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Emergency Medicine›Condition·Updated Jul 11, 2026·v1

Acute Poisoning and Overdose

Acute poisoning and overdose require a systematic approach: recognize the toxidrome, stabilize the airway and circulation, decontaminate if appropriate, administer specific antidotes, and monitor for delayed toxicity. The vast majority of cases involve opioids, acetaminophen, or sedative-hypnotics. Timely intervention with naloxone, NAC, sodium bicarbonate, or fomepizole can be life-saving. Psychiatric assessment is mandatory for intentional overdoses. The key to safe discharge is resolution of symptoms, normal ECG, and completed treatment course.

High Evidence0 references·478 words·2 min read·v1
poisoningoverdosetoxicologyemergency medicinenaloxoneN-acetylcysteinetoxidromes

Quick Reference

RxDrug of choiceNaloxone for opioid overdose; N-acetylcysteine for acetaminophen; fomepizole for toxic alcohols; sodium bicarbonate for tricyclic antidepressants
AltAlternativesFlumazenil (benzodiazepine reversal, but contraindicated in mixed overdose); calcium gluconate for CCB; glucagon for beta-blocker; cyproheptadine for serotonin syndrome
⊘AvoidIpecac (all overdoses); flumazenil in patients with seizure history or TCA co-ingestion; activated charcoal for caustics, hydrocarbons, or aspiration risk
DxTest of choiceECG (QRS, QTc) for cardiotoxic agents; serum acetaminophen level at 4 hours post-ingestion; osmolal gap for toxic alcohols; arterial blood gas for acid-base disturbance
ScKey scoreRumack-Matthew nomogram (acetaminophen); Glasgow Coma Scale (severity of CNS depression); Poison Severity Score (PSS) for research
→When to referICU for any poisoning requiring vasopressors, dialysis, or intubation; psychiatry for all intentional overdoses; medical toxicology specialist for complex cases
All poisoned patients with altered mental status or abnormal vital signs require immediate resuscitation, toxidrome recognition, and targeted antidote administration; time is brain, liver, and heart.
Acute poisoning and overdose represent a leading cause of emergency department visits and critical illness, with over 2 million reported cases annually in the U.S. and a rising toll from opioid and acetaminophen exposures. The cornerstone of management is rapid recognition of toxidromes, aggressive resuscitation, and administration of specific antidotes when indicated. This page provides a structured approach to the poisoned patient, from the initial assessment through definitive therapy and disposition, with emphasis on time-sensitive interventions such as naloxone for opioid overdose, N-acetylcysteine for acetaminophen, and decontamination within the appropriate window.

Overview and Recommendations

Key Facts

  • •Acute poisoning accounts for ~5% of all ED visits and is the leading cause of cardiac arrest in patients under 40 years. The most common agents involved include opioids, acetaminophen, benzodiazepines, antidepressants, and alcohol, though regional variation exists.
  • •The toxicology paradigm is shifting: the opioid epidemic drives a disproportionate share of fatalities (over 80,000 deaths/year in the U.S. from synthetic opioids alone), while acetaminophen remains the most common cause of acute liver failure requiring transplantation.
  • •A systematic approach using toxidromes, anticholinergic, cholinergic, sympathomimetic, opioid, sedative-hypnotic, and serotonin syndrome, enables rapid identification of the poison class before laboratory confirmation.
  • •Time-critical interventions exist for specific overdoses: naloxone for opioid-induced respiratory depression, N-acetylcysteine (NAC) within 8 hours of acetaminophen ingestion, activated charcoal within 1-2 hours, and fomepizole for methanol or ethylene glycol poisoning.
  • •The Rumack-Matthew nomogram guides treatment for acetaminophen overdose; the Glasgow Coma Scale (GCS) and the QRS duration on ECG are critical for risk stratification in tricyclic antidepressant and other cardiotoxic overdoses.
  • •Co-ingestions are common (up to 40% of cases) and can mask or unmask toxidromes, requiring a high index of suspicion and a broad toxicology screen.

Evaluation

  • •Suspect acute poisoning in any patient with altered mental status, unexplained vital sign abnormalities, seizure, or cardiac arrest, especially in young adults or those with a history of substance use, depression, or suicide attempt.
  • •Ask about the substance(s) ingested, dose, time of ingestion, route (oral, inhalation, injection), and any co-ingestants. Obtain the medication bottle or pill identification via online databases (e.g., Pill ID).
  • •Examine for toxidromes: anticholinergic (hyperthermia, mydriasis, flushed skin, urinary retention, ileus, delirium), cholinergic (SLUDGE: salivation, lacrimation, urination, defecation, GI upset, emesis; also miosis, bradycardia), sympathomimetic (mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis), opioid (miosis, respiratory depression, CNS depression), sedative-hypnotic (nystagmus, slurred speech, ataxia, coma), and serotonin syndrome (hyperthermia, clonus, hyperreflexia, tremor, autonomic instability).
  • •Order an ECG immediately, measure QRS duration and QTc interval. A QRS > 100 ms suggests sodium-channel blockade (tricyclic antidepressants, cocaine, diphenhydramine) and need for sodium bicarbonate. A QTc > 500 ms increases risk of torsades de pointes.
  • •Check serum acetaminophen and salicylate levels in all intentional overdoses, regardless of history, acetaminophen is often co-ingested and can be missed until liver failure develops.
  • •Obtain a basic metabolic panel, serum osmolality, and calculate the osmolal gap (measured - calculated). An elevated gap suggests methanol, ethylene glycol, isopropanol, or propylene glycol toxicity.
  • •Arterial blood gas with lactate and anion gap calculation: metabolic acidosis with high anion gap and elevated lactate is seen in cyanide, metformin, salicylate, and toxic alcohol poisonings.
  • •Consider a comprehensive urine drug screen, but be aware of its limitations: false positives, false negatives, and lack of correlation with clinical toxicity. The screen is confirmatory, not diagnostic.
  • •For suspected opioid overdose, assess respiratory rate, oxygen saturation, and response to naloxone challenge. A rapid reversal of respiratory depression and pinpoint pupils is diagnostic.
  • •Perform a head CT and lumbar puncture if there is concern for intracranial pathology (e.g., trauma, infection) that could mimic poisoning, especially in patients with focal neurologic signs or fever.

Management

  • •Secure the airway and ensure adequate oxygenation and ventilation. Administer high-flow oxygen or perform endotracheal intubation if GCS < 8, respiratory rate < 10, or PaO2 < 60 despite supplementation.
  • •Administer 0.4-2 mg IV/IM/IN for suspected opioid overdose with respiratory depression. Repeat every 2-3 minutes up to 10 mg total. For long-acting opioids (e.g., methadone, buprenorphine), start an infusion: 2/3 of the effective bolus dose per hour, titrated to respiratory rate.
  • •Give activated charcoal 1 g/kg PO (max 50 g) only if the patient presents within 1-2 hours of a potentially toxic ingestion and has an intact airway, no risk of aspiration, and no contraindications (caustic, hydrocarbon, or bowel obstruction).
  • •For acetaminophen overdose: administer (NAC) 150 mg/kg IV over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. Alternatively, the oral 72-hour protocol: 140 mg/kg loading, then 70 mg/kg every 4 hours. Start NAC immediately if the level is above the treatment line on the Rumack-Matthew nomogram (≥ 150 mcg/mL at 4 hours) or if ingestion is > 10 g or > 200 mg/kg.
  • •For tricyclic antidepressant overdose with QRS > 100 ms: give 1-2 mEq/kg IV bolus, repeat until QRS < 100 ms. Then maintain with a bicarbonate drip (150 mEq NaHCO3 in 1 L D5W at 250 mL/h) to keep serum pH 7.5-7.55.
  • •For calcium channel blocker or beta-blocker overdose: administer 1-2 g IV (for CCB) or 5-10 mg IV bolus followed by infusion (5 mg/h) for beta-blocker. High-dose insulin euglycemia therapy (HIE) is also used for CCB: regular insulin 1 U/kg IV bolus, then 0.5-1 U/kg/h with dextrose infusion to maintain glucose > 100 mg/dL.
  • •For toxic alcohol poisoning (methanol, ethylene glycol): give 15 mg/kg IV loading dose, then 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethanol level < 20 mg/dL. Indications for hemodialysis: severe metabolic acidosis (pH < 7.25), renal failure, visual symptoms, or methanol level > 50 mg/dL.
  • •For salicylate overdose: administer if ingestion < 1 hour. Treat with sodium bicarbonate infusion to alkalinize urine (target urine pH 7.5-8.0) for serum levels > 30 mg/dL. Hemodialysis is indicated for levels > 100 mg/dL, severe acidosis, altered mental status, or pulmonary edema.
  • •For serotonin syndrome with hyperthermia (> 38.5°C) and agitation: give 12 mg PO/NG (or 4 mg every 2 hours until response) or (lorazepam 2-4 mg IV) for muscle rigidity. Severe cases require paralysis, intubation, and cooling.
  • •For anticholinergic delirium: administer 0.5-2 mg IV slowly over 5 minutes, repeated every 10-30 minutes if needed. Use only if QRS < 100 ms on ECG; avoid in patients with asthma, bradycardia, or intestinal obstruction.
  • •Monitor the patient with serial ECGs, pulse oximetry, and mental status assessments. Obtain a psychiatric consultation for all intentional overdoses before discharge.
  • •Discharge criteria: asymptomatic, no evidence of delayed toxicity, normal mental status, ECG normal, and follow-up arranged. For acetaminophen overdose, ensure NAC course completed and liver function normal.
  • •What NOT to do: do not induce emesis with ipecac; do not use activated charcoal more than 2 hours after ingestion unless the substance is enteric-coated or sustained-release; do not routinely administer flumazenil for benzodiazepine overdose (risk of seizures in mixed ingestions).

Board Review — High Yield

  • •Toxidromes, Anticholinergic: hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter. Cholinergic: SLUDGE syndrome. Opioid: miosis, respiratory depression, coma.
  • •Rumack-Matthew nomogram, Used for acetaminophen overdose; plot level at ≥4 hours post-ingestion; treatment line at 150 mcg/mL at 4 hours. NAC started within 8 hours prevents liver injury.
  • •Sodium bicarbonate for TCA overdose, Alkalinizes serum, increases protein binding of tricyclics, and narrows QRS; give 1-2 mEq/kg IV bolus if QRS > 100 ms.
  • •Osmolal gap, Measured osm - calculated osm. Normal < 10. Elevated in methanol, ethylene glycol, isopropanol, propylene glycol. Use to screen for toxic alcohol ingestion.
  • •Opioid overdose reversal, Naloxone 0.4-2 mg IV, repeat as needed. Infusion for long-acting opioids. Beware of acute withdrawal in opioid-dependent patients.
  • •Activated charcoal, 1 g/kg PO within 1-2 hours of ingestion. Not for caustics, hydrocarbons, or aspiration risk. Must be given with intact airway.
  • •Serotonin syndrome vs NMS, Serotonin: clonus, hyperreflexia, tremor, diaphoresis, hyperthermia. Neuroleptic malignant syndrome: lead-pipe rigidity, bradykinesia, fever, autonomic instability.
  • •Flumazenil caution, Avoid in mixed benzodiazepine/TCA overdose; high risk of seizures. Use only for reversal of iatrogenic benzodiazepine oversedation.
  • •Calcium for CCB overdose, Calcium gluconate 1-2 g IV; if ineffective, high-dose insulin euglycemia (HIE) therapy: insulin 1 U/kg IV bolus + dextrose infusion.
  • •Hemodialysis indications, Methanol level > 50 mg/dL, ethylene glycol level > 50 mg/dL, severe acidosis, visual symptoms, renal failure; salicylate level > 100 mg/dL, acidosis, pulmonary edema.

Deep Dive — Evidence Details

References

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