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.
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:
|
qSOFA (adapted SOFA score tool to assess risk of poor outcome in sepsis): | At least 2 of the following indicates higher rate of mortality:
|
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.
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:
- Stabilize the Airway: Administer supplemental oxygen to maintain oxygen saturation levels at ≥92%.
- Cardiac Monitoring: Place the patient on a cardiac monitor to assess rhythm and hemodynamic status.
- Intravenous Access: Establish intravenous access and anticipate the need for a central venous catheter and invasive blood pressure monitoring if necessary.
- 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:
- Restoring Tissue Perfusion
- 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
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.
Ardeshir Kianercy
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.”
Listen to the chapter
References
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Reviewed and Edited By
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.
