Category: Toxicologic Problems

Beta-blocker Intoxication (2024)

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by Alessandro Lamberti-Castronuovo & Filippo Pedretti Magli

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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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References

  1. Definitive Healthcare. Beta-blocker prescription patterns. Definitive Healthcare Blog. Published March 23, 2022. Accessed December 25, 2024. https://www.definitivehc.com/blog/beta-blocker-prescription-patterns.
  2. Soave PM, Curatola A, Ferretti S, et al. Acute poisoning in children admitted to pediatric emergency department: a five-year retrospective analysis. Acta Biomed. 2022;93(1):e2022004. doi:10.23750/abm.v93i1.11602.
  3. Gummin DD, Mowry JB, Beuhler MC, et al. 2021 Annual Report of the National Poison Data System (NPDS) from America’s Poison Centers: 39th Annual Report. Clin Toxicol (Phila). 2022;60(12):1381-1643. doi:10.1080/15563650.2022.2132768.
  4. Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual Report of the America’s Poison Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021;59(12):1282-1501. doi:10.1080/15563650.2021.1989785.
  5. Sharma A. Beta-Blocker Toxicity: Practice Essentials, Pathophysiology, Epidemiology. Medscape eMedicine. Updated May 30, 2020. Accessed December 25, 2024. https://emedicine.medscape.com/article/813342-overview.
  6. Khalid MM, Hamilton RJ. Beta-Blocker Toxicity. StatPearls [Internet]. Updated July 18, 2022. Accessed December 25, 2024. https://www.ncbi.nlm.nih.gov/books/NBK448097/.
  7. Cline DM, Ma OJ. Tintinalli’s Emergency Medicine: Just the Facts. 3rd ed. McGraw Hill Professional; 2012.
  8. Huang CH, et al. Management of beta-blocker overdose: A review. Emerg Med J. 2020;37(8):487-493. doi:10.1136/emermed-2020-209493.
  9. Dargan PI, et al. Lipid emulsion therapy for severe beta-blocker toxicity. Clin Toxicol (Phila). 2015;53(9):853-855. doi:10.3109/15563650.2015.1090595.
  10. Sweeney TE, et al. Lipid emulsion therapy for beta-blocker toxicity: A systematic review. J Med Toxicol. 2016;12(3):267-276. doi:10.1007/s13181-016-0559-1.
  11. Weinberg GL, et al. Lipid emulsion infusion in the management of drug toxicity: A systematic review. Toxicol Rev. 2018;37(4):234-245. doi:10.1080/15563650.2018.1453385.
  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.

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.

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.

Emergency Department Triage (2024)

~ iEM Education Project Team ~ Leave a comment

by Priya Arumuganathan and Scott Findley

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Introduction

Triage is the process of sorting patients by severity of illness to ensure care is administered in a timely fashion according to each patient’s need. When specifically applied to the emergency department, “Emergency Department (ED) Triage” is used to quickly assess, risk-stratify, and manage incoming patients before their complete evaluation. A triage process allows systems to safely operate an influx of multiple patients with varying acuity levels in situations when clinical demand exceeds capacity. Formal triage systems have been employed since as early as the 19th century in warfare settings to effectively handle the growing amounts of field casualties [1].

Today, emergency triage can be generally separated into three distinct phases: prehospital triage, triage at the scene, and emergency department triage. Many different types of triage systems have been developed and implemented worldwide [2]. In this section, we will focus on emergency department triage and some of the most well-known triage systems globally.

Performing a Rapid Triage Assessment

The “rapid triage assessment” is essential to any triage system. Those performing the rapid triage assessment should have some clinical experience and a keen eye to quickly identify patients who need to be seen urgently. The goal of triage is to determine which patients need immediate attention, which patients can wait to be seen, and to manage large patient volumes safely. To accomplish this, one must gather pertinent history and physical exam findings quickly and efficiently.

Performing a Focused History

Obtaining a quick and focused history is of utmost importance during the rapid triage assessment. To summarize, providers must be able to get symptoms pertinent to the patient’s presentation, any relevant events leading to their presentation, and pertinent past medical history and allergies. One mnemonic that is useful and used by many for history-gathering is SAMPLE (as below) [3]:

The SAMPLE mnemonic is a structured method for gathering key clinical information during an emergency assessment. It serves as a framework for emergency medical personnel to obtain essential details quickly and efficiently, allowing them to prioritize care and decide on the best course of action. Each component of the mnemonic corresponds to a specific area of focus in history-gathering, which is vital for rapid triage in the emergency department or pre-hospital setting. Below is a more detailed breakdown of each element:

S – Signs & Symptoms
The first and most immediate part of the assessment focuses on the patient’s presenting signs and symptoms. These may include both subjective (what the patient describes) and objective (what the healthcare provider observes) data. For example, a patient may report chest pain, difficulty breathing, or nausea, while a provider might note abnormal vital signs or physical findings. It’s crucial to obtain a clear description of the symptoms, including onset, duration, intensity, and any factors that may have worsened or alleviated them. Understanding the signs and symptoms will help determine the severity of the condition and direct the urgency of intervention.

A – Allergies
Gathering information about any known allergies is vital in guiding treatment decisions, especially in emergencies where medications or interventions are required quickly. For example, if a patient has a known allergy to penicillin, it is essential to avoid using antibiotics in that class. Allergies to food, medications, environmental triggers, and latex should all be considered. In addition, healthcare providers should be mindful of potential allergic reactions that could complicate the management of the patient’s condition.

M – Medications
A comprehensive medication history helps identify substances that may impact the patient’s current clinical situation. This includes prescribed medications, over-the-counter drugs, supplements, and any recent changes to a medication regimen. For example, a patient taking blood thinners such as warfarin may require careful monitoring for signs of bleeding, while those on insulin may need their blood sugar levels closely monitored. Knowledge of recent changes, doses, and the possibility of drug interactions is crucial in the emergency setting.

P – Past Pertinent History
Past medical history (PMH) can provide essential context for understanding the patient’s current presentation. This includes chronic conditions such as diabetes, hypertension, or asthma, as well as previous hospitalizations, surgeries, or significant illnesses. Understanding a patient’s medical history helps healthcare providers anticipate complications and tailor their approach. For instance, if a patient with a history of seizures presents with altered mental status, healthcare providers will prioritize ruling out or treating seizure activity or postictal states.

L – Last Oral Intake
Knowing the last oral intake—what the patient has eaten or drunk—can provide valuable information about the patient’s condition, especially in cases of poisoning, drug overdoses, or gastrointestinal distress. For example, the timing of food or drink ingestion could suggest an issue with digestion or absorption, which may influence the choice of interventions. In cases of poisoning, knowing whether the patient ingested a toxic substance recently can impact the decision to administer activated charcoal or other antidotes. Additionally, the last oral intake can be crucial if the patient is scheduled for surgery or other procedures, as it helps assess the risk of aspiration or anesthesia complications.

E – Events Leading to the Incident
Understanding the sequence of events that led to the current emergency is essential for diagnosing the cause and assessing the patient’s clinical needs. For example, was the patient involved in a motor vehicle accident, or did they experience a sudden onset of chest pain while exercising? Gathering this information helps to identify the mechanism of injury or the type of acute event, which could significantly alter the emergency management plan. It also provides insight into potential causes of the symptoms and any necessary preventive or therapeutic actions.

Purpose and Application of the SAMPLE Mnemonic in Rapid Triage

The SAMPLE mnemonic is a concise tool designed to quickly gather relevant historical information that can significantly impact clinical decision-making in the emergency department. This structured approach is particularly helpful in high-pressure environments where time is critical, such as during triage or when managing patients with complex or time-sensitive conditions.

The goal during history-gathering in an emergency is to obtain just enough, but not too much detail. Too much detail may delay treatment, while too little may result in missing critical information. For example, a lengthy review of a patient’s family history may be less pertinent in an acute situation compared to knowing their current medication list or the events leading to the emergency. The SAMPLE framework ensures that the provider gathers relevant information to make informed decisions about the next steps in care, whether that be immediate intervention, further diagnostics, or a more detailed secondary assessment.

The SAMPLE mnemonic is an effective tool for emergency practitioners to rapidly gather crucial information during triage and initial assessment. By focusing on the most important elements—signs and symptoms, allergies, medications, past medical history, last oral intake, and events leading up to the incident—providers can prioritize interventions, anticipate potential complications, and provide optimal care in emergency settings.

Performing a Focused Physical Exam

After performing a focused history, it is important to use the information gathered to guide your focused physical exam. For example, a patient presenting with the chief complaint of sore throat should receive an expedited examination of the head, ears, mouth, and neck. The rest of the physical exam should be deferred unless the patient has another complaint that is not covered by these sections. The purpose of the focused physical exam is to look for “red flag” exam findings that would warrant more immediate attention and intervention, such as the peritonitic abdomen in the patient presenting with abdominal pain, oropharyngeal swelling in the patient presenting with shortness of breath and rash, left-sided flaccidity in the patient presenting with sudden onset weakness and tingling, and other concerning findings [4].

Vital Signs and Objective Data

There are clues to key providers about how sick their patients are. One of the most important clues is a patient’s set of vitals; therefore, it is exceedingly important to obtain a full set of vitals for all patients arriving at the emergency department. Vitals at either extreme of the spectrum are equally important, and grossly abnormal vitals should prompt a more expedited triage and shorter waiting times. Other clues that help identify sick patients include the level of pain, duration of symptoms, level of consciousness, and mechanism of injury. Suppose someone is determined to be in distress at any point during the triage process. In that case, they must be brought to a designated patient care area for immediate ED provider attention. In the paragraphs below, we will discuss this further regarding adult populations.

a-photo-of-a-female-patient-in-the-emergency-department-triage (the image was produced by using ideogram 2.0)

Heart Rate

Bradycardia is a heart rate of less than 60 bpm, while tachycardia is a heart rate of more than 100 bpm [5]. If a patient is experiencing associated hypotension with an abnormal heart rate, then it is obvious that they are sick. However, there are other key questions that you may ask in the physical exam to elucidate further a patient’s severity of illness regarding an abnormal heart rate. For example, experiencing associated chest pain, palpitations, extreme fatigue or weakness, altered mental status, shortness of breath, or nausea can be signs that the abnormal heart rate is due to a concerning underlying pathology in the patient. Tachycardia can be indicative of infection, dysrhythmia, acute blood loss, and toxin exposure amongst other etiologies. It is also important to ask about medication use in these patients as this can be your first sign of an accidental (or intentional) chronotropic medication overdose – such as with beta-blockers, calcium channel blockers, and other medications that need to be seen by a medical provider quickly.

Blood Pressure

Hypotension is defined as a blood pressure less than 90/60 mmHg, while hypertension is defined as more than 140/90 mmHg [5]. With hypotension, it is important to first quickly assess if a patient is experiencing a decreased mental status and level of alertness in order to determine if any immediate interventions are needed – if so, this patient is definitely sick and cannot wait for care. Next, it is important to assess for possible causes of hypotension and severe illness, such as septic, hemorrhagic, neurogenic, and anaphylactic shock. For hypertension, it is important to assess for signs that could indicate end-organ failure, such as chest pain, shortness of breath, and focal neurologic deficits. Patients exhibiting the above symptoms should be evaluated sooner rather than later.

Respiratory Rate

Tachypnea is defined as a respiratory rate above 20 bpm, while bradypnea is defined as a respiratory rate below 12 bpm [5]. Apnea is the total absence of breathing. Bradypnea and apnea can be seen in many conditions, including traumatic brain injury and heroin overdose. Tachypnea is seen in many conditions, including asthma exacerbation and conditions causing metabolic derangement, such as diabetic ketoacidosis. If a patient is not breathing or experiencing decreased oxygen saturation along with abnormal respirations, then it is obvious they are sick. However, for those cases that are less obvious, it is important to observe the patient’s work of breathing with their respirations. Those who appear to have a significantly increased respiratory effort, are becoming tired, or are experiencing shallow respirations will need medical evaluation and care sooner rather than later. Their fatiguing respiratory effort will eventually lead to respiratory failure and hypoxia. Those with stories concerning an underlying process that could quickly compromise respiratory function should also be prioritized. For example, a patient who presents with a story suspicious of intracranial hemorrhage who appears sleepy and only moans in response to questions is at high risk for respiratory decompensation.

Oxygen Saturation

Hypoxia is defined as an oxygen saturation below 92% [5]. While different patients can tolerate various oxygen saturation levels depending on their smoking status, history of lung disease, and other past medical history, it is important to assess the work of breathing and level of alertness in patients with low readings. Patients who appear to have increased work of breathing, decreased respirations, or decreased level of alertness are at risk for respiratory decompensation. These patients should be evaluated and treated sooner rather than later.

Temperature

Hypothermia is defined as a temperature below 35 C. In contrast, hyperthermia is defined as a temperature above 38 C [5]. Hypothermic patients must be rewarmed depending on the degree of hypothermia (this will be discussed in later chapters). It is important to determine the reason for their hypothermia – such as sepsis, submersion injury, and prolonged cold exposure. There are many reasons for hyperthermia, including but not limited to infection, prolonged heat exposure, and certain types of medication overdose. The hyperthermic patient must be physically cooled and given antipyretics or other medications depending on the cause of their hyperthermia. These are all causes for concern and immediate interventions.

Pain

The severity and location of pain can also help identify patients who need prompt attention. Patients in severe pain will need immediate attention and medications to alleviate their pain. The location of pain can also be a clue to a patient’s severity of illness. For example, chest pain radiating to the back could represent an aortic dissection, right lower quadrant abdominal pain could represent appendicitis, and headache with neck stiffness could represent bacterial meningitis. Patients with concerning pain severity and location should be prioritized [6].

Duration and Mechanism

The duration of symptoms can also be a clue to a patient’s severity of illness. In general, acute complaints, or complaints that occur with a sudden or recent onset, should raise higher suspicion for serious etiologies than a chronic complaint that has been occurring without change for weeks to months [6]. A patient’s mechanism of injury is also important to consider; for example, a person who has fallen from a significant height or has been involved in a high-speed accident should be evaluated quickly as well.

Level of Consciousness

Level of consciousness exists on a spectrum, from those who are unresponsive to those who are completely awake and alert. Unresponsive patients should receive immediate attention and interventions, including chest compressions if they are without a pulse and intubation. Lethargic patients and those experiencing quickly decreasing levels of alertness should also be prioritized. Those sleepy or confused should be seen urgently, while those fully awake and alert may wait to be seen if they are without other concerning signs/symptoms [6].

Triage is a complex process involving several components, and it can be challenging. Triage providers play a crucial role in ensuring the efficiency and safety of the ED. They must quickly and accurately assess a patient’s severity of illness to determine how long different patients can safely wait for care. It is essential that they do not focus on diagnosing the patient’s condition during triage, as this can delay the process. Such delays can compromise care for all patients, allowing seriously ill individuals to go unnoticed for extended periods while their condition worsens. Remember that a comprehensive history, examination, diagnostic work-up, and treatment will occur once the patient is admitted to a care area.

Triage Systems

Triage is a complex process that needs to be done expediently, especially when facing large patient volumes. Fortunately, many triage systems have been developed to help guide providers in quickly and accurately risk-stratifying patients during the rapid triage assessment. We will discuss some of the most popular and widely used triage systems, such as the Manchester Triage System and the Emergency Severity Index.

Manchester Triage System

One of the most well-known and globally used triage systems is the Manchester Triage System (MTS). It was developed in the UK and is widely used worldwide. This triage system helps ensure patient safety by defining the maximum time each patient can wait before being seen and treated. The MTS contains flowcharts for various presenting complaints that help to distinguish the severity of illness based on key “discriminators” (signs and symptoms) [7]. Each level of severity is assigned a different color. Red indicates immediate evaluation, while blue indicates non-urgent evaluation (can wait up to 240 minutes). Flowcharts are available for various chief complaints in adult and pediatric patients. The MTS (Figure) for the adult chief complaint of “chest pain” is discussed below [8].

The Manchester Triage System

RED: Immediate/Life-Threatening

The red category signifies the highest level of urgency, where the situation is life-threatening and requires immediate medical intervention. The maximum waiting time is 0 minutes, indicating that the patient must receive attention without delay. Correlating examples for chest pain in this category include airway compromise, inadequate breathing, or shock. These conditions are critical as they can lead to rapid deterioration or death if not addressed promptly. Immediate treatment might involve airway management, advanced resuscitation, or stabilization of vital signs.

ORANGE: Emergent/Could Become Life-Threatening

The orange category represents conditions that are not immediately life-threatening but could escalate to critical levels if left untreated. The maximum waiting time in this category is 10 minutes, emphasizing the need for swift medical evaluation and intervention. Examples of chest pain scenarios in this category include severe pain, cardiac pain, acute shortness of breath, or abnormal pulse. These symptoms often indicate serious underlying issues such as myocardial infarction, severe arrhythmias, or pulmonary embolism, all of which require urgent diagnostic and therapeutic measures to prevent deterioration.

YELLOW: Urgent/Not Life-Threatening

In the yellow category, conditions are urgent but not immediately life-threatening. The maximum waiting time is 60 minutes, providing a moderate window for assessment and treatment. Correlating examples for chest pain include pleuritic pain, persistent vomiting, history of cardiac disease, or moderate pain. These symptoms may point to less severe causes, such as musculoskeletal issues, gastroesophageal reflux, or pleurisy. However, the history of cardiac disease suggests a need for careful evaluation to rule out more serious conditions.

GREEN: Semi-Urgent/Not Life-Threatening

The green category involves semi-urgent conditions where the likelihood of life-threatening complications is low. Patients in this category can wait up to 120 minutes for treatment. Examples include vomiting, mild pain, or recent problems. Chest pain in this category is typically associated with benign causes, such as anxiety, mild gastrointestinal issues, or a musculoskeletal strain. While these cases are not critical, timely assessment ensures patient comfort and prevents unnecessary progression of symptoms.

BLUE: Non-Urgent/Needs Treatment When Time Permits

The blue category is for non-urgent conditions that require treatment only when time permits. The maximum waiting time is 240 minutes, as these cases are unlikely to escalate to a critical level. Examples include other complaints that may not even directly relate to chest pain or are minor in nature. These could involve mild discomfort or non-specific symptoms that do not pose any immediate threat to the patient’s health. Such cases can be safely managed without priority over more urgent categories.

Emergency Severity Index

Much like the Manchester Triage System, the Emergency Severity Index triage system (developed in the USA) is also globally known and used. It stratifies patients into five levels: level 1, the most urgent, and level 5, the least urgent. It also helps to determine what resources are necessary to move a patient toward disposition. It is based on four key decision points: does the patient require life-saving interventions (Step A), are they in a high-risk situation (Step B), how many resources do they need (Step C), and what are their vitals (Step D)? The ESI Triage Algorithm, types of resources, and level of urgency, along with examples, are discussed below [9].

Step-by-Step ESI Triage Algorithm

  1. Step A: The first question asks whether the patient requires immediate, life-saving interventions. If the answer is “Yes,” the patient is classified as Level 1, indicating the highest level of urgency. If “No,” the triage proceeds to Step B.

  2. Step B: This step evaluates whether the patient is in a high-risk situation, is lethargic, confused, or in severe pain. A “Yes” response classifies the patient as Level 2, while a “No” response advances the process to Step C.

  3. Step C: At this stage, the need for medical resources is assessed. If the patient requires only one resource, they are categorized as Level 4. If multiple resources are needed, they may qualify for a higher urgency level, prompting a review in Step D.

  4. Step D: This step determines whether the patient exhibits “danger zone” vital signs, such as abnormal heart rate, respiratory rate, or oxygen saturation. A “Yes” response results in a Level 2 classification, while “No” leads to a Level 3 classification.

Types of Resources Defined by ESI

Resources play a critical role in the ESI system, as they help determine patient levels during Step C. Common resource types include:

  • Diagnostic Tools: Labs, EKG/ECG, X-rays, CT scans, MRI, or ultrasounds.
  • Treatment: IV fluids, IV/IM/nebulized medications, and specialist consultations.
  • Procedures: Simple procedures, such as laceration repair or Foley catheter insertion, are counted as one resource. Complex procedures, including conscious sedation, fracture reduction, and intubation, may require additional considerations.

Points according to required resources;

  • 1 point for Labs (e.g., blood tests), EKG/ECG or X-rays, or Advanced Imaging (e.g., CT, MRI, or ultrasound).
  • 1 point for IV fluids.
  • 1 point for IV, IM, or nebulized medications.
  • 1 point for a Specialist consultation.
  • 1 point for a Simple procedure, such as laceration repair or Foley catheter placement.
  • 2 points for a Complex procedure, such as conscious sedation, fracture reduction, or intubation.

These resource definitions allow triage staff to assess patient needs objectively. A higher number of resources often correlates with a more urgent ESI level.

ESI Levels and Their Corresponding Urgency

The ESI system categorizes patients into five levels of urgency based on their condition and resource needs:

  1. Level 1 (Immediate): Patients need immediate attention due to life-threatening conditions like cardiac arrest.
  2. Level 2 (Emergent): These patients are at high risk of rapid deterioration, such as those experiencing an asthma attack.
  3. Level 3 (Urgent, Multiple Resources): Patients with conditions requiring multiple resources, like abdominal pain, fall into this category.
  4. Level 4 (Stable, One Resource): These patients need only one resource, such as laceration repair.
  5. Level 5 (Stable, No Resources): Patients with stable conditions requiring no resources, such as a prescription refill, are classified here.

Advanced Triage

Once you are comfortable with the above basic triage concepts, you can familiarize yourself with advanced triage considerations, such as ordering an initial diagnostic work-up and treatments.

Ordering an Initial Diagnostic Work-Up and Other Orders

As soon as a patient is determined to be sick or unstable, your priority should be to place them in a patient care area as quickly as possible for medical attention. You can then place initial orders, which should be directed toward stabilizing them. Placing IVs early and facilitating early medication/fluid administration can be life-saving measures. Be sure to ask these patients (or their loved ones) early in their evaluation regarding their wishes for cardiopulmonary resuscitation (CPR) and intubation. Once a patient is stable, or if they’re already stable, you can use their pertinent history and physical exam findings to guide your initial diagnostic imaging and labs. Consider your most likely diagnoses and “can’t miss diagnoses” when placing these initial orders [10].

Author

Picture of Priya Arumuganathan

Priya Arumuganathan

Priya Arumuganathan, MD is a third year Emergency Medicine resident at West Virginia University. After residency, she will be completing a Global Emergency Medicine Fellowship at the University of Pennsylvania. During residency, Priya served as a Chief Resident and was very active in teaching core EM content, ultrasound skills, and procedural basics to medical students and new residents. Her rural background and training at several critical access hospitals have helped her build a foundation for working in low-resource environments, and she has been able to translate these skills to her global work. Her academic interests include EM education & training in low-resource environments, telemedicine, and rural health.

Picture of Scott Walker Findley

Scott Walker Findley

Dr. Findley is an associate professor with the WVU Department of Emergency Medicine. He splits time between the larger WVU academic centers and outlying rural emergency departments, spending most of his clinical time in single coverage facilities. After recognizing the challenges inherent in rural emergency medicine (EM), he designed and developed the WVU Division of Rural EM. Dr. Findley secured a federal telemedicine grant to expand telemedicine services in WV critical access hospitals, an institutional HOPE grant to assess per-birth needs in rural emergency departments, assisted with a rural specific response to COVID – 19, secured a position as medical director and advisor for Adventure WV, successfully launched a multisite rural EM rotation for residents, facilitated rural rotations for medical students, and oversaw the integration of rural EM lectures and simulated cases into the resident curriculum. In addition to remaining academically connected, Dr. Findley works closely with the WVU Emergency Department Divisions of ultrasound, EMS and Education to bring resources into the community sites and rural areas. Dr. Findley also sits on the national American College of Emergency Physicians (ACEP) Rural Emergency Medicine’s Task Force. He has taken an active role in research with local and national presentations as well as publishing in academic journals. Although these opportunities have been rewarding, Dr. Findley believes nothing teaches you more, maintains drive and sharpens focus better than pulling shifts and seeing patients and he plans to continue working the majority of his clinical hours in smaller departments.

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References

  1. Robertson-Steel I. Evolution of triage systems. Emerg Med J. 2006;23(2):154-155. doi:10.1136/emj.2005.030270
  2. Yancey CC, O’Rourke MC. Emergency Department Triage. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 31, 2022.
  3. West Virginia Office of Emergency Medical Services. (2016, January 1). Assessment Mnemonics. Appendix D. Retrieved April 23, 2023, from https://www.wvoems.org/files/protocols/appendix/appendix-d-assessment-mnemonics
  4. Society for Academic Emergency Medicine. (2008). Performing a complaint-directed history and Physical Examination. Clerkship Directors in Emergency Medicine. Retrieved April 23, 2023, from https://www.saem.org/about-saem/academies-interest-groups-affiliates2/cdem/for-students/online-education/m3-curriculum/group-focused-chief-complaint-history-physical-examination-and-differential-diagnosis/performing-a-complaint-directed-history-and-physical-examination
  5. Balakumaran, J. (2020, June 30). Interpreting critical vital signs. Medical Concepts. Retrieved April 23, 2023, from https://canadiem.org/interpreting-critical-vital-signs/
  6. Mackway-Jones, K., Marsden, J., & Windle, J. (2014). The Triage Method. In Emergency Triage (2nd ed., pp. 10–21). John Wiley & Sons.
  7. Cicolo, E. A., Ayache Nishi, F., Ciqueto Peres, H. H., & Cruz, D. A. (2017). Effectiveness of the Manchester Triage System on time to treatment in the emergency department: a systematic review protocol. JBI database of systematic reviews and implementation reports, 15(4), 889–898. https://doi.org/10.11124/JBISRIR-2016-003119
  8. Ganley, L., & Gloster, A. S. (2011). An overview of triage in the emergency department. Nursing standard (Royal College of Nursing (Great Britain) : 1987, 26(12), 49–58. https://doi.org/10.7748/ns2011.11.26.12.49.c8829
  9. Gilboy N, Tanabe T, Travers D, Rosenau AM. (2011). Emergency Severity Index (ESI): A Triage Tool for Emergency Department Care, Version 4. Implementation Handbook 2012 Edition. AHRQ Publication No. 12-0014. Rockville, MD. Agency for Healthcare Research and Quality.
  10. International Emergency Medicine Education Project. (2019, March 4). Core Senior EM Clerkship Topics. Emergency Medicine Clerkship – Approach to Chief Complaints. Retrieved April 23, 2023, from https://iem-student.org/em-clerkship-topics/

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.

Antidotes (2024)

~ iEM Education Project Team ~ Leave a comment

by Sarah Alzaabi

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Introduction

An antidote is a specific agent designed to counteract the toxic effects caused by drugs or poisons [1]. These substances play a crucial role in toxicology, as they can effectively mitigate or reverse the harmful consequences of various toxic exposures. In clinical practice, the availability of antidotes is somewhat limited, with only a select number approved for use depending on the type of toxin involved [2].

It’s important to note that antidotes are not administered indiscriminately; instead, they are used based on clearly defined clinical guidelines. Each antidote has specific indications that dictate when it should be given, ensuring that patients receive the appropriate treatment in situations of toxicity. Proper identification of the toxin and the clinical scenario is essential to determine the need for an antidote and to maximize its therapeutic efficacy.

Many poisons have no true antidote, and the poison(s) involved may initially be unknown [3, 4]. Furthermore, limiting the differential diagnosis to poisoning can deter the identification of other pathologies that may exist in these patients [3, 4]. Therefore, the initial approach should be to assess and stabilize [4, 5] thoroughly. Similar to any compromised patient, the attention is directed toward securing the airway, breathing, circulation, and decontamination [4, 5]. There are only a few indications where antidotes are prioritized over cardiopulmonary stabilization, i.e., naloxone for opioid toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning [5]. Otherwise, most patients will have good outcomes with supportive management and a period of observation [1, 3, 4, 5].

Administration of pharmacologic antagonists may worsen the outcome in some situations and is not recommended [2, 3]. Therefore, the physician should know the indications and contraindications of each antidote [2, 3]. When in doubt, consult a poison control center or a medical or clinical toxicologist [2, 4].
In summary, it’s important to understand that antidotes should be utilized as complementary treatments rather than the sole focus in managing poisoning cases [1]. The primary objective should always be to address the patient’s overall condition, taking into account their symptoms and needs, rather than concentrating exclusively on the specific toxin involved [4]. This approach ensures a more comprehensive and effective care strategy for individuals affected by poisoning.

Pregnant Patients and Antidotes

Limited data is available on the use of antidotes in pregnancy [4]. Hence, the teratogenic potential of antidotes is not fully understood [7]. The general initial management principles are the same, and stabilization of the mother is the priority [6].

The risks and benefits of using or withholding antidotes must be assessed. In general, antidotes are not used for uncertain indications, but proven effective treatments should not be withheld from the mother based on theoretical danger to the fetus [4].

There is no known indication for fetal antidote therapy [7]. However, if an antidote is to be given for fetal benefit, it should be done rapidly in the acute setting [7]. This specifically applies to chelators such as dimercaprol, calcium EDTA, and deferoxamine, which will prevent the toxin from passing into fetal circulation [7].

The following section presents information about various antidotes, organized in alphabetical order.

Antidotes

Atropine

General Information

  • Anticholinergic agent, competitive muscarinic antagonist [3, 4, 5, 8].

Indications

  • Organophosphate poisoning, carbamates, nerve agents [3, 4, 5, 8].

Precautions

  • Excessive doses may cause anticholinergic symptoms [5].

Dose/Administration

  • Adults: Start with 1-2 mg IV, double the dose every 2-3 minutes to reach the goal [3, 4, 5, 8].
  • Children: 0.02 mg/kg IV (minimum of 0.1 mg) [3].

Other Notes

  • Large doses may be required.
  • Goal: Drying of respiratory secretions/improved work of breathing [3, 8].
  • Tachycardia is not the endpoint (atropine helps with muscarinic effects; pralidoxime is used for nicotinic effects) [3, 8].

Calcium

General Information

  • Calcium chloride 10% (1 g/10 mL, 27.2 mg/mL elemental Ca).
  • Calcium gluconate 10% (9 mg/mL elemental Ca), one-third strength of calcium chloride [5].

Indications

  • Calcium channel blocker toxicity, hydrofluoric acid exposure, hyperkalemia, hypermagnesemia [4, 5, 9].

Precautions

  • Calcium chloride extravasation can cause soft tissue necrosis; prefer central line administration [9].
  • Continuous monitoring is recommended [9].

Dose/Administration

  • Adults:
    • Calcium chloride: 0.5-1 g IV (5-10 mL) [5, 9].
    • Calcium gluconate: 1-3 g IV (10-30 mL) [5].
  • Children: 0.15 mL/kg calcium chloride IV [5].
  • IV bolus over 5-10 minutes; repeated doses every 10-20 minutes as needed, guided by serum Ca+ or QT interval [9].
  • Infusion available [9].

Other Notes

  • For HF acid skin burns: Topical 2.5% calcium gel or local injection of calcium gluconate [9].
  • Regional block with intra-arterial or IV calcium gluconate for extremity exposure [9].
  • Nebulized calcium gluconate for HF acid inhalation injury [9].

Cyproheptadine

General Information

  • Antihistaminic and antiserotonergic agent; also has anticholinergic activity [10].

Indications

  • Serotonin syndrome [4, 10].

Dose/Administration

  • Adults: 8 mg every 8 hours for 24 hours (if response observed) [10].
  • Children: 4 mg (not well established) [10].

Deferoxamine

General Information

  • Iron-chelating agent that converts iron to a water-soluble complex for renal clearance [3, 11].

Indications

  • Systemic iron toxicity (e.g., severe gastroenteritis, shock, metabolic acidosis, altered mental status) [3, 4, 11].
  • Iron levels >500 µg/dL or multiple pills on radiography [3, 4, 11].
  • Chronic iron overload [3, 4, 11].

Precautions

  • Hypotension may occur at rapid infusion rates; ensure adequate hydration [3].
  • Cardiac monitoring is needed [11].

Dose/Administration

  • Start with IV infusion: 15 mg/kg/h (maximum 1 g/h) over 6 hours; re-evaluate [3, 11].
  • Infusion rate can be increased in critical patients if blood pressure allows [11].

Other Notes

  • Urine may become rusty-red as iron is excreted [3, 11].

Digoxin Immune Fab

General Information

  • Fab fragments of antibodies to digoxin, reversing cardiotoxic effects [1, 3].

Indications

  • Digoxin overdose with potassium >5 mEq/L after acute ingestion, hemodynamic instability, or life-threatening dysrhythmias [3].
  • Poisoning by other cardiac glycosides (e.g., Oleander) [1, 3, 5, 12].

Precautions

  • Close monitoring of digoxin serum levels, vital signs, and ECG. Resuscitation equipment should be ready [12].

Dose/Administration

  • Acute overdose:
    • Stable patients: 5 vials.
    • Unstable patients: 10-20 vials [3, 5].
  • Chronic overdose: Start with 1-2 vials, repeat after 60 minutes if needed [12].
  • Calculate dose if the ingested dose is known (40 mg Fab binds 0.6 mg digoxin) [3, 5].
  • Bolus in life-threatening conditions (e.g., cardiac arrest) or infusion over 30 minutes, monitoring clinical response [3, 12].

Other Notes

  • For other cardiac glycoside poisoning: Start with 5 vials [3, 12].

Dimercaprol (BAL)

General Information

  • Heavy metal chelator [1, 14].

Indications

  • Severe lead, inorganic arsenic, and mercury poisoning [1, 4, 13].

Precautions

  • Severe adverse effects include nephrotoxicity; consider using EDTA or succimer instead if possible [13].

Dose/Administration

  • 3 mg/kg IM every 4 hours for 48 hours, then every 12 hours for 7-10 days based on clinical response [13].

Ethanol

General Information

  • Blocks formation of toxic metabolites of alcohols [14].

Indications

  • Methanol and ethylene glycol poisoning (second-line to fomepizole) [5, 14].

Precautions

  • Maintain blood ethanol concentration between 100-150 mg/dL [14].

Dose/Administration

  • IV:
    • Loading: 10 mL/kg of 10% ethanol.
    • Maintenance: 1-2 mL/kg/h of 10% ethanol [14].
  • Oral:
    • Loading: 1.8 mL/kg of 43% ethanol.
    • Maintenance: 0.2-0.4 mL/kg/hour of 43% ethanol [14].

Flumazenil

General Information

  • Competitive antagonist of GABA-benzodiazepine receptors [1, 2, 3, 15].

Indications

  • Benzodiazepine overdose (limited role), reversal of procedural sedation, accidental pediatric ingestion [1, 3, 5, 15].

Precautions

  • May cause withdrawal or seizures, especially in benzodiazepine dependence or mixed overdoses [2, 3, 15].

Dose/Administration

  • Adults: 0.2 mg IV over 30 seconds, repeat every minute until reversal (maximum 3 mg) [1, 3, 5, 15].
  • Children: 0.01-0.02 mg/kg, repeat every minute [1, 5, 15].

Other Notes

  • Limited role due to risk of seizures [1, 3, 15].

Fomepizole

General Information

  • Alcohol dehydrogenase inhibitor [1, 3, 16].

Indications

  • Methanol and ethylene glycol toxicity (first-line due to better side effect profile) [1, 3, 5, 16].

Dose/Administration

  • Loading dose: 15 mg/kg IV infusion in 100 mL normal saline or 5% dextrose over 30 minutes [1, 3, 16].
  • Maintenance dose: 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every 12 hours until alcohol concentrations <20 mg/dL [1, 16].
  • In dialyzed patients: Give every 4 hours or continuous infusion of 1 mg/kg/h [16].

Other Notes

  • Continue therapy until alcohol concentrations are <20 mg/dL and the patient is asymptomatic [3].

Glucagon

General Information

  • Increases cyclic AMP (cAMP).
  • Positive inotropic and chronotropic properties, similar to beta-agonists [18].

Indications

  • β-blocker toxicity (adjunct).
  • Calcium channel blocker toxicity [5, 17, 18].

Precautions

  • Induces vomiting; consider anti-emetics and airway management [18, 19].

Dose/Administration

  • Adults: 5-10 mg IV bolus over 1-2 minutes [5, 18, 19].
  • Children: 0.05-0.1 mg/kg IV [19].

Other Notes

  • If there is a clinical response, start an infusion [18].
  • Intravenous fluids, vasopressors, and high-dose insulin with dextrose are first-line treatments for β-blocker toxicity [19].

Hydroxocobalamin

General Information

  • Precursor of Vitamin B12 [20].

Indications

  • Cyanide toxicity (forms cyanocobalamin by displacing hydroxyl group) [3, 5, 20].

Precautions

  • Safe drug with low side effects.

Dose/Administration

  • Adults: 5 g in 100 mL normal saline IV infusion over 15 minutes; repeat if needed [3, 5, 20].
  • Children: 70 mg/kg IV over 15 minutes (maximum 5 g) [3, 5].

Other Notes

  • Causes orange-red discoloration of skin and urine, resolving within 24-48 hours [3].

Insulin (High Dose)

General Information

  • Strong inotropic effects [21].

Indications

  • Calcium channel blocker and β-blocker toxicity [5, 21].

Precautions

  • Monitor for hypoglycemia, hypokalemia, hypomagnesemia, and hypophosphatemia [21].

Dose/Administration

  • Adults:
    • Glucose 25 g (50 mL of dextrose 50%) IV bolus → 1 IU/kg IV bolus of short-acting insulin → 25 g/h glucose and 0.5-1 IU/kg/h short-acting insulin infusion [21].
  • Titrate glucose to maintain levels between 6-8 mmol/L [21].

Intravenous Lipid Emulsion

General Information

  • 20% lipid emulsion as a parenteral nutrient.
  • Expands the lipid compartment within the intravascular space, sequestering lipid-soluble drugs from tissues [1, 5].

Indications

  • Overdose by drugs with high protein binding and large volume of distribution, e.g., local anesthetics (bupivacaine), β-blockers, and calcium channel blockers [1, 5].

Dose/Administration

  • Adults: 100 mL IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 18 mL/min IV infusion for 20 minutes [5].
  • Children: 1.5 mL/kg IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 0.25 mL/kg/min IV infusion for 20 minutes [5].

Methylene Blue

General Information

  • Reduces methemoglobin (MetHb) to hemoglobin [5, 22].

Indications

  • Symptomatic methemoglobinemia.
  • MetHb levels >20% in asymptomatic patients.
  • Oxidizing toxins (e.g., nitrites, benzocaine, sulfonamides) [5, 22].

Precautions

  • Pulse oximetry is unreliable in methemoglobinemia.
  • May cause hemolysis in G6PD deficiency [3, 22].

Dose/Administration

  • 1-2 mg/kg slow IV injection over 5 minutes; may repeat after 30-60 minutes [5, 22].

Other Notes

  • Monitor MetHb levels frequently until a consistent decrease is observed [22].

N-acetylcysteine (NAC)

General Information

  • Prevents hepatocellular injury by restoring glutathione stores, which conjugate the toxic metabolite NAPQI [1, 3, 23].

Indications

  • Serum acetaminophen levels above toxic threshold (>4 hours after ingestion).
  • Single ingestion >150 mg/kg.
  • Evidence of liver injury [1, 3, 4, 23].

Dose/Administration

  • Oral: 140 mg/kg loading dose → 70 mg/kg every 4 hours for 17 doses [1, 3, 23].
  • IV: 150 mg/kg in 200 mL of 5% dextrose over 60 minutes → 50 mg/kg diluted in 500 mL of 5% dextrose over 4 hours → 100 mg/kg diluted in 1000 mL of 5% dextrose over 16 hours [1, 3, 23].

Other Notes

  • Oral therapy may not be well tolerated due to taste and odor [23].

Naloxone

General Information

  • Opioid antagonist, diagnostic, and therapeutic agent [1, 2, 3].

Indications

  • Opioid toxicity with respiratory and CNS depression [1, 2, 3, 5].

Precautions

  • Re-sedation may occur due to naloxone’s short half-life; monitor for at least 4 hours.
  • Withdrawal in chronic/opioid-dependent users [1, 2, 3].

Dose/Administration

  • Adults: 0.4-2 mg IV; repeat every 2-3 minutes up to a maximum of 10 mg [1, 2, 3].
  • Children: 0.01 mg/kg IV [1, 3].

Other Notes

  • Goal: Adequate respiratory rate, normal oxygen saturation on room air, improved level of consciousness [3, 5].
  • Miosis is an unreliable indicator [5].

Octreotide

General Information

  • Synthetic analogue of somatostatin [24].

Indications

  • Hypoglycemia secondary to sulfonylurea [24].

Precautions

  • Breakthrough hypoglycemia may occur [24].

Dose/Administration

  • Adults:
    • 50 µg IV bolus → 25 µg/h infusion.
    • Alternatively, 100 µg IM or SC every 6 hours [24].
  • Children: 1 µg/kg IV bolus or SC → 1 µg/kg/h IV infusion [24].

Other Notes

  • Euglycemia needs to be maintained for 12 hours off the infusion before the patient is medically cleared [24].

Physostigmine

General Information

  • Reversible acetylcholinesterase inhibitor [25].

Indications

  • Neurological anticholinergic symptoms, e.g., delirium and seizures (crosses the blood-brain barrier) [5, 25].

Precautions

  • Contraindicated in bradycardia, AV block, and bronchospasm [25].

Dose/Administration

  • Adults: 0.5-1 mg slow IV push over 5 minutes; repeat in 10-30 minutes if needed [25].
  • Children: 0.02 mg/kg IV (maximum dose of 0.5 mg) [25].

Other Notes

  • Confirm absence of conduction defects on a 12-lead ECG before administration.
  • Rapid administration may cause a cholinergic crisis; treat with atropine if this occurs [25].

Pralidoxime

General Information

  • Reactivates acetylcholinesterase inhibition [1, 3, 26].

Indications

  • Early organophosphate poisoning (<2 hours).
  • Nerve agents [1, 3, 5, 26].

Precautions

  • Rapid administration can cause laryngospasm, muscle rigidity, and transient respiratory impairment [3].

Dose/Administration

  • Adults: 1-2 g IV in 100 mL of 0.9% saline over 15-30 minutes → 500 mg/h IV infusion [3, 26].
  • Children: 25-50 mg/kg → 10-20 mg/kg/h infusion [3, 26].

Other Notes

  • Administer in the early phase before irreversible acetylcholinesterase binding occurs.
  • Adequate atropine doses should be given concurrently [1, 3, 26].

Pyridoxine (Vitamin B6)

General Information

  • Vitamin B6, essential for GABA production [3, 27].

Indications

  • Isoniazid, hydrazine, and Gyromitra poisoning.
  • Ethylene glycol poisoning (adjunct therapy) [3, 5, 27].

Dose/Administration

  • Adults:
    • For isoniazid poisoning: 1 g per gram of ingested isoniazid, given as 0.5 g/min infusion until seizures stop. If unknown, give 5 g IV empirically [3, 5, 27].
  • Children: 70 mg/kg IV, maximum 5 g [5, 27].

Other Notes

  • For ethylene glycol toxicity: 50 mg IV every 6 hours [27].

Sodium Bicarbonate

General Information

  • Hyperosmolar sodium bicarbonate injection [28].

Indications

  • Cardiotoxicity due to fast sodium channel blockade presenting as QRS widening and ventricular dysrhythmias (e.g., TCA poisoning).
  • Urine alkalinization [2, 5, 28].

Precautions

  • Monitor for hypokalemia and hypernatremia.
  • Maintain serum pH between 7.50-7.55 [28].

Dose/Administration

  • Start with 1-2 mEq/kg IV over 1-2 minutes → 0.3 mEq/kg per hour IV infusion if needed [5].
  • Repeated doses may require intubation and hyperventilation to maintain pH >7.5-7.55 [28].

Sodium Calcium Edetate (EDTA)

General Information

  • IV heavy metal chelator [29].

Indications

  • Severe lead toxicity with lead levels >70 µg/dL [29].

Precautions

  • Risk of nephrotoxicity, ECG changes, and transaminitis.
  • Hospital admission required [29].

Dose/Administration

  • Dilute 25-50 mg/kg in 500 mL of 0.9% saline or 5% dextrose; infuse over 24 hours, starting 4 hours after the first dose of dimercaprol [29].
  • In encephalopathy, continuous infusion for 5 days until stabilization [29].

Other Notes

  • Once clinically improved, switch to oral succimer if tolerated [29].

Sodium Thiosulfate

General Information

  • Assists the body in detoxifying cyanide [1, 30].

Indications

  • Cyanide poisoning [1, 5, 30].

Precautions

  • In severe cases, use with other antidotes (e.g., hydroxocobalamin) [30].

Dose/Administration

  • Adults: 50 mL of 25% solution (12.5 g; 1 ampoule) IV over 10 minutes [1, 5, 30].
  • Children: 1.65 mL/kg IV; repeat after 30 minutes if clinically indicated [30].

Succimer (DMSA)

General Information

  • Oral heavy metal chelator [31].

Indications

  • Symptomatic lead poisoning.
  • Asymptomatic lead poisoning with lead levels >60 µg/dL in adults or >45 µg/dL in children [5, 31].

Precautions

  • Reversible neutropenia, gastrointestinal upset, and liver function abnormalities [31].

Dose/Administration

  • 10 mg/kg three times a day for 1 week → two times a day for 2 weeks [31].

Other Notes

  • Monitor serum lead levels during treatment [31].

Antidotes play a crucial role in managing toxicological emergencies in the emergency department. While their use is often specific and limited, they provide life-saving interventions in cases of confirmed poisonings such as opioid overdoses, cyanide poisoning, or organophosphate exposure. However, their administration requires careful assessment of indications, contraindications, and potential adverse effects. Emergency clinicians must prioritize stabilizing airway, breathing, and circulation before considering antidote administration, except in scenarios where antidotes are critical to immediate survival. The decision to use an antidote should be guided by clinical judgment, toxicology consultation, and evidence-based guidelines. Ultimately, antidotes should be viewed as adjunctive therapies, emphasizing the principle of treating the patient comprehensively rather than focusing solely on the poison.

Author

Picture of Sarah Alzaabi

Sarah Alzaabi

Sarah Alzaabi, MD is a graduate from the United Arab Emirates University. She is currently a medical intern at Sheikh Shakhbout Medical City, Abu Dhabi, with a longstanding interest in Emergency Medicine. She is a big advocate for the FOAMed movement; and is proud to be a part of the fantastic team at iEM. She is excited to develop innovative ways to provide accessible education for anyone in need. Sarah has a particular interest in lifestyle and nutrition and spends time learning about how to educate others about succeeding in medicine while maintaining a healthy lifestyle.

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References

  1. Chacko B, Peter JV. Antidotes in Poisoning. Indian J Crit Care Med. 2019;23(Suppl 4):S241-S249. doi:10.5005/jp-journals-10071-23310
  2. Erickson TB, Thompson TM, Lu JJ. The Approach to the Patient with an Unknown Overdose. Emerg Med Clin N Am. 2007;25(2):249-81.
  3. Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emerg Med Clin North Am. 2008;26(3):715-39.
  4. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Principles of Managing the Acutely Poisoned or Overdosed Patient. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw Hill; 2019. Accessed March 04, 2023. https://accessemergencymedicine-mhmedical-com.uaeu.idm.oclc.org/content.aspx?bookid=2569&sectionid=210267250
  5. Greene S. General Management of Poisoned Patients. Tintinalli’s Emergency Medicine. 8 ed: MC Graw Hill; 2014. p. 1207.
  6. Gei AF, Suarez VR. Poisoning in Pregnancy. In: Foley MR, Strong, Jr TH, Garite TJ. eds. Obstetric Intensive Care Manual, 5e. McGraw Hill; . Accessed March 04, 2023. https://obgyn-mhmedical-com.uaeu.idm.oclc.org/content.aspx?bookid=2379&sectionid=185993887
  7. Bailey, B. (2003), Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?. Birth Defects Research Part A: Clinical and Molecular Teratology, 67: 133-140. https://doi-org.uaeu.idm.oclc.org/10.1002/bdra.10007
  8. Long N. Atropine. Life in the Fast Lane. https://litfl.com/atropine/. Published November 3, 2020. Accessed March 23, 2023.
  9. Long N. Calcium. Life in the Fast Lane. https://litfl.com/calcium/. Published November 3, 2020. Accessed March 23, 2023.
  10. Long N. Cyproheptadine. Life in the Fast Lane. https://litfl.com/cyproheptadine/. Published November 3, 2020. Accessed March 23, 2023.
  11. Long N. Desferrioxamine. Life in the Fast Lane. https://litfl.com/desferrioxamine/. Published November 3, 2020. Accessed March 23, 2023.
  12. Long N. Digoxine Immune Fab. Life in the Fast Lane. https://litfl.com/digoxin-immune-fab/. Published November 3, 2020. Accessed March 23, 2023.
  13. Long N. Dimercarpol. Life in the Fast Lane. https://litfl.com/dimercaprol/. Published November 3, 2020. Accessed March 23, 2023.
  14. Long N. Ethanol. Life in the Fast Lane. https://litfl.com/ethanol/. Published November 3, 2020. Accessed March 23, 2023.
  15. Long N. Flumazenil. Life in the Fast Lane. https://litfl.com/flumazenil/. Published November 3, 2020. Accessed March 23, 2023.
  16. Long N. Fomepizole. Life in the Fast Lane. https://litfl.com/fomepizole/#:~:text=Fomepizole%20is%20an%20alcohol%20dehydrogenase,methanol%20and%20ethylene%20glycol%20poisoning. Published June 15, 2021. Accessed March 23, 2023.
  17. Long N. Glucagon. Life in the Fast Lane. https://litfl.com/glucagon/. Published November 3, 2020. Accessed March 24, 2023.
  18. Nickson C. Glucagon Therapy. Life in the Fast Lane. https://litfl.com/glucagon-therapy/. Published November 3, 2020. Accessed March 24, 2023.
  19. Atlantic Canada Poison Centre. https://atlanticcanadapoisoncentre.ca/glucagon-pediatric.html. Published March 2017. Accessed March 30, 2023.
  20. Long N. Hydroxocobalamin. Life in the Fast Lane. https://litfl.com/hydroxocobalamin/. Published November 3, 2020. Accessed March 24, 2023.
  21. Long N. Insulin (High dose). Life in the Fast Lane. https://litfl.com/insulin-high-dose/. Published November 3, 2020. Accessed March 24, 2023.
  22. Long N. Methylene Blue. Life in the Fast Lane. https://litfl.com/methylene-blue/. Published November 3, 2020. Accessed March 24, 2023.
  23. Long N. N-acetylcysteine. Life in the Fast Lane. https://litfl.com/n-acetylcysteine/#:~:text=Acetylcysteine%20is%20the%20most%20widely,of%20NAPQI%20(toxic%20paracetamol%20metabolite. Published November 3, 2020. Accessed March 24, 2023.
  24. Long N. Octreotide. Life in the Fast Lane. https://litfl.com/octreotide/. Published November 3, 2020. Accessed March 24, 2023.
  25. Long N. Physostigmine. Life in the Fast Lane. https://litfl.com/physostigmine/. Published November 3, 2020. Accessed March 24, 2023.
  26. Long N. Pralidoxime. Life in the Fast Lane. https://litfl.com/pralidoxime/#:~:text=This%20is%20the%20oxime%20commonly,and%20the%20OP%2FCarbamate%20involved. Published November 3, 2020. Accessed March 24, 2023.
  27. Long N. Pyridoxine. Life in the Fast Lane. https://litfl.com/pyridoxine/. Published November 3, 2020. Accessed March 24, 2023.
  28. Long N. Sodium Bicarbonate. Life in the Fast Lane. https://litfl.com/sodium-bicarbonate/. Published November 27, 2022. Accessed March 24, 2023.
  29. Long N. Sodium Calcium edetate. Life in the Fast Lane. https://litfl.com/sodium-calcium-edetate/#:~:text=Sodium%20Calcium%20Edetate%20(EDTA)%20is,3.38%20micro%20mol%2FL). Published November 3, 2020. Accessed March 24, 2023.
  30. Long N. Sodium thiosulphate. Life in the Fast Lane. https://litfl.com/sodium-thiosul phate/#:~:text=Sodium%20thiosulfate%20enhances%20the%20endogenous,hydroxocobalamin%20in%20severe%20cyanide%20toxicity.Published November 3, 2020. Accessed March 24, 2023.
  31. Long N. Succimer. Life in the Fast Lane. https://litfl.com/succimer/#:~:text=Succimer%20(DMSA)%20is%20an%20orally,2.9%20micro%20mol%2FL). Published November 3, 2020. Accessed March 24, 2023.

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.

Carbon Monoxide Poisoning (2024)

~ iEM Education Project Team ~ Leave a comment

by Mohammad Issa Naser & Abdulla Alhmoudi

Authors
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You have a new patient!

A 48-year-old male with a known medical history of hypertension, depression, and prior suicidal attempts was brought into the Emergency Department by EMS after he was found unconscious by his wife after she arrived from work. He was lying down in an enclosed garage at home with the car engine running. She states that her husband was having difficulty breathing when she found him and was not responding to her. She reported that he had been depressed for the last few weeks because of financial problems. Upon arrival at the ED, the patient was unresponsive, with the following vital signs noted: BP 113/74 mmHg, HR 114 bpm, RR 10 bpm, and oxygen saturation at 98%.

a-photo-depicts-a-48-year-old-man-found-in-the-garage (image was created by using ideogram 2.0)

What do you need to know?

Importance and Epidemiology

Carbon Monoxide (CO) is often called the “silent killer” as it lacks any warning or alarming signs of its presence. It is a colorless, odorless, tasteless, and non-irritating gas formed by the incomplete combustion of hydrocarbon fuels.

Despite a historical decline in the number of cases, CO continues to be one of the major causes of poisoning-related ED visits, accounting for approximately 50,000 cases every year in the United States, with a mortality rate of 1% to 3% [1]. Although many of these are nonfatal exposures with various degrees of toxicity, an estimated 1,000 to 2,000 patients a year die from severe toxicity [2]. Intentional poisoning cases have higher mortality rates compared to accidental cases and account for two-thirds of deaths [3,4]. Although cases can occur around the year, CO poisoning has a seasonal and geographic relation with cold climates, peaking during winter months, most commonly from faulty furnaces [5].

CO poisoning often has nonspecific toxicologic presentations ranging from minimal symptoms to unresponsiveness. It requires higher suspicion from clinicians to recognize, diagnose, and provide timely and appropriate management to avoid morbidity, mortality, and long-lasting complications. ED physicians should always consider CO poisoning when multiple patients present to the ED from a single location with similar correlating findings [3].

Pathophysiology

CO poisoning causes tissue hypoxia by impairing oxygen delivery and utilization and generating reactive oxygen species. CO can rapidly diffuse into the pulmonary circulation and reversibly bind the iron moiety of heme with approximately 240 times the affinity of oxygen-forming carboxyhemoglobin (COHb). CO impairs heme’s ability to deliver oxygen by directly occupying oxygen-binding sites and causing a conformational change to the other three oxygen-binding sites. This allosteric change increases the affinity of the oxygen binding site and decreases the oxygen delivery to the peripheral tissues, causing a leftward shift in the oxyhemoglobin dissociation curve. The amount of carboxyhemoglobin formed depends on the amount of CO and oxygen in the environment, duration of exposure, and minute ventilation [6].

CO also binds to myoglobin and NADPH reductase, which can worsen the hypoxia of cardiac muscle by affecting the mitochondria and ATP production, potentially leading to atraumatic rhabdomyolysis [2]. Like cyanide, CO inactivates cytochrome oxidase, which is involved in mitochondrial oxidative phosphorylation, causing a switch to anaerobic metabolism, and their combined effects can be synergistic in smoke inhalation [7]. Other effects of CO poisoning include neutrophil degranulation, free radical formation, lipid peroxidation in the brain and other tissues, and cellular apoptosis [2,8]. The half-life of COHb is about 300 minutes; thus, it begins to accumulate in the blood within a short exposure time. With normobaric oxygen (NBO) therapy (which is 100% inhaled oxygen at normal atmospheric pressure), the half-life is decreased to between 50 and 100 minutes; with Hyperbaric oxygen therapy, the half-life can be reduced to 30 minutes [9,10].

Medical History

A thorough history can be very helpful for early recognition of CO-related poisoning. Clinical findings can be variable and highly unspecific. The most common complaint in patients with mild to moderate CO poisoning is headache, present in up to 58% of patients, followed by the wide range of unspecific findings of nausea, dizziness, drowsiness, vomiting, cough or choking, confusion, shortness of breath, syncope, throat and eye irritation and chest pain [3]. It is important for clinicians to inquire about potential CO sources such as residential heating systems, gas appliances, or recent fires. In addition, clinicians should specifically inquire about transient loss of consciousness, as the presence or absence of this finding can be important in determining the severity of the presentation and the need for further interventions like hyperbaric oxygen [6]. Delayed neurological sequelae (DNS) is a well-known complication and can occur in 15 to 40 percent of patients presenting with significant CO poisoning [11]. DNS has been reported to appear 3 to 240 days after apparent recovery, with the majority of cases occurring within 20 days of CO poisoning. Deficits can last a year or more and are typically not found on acute presentation. Patients may present with cognitive impairment, memory deficits, movement disorders, or psychiatric symptoms. Any neurological or neuropsychiatric symptoms persisting beyond the acute phase of CO poisoning should raise suspicion for DNS and warrant appropriate evaluation and management [6]. Risk factors that predict the development of delayed neurologic sequelae include extremes of age and loss of consciousness. Because most CO-poisoned patients reaching the ED survive with minimal intervention, prevention of delayed neurologic and neuropsychiatric sequelae is a primary goal of therapy [12].

Physical Examination

Physical examination in suspected CO poisoning patients should focus on vital signs, cardiac and pulmonary examination, and a thorough neurological assessment. Findings in CO poisoning are usually limited to changes in mental status, tachycardia, and tachypnea in the absence of history of trauma or burns. Symptoms can range from mild confusion to coma [6]. The presence of “cherry-red” skin or mucous membranes may be observed in severe cases or even noted postmortem. However, it’s neither a sensitive nor specific sign, and it does not exclude CO poisoning [13]. Severe CO poisoning can be associated with neurologic, metabolic, and cardiovascular red flags such as seizures, syncope, lactic acidosis, acute myocardial infarction, ventricular arrhythmia, and pulmonary edema [6].

Alternative Diagnoses

Carbon monoxide poisoning can be a “great mimic,” but the early presentations are often nonspecific and readily confused with other conditions, typically a viral syndrome, explaining why influenza is the most common misdiagnosis [14]. CO poisoning can also be misdiagnosed frequently as gastroenteritis, food poisoning, or even colic in infants. Like adults, children tend to develop nonspecific symptoms that complicate the diagnosis [15]. More severe poisoning may be confused with other causes of altered mental status, such as trauma, diabetic ketoacidosis, meningitis, hypoglycemia, and intoxication [16]. The differential diagnosis remains broad without a known exposure source or sick contacts as clues. Cyanide poisoning, especially in patients with smoke inhalation, should also be considered due to the potential for concurrent exposure. In cases of chronic CO exposure, chronic fatigue, mood disorders, sleep disorders, and memory problems should be considered as an alternate diagnosis [17]. Recognizing risk factors for CO poisoning can be crucial in determining the likelihood of CO poisoning; focusing on potential sources of CO poisoning, the presence of multiple individuals with similar symptoms from the same location increases the likelihood of CO poisoning. The CNS is the organ system most sensitive to CO poisoning. Acutely, otherwise healthy patients may manifest headache, dizziness, and ataxia at COHb level as low as 15% to 20%; with higher levels and longer exposures, syncope, seizures, or coma may result [15]. At the same time, history of consuming contaminated food or recent sick contact with flu-like symptoms would make the diagnosis less likely.

Acing Diagnostic Testing

The single most useful diagnostic test to use in a suspected CO poisoning is COHb levels.15 An arterial or venous blood gas analysis with elevated carboxyhemoglobin levels (usually ≥ 3%-4% for nonsmokers or ≥ 10% for smokers) confirms the diagnosis of CO poisoning and provides information about lactate levels and any concurrent metabolic acidosis. It is important to obtain lactate levels to screen for possible concurrent cyanide toxicity (Lactate > 10 mmol/L) if the source of CO was a fire [18]. While an abnormally elevated COHb level indicates CO poisoning, it is important to note that the COHb levels do not accurately represent the severity of the poisoning. This is particularly true if there has been a significant time lapse between the exposure and when the levels were obtained due to CO clearance. Patients with major symptoms such as loss of consciousness altered mental status, or cardiac ischemia should be considered as severe poisoning with any abnormally elevated COHb level. CO poisoning management should focus primarily on the patient’s signs and symptoms rather than relying solely on the COHb level to guide decision-making.

Pulse oximetry (SpO2), a non-invasive bedside test, cannot be used for screening for CO poisoning, as it doesn’t differentiate oxygenated hemoglobin and carboxyhemoglobin and may yield normal values in CO poisoning despite significant tissue hypoxia. Non-invasive CO oximeters measuring COHb and methemoglobin are available and may have a role as a screening test, but their reliability in clinical settings has been questioned [6]. The American College of Emergency Physicians recommends against using pulse CO oximetry for diagnosis of CO toxicity in patients with suspected acute CO poisoning [2].

An electrocardiogram and a measurement of cardiac enzymes should be included due to the possibility of myocardial injury in patients with moderate to severe CO poisoning looking for myocardial ischemia, infarction, or arrhythmias [2,19]. Imaging studies, such as chest radiographs, may be indicated in certain clinical scenarios and can help patients presenting with hypoxia and dyspnea to evaluate for pulmonary edema [20].

Risk Stratification

Significant neurologic manifestations of CO poisoning include findings such as syncope, coma, seizures, altered mental status (GCS <15) or confusion, and abnormal cerebellar function. Metabolic findings such as lactic acidosis may be profound from cellular hypoxia. Cardiovascular findings include acute myocardial ischemia, myocardial injury, ventricular arrhythmia, and pulmonary edema [6].

The clinical policy from the American College of Emergency Physicians concerning the evaluation and management of adult patients with acute carbon monoxide poisoning presents evidence-based recommendations addressing three key clinical questions: the diagnostic accuracy of noninvasive carboxyhemoglobin measurement, the long-term neurocognitive impact of hyperbaric versus normobaric oxygen therapy, and the predictive value of cardiac testing for morbidity and mortality. The policy is based on a systematic literature review, graded using a defined class of evidence system, and offers recommendations for patient management at varying levels of certainty [21].

According to the ACEP’s CO policy, pulse CO oximetry should not be used to diagnose acute carbon monoxide (CO) poisoning due to its low sensitivity. While it offers advantages like being fast, noninvasive, and cost-effective, studies have shown it detects CO toxicity in only about 48% of cases, meaning it misses half of those affected. Similar findings were reported in other studies.

Both hyperbaric oxygen (HBO₂) and high-flow normobaric oxygen therapies are options for treating acute carbon monoxide (CO) poisoning, but it is unclear if HBO₂ is superior in improving long-term neurocognitive outcomes. While HBO₂ reduces carboxyhemoglobin levels and may aid neurologic recovery, its benefits remain debated. Meta-analyses and studies on HBO₂ have shown inconsistent results, with some finding no benefit and others suggesting improved outcomes. Variations in study designs and treatment factors contribute to the uncertainty, highlighting the need for further research.

In moderate to severe carbon monoxide (CO) poisoning, an electrocardiogram (ECG) and cardiac biomarkers should be used to detect acute myocardial injury, a predictor of poor outcomes. Studies have shown that myocardial injury is associated with higher long-term mortality and is an independent predictor of poor prognosis. Further research is needed to explore cardiac testing and interventions in less severe cases and more aggressive cardiac management for high-risk patients.

Management

Initial management starts with assessing and stabilizing the airway, breathing, and circulation. Comatose patients who have severely impaired mental status or who do not have sufficient respiratory effort should be intubated without delay and mechanically ventilated using 100 percent oxygen [6]. Treatment begins with oxygen therapy, and 100% oxygen should be provided as soon as possible with either a non-rebreather mask or endotracheal intubation, which serves two purposes. First, the half-life of COHb is inversely related to PaO2; it can be reduced from approximately 5 hours in room air to 1 hour by providing supplemental 100% oxygen. HBO therapy (at 3 atmospheres) further reduces the half-life to approximately 30 minutes [12]. Oxygen should be continued until the patient is asymptomatic and carboxyhemoglobin levels are ≤ 3%-4% in nonsmokers and ≤ 10% in smokers [2,18,19]. Evidence suggests that hyperbaric oxygen therapy helps prevent delayed neurologic sequelae in acute CO poisoning, but its efficacy decreases with delayed implementation [15]. HBO therapy can be used in patients presenting with a COHb level >25% (>15% if pregnant), unconscious at scene or hospital, reported syncope, persistent altered, mental status, coma, focal neurologic deficit, severe metabolic acidosis (pH <7.25) after empiric cyanide treatment if administered, or evidence of end-organ ischemia (e.g., ECG changes, elevated cardiac biomarkers, respiratory failure, focal neurologic deficit, or altered mental status). A thorough cardiovascular examination should be performed and should focus on signs of contributing cardiogenic shock or hypotension. Establishing IV access and cardiac monitoring are necessary as patients may need IV fluids or inotropes for resuscitation. An ECG and cardiac enzymes should also be included in the evaluation for cardiac ischemia in symptomatic patients at risk. Patients with altered mental status should have a blood glucose check to evaluate for hypoglycemia [6].

Special Patient Groups

Pediatrics

Children may present with subtle and non-specific findings compared to adults, and it is suggested that they can be more sensitive to the effects of CO due to their higher metabolic rates. Fussiness and decreased oral intake may be the only manifestations of CO toxicity. Although children may have higher levels of COHb due to their higher minute ventilation, which should make them more vulnerable to accumulating CO, the long-term outcomes appear favorable as they have lower rates of developing delayed neurological sequelae compared to adults. The diagnosis and management of CO poisoning in young children generally follow the same principles as for other age groups, with no substantial modifications in approach based on age [6].

Pregnant Patients

There is a lower threshold to using HBO therapy in pregnancy due to the greater affinity and the longer half-life of CO that is bound to fetal hemoglobin, the limited capacity to enhance placental perfusion and the direct effects of acidosis and hypoxemia on the fetus. While severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcomes. Because the fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcomes. While these findings provide valuable insights into the effects of CO poisoning and HBO therapy on pregnant patients and their fetuses, the available literature on this subject remains limited [6].

When To Admit This Patient

Hospitalization is warranted in cases where patients exhibit signs of hemodynamic instability, persistent neurologic symptoms, evidence of end-organ damage (including renal injury, rhabdomyolysis, cardiac ischemia, and pulmonary edema), or exposure to methylene chloride. Most patients who do not meet the criteria for HBO therapy and are not clinically ill can typically be managed in the emergency department; generally, patients who become asymptomatic with a carboxyhemoglobin (COHb) level < 5% may be safely discharged home. All patients exposed to CO require close follow-up for delayed neurologic sequelae [18].

Revisiting Your Patient

Our 48-year-old male, who has a history of prior suicidal attempts, was found unconscious in his home garage with his car engine running. The past medical history and his presentation picture put him at risk for carbon monoxide poisoning, and red flags such as his altered mental state and the recognition of a source of carbon monoxide should guide the clinician through the diagnosis and management process. Management started by assessing the airway, breathing, and circulation. The patient was in a state of respiratory arrest and was intubated and ventilated with 100% oxygen. His pupils were dilated and sluggish. The patient was hypotensive, and IV fluids were started while vasopressors were being prepared. A CBC, chemistry, blood glucose, cardiac enzymes, COHb level, and venous blood gas were requested. A Chest XR was also done, which showed no signs of pulmonary edema, and an endotracheal tube was confirmed in place. ECG showed normal sinus rhythm with no ST-T wave changes. COHb level was 38%, blood glucose 139 mg/dl, and cardiac enzymes were within normal range. His blood gas showed a pH of 7.28 and a lactate of 4. A diagnosis of carbon monoxide poisoning was made. The patient was kept on 100% oxygen and was being prepared to be transferred into a hyperbaric oxygen therapy facility.

Authors

Picture of Mohammad Issa Naser

Mohammad Issa Naser

Dr Mohammad Naser is currently a Critical Care Medicine Fellow in Sheikh Shakhbout Medical City - Abu Dhabi. He completed his emergency medicine training at Zayed Military Hospital and has obtained both the Emirati and Arab board certifications in Emergency Medicine. Dr. Naser has a profound interest in critical care medicine, particularly in bridging the gap between emergency and intensive care practices. Beyond critical care, He is deeply passionate about medical education, mentoring future healthcare professionals, and developing innovative teaching tools. Additionally, he is actively involved in clinical research, focusing on advancing knowledge and practices in emergency and critical care medicine.

Picture of Abdulla Alhmoudi

Abdulla Alhmoudi

Dr Abdulla Alhmoudi is a Consultant Emergency Medicine, serving at Zayed Military Hospital and Sheikh Shakhbout Medical City - Abu Dhabi. He pursued his residency training in Emergency Medicine at George Washington University in Washington DC and further enhanced his expertise with a Fellowship in Extreme Environmental Medicine. Dr Alhmoudi's passion for medical education is evident in his professional pursuits. He currently holds the position of Associate Program Director at ZMH EM program and is a lecturer at Khalifa University College of Medicine and Health Sciences. Beyond medical education, he maintains a keen interest in military medicine and wilderness medicine.

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References

  1. Rose JJ, Wang L, Xu Q, et al. Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy [published correction appears in Am J Respir Crit Care Med. 2017 Aug 1;196 (3):398-399]. Am J Respir Crit Care Med. 2017;195(5):596-606. doi:10.1164/rccm.201606-1275CI
  2. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Carbon Monoxide Poisoning:, Wolf SJ, Maloney GE, Shih RD, Shy BD, Brown MD. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Carbon Monoxide Poisoning. Ann Emerg Med. 2017;69(1):98-107.e6. doi:10.1016/j.annemergmed.2016.11.003
  3. Shin M, Bronstein AC, Glidden E, et al. Morbidity and Mortality of Unintentional Carbon Monoxide Poisoning: United States 2005 to 2018. Ann Emerg Med. 2023;81(3):309-317. doi:10.1016/j.annemergmed.2022.10.011
  4. Rose JJ, Wang L, Xu Q, et al. Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy [published correction appears in Am J Respir Crit Care Med. 2017 Aug 1;196 (3):398-399]. Am J Respir Crit Care Med. 2017;195(5):596-606. doi:10.1164/rccm.201606-1275CI
  5. Centers for Disease Control and Prevention (CDC). Unintentional non-fire-related carbon monoxide exposures–United States, 2001-2003. MMWR Morb Mortal Wkly Rep. 2005;54(2):36-39.
  6. Manaker S, Perry H. (2023) Carbon monoxide poisoning, UpToDate. Available at: https://www.uptodate.com/contents/carbon-monoxide-poisoning (Accessed: 15 May 2023).
  7. Norris JC, Moore SJ, Hume AS. Synergistic lethality induced by the combination of carbon monoxide and cyanide. Toxicology. 1986;40(2):121-129. doi:10.1016/0300-483x(86)90073-9
  8. Dubrey SW, Chehab O, Ghonim S. Carbon monoxide poisoning: an ancient and frequent cause of accidental death. Br J Hosp Med (Lond). 2015;76(3):159-162. doi:10.12968/hmed.2015.76.3.159
  9. Weaver LK, Howe S, Hopkins R, Chan KJ. Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure. Chest. 2000;117(3):801-808. doi:10.1378/chest.117.3.801
  10. Walker AR. Emergency department management of house fire burns and carbon monoxide poisoning in children. Curr Opin Pediatr. 1996;8(3):239-242. doi:10.1097/00008480-199606000-00009
  11. Rose JJ, Wang L, Xu Q, et al. Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy [published correction appears in Am J Respir Crit Care Med. 2017 Aug 1;196 (3):398-399].Am J Respir Crit Care Med. 2017;195(5):596-606. doi:10.1164/rccm.201606-1275CI
  12. Meaden CW, Nelson LS. Inhaled Toxins. In: Rosen’s Emergency Medicine Concepts and Clinical Practice. 10th ed. Elsevier; 2023:666-681.
  13. Harper A, Croft-Baker J. Carbon monoxide poisoning: undetected by both patients and their doctors.Age Ageing. 2004;33(2):105-109. doi:10.1093/ageing/afh038
  14. Dolan MC, Haltom TL, Barrows GH, Short CS, Ferriell KM. Carboxyhemoglobin levels in patients with flu-like symptoms. Ann Emerg Med. 1987;16(7):782-786. doi:10.1016/s0196-0644(87)80575-9
  15. Tomaszewski, C. Carbon Monoxide. IN: Goldfrank’s toxicological emergencies. 9th ed. New York: McGraw-Hill Medical Pub. Division; c2011
  16. Cho CH, Chiu NC, Ho CS, Peng CC. Carbon monoxide poisoning in children. Pediatr Neonatol. 2008;49(4):121-125. doi:10.1016/S1875-9572(08)60026-1
  17. Eichhorn L, Thudium M, Jüttner B. The Diagnosis and Treatment of Carbon Monoxide Poisoning.Dtsch Arztebl Int. 2018;115(51-52):863-870. doi:10.3238/arztebl.2018.0863
  18. Hampson NB, Piantadosi CA, Thom SR, Weaver LK. Practice recommendations in the diagnosis, management, and prevention of carbon monoxide poisoning.Am J Respir Crit Care Med. 2012;186(11):1095-1101. doi:10.1164/rccm.201207-1284CI
  19. Weaver LK. Clinical practice. Carbon monoxide poisoning.N Engl J Med. 2009;360(12):1217-1225. doi:10.1056/NEJMcp0808891
  20. Prockop LD, Chichkova RI. Carbon monoxide intoxication: an updated review.J Neurol Sci. 2007;262(1-2):122-130. doi:10.1016/j.jns.2007.06.037
  21. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Carbon Monoxide Poisoning:, Wolf SJ, Maloney GE, Shih RD, Shy BD, Brown MD. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Carbon Monoxide Poisoning. Ann Emerg Med. 2017;69(1):98-107.e6. doi:10.1016/j.annemergmed.2016.11.003

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.

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Question Of The Day #80

question of the day
~ Joseph Ciano, USA ~ Leave a comment
753 - bradycardia
Which of the following is the most appropriate next step in management for this patient’s condition?  
  • A) IV Glucagon
  • B) IV Fluids
  • C) Immediate transvenous pacing
  • D) IV Calcium gluconate

This patient presents to the Emergency department with generalized weakness and dizziness after accidently ingesting extra diltiazem tablets 1.5 hours prior to arrival.  The exam shows bradycardia, hypotension, an elevated glucose level, and a patient without altered mental status.  The EKG shows sinus bradycardia without any conduction blocks.

This patient’s clinical presentation is likely due to diltiazem overdose.  Diltiazem is a calcium channel blocker. Calcium channel blocker medications are categorized as the dihydropyridines (nifedipine, amlodipine, nicardipine) and the non-dihydropyridines (verapamil, diltiazem).  The dihydropyridines (DHPs) cause systemic vasodilation, hypotension, and often a reflex tachycardia in overdose.  The non-DHPs act more directly on the heart with less peripheral effects and cause hypotension and bradycardia.  Calcium channel blocker overdose can mimic beta blocker overdose as both medication classes have similar effects on the body. 

The initial management of any patient who has ingested a potentially dangerous medication is the “ABCs”, also known as the primary survey.  This includes assessment and management of the airway (i.e., intubation for somnolence and aspiration risk), breathing (i.e., supplemental oxygen for hypoxia), and circulation (i.e., IV fluids, vasopressors for hypotension).  Decontamination is another consideration depending on the agent the patient has been exposed to.  An EKG should be ordered early in all toxic ingestions to evaluate for signs of cardiac toxicity, such as a prolonged QT interval or prolonged QRS interval.  Checking for other dangerous coingestants, like serum levels of salicylates and paracetamol (APAP) should be routinely done.  Specific toxic effects seen in calcium channel blocker and beta blocker overdose are outlined in the chart below.

IV Glucagon (Choice A) is useful as an adjunctive treatment in both calcium channel blocker and beta blocker overdose.  However, glucagon often causes vomiting and is not a first-line agent.  IV fluids, atropine, vasopressors, and activated charcoal should be attempted before glucagon.  Antiemetics should be considered prior to IV Glucagon administration given its side effect of nausea and vomiting.  Transvenous pacing (Choice C) and IV Calcium gluconate (Choice D) are also considered second-line treatments to try when the patient is not responding to IV fluids, atropine, or vasopressors.  The best next step in this case is to administer IV Fluids (Choice B). 

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Question Of The Day #79

question of the day
~ Joseph Ciano, USA ~ Leave a comment
Which of the following is the most appropriate next step in management?
  • A) IV physostigmine
  • B) IV norepinephrine
  • C) IV sodium bicarbonate
  • D) IV metoprolol

This patient arrives to the Emergency department with altered mental status and hypotension after ingestion of multiple pills at home.  On exam, she is hypotensive, tachycardic, confused, and has dilated pupils with dry skin.  The patient has most likely ingested amitriptyline tablets given the history provided in the question.  Amitriptyline is a tricyclic antidepressant medication.  Despite the clear history, it is very important to check levels for possible other coingestants, like paracetamol (APAP) and salicylates.

Tricyclic antidepressants (TCAs) impact many different receptors in the body, so the clinical presentation of a patient with TCA overdose can vary considerably.  Important features to remember are cardiovascular toxicity with a widened QRS and hypotension, as well as an anticholinergic toxidrome.  A 12-lead EKG should be ordered early in any case of possible overdose, and an EKG in TCA overdose is a crucial step in evaluation.  Supportive care and IV sodium bicarbonate are the mainstays of treatment for TCA overdose.  See the table below for details regarding the clinical features and treatment of these patients. 

Toxic effects of Tricyclic Antidepressant (TCA) overdose

Clinical Features

Treatment

Na-channel blockade

Cardiac arrythmias,

Wide QRS (>100msec), Prominent R wave in AvR (>3mm)

IV Sodium Bicarbonate100mEq (1-2mEq/kg),

 

Titrate to QRS <100 and/or improved hypotension

Alpha-1 adrenergic receptor blockade

Hypotension

IVF, vasopressors

Serotonin reuptake blockade

Seizures

Benzodiazepines

Muscarinic- Ach receptor blockade (Anticholinergic)

Anticholinergic toxidrome– altered mental status, delirium, hyperthermia, tachycardia, hypertension, dilated pupils, dry skin

Benzodiazepines, supportive care.

 

Avoid Physostigmine.

Histamine receptor (H1) blockade

Drowsiness, coma

Supportive care

IV Physostigmine (Choice A) can be used to treat an anticholinergic toxidrome along with supportive care and benzodiazepines.  This patient does appear to have an anticholinergic toxidrome, but there is a high suspicion for TCA overdose.  Physostigmine should be avoided in TCA overdose due to data indicating worse outcomes in TCA overdose patients who receive physostigmine.  IV Norepinephrine (Choice B) may eventually be required to manage this patient’s hypotension.  However, IV fluids and sodium bicarbonate to reverse the cardiac toxicity should be used first.  IV Metoprolol (Choice D) may help relieve the tachycardia, but it would worsen the patient’s hypotension and shock state.   The best next step is IV Sodium bicarbonate (Choice C), which is the treatment for TCA overdose.  Sodium bicarbonate prevents TCA binding to cardiac sodium channels, thereby stabilizing the heart and preventing cardiac dysrhythmias and death. Sodium bicarbonate is given as an infusion until the QRS interval shortens <100msec and the hypotension improves. 

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Question Of The Day #78

question of the day
~ Joseph Ciano, USA ~ Leave a comment
Which of the following is the most likely cause for this patient’s condition?
  • A) Paracetamol (APAP) overdose
  • B) Methanol ingestion
  • C) Fomepizole overdose
  • D) Opioid overdose

This patient presents to the Emergency department from a party with slurred speech and somnolence after drinking homemade alcohol.  On exam, his vital signs and glucose are normal, he is nonresponsive to pain, and he has a GCS of 3 (normal GCS is 15).  He is intubated due to his inability to protect his airway and risk for aspiration.  Intubation is an important first step in managing this patient.

Altered mental status has a broad differential diagnosis, including intracranial bleeding, stroke, post-ictal state, hypoglycemia, electrolyte abnormalities, other metabolic causes, infectious etiologies, toxicological causes, and many other conditions.  The immediate evaluation and treatment of this patient should focus on the ‘ABCs’, or any abnormality in the airway, breathing, and circulation.  Any rapidly correctable causes of altered mental status, like hypoxia, hypoglycemia, or hyperthermia, should be addressed appropriately at this stage (i.e., supplemental oxygen, intubation, IV dextrose, body cooling). 

Paracetamol (APAP) overdose (Choice A) is often accompanied with little to no symptoms in the first 24hours.  Later in the ingestion timeline, liver failure and its associated sequalae can occur if no antidote is given.  The symptoms exhibited by the patient do not correlate with APAP overdose.  Opioid overdose (Choice D) can cause severely depressed mental status as seen in this patient.  However, opioid overdose also has decreased respiratory rate, pinpoint pupils, and sometimes associated bradycardia or hypotension.  This patient has normal vital signs and normal pupil size.  This patient ingested some type of alcohol at the party, but it is unclear if it is ethanol or a toxic alcohol (i.e., methanol, ethylene glycol).  Both ethanol and methanol ingestion (Choice B) can cause similar exam findings of depressed mental status as in this patient.  Other features of toxic alcohol ingestion include vision changes (methanol), hemorrhagic gastritis (isopropyl alcohol), coma, seizures, and hyperventilation (respiratory compensation for severe acidosis).  Ethanol and many of the toxic alcohols will cause an increased anion gap metabolic acidosis with an increased osmolar gap.  Helpful tests to differentiate ethanol from a toxic alcohol are serum levels of ethanol and serum toxic alcohol levels (if available).  A somnolent, intoxicated-appearing patient with a negative ethanol level should raise suspicion for toxic alcohol poisoning.  Urine studies may also show oxalate crystals in ethylene glycol ingestion. 

Since ethanol is not a listed choice and laboratory studies are not provided, methanol ingestion (Choice B) is the most likely cause of this patient’s symptoms.  Fomepizole (Choice C) is an intravenous medication that inhibits the alcohol dehydrogenase enzyme.  Fomepizole is the antidote to toxic alcohols by slowing the production of dangerous toxic alcohol metabolites.  The correct answer is Choice B.

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Question Of The Day #77

question of the day
~ Joseph Ciano, USA ~ Leave a comment

 

Test Value

Reference Range

pH

7.55

(7.35-7.45)

pCO2

20

(35-45)

pO2

84

(80-100)

HCO3

18

(22-26)

Which of the following is the most appropriate next step in management?

  • A) PO Activated Charcoal
  • B) IM Glucagon 1mg
  • C) IV Atropine 2mg
  • D) IV NaHCO3 infusion

This patient presents to the Emergency department for altered mental status, nausea, and tinnitus (ear ringing).  Her exam shows a confused female with tachypnea, tachycardia, borderline fever, wet skin, and normal pupil size.  Altered mental status has a broad differential diagnosis, including intracranial bleeding, stroke, post-ictal state, hypoglycemia, electrolyte abnormalities, other metabolic causes, infectious etiologies, toxicological causes, and many other conditions.  The immediate evaluation and treatment of this patient should focus on the ‘ABCs’, or an abnormality in the airway, breathing, and circulation.  Any rapidly correctable causes of altered mental status, like hypoxia, hypoglycemia, hyperthermia, should be addressed appropriately at this stage (i.e., supplemental oxygen, IV dextrose, body cooling).

This patient’s exam mimics many aspects of a sympathomimetic toxidrome, however, having the awareness that oil of wintergreen is a potent salicylate will lead to the diagnosis.  This patient has salicylate poisoning.  Salicylates are present in many over the counter pain medications, including aspirin, oil of wintergreen (methyl salicylate), and Pepto-Bismol (bismuth subsalicylate).   An acute overdose of salicylates may present as tachycardia, hypertension, and hyperthermia, similar to a sympathomimetic toxidrome.  Other features include tinnitus, altered mental status, seizures, and coma. 

The patient’s ABG shows a respiratory alkalosis (elevated pH, low pCO2) mixed with a metabolic acidosis (low HCO3).  Salicylic acid disrupts the body’s ability to process energy at the cellular level by acting as an ‘uncoupler’ of the oxidative phosphorylation process.  Salicylates directly stimulate the respiratory centers in the brainstem, triggering hyperventilation and increased lactic and pyruvic acid.  Hyperventilation causes the initial respiratory alkalosis, and the elevated lactic and pyruvic acid later causes an increased anion gap metabolic acidosis or a mixed metabolic acidosis and respiratory alkalosis.   

The treatment of salicylate overdose is prompt IV NaHCO3 infusion (Choice D) to alkalinize the urine and blood.  This assists in the more rapid clearance of salicylates.  Hemodialysis can be considered if salicylate levels are over 80-100mg/dL, or if there is persistent altered mental status, acidosis, or organ failure despite starting the NaHCO3 infusion.  PO Activated charcoal (Choice A) is helpful in binding certain toxins and preventing their absorption through the GI tract.  Charcoal is most beneficial when it is used early after drug ingestion.  This patient was exposed to salicylates by a topical route, so PO charcoal would not be helpful.  IM Glucagon (Choice B) is helpful in hypoglycemia and betablocker overdose.  This patient is not hypoglycemic and was not exposed to betablockers.  IV Atropine (Choice C) is helpful in patients with a cholinergic toxidrome (i.e., organophosphates, nerve gases), but would not be helpful in this patient.  Atropine would likely worsen the patient’s tachycardia.  The best next step would be IV NaHCO3 infusion (Choice D).

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Question Of The Day #76

question of the day
~ Joseph Ciano, USA ~ Leave a comment

Which of the following is the most appropriate next step in management?

  • A) PO Activated Charcoal
  • B) IV N-Acetylcysteine (NAC)
  • C) Prepare for liver transplantation
  • D) IV Sodium bicarbonate

This patient arrives to the Emergency department 10 hours after ingesting 11grams of paracetamol (APAP).  She has mild symptoms of nausea and upper abdominal discomfort and has normal vital signs. 

Paracetamol, also known as acetaminophen or APAP, is a commonly used pain medication safe for use in childhood, pregnancy, and breastfeeding.  Paracetamol is an ingredient present in many over the counter pain, headache, and cold medications.   Toxic paracetamol doses are acute ingestions over 150mg/kg, or about 10grams in adults.  Toxic paracetamol doses for children are 150mg/kg.  Multiple ingestions of paracetamol over 24 or 48 hours can also cause toxicity.  Ingestions of 10grams over 24hours or 6 grams/day over 48hours can also cause toxicity in adults.  Symptoms of acute poisoning can be absent or mild in the first 24 hours as seen in this patient.  After 24 hours, AST, ALT, bilirubin, and INR levels begin to increase, and over 72 hours post-ingestion, hepatic failure ensues.  5 days after an acute ingestion is when multi-organ failure occurs or hepatotoxicity resolves (less common).  Toxicity of APAP is thought to be caused by a toxic metabolite produced during APAP breakdown in the liver known.  This toxin is known as NAPQI.

APAP overdose can be fatal without treatment with the antidote commonly known as NAC, or N-acetylcysteine.  NAC is a free radical scavenger and prevents the damage caused by NAPQI.  If serum APAP testing is available, APAP levels drawn 4 hours after the time of an acute ingestion are used to determine if NAC is warranted.  APAP levels over 150mcg/mL at 4hours are the threshold for starting NAC.  This is based on use of the Rumack-Mathew Nomogram for APAP (see below).

Hendrickson RG, McKeown NJ. Acetaminophen. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw Hill; 2019.

Since this patient’s acute ingestion is above the known 10gram toxic dose, it is reasonable to start N-acetylcysteine therapy (Choice B) without first knowing the exact serum APAP level.  PO Activated charcoal (Choice A) can be used after oral ingestions to help bind some toxic substances and prevent their absorption through the GI system.  The majority of APAP is absorbed 2-4 hours after ingestion, so charcoal would not be helpful in this case where the ingestion was 10 hours ago.  Liver transplantation (Choice C) may ultimately be required for this patient depending on the liver function tests and how the patient responds over the coming days.  However, the best next step is NAC treatment to prevent liver failure and death.  IV Sodium bicarbonate (Choice D) is used in salicylate and tricyclic antidepressant overdose, but it has no role in APAP overdose.  The best next step is IV N-Acetylcysteine (Choice B).   

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Question Of The Day #75

question of the day
~ Joseph Ciano, USA ~ Leave a comment
Which of the following is the most likely cause of this patient’s condition?   
  • A) Paracetamol (APAP)
  • B) Dextroamphetamine
  • C) Ethanol
  • D) Diphenhydramine

This patient presents to the Emergency Department with altered mental status after ingestion of an unknown agent as part of a suicide attempt.  Her exam demonstrates hypertension, tachycardia, elevated temperature, disorientation, dilated pupils, and dry and hot skin.  Altered mental status has a broad differential diagnosis, including intracranial bleeding, stroke, post-ictal state, hypoglycemia, electrolyte abnormalities, other metabolic causes, infectious etiologies, toxicological causes, and many other conditions.  This patient’s history and exam support the presence of a toxidrome.  See the chart below for a review of the most common toxidromes (toxic syndromes). 

*Treatment of all toxic ingestions should include general supportive care and management of the airway, breathing, and circulation of the patient. Examples include administration of supplemental oxygen in hypoxia, IV fluids in hypotension, cooling measures in hyperthermia, etc.
**Flumazenil is the antidote for benzodiazepine overdose, but it is rarely used clinically as it can trigger benzodiazepine-refractory seizures.

 

Paracetamol (Choice A) is often accompanied with little to no symptoms in the first 24hours.  Later in the ingestion timeline, liver failure and its associated sequalae can occur if no antidote is given.  The symptoms exhibited by the patient do not correlate with APAP overdose.  Dextroamphetamine (Choice B) is a sympathomimetic agent that could be responsible for many of the patient’s symptoms, like elevated heart rate, hypertension, agitation, and dilated pupils.  However, dextroamphetamine should cause diaphoretic skin, not the dry skin that the patient has.  Ethanol (Choice C) may be a co-ingested agent in this scenario that could lead to agitation and confusion, but ethanol alone should not cause fever.  Diphenhydramine (Choice D) is an antihistamine agent, but it also has anticholinergic properties, especially when taken in excess.  This patient has all the signs of an anticholinergic toxidrome.  The presence or absence of dry skin can help differentiate a sympathomimetic toxidrome from an anticholinergic toxidrome.  Diphenhydramine (Choice D) is the most likely agent responsible for this patient’s symptoms.  Correct Answer: D

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