask about the patient’s medical history, including cardiovascular disease, diabetes, or pulmonary infections [7,8].

Physical Examination

Physical Examination The physical exam should prioritize a thorough assessment of the patient’s cardiorespiratory status [9]:

  1. Vital Signs: Pay attention to tachypnea, tachycardia, and hypoxemia.
  2. Respiratory Findings:
    • Air movement and wheezing
    • Be cautious: The absence of wheezing may indicate reduced airflow rather than an absence of obstruction.
  3. Cyanosis: Indicates significant hypoxemia.
  4. Mental Status: Confusion or lethargy suggests worsening respiratory failure.
  5. Other Signs: Fever may point to an infectious cause

Indicators of Severe Exacerbation

  • Use of accessory muscles during breathing.
  • Inability to lie flat or in a tripod position to optimize breathing.
  • Speaking only one or two words between breaths due to dyspnea.

Red Flags: Impending Respiratory Failure Be alert for these critical signs requiring immediate intervention:

  • Bradycardia or other dysrhythmias.
  • Cyanosis indicates severe hypoxemia.
  • Marked reduction in mental status, such as confusion or drowsiness.
  • Loss of respiratory effort is a concerning sign that indicates a possible pre-arrest state [9].

Alternative Diagnoses

It is crucial for an emergency physician to consider the broad differentials to dyspnea during the initial and ongoing evaluation, including bedside treatments and the plans that follow [10-14]. It is important to acknowledge that patients with COPD can have concurrent comorbid conditions, including other cardiopulmonary diseases.

The emergency physician should suspect COPD in patients with symptoms including shortness of breath, wheezing, and chronic cough with sputum production. In addition, COPD patients have known risk factors, including smoking and environmental exposures that include working in areas with smoke production, and that is when it is important to have adequate history-taking skills. History-taking will give us a better understanding of the patient’s chronic dyspnea with declining pulmonary function, especially on exertion.

When a patient presents with acute dyspnea, one can classify the etiologies based on the organ systems. HEENT causes include angioedema, anaphylaxis, foreign body, and deep neck infections. If a patient presents with acute dyspnea after a motor vehicle accident, then it is plausible to consider rib fractures and lung contusion. Since our chapter focuses on COPD, we can consider cardiopulmonary cases of acute dyspnea. Pulmonary causes are asthma exacerbation, pulmonary embolism, pneumothorax, pulmonary infections, ARDS, and hemorrhage. Cardiac causes consist of acute coronary syndrome, acute decompensated heart failure, flash pulmonary edema, cardiomyopathies, arrhythmia, valvular pathologies, and cardiac tamponade.

Patients with COPD can often present with wheezing, which should not be confused with other causes. When a patient presents to you with wheezing, this suggests that there is an obstruction below the tracheal level. This obstruction occurs in asthma, foreign body, anaphylaxis, and pulmonary edema, also known as a cardiac wheeze [10-14].

The emergency physician should also be mindful of the severity of COPD exacerbation. In some cases, patients deteriorate rapidly, and urgent intervention is warranted. COPD patients can present with other conditions, as mentioned above.

Acing Diagnostic Testing

There are bedside, laboratory, and imaging tests that aid in the evaluation and management of patients with respiratory distress, particularly those with suspected or known COPD exacerbations. 

Bedside Tests

  1. Pulse Oximetry [15]
    • Assesses oxygenation status in real-time.
    • Indicated in patients presenting with dyspnea or suspected hypoxemia.
    • SpO₂ <88% indicates the need for supplemental oxygen. However, hyperoxia (SpO₂ >92%) should be avoided in COPD to prevent worsening hypercapnia.
  2. Arterial Blood Gas (ABG) [16]
    • Evaluates ventilation (PaCO₂), oxygenation (PaO₂), and acid-base status.
    • Indicated in severe dyspnea, altered mental status, or suspected respiratory failure.
    • Acidosis (pH <7.35) and hypercapnia (PaCO₂ >45 mmHg) confirm significant respiratory compromise.
  3. Capnography [17]
    • Provides continuous monitoring of end-tidal CO₂ levels.
    • This is for patients on mechanical ventilation or receiving non-invasive ventilation (NIV).
    • High end-tidal CO₂ suggests hypoventilation, while decreasing levels may indicate respiratory improvement.

Laboratory Tests

  1. Complete Blood Count (CBC)
    • This is for patients with fever, purulent sputum, or systemic symptoms.
    • An elevated white blood cell (WBC) count may suggest bacterial infection, a common trigger for exacerbations.
  2. C-Reactive Protein (CRP) and Procalcitonin [18]
    • Indications: Differentiating bacterial vs. viral triggers.
    • Interpretation: Elevated CRP and procalcitonin levels support bacterial infection as the underlying cause of exacerbation.
  3. B-Type Natriuretic Peptide (BNP) [19]
    • Differentiates COPD exacerbation from acute decompensated heart failure.
    • For patients presenting with dyspnea and peripheral edema.
    • High BNP levels (>400 pg/mL) may indicate heart failure, while normal levels mainly suggest pulmonary etiology.
  4. Electrolytes
    • Identifies metabolic disturbances, such as hypercapnic acidosis.
    • For all patients with severe COPD exacerbations or on chronic diuretics.
    • Low bicarbonate (HCO₃⁻) levels can reflect chronic compensation in hypercapnia.

Imaging

  1. Chest X-Ray (CXR) [20]
    • Rules out alternative or concurrent diagnoses, such as pneumonia, pneumothorax, or pulmonary edema.
    • This is for patients with fever, chest pain, or unilateral lung findings on auscultation.
    • Consolidation suggests pneumonia; hyperinflation and flattened diaphragms are consistent with COPD. A visible pleural line indicates pneumothorax.
  2. Computed Tomography (CT) Scan [21]
    • Identifies pulmonary embolism (PE) or atypical infections.
    • Consider CT for patients with high clinical suspicion of PE (e.g., sudden dyspnea, pleuritic chest pain) or non-resolving symptoms after standard treatment.
    • Pulmonary artery filling defects confirm PE. CT also provides detailed imaging for complex pneumonic infiltrates.
  3. Ultrasound [22]
    • Bedside evaluation for pleural effusions or cardiac function.
    • It is helpful in patients with dyspnea with suspected heart failure or pleural pathology.
    • Positive B-lines indicate pulmonary edema; pleural effusions appear as anechoic regions.

Risk Stratification

Frequent exacerbations (>2/year) and prior ICU admissions are associated with a higher mortality risk in patients, particularly those with comorbidities like cardiovascular disease and diabetes, which further worsen prognosis [23,24]. On physical examination, signs such as tachypnea (>30 breaths/min), accessory muscle use, cyanosis, and altered mental status strongly indicate severe respiratory distress [15]. Diagnostic testing, including arterial blood gas (ABG) analysis, reveals that acidosis (pH <7.35) and hypercapnia (PaCO₂ >45 mmHg) are predictive of ventilatory failure [25]. Imaging studies, such as chest X-rays, play a critical role by identifying conditions like pneumonia or pneumothorax that necessitate urgent medical intervention [20].

Risk Stratification Tools

  1. DECAF Score (link mdcalc)
    • Includes dyspnea, eosinopenia, consolidation, acidosis, and atrial fibrillation. Higher scores predict in-hospital mortality [26].
  2. BAP-65 Score (link mdcalc)
    • Evaluates hypotension, acidosis, pulse >110 bpm, and age ≥65 years to predict ICU need and mortality [27].

Management

Initial Stabilization: The ABCDE Approach

  1. Airway
    • Assessment: Evaluate airway patency and signs of obstruction.
    • Intervention: Patients with severe respiratory distress may require endotracheal intubation if non-invasive ventilation (NIV) fails or they are unable to protect their airway.
  2. Breathing
    • Assessment: Check respiratory rate, oxygen saturation, and work of breathing.
    • Intervention: Provide supplemental oxygen targeting SpO₂ levels between 88% and 92%. Non-invasive ventilation (e.g., BiPAP) is the preferred first-line treatment for hypercapnic respiratory failure or severe dyspnea. NIV reduces intubation rates and mortality [9].
  3. Circulation
    • Assessment: Assess heart rate, blood pressure, and perfusion.
    • Intervention: Establish IV access and administer fluids judiciously, particularly in hemodynamically unstable patients.
  4. Disability
    • Assessment: Monitor neurological status for signs of hypoxia or hypercapnia (e.g., confusion, agitation).
    • Intervention: Correct hypoxemia and hypercapnia promptly to prevent further deterioration [9].
  5. Exposure
    • Assessment: Perform a thorough examination to identify underlying triggers (e.g., infections, pneumothorax).
    • Intervention: Obtain chest imaging to evaluate for pneumonia, pneumothorax, or other contributing factors [9].

Medications

The management of COPD exacerbations often includes a combination of pharmacological treatments tailored to address airway obstruction, inflammation, and potential infections. Key medications include bronchodilators like albuterol and ipratropium to relieve bronchospasm, corticosteroids such as prednisone to reduce inflammation, and magnesium sulfate for severe bronchospasm. Antibiotics are considered when infection is suspected. Each drug requires careful dosing and monitoring, with specific precautions based on patient factors and pregnancy category [15].

Albuterol (Nebulizer):

  • Dose: 2.5 mg
  • Frequency: Every 20 minutes as needed
  • Maximum Dose: 10 mg/hour
  • Pregnancy Category: C
  • Cautions/Comments: Monitor for tachycardia and tremors.

Ipratropium (Nebulizer):

  • Dose: 500 mcg
  • Frequency: Every 6 hours
  • Maximum Dose: Not applicable
  • Pregnancy Category: B
  • Cautions/Comments: Use in combination with albuterol for synergistic effects.

Prednisone (Oral):

  • Dose: 40-60 mg
  • Frequency: Once daily
  • Maximum Dose: Not applicable
  • Pregnancy Category: C
  • Cautions/Comments: Use cautiously in diabetic patients.

Magnesium Sulfate (IV):

  • Dose: 2 g
  • Frequency: Single dose
  • Maximum Dose: 2 g
  • Pregnancy Category: C
  • Cautions/Comments: Consider in severe cases with bronchospasm.

Antibiotics:

  • Dose: Based on local guidelines
  • Frequency: Per protocol
  • Maximum Dose: Not applicable
  • Pregnancy Category: Varies
  • Cautions/Comments: Initiate if infection is suspected.
  •  

Procedural Interventions

In the management of acute COPD exacerbations, advanced interventions play a crucial role in stabilizing respiratory function and addressing underlying complications. Non-invasive ventilation (NIV) is a first-line strategy for patients with hypercapnic respiratory failure or persistent hypoxemia, offering improved gas exchange and reducing the likelihood of intubation [15]. For patients who do not respond to NIV or have contraindications, endotracheal intubation with lung-protective ventilation strategies becomes necessary to manage severe respiratory distress while minimizing barotrauma [15]. Additionally, imaging modalities such as chest X-rays or ultrasounds are essential for identifying structural abnormalities like pneumonia or pneumothorax, ensuring comprehensive evaluation and treatment [15].

Special Patient Groups

Pediatrics

Although COPD is primarily an adult disease, children with chronic respiratory conditions, such as bronchopulmonary dysplasia or severe asthma, may exhibit symptoms resembling COPD exacerbations.

  • Clinical Differences:
    • Symptoms may mimic asthma exacerbations, presenting as wheezing and breathlessness.
    • Pulmonary function tests are often challenging to interpret in younger children.
    • A history of prematurity or recurrent lower respiratory tract infections may predispose children to COPD-like symptoms.
  • Management Implications:
    • Employ pediatric-specific dosing for bronchodilators and corticosteroids.
    • Avoid overuse of systemic steroids due to potential risks, such as growth suppression and adrenal insufficiency [15].

Geriatrics

The elderly population often presents unique challenges in COPD exacerbations due to comorbidities and altered physiological responses.

  • Clinical Differences:
    • Exacerbations may manifest atypically, such as confusion or lethargy, rather than standard respiratory symptoms.
    • Comorbidities, including heart failure and frailty, complicate diagnosis and treatment.
    • There is an increased risk of medication side effects, including corticosteroid-induced hyperglycemia and osteoporosis.
  • Management Implications:
    • Emphasize non-pharmacological interventions, such as pulmonary rehabilitation.
    • Closely monitor for potential drug interactions and side effects [28].

Pregnant Patients

Pregnant individuals with COPD exacerbations face unique clinical challenges stemming from physiological changes and fetal considerations.

  • Clinical Differences:
    • Increased respiratory rate and reduced functional residual capacity may exacerbate symptoms.
    • Exacerbations pose risks to maternal and fetal health, including preterm labor and fetal growth restriction.
  • Management Implications:
    • Prioritize non-teratogenic medications, such as inhaled corticosteroids and short-acting beta-agonists.
    • Monitor maternal oxygen saturation to ensure adequate fetal oxygenation [29].

When To Admit This Patient

Indications for Hospital Admission

Hospitalization is indicated for patients with any of the following:

Severe Symptoms:

  • Marked dyspnea interfering with daily activities.
  • Respiratory rate >30 breaths/min, use of accessory muscles.
  • Cyanosis or signs of hypoxemia (oxygen saturation <90% despite supplemental oxygen) [15,30].

Hemodynamic Instability:

  • Hypotension or signs of poor perfusion (e.g., confusion, altered mental status) [31].

Failure of Outpatient Management:

  • Lack of improvement or worsening symptoms despite appropriate outpatient therapy, including bronchodilators, corticosteroids, and antibiotics [32].

Comorbidities:

  • Exacerbations complicated by comorbid conditions such as congestive heart failure, diabetes mellitus, or arrhythmias [33].

Acute Respiratory Failure:

  • Arterial blood gases (ABGs) showing PaO2 <60 mmHg or PaCO2 >50 mmHg with pH <7.35 [16].

High-Risk Features:

  • Frequent exacerbations (e.g., ≥2/year) [11, 23].
  • Recent hospitalizations for COPD exacerbation [11, 23],
  • Advanced COPD with significant functional limitations (e.g., home oxygen use) [15].

ICU Admission Criteria [30,34,35]

Intensive care unit (ICU) management is required if:

  • Non-invasive ventilation (NIV) fails, or mechanical ventilation is necessary.
  • Life-threatening hypoxemia or severe hypercapnia.
  • Persistent hemodynamic instability.

Criteria for Safe Discharge [32,33,36]

Patients can be discharged or managed on an outpatient basis if:

  • Symptoms are mild and improving with therapy [15,30]
  • No significant hypoxemia or hypercapnia (oxygen saturation ≥90%, stable ABGs).
  • No significant comorbidities or recent hospitalizations.
  • The patient has a reliable social support system and access to follow-up care.

Follow-Up Recommendations [8,15,37]

Patients managed as outpatients should have the following:

  • Clear instructions for medication use (e.g., short-acting bronchodilators, oral corticosteroids, antibiotics if indicated).
  • A follow-up appointment within 2 weeks.
  • Education on recognizing warning signs of worsening symptoms.

Discharge Information [15,34,35]

Before sending a patient home, provide:

  • A detailed medication plan, including proper inhaler technique.
  • Instructions on the duration of oral corticosteroid and antibiotic therapy.
  • Education on lifestyle modifications (e.g., smoking cessation, pulmonary rehabilitation).

Safety-Netting Measures [30,33]

  • Clear guidance on when to seek medical attention (e.g., worsening dyspnea, fever, confusion).
  • Contact information for emergency services and primary care provider.

Closing Loops [31,32,36]

  • Arrangements for follow-up appointments and pulmonary function testing.
  • Discuss long-term COPD management strategies, such as home oxygen therapy or vaccinations (influenza, pneumococcal).
  • Confirm that the patient understands the discharge instructions and can to prescribed medications.

Revisiting Your Patient

The management of the patient who presented with a COPD exacerbation followed a structured approach. Oxygen therapy was initiated, targeting SpO₂ levels of 88–92% using a nasal cannula or a Venturi mask, with BiPAP considered for cases of persistent hypoxemia or hypercapnic respiratory failure. Medications included nebulized bronchodilators, such as albuterol (2.5 mg) combined with ipratropium (0.5 mg), which were administered every 20 minutes for the first hour. Systemic steroids, like oral prednisone (40 mg) or IV methylprednisolone, were given as needed. Empiric antibiotics, such as doxycycline or amoxicillin-clavulanate, were started when an infection was suspected. Diagnostics involved chest X-rays, arterial blood gas analysis, a complete blood count (CBC), and electrolyte evaluation, with an ECG performed due to concerns about potential cardiac involvement. Continuous monitoring of SpO₂, respiratory rate, and ABG was conducted to track the patient’s progress. Regarding disposition, the patient was admitted due to severe hypoxemia and hypercapnia, with plans for outpatient follow-up scheduled within 1–2 weeks after discharge. Finally, the patient received education, including smoking cessation support and instructions on proper inhaler use, to reduce the risk of future exacerbations.

Authors

Picture of Noura Aldosari

Noura Aldosari

Emergency medicine resident at Cleveland Clinic Abudhabi. Interested in neurocritical and trauma resuscitation. Rotated in the neurocritical ICU department of Brigham and Women's Hospital (Harvard University) and worked in a research lab to detect genes involved in the pathophysiology of glioblastoma in Virginia University. Outside of medicine, I am a musician where I play the guitar and I cook.

Picture of Omar Ghazanfar

Omar Ghazanfar

Dr Omar Ghazanfar is the Medical Director HIMS and Emergency Physician Cleveland Abu Dhabi.Dr Ghazanfar has a keen interest in research and is part of the IFEM research committee as well as the scientific committee for ESEM. He is triple board certified with boards in Emergency and Disaster Medicine as well as Medical Quality. He has also completed an MBA.

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  35. Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2008;133(3):756-766. doi:10.1378/chest.07-0822.
  36. Miravitlles M, et al. COPD exacerbations: management and hospital discharge. Pulmonology. 2018;24(4):204-210. doi:10.1016
  37. Vollenweider DJ, Frei A, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;10:CD010257. doi:10.1002/14651858.CD010257.pub2.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Organophosphate and Carbamate Poisoning (2024)

~ iEM Education Project Team ~ Leave a comment

by Tasnim Ahmed & Rauda Alnuaimi

Authors
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You Have A New Patient!

A 32-year-old male who works as a farmer was brought to the Emergency Department by ambulance following a seizure episode. The patient has no known medical history and does not regularly take medications. According to his co-worker, he had been experiencing nausea and difficulty breathing throughout the day after engaging in crop fertilization work. The paramedic reported finding the patient lying on the ground in a confused state, with drooling and having vomited twice in the ambulance.

The image was produced by using ideogram 2.0

Initial vital signs upon assessment revealed a pulse rate of 52 beats per minute, blood pressure of 100/60 mmHg, respiratory rate of 40 breaths per minute, oxygen saturation of 89% on room air, and a temperature of 37°C. The patient’s Glasgow Coma Scale score was 9 out of 15. Upon arrival at the Emergency Department, the patient experienced another seizure episode. Primary assessment revealed excessive secretions in the airway, bilateral chest crepitations upon auscultation, and bowel and bladder incontinence. The patient also presented with pinpoint pupils bilaterally and diaphoretic skin. A quick check of glucose levels showed 110 mg/dL (6.1 mmol/L).

What Do You Need To Know?

Epidemiology

Organophosphates (OP) and carbamates, highly toxic classes of insecticides, were initially developed in the mid-1800s but saw extensive use as nerve agent weapons after World War II. Presently, they find predominant application in agricultural and indoor pest control, placing individuals such as pesticide applicators, manufacturing workers, and farm workers at significant risk of exposure. It is estimated that over 3 million people worldwide experience organophosphate exposure annually, resulting in approximately 300,000 deaths [1]. Examples of organophosphate pesticides include acephate, diazinon, parathion, ethoprophos, malathion…etc. 

Importance

While unintentional exposure to organophosphates is not commonly encountered in emergency departments, pesticide poisoning remains a significant contributor to suicides, accounting for one-third of global suicide attempts [2]. The mortality rate associated with organophosphate poisoning rises with increasing lag time from the absorption of the compound [3]. Therefore, prompt recognition and timely management are imperative to prevent death from organophosphate poisoning.

Pathophysiology

Organophosphates

Organophosphates are through various routes, including dermal, respiratory, gastrointestinal, and parenteral pathways. It works through the inhibition of acetylcholinesterase, an enzyme responsible for the breakdown of acetylcholine. This inhibition leads to an excessive accumulation of acetylcholine at the postsynaptic cleft, resulting in overstimulation of cholinergic pathways and subsequent cholinergic toxicity (Figure 1).

Figure 1 - Mechanism of organophosphate toxicity.

Cholinergic overstimulation affects two key sites within the peripheral nervous system: the muscarinic and nicotinic receptors (Figure 2).

Figure 2 - Cholinergic effect on nervous system. ACh, Acetylcholine; HTN, hypertension; M, Muscarinic; N, nicotinic; NE, norepinephrine. Adapted from Walls RM, Thompson TM, Welker K. Pesticides. In: Bakes R, ed. Rosen’s Emergency Medicine Concepts and Clinical Practice. Elsevier; 2018:1947-1950.

Muscarinic receptors are located in tear glands, sweat glands, bronchial secretion glands, and the sinoatrial and atrioventricular nodes of the heart. Stimulation of these muscarinic receptors leads to increased body secretions and cardiorespiratory depression, which will be further discussed in the history section.

Nicotinic receptors, on the other hand, are found at the neuromuscular junctions and adrenal glands. Excessive stimulation of nicotinic receptors can result in a spectrum of manifestations, including muscular fasciculations, profound muscular weakness, and, ultimately, flaccid paralysis due to depolarizing block. Stimulation of nicotinic receptors in the adrenal glands contributes to hypertension, sweating, tachycardia, and increased white blood cells with a left shift [4]. However, as acute intoxication progresses, the effects of muscarinic receptor stimulation predominate, leading to a subsiding of hypertension and tachycardia.

Central nervous system: Due to lipid solubility, organophosphates can cross the blood-brain barrier, leading to central nervous system effects such as confusion, seizures, and coma.

The binding process between organophosphates and acetylcholinesterase occurs in two distinct stages. The first stage is reversible, wherein the antidote can regenerate the acetylcholinesterase enzyme, restoring its normal function. The second stage, known as the “Aging” stage, represents a distinctive characteristic of organophosphate toxicity. During this stage, an irreversible bond is formed between the organophosphate and the enzyme. As a result, the enzyme becomes resistant to reactivation by the antidote.

Carbamates

Carbamates possess a distinct structural composition compared to organophosphates, yet they share a similar mechanism of toxicity. However, carbamates cause trainset cholinesterase inhibition with a duration of toxicity that is typically less than 24 hours. Furthermore, they exhibit poor lipid solubility and demonstrate a reduced ability to traverse the blood-brain barrier compared to organophosphates. As a result, the clinical course of carbamate toxicity tends to be more benign than organophosphate toxicity. 

Medical History

Obtaining a detailed history from a patient with suspected organophosphate poisoning might be challenging based on the initial presenting state of the patient. In unconscious patients, collateral history from patient relatives, friends, or emergency responders should be obtained if feasible.

The following are key elements of history that should be obtained:

Route of Exposure

Occupation: Commonly encountered individuals include farm workers or those involved in pesticide manufacturing, who are at the highest risk of exposure to organophosphates through inhalation. Organophosphate molecules readily vaporize, making inhalation an easily accessible route of exposure. Other potential routes of exposure include direct dermal or ocular contact with pesticides. Therefore, it is also important to ask about the use of personal protective measures during work.

Suicidal history: A history of suicidal ideation or previous suicide attempts may provide a clue of intentional ingestion.

Household pesticides: Accidental ingestion, however, is more commonly seen in children and often involves pesticide exposure within the storage areas.

Time to Exposure

Time of exposure significantly influences the clinical manifestations of toxicity. Symptoms can manifest within minutes to hours after exposure. However, manifesting intermediate and delayed neurological complications may take several days to weeks. Therefore, knowing the onset of symptoms aids in determining the potential reversibility of symptoms and the effectiveness of treatment interventions.

Acute Toxicity

Local Toxicity: In the early stages of local toxicity, patients may exhibit a range of seemingly vague symptoms. Inhalational exposure can lead to mucous membrane irritation and chest tightness. Direct skin exposure may cause local skin irritation, sweating, and muscle fasciculations. Ingestion of organophosphorus insecticides and their solvents can irritate the gastrointestinal tract, resulting in burning sensations in the mouth and throat, gastric cramping, vomiting, and diarrhea.

Systemic Toxicity: As systemic cholinergic toxicity develops, patients present with symptoms affecting the central and peripheral nervous systems. Central nervous system manifestations include headache, vertigo, seizures, confusion, and coma. Peripheral nervous system symptoms can be categorized into nicotinic and muscarinic manifestations. The days of the week acronym “MTWThF” is used to recall nicotinic manifestations (Figure 3). Muscarinic manifestations of cholinergic toxicity are represented by the mnemonic “DUMBELS” (Figure 4).

Figure 3 - MTWThF
Figure 4 - DUMBELS

Intermediate Toxicity

Intermediate neurologic symptoms typically occur 24 to 96 hours after exposure [5]. Symptoms include proximal muscle weakness, cranial nerve abnormalities, and respiratory insufficiency. It can last for days or weeks and require ventilatory support.

Delayed Toxicity

Delayed polyneuropathy is rare. It starts 2-3 weeks after exposure and is a mixed type of sensory and motor neuropathy. The lower limbs are predominantly affected, manifesting as stocking-glove paraesthesia, cramping, and flaccid paralysis that progresses from the lower to the upper extremities.  

Chronic Toxicity

Because it is lipid soluble, organophosphate can deposit in the adipose tissues at cumulative doses, resulting in chronic neurotoxicity and neuropsychiatric deficits, including confusion, memory impairment, psychosis, and Parkinson ‘s-like syndrome [1].

Medications

Inquire about the recent administration or use of acetylcholinesterase inhibitor medications, such as felbamate, which is used in severe epilepsy; physostigmine and rivastigmine, which are used to treat mild to moderate dementia in Alzheimer’s disease; ophthalmic agents such as echothiopate, sulforaphane, and neostigmine, which are used in myasthenia gravis; and neostigmine, which is used in myasthenia gravis. 

Physical Examination

It is important to perform a head-to-toe examination aimed at identifying systemic signs of cholinergic effects, keeping in mind that patients may present with signs of muscarinic or nicotinic predominance or a mixed clinical picture.

Vital signs

Clinical assessment should start with a full set of vital signs, including heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature.

General Appearance

Alertness: The level of consciousness should be assessed, prioritizing immediate attention to unconscious or unstable patients using the ABCDE approach (Airway, Breathing, Circulation, Disability, and Exposure), as discussed in detail in the management section.

Irritability: Look for restlessness, agitation, or confusion, which indicates central neurotoxicity.

Smell: Some organophosphates have distinctive odors resembling garlic or petroleum, which can be detected upon approaching the patient.

Increased secretions: Additional suggestive features include diaphoresis, active emesis, and urinary incontinence.

Respiratory System

Look for signs of respiratory failure or distress. These should be assessed, including tachypnea, oxygen desaturation, cyanosis, increased work of breathing, poor respiratory effort, and fatigue. Auscultation of the chest may reveal wheezing due to bronchospasm or diffuse transmitted sounds and crepitations due to increased respiratory secretions and pulmonary edema, respectively [6].

Cardiovascular System

Check for tachyarrhythmia or bradyarrhythmia associated with inadequate peripheral perfusion. Ideally, these abnormalities should be identified early during the initial assessment of vital signs.

Nervous System

Carefully assess for cranial nerve palsies, muscle weakness, fasciculations, loss of deep tendon reflexes, and sensory deficits. In particular, check for signs of intermediate neurological syndrome.

Gastrointestinal System

Check for signs of excessive gastrointestinal motility, such as generalized abdominal tenderness on palpation or hyperactive bowel sounds on auscultation.

Integumentary System

Sweating, often accompanied by a distinctive odor, can be observed due to muscarinic activation of sweat glands. Excessive secretions, including salivation and tearing, may also be evident. Moist and pale mucous membranes reflect autonomic dysfunction and potential hypoperfusion.

Alternative Diagnoses

The differential diagnosis for poisoning related to acetylcholinesterase inhibitors is relatively narrow, including (1) cholinesterase inhibitors, (2) cholinomimetics, and (3) nicotine alkaloids [7].

Cholinesterase inhibitors: Non-insecticidal medications include pyridostigmine, physostigmine, neostigmine, and echothiopate. 

Cholinomimetics: Mushroom toxicity, particularly the Aminata muscaria species, can be categorized as cholinomimetics. Clinical manifestations typically occur within 6-24 hours after ingestion and primarily present with gastrointestinal symptoms. Based on the history of ingestion, it can be relatively identifiable.

Nicotine and nicotine alkaloids: At high doses, these agents can activate muscarinic receptors, resembling or full clinical picture of organophosphate and carbamate toxicity.

Medical conditions: Other conditions include severe gastroenteritis, acute respiratory distress, thyrotoxicosis, sepsis, and neuromuscular disorders like Guillain-Barre, botulism, and amyotrophic lateral sclerosis. However, a thorough clinical evaluation and detailed history-taking can differentiate these medical conditions.

Acing Diagnostic Testing

Organophosphate poisoning is a clinical diagnosis. If there is no obvious history of exposure, a high index of suspicion should be maintained. If patients present with the characteristic toxidrome, empirical treatment with atropine is recommended. If symptoms improve, it strengthens the likelihood of organophosphate poisoning.

Bedside Tests

Electrocardiogram (ECG) and echocardiography should be obtained to evaluate for arrhythmias and myocardial infarction.

Laboratory Tests

Plasma and red blood cell (RBC) cholinesterase concentrations can help evaluate known or suspected exposures to organophosphates. However, these measurements are not readily available in real-time clinical settings. During acute toxicity, plasma cholinesterase levels tend to decrease first. However, in chronic toxicity, low-level exposure may cause plasma enzyme levels to appear normal while RBC cholinesterase levels remain decreased. This discrepancy arises from the longer recovery time needed for RBC cholinesterase, which can take up to 12 weeks to fully recover compared to 4 to 6 weeks for plasma cholinesterase.

Other tests: further laboratory studies should focus on assessing pulmonary, cardiovascular, renal function, and electrolyte balance. Obtaining blood gases is crucial as it allows for the measurement of acid-base status, considering that patients with acidosis have higher mortality rates.

Imaging

Brain computed tomography (CT) can aid in ruling out ischemic or hemorrhagic stroke and other structural brain abnormalities as a cause of the seizure and depressed mental state. Chest X-ray can help assess for the presence of pulmonary edema or aspiration pneumonia in a confused patient with vomiting and compromised respiration.

Risk Stratification

Organophosphate poisoning severity is directly correlated with the quantity, type, and duration of exposure. Mortality rates for organophosphate insecticides range from 2% to 25%. Among the insecticides associated with fatal outcomes, fenitrothion, dichlorvos, malathion, and trichlorfon are the most commonly implicated. Respiratory failure stands as the primary cause of death in these cases [1].

In addition to the aforementioned factors, the Glasgow Coma Scale (GCS) serves as a valuable prognostic tool. In a prospective study including patients acutely poisoned by either organophosphates (OPs) or carbamates, it was observed that an initial GCS score below 13 indicated poor prognosis [7].

Senanayake et al. (1993) introduced the Peradeniya Organophosphorus Poisoning (POP) scale as a valuable prognostic tool for assessing organophosphate (OP) poisoning (Table 1) [8]. This scale evaluates five frequently observed clinical manifestations, each rated on a 3-point scale ranging from 0 to 2. Upon initial presentation, the severity of poisoning is classified as mild (score 0-3), moderate (score 4-7), or severe (score 8-11) based on these assessments.

Parameter

Criteria

Score

Pupil Size

>2 mm

0

 

<2 mm

1

 

Pinpoint

2

Respiratory Rate

<20/min

0

 

>20/min

1

 

>60/min

2

Heart Rate

>60/min

0

 

41–60/min

1

 

<40/min

2

Fasciculation

None

0

 

Present, generalized/continuous

1

 

Both generalized and continuous

2

Level of Consciousness

Conscious and rational

0

 

Impaired response to verbal command

1

 

No response to verbal command

2

Seizures

Absent

0

 

Present

1


Scoring:

  • 0–3: Mild poisoning
  • 4–7: Moderate poisoning
  • 8–11: Severe poisoning

In subsequent validation studies, the POP scale on admission was found to significantly correlate with critical outcomes such as the requirement for ventilator support, the total dose of atropine needed, duration of stay in the intensive care unit, the occurrence of complications, and mortality [9] [10].

Management

The management approach for organophosphate poisoning has around four primary objectives: (1) decontamination, (2) initial stabilization following the ABCDE approach, (3) counteracting the effect of acetylcholine, and (4) reversing the toxin’s binding to the cholinesterase.

Decontamination

Personal protective equipment (PPE): Healthcare providers should utilize PPE as the initial step in managing organophosphate poisoning due to the potential presence of residual toxic substances on the patients. Latex gloves do not offer sufficient protection against insecticides; thus, neoprene or nitrile gloves should instead be used [11].

Skin decontamination: Decontamination involves completely removing and properly disposing all clothing, as residual contamination can persist even after washing. Cleanse the patient’s skin with water, soap, or dry substances such as flour, sand, or bentonite.

GI decontamination: In cases of toxin ingestion, gastrointestinal decontamination procedures and the administration of activated charcoal do not provide significant advantages. This is attributed to the rapid absorption of anticholinergic agents and the occurrence of profuse vomiting and diarrhea early in the ingestion process.

Initial Stabilization

Secure a cardiac monitor, pulse oximeter, blood pressure cuff, and 2 large-bore peripheral vascular access points before initiating medical resuscitation to ensure the efficient administration of medications and fluids.

Airway: The priority is maintaining a clear airway. To prevent obstruction, continuous suctioning of secretions or vomitus should be performed. Early endotracheal intubation is recommended for patients with excessive respiratory secretions, bronchospasm, impaired mental status, or severe skeletal muscle weakness. However, succinylcholine should be avoided during intubation as it is metabolized by acetylcholinesterase, which can lead to prolonged paralysis of 4 to 6 hours.

Breathing: Maintain sufficient ventilation and oxygenation. Target peripheral oxygen saturation (SPO2) > 94%. This is crucial as respiratory failure and hypoxemia are the primary cause of mortality in cholinergic toxicity.

Circulation: Evaluate for the presence of life-threatening arrhythmias, particularly bradycardia. Among the detrimental effects of cholinergic toxicity, bradycardia, bronchospasm, and bronchorrhea are collectively referred to as the “killer Bs” [12]. Tachydysrhythmia, if present, typically resolves as the underlying cholinergic excess is appropriately managed. Therefore, it is not advisable to administer symptomatic treatment with beta-blockers.

Antidote

The definitive treatment for organophosphate poisoning is the intravenous administration of atropine and Pralidoxime.

Atropine is the first-line treatment for cholinergic toxicity. It binds to muscarinic receptors, counteracting the cholinergic effects. In adults, the initial intravenous dose ranges from 2 to 5 mg, while in children, it is administered at a dose of 0.05 to 0.1 mg/kg via intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes, gradually increasing until the adult dosage is achieved. Doses can be doubled every 3 to 5 minutes until “Atropinisation” is achieved, which includes clearing respiratory secretions, resolving bronchoconstriction, maintaining a systolic blood pressure of >80 mmHg, and achieving a heart rate of >80 beats per minute. Once the stabilizing dose is reached, atropine infusion is maintained at a rate of 10–20% of the total cumulative dose per hour.

Mydriasis and tachycardia may occur after atropine administration, but they are not endpoints of therapy and do not contraindicate continued use. However, atropine does not affect nicotinic receptors, limiting its ability to manage neuromuscular dysfunction associated with cholinergic toxicity. Therefore, Pralidoxime should be added to the treatment regimen, ideally within 1 to 2 hours of exposure, before “aging” occurs [13]. This drug has three advantageous effects: detoxifying unbound organophosphates, reactivating acetylcholinesterase, and possessing endogenous anticholinergic properties.

For adults, a bolus dose of at least 1 to 2 grams of pralidoxime should be administered over 30 minutes, with caution to prevent cardiac arrest. For children, the bolus dose is 20 to 50 mg/kg. Following this, a continuous infusion should be initiated, delivering 8 mg/kg/hr for adults and 10 to 20 mg/kg/hr for children. This infusion can continue several days if necessary.

Specific Dosage Summary

Atropine:

  • Adult Dose: 2–5 mg IV/IM/SC every 5–30 minutes, with no maximum dose.
  • Pediatric Dose: 0.05–0.1 mg/kg IV/IM/SC every 5–30 minutes, followed by infusion at 10–20% of the cumulative dose needed to achieve symptom control.
  • Cautions/Comments:
  • Tachycardia or mydriasis are not contraindications to continued use.
  • Pregnancy Category: C.

Pralidoxime:

  • Adult Dose: 1–2 grams IV/IM/SC, followed by an infusion of 8 mg/kg/hr.
  • Pediatric Dose: 25–50 mg/kg IV/IM/SC, followed by an infusion of 10–20 mg/kg/hr.
  • Frequency: Administered over 1 hour.
  • Maximum Dose: 1 gram for pediatric doses; no maximum dose for adults.
  • Cautions/Comments:
    • Given over 30 minutes to avoid the risk of cardiac arrest.
    • Should be administered within 1–2 hours of exposure.
    • Pregnancy Category: C.

Supportive Management

Benzodiazepine:  Should be administration for patients with low GCS, anxiety, or seizures should be managed with benzodiazepines.

Sodium bicarbonate: For patients with metabolic acidosis despite correction of hypoxia and fluid resuscitation, consider administering sodium bicarbonate. The initial adult dose is 50-100 mmol (1-2 mmol/kg for children), and it may be repeated as needed, guided by arterial blood gas monitoring, aiming for a normal pH.

Special Patient Groups

The principles of managing organophosphate toxicity remain consistent across all age groups, including pregnant patients. However, in individuals who have undergone cardiac transplantation, the use of atropine and other anticholinergic agents is not effective due to heart denervation. In such cases, bradycardia should be managed with sympathomimetic agents such as epinephrine. It is also important to use atropine cautiously in patients with predisposing factors for angle closure glaucoma, as it can precipitate this condition.

When To Admit This Patient

Patients who have had minimal exposure and have been free of symptoms for at least 12 hours can be safely discharged. However, it is crucial to admit and closely monitor individuals with severe symptoms, especially those experiencing acute respiratory compromise accompanied by low cholinesterase levels. Such patients often require admission to the intensive care unit (ICU). For patients who exhibit self-harm or suicidal ideation, psychiatric counseling and admission to a supervised setting with 1:1 observation and mental assessment are necessary.

Discharge instructions: Upon discharge, clear instructions should be provided to patients to avoid further exposure to insecticides and to remain vigilant for the recurrence of respiratory or neurological symptoms. These measures are necessary to promptly identify and manage intermediate syndrome and delayed neuropathy [14].

Revisiting Your Patient

As the patient was actively seizing, he was promptly triaged to the resuscitation bay, connected to a cardiac monitor, pulse oximeter, and blood pressure monitor. The patient was positioned on the left recumbent position to prevent aspiration, oral secretions were suctioned, and oxygen support was provided through a non-rebreather mask. An intravenous administration of 4mg lorazepam was given to control the seizure activity.

Following the cessation of the seizure, a repeat set of vital signs revealed a heart rate of 50 beats per minute, blood pressure of 98/50 mmHg, oxygen saturation of 85%, and a respiratory rate of 10 breaths per minute. Considering the worsening level of consciousness, bradycardia, increased respiratory distress, and the patient’s occupational history on a farm, organophosphate toxicity was suspected, and the patient was prepared for endotracheal intubation to maintain a patent airway and provide adequate ventilation. A bolus of 1L of 9% sodium chloride solution was administered to manage hypotension. Atropine 5mg and pralidoxime 2g were given, followed by an infusion of atropine at a rate of 1mg/hr as definitive management for the suspected cholinergic toxicity. A post-intubation chest X-ray revealed proper endotracheal tube placement and bilateral haziness suggestive of acute respiratory distress syndrome. The electrocardiogram showed sinus bradycardia, which can be explained by the muscarinic effect of cholinergic toxicity. Initial arterial blood gas demonstrated mixed respiratory failure with a pH of 7.25, PCO2 of 56mmHg, PO2 of 60mmHg, and HCO3 of 28meq/L, attributed to pulmonary edema and decreased ventilation.

After the initial stabilization, the patient was fully exposed, and his wet clothes were appropriately disposed of. His diaphoretic skin, with a garlic odor, was cleansed with soap and water. Additional history was obtained from the co-worker, who indicated that the patient has no history of smoking, alcohol consumption, cardiac or pulmonary conditions, seizures, or previous suicidal attempts, which aids in ruling out acute coronary syndrome, pulmonary hypertension, or severe exacerbation of asthma.

Further investigations were initiated to evaluate other potential causes, including intracranial hemorrhage or lesions, sepsis, thyrotoxicosis, and electrolyte imbalances. Brain CT revealed no abnormalities or intracranial bleeding. The white blood cell count showed leucocytosis, while serum electrolyte levels were within the normal range. Procalcitonin levels were unremarkable, further undermining the possibility of sepsis.

Given the provisional diagnosis of organophosphate toxicity, the patient was admitted to the intensive care unit for close monitoring and further management.

Authors

Picture of Tasnim Ahmed

Tasnim Ahmed

Emergency Medicine Residency graduate from Zayed Military Hospital, Abu Dhabi, UAE. Deputy Editor-in-Chief of the Emirates Society of Emergency Medicine (ESEM) newsletter. Senior Board Member and Website Manager of the Emirates Collaboration of Residents in Emergency Medicine (ECREM). Awarded Resident of the Year twice, at ESEM23 and Menatox23. Passionate about medical education, with a focus on blending art and technology into innovative teaching strategies.

Picture of Rauda Alnuaimi

Rauda Alnuaimi

Emergency Medicine Department
Zayed Miliraty Hospital, Abu Dhabi, UAE

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References

  1. Robb EL, Baker MB. Organophosphate Toxicity. [Updated 2022 May 1]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470430/#_NBK470430_pubdet_

  2. Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: Systematic review. BMC Public Health. 2007;7(1):357. doi:10.1186/1471-2458-7-357.

  3. Banday T, Desai M, Naik V, Tathineni B. Predictors of morbidity and mortality in organophosphorus poisoning: A case study in a rural hospital in Karnataka, India. North Am J Med Sci. 2015;7(6):259-263. doi:10.4103/1947-2714.159331.

  4. Sikary AK. Homicidal poisoning in India: A short review. J Forensic Leg Med. 2019;61:13-16. doi:10.1016/j.jflm.2018.10.003.

  5. Jayawardane P, Dawson AH, Weerasinghe V, Karalliedde L, Buckley NA, Senanayake N. The spectrum of intermediate syndrome following acute organophosphate poisoning: A prospective cohort study from Sri Lanka. PLoS Med. 2008;5(7):e147. doi:10.1371/journal.pmed.0050147.

  6. Suveer S. Respiratory symptoms and signs. Medicine (Baltimore). 2023. doi:10.1016/j.mpmed.2023.07.005.

  7. Silberman J, Taylor A. Carbamate Toxicity. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482183

  8. Senanayake N, de Silva HJ, Karalliedde L. A scale to assess severity in organophosphorus intoxication: POP scale. Hum Exp Toxicol. 1993;12(4):297-299. doi:10.1177/096032719301200407.

  9. Kamath S, Gautam V. Study of organophosphorus compound poisoning in a tertiary care hospital and the role of Peradeniya organophosphorus poisoning scale as a prognostic marker of the outcome. J Fam Med Prim Care. 2021;10(11):4160-4165. doi:10.4103/jfmpc.jfmpc_518_21.

  10. Amir A, Raza A, Qureshi T, et al. Organophosphate poisoning: Demographics, severity scores and outcomes from National Poisoning Control Centre, Karachi. Cureus. 2020;12(7):e8371. doi:10.7759/cureus.8371.

  11. Roberts DM, Aaron CK. Management of acute organophosphorus pesticide poisoning. BMJ. 2007;334(7594):629-634. doi:10.1136/bmj.39134.566979.BE.

  12. Hilmas CJ, Adler M, Baskin SI, Gupta RC. Pulmonary Toxicity of Cholinesterase Inhibitors. In: Gupta RC, ed. Toxicology of Organophosphate and Carbamate Compounds. Burlington, MA: Elsevier; 2006:29-38. doi:10.1016/B978-012088523-7/50029-6.

  13. Pralidoxime and oximes. In: Gupta RC, ed. Biomarkers in Toxicology. 2nd ed. Elsevier; 2022. doi:10.1016/B978-0-12-822218-8.00030-2.

  14. Ahmed HA, Ayoub MI, Soliman MA, Hussein MT, Tawfik R, Rageh MA. Delayed onset intermediate syndrome after organophosphate poisoning. Anaesthesia, Pain & Intensive Care. 2022;26:1-5. doi:10.35975/apic.v26.

Reviewed and Edited By

Picture of Jonathan Liow

Jonathan Liow

Jonathan conducts healthcare research in the Emergency Department at Tan Tock Seng Hospital. A graduate of the University at Buffalo with a BA in Psychology and Communication, he initially worked on breast cancer research studies at GIS A*STAR. His research interests focus on integrating AI into healthcare and adopting a multifaceted approach to patient care. In his free time, Jonathan enjoys photography, astronomy, and exploring nature as he seeks to understand our place in the universe. He is also passionate about sports, particularly badminton and football.

Picture of James Kwan

James Kwan

James Kwan is the Vice Chair of the Finance Committee for IFEM and a Senior Consultant in the Department of Emergency Medicine at Tan Tock Seng Hospital in Singapore. He holds academic appointments at the Lee Kong Chian School of Medicine, Nanyang Technological University, and the Yong Loo Lin School of Medicine, National University of Singapore. Before relocating to Singapore in 2016, James served as the Academic Head of Emergency Medicine and Lead in Assessment at Western Sydney University's School of Medicine in Australia. Passionate about medical education, he has spearheaded curriculum development for undergraduate and postgraduate programs at both national and international levels. His educational interests focus on assessment and entrustable professional activities, while his clinical expertise includes disaster medicine and trauma management.

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Upper Gastrointestinal Bleeding (2024)

~ iEM Education Project Team ~ Leave a comment

by Resshme Kannan Sudha & Thiagarajan Jaiganesh

Authors
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You have a new patient!

A 55-year-old male with alcoholic liver cirrhosis was brought to the emergency department by his wife, presenting with two episodes of haematemesis (containing fresh blood) and light-headedness. This is the first occurrence of such symptoms. Vital signs: Temperature: 36.8°C, Heart Rate: 115 bpm, SpO₂: 95%, BP: 88/65 mmHg. On examination, the patient appears pale, lethargic, and jaundiced, with abdominal distension noted.

The image was produced by using ideogram 2.0.

What do you need to know?

Upper gastrointestinal (GI) bleeding is defined as bleeding occurring above the level of the ligament of Treitz. It is more common than lower GI bleeding [1]. Upper GI bleeding is a significant clinical condition that can lead to morbidity and mortality if not promptly diagnosed and managed. It encompasses bleeding from the esophagus, stomach, or duodenum, often presenting as hematemesis or melena. The importance of recognizing and treating upper GI bleeding lies in its potential to indicate serious underlying conditions. Early intervention is crucial, as the severity of bleeding can lead to hypovolemic shock, necessitating urgent medical care. Upper GI bleeding is a common emergency, with an estimated incidence of 50 to 150 cases per 100,000 individuals annually [2]. The prevalence varies based on demographic factors such as age, gender, and geographical location. The condition is more prevalent in older adults, particularly those over 60 years.

The most common cause is peptic ulcer disease, with duodenal ulcers being the most frequent. Other causes include varices, erosive esophagitis, duodenitis, Mallory-Weiss tear, gastrointestinal malignancies, and arterial and venous malformations (e.g., aorto-enteric fistula, Dieulafoy lesion) [1,3]. Causes of peptic ulcer disease include NSAID (Non-Steroidal Anti-inflammatory Drug) intake, Helicobacter pylori infection, and stress ulcers. In recent years, the incidence of upper gastrointestinal bleeding admissions due to peptic ulcer disease has decreased in the USA. This trend has been attributed to the use of triple therapy for Helicobacter pylori and the co-administration of proton pump inhibitors with NSAIDs [4].

Clinical manifestations include vomiting coffee ground material or fresh blood, and/or passing fresh blood in the stool or black, tarry stool (melena) [1].

Goals in the management of a patient with upper gastrointestinal bleeding include identifying the site and nature of the bleeding, stabilizing the patient, and controlling the source of the bleed [4].

Medical History

After performing a primary survey and stabilizing the patient, it is important to fine-tune your history, physical examination, and investigations to identify the source of bleeding and guide further management and disposition.

Upper GI bleeding commonly presents with haematemesis (coffee-ground or fresh blood), haematochezia, and/or melena [4]. Certain foods, such as beets, and medications like cefdinir, can cause red-colored stool, while bismuth and iron supplements may cause black-colored stool [4].

Associated Symptoms
  • Peptic ulcer disease may be associated with epigastric pain (gastric ulcer) and dysphagia, gastroesophageal reflux disease (GERD), or odynophagia (esophageal ulcer).
  • Haematemesis associated with retching may indicate a Mallory-Weiss tear.
  • The presence of jaundice and ascites suggests variceal bleeding [4].

A prior history of GI bleeding should be assessed, as patients are more likely to bleed from the same lesion.

Key Past Medical History and Risk Factors

Peptic Ulcer Disease:

  • Ulcers can occur in the esophagus, stomach, or duodenum, with duodenal ulcers being more common.
  • However, gastric ulcers account for a higher incidence of bleeding.
  • Known causes include Helicobacter pylori, NSAIDs, alcohol, and steroid use.
  • Symptoms may include epigastric pain, nausea, vomiting, upper GI bleeding (painless haematemesis and melena), and signs of anaemia.
  • Upper GI bleeding after NSAID use, stress, or a history of dyspepsia may indicate erosive gastritis [5,6].

Esophageal Varices:

  • Caused by portal hypertension secondary to liver diseases such as cirrhosis.
  • Symptoms include jaundice, spider angiomata, palmar erythema, hepatic encephalopathy (confusion), coagulopathy (petechiae/purpura), ascites, and variceal bleeding (painless haematemesis with large amounts of fresh blood) [6].
  • Ask about chronic alcohol use, hepatitis, and hepatocellular carcinoma.
  •  

Mallory-Weiss Syndrome:

  • Caused by forceful retching or vomiting, often after heavy alcohol intake.
  • Leads to a tear in the esophagus or stomach, resulting in haematemesis (large amounts of fresh blood).
  • This condition is usually self-limiting [6].

Malignancy:

  • Gastric cancers may present with haematemesis, anaemia, and dyspepsia [6].
  • Enquire about sudden weight loss, loss of appetite, and risk factors like prior Helicobacter pylori infection.

Angiodysplasia:

  • Dieulafoy’s disease is a rare vascular malformation affecting young individuals.
  • It involves small aneurysms in the stomach that rupture, leading to massive spontaneous haematemesis [6].

Aorto-enteric Fistula:

  • A rare condition, usually occurring post-repair of an abdominal aortic aneurysm.
  • Presents with profuse haematemesis and rectal bleeding [6].

Gastro-enteric Anastomosis:

  • Ulcers may develop at the site of gastro-enteric anastomosis, presenting with upper GI bleeding [7].
Comorbid Illnesses

Enquire about conditions such as:

  • Ischemic heart disease or pulmonary conditions (higher haemoglobin levels required).
  • Coagulopathies (may necessitate additional therapies).
  • Dementia or hepatic encephalopathy (risk of aspiration due to altered mental state).
  • Heart failure or renal failure (risk of fluid overload during blood transfusion).
Medication History

Assess for [8]:

  • NSAIDs (associated with peptic ulcers).
  • Anticoagulants and antiplatelets.
  • Chemotherapeutic agents.
  • Iron supplements (black stool).
Symptoms of Severe Bleeding and Poor Prognosis [1,4,7,9]
  • Light-headedness, confusion, syncope (cerebral hypoperfusion).
  • Chest pain and palpitations (coronary hypoperfusion) .

Physical Examination

The severity of bleeding should be assessed based on clinical signs of shock rather than the color of the blood [4]. Upper GI bleeding typically presents with haematemesis (frank blood or coffee-ground emesis) and/or melena [4]. In cases of brisk upper GI bleeding, the patient may present as vitally unstable with haematochezia [4].

Vital Signs

Monitor for signs of hemodynamic instability, including:

  • Tachycardia, tachypnea, and hypotension [1,7].
  • Supine hypotension is associated with greater blood loss than orthostatic hypotension [1].

General Examination

  • Confusion may indicate hemodynamic instability.
  • Gynecomastia may be seen in patients with liver disease [10].
  • Haematemesis strongly suggests an upper GI bleed [4].

ENT Examination

  • Inspect the nose for epistaxis, which can present as haematemesis if the blood is swallowed [11].

Skin Examination

  • Palmar erythema, spider angiomata, caput medusae, and jaundice are suggestive of liver disease [11].

Abdominal Examination

  • Abdominal tenderness, guarding, rigidity, and rebound tenderness may indicate perforation.
  • The presence of ascites suggests liver disease [4,7].

Rectal and Stool Examination

  • A digital rectal examination and stool analysis can help identify the location of the bleed:
    • Melena typically indicates an upper GI bleed.
    • Haematochezia may suggest a lower GI bleed or a massive upper GI bleed [4].

Alternative Diagnoses

The differential diagnosis for gastrointestinal bleeding includes several conditions that may mimic an upper or lower GI bleed:

  1. Epistaxis: Bleeding from the nose can present as haematemesis if the blood is swallowed. Careful examination of the nasal cavity is essential to rule this out.

  2. Vaginal Bleeding: In some cases, vaginal bleeding can be mistaken for haematochezia. A thorough history and physical examination can help differentiate these sources.

  3. Food-Induced Discoloration: Certain foods may alter the color of stool, leading to a false suspicion of GI bleeding. For example, beets can cause red-colored stools, which may mimic haematochezia.

  4. Medication-Induced Changes: Some medications can also discolor stool:

    • Cefdinir may produce red-colored stool.
    • Iron supplements and bismuth-containing products can result in black stool, resembling melena [4].

  5. Neonatal Swallowed Blood: In neonates, vomiting swallowed maternal blood during delivery or breastfeeding may be mistaken for upper GI bleeding [12].

Acing Diagnostic Testing

Bedside Tests

Several bedside tests can aid in the initial evaluation of upper GI bleeding:

  • Point-of-care venous blood gas: Useful for detecting acidosis, electrolyte disturbances, and haemoglobin levels. Haemoglobin levels < 8 g/dL in previously healthy patients, or < 9 g/dL in patients with known coronary artery disease or anaemia-related complications, suggest the need for blood transfusion [4].
  • Point-of-care PT (Prothrombin Time) and INR (International Normalized Ratio): Essential for patients taking medications like warfarin to determine the need for reversal agents.
  • Bedside ultrasound: Helpful in identifying ascites, which may aid in diagnosing variceal bleeding.
Ascites in Cirrhotic Patient

Laboratory Tests

The following blood tests are useful when there is a clinical suspicion of upper GI bleeding [4,6,11,13]:

  • Complete Blood Count (CBC): To assess haemoglobin and haematocrit levels.
  • Blood Urea Nitrogen (BUN), Creatinine, and electrolytes: A BUN:Creatinine ratio > 35 is highly suggestive of upper GI bleeding (90%).
  • Coagulation Screen: INR levels are important in patients on anticoagulant therapy (e.g., warfarin) to guide reversal strategies.
  • Liver Function Tests: Elevated parameters are suggestive of liver disease and potential variceal bleeding.
  • Type and Crossmatch: Crucial for patients who may require blood transfusion.

Imaging

Radiological imaging is rarely needed in hemodynamically unstable patients as it may delay resuscitation. In such cases, endoscopy should take precedence [4].

  • Upright chest X-ray: Helpful in detecting free air under the diaphragm, which is suggestive of perforation.
  • CT Angiography: Recommended for hemodynamically stable patients when identifying the bleeding etiology before endoscopy is crucial. It can detect slow bleeding (approximately 0.3 mL/min) and guide management decisions (endoscopy, surgery, or angiography). However, it is not suitable for unstable patients due to delays in management. In such cases, conventional angiography with embolization is preferred [4].

Endoscopy

Endoscopy is both diagnostic and therapeutic [14,15]:

  • There is no evidence to support that emergent endoscopy is superior to routine endoscopy.
  • Immediate gastroenterology consultation for emergent endoscopy is advised in patients with ongoing severe upper GI bleeding.
  • Endoscopy is recommended within 24 hours for all admitted patients with UGIB after stabilizing hemodynamic parameters and addressing other medical issues.
  • Patients with high-risk clinical features such as tachycardia, hypotension, haematemesis, or blood in nasogastric aspirate should undergo endoscopy within 12 hours, as this may improve clinical outcomes.

Additional Considerations

  • A screening ECG is recommended in patients > 35 years of age with cardiac risk factors, as co-existing acute coronary syndrome may complicate GI bleeding [4].
  • Nasogastric lavage is generally not recommended due to risks of perforation, pneumothorax, and aspiration [4].
  • Erythromycin can be used as an alternative prokinetic to clear gastric contents before endoscopy [4,8].

Risk Stratification

To effectively manage gastrointestinal (GI) bleeding, patients must be categorized into high-risk and low-risk groups. High-risk patients require prompt intervention, whereas low-risk patients can be managed through outpatient treatment [4]. A combination of clinical, endoscopic, and laboratory features, along with risk scores, can aid in risk stratification. While risk scores may not always predict high-risk patients accurately, they are effective in identifying patients at very low risk of harm. When selecting patients for outpatient management, ensuring high sensitivity is essential to prevent the inadvertent discharge of high-risk individuals [16].

Risk Assessment Tools

Commonly used scoring systems for GI bleeding include:

  1. Glasgow-Blatchford Score (GBS)
  2. Rockall Score
  3. AIMS65 Score

The AIMS65 score assesses parameters such as:

  • Albumin < 3 mg/dL
  • International Normalized Ratio (INR) > 1.5
  • Altered mental status
  • Systolic blood pressure < 90 mmHg
  • Age > 65 years

Studies show that the GBS is more effective at predicting a combined outcome of intervention or death [16].

Glasgow-Blatchford Score (GBS)

The Glasgow-Blatchford Score is particularly useful for predicting the need for intervention, hospital admission, blood transfusion, surgery, and mortality. A significant advantage of the GBS is that it can be calculated at the time of patient presentation, as it does not require endoscopic data (unlike the Rockall score).

The GBS includes the following parameters:

  • Blood urea nitrogen (BUN)
  • Haemoglobin levels
  • Systolic blood pressure
  • Pulse rate
  • Symptoms such as melena, syncope, and a history of hepatic disease or cardiac failure.

The score ranges from 0 to 23, with a higher score indicating a greater risk of requiring endoscopic intervention [4].

Glasgow-Blatchford Risk Score

CategoryScore
BUN in mg/dL
18.2 to 22.42
22.5 to 283
28.1 to 704
70.1 or greater6
Hemoglobin, men g/dL
12 to 131
10 to 11.93
9.9 or less6
Hemoglobin, women g/dL
10 to 121
9.9 or less6
Systolic Blood Pressure, mmHg
100-1091
90-992
<903
Heartrate >100 peats per minute1
Melena1
Syncope2
Hepatic Diseases2
Heart failure2
Glasgow-Blatchford Risk Score is useful for predictive of inpatient mortality, blood transfusions, re-bleeding, ICU monitoring, and hospital length of stay. Patients with a score of zero may be discharged home, those with score 2 or higher are usually admitted, and those with score of 10 or more are at highest risk for morbidity and resource utilization. Maximum score is 23.
Outpatient Management

Patients with a Glasgow-Blatchford Score of 0 are considered at low risk for rebleeding. According to international consensus guidelines, these patients may be safely discharged with early outpatient follow-up [8,17].

Management

Initial Stabilization

Airway and Breathing:
Patients with massive upper GI bleeding presenting with uncontrollable haematemesis, respiratory distress, or severe shock require immediate airway protection and intubation. It is essential to improve hemodynamic status before administering induction and paralytic drugs for intubation and initiating positive pressure ventilation, as this can mitigate a sharp decrease in cardiac output. However, intubation is associated with poor outcomes and should only be performed when absolutely necessary [4].

Circulation:
Massive GI haemorrhage is characterized by ongoing active bleeding (haematemesis or haematochezia), signs of hemodynamic compromise (e.g., tachycardia, hypotension, altered mental status), or a shock index ≥ 0.9 [4].

Immediate volume resuscitation is critical and includes:

  • Placement of two large-bore IV catheters.
  • Infusion of balanced isotonic crystalloids (e.g., 2 liters of normal saline or Plasmalyte over 30 minutes).
  • Transfusion of uncrossmatched blood, if required [4].
Transfusion Strategies

For stable patients, a restrictive transfusion strategy is recommended. While the ideal haemoglobin target is not universally defined:

  • In stable patients without known coronary artery disease (CAD), maintain haemoglobin ≥ 8 g/dL.
  • For patients with known CAD, a higher target of ~9 g/dL is appropriate to reduce the risk of anaemia-related complications [4].

In patients requiring massive transfusion (more than 4 units of PRBCs), a balanced transfusion ratio of 1:1:1 (PRBC:Platelets:Fresh Frozen Plasma) is advised. Cryoprecipitate should be administered if fibrinogen levels remain < 1.5 g/L [18]. A platelet count > 50,000 platelets/μL should be maintained [4].

Coagulation Management
  • Vitamin K antagonists (e.g., warfarin) should be stopped and reversed to achieve a target INR of 1.5–2.5. Treatment options include Fresh Frozen Plasma (FFP) and Prothrombin Complex Concentrate (PCC). Vitamin K is an appropriate choice for hemodynamically stable GI bleeding.
  • Direct oral anticoagulant reversal:
    • Idarucizumab for dabigatran reversal.
    • PCC or coagulation factor Xa (recombinant/inactivated-zhzo) for factor Xa inhibitors.
  • For heparin reversal, protamine sulfate may be used.

Before administering reversal agents, the risks of reversing anticoagulant therapy must be carefully weighed against the risk of thromboembolism [19].

PCC is preferred over FFP for rapid coagulopathy correction, especially in patients at risk of fluid overload, as it requires lower volume administration [4]. Over-transfusion or empiric correction of PT/INR with FFP or PCC in portal hypertension may worsen portal hypertension and exacerbate bleeding [4].

Medications

Proton Pump Inhibitors (PPIs)

PPIs are the mainstay in the management of acute GI bleeding. They work by inhibiting the hydrogen potassium ATPase pump, thereby reducing gastric acid secretion [20]. Studies have shown that PPIs reduce the risk of re-bleeding, the need for surgery, and mortality in patients with bleeding ulcers [4].

Both intermittent PPI therapy and continuous infusion are equally effective in reducing bleeding [8]. Available IV formulations include esomeprazole and pantoprazole. The recommended dose is:

  • Pantoprazole or esomeprazole: 80 mg IV as a single initial dose, followed by either:
    • Continuous infusion at 8 mg/hr, or
    • 40 mg IV BID [8].

If IV formulations are unavailable, oral alternatives such as 40 mg of esomeprazole twice daily may be used [8].

PPIs are classified as Category B in pregnancy, except for omeprazole, which is Category C [21]. Caution should be exercised due to the risk of Clostridium difficile infection, Steven Johnson syndrome, kidney and liver impairment, and pancreatitis [20]. Omeprazole is particularly associated with the risk of acute interstitial nephritis [22].

Somatostatin Analogues

Somatostatin and its synthetic analogue, octreotide, are predominantly used in variceal bleeding. These agents reduce the risk of bleeding, need for transfusion, and portal hypertension. Indications include acute GI bleeding in patients with variceal bleeding, abnormal liver function tests, liver disease, or alcoholism [4].

The dosing regimen for octreotide is:

  • Adults: 50 mcg IV bolus, followed by 25–50 mcg/hr continuous infusion [23,24].
  • Paediatrics: 1 mcg/kg IV bolus (maximum: 100 mcg), followed by 1 mcg/kg/hr infusion [23,24].

Octreotide crosses the placenta and is expressed in breast milk. Common adverse effects include arrhythmias, pancreatitis, abnormal glucose regulation, and low platelet count [23]. It also crosses the blood-brain barrier [23].

Terlipressin

Terlipressin is a synthetic vasopressin receptor agonist that causes splanchnic vasoconstriction, thereby reducing portal hypertension. It is primarily indicated for variceal bleeding [25].

The recommended dose is 2 mg IV every 6 hours [26]. Terlipressin may cause teratogenic effects (limited data available) [27] and can result in painful hands and feet due to peripheral vasoconstriction [26]. While studies suggest that terlipressin, somatostatin, and octreotide have similar efficacy, data regarding their use in paediatric patients remains limited [24,28].

Prokinetic Agents (Erythromycin and Metoclopramide)

Prokinetic agents are used to improve visualization during endoscopy by clearing gastric contents.

  • Erythromycin:

    • Adult dose: 3 mg/kg IV, administered over 20–30 minutes, 20–90 minutes before endoscopy [29].
    • Classified as Category B in pregnancy and is safe for breastfeeding mothers [29].
    • Adverse effects include QT prolongation, pseudomembranous colitis, seizures, and hypertrophic pyloric stenosis [4,29].

  • Metoclopramide:

    • Adult dose: 10 mg IV.
    • Paediatric dose: 0.1–0.2 mg/kg IV [30].
    • Classified as Category B in pregnancy [30].
    • Caution is advised in patients with a history of extrapyramidal symptoms due to its association with extrapyramidal side effects [30].

Tranexamic Acid

Tranexamic acid is an antifibrinolytic agent. However, according to the HALT-IT Trial, it has not been shown to reduce mortality associated with gastrointestinal bleeding. As a result, its routine use in GI bleeding is not recommended [31].

Antibiotic Prophylaxis

Antibiotic prophylaxis is recommended for patients with cirrhosis or suspected cirrhotic liver disease to reduce the risk of infection and mortality [4].

The recommended antibiotics include:

  • Fluoroquinolones (e.g., ciprofloxacin 400 mg IV)

  • Third-generation cephalosporins (e.g., ceftriaxone 1–2 g IV) [4].

  • Ceftriaxone: Classified as Category B in pregnancy but contraindicated in hyperbilirubinemic neonates due to the risk of kernicterus and those receiving IV calcium-containing solutions due to ceftriaxone–calcium precipitation [32].

  • Ciprofloxacin: Classified as Category C in pregnancy. Adverse effects include Clostridium difficile infection, dysglycemia, tendon rupture, neurotoxicity, QT prolongation, hepatotoxicity, and Stevens-Johnson syndrome/toxic epidermal necrolysis [33].

Procedures

Balloon tamponade [4,6,34], using devices such as the Sengstaken-Blakemore tube, Minnesota tube, or Linton-Nachlas tube, can serve as a temporizing measure for suspected life-threatening variceal bleeding when endoscopy is not immediately available. These devices must be stored in refrigerators to maintain readiness.

Before the procedure, patients must be intubated to reduce the risk of aspiration. The device is inserted through the mouth, passed via the esophagus into the stomach. The tube consists of two balloons—a gastric balloon and an esophageal balloon:

  • The gastric balloon of the Sengstaken-Blakemore tube can be inflated with 250–300 cc of air, while the Minnesota tube can accommodate up to 450–500 cc to secure the tube in place.
  • The esophageal balloon can be inflated to a pressure of 20–40 mmHg, with a strict upper limit of 45 mmHg to avoid injury. Pressure should be carefully monitored using a manometer.

Balloon tamponade is a temporary measure, and definitive management, such as endoscopic therapy, should be arranged as soon as possible. The procedure is associated with significant risks, including ulceration, esophageal rupture, and aspiration [4].

Special Patient Groups

Paediatrics

The causes of upper GI bleeding in the pediatric population are generally similar to those seen in adults [12,15,35]. However, there are additional causes specific to neonates and infants that require consideration. In neonates, vitamin K deficiency, also referred to as the haemorrhagic disease of the newborn, is an important cause. Other causes include congenital vascular anomalies, such as telangiectasia, and coagulopathy, which may result from infections, liver disease, or coagulation factor deficiencies. Milk protein intolerance is also a recognized cause of upper GI bleeding in this age group. During the neonatal period and the first few months of life, it is crucial to differentiate swallowed maternal blood from true upper GI bleeding. The Apt-Downey test is a reliable diagnostic tool used to confirm the presence of fetal blood and rule out swallowed maternal blood as the source.

The management of upper GI bleeding in children largely follows the same principles as in adults, with necessary adaptations for the pediatric population. Intravenous proton pump inhibitors (IV PPIs) are effective and can be administered to reduce gastric acid secretion, thereby promoting hemostasis. In cases of suspected variceal bleeding, somatostatin analogues can be given to reduce portal hypertension and minimize bleeding risk. When severe acute bleeding is ongoing, endoscopy plays a key role in diagnosis and intervention. It is recommended that endoscopy be performed within 24 to 48 hours of presentation. However, it is critical to ensure that the patient is as hemodynamically stable as possible before proceeding with the procedure to minimize complications.

In cases where endoscopy cannot control the bleeding or fails to identify the source, further interventions may be necessary. Angiography with embolization is a useful modality in such instances, as it can help detect and address underlying vascular abnormalities contributing to the bleeding. This approach is particularly helpful when other methods have proven unsuccessful.

Overall, a multidisciplinary approach that includes appropriate stabilization, pharmacologic therapy, and procedural intervention is essential to effectively manage upper GI bleeding in the pediatric population [12,15,35].

Geriatrics

Upper GI bleeding in elderly patients presents unique challenges due to the high-risk nature of this population and the limitations of existing risk assessment tools. Studies indicate that traditional pre-endoscopic risk scores, such as the Glasgow-Blatchford and AIMS65, often fail to accurately predict outcomes like mortality and hospital stay length in geriatric patients, particularly those aged 82 and older, suggesting a need for age-adjusted scoring systems [36]. Despite these challenges, emergency oesophagogastroduodenoscopy is generally safe for elderly patients, with a high survival rate at 90 days post-procedure, although a significant proportion of OGDs yield normal findings, highlighting the importance of careful patient selection [37]. The management of Upper GI bleeding in the elderly is further complicated by recurrent bleeding, as seen in cases involving peptic ulcer disease, which necessitate a multidisciplinary approach and close monitoring to improve outcomes [38]. Recent efforts to develop novel risk scores tailored for the elderly have shown promise, with a new score incorporating factors like comorbidity index and blood pressure demonstrating good discriminative performance for identifying patients suitable for outpatient management [39].

Pregnant Patients

The causes of upper GI bleeding in pregnant women are similar to those in the general population, including conditions such as esophageal ulcers, gastroesophageal reflux disease, and portal vein thrombosis leading to esophageal varices [40]. Haematemesis, or the vomiting of blood, is a common manifestation of upper GI bleeding and can present as bright red or coffee-ground emesis, indicating bleeding from the upper gastrointestinal tract [1, 40]. In rare cases, UGIB in pregnancy can be caused by gastrointestinal stromal tumors (GISTs), as illustrated by a case where a pregnant woman presented with coffee-ground vomiting and was diagnosed with a bleeding GIST at the stomach cardia [41]. Endoscopy is a critical diagnostic and therapeutic tool for upper GI bleeding, but its use in pregnant women is generally reserved for severe or persistent cases due to potential risks to the mother and fetus [42]. Despite the need for endoscopic evaluation in over 12,000 pregnant women annually in the U.S., research on the safety and outcomes of such procedures remains limited [43]. Therefore, careful consideration of the risks and benefits is essential when managing upper GI bleeding in pregnant patients.

When To Admit This Patient

Admission is required for elderly patients over the age of 60 years, those who require blood transfusions, and patients with a Glasgow-Blatchford Score (GBS) greater than 0 [4,8]. Patients with high-risk bleeding sources should be admitted to a monitored setting or an intensive care unit (ICU) to allow close monitoring for signs of rebleeding and other potential complications.

The decision to discharge a patient following endoscopy depends on the identification of the bleeding source and the associated risk of rebleeding. Patients can be considered for discharge if they meet all of the following criteria: a GBS of 0, blood urea nitrogen (BUN) less than 18 mg/dL, haemoglobin >13 g/dL in men and >12 g/dL in women, heart rate less than 100 beats per minute, systolic blood pressure greater than 110 mmHg, no evidence of melena or syncope since the initial presentation, absence of heart failure or liver failure, and prompt access to outpatient follow-up care.

However, it is important to note that this recommendation is based on low-quality evidence, and clinical judgment should play a significant role in the final decision to discharge a patient. Clinicians should carefully assess each patient’s overall condition, risk of rebleeding, and ability to follow up in an outpatient setting to ensure safe discharge planning [15].

Revisiting Your Patient

In managing this patient, the immediate priority is to assess airway, breathing, and circulation and provide stabilization. Given the patient’s vital instability, they should be promptly transferred to the resuscitation bay for further management.

The image was produced by using ideogram 2.0.

Airway and Breathing: The patient’s airway is currently patent, and they are communicating comfortably, with no signs of obstruction such as pooling of blood or secretions. There have been no further episodes of haematemesis, and the patient is maintaining adequate oxygen saturation on room air. Chest auscultation is clear. At this time, the patient does not require airway adjuncts or intubation, but close observation is essential to detect any deterioration.

Circulation: The patient is hypotensive, indicating the need for immediate intervention. Two large-bore IV cannulas should be inserted to initiate intravenous fluid resuscitation. Crossmatched and uncrossmatched blood should be arranged as a precaution. A point-of-care venous blood gas test must be performed to quickly evaluate acidosis, haemoglobin levels, and other critical parameters. Care should be taken to avoid fluid overload, especially in patients with underlying liver disease.

Further History and Review of Systems: On further evaluation, the patient denies haematochezia, haemoptysis, epistaxis, melena, chest pain, palpitations, syncope, loss of consciousness, or confusion.

Past Medical and Surgical History and Risk Factors: The patient has a history of alcoholic liver disease and is a smoker. There is no history of chronic NSAID use, Helicobacter pylori infection, recent forceful retching, or ingestion of foods or medications that might cause red-colored secretions. There are no known coagulopathies, recent anticoagulant use, vascular abnormalities, weight loss, or loss of appetite. Additionally, the patient has no history of prior surgery.

Examination: Clinical signs of hemodynamic instability, such as hypotension, suggest hypovolemic shock, requiring prompt management with IV fluids and blood transfusion. Examination findings of jaundice, abdominal distension with shifting dullness, and caput medusae are consistent with alcoholic liver disease and indicate probable variceal bleeding. There is no abdominal tenderness, guarding, rigidity, or rebound tenderness to suggest another abdominal pathology.

Laboratory Investigations: Laboratory tests sent include a complete blood count, urea, electrolytes, creatinine, coagulation screen, liver function tests, and type and crossmatch for transfusion. The point-of-care venous blood gas reveals acidosis, haemoglobin <8 g/dL, negative base excess, and elevated lactate, indicating ongoing active bleeding. These findings necessitate urgent gastroenterology consultation for endoscopic intervention and the arrangement of blood transfusion. In addition, the patient must be monitored for liver disease-induced coagulopathy, and a haematology consultation is warranted.

Diagnostic Test: The patient’s Glasgow-Blatchford Score is greater than 0, further confirming the need for urgent endoscopy to identify and control the source of bleeding, which is most likely esophageal varices. Simultaneously, resuscitation measures must continue.

Medications: Given the patient’s history of alcoholic liver disease and suspected variceal bleeding, appropriate pharmacological management should include vasoactive agents such as somatostatin, octreotide, or terlipressin to reduce portal pressure. Empirical antibiotics (fluoroquinolones or third-generation cephalosporins) should be administered to reduce the risk of infection. Additionally, proton pump inhibitors (PPIs) should be started as part of the management protocol.

Disposition: This patient requires urgent gastrointestinal consultation for endoscopy to achieve source control of the bleeding. Admission is necessary to allow for close monitoring of potential complications, including rebleeding and complications of alcoholic liver cirrhosis, such as hepatic encephalopathy and renal failure.

Authors

Picture of Resshme Kannan Sudha

Resshme Kannan Sudha

Resshme Kannan Sudha graduated from RAK Medical and Health Sciences University and is currently an Emergency Medicine Graduate Resident at STMC Hospital, Al Ain. She is a keen follower of FOAMed projects and an enthusiastic educator. Her special interests include critical care, POCUS, global health, toxicology and wilderness medicine.

Picture of Thiagarajan Jaiganesh

Thiagarajan Jaiganesh

STMC Hospital, Al Ain

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  10. Chen ZJ, Freeman ML. Management of upper gastrointestinal bleeding emergencies: evidence-based medicine and practical considerations. World J Emerg Med. 2011;2(1):5-12. doi:10.5847/wjem.j.1920-8642.2011.01.001
  11. (Sokolosky MC. Gastrointestinal bleeding. In: Tintinalli’s Emergency Medicine Manual. New York, NY: McGraw-Hill Education; 2018:237-238.
  12. Donaldson R, Swartz J, Claire, et al. Gastrointestinal bleeding (peds) – WikEM. WikEM. Updated March 29, 2022. Accessed April 10, 2023. https://www.wikem.org/wiki/Gastrointestinal_bleeding_(peds)
  13. Wilkins T, Wheeler B, Carpenter M. Upper gastrointestinal bleeding in adults: Evaluation and management. American Family Physician. Published March 1, 2020. Accessed March 20, 2023. https://www.aafp.org/pubs/afp/issues/2020/0301/p294.html
  14. Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG clinical guideline: Upper gastrointestinal and ulcer bleeding. Am J Gastroenterol. 2021;116(5):899-917. doi:10.14309/ajg.0000000000001245
  15. Woodfield A, Donaldson R, Reynolds C, Young N. Upper GI bleeding guidelines. WikEM. Published March 12, 2022. Accessed March 20, 2023. https://www.wikem.org/wiki/Upper_GI_bleeding_guidelines
  16. Stanley AJ, Laine L. Management of acute upper gastrointestinal bleeding. BMJ. 2019;364:l536. Published March 25, 2019. Accessed February 15, 2023. https://www.bmj.com/content/364/bmj.l536
  17. Barkun AN, Almadi M, Kuipers EJ, et al. Management of nonvariceal upper gastrointestinal bleeding: Guideline recommendations from the International Consensus Group. Ann Intern Med. 2019;171(11):805. doi:10.7326/m19-1795
  18. Farkas J. GI bleeding. EMCrit Project. Published September 18, 2021. Accessed April 11, 2023. https://emcrit.org/ibcc/gib/
  19. Gnanapandithan K, Muniraj T. Management of antithrombotics around gastrointestinal procedures. PubMed. Published 2023. Accessed April 11, 2023. https://www.ncbi.nlm.nih.gov/books/NBK553210/
  20. Carmen Fookes B. List of proton pump inhibitors + uses, side effects. Drugs.com. Accessed April 11, 2023. https://www.drugs.com/drug-class/proton-pump-inhibitors.html
  21. Richter JE. Gastroesophageal reflux disease during pregnancy. Gastroenterol Clin North Am. 2003;32(1):235-261. doi:10.1016/s0889-8553(02)00065-1
  22. Reynolds C, Cunningham R, Ostermayer D, Donaldson R, Young N. Omeprazole. WikEM. Updated March 5, 2021. Accessed April 11, 2023. https://wikem.org/wiki/Omeprazole
  23. Ostermayer D, Murray B, Lee E, Donaldson R, Cunningham R. Octreotide. WikEM. Published February 10, 2021. Accessed March 20, 2023. https://wikem.org/wiki/Octreotide
  24. Sandostatin, Sandostatin LAR (octreotide) dosing, indications, interactions, adverse effects, and more. Medscape. Accessed April 11, 2023. https://reference.medscape.com/drug/sandostatin-lar-octreotide-342836
  25. Nickson C. Terlipressin. Life in the Fast Lane. Published January 4, 2019. Accessed April 11, 2023. https://litfl.com/terlipressin/
  26. Tripathi D, Stanley AJ, Hayes PC, et al. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut. 2015;64(11):1691-1692. doi:10.1136/gutjnl-2015-309262
  27. Terlivaz. Medscape. Published July 15, 2024. Accessed December 7, 2024. https://reference.medscape.com/drug/terlivaz-terlipressin-4000107#6
  28. Seo YS, Park SY, Kim MY, et al. Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage. Hepatology. 2014;60(3):962. doi:10.1002/hep.27006
  29. Donaldson R, Claire, Lee E, Ostermayer D, Holtz M. Erythromycin. WikEM. Published September 22, 2019. Accessed March 20, 2023. https://www.wikem.org/wiki/Erythromycin
  30. Fernando T, Donaldson R, Grove G, et al. Metoclopramide. WikEM. Updated March 7, 2021. Accessed April 11, 2023. https://www.wikem.org/wiki/Metoclopramide
  31. Roberts I, Shakur-Still H, Afolabi A, et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10241):1927-1936. doi:10.1016/s0140-6736(20)30848-5
  32. Donaldson R, Shah M, Ostermayer D, Young N, Claire. Ceftriaxone. WikEM. Updated September 19, 2019. Accessed April 10, 2023. https://www.wikem.org/wiki/Ceftriaxone
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  34. Balloon tamponade for massive GI bleeding – WikEM. WikEM. Accessed March 23, 2023. https://www.wikem.org/wiki/Balloon_tamponade_for_massive_GI_bleeding
  35. Lirio RA. Management of upper gastrointestinal bleeding in children. Gastrointest Endosc Clin N Am. 2016;26(1):63-73. doi:10.1016/j.giec.2015.09.003
  36. Di Gioia G, Sangineto M, Paglia A, et al. Limits of pre-endoscopic scoring systems in geriatric patients with upper gastrointestinal bleeding. Sci Rep. 2024;14(1). doi:10.1038/s41598-024-70577-2.
  37. McWhirter A, Mahmood S, Mensah E, Nour H, Olabintan O, Mrevlje Z. Evaluating the safety and outcomes of oesophagogastroduodenoscopy in elderly patients presenting with acute upper gastrointestinal bleeding. Cureus. 2023. doi:10.7759/cureus.47116.
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Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Benzodiazepine Overdose (2024)

~ iEM Education Project Team ~ Leave a comment

by Gina Rami Abdelmesih & Rauda Alnuaimi

Authors
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You have a new patient!

A 21-year-old female with no significant past medical history was brought to the emergency department by ambulance after her friends found her unresponsive in her bedroom. According to her friends, she had been experiencing significant anxiety related to an upcoming exam. The only notable finding in her room was a half-empty bottle of alcohol.

The image was produced by using ideogram 2.0

On arrival, the patient was arousable only to painful stimuli. Despite slurred speech, she admitted to taking “a few pills” provided by a friend to help her relax. Physical examination revealed nystagmus, but a complete neurological assessment was limited as the patient was not following commands. Her condition rapidly deteriorated, and she became obtunded with a Glasgow Coma Scale (GCS) score of 3/15. The vital signs are as follows: Respiratory rate: 10 breaths per minute, oxygen saturation (SpO₂): 92%, blood pressure: 60/45 mmHg, heart rate: 48 beats per minute, temperature: 36.1°C, and blood glucose at triage: 110 mg/dL.

How would you proceed with further evaluation for this patient?

What do you need to know?

Benzodiazepines are modulators of gamma-aminobutyric acid-A (GABA-A) receptors, which mediate the main inhibitory neurotransmitter in the central nervous system (CNS). By binding to GABA-A receptors, benzodiazepines indirectly potentiate the inhibitory action of GABA by increasing its affinity for the receptor [1].

Benzodiazepines are among the safest drugs within the sedative-hypnotic class. They are widely used in emergency medicine for seizure management, sedation of agitated patients, alcohol withdrawal, and procedural sedation. Additionally, benzodiazepines are commonly prescribed for various conditions, including anxiety and sleep disorders. However, their widespread availability poses a risk of misuse, whether intentional or accidental [2].

Benzodiazepines are the most commonly prescribed psychiatric medications and rank as the third most misused drug class among adults and adolescents in the United States. While data from the Middle East are limited, benzodiazepine misuse is recognized as a significant concern in the region [3,4]. Policies are being implemented to restrict inappropriate prescriptions and raise awareness about their safe use. Patients should be educated on the proper use of benzodiazepines to mitigate risks [5]. When taken alone, benzodiazepine overdoses are rarely lethal, unlike opioids. However, abrupt withdrawal after prolonged use can carry a high risk of mortality, particularly due to the potential for withdrawal seizures.

Benzodiazepines can be administered orally, intramuscularly, intravenously, or rectally. Oral administration is the most common route due to rapid absorption. Intramuscular administration has erratic absorption but may be useful in emergencies when IV access is unavailable. Rectal administration is primarily used in pediatric patients, providing faster and more predictable effects than the IM route. After absorption, benzodiazepines distribute readily throughout the body and rapidly penetrate the blood-brain barrier due to their high lipophilicity. Most benzodiazepines are highly protein-bound in plasma [6].

Benzodiazepines are metabolized in the liver into active or inactive compounds. Based on their elimination half-life, they are classified as short-acting (e.g., midazolam), intermediate-acting (e.g., alprazolam, lorazepam), and long-acting (e.g., diazepam, chlordiazepoxide, clonazepam). The duration of a benzodiazepine’s effect can be prolonged in the presence of active metabolites, liver dysfunction, or co-ingestion of substances that inhibit their metabolism (e.g., alcohol, cytochrome P450 inhibitors) [7].

Chronic benzodiazepine use can lead to tolerance, characterized by reduced receptor sensitivity. Abrupt discontinuation or dose reduction after tolerance develops can cause a pro-excitatory state, increasing the risk of seizures. The risk of tolerance and withdrawal is dose- and duration-dependent, though specific thresholds have not been clearly established.

Medical History

Taking a medical history from an intoxicated or withdrawing patient can be challenging due to their altered mental status. In such cases, information from family members, bystanders, or emergency medical services (EMS) can be invaluable in filling gaps in the patient’s history [8].

As with any toxidrome, the most critical aspect of the medical history is identifying the causative agent—or agents, as co-ingestion of multiple substances is common. Clues such as empty medication bottles or blister packs found near the patient can be helpful.

If benzodiazepine use is suspected, it is crucial to determine the specific agent, dosage, and duration of use to guide management effectively. Signs and symptoms of benzodiazepine overdose often mimic ethanol intoxication. Mild to moderate cases may present with drowsiness, slurred speech, nystagmus, and ataxia, which is the most common symptom in pediatric patients. Severe cases, particularly those involving co-ingestion, may present with hypotension and hypoventilation. Symptoms of benzodiazepine withdrawal, such as tremors, anxiety, hallucinations, dysphoria, psychosis, seizures, and autonomic instability, should also be investigated [9].

Past medical history is significant, especially for conditions like epilepsy, liver disease, or the use of medications that inhibit liver enzymes (e.g., cimetidine, valproate, fluoxetine, ciprofloxacin), as these factors can prolong the half-life of benzodiazepines. Psychiatric history is equally important, as conditions like depression, previous withdrawal episodes, intoxication, or suicide attempts may provide insights into the likely ingested compounds [10].

Physical Examination

The initial assessment begins with vital signs, including temperature, as severe benzodiazepine ingestion can cause hypothermia. Blood glucose levels should also be measured to exclude easily treatable causes of AMS, such as hypoglycemia. An ECG is recommended to assess for potential cardiac involvement.

A comprehensive head-to-toe examination is essential. This includes checking the skin for needle tracks and unusual odors, performing a full neurological examination (pupil size, signs of seizures, or meningeal irritation), and looking for indications of head trauma, drug toxicity, or metabolic disturbances. Specific attention should be given to acute limb ischemia, which can occur after accidental arterial injection of benzodiazepines; severe limb pain or agitation warrants a focused limb examination.

If the patient is responsive, a mental status examination can be conducted. Once the patient is stable and oriented, a thorough psychiatric evaluation should be undertaken.

Alternative Diagnoses

Benzodiazepine overdose is primarily a clinical diagnosis. Pure overdoses typically present with a depressed mental state while maintaining hemodynamic stability, and the history of benzodiazepine ingestion may align with a sedative-hypnotic toxidrome.

Co-ingestion or altered mental status may complicate the clinical picture and necessitate consideration of alternative diagnoses. Focal neurological deficits, seizures, or severe hemodynamic instability could point to intracranial pathologies (e.g., head trauma, intracerebral hemorrhage, stroke, meningitis, encephalitis) or other co-ingested substances (e.g., opiates, ethanol, tricyclic antidepressants, gamma-hydroxybutyrate). Delirium or sedation due to non-toxicological causes, such as hypoglycemia, should also remain part of the differential diagnosis.

Acing Diagnostic Testing

Pure benzodiazepine overdose presents with a characteristic sedative-hypnotic toxidrome and is primarily a clinical diagnosis. Diagnostic testing is often aimed at ruling out alternative causes of depressed consciousness.

Essential tests include blood glucose to exclude hypoglycemia and a CT head scan if head trauma is suspected. Testing for common co-ingestants such as paracetamol, salicylates, and ethanol may be warranted. ECG should be performed, as transient first- and second-degree heart blocks or QT prolongation may be seen in benzodiazepine toxicity. Patients with such ECG changes should be monitored for progression to arrhythmias. Arterial blood gas (ABG) analysis may be indicated for patients with hypoventilation. Basic laboratory tests, including electrolytes, liver function tests (which may show mild elevation), and creatine kinase levels, are recommended to monitor for rhabdomyolysis in severe cases.

Benzodiazepine detection in urine is possible via qualitative immunoassay, though this method is not diagnostic of overdose [11]. False negatives can occur as not all benzodiazepines are detected, and a positive result only indicates exposure without providing timing or dosage information. False positives may result from medications such as efavirenz and sertraline. Urine tests can detect benzodiazepines within three hours of ingestion and remain positive for up to two weeks. Serum benzodiazepine levels are rarely needed except in forensic cases, as they do not correlate well with the ingested dose.

Risk Stratification

Patients presenting with benzodiazepine overdose or withdrawal must be thoroughly assessed before discharge, even if they remain asymptomatic or their symptoms have been controlled in the ED. Psychiatric consultation is recommended in all cases, regardless of whether the overdose was intentional or accidental.

Suicidal ideation and suicide risk should be evaluated using tools like the SAD PERSONS score (Table 1) [12]. Patients with high scores require admission for further evaluation and intervention. Patients in withdrawal need to be referred for rehabilitation, with the choice of inpatient or outpatient care determined by the psychiatric assessment.

Table 1: SAD PERSONS Score

S

Male sex

1

A

Age (<19 or >45 years)

1

D

Depression

1

P

Previous attempt

1

E

Excessive alcohol or substance use

1

R

Rational thinking loss

1

S

Social supports lacking

1

O

Organized plan

1

N

No spouse

1

S

Sickness

1

   

0-4

Low risk

Consider discharge to home with follow-up.

5-6

Medium risk

Admit or discharge based on clinical judgment, ensuring appropriate follow-up arrangements.

7-10

High risk

Admit to hospital

Management

Initial Stabilization

Management of a patient with altered mental status (AMS) and suspected overdose begins with resuscitation. The ABCDEFG approach in toxicology is a structured method [13]:

A: Airway/C-Spine

  • Endotracheal intubation should be promptly performed in severely intoxicated patients or those unable to maintain their airway.
  • Nasopharyngeal or oropharyngeal airways may be used temporarily.
  • C-spine immobilization is indicated if head trauma is suspected.

B: Breathing

  • Hypoventilation is a critical sign of severe overdose, often indicating co-ingestion with alcohol or other central nervous system (CNS) depressants.
  • Monitor respiratory rate and oxygen saturation. Administer oxygen for hypoxemia. Consider ventilatory support in cases of hypoventilation (e.g., Bag-valve-mask ventilation). 

C: Circulation

  • Two large-bore intravenous lines should be placed, and fluid resuscitation with isotonic solutions (e.g., 0.9% saline or Ringer’s lactate) initiated for hypotension.
  • Monitor for signs of shock and consider vasopressors if hypotension persists despite adequate fluid resuscitation.

D: Disability/Decontamination/Draw Bloods

  • Perform a rapid neurological exam; pupillary changes and other symptoms can help identify the toxidrome.
  • Decontamination measures: Activated charcoal (1 g/kg for children or 50–100 g for adults) can be effective if administered within an appropriate timeframe. Multiple doses are not typically beneficial. Gastric lavage, hemodialysis, and urine alkalinization are ineffective for benzodiazepine toxicity.
  • Draw blood samples for complete blood count (CBC), renal and liver function tests (U&E, RFT, LFT), creatine kinase (CK), arterial blood gases (ABG), osmolality, and a toxicology screen (ethanol, acetaminophen, salicylate).

E: Exposure

  • Examine for track marks, odors, nasal septum erosion, and signs of trauma or assault. The lack of signs of trauma or assault does not totally rule out in patients with altred mental status.
  • Check for evidence of seizures (incontinence, tongue biting) or meningeal irritation.
  • Ensure the patient is kept warm.

F: Full Monitoring

  • Continuous monitoring of vital signs, end-tidal carbon dioxide, and ECG is essential.

G: Give Antidote

  • Administer antidotes based on the identified or suspected toxic agent.
  • The universal antidotes—dextrose, oxygen, naloxone, and thiamine—can be administered as appropriate. Administer dextrose for hypoglycemia and oxygen for hypoxemia, as indicated. Naloxone, administered intranasally or intravenously, is beneficial for any patient with respiratory depression suggestive of opioid exposure. With a rapid onset of action (~1 minute), it serves both diagnostic and therapeutic purposes. Administer thiamine to prevent Wernicke’s encephalopathy in at-risk patients. If glucose administration is indicated but thiamine is unavailable, glucose should not be delayed.
  • Most benzodiazepine overdoses can be effectively managed with supportive care alone, without the need for specific antidotes. In rare cases where specific treatment is required, flumazenil, unlike naloxone, should not be administered empirically.

Flumazenil 

Adult
  • Initial Dose: 0.2 mg over 1-2 minutes
  • Frequency: 0.3 – 0.5 mg IV every 1-2 minutes
  • Maximum Dose: 1 mg
  • Cautions / Comments:
    • Category C in Pregnancy.
    • Short duration of action (45–75 minutes); re-sedation may require re-dosing or continuous infusion (0.25 to 1.0 mg/h).
    • Adverse reactions include seizures (treat with barbiturates or propofol) and arrhythmias.
    • Adverse drug reactions are less common in pediatric patients.
Paediatrics
  • Initial Dose: 0.01 mg/kg over 1-2 minutes
  • Frequency: Up to 4 doses of 0.005 – 0.01 mg/kg
  • Maximum Dose:
    • 0.2 mg per dose.
    • Should not exceed 1 mg total or 0.05 mg/kg.

Flumazenil, a competitive antagonist of the benzodiazepine receptor, is primarily used in benzodiazepine-naïve patients [14]. Common scenarios include iatrogenic overdoses during monitored procedural sedation to reverse respiratory depression and pediatric accidental ingestion.

Flumazenil administration in patients with chronic benzodiazepine use can precipitate withdrawal symptoms, including intractable seizures and status epilepticus. Flumazenil is contraindicated in the following situations:

  • Chronic benzodiazepine use (e.g., for seizure disorders or in known substance use).
  • In patients where the cause of altered mental status is unknown or seizure activity is suspected.
  • Co-ingestion with pro-convulsant agents, such as tricyclic antidepressants, cocaine, diphenhydramine, carbamazepine, chloral hydrate, or bupropion.
  • Iatrogenic overdose during management of status epilepticus.

Benzodiazepine withdrawal syndrome can occur in chronic users following flumazenil administration or abrupt cessation of the drug. The risk is proportional to the dose and duration of benzodiazepine use, increasing significantly after 3–4 months of regular use.

Acute withdrawal requires resuscitation aligned with the standard ABCDE approach:

  • Administer long-acting benzodiazepines (e.g., diazepam or chlordiazepoxide) in mild or moderate cases to alleviate symptoms and allow tapering under medical supervision.
  • Seizures during withdrawal should be treated with propofol or barbiturates rather than benzodiazepines [6].

Special Patient Groups

In the elderly, liver metabolism can be significantly impaired, necessitating dose adjustments [15]. For patients with known liver disease, benzodiazepines without active metabolites are preferred (e.g., lorazepam, oxazepam, temazepam—LOT).

In children under 5 years of age, accidental benzodiazepine ingestion may present primarily with ataxia, which is more common than AMS [16]. Both children and elderly patients may experience paradoxical reactions following benzodiazepine administration for procedural sedation.

When To Admit This Patient

In cases of suspected suicidal attempts, a psychiatric evaluation should be conducted in the emergency department (ED) [17]. Patients with mild, accidental, or pure benzodiazepine overdoses successfully managed in the ED who remain asymptomatic for 4–6 hours can be discharged. However, if mild symptoms persist, admission to a general ward for observation may be warranted until symptom resolution. Patients with severe overdoses requiring monitoring, oxygen therapy, or ventilatory support should be admitted to the ICU [1].

Revisiting Your Patient

The patient was rapidly transferred to the resuscitation room and connected to a monitor. A structured A to E approach was used for further assessment.

Airway: With a GCS of 3/15, a nasopharyngeal airway (NPA) was inserted as a precaution, and an intubation kit was prepared. There were no visible signs of airway trauma, foreign body obstruction, or excessive secretions.

Breathing: The patient was bradypneic with oxygen saturation below 94%. Oxygen at 10 L/min via a non-rebreather mask was administered, improving her saturation to 98%. End-tidal CO₂ measured 35 mmHg.

Circulation: To address hemodynamic instability, two large-bore intravenous cannulas were placed, blood samples were drawn, and an intravenous bolus of 0.9% NaCl was administered. Continuous monitoring showed an improvement in her blood pressure to 85/50 mmHg and her heart rate to 52 bpm. An ECG revealed sinus bradycardia.

Disability: Neurological examination showed constricted pupils. Activated charcoal was not administered, as the ingestion was presumed to have occurred 2–5 hours earlier.

Exposure: On physical examination, no track marks or septal erosion were noted. A mild odor of alcohol was detected. There were no overt signs of seizures, trauma, or assault. However, given the altered mental state, trauma or assault could not be definitively ruled out.

Management included supportive care with oxygen and a trial of naloxone (0.4 mg IV), which had no effect within two minutes. Thiamine (100 mg IV) was administered as part of the standard protocol. Flumazenil was withheld due to concerns about potential withdrawal seizures in the context of possible chronic benzodiazepine use, particularly since the patient was improving with supportive treatment alone.

Further questioning of her friends revealed that they had given her Xanax (alprazolam), though they were unsure of the quantity. They also confirmed that she had consumed alcohol. Laboratory investigations were largely unremarkable, apart from a blood ethanol level of 150 mg/dL.

The patient’s condition showed gradual improvement in the emergency department. Her GCS increased to 9/15 (E3V2M4), and intubation was deferred as she maintained her airway. Hemodynamic stability was achieved, with a blood pressure of 90/55 mmHg, a heart rate of 62 bpm, and oxygen saturation of 95% on a 5 L face mask. Although she remained confused and unable to provide a detailed history, her overall status warranted further supportive care. She was admitted to the telemetry ward for ongoing monitoring and management.

Authors

Picture of Gina Rami Abdelmesih

Gina Rami Abdelmesih

Emergency Department, Zayed Military Hospital

Picture of Rauda Alnuaimi

Rauda Alnuaimi

Emergency Department, Zayed Military Hospital

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References

  1. Overbeek DL, Erickson TB. Sedative-Hypnotics. In: Walls RM, Hockberger RS, Gausche-Hill M, Erickson TB, Wilcox SR, ed. Rosen’s Emergency Medicine Concepts and Clinical Practice, 10th edition. Philadelphia, PA, USA: Elsevier; 2023: 1986-1993.
  2. United Nations Office on Drugs and Crime. Non-medical use of benzodiazepines: a growing threat to public health? https://www.unodc.org/documents/scientific/Global_SMART_Update_2017_Vol_18.pdf Published September 2017. Accessed December 11, 2024.
  3. AlMarri TS, Oei TP. Alcohol and substance use in the Arabian Gulf region: a review. Int J Psychol. 2009;44(3):222-233.
  4. El Zahran T, Kanaan E, Kobeissi L, et al. Benzodiazepine use disorder: A cross-sectional study at a tertiary care center in Lebanon. Medicine (Baltimore). 2022;101(38):e30762.
  5. Naja WJ, Pelissolo A, Haddad RS, Baddoura R, Baddoura C. A general population survey on patterns of benzodiazepine use and dependence in Lebanon. Acta Psychiatr Scand. 2000;102(6):429-431.
  6. Greller H, Gupta A. Benzodiazepine poisoning and withdrawal. UpToDate. https://www.uptodate.com/contents/benzodiazepine-poisoning Updated July 11, 2022. Accessed May 1, 2023.
  7. Yin S. Sedatives and Hypnotics. In: Cydulka RK, Fitch MT, Wang VJ, Cline DM, Ma, OJ, ed. Tintinalli’s Emergency Medicine Manual, 8th Edition. New York, NY, USA: McGraw-Hill Education; 2018: 574-579.
  8. National Poisons Information Service. Street Benzodiazepines. TOXBASE. https://www.toxbase.org/poisons-index-a-z/s-products/street-benzodiazepines/. Updated August, 2022. Accessed May 1, 2023.
  9. Wright SL. Benzodiazepine withdrawal: clinical aspects. In: Peppin J, ed. The Benzodiazepines Crisis. New York, NY: Oxford University Press; 2020. doi:10.1093/med/9780197517277.003.0008. Accessed December 17, 2024.
  10. Rockett IRH, Caine ED, Connery HS, et al. Discerning suicide in drug intoxication deaths: paucity and primacy of suicide notes and psychiatric history. PLoS One. 2018;13(1):1-13. doi:10.1371/journal.pone.0190200.
  11. DeRienz RT, Holler JM, Manos ME, Jemionek J, Past MR. Evaluation of four immunoassay screening kits for the detection of benzodiazepines in urine. J Anal Toxicol. 2008;32(6):433-437. doi:10.1093/jat/32.6.433.
  12. Bolton JM, Spiwak R, Sareen J. Predicting suicide attempts with the SAD PERSONS scale: a longitudinal analysis. J Clin Psychiatry. 2012;73(6):735-741. doi:10.4088/JCP.11M07362.
  13. Emergency Management of Poisoning. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose. 2007;13-61. doi:10.1016/B978-0-7216-0693-4.50007-4
  14. Brogden RN, Goa KL. Flumazenil: a reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs. 1991;42(6):1061-1089. doi:10.2165/00003495-199142060-00010.
  15. Cook PJ. Benzodiazepine hypnotics in the elderly. Acta Psychiatr Scand. 1986;74:149-158. doi:10.1111/j.1600-0447.1986.tb08992.x.
  16. Friedrich JM, Sun C, Geng X, et al. Child and adolescent benzodiazepine exposure and overdose in the United States: 16 years of poison center data. Clin Toxicol (Phila). 2020;58(7):725-731. doi:10.1080/15563650.2019.1674321.
  17. Ronquillo L, Minassian A, Vilke GM, Wilson MP. Literature-based recommendations for suicide assessment in the emergency department: a review. J Emerg Med. 2012;43(5):836-842. doi:10.1016/j.jemermed.2012.08.015.

Reviewed and Edited By

Picture of Elif Dilek Cakal, MD, MMed

Elif Dilek Cakal, MD, MMed

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.