Study guide
26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes
ABIM Critical Care Medicine Study Guide Exam
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1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy
1.1 ABIM Critical Care Medicine Exam: Format, Blueprint & Study Strategy
2 Chapter 2: Acute Respiratory Failure & ARDS
2.1 ARDS Definition, Pathophysiology & Phenotypes 2.2 Lung-Protective Mechanical Ventilation 2.3 Refractory ARDS: Prone Positioning, Neuromuscular Blockade & VV-ECMO
3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies
3.1 Severe Asthma & COPD Exacerbations in the ICU 3.2 Massive & Submassive Pulmonary Embolism 3.3 Pulmonary Hypertension & Right Ventricular Failure in the ICU 3.4 Massive Hemoptysis, Complex Pleural Effusions & Thoracic Drainage
4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies
4.1 Airway Management, Upper-Airway Obstruction & Artificial-Airway Complications 4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema 4.3 Severe Community-Acquired & Viral Pneumonia 4.4 Nonthrombotic Embolism (Air, Fat, Amniotic Fluid, Tumor, Septic) & Acute Chest Syndrome
5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation
5.1 Mechanical Ventilator Modes & Advanced Breath Delivery 5.2 Patient-Ventilator Dyssynchrony & Waveform Analysis 5.3 Ventilator Liberation, Spontaneous Breathing Trials & Post-Extubation Support
6 Chapter 6: Shock Syndromes & Hemodynamic Principles
6.1 Shock Classification, Cellular Pathophysiology & Biomarkers 6.2 Hemodynamic Monitoring: Arterial Lines, CVP & Pulmonary Artery Catheter 6.3 Dynamic Assessment of Fluid Responsiveness & Resuscitation Targets
7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support
7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication
8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy
8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI
9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies
9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis
10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders
10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency
11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias
11.1 Acute Coronary Syndromes & Mechanical Complications of Myocardial Infarction 11.2 Critical Tachyarrhythmias: Atrial Fibrillation with RVR, VT & VF 11.3 Critical Bradyarrhythmias, Conduction Blocks & Temporary Cardiac Pacing
12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies
12.1 Acute Decompensated Heart Failure & Cardiogenic Pulmonary Edema 12.2 Acute Valvular Regurgitation & Prosthetic Valve Emergencies 12.3 Pericardial Tamponade & Acute Aortic Syndromes
13 Chapter 13: Myocardial Disease, Hypertensive & Cardiac Device Emergencies
13.1 Fulminant Myocarditis, Stress & Peripartum Cardiomyopathy, and Hypertrophic Cardiomyopathy 13.2 Hypertensive Emergencies & Ruptured Abdominal Aortic Aneurysm 13.3 Implanted Cardiac Devices, LVAD Emergencies & Electrical Storm
14 Chapter 14: Sepsis & Systemic Infectious Diseases
14.1 Sepsis-3 Definitions & Surviving Sepsis Campaign 2026 Guidelines 14.2 Refractory Septic Shock & Adjunctive Therapies 14.3 Multidrug-Resistant Pathogens & Antimicrobial Stewardship in the ICU
15 Chapter 15: ICU-Acquired & Severe Focal Infections
15.1 Hospital-Acquired & Ventilator-Associated Pneumonia 15.2 Central Line-Associated Bloodstream Infections & Catheter-Associated UTIs 15.3 Intra-Abdominal Sepsis, Necrotizing Soft Tissue Infections & CNS Infections
16 Chapter 16: Focal, Special-Host & Systemic Infections
16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses
17 Chapter 17: Neurocritical Care & Coma
17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage
18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States
18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome 18.2 Alcohol & Sedative Withdrawal, Wernicke Encephalopathy & Drug-Induced Encephalopathy
19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness
19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination
20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis
20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis
21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies
21.1 Acute Upper & Lower Gastrointestinal Bleeding in the ICU 21.2 Acute Liver Failure & Severe Acute Pancreatitis 21.3 Abdominal Compartment Syndrome & Acute Mesenteric Ischemia
22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis
22.1 Esophageal, Gastric & Bowel Emergencies: Perforation, Obstruction, Ogilvie Syndrome & Colonic Ischemia 22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes
23 Chapter 23: Trauma, Burns & Perioperative Critical Care
23.1 Polytrauma Resuscitation, Damage Control & Massive Transfusion 23.2 Severe Burn Injury, Inhalation Injury & Environmental Emergencies 23.3 Perioperative Critical Care for High-Risk Surgical Patients
24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care
24.1 Thoracic Trauma: Flail Chest, Pulmonary Contusion, Great Vessel & Tracheobronchial Injury 24.2 Environmental Injury: Drowning, Diving, Altitude, Heat, Cold, Electrical & Radiation 24.3 Obstetric & Genitourinary Emergencies and the Physiology of Pregnancy
25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care
25.1 Solid Organ Transplant Recipients & Deceased Donor Management 25.2 Post-Cardiac Surgery Critical Care: Bleeding, Tamponade, Low Output & Vasoplegia
26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation
26.1 Hematologic Emergencies in the ICU: HIT, DIC, TMA & Anticoagulant Reversal 26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes 26.3 Critical Care Point-of-Care Ultrasound (POCUS) 26.4 ICU Liberation, Analgosedation, Goals of Care & Critical Care Ethics
27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders
27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity
28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings
28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia
29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound
29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound
26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes
Key Takeaways Explain This Topic AI
Clinical toxidromes allow rapid empiric classification: Sympathomimetic toxicity presents with hyperthermia, mydriasis, hypertension, and prominent diaphoresis, whereas anticholinergic toxicity is distinguished by anhidrosis ('dry as a bone') and urinary retention.
Pure beta-blockers must be strictly avoided in severe sympathomimetic (cocaine/amphetamine) toxicity due to the risk of unopposed alpha-adrenergic vasoconstriction precipitating coronary vasospasm and hypertensive crisis.
Acetaminophen toxicity requires prompt treatment with N-acetylcysteine (NAC) guided by the Rumack-Matthew nomogram; NAC therapy should continue beyond 21 hours if transaminases remain elevated, coagulopathy persists, or acetaminophen remains detectable.
Salicylate toxicity causes mixed primary respiratory alkalosis and high anion gap metabolic acidosis; management relies on aggressive potassium repletion and intravenous sodium bicarbonate for urinary and systemic alkalinization, with emergent hemodialysis indicated for levels > 100 mg/dL, altered mental status, or pulmonary edema.
High-Dose Insulin-Euglycemia Therapy (HIET) is the premier metabolic inotropic rescue for severe beta-blocker and calcium channel blocker overdoses, providing direct carbohydrate substrate to failing myocytes while reversing shock.
Last updated: October 2026
Clinical Toxidrome Recognition in the ICU
When evaluating a patient with suspected acute poisoning or an undifferentiated altered mental status, identifying a characteristic toxidrome —a constellation of physical signs and symptoms associated with specific pharmacological classes—allows immediate, targeted resuscitation before definitive laboratory confirmation is available.
1. Sympathomimetic Toxidrome
Causative Agents : Cocaine, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA / "ecstasy"), synthetic cathinones ("bath salts"), ephedrine, pseudoephedrine.
Pathophysiology : Massive central and peripheral release and reuptake inhibition of catecholamines (norepinephrine, epinephrine, dopamine, serotonin), stimulating alpha- and beta-adrenergic receptors.
Clinical Manifestations : Severe agitation, hypervigilance, delirium, hyperthermia, tachycardia, hypertension, mydriasis (dilated pupils), hyperactive bowel sounds, tremors, seizures, and profuse diaphoresis .
Critical Management Nuance : Diaphoresis is the key physical finding distinguishing sympathomimetic toxicity from anticholinergic toxicity. First-line therapy relies on aggressive intravenous benzodiazepines (lorazepam or diazepam) to blunt central sympathetic outflow, control seizures, and facilitate evaporative cooling. Direct-acting vasodilators (phentolamine, nicardipine, nitroglycerin, or nitroprusside) may be added for refractory hypertension.
Warning
Avoid Pure Beta-Blockers in Cocaine and Sympathomimetic Toxicity : The administration of pure beta-adrenergic antagonists (such as propranolol or metoprolol) in severe cocaine or amphetamine intoxication blocks beta-2 mediated peripheral vasodilation while leaving alpha-1 adrenergic receptors uninhibited. This "unopposed alpha-adrenergic stimulation" can precipitate catastrophic arterial vasoconstriction, severe hypertensive crisis, acute coronary vasospasm, and acute myocardial infarction.
2. Anticholinergic (Antimuscarinic) Toxidrome
Causative Agents : First-generation antihistamines (diphenhydramine, hydroxyzine), tricyclic antidepressants (amitriptyline, nortriptyline), scopolamine, atropine, benztropine, antispasmodics (oxybutynin), and plants ( Datura stramonium [Jimson weed], Atropa belladonna ).
Pathophysiology : Competitive inhibition of acetylcholine at central and peripheral muscarinic ( M 1 − M 5 M_1 - M_5 M 1 − M 5 ) receptors.
Clinical Manifestations : The classic mnemonic details the syndrome:
- "Blind as a bat" (mydriasis with loss of visual accommodation / cycloplegia)
- "Mad as a hatter" (delirium, hallucinations, picking at non-existent objects, speech dyspraxia)
- "Red as a beet" (cutaneous flushing from compensatory peripheral vasodilation)
- "Hot as a hare" (hyperthermia from loss of thermoregulatory sweating)
- "Dry as a bone" (marked anhidrosis, parched oral mucosa, dry axillae)
- "Full as a flask" (urinary retention from detrusor relaxation and internal sphincter contraction)
Additional features: Absent or hypoactive bowel sounds, sinus tachycardia.
Critical Management Nuance : Supportive therapy includes Foley catheterization to relieve bladder distension, active cooling, and benzodiazepines for psychomotor agitation. Physostigmine (a tertiary amine carbamate that inhibits acetylcholinesterase and crosses the blood-brain barrier; dose 0.5 − 2 mg 0.5 - 2\text{ mg} 0.5 − 2 mg slow IV over 5 minutes) can reverse central and peripheral delirium in pure anticholinergic poisoning. However, physostigmine is strictly contraindicated if tricyclic antidepressant (TCA) toxicity or cardiac conduction abnormalities (prolonged QRS > 100 ms > 100\text{ ms} > 100 ms , terminal R R R wave in aVR, PR prolongation) are present, as it can precipitate severe refractory bradyasystole and cardiac arrest.
3. Cholinergic Toxidrome
Causative Agents : Organophosphate and carbamate insecticides, chemical nerve agents (sarin, tabun, soman, VX), and acetylcholinesterase-inhibiting medications (neostigmine, pyridostigmine, donepezil).
Pathophysiology : Irreversible (organophosphates) or reversible (carbamates) inhibition of acetylcholinesterase, leading to toxic accumulation of acetylcholine at muscarinic, nicotinic, and central nervous system synapses.
Clinical Manifestations :
Muscarinic Overstimulation : Remembered by the mnemonics SLUDGEM (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal motility, Emesis, Miosis) or DUMBELS (Diarrhea, Urination, Miosis, Bronchorrhea / Bronchospasm / Bradycardia , Emesis, Lacrimation, Salivation). The "Killer B's" —profuse pulmonary bronchorrhea, severe bronchospasm, and bradycardia—represent the leading cause of lethal asphyxiation.
Nicotinic Overstimulation : Fasciculations, muscle cramping, profound flaccid paralysis (including diaphragmatic arrest), hypertension, and initial tachycardia.
Central Nervous System : Encephalopathy, coma, and intractable seizures.
Management Algorithm :
Personal Protective Equipment (PPE) & Decontamination : Healthcare workers must don chemical-resistant PPE. Remove all patient clothing and copiously wash skin with soap and water.
Atropine : Competitive antagonist at muscarinic receptors. Administer 2 2 2 to 4 mg 4\text{ mg} 4 mg IV bolus, doubling the dose every 3 to 5 minutes until muscarinic toxicity resolves. The sole therapeutic endpoints for atropinization are cessation of bronchorrhea, clearance of lung crackles, and resolution of bronchospasm (with heart rate > 80 bpm > 80\text{ bpm} > 80 bpm ). Pupil size and heart rate are not the primary endpoints for halting atropine.
Pralidoxime (2-PAM) : A nucleophilic oxime that reactivates phosphorylated acetylcholinesterase at neuromuscular nicotinic junctions, treating muscle fasciculations and weakness. Administer a loading dose of 1 1 1 to 2 g 2\text{ g} 2 g IV over 30 minutes followed by a continuous infusion of 500 mg/h 500\text{ mg/h} 500 mg/h . Pralidoxime must be initiated early, before the phosphorylated enzyme undergoes covalent "aging" (chemical dealkylation), rendering inhibition irreversible.
4. Opioid Toxidrome
Pathophysiology : Agonism at mu-, kappa-, and delta-opioid receptors within the central nervous system and gastrointestinal tract.
Clinical Manifestations : The classic triad consists of central nervous system depression (stupor/coma) , miosis (pinpoint pupils) , and severe respiratory depression (bradypnea, hypopnea, or apnea) . Hypothermia, bradycardia, hypotension, and absent bowel sounds are frequent. Note that miosis may be absent in overdoses involving meperidine (anticholinergic properties), tramadol, co-ingested sympathomimetics, or profound cerebral anoxia.
Critical Management Nuance : The primary goal of Naloxone therapy in a non-cardiac arrest setting is not the complete restoration of full alertness, but the restoration of adequate spontaneous alveolar ventilation (respiratory rate ≥ 10 − 12 breaths/min \ge 10 - 12\text{ breaths/min} ≥ 10 − 12 breaths/min ). Start with low-dose titrated intravenous naloxone ( 0.04 − 0.1 mg 0.04 - 0.1\text{ mg} 0.04 − 0.1 mg IV), doubling every 2 minutes. Administering large empiric boluses ( 2 − 4 mg 2 - 4\text{ mg} 2 − 4 mg ) in opioid-dependent individuals triggers severe acute withdrawal, violent delirium, and a massive catecholamine surge precipitating non-cardiogenic flash pulmonary edema. High initial doses ( 2 − 10 mg 2 - 10\text{ mg} 2 − 10 mg ) are indicated only in patients with synthetic ultra-potent opioid exposure (fentanyl analogs, carfentanil) or primary cardiac arrest.
5. Sedative-Hypnotic Toxidrome
Causative Agents : Benzodiazepines, barbiturates, gamma-hydroxybutyrate (GHB), z-drugs (zolpidem).
Pathophysiology : Enhanced GABA-mediated inhibitory neurotransmission.
Clinical Manifestations : Central nervous system depression, lethargy, slurred speech, ataxia, and stupor with relatively preserved vital signs in isolated benzodiazepine ingestion. Barbiturates cause marked hypothermia, hypotension, and respiratory depression.
Critical Management Nuance : Flumazenil (competitive GABA-A antagonist) is contraindicated in the routine management of undifferentiated coma, chronic benzodiazepine users, or suspected multi-substance ingestions (especially tricyclic antidepressants). Flumazenil precipitates sudden, refractory status epilepticus and lethal withdrawal that cannot be overcome with readministered benzodiazepines. Treatment is strictly supportive airway protection and mechanical ventilation.
Specific Critical Care Ingestions & Protocols
Toxin / Drug Class Clinical Manifestations & Pathophysiology Key Diagnostic Workup & Thresholds First-Line Antidote & ICU Dosing Protocol
Acetaminophen (APAP) Hepatocellular necrosis due to CYP2E1 oxidation to NAPQI , exhausting glutathione stores ( < 30 % < 30\% < 30% ) with Zone 3 centrilobular necrosis. Serum APAP level plotted on the Rumack-Matthew Nomogram between 4 and 24 hours post-ingestion. Action line starts at 150 mcg/mL 150\text{ mcg/mL} 150 mcg/mL at 4 hours. N-Acetylcysteine (NAC) : IV 21-hour protocol: 150 mg/kg 150\text{ mg/kg} 150 mg/kg in 200 mL 200\text{ mL} 200 mL D5W over 1 h 1\text{ h} 1 h , then 50 mg/kg 50\text{ mg/kg} 50 mg/kg in 500 mL 500\text{ mL} 500 mL D5W over 4 h 4\text{ h} 4 h , then 100 mg/kg 100\text{ mg/kg} 100 mg/kg in 1000 mL 1000\text{ mL} 1000 mL D5W over 16 h 16\text{ h} 16 h . Continue beyond 21 hours if APAP detectable, AST/ALT rising, or INR > 1.5 > 1.5 > 1.5 .
Salicylates (Aspirin) Mitochondrial uncoupling of oxidative phosphorylation combined with direct medullary respiratory center stimulation. Mixed primary respiratory alkalosis and high anion gap metabolic acidosis . Serial salicylate levels (toxic > 30 − 40 mg/dL > 30-40\text{ mg/dL} > 30 − 40 mg/dL ; severe > 80 − 100 mg/dL > 80-100\text{ mg/dL} > 80 − 100 mg/dL ), blood gas, urine pH, serum potassium. Sodium Bicarbonate infusion ( 100 − 150 mEq 100-150\text{ mEq} 100 − 150 mEq in 1 L D5W at 1.5 − 2 × 1.5-2\times 1.5 − 2 × maintenance) targeting urine pH 7.5 − 8.0 7.5-8.0 7.5 − 8.0 and blood pH 7.45 − 7.55 7.45-7.55 7.45 − 7.55 for ion trapping. Replete potassium aggressively to ≥ 4.0 − 4.5 mEq/L \ge 4.0-4.5\text{ mEq/L} ≥ 4.0 − 4.5 mEq/L . Hemodialysis (EXTRIP) if level > 100 mg/dL > 100\text{ mg/dL} > 100 mg/dL ( > 90 > 90 > 90 with impaired kidney function), altered mental status, new hypoxemia requiring oxygen, or failure of standard therapy; suggested for pH ≤ 7.20 \le 7.20 ≤ 7.20 or a level above 90 mg/dL 90\text{ mg/dL} 90 mg/dL .
Ethylene Glycol Metabolized by ADH to glycolic acid and oxalic acid. Oxalate complexes with calcium, forming calcium oxalate crystals , causing acute tubular necrosis, renal failure, and tetany/QTc prolongation. Elevated osmolar gap early; severe high anion gap metabolic acidosis late. Urine microscopy demonstrates envelope- or needle-shaped calcium oxalate crystals. Fomepizole : 15 mg/kg 15\text{ mg/kg} 15 mg/kg IV loading dose over 30 min 30\text{ min} 30 min , then 10 mg/kg 10\text{ mg/kg} 10 mg/kg every 12 h 12\text{ h} 12 h for 4 doses. Add Thiamine 100 mg 100\text{ mg} 100 mg IV and Pyridoxine 50 mg 50\text{ mg} 50 mg IV q6h. Hemodialysis (EXTRIP 2023) is recommended for an anion gap above 27 mmol/L 27\text{ mmol/L} 27 mmol/L , glycolate above 12 mmol/L 12\text{ mmol/L} 12 mmol/L , coma, seizures, or AKI (suggested for an anion gap of 23 to 27); with fomepizole, it is suggested for an EG concentration above 50 mmol/L 50\text{ mmol/L} 50 mmol/L (about 310 mg/dL 310\text{ mg/dL} 310 mg/dL ) or an osmolal gap above 50.
Methanol Metabolized by ADH to formaldehyde and formic acid , which inhibits cytochrome c oxidase, causing retinal toxicity ("snowfield" blindness) and bilateral putaminal necrosis . Elevated osmolar gap early, severe HAGMA late. Visual acuity deficit, optic disc hyperemia on fundoscopy, putaminal hypodensities on head CT/MRI. Fomepizole : 15 mg/kg 15\text{ mg/kg} 15 mg/kg IV loading dose, then 10 mg/kg 10\text{ mg/kg} 10 mg/kg every 12 h 12\text{ h} 12 h . Add Folinic acid (or folic acid) 50 mg 50\text{ mg} 50 mg IV q4-6h to enhance formate clearance. Emergent Hemodialysis (EXTRIP 2015) for coma, seizures, new visual deficits, pH ≤ 7.15 \le 7.15 ≤ 7.15 , persistent acidosis, or an anion gap above 24; or a methanol level above 70 mg/dL 70\text{ mg/dL} 70 mg/dL on fomepizole, above 60 mg/dL 60\text{ mg/dL} 60 mg/dL on ethanol, or above 50 mg/dL 50\text{ mg/dL} 50 mg/dL without an alcohol dehydrogenase blocker.
Beta-Blockers & Calcium Channel Blockers Profound bradycardia, high-grade AV block, myocardial depression, vasoplegic shock. CCBs cause marked hyperglycemia (inhibiting insulin release); beta-blockers (propranolol) cause seizures and wide QRS. Point-of-care glucose, serial 12-lead ECGs, focused cardiac ultrasound for depressed left ventricular ejection fraction. High-Dose Insulin-Euglycemia Therapy (HIET) : Regular insulin 1 unit/kg 1\text{ unit/kg} 1 unit/kg IV bolus with 25 − 50 g 25-50\text{ g} 25 − 50 g D50W, followed by 1 unit/kg/h 1\text{ unit/kg/h} 1 unit/kg/h infusion (titrated up to 2 − 10 U/kg/h 2-10\text{ U/kg/h} 2 − 10 U/kg/h ) with concentrated dextrose and potassium maintenance. Adjuncts: Calcium chloride 1 − 2 g 1-2\text{ g} 1 − 2 g IV, Glucagon 5 − 10 mg 5-10\text{ mg} 5 − 10 mg IV, Intralipid 20% emulsion rescue, and VA-ECMO.
Digoxin Inhibition of Na + / K + \text{Na}^+/\text{K}^+ Na + / K + -ATPase pump increases intracellular calcium (arrhythmogenicity) and increases vagal tone. Acute overdose causes severe hyperkalemia ; chronic toxicity worsened by hypokalemia. Serum digoxin level, serum potassium, ECG (frequent PVCs, bidirectional VT, atrial tachycardia with variable block). Digoxin-Specific Fab (DigiFab) : Empiric 10 − 20 vials 10 - 20\text{ vials} 10 − 20 vials IV for cardiac arrest or life-threatening instability. In non-arrest, calculate vials: Vials = [ Digoxin ( ng/mL ) ] × Weight ( kg ) 100 \text{Vials} = \frac{[\text{Digoxin } (\text{ng/mL})] \times \text{Weight } (\text{kg})}{100} Vials = 100 [ Digoxin ( ng/mL )] × Weight ( kg ) . Treat hyperkalemia > 5.0 − 5.5 mEq/L > 5.0-5.5\text{ mEq/L} > 5.0 − 5.5 mEq/L with Fab; IV calcium is no longer considered absolutely contraindicated, but Fab is the treatment of choice.