Toxidromes and Approach to the Poisoned Patient

A toxidrome is a cluster of vital-sign, pupil, skin, bowel and neurologic findings that points to a class of poison. When the history is missing or wrong, the pattern is what you have. Extremely agitated patient? Drowsy patient? The pattern can point to the exposure before the labs come back. The classic toxidromes are opioid, sympathomimetic, serotonergic, antimuscarinic, muscarinic and nicotinic. Bradycardia with hypotension, knockdown, mushroom poisoning, neuroleptic malignant-like and uncoupler syndromes deserve careful thought too.

• Mechanism: each toxidrome comes from one receptor or transmitter system. Opioids hit mu receptors and depress the brainstem. Antimuscarinics block acetylcholine at muscarinic receptors. Organophosphates stop cholinesterase from clearing acetylcholine, so it piles up at muscarinic and nicotinic sites. Sympathomimetics turn up catecholamine effect. Serotonergic agents raise serotonin activity.
• Limits: a toxidrome is a pattern, not a diagnosis. Mixed ingestions blur the lines. Polysubstance use or advanced hypoxia can mask an opioid toxidrome.

Let the toxidrome pick the antidote and the monitoring. Then confirm with the history, the glucose and the ECG. A tricyclic antidepressant (TCA) overdose is its own high-risk pattern. It needs a QRS measurement.

Toxidrome Comparison

Serotonin Toxicity (Hunter Criteria)

The Hunter criteria only apply to a patient who has taken a serotonergic drug. In the derivation study, clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were what it took to predict serotonin toxicity accurately. Hypertonicity and a temperature above 38 °C were universal in life-threatening cases. The learning dataset, though, held no life-threatening cases, so these features were added. After a serotonergic exposure, any one of these five rule sets meets the criteria:

• Spontaneous clonus
• Inducible clonus plus agitation or diaphoresis
• Ocular clonus plus agitation or diaphoresis
• Tremor plus hyperreflexia
• Hypertonia plus temperature above 38 °C plus ocular or inducible clonus

A rigid, hot patient on a serotonergic drug needs urgent treatment. The rule output doesn't change that.

Toxins That Do Not Fit a Toxidrome

Some high-yield poisons never produce a classic toxidrome. When the pattern does not fit, check for these.

• Salicylate: expect tachypnea, tinnitus and a mixed respiratory alkalosis with metabolic acidosis. Check arterial gas and glucose.
• Carbon monoxide: headache, nausea and confusion. Pulse oximetry can read normal, so measure carboxyhemoglobin and give high-flow oxygen. Consider cyanide after smoke exposure.
• Cyanide: see hydroxocobalamin in the antidote matrix below.
• Toxic alcohols (methanol, ethylene glycol): look for an osmolar gap with an anion gap. Fomepizole per toxicology advice.
• Calcium channel or beta-blocker: bradycardia and hypotension. Calcium channel blockers also cause hyperglycemia. Glucagon and high-dose insulin per toxicology advice.
• Sulfonylurea: hypoglycemia that drags on for days and can come back. Give dextrose, repeat glucose checks and seek toxicology advice on octreotide.
• Clonidine and other alpha-2 agonists: miosis, bradycardia, hypotension and sedation.
• Acetaminophen: early symptoms are minimal. The treatment line depends on the level and the time since ingestion (see acetylcysteine).

Red Flags

• Respiratory depression or apnea with miosis: call it opioid toxicity until shown otherwise
• Seizures, wide QRS or ventricular dysrhythmia after a TCA ingestion. In a TCA overdose, a limb-lead QRS of 0.10 second or longer predicts seizures, and 0.16 second or longer predicts ventricular arrhythmias (one 49-patient study; a predictive aid, not a cut-off)
• Temperature above 38 °C with rigidity or clonus: serotonin toxicity or a sympathomimetic syndrome
• Bronchorrhea, bradycardia and hypotension with miosis: cholinergic toxicity. It is the same pattern you see in organophosphate poisoning

The ABCs come first: airway, breathing and circulation. Only then move on to the toxidrome signs, the glucose and the rhythm.

• Hypoglycemia: altered mental status with normal pupils. Check the glucose before you name a toxidrome.
• Hypoxia or intracranial injury: miosis disappears in advanced hypoxia. Pupil findings alone do not confirm an opioid toxidrome.
• Sepsis: fever and tachycardia without the clonus, mydriasis or dry skin that serotonin or antimuscarinic toxicity brings.
• Serotonin toxicity versus neuroleptic malignant syndrome: serotonin toxicity comes on after a serotonergic drug. Look for clonus and hyperreflexia, with onset usually within 24 hours. NMS comes on over days after an antipsychotic or other dopamine blocker. Look for bradyreflexia and lead-pipe rigidity.
• Antimuscarinic versus cholinergic: dry skin and mydriasis point to antimuscarinic. Diaphoresis, salivation and miosis point to cholinergic.

1. Scene and decontamination: confirm the scene is safe and wear protective gear for unknown or organophosphate exposure. Remove contaminated clothing and wash skin and hair (organophosphate label guidance).
2. Airway and oxygen: position for breathing and suction secretions. Provide bag-valve-mask ventilation for slow or absent breathing.
3. Naloxone: for an opioid toxidrome with breathing depression, ventilate and help the patient or bystander use the unit's naloxone per local protocol (IM, intranasal or IV routes by protocol). Pulseless? Start CPR first. Naloxone does not replace resuscitation. It can cause withdrawal, agitation or vomiting.
4. Glucose check: check and treat hypoglycemia per protocol.
5. Heat and seizures: cool a hyperthermic patient; protect from injury during seizures; do not restrain.
6. Collect and report: bring containers, pill counts and the time of ingestion. Call ALS early and report the toxidrome signs you saw.

Doses vary by protocol; follow local protocols and medical direction. The numbers below come from the label or from common protocol. For the current protocol, open the linked medication page.

• Naloxone (Paramedic/RN/CCT): adult 0.4–2 mg IV, IO or IM (the label also lists subcutaneous; intranasal per protocol), repeated every 2–3 min to adequate breathing. If there is no response after 10 mg, question the opioid diagnosis. Known physical dependence: titrate in small increments to breathing; full reversal can precipitate withdrawal (agitation, vomiting, pulmonary edema). Child: 0.1 mg/kg IV or IO (max 2 mg per dose), repeated every 2–3 min to breathing (dose per the Naloxone page; protocols vary). See Naloxone
• Atropine (Paramedic/RN/CCT): for organophosphate or muscarinic toxicity with bronchorrhea or bradycardia, give 1–2 mg IV or IO (2–3 mg per the Hospira label; 2–4 mg per the Protopam label), then repeat every 5 min and double the dose until secretions are dry, the chest is clear and the patient is not bradycardic or hypotensive. The Hospira label's 20–30 min interval is the slow label minimum. For severe poisoning it is too slow. Give oxygen, ventilation and atropine together. Don't hold back or delay atropine for hypoxia. Atropine does not treat nicotinic weakness. Child: 0.02 mg/kg IV or IO, then double every 5 min, with no fixed maximum (protocol-dependent). See Atropine
• Pralidoxime (ED/ICU; per protocol): organophosphate poisoning with weakness or respiratory depression, given with atropine. Adult 20–50 mg/kg IV (max 2,000 mg per dose; usually 1–2 g) over 15–30 min, followed by an infusion per protocol. Give over 15–30 min, not as a rapid push: rapid injection can cause tachycardia, laryngospasm, muscle rigidity or paralysis. Dose is reduced in renal insufficiency. Child 20–50 mg/kg IV (max 2,000 mg per dose). Not indicated for carbamate insecticides (label). See Pralidoxime
• Auto-injector (EMS, military): DuoDote combines atropine and pralidoxime in one IM device, for organophosphate nerve agents and insecticides in adults and children over 41 kg. Label dosing: one injection for mild symptoms (two or more mild symptoms); three injections in rapid succession into the mid-lateral thigh for severe symptoms. Carry it per local protocol; there is no E3 page for this product yet.
• Flumazenil (Paramedic/RN per protocol): suspected benzodiazepine overdose only, and not for routine use in undifferentiated coma. Adult 0.2 mg IV over 30 seconds, then 0.3 mg, then 0.5 mg at 1-minute intervals, cumulative maximum 3 mg. Label warning: seizures are most frequent in patients on long-term benzodiazepines (physical dependence), in patients with a seizure disorder, and in serious cyclic antidepressant or mixed overdose. Withhold it when there is serious cyclic antidepressant toxicity (twitching, rigidity, focal seizure, wide QRS, ventricular dysrhythmia, heart block). Do not use it after a benzodiazepine given for a life-threatening condition such as raised intracranial pressure or status epilepticus. It does not reverse opioids. Have airway equipment and seizure treatment ready. Monitor for resedation for up to 120 min. See Flumazenil
• Benzodiazepines (Paramedic/RN per protocol): first-line for seizures, agitation and sympathomimetic or serotonergic toxicity. Titrate to effect; see Lorazepam, Diazepam or Midazolam
• Sympathomimetic hypertension or tachyarrhythmia: benzodiazepines come first. Beta-blockers should not be given as monotherapy
• Opioid-associated arrest: CPR and ventilation come first. Naloxone can go in with ventilation for opioid-associated respiratory arrest (AHA 2025 Part 10), but it does not replace resuscitation. Keep running ACLS. Then apply the toxin-specific steps in this section (bicarbonate for sodium-channel blockers, atropine for organophosphates) per the toxicology sections of this page and local protocol
• Monitoring: cardiac monitor, 12-lead ECG, capnography when available, and point-of-care glucose; establish IV or IO access

Antidote Matrix

Physostigmine

Physostigmine reverses central antimuscarinic toxicity, but it is a medical toxicology decision, not a first-line drug for an agitated patient. Benzodiazepines and cooling come first. Keep atropine at the bedside for cholinergic effects. The imported Anticholium label (text revised July 2023) lists tricyclic antidepressant overdose among its indications, and it warns that acute cardiac arrest may occur with TCAs. That is why ECG monitoring is required. Avoid physostigmine when the QRS is 0.10 second or longer, or with conduction delay, bradycardia, dysrhythmia, or a likely TCA or mixed sodium-channel-blocker ingestion. Asystole has been reported after physostigmine given for TCA overdose. Per the label, it is also contraindicated after organophosphate or phosphoric acid ester poisoning, after depolarizing muscle relaxants, and with bronchial asthma, coronary heart disease, mechanical bowel or urinary obstruction, closed traumatic brain injury, barbiturate intoxication or hypersensitivity.

• Adult (imported label): 0.04 mg/kg (about 2 mg) IV, injected slowly at about 1 mg per minute (never as a rapid push); then 1–4 mg every 20 min if needed.
• Infant (imported label): 0.5 mg IV, repeated every 5 min to a total of 2 mg while anticholinergic signs persist and no cholinergic signs appear.

Other ED and ICU Care

• Sodium-channel toxicity (TCA): sodium bicarbonate 1–2 mEq/kg IV/IO bolus, repeated for persistent QRS widening (see Sodium Bicarbonate). A review of the clinical series notes dosing for this indication still needs clarifying, so follow local protocol. Aim for a serum pH of about 7.50–7.55, the target in the reviewed series. Correct hypokalemia. Avoid hyperventilation. Stay away from class I antiarrhythmics and phenytoin. Benzodiazepines treat seizures first. TCA cardiotoxicity can worsen within hours of ingestion. Keep the patient on the monitor and repeat the QRS.
• Unstable poisoned patient: hypotension gets fluids, then vasopressors per protocol. Seizure gets a benzodiazepine first, with airway support. Wide QRS or a ventricular dysrhythmia gets bicarbonate for sodium-channel toxicity. Refractory toxic cardiac arrest may need lipid emulsion or ECMO per toxicology advice.
• Decontamination: single-dose activated charcoal is not routine. Consider it with poison center advice, within about 1 hour of a potentially toxic ingestion, in a patient whose airway is protected. Not for caustics, hydrocarbons, metals, alcohols, or patients with an unprotected airway or bowel obstruction (AACT/EAPCCT position statement). Don't induce emesis with ipecac.
• Serotonin toxicity, severity: mild toxicity (tremor, clonus, agitation) is handled by stopping serotonergic drugs and giving benzodiazepines. Severe toxicity (temperature above about 41 °C, rigidity or shock) needs sedation, non-depolarizing paralysis and intubation. Avoid succinylcholine, because of hyperkalemia risk with rhabdomyolysis. Avoid physical restraint. It makes the heat worse. Cyproheptadine is an oral antidote, given per toxicology advice. No dose is listed here.
• Airway: intubate for loss of protective reflexes, persistent respiratory depression, or seizures with secretions. Organophosphate poisoning can need ventilation for a long time.
• Hyperthermia: cool actively from the outside. Acetaminophen and ibuprofen do little for toxin-induced hyperthermia.
• Re-narcotization: naloxone can wear off before some opioids do. Watch the patient after the last dose, and repeat naloxone as needed.
• Consult: call the poison center or a medical toxicologist early. It matters most with a TCA, an organophosphate or a mixed ingestion.

• EMS: transport any patient with a toxidrome sign that needs monitoring. Transport any patient who has received naloxone, atropine or a benzodiazepine too. Local protocol and medical direction set the release rules.
• Transport: keep cardiac and capnography monitoring running. Have naloxone, atropine and suction ready. Watch for sedation that returns, seizures and hyperthermia, and carry cooling supplies.
• Handoff: include the toxidrome signs, the time and dose of every antidote, the QRS width, the glucose, the temperature and any ingestion details.
• Flumazenil: don't give it in transit when TCA signs are present, when a seizure is likely, or when the benzodiazepine history is unknown. Document any dose and the response. Monitor for resedation.

• Pediatrics: use weight-based dosing and age-specific vital signs. Naloxone 0.1 mg/kg IV or IO (max 2 mg per dose), repeated to breathing (see Naloxone); protocol-dependent. Pralidoxime 20–50 mg/kg IV (max 2,000 mg per dose). Atropine for organophosphate poisoning 0.02 mg/kg IV or IO (label initial range 0.01–0.03 mg/kg), then double every 5 min to a clear chest and age-appropriate heart rate and blood pressure (protocol-dependent). Infants receive physostigmine 0.5 mg every 5 min up to 2 mg, with toxicology input. One pill of a sulfonylurea, opioid or TCA can be fatal in a small child. Check the glucose, watch for hypoglycemia and call the poison center. Hydroxocobalamin 70 mg/kg has been used outside the US. US labeling says safety and effectiveness are not established in children. See weight-based dosing and pediatric vital signs.
• Pregnancy: treat the mother first. Don't hold back antidotes because of fetal concerns. The atropine label says life-sustaining therapy should not be withheld for fear of fetal effects. It also says severe muscarinic poisoning in pregnancy is a medical emergency. Give naloxone to a pregnant patient with opioid toxicity. Physostigmine is used in pregnancy only when absolutely necessary. Call the poison center and obstetrics early.
• Older Adults: expect more anticholinergic drug burden and more benzodiazepine sensitivity. Check the Beers criteria for anticholinergic burden. Antimuscarinic delirium and conduction disease are more likely. Monitor for arrhythmia after atropine and for hypotension with sympathomimetic toxicity.
• Patients on Serotonergic Drugs: stop all serotonergic drugs. Avoid methylene blue in this setting. Its label carries a boxed warning for serotonin syndrome with serotonergic drugs and opioids.
• Renal Impairment: pralidoxime leaves the body in the urine, so renal insufficiency calls for a lower dose (label). Dose other antidotes by protocol and monitor the response.
• Hepatic Impairment: no specific adjustment is established for the agents in this table. Dose by protocol and monitor the response.

• Error: naming a toxidrome without a glucose check. Hypoglycemia mimics intoxication. Treat the wrong cause and the right treatment waits.
• Error: giving flumazenil in a mixed or TCA overdose, to a patient on long-term benzodiazepines or with a seizure disorder, or empirically to an undifferentiated comatose patient. The label warns about seizures. It says flumazenil has no known benefit in a seriously ill mixed overdose except reversing sedation. It does not reverse opioids.
• Error: giving physostigmine with a wide QRS, conduction delay or dysrhythmia, with a possible TCA or mixed sodium-channel-blocker overdose, or after organophosphate poisoning. Asystole has followed physostigmine in TCA overdose. The label requires continuous ECG monitoring for TCA use.
• Error: withholding or delaying atropine in organophosphate bronchorrhea because of hypoxia. Give oxygen and ventilation at the same time as atropine. The Protopam label says to give atropine as soon as hypoxemia is improved. It also warns about atropine-induced ventricular fibrillation in significant hypoxia. That warning has to be weighed against the secretions atropine treats. Decide with medical direction.
• Error: stopping naloxone after one dose or after a single good response. Repeat as needed and watch for re-narcotization.
• Error: giving a beta-blocker as monotherapy for sympathomimetic toxicity. Benzodiazepines come first.
• Error: pushing pralidoxime too fast. Rapid injection can cause tachycardia, laryngospasm, muscle rigidity or paralysis. Give it over 15–30 minutes.