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150 mg/kg IV over 1h, then 50 mg/kg over 4h, then 100 mg/kg over 16h for APAP toxicity
0.04–0.4 mg IV (titrate to spontaneous ventilation, avoiding acute withdrawal)
1 unit/kg regular insulin IV bolus + 1 unit/kg/h infusion + D10W/D20W for CCB/BB overdose
1–2 mEq/kg IV push for QRS > 100 ms in TCA overdose or alkalinization in aspirin
2–4 mg IV q3–5min (double dose until pulmonary secretions are dry)
Bottom-Line Clinical Pearl
Master the 5 classic toxidromes: Anticholinergic (dry skin), Cholinergic (SLUDGEM/killer B's), Opioid (pinpoint pupils + bradypnea), Sympathomimetic (diaphoretic skin), and Sedative-Hypnotic. In acetaminophen ingestion, check a 4-hour level and start NAC based on the Rumack-Matthew nomogram. For calcium channel and beta-blocker shock, start High-Dose Insulin Euglycemia Therapy (HIET) early. In salicylate poisoning, alkalinize the urine with IV sodium bicarbonate (target urine pH 7.5–8.0) to trap salicylate ions.
A toxidrome is a constellation of physical signs and symptoms characteristic of a specific drug class or toxin. Rapid identification of the toxidrome directs targeted antidote administration before laboratory confirmation is available:
| Toxidrome | Pupils | Vital Signs | Skin/Mucosa | Mental Status & Other Signs | Common Causative Agents |
|---|---|---|---|---|---|
| Anticholinergic | Mydriasis (dilated, sluggish) | Tachycardia, Hyperthermia, Hypertension | DRY, flushed, hot skin; dry axillae and oral mucosa | Agitated delirium ('mad as a hatter'), visual hallucinations, urinary retention, absent bowel sounds | Diphenhydramine, atropine, scopolamine, TCAs, benztropine, jimson weed. |
| Cholinergic | Miosis (pinpoint) | Bradycardia (or tachycardia), Hypotension | PROFOUND DIAPHORESIS, excessive salivation, lacrimation | DUMBELS: Defecation, Urination, Miosis, Bronchorrhea/Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation | Organophosphates, carbamate pesticides, nerve agents (sarin, VX), physostigmine. |
| Opioid | Miosis (pinpoint, 1–2 mm) | Bradypnea (< 8–10/min), Bradycardia, Hypotension, Hypothermia | Cool, pale skin | CNS depression, stupor, coma, hyporeflexia, decreased bowel sounds, pulmonary edema | Morphine, heroin, fentanyl, oxycodone, methadone, tramadol. |
| Sympathomimetic | Mydriasis (dilated, reactive) | Severe Tachycardia, Severe Hypertension, Hyperthermia | DIAPHORETIC, drenched skin (distinguishes from anticholinergic!) | Agitation, psychomotor excitement, paranoia, tremors, hyperreflexia, seizures | Cocaine, methamphetamine, MDMA (ecstasy), cathinones ('bath salts'), PCP. |
| Sedative-Hypnotic | Variable (normal to small) | Hypoventilation, mild bradycardia, mild hypotension | Normal skin | CNS depression, dysarthria, ataxia, stupor, coma with relatively preserved vital signs | Benzodiazepines, barbiturates, z-drugs (zolpidem), GHB, ethanol. |
| Toxin/Drug | Primary Antidote | Specific Dosing & Administration Protocol | Mechanisms & High-Yield Pearls |
|---|---|---|---|
| Acetaminophen (APAP) | N-Acetylcysteine (NAC) | IV 3-bag protocol: 150 mg/kg in 200 mL D5W over 1h; 50 mg/kg in 500 mL over 4h; 100 mg/kg in 1000 mL over 16h (or oral 140 mg/kg load + 70 mg/kg q4h x 17) | Replenishes glutathione stores, binding toxic metabolite NAPQI. 100% hepatoprotective if started within 8h of acute ingestion. |
| Salicylates (Aspirin) | Sodium Bicarbonate | 1–2 mEq/kg IV bolus, then continuous infusion (150 mEq in 1L D5W at 2–3x maintenance) + KCl | Alkalinizes urine (target urine pH 7.5–8.0). Traps ionized salicylate in renal tubules, preventing reabsorption. Dialysis if level > 90 mg/dL. |
| Organophosphates | Atropine + Pralidoxime (2-PAM) | Atropine 2–4 mg IV q3–5min (double dose until tracheobronchial secretions are dry); 2-PAM 1–2g IV over 30 min | Atropine competitively blocks muscarinic receptors (titrate to DRY LUNGS, not heart rate). 2-PAM reactivates phosphorylated acetylcholinesterase. |
| Calcium Channel Blockers | High-Dose Insulin (HIET) + Calcium | Regular Insulin 1 unit/kg IV bolus + 1 unit/kg/h infusion (titrate to 10 U/kg/h) with D10W/D20W; Calcium gluconate 3–6g IV | In myocytes under CCB toxicity, carbohydrate utilization stalls; high-dose insulin restores myocardial glucose uptake and contractility. |
| Beta-Blockers | Glucagon + HIET | Glucagon 3–5 mg IV push over 2 min (followed by 2–5 mg/h infusion); High-Dose Insulin (HIET) | Glucagon bypasses adrenergic beta-receptors, activating adenylate cyclase directly to increase intracellular cyclic AMP and inotropy. |
| Digoxin | Digoxin Immune Fab (DigiFab) | Empiric 10–20 vials IV in cardiac arrest/shock; calculated: [Serum Digoxin (ng/mL) * Weight (kg)]/100 | Binds free digoxin molecules. Indications: Serum K > 5.0 in acute toxicity, life-threatening ventricular dysrhythmias, shock. |
| Toxic Alcohols (Methanol/EG) | Fomepizole (4-MP) | 15 mg/kg IV loading dose over 30 min, then 10 mg/kg q12h x 4 doses (then 15 mg/kg q12h) | Competitive antagonist of Alcohol Dehydrogenase (ADH). Blocks conversion of methanol to formic acid and ethylene glycol to oxalic acid. |
| Tricyclic Antidepressants (TCA) | Sodium Bicarbonate | 1–2 mEq/kg IV push repeated until QRS narrows < 100 ms; follow with infusion | Overcomes fast inward sodium channel blockade and alkalinizes serum (target serum pH 7.50–7.55), detaching TCA from the receptor. |
| Cyanide/Smoke Inhalation | Hydroxocobalamin (Cyanokit) | 5g IV infusion over 15 minutes (may repeat second 5g dose) | Chelates cyanide to form non-toxic cyanocobalamin (Vitamin B12), excreted in urine. Causes benign transient red skin/urine discoloration. |
| Local Anesthetics (LAST) | 20% Intravenous Lipid Emulsion (ILE) | 1.5 mL/kg IV bolus over 1 min, followed by continuous infusion of 0.25 mL/kg/min (repeat bolus x 2 if pulseless) | 'Lipid sink' mechanism extracts lipophilic local anesthetics (Bupivacaine, Lidocaine) from cardiac tissue and restores mitochondrial metabolism. |
Acetaminophen (APAP) is the most common cause of acute liver failure in the Western world. In therapeutic doses, 90% is metabolized by glucuronidation/sulfation. In overdose, these pathways saturate, shunting APAP to cytochrome P450 (CYP2E1), producing the highly toxic, reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI depletes glutathione and causes centrilobular hepatic necrosis.
- The Rumack-Matthew Nomogram: Applies strictly to single acute ingestions of known timing between 4 and 24 hours. The treatment line starts at 150 mcg/mL (993 umol/L) at 4 hours post-ingestion. Any level on or above this line mandates full N-acetylcysteine (NAC) therapy.
- Delayed/Staggered Ingestions: If presentation is > 8 hours post-ingestion, start NAC immediately while awaiting laboratory results; do not delay therapy. If ingestion was repeated or timing is unknown, treat with NAC if APAP is detectable OR AST/ALT are elevated.
- Criteria for Discontinuing NAC: Do NOT stop NAC simply because the 21-hour infusion completed. Continue NAC until ALL THREE criteria are met: 1) Serum APAP is undetectable (< 10 mcg/mL); 2) Serum AST and ALT are normal or clearly downtrending; 3) INR is normal (< 1.5) or downtrending, and the patient is clinically well.
Clinical Caution
Salicylate Poisoning Acid-Base Pearl: Salicylates directly stimulate the medullary respiratory center to cause hyperventilation (primary Respiratory Alkalosis) while simultaneously uncoupling oxidative phosphorylation in mitochondria to cause anaerobic metabolism and ketoacidosis (primary High Anion Gap Metabolic Acidosis). The classic blood gas demonstrates a mixed Respiratory Alkalosis + Anion Gap Metabolic Acidosis with a near-normal pH, low PaCO2, and low HCO3.
Test Your Toxicology: Toxidromes & Critical Antidotes Clinical Acumen
Directly launch an active-recall practice block from our validated question bank with comprehensive explanations and distractor analyses.
Distinguish primary life-threats from mimics. On board exams (COMLEX Level 1, 2-CE, 3 & USMLE), initial stabilizing interventions (airway, IV access, non-invasive ventilation, empiric reversal) always take precedence over diagnostic imaging.
Evaluate autonomic tone: Sympathetic viscerosomatics (T1–L2) cause acute paraspinal tissue texture changes (erythema, bogginess, hypertonicity). Suboccipital release (CN X Vagus) and rib raising normalize autonomic outflow and thoracic cage mechanics.