Residency · Residency · Emergency Medicine
The Poisoned Patient: General Approach and Toxidromes
General Approach
Initial Stabilization
The approach to the poisoned patient begins with the ABCs, which always take priority over identifying the specific toxin. Airway management may require intubation for CNS depression, loss of protective reflexes, or caustic ingestion. Breathing should be assessed for respiratory depression (as seen with opioids), bronchospasm (organophosphates), or compensatory tachypnea (salicylates and metabolic acidosis). Circulation assessment focuses on hemodynamics, recognizing that toxin-related shock may require specific antidotes rather than standard resuscitation alone. The disability assessment includes GCS, pupil size (miosis versus mydriasis), and temperature. In any patient with altered mental status, dextrose, naloxone, and thiamine should be considered empirically.
History Taking
The history in a poisoning case aims to establish what was taken, how much, when, the route of exposure, and whether co-ingestants were involved. It is important to determine whether the exposure was intentional, accidental, or occupational, and to assess access to medications in the household, which is particularly relevant in pediatric cases. Psychiatric history should be explored to evaluate suicidal intent. In every intentional overdose, co-ingestion should be assumed until proven otherwise.
Key Diagnostic Studies
The ECG is one of the most important early tests, revealing QRS widening (sodium channel blockade), QTc prolongation, or bradycardia and tachycardia patterns that point toward specific toxins. A basic metabolic panel provides the anion gap, electrolytes, glucose, and renal function. Serum osmolality with an osmolar gap calculation helps identify toxic alcohols. Acetaminophen and salicylate levels should be checked in all intentional ingestions, even if not reported, because co-ingestion is common and both are treatable. Lactate elevation raises concern for metformin toxicity, cyanide, carbon monoxide, or toxic alcohols. A pregnancy test should be obtained because it affects management decisions. A venous or arterial blood gas clarifies acid-base status. The urine drug screen, by contrast, is generally unhelpful for acute management and rarely changes ED care. It suffers from many false negatives (fentanyl and synthetic cannabinoids are not detected) and false positives.
Toxidrome Recognition
| Toxidrome | Pupils | Skin | HR/BP | Temperature | Mental Status | Key Distinguishing Feature |
|---|---|---|---|---|---|---|
| Sympathomimetic | Mydriasis | Diaphoretic (WET) | ↑HR, ↑BP | Hyperthermia | Agitated | Diaphoresis |
| Anticholinergic | Mydriasis | Dry, flushed | ↑HR | Hyperthermia | Delirious | Dry skin, urinary retention, ↓bowel sounds |
| Cholinergic | Miosis* | Diaphoretic | ↓HR (muscarinic) | Normal | Variable | SLUDGE-BBB secretions |
| Opioid | Miosis | Normal | ↓HR, ↓BP | Hypothermia | Depressed | Respiratory depression |
| Sedative-Hypnotic | Normal/small | Normal | Normal/↓ | Normal | Depressed | Normal vitals, CNS depression |
| Serotonin Syndrome | Mydriasis | Diaphoretic | ↑HR, ↑BP | Hyperthermia | Agitated | Clonus, hyperreflexia (lower extremities) |
*Nicotinic effects may cause mydriasis in cholinergic toxicity
Sympathomimetic
The sympathomimetic toxidrome is caused by agents such as cocaine, amphetamines, MDMA, and synthetic cathinones (bath salts). The clinical picture includes tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, agitation, and seizures. Treatment centers on benzodiazepines, which are the cornerstone of management, along with cooling for hyperthermia. Beta-blockers are traditionally avoided in cocaine toxicity due to the theoretical risk of unopposed alpha stimulation, though this concern is debated in current literature.
Anticholinergic
Anticholinergic toxicity results from agents like diphenhydramine, atropine, tricyclic antidepressants, jimsonweed, and antihistamines. The classic mnemonic captures the presentation: "Red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask." Findings include tachycardia, mydriasis, dry skin, urinary retention, decreased bowel sounds, hyperthermia, agitation, delirium, and flushing. The critical distinction from the sympathomimetic toxidrome is the skin: anticholinergic patients are dry, whereas sympathomimetic patients are diaphoretic (wet). Treatment involves benzodiazepines for agitation and seizures. Physostigmine at 1 to 2 mg slow IV push is effective for severe anticholinergic delirium, but it is contraindicated in tricyclic antidepressant overdose because of the risk of asystole.
Cholinergic
The cholinergic toxidrome is caused by organophosphates, carbamates, nerve agents, and certain mushrooms. The muscarinic effects are captured by the SLUDGE-BBB mnemonic: salivation, lacrimation, urination, defecation, GI distress, and emesis, along with bradycardia, bronchorrhea, and bronchospasm. Nicotinic effects (remembered by MATCH) include mydriasis (which can override muscarinic miosis), muscle fasciculations, adrenal stimulation, tachycardia, cramping, and hypertension. Treatment consists of atropine titrated to dry secretions with no dose ceiling (massive doses may be required), and pralidoxime (2-PAM) for organophosphate exposures, which reactivates acetylcholinesterase before the enzyme ages and becomes irreversibly bound.
Opioid
The opioid toxidrome is produced by morphine, heroin, fentanyl, methadone, oxycodone, and related agents. It is characterized by CNS depression, respiratory depression, miosis (pinpoint pupils), decreased bowel sounds, hypotension, and bradycardia. Treatment is naloxone, which should be titrated to restore respiratory effort rather than full consciousness. The starting dose is typically 0.04 to 0.4 mg IV, titrated upward as needed.
Sedative-Hypnotic
Sedative-hypnotic toxicity is caused by benzodiazepines, barbiturates, GHB, ethanol, and zolpidem. The presentation includes CNS depression and respiratory depression with normal or small pupils and normal or mildly depressed vital signs. Treatment is primarily supportive. Flumazenil can be used for benzodiazepine overdose, but it must be used cautiously because it carries a risk of precipitating seizures in chronic benzodiazepine users or patients with mixed ingestions.
Serotonin Syndrome
Serotonin syndrome typically results from a combination of serotonergic drugs, including SSRIs, SNRIs, MAOIs, tramadol, linezolid, dextromethorphan, and St. John's wort. The classic triad consists of mental status changes (agitation, confusion), autonomic instability (tachycardia, hypertension, hyperthermia, diaphoresis), and neuromuscular excitability (clonus, hyperreflexia, rigidity), with the neuromuscular findings especially prominent in the lower extremities. The key distinguishing features are clonus (both spontaneous and inducible) and hyperreflexia. Serotonin syndrome is distinguished from neuroleptic malignant syndrome by its rapid onset (hours rather than days), the predominance of clonus over rigidity, and a recent serotonergic drug change. Treatment involves discontinuing all serotonergic agents, administering benzodiazepines, and giving cyproheptadine (a serotonin antagonist) at 12 mg PO initially followed by 2 mg every two hours. Cooling is needed for hyperthermia. Paralysis should be avoided because it masks the clonus that is used to monitor the condition. Severe cases may require intubation.
Neuroleptic Malignant Syndrome (NMS)
NMS is caused by antipsychotics (haloperidol, olanzapine), antiemetics (metoclopramide, prochlorperazine), or withdrawal of dopaminergic agents. It presents with hyperthermia, severe muscular rigidity described as "lead-pipe," altered mental status, and autonomic instability. It is distinguished from serotonin syndrome by its slow onset (days to weeks), the predominance of rigidity over clonus, markedly elevated CK (often above 1000), and its association with dopamine antagonists rather than serotonergic agents. Treatment includes discontinuing the offending agent, dantrolene at 1 to 2.5 mg/kg IV as a muscle relaxant, bromocriptine at 2.5 mg PO every eight hours as a dopamine agonist, active cooling, and supportive care.
Decontamination
Activated Charcoal
The use of activated charcoal has declined significantly, and its benefit is most likely when administered within one hour of ingestion. The dose is 1 g/kg (maximum 50 g in adults) given orally or via nasogastric tube. It is indicated for potentially toxic ingestions within one hour when the airway is protected and the substance is neither caustic nor a hydrocarbon. Contraindications include an unprotected airway, caustic ingestion, hydrocarbon ingestion, GI perforation or obstruction, and anticipated endoscopy. Charcoal is not effective against lithium, iron, potassium, alcohols, or heavy metals, recalled by the mnemonic PHAILS (Pesticides/Potassium, Hydrocarbons, Acids/Alcohols/Alkali, Iron, Lithium, Solvents).
Whole Bowel Irrigation
Whole bowel irrigation uses polyethylene glycol (GoLYTELY) at 1 to 2 liters per hour via nasogastric tube until clear rectal effluent is produced. It is indicated for body packers, sustained-release preparations, iron, lithium, and large ingestions not adsorbed by charcoal. It is contraindicated in ileus, obstruction, perforation, and hemodynamic instability.
Gastric Lavage
Gastric lavage is rarely indicated and has been largely abandoned in modern practice. It should only be considered within one hour of a massive, life-threatening ingestion when charcoal alone is insufficient, and it requires intubation for airway protection.
Enhanced Elimination
Urinary alkalinization with sodium bicarbonate to achieve a urine pH of 7.5 to 8.0 enhances elimination of salicylates and phenobarbital. Hemodialysis effectively removes methanol, ethylene glycol, lithium, salicylates, theophylline, valproic acid, and metformin (remembered by the mnemonic I STUMBLE). Multi-dose activated charcoal creates a "gut dialysis" effect and is useful for carbamazepine, dapsone, phenobarbital, quinine, and theophylline.
Poison Control
The National Poison Control Center (1-800-222-1222 in the United States) is available 24 hours a day, seven days a week, staffed by toxicology-trained specialists. It should be consulted for dosing guidance, antidote recommendations, and disposition planning. The consultation should be documented in the chart.
<image>A comprehensive toxidrome comparison chart with six columns, one for each major toxidrome (sympathomimetic, anticholinergic, cholinergic, opioid, sedative-hypnotic, and serotonin syndrome). Each column shows: pupil size (mydriasis vs. miosis), skin findings (diaphoretic vs. dry vs. flushed), vital sign patterns (heart rate, blood pressure, temperature, respiratory rate), mental status (agitated vs. depressed), bowel sounds (increased vs. decreased), and key distinguishing features. The chart highlights the critical distinction between sympathomimetic (WET/diaphoretic) and anticholinergic (DRY) syndromes.</image>
<image>A flowchart for the initial approach to the poisoned patient. Starting with ABCs and stabilization, then branching to: check glucose (treat hypoglycemia), obtain ECG (look for QRS widening, QTc prolongation, dysrhythmias), and obtain labs (BMP with anion gap, osmolality with osmolar gap, APAP and ASA levels in all intentional ingestions, lactate, pregnancy test). Then: identify toxidrome from exam findings (vital signs, pupils, skin, mental status). Then: consider decontamination (activated charcoal if within 1 hour, protected airway, appropriate ingestion). Then: specific antidotes based on identified toxin. Contact Poison Control (1-800-222-1222) at any point in the algorithm.</image>
<image>A visual comparison of serotonin syndrome versus neuroleptic malignant syndrome. Two human body diagrams side by side. Serotonin syndrome: highlighted lower extremities showing clonus and hyperreflexia, agitated facial expression, diaphoretic skin, with annotations showing rapid onset (hours), recent serotonergic drug addition, tremor and myoclonus, and diarrhea. NMS: highlighted trunk and extremities showing lead-pipe rigidity, obtunded facial expression, with annotations showing slow onset (days-weeks), recent antipsychotic use or dopaminergic withdrawal, markedly elevated CK (often greater than 1000), and bradykinesia. A center box lists shared features: hyperthermia, altered mental status, autonomic instability.</image>
Clinical Pearls
Always check acetaminophen and salicylate levels in all intentional ingestions, because co-ingestion is common and both are treatable. Urine drug screens rarely change acute ED management and should not be relied upon, as many dangerous substances are not detected. The anticholinergic versus sympathomimetic distinction is made by examining the skin: dry skin indicates anticholinergic toxicity, while diaphoresis points to sympathomimetic poisoning. Activated charcoal is most effective within one hour of ingestion, and benefit after that window is marginal for most substances. Serotonin syndrome is characterized by clonus, hyperreflexia (predominant in the lower extremities), and rapid onset, whereas NMS presents with rigidity, elevated CK, and slow onset. Physostigmine is effective for anticholinergic toxicity but contraindicated in TCA ingestion. Naloxone should be titrated to respiratory effort rather than full consciousness, because over-dosing naloxone in opioid-dependent patients causes acute withdrawal, agitation, and can provoke violence. QRS widening on ECG is an emergency that should prompt consideration of sodium channel blockers such as TCAs, cocaine, or diphenhydramine, and treatment with sodium bicarbonate.
References
- Mowry JB, et al. Annual Report of the American Association of Poison Control Centers. Clin Toxicol. 2016;54:924-1109.
- Position paper: single-dose activated charcoal. American Academy of Clinical Toxicology, European Association of Poisons Centres. Clin Toxicol. 2005;43:61-87.
- Boyer EW, Shannon M. The serotonin syndrome. NEJM. 2005;352:1112-1120.
- Strawn JR, et al. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164:870-876.
- Hoffman RS, et al. Goldfrank's Toxicologic Emergencies. 11th ed. McGraw-Hill; 2019.
