Toxidromes and approach to the poisoned patient

• Poisoning is a dynamic illness: most patients recover with supportive care, but the first hour is about airway, breathing, circulation, glucose, temperature and a few specific antidotes.
• Most poisonings fit a recognisable toxidrome: cholinergic, anticholinergic, sympathomimetic, opioid, sedative-hypnotic, serotonin syndrome or neuroleptic malignant syndrome.
• An electrocardiogram, arterial blood gas, urea and electrolytes, glucose and measured osmolality are the early tests that change management; a 12-lead ECG is mandatory in significant poisoning.
• Activated charcoal at 50 g by mouth in adults helps only for adsorbable drugs, best within about 2 hours, and is not used for acids, alkalis, alcohols, ions or metals. ^[2]
• Urine alkalinisation, multiple-dose charcoal and haemodialysis are the main tools for removing drug that is already absorbed.
• Always take advice from a poisons service: in the UK that means TOXBASE first, then the National Poisons Information Service by telephone for severe or complex cases.

By the end of this page you should be able to:

1. Run a systematic primary survey on a poisoned patient and stabilise airway, breathing, circulation, disability and exposure.
2. Take a toxicology history that identifies the agent, the dose, the time and the patient factors that matter.
3. Recognise the seven major toxidromes from their clinical features and separate serotonin syndrome from neuroleptic malignant syndrome.
4. Use the 12-lead ECG, the anion gap and the osmolar gap to detect life-threatening poisoning and its complications.
5. Choose the right decontamination and enhanced elimination method for the exposure, and know when it does not help.
6. Know when and how to seek national poisons service advice and when transfer or critical care is needed.

This page draws on the 2007 edition of Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose (chapter 2A, covering the general approach, ECG, anion and osmolar gaps, fluid and vasopressor therapy, and decontamination), the 2023 Ghannoum and Roberts review of management of poisonings and intoxications, the UK National Poisons Information Service guidance available through TOXBASE (accessed 2026), World Health Organization advice on opioid overdose (updated 2025), the AACT/EAPCCT position statements on ipecac and gastric lavage (as summarised in the Haddad chapter), the 2019 serotonin syndrome review by Scotton and colleagues, and the 2015 neuroleptic malignant syndrome review by Tse and colleagues.

Poisoning is any clinical illness caused by a substance that is harmful. An overdose implies a toxic dose, whether accidental or intentional. The two terms are often used interchangeably once clinical effects appear. Poisoning has a bimodal pattern: it is most common in children aged 1 to 5 years and in elderly people, while intentional overdose and drug abuse mainly affect adults. ^[1]

Most patients with poisoning survive. The cornerstones are supportive care, a good history, recognition of the toxidrome, an ECG, and a small number of targeted interventions that are time-critical: activated charcoal, specific antidotes, and elimination enhancement for a short list of drugs. The AACT/EAPCCT position statements that underpin modern decontamination practice conclude that syrup of ipecac should not be given routinely and that gastric lavage should not be used routinely, if ever, in the management of poisoned patients. ^[1]

A poison has to be absorbed before it works, unless it is corrosive or a direct gut toxin. Poisoning therefore presents after absorption, and management divides into six phases: stabilisation, laboratory assessment, decontamination of the eyes, skin or gut, antidotes, enhanced elimination of the absorbed substance, and observation with disposition. ^[1]

Because overdose patients are often unstable when first seen, airway, ventilation, perfusion and all vital signs, including temperature, are stabilised first. Continuous cardiac and pulse oximetry monitoring is essential. ^[1]

Airway. Assess gag reflex, pooling of secretions and ability to protect the airway. Rapid-sequence intubation is indicated for many poisoned patients, including those with coma, airway soiling, apnoea, severe hypoxia, pulmonary oedema or seizures. Common clinical situations that may require intubation after poisoning include corrosive or inhaled caustic injury, envenomation, anaphylaxis, pulmonary oedema from opioids, bronchorrhoea from organophosphates, severe CNS depression, seizures, aspiration and hypercapnia. ^[1]

For any adult in coma, once intravenous access and blood tests are in place, naloxone 2 mg IV, thiamine 100 mg IV, and 50% dextrose 50 mL IV (if Dextrostix testing shows hypoglycaemia) are generally given. ^[1] This is the classic "coma cocktail" and it treats three reversible causes before a diagnosis is made.

Breathing. Give oxygen to correct hypoxia. Support ventilation, including intubation when needed. Opioids and sedatives depress respiration; organophosphates and nerve agents flood the airway with secretions and bronchospasm. ^{[1] [6]}

Circulation. Many toxins cause hypotension through reduced contractility, vasodilatation, fluid loss or acid-base disturbance. Volume expansion is first-line: adults receive up to 500 to 1000 mL boluses of isotonic fluid with reassessment after each bolus; children receive 10 to 40 mL per kilogram. ^[1] If blood pressure remains inadequate, add vasopressors (adrenaline, noradrenaline, dopamine, dobutamine, phenylephrine) by infusion, choosing the receptor profile that matches the toxin. Correct fluid and electrolyte disturbances, because these reduce arrhythmia. ^[1]

Disability. Record the level of consciousness with GCS or AVPU. Assess pupils, ocular movements, motor function and reflexes. Check glucose and treat hypoglycaemia. Seizures are common in poisoning and are managed first with airway, oxygenation, then benzodiazepines in full therapeutic doses, with phenytoin or a barbiturate if needed, and pyridoxine for isoniazid-induced seizures. ^{[1] [2]}

Exposure and temperature. Measure a core temperature. Hyperthermia occurs with salicylates, anticholinergics, monoamine oxidase inhibitors and dinitrophenol, and occasionally with phencyclidine, LSD or cocaine after seizures. Hypothermia is common with barbiturates, ethanol, carbamazepine, narcotics and phenothiazines, or after cold exposure. Remove the patient's clothing, look for needle tracks, bruises, burns, tongue biting and toxin residues, and decontaminate skin and eyes early. ^[1]

The primary goal of the history is to identify the toxic agent. When the patient is drowsy or mute, ask family or carers. ^[1] The five parts of a toxicology risk assessment are: what was taken, how much, for how long, who took it (age, weight, prior illness, genetics), and when. ^[2]

Useful questions include: ^[1]

• What substance, preparation and strength was it? How many tablets, capsules or millilitres?
• When was it taken, and over what time? Was it a single ingestion or repeated?
• Were there co-ingestants, alcohol or illicit drugs?
• Is there a suicide note, a previous attempt or recent life events?
• What prescription and over-the-counter medicines are in the house?
• Could this be therapeutic excess, a dosing error or an environmental or occupational exposure?
• For body stuffers or packers, ask about wrapped packets and abdominal pain.
• Ask about special diets, herbal or alternative medicines and performance enhancers.

Risk assessment runs in parallel with resuscitation and is refined as new information arrives. It predicts the likely clinical course and guides triage, antidotes, decontamination and observation. ^[2] Advice from a clinical toxicologist or poisons service is valuable and is recommended in most cases. ^[2]

A toxidrome is a group of signs and symptoms produced by a class of poisons, or by excess of a drug. Recognising one narrows the unknown exposure dramatically. The classic complexes are listed below. ^[1]

Organophosphates and carbamates inhibit acetylcholinesterase, causing an excess of acetylcholine at muscarinic and nicotinic receptors and in the CNS. The picture is often remembered by muscarinic effects such as salivation, lacrimation, urination, defaecation, gastric cramping and emesis, plus miosis, bronchorrhoea, bronchospasm, fasciculations and weakness. The leading cause of death is respiratory failure from bronchorrhoea and bronchospasm. ^[1]

The specific treatment is atropine to compete with acetylcholine at muscarinic receptors, given in doses that may have to become very large, plus pralidoxime (2-PAM) to reactivate acetylcholinesterase when nicotinic or central features are present. ^[1]

Anticholinergic drugs block muscarinic receptors. Patients are hot, dry, flushed and tachycardic, with dilated pupils, blurred vision, urinary retention and delirium, hallucinations or coma. Seizures and arrhythmias occur. Supportive care is usually enough; agitation that is difficult to control is the main therapeutic problem and is treated first with benzodiazepines. Physostigmine, a reversible acetylcholinesterase inhibitor, may be considered in selected severe cases, but it can cause seizures and bradycardia. ^[1]

Excess catecholamine activity produces heightened alertness, mydriasis, tachycardia, hypertension, sweating, agitation and hallucinations, with progression to increased muscle tone, hyperreflexia, delirium, hyperthermia, rhabdomyolysis, renal injury, coronary or cerebral ischaemia, seizures, metabolic acidosis and cardiovascular collapse. Cocaine, amphetamines, theophylline and caffeine are typical causes. ^[1]

The opioid triad is decreased level of consciousness, respiratory depression and pinpoint pupils. Other clues are slow or shallow breathing, cyanosis, track marks, hypothermia and hypotension. Pupils may dilate if hypoxia becomes severe, and some opioids cause midpoint pupils or mydriasis. ^{[1] [6]} WHO advises that naloxone is an antidote that reverses the effects of opioid overdose if given in time and has virtually no effect in people who have not taken opioids; first responders should focus on airway management, assisting ventilation and giving naloxone. ^[6] Naloxone doses in references run from 0.4 to 2.0 mg IV in adults and 0.01 to 0.1 mg per kilogram in children, with larger doses for synthetic or high-potency opioids; watch for non-cardiogenic pulmonary oedema. ^[1]

Isolated benzodiazepine overdose often produces CNS depression with normal or near-normal vital signs: slurred speech, ataxia, altered consciousness and sometimes hypotension and hypothermia. Respiratory depression is uncommon with benzodiazepines alone but becomes likely with ethanol or other depressants, which is what makes mixed overdoses dangerous. Barbiturates and other sedatives depress reflexes more and may cause coma, hypothermia and hypotension. ^[1] Supportive care, including airway protection and ventilation, is the main treatment; flumazenil reverses pure benzodiazepine effects but is reserved for selected cases. ^[1]

Serotonin syndrome (serotonin toxicity) is a dose-related spectrum of findings caused by increased serotonergic activity in the central and peripheral nervous systems. Symptoms usually begin within 24 hours of starting or adding a serotonergic drug, and most patients present within 6 hours. ^[4]

The classic triad is altered mental status (anxiety, agitation, confusion), autonomic overactivity (diaphoresis, tachycardia, hyperthermia, hypertension, vomiting, diarrhoea), and neuromuscular hyperactivity (tremor, myoclonus, clonus, hyperreflexia, muscle rigidity). Mild cases are normothermic; moderate cases have hyperthermia above 40 degrees C with eye movement abnormalities, agitation, pressured speech and hypervigilance; severe cases exceed 41.1 degrees C with autonomic instability, hyperactive bowel sounds, delirium and rigidity. Complications include seizures, rhabdomyolysis, metabolic acidosis, disseminated intravascular coagulation, renal failure, ARDS and death. ^[4]

Diagnosis is clinical and one useful framework is the Hunter Serotonin Toxicity Criteria, which depend on clonus (spontaneous, inducible or ocular), agitation, diaphoresis, tremor and hyperreflexia. Management is to stop all serotonergic drugs, then support airway, breathing and circulation, give benzodiazepines for agitation and muscle activity, cool the patient, and reserve serotonin antagonists such as cyproheptadine (initially 12 mg by mouth or via a nasogastric tube, then 2 mg every 2 hours until improvement) for cases not controlled by supportive care. Severe cases need paralysis, intubation and intensive care. Most cases resolve in 24 to 72 hours after the drug is stopped. ^[4]

NMS is a rare but life-threatening reaction to dopamine-blocking drugs, classically antipsychotics. It presents over hours to days with delirium, generalised symmetric rigidity, very high fever that responds poorly to antipyretics, and autonomic instability with tachycardia, labile blood pressure and profuse sweating (sometimes "greasy"). Creatine kinase is usually above 600 units per litre and leukocytosis is common. Onset is usually within 2 weeks of starting or changing the drug, and within 30 days in almost all cases. ^[5]

Management is to stop the offending drug, then provide aggressive supportive care: fluids, correction of electrolyte disturbance, cooling, and treatment of complications such as rhabdomyolysis and renal failure. Specific agents sometimes used are bromocriptine, starting at 2.5 mg three times daily and increasing up to 45 mg per day, and dantrolene 1 to 10 mg per kilogram intravenously (or 50 to 600 mg per day orally in milder cases). Evidence for these is limited and comes mainly from case series. Anticholinergic drugs and benzodiazepines are sometimes used. Resolution usually takes 3 to 14 days and mortality is around 10%. ^[5]

Both conditions cause fever, rigidity and autonomic disturbance, which makes them hard to separate. Clues that favour serotonin syndrome are a serotonergic drug history, rapid onset within 24 hours, lower-limb hyperreflexia and clonus, normal or only modestly raised creatine kinase, and diaphoresis with hyperactive bowel sounds. Features that favour NMS are antipsychotic or dopamine-withdrawal exposure, onset over days, stable high fever without chills, lead-pipe rigidity, creatine kinase usually above 600 units per litre (often very much higher), and no clonus. In practice both can overlap, and severe cases of either need the same priorities: stop the drug, support the airway and circulation, and control temperature and muscle activity. ^{[4] [5]}

A 12-lead ECG and continuous cardiac monitoring are essential for any significant poisoning. A widened QRS complex points to cyclic antidepressants and related drugs; a prolonged QT interval is seen with tricyclics, phenothiazines, haloperidol, quinidine and many others. ^[1]

• Widened QRS and sodium bicarbonate. Cardiac arrhythmias and conduction disturbances are treated by the usual resuscitation principles. If cyclic antidepressant overdose is suspected, intravenous sodium bicarbonate is indicated for ventricular arrhythmia or conduction disturbance. Sodium bicarbonate can also help other overdoses associated with QRS prolongation, such as diphenhydramine and cocaine. It is given if the QRS is 100 ms or wider, aiming for a serum pH of 7.45 to 7.55 without severe alkalosis. ^[1]
• Prolonged QT and torsades. Magnesium has a specific role in drug-induced QT prolongation, which can lead to torsades de pointes. ^[1]
• Other conduction clues. Prolonged PR interval suggests digoxin and other digitalis compounds, or lithium. Prolonged QRS also occurs with chloroquine, quinine, quinidine, diphenhydramine and plant cardiac glycosides. A prolonged QT list also includes arsenic, disopyramide, droperidol, erythromycin, pentamidine, phenothiazines, sotalol, thioridazine, and hypocalcaemia after hydrofluoric acid exposure. ^[1]
• Rhythm disturbances. Beta-blockers, calcium channel blockers, carbon monoxide, clonidine, cocaine and theophylline all cause rhythm disturbance. ^[1]
• Bradycardia and hypotension. Bradycardia is common after overdose of four classes: calcium channel blockers, beta-blockers, digitalis preparations and central alpha-2 agonists such as clonidine. ^[1]

Causes of a high-anion-gap metabolic acidosis in poisoning include alcoholic ketoacidosis, cyanide, diabetic ketoacidosis, ethylene glycol, iron, isoniazid, lactic acidosis, metformin, methanol, salicylates and uremia. ^[1]

Serum osmolality can be measured directly or calculated. With conventional units the formula is 2 times sodium (mEq per litre) plus BUN (mg per dL) divided by 2.8 plus glucose (mg per dL) divided by 18. In SI units it is simply 2 times sodium plus BUN plus glucose. Normal serum osmolality is 280 to 295 mOsm per litre. ^[1]

An osmolar gap exists when measured osmolality exceeds calculated osmolality by more than 10 mOsm per litre, suggesting an osmotically active substance that the formula does not account for. Common causes are hyperproteinemia, hyperlipidaemia, acetone, ethanol, ethylene glycol, isopropyl alcohol, methanol, propylene glycol, intravenous contrast and mannitol. ^[1] The most common cause of an osmolar gap is consumption of an alcohol. A substance contributes to osmolality only if it reaches high blood levels and has a low molecular weight. ^[1]

Molecular weights and contributions at 100 mg per dL are: methanol 32 daltons giving an osmolar gap of 31 mOsm per kg; ethanol 46 daltons giving 22; isopropyl alcohol 60 daltons giving 17; ethylene glycol 62 daltons giving 16. ^[1]

Interpretation in practice is that a high anion gap with (or without) a high osmolar gap suggests toxic alcohols. Extracorporeal treatment thresholds from specialist reviews include an anion gap above 23 mmol per litre for ethylene glycol and above 24 mmol per litre for methanol. ^[2]

Once the patient is stable, prevent further absorption.

Skin and eyes. Remove clothing, jewellery and shoes completely, then brush off solids before washing. Water or a solution chosen for the toxin is used; for most dermal exposures water is the main decontaminant. Eye irrigation is commonly 15 to 30 minutes. Particular toxins need specific measures, such as calcium gluconate gel for hydrofluoric acid. ^[1]

Gastrointestinal decontamination. The possible components are gastric evacuation, adsorbents and catharsis. ^[1]

• Ipecac. The AACT and EAPCCT concluded that syrup of ipecac should not be given routinely in the management of poisoned patients, because there is no evidence that it improves outcome. It has a narrow role only under poisons service direction. ^[1]
• Gastric lavage. Not routinely, if ever: the AACT and EAPCCT position statement says gastric lavage should not be employed routinely in the management of poisoned patients, and it requires an intact or protected airway, with aspiration risks. ^[1]
• Activated charcoal. This is the usual adsorbent. Dose is 50 g in adults, best given within about 2 hours of ingestion (exceptions include extended-release and enteric-coated preparations), and it is not effective for acids or alkalis, alcohols, ions or metals such as lithium and iron. A second 50 g dose may be given 2 to 4 hours later after large exposures. Multiple-dose activated charcoal at 25 g every 2 hours enhances elimination for selected drugs. An intact or protected airway is required. ^{[1] [2]}
• Whole bowel irrigation. Polyethylene glycol at 1 litre per hour by mouth or tube until rectal effluent is clear. Indications are exposures non-responsive to charcoal, extended-release formulations, body packers, and highly toxic ingestions. ^[2]
• Caution with aspiration risk. In patients with vomiting, altered consciousness or seizures, decontamination is given through a nasogastric or orogastric tube after the airway has been protected by intubation. ^[2]

For a few drugs that are already absorbed, clearance can be increased.

• Multiple-dose activated charcoal interrupts enterohepatic circulation and promotes gut dialysis; standard indication is carbamazepine, dapsone, phenobarbital, quinine and theophylline poisoning. ^[2]
• Urinary alkalinisation increases elimination of weak acids by ion trapping. Target urine pH is 7.5 to 8.5 with blood pH kept at or below 7.55. Sodium bicarbonate 100 mmol is given as a bolus, then 100 to 150 mmol per litre in 5% dextrose at up to 200 mL per hour. It is used most often for salicylates, and also for phenobarbital, chlorpropamide, methotrexate and certain herbicides and fluoride. Serum potassium should be at least 4 mmol per litre before starting. ^[2]
• Haemodialysis and related extracorporeal treatments are highly efficient removal methods for lithium, ethylene glycol, methanol, salicylates, theophylline and valproate (severe overdose), and for selected others. Choice depends on molecular weight, protein binding, volume of distribution and endogenous clearance; intermittent haemodialysis is generally preferred. ^{[1] [2]}
• Forced diuresis has little role now because of low efficacy and the risk of pulmonary oedema. ^[2]

Poisoning management is increasingly protocolised through national poisons services. In the UK the first port of call for health professionals is TOXBASE, the clinical toxicology database of the NPIS, with monographs covering more than 21,000 substances. Telephone advice from the NPIS is recommended for severe or complex poisoning, significant morbidity, uncertainty after consulting TOXBASE, or an unknown poison. Other UK resources include the BNF and BNF for Children treatment summaries, NICE Clinical Knowledge Summaries, and summaries of product characteristics. ^[3]

In the US, the American Association of Poison Control Centers operates a national poisons data system and poison centres provide round-the-clock advice; consultation with a poisons centre is recommended in most cases. ^{[1] [2]} WHO recommends that first responders in suspected opioid overdose focus on airway management, assisting ventilation and giving naloxone, and that naloxone be made available to people likely to witness an overdose with training. ^[6]

This topic is the front door: recognise, resuscitate and decide what needs removing. Agent-specific antidotes and their doses (N-acetylcysteine for paracetamol, naloxone for opioids, fomepizole or ethanol for toxic alcohols, atropine and pralidoxime for organophosphates, sodium bicarbonate for tricyclics, digoxin-specific antibody fragments, and the rest) are kept consistent with the companion topic on antidotes and management of poisonings, with doses matching standard emergency references such as the emergency antidote table in the Haddad chapter. ^[1]

• Stabilisation comes first: airway, breathing, circulation, disability, exposure and temperature.
• Naloxone 2 mg IV, thiamine 100 mg IV, and dextrose 50 mL of 50% IV if hypoglycaemic are the standard coma measures in adults.
• A toxicology history has five parts: what, how much, how, when and who.
• The seven key toxidromes are cholinergic, anticholinergic, opioid, sympathomimetic, sedative-hypnotic, serotonin syndrome and neuroleptic malignant syndrome.
• Opioid poisoning presents with decreased consciousness, respiratory depression and pinpoint pupils; naloxone reverses it.
• Serotonin syndrome usually begins within 24 hours of a serotonergic drug, with clonus, hyperreflexia and hyperthermia; severe cases exceed 41.1 degrees C. ^[4]
• NMS develops over days after a dopamine-blocking drug, with fever, lead-pipe rigidity, autonomic instability and creatine kinase usually above 600 units per litre.
• A 12-lead ECG is mandatory; sodium bicarbonate is used when a QRS is 100 ms or wider in cyclic antidepressant poisoning and other QRS-widening overdoses.
• A high anion gap points to lactic acidosis, ketosis, renal failure and specific toxins including methanol, ethylene glycol, salicylates, cyanide, iron and isoniazid.
• An osmolar gap above 10 mOsm per litre suggests an unmeasured osmotically active substance, most often an alcohol.
• Activated charcoal is 50 g by mouth in adults, best within about 2 hours, and useless for acids, alkalis, alcohols, ions and metals; it needs a protected airway.
• Urinary alkalinisation targets urine pH 7.5 to 8.5 with blood pH kept at or below 7.55; it is most used for salicylates.
• Ipecac and gastric lavage are not routine decontamination; rely on poison centre advice.
• In the UK consult TOXBASE first, then the NPIS by telephone for severe or complex cases.