Study guide
9.1 Toxicology and Antidote Therapy in the ICU
Board Certified Critical Care Pharmacist Study Guide Exam
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1 Chapter 1: Pathophysiology and Recognition of Critical Illness
1.1 Pathophysiology of Shock and Sepsis 1.2 Respiratory Failure and ARDS Pathophysiology 1.3 ICU-Acquired Weakness and Post-Intensive Care Syndrome 1.4 Chronic Disease States and Risk Factors for Critical Illness
2 Chapter 2: Medical Devices and Circulatory Support
2.1 Hemodynamic Monitoring and Interpretation 2.2 Mechanical Circulatory Support 2.3 Mechanical Ventilation Modes and Settings 2.4 Continuous Renal Replacement Therapy 2.5 Lines, Tubes, and Drains in Critical Care
3 Chapter 3: Fluid, Electrolyte, and Acid-Base Management
3.1 Resuscitation Fluids: Crystalloids vs. Colloids 3.2 Electrolyte Disorders in the ICU 3.3 Acid-Base Disorders and Interpretation
4 Chapter 4: Vasoactive and Inotropic Therapy in Shock
4.1 Vasopressors in Distributive Shock 4.2 Inotropes and Vasopressors in Cardiogenic and Obstructive Shock
5 Chapter 5: Sedation, Analgesia, and Delirium (PADIS)
5.1 Pain and Analgesia in the ICU 5.2 Sedation Strategies and Medication Selection 5.3 Delirium Assessment, Prevention, and Treatment 5.4 Neuromuscular Blockade in Critical Illness
6 Chapter 6: Cardiovascular Emergencies
6.1 Acute Coronary Syndromes in ICU Patients 6.2 Acute Decompensated Heart Failure 6.3 Hypertensive Emergencies and Arrhythmias
7 Chapter 7: Pulmonary and Infectious Diseases in the ICU
7.1 Severe Sepsis and Septic Shock Antimicrobial Selection 7.2 Pharmacotherapy for Mechanical Ventilation and ARDS 7.3 Severe Infections in the ICU
8 Chapter 8: Neurocritical Care
8.1 Ischemic and Hemorrhagic Stroke Management 8.2 Intracranial Hypertension and Brain Edema 8.3 Status Epilepticus and Sedation in Brain Injury
9 Chapter 9: Toxicology, Endocrine, and Hematologic Emergencies
9.1 Toxicology and Antidote Therapy in the ICU 9.2 Endocrine Emergencies 9.3 Hematologic Emergencies, Anticoagulant Reversal, and Transfusions 9.4 Gastrointestinal and Hepatic Emergencies in the ICU 9.5 Dermatologic and Immunologic Conditions in the ICU 9.6 Trauma, Burns, Supportive Care, and End-of-Life Pharmacotherapy
10 Chapter 10: Special Populations, Pharmacokinetics, and Nutrition
10.1 Altered Pharmacokinetics in Critically Ill Patients 10.2 Therapeutic Drug Monitoring in the ICU 10.3 Nutrition Support: Enteral vs. Parenteral
11 Chapter 11: Quality, Safety, and Clinical Guidelines
11.1 Medication Safety and Error Prevention in the ICU 11.2 Antimicrobial Stewardship and Infection Prevention 11.3 Implementation of Clinical Practice Guidelines 11.4 Healthcare Regulations, Standards, and Drug Interactions
12 Chapter 12: Practice Management, Biostatistics, and Evidence-Based Medicine
12.1 ICU Formulary Management and Cost-Effectiveness 12.2 Biostatistics and Literature Evaluation 12.3 Clinical Trial Interpretation in Critical Care 12.4 Professional Development, Precepting, and ICU Pharmacy Services 12.5 Alternative ICU Delivery Models and Disaster Healthcare Management
13 Chapter 13: Treatment Planning and Care Coordination
13.1 Goals of Care, Perioperative Care, and Transitions of Care 13.2 Medication Delivery Routes and Devices in Critical Illness 13.3 Social Determinants of Health and Patient/Caregiver Education
9.1 Toxicology and Antidote Therapy in the ICU
Key Takeaways Explain This Topic AI
High-dose insulin euglycemia therapy (HIET) is a first-line treatment for severe calcium channel blocker and beta-blocker toxicity, improving inotropy by facilitating myocardial carbohydrate utilization.
The Rumack-Matthew nomogram is used to determine the need for N-acetylcysteine (NAC) in acute acetaminophen ingestions, provided the time of ingestion is known and between 4 and 24 hours.
Fomepizole is a competitive inhibitor of alcohol dehydrogenase used for methanol and ethylene glycol poisoning, preventing the formation of toxic metabolites.
Sodium bicarbonate is indicated for tricyclic antidepressant (TCA) toxicity when the QRS complex is widened (> 100 msec), acting to overcome sodium channel blockade.
Intravenous lipid emulsion (ILE) therapy can act as a "lipid sink" for highly lipophilic drugs, most notably in local anesthetic systemic toxicity (LAST) and severe refractory cases of other lipophilic drug overdoses.
Last updated: July 2026
Toxicology and Antidote Therapy in the ICU
The management of the poisoned patient in the intensive care unit requires a systematic approach. While specific antidotes exist for a minority of toxins, excellent supportive care—managing the airway, breathing, and circulation (the ABCs)—remains the cornerstone of toxicologic resuscitation.
General Approach to the Poisoned Patient
Initial evaluation focuses on resuscitation and stabilization. Following stabilization, the clinician must focus on risk assessment, decontamination, enhanced elimination, and targeted antidote therapy.
Toxidromes
Recognizing a "toxidrome" (toxic syndrome) can help identify the offending agent when the history is unknown.
Toxidrome Clinical Features Common Causes Targeted Therapy
Anticholinergic Tachycardia, hyperthermia, mydriasis, dry/flushed skin, delirium, urinary retention. ("Mad as a hatter, hot as a hare, blind as a bat, dry as a bone, red as a beet") Antihistamines, TCAs, atropine, scopolamine Physostigmine (for severe delirium, though contraindicated if TCA suspected)
Cholinergic DUMBBELS: Diarrhea, Urination, Miosis, Bradycardia, Bronchorrhea, Emesis, Lacrimation, Salivation Organophosphates, carbamates, nerve agents Atropine (for muscarinic symptoms), Pralidoxime (for nicotinic/muscarinic in OP poisoning)
Sympathomimetic Tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis (distinguishes from anticholinergic), agitation Cocaine, amphetamines, synthetic cathinones Benzodiazepines, cooling, avoid pure beta-blockers
Opioid CNS depression, respiratory depression, miosis (pinpoint pupils), bradycardia Heroin, fentanyl, oxycodone, methadone Naloxone
Sedative-Hypnotic CNS depression, normal or slightly decreased vital signs, ataxia Benzodiazepines, barbiturates, alcohol Flumazenil (rarely used due to seizure risk in chronic users)
- Specific Poisonings and Antidotes
- Acetaminophen (APAP)
Acetaminophen toxicity is a leading cause of acute liver failure. In overdose, the sulfation and glucuronidation pathways are saturated, leading to increased metabolism via CYP2E1 to NAPQI, a toxic free radical. Depletion of glutathione prevents the neutralization of NAPQI, resulting in centrilobular hepatic necrosis.
Management:
N-acetylcysteine (NAC): Restores hepatic glutathione stores and serves as a glutathione substitute. It is nearly 100% effective in preventing hepatotoxicity if started within 8 hours of ingestion.
Rumack-Matthew Nomogram: Used for acute , single ingestions. A serum APAP level drawn between 4 and 24 hours post-ingestion is plotted on the nomogram. Levels above the treatment line warrant NAC therapy. It is not used for chronic ingestions or staggered overdoses.
Toxic Alcohols: Methanol and Ethylene Glycol
Both methanol and ethylene glycol cause an elevated anion gap metabolic acidosis and an elevated osmolar gap (though the osmolar gap closes as the parent alcohol is metabolized to toxic acids).
Methanol: Metabolized to formic acid. Causes retinal toxicity ("snowstorm" vision) and basal ganglia putaminal necrosis.
Ethylene Glycol: Metabolized to glycolic and oxalic acid. Causes acute kidney injury (calcium oxalate crystals in urine).
Management:
Fomepizole (4-MP): A competitive inhibitor of alcohol dehydrogenase (ADH). By blocking ADH, it prevents the parent alcohol from being converted into its toxic metabolites.
Hemodialysis: Indicated for severe metabolic acidosis, renal failure, visual disturbances (methanol), or very high serum levels. Fomepizole is dialyzable, so the dosing frequency must be increased during hemodialysis.
Cofactors: Folic acid (for methanol) and thiamine/pyridoxine (for ethylene glycol) to drive metabolism toward non-toxic pathways.
Cardiovascular Toxins: Beta-Blockers and Calcium Channel Blockers
Overdoses of beta-blockers (BBs) and calcium channel blockers (CCBs) frequently present with severe bradycardia, hypotension, and cardiogenic shock.
Management Strategies:
Atropine & Fluids: Often ineffective but used initially.
Calcium: (Gluconate or Chloride) Used particularly for CCB overdose to overcome competitive blockade, though it rarely corrects hypotension fully.
Glucagon: Historically a first-line agent, especially for BB toxicity. It stimulates adenylate cyclase independently of the beta-receptor, increasing intracellular cAMP. Efficacy is variable and it causes significant vomiting.
High-Dose Insulin Euglycemia Therapy (HIET): A cornerstone of severe CCB/BB toxicity. The ischemic/stressed myocardium shifts from using free fatty acids to carbohydrates. HIET facilitates myocardial carbohydrate uptake, acting as a potent inotrope. Dosing typically starts at 1 Unit/kg bolus followed by 1-10 Units/kg/hr infusion, requiring aggressive dextrose (to prevent hypoglycemia) and potassium (to prevent hypokalemia) supplementation.
Intravenous Lipid Emulsion (ILE): Acts as a "lipid sink" for highly lipophilic drugs (e.g., verapamil, propranolol, local anesthetics) and may also provide a direct myocardial energy source.
Tricyclic Antidepressants (TCAs)
TCA overdose can be fatal due to sodium channel blockade, leading to QRS widening and fatal ventricular dysrhythmias, as well as anticholinergic toxicity and alpha-1 blockade (hypotension).
Management:
Sodium Bicarbonate: The primary treatment for TCA-induced cardiotoxicity. It works by increasing the serum pH (which increases the non-ionized fraction of the drug, decreasing sodium channel binding) and providing a large sodium load to overcome the competitive sodium channel blockade. It is indicated when the QRS complex is > 100 msec or for ventricular dysrhythmias.
Avoid Physostigmine: Although TCAs cause anticholinergic toxicity, physostigmine can precipitate asystole in the setting of TCA overdose.
Salicylates (Aspirin)
Salicylates cause a mixed primary respiratory alkalosis (direct stimulation of the medullary respiratory center) and a primary elevated anion gap metabolic acidosis (uncoupling of oxidative phosphorylation).
Management:
Urinary Alkalinization: Sodium bicarbonate infusion targets a urine pH of 7.5 to 8.0. Salicylic acid is a weak acid; alkalinizing the urine traps it in its ionized form within the renal tubules, preventing reabsorption and enhancing excretion (ion trapping). Hypokalemia must be corrected, as the kidneys will excrete H+ instead of K+ in the presence of hypokalemia, preventing urine alkalinization.
Hemodialysis: The definitive treatment for severe toxicity (e.g., altered mental status, pulmonary edema, renal failure, or very high levels, typically > 100 mg/dL).