Poisoning Overview & Toxidromes

Meet the patient

A 24-year-old is brought unconscious to the emergency department at midnight. Her pupils are 1 mm, her respiratory rate is 6, and there are needle-track marks on her arm. The paramedics found empty blister packs beside her and a bottle of paracetamol.[1]

Two traps are already live. The first is the opioid — pinpoint pupils and a slow respiratory rate mean naloxone, titrated to the respiratory rate and not to full consciousness. The second is the paracetamol she may not even remember taking, whose hepatotoxicity peaks a day from now and is silent until then. Everything below exists to run the four layers in order, to read the toxidrome in seconds, and to send a paracetamol level on every overdose regardless of the history.[1][2]

Four layers, in order — never out of order

Resuscitation precedes diagnosis and is the most heavily examined single step in the topic. Every poisoned patient gets the same first move — ABCDE — which finds and fixes the immediate threats of airway obstruction, hypoxia, hypotension, hypoglycaemia and seizures. Only once the patient is stable does the focused toxicological assessment begin: the history of what, when, how much, by what route, and with what co-ingestants, the examination for the toxidrome, and the targeted investigations.[1]

The four layers that follow resuscitation are decontamination, enhanced elimination, antidotes, and supportive care — each applied only when the indication is met, because over-treatment is harmful. Universal charcoal, routine ipecac, and abandoning dialysis thresholds all cost lives. The single highest-yield factual recall in toxicology is the antidote table, and the single most dangerous cognitive error is assuming a coma is toxic before checking the glucose.[1][2]

How common, and which agents kill where

Poisoning is among the commonest emergencies in medicine and in examinations, and the agent that kills is profoundly region-dependent. The WHO estimates over 800,000 suicide deaths a year, and pesticide self-poisoning is the single most common means in low- and middle-income countries. In India, organophosphate and aluminium phosphide ingestion dominate the toxicology caseload; in high-income countries, paracetamol, opioids and psychiatric medications lead.[1]

[1]

The region matters for the viva. In high-income countries the top adult agents are paracetamol, NSAIDs, benzodiazepines, antidepressants, opioids, cardiovascular drugs and antipsychotics, and in under-fives the household products, cosmetics, button batteries, paracetamol and iron. In Australia and New Zealand, paracetamol and benzodiazepines dominate the in-hospital caseload while snake and spider envenomation drive the out-of-hospital mortality. In the United Kingdom, the legislated 1998 pack-size restriction cut fatal paracetamol overdose and severe hepatotoxicity by about 40 per cent. In India and South Asia, organophosphates and carbamates, aluminium phosphide, oleander, copper sulphate and corrosives dominate, and aluminium phosphide carries 50 to 90 per cent mortality from refractory phosphine-induced cardiogenic shock.[1][2]

The risk factors for a severe outcome are very young or old age, polypharmacy with a co-ingestant in more than half, delayed presentation, pre-existing cardiac, hepatic or renal disease, pregnancy, and an agent with a narrow therapeutic index — digoxin, lithium, warfarin, insulin, theophylline, methotrexate.[1]

The six toxidromes — read the pupils, skin, temperature and reflexes

A toxidrome is a constellation of autonomic, ocular, dermal, neurological and cardiorespiratory signs produced by a class of poisons acting on a common receptor or pathway. It is the bedside shortcut that narrows an infinite differential to a handful of toxin classes within seconds, often before any laboratory result is back.[1]

Classify poisoning along three independent axes — by intent, by tempo, and by the toxidrome produced — and the third axis is the one that drives bedside management. The agent-specific classifications (paracetamol, salicylate, organophosphate, tricyclic, opioid, toxic alcohol, carbon monoxide, lead) each have their own topic; this chapter is the general framework that precedes them.[1]

The receptor signatures of the five autonomic toxidromes are the viva core. Sympathomimetic agonism (cocaine, amphetamines, MDMA, pseudoephedrine) gives mydriasis, tachycardia, hypertension, hyperthermia and diaphoresis. Anticholinergic muscarinic blockade (atropine, antihistamines, tricyclics, Jimson weed) gives the dry-hot-blind-mad-red-retained picture. Cholinergic acetylcholinesterase inhibition (organophosphates, carbamates, nerve agents) gives DUMBELSS — miosis, bronchorrhoea, bronchospasm, salivation, lacrimation, sweating. Opioid mu-receptor agonism gives pinpoint pupils, respiratory depression and hyporeflexia. Serotonergic excess gives clonus and hyperreflexia.[1]

[1]

What the poison does — toxicokinetics and toxicodynamics

The clinical effect of a poison is the integrated result of toxicokinetics — what the body does to the poison — and toxicodynamics — what the poison does to the body. Examiners probe both, and one number above all decides whether dialysis will work: the volume of distribution.[1]

Absorption depends on route — oral is slowest and most variable, inhalational and intravenous are fastest, dermal is slow but significant for organophosphates and solvents — and first-pass hepatic metabolism reduces the oral bioavailability of many drugs. Distribution is governed by the volume of distribution: a drug with a large volume, such as digoxin at 7 L/kg, amiodarone at 60 L/kg, or the tricyclics at 10 to 20 L/kg, distributes widely into tissue and is poorly removed by haemodialysis; a drug with a small volume, such as lithium at 0.8 L/kg, salicylate at 0.2 to 0.6 L/kg, or methanol and ethylene glycol at 0.6 L/kg, stays in the plasma-water compartment and is dialysable. Highly protein-bound drugs — warfarin, phenytoin, valproate — are not dialysable until binding is saturated.[1]

Biotransformation occurs overwhelmingly in the liver in two phases. Phase I, mostly CYP450 oxidation, reduction and hydrolysis, may produce active metabolites — codeine to morphine via CYP2D6, paracetamol to NAPQI via CYP2E1, methanol to formaldehyde and formic acid via alcohol dehydrogenase, ethylene glycol to glycolate and oxalate. Phase II conjugation — glucuronidation, sulfation, glutathione, glycine, acetylation — almost always produces inactive, water-soluble metabolites. Elimination is renal for lithium, salicylate and digoxin, biliary for digoxin and lead, and pulmonary for the volatiles — ethanol, methanol, chloroform, inhaled anaesthetics, carbon monoxide.[1]

First-order versus zero-order kinetics is heavily examined. In first-order kinetics a constant fraction of the drug is eliminated per unit time, the concentration falls exponentially, and a half-life is meaningful — most drugs within the therapeutic range. In zero-order or saturation kinetics a constant amount is eliminated per unit time because the metabolising enzyme is saturated, so small dose increments produce large and unpredictable rises and the apparent half-life lengthens with the dose. The classic saturable drugs are ethanol, phenytoin, salicylate at high dose, theophylline and voriconazole — which is why salicylate toxicity worsens disproportionately as the dose rises.[1]

The cellular mechanisms of organ injury

Beyond the autonomic toxidromes, toxins damage organs through several distinct mechanisms that examiners probe. Direct tissue injury comes from corrosives, paraquat and hydrocarbons; mitochondrial toxicity from cyanide, salicylate, metformin and the antiretrovirals; receptor blockade from the beta-blockers, calcium-channel blockers and opioids; enzyme inhibition from the organophosphates, methotrexate and cyanide; oxidative stress from iron, paracetamol's NAPQI and carbon tetrachloride; and ion-channel effects from the tricyclics, digoxin and the local anaesthetics.[1]

The dose-response curve is sigmoid, with the NOAEL, the LOAEL, and the LD50 as landmarks. The therapeutic index is the ratio of the toxic dose to the effective dose, and a narrow index — digoxin, lithium, warfarin, insulin, theophylline, methotrexate — means small dose increments are dangerous and these drugs carry disproportionate mortality in overdose.[1]

Resuscitation — ABCDE and the coma cocktail

Phase one is resuscitation, performed before any diagnostic effort. Address the airway — intubate early if the GCS is under 8, secretions are copious in organophosphate poisoning, or protective reflexes are lost. Address breathing — high-flow oxygen for hypoxia and ventilation for respiratory failure, avoiding unnecessary oxygen in paraquat. Address circulation with IV fluids for hypotension and noradrenaline for refractory shock, treating the cause — sodium bicarbonate for tricyclic cardiotoxicity, calcium for the calcium-channel blocker, glucagon for the beta-blocker. In disability, check the capillary glucose at the bedside in every coma and give a naloxone trial for pinpoint pupils or respiratory depression; in exposure, remove contaminated clothing, do a full skin wash for organophosphate or corrosive exposure, and take a core temperature.[1]

The empirical coma cocktail is DONT — dextrose, oxygen, naloxone, thiamine — given to any coma of unknown cause while the results are awaited. Give thiamine 100 mg IV before the dextrose bolus in any chronic alcoholic, malnourished patient or known Wernicke risk, because glucose alone can precipitate Wernicke encephalopathy in a thiamine-deficient patient. Titrate naloxone — give 0.04 mg first in the opioid-tolerant to avoid precipitated withdrawal and acute pulmonary oedema, then escalate to 0.4 mg, then 2 mg, to a total of 10 mg, targeting a respiratory rate over 12 rather than full consciousness.[1]

[1] [1] [1]

Sodium bicarbonate for the widened QRS

A QRS over 120 ms after a tricyclic, cocaine, class I antiarrhythmic or other sodium-channel blocker is a medical emergency. Give IV sodium bicarbonate 8.4 per cent as a bolus of 1 to 2 mEq/kg — 50 to 100 mL of 8.4 per cent in the adult — repeated to a maximum of 3 mEq/kg, titrated to a narrowing of the QRS and a plasma pH of 7.45 to 7.55, followed by an infusion if dysrhythmia recurs. Hyperventilation to the same pH is an adjunct. Avoid the class Ia, Ic and III antiarrhythmics, which prolong the QRS or QT, avoid flumazenil for the seizure risk, and treat ventricular dysrhythmia refractory to bicarbonate with lipid emulsion.[1][7]

Seizures and hyperthermia

Treat seizures first-line with a benzodiazepine — IV lorazepam 4 mg or diazepam 10 mg — and avoid phenytoin in tricyclic overdose because it is itself a sodium-channel blocker. Treat hyperthermia with active cooling and benzodiazepines to reduce muscle activity, and reach for the specific antidote — cyproheptadine for serotonin syndrome, dantrolene for malignant hyperthermia and severe neuroleptic malignant syndrome.[1]

Decontamination — the first pillar

Beyond resuscitation, definitive management has four pillars — decontamination, enhanced elimination, antidotes and supportive care — and each is applied only when the indication is met. The position papers of the AACT and the EAPCCT are the evidence backbone for decontamination, and they have retired several once-popular manoeuvres.[1]

[1] [3] [4] [5] [6]

The single-dose charcoal position paper (Chyka 2005) recommends it within an hour of a potentially toxic ingestion; the 2021 systematic review (Hoegberg) confirmed a modest reduction in absorption but noted that benefit falls with delayed presentation, so routine use has declined. Whole-bowel irrigation (Thanacoody 2015) has narrow indications, and ipecac (Hojer 2013) is no longer recommended.[3][4][5][6]

Enhanced elimination — the second pillar

Three techniques enhance elimination, and the dialysability of the toxin turns on the volume of distribution. Urine alkalinisation, haemodialysis, and multi-dose charcoal each have a defined indication.[1]

Urine alkalinisation with IV sodium bicarbonate to a urinary pH above 7.5 ion-traps the weak acid salicylate in the renal tubule and increases its excretion 10- to 20-fold — replace potassium first, because hypokalaemia prevents alkalinisation. Haemodialysis is effective only for small-volume, low-protein-bound, low-molecular-weight toxins, and the dialysable poisons cluster into one mnemonic. Multi-dose charcoal, already described under decontamination, is also an enhanced-elimination technique for carbamazepine, dapsone, phenobarbital, theophylline and quinine.[1][2]

[1] [1]

The EXTRIP workgroup issues toxin-specific recommendations on haemodialysis and haemoperfusion for lithium, salicylate, metformin, methanol, ethylene glycol, valproate, carbamazepine, theophylline, phenytoin and digoxin — the last not dialysable, where Fab is the answer.[2]

Antidotes — the third pillar

The antidote table is the single highest-yield piece of factual recall in toxicology, reproduced exactly — agent, dose, indication. Know the dose and the one contraindication that turns each antidote into a poison.[1]

[1] [1] [7]

The investigations that change the plan

Run the mandatory panel on every overdose, then the targeted levels, then the two gap calculations and the paracetamol nomogram. The bedside set is capillary glucose in every coma and every seizure, a 12-lead ECG in every symptomatic overdose, a urine pregnancy test in every woman of childbearing age, pulse oximetry and temperature. The bloods are urea, electrolytes, creatinine, liver function, coagulation, a venous gas for pH, bicarbonate, lactate, anion gap and osmolal gap, creatine kinase for rhabdomyolysis, and the specific drug levels — paracetamol always at 4 hours, salicylate when suspected, lithium, digoxin in any unexplained bradycardia or hyperkalaemia, iron, theophylline, valproate, methotrexate, and the toxic alcohols.[1]

The ECG is the single most useful investigation in the symptomatic overdose. A QRS over 120 ms in a wide-complex tachydysrhythmia or after a sodium-channel-blocker ingestion is the trigger for IV sodium bicarbonate; a QTc over 470 ms in men or 480 ms in women, high-risk over 500 ms, mandates monitoring and electrolyte correction; and a bradyarrhythmia with hyperkalaemia in a patient on digoxin means acute digoxin toxicity and digoxin Fab. An abdominal X-ray finds the radiopaque toxins — iron, lead, lithium, potassium, enteric-coated and sustained-release preparations — and decides whole-bowel irrigation.[1]

The two gap calculations are central to toxicological reasoning. The anion gap, calculated as sodium plus potassium minus chloride plus bicarbonate, with a normal range of 8 to 12 mmol/L, points a high-anion-gap metabolic acidosis to MUDPILES — methanol, uraemia, diabetic or alcoholic ketoacidosis, propylene glycol or paraldehyde, iron or isoniazid, lactic acidosis, ethylene glycol, salicylates. The osmolal gap, measured minus calculated osmolality with calculated as twice sodium plus glucose plus urea, is raised above 10 mOsm/kg by an unmeasured osmotically active solute — methanol, ethanol, ethylene glycol, isopropanol — and the combination of a high anion gap with a high osmolal gap is highly specific for a toxic alcohol.[1][9]

The paracetamol nomogram decides the antidote. Plot a 4-hour post-ingestion level on the Rumack-Matthew nomogram; a level above the treatment line, starting at 100 mg/L at 4 hours and declining with a 4-hour half-life to zero at 24 hours, triggers N-acetylcysteine. The nomogram is not valid in repeated or staggered ingestion, unknown time of ingestion, extended-release or modified-release formulations, or chronic supratherapeutic ingestion — in each, treat empirically.[1]

The mimics — and the discriminator that ends each

The poisoned patient rarely arrives with a reliable label, so the differential is built around the dominant clinical feature — coma, hyperthermia, metabolic acidosis, a wide QRS — with the toxidrome one of several explanations. The most dangerous trap is to assume a coma is toxic before checking the glucose.[1]

Every coma gets a bedside glucose and a naloxone trial, but the examiner expects you to also exclude hypoglycaemia — the commonest reversible cause — a post-ictal state, intracranial haemorrhage or stroke, CNS infection, septic encephalopathy, hepatic or uraemic encephalopathy, and electrolyte disturbance such as hyponatraemia or hypercalcaemia. A high anion-gap metabolic acidosis with a raised osmolal gap is highly specific for a toxic alcohol, and is separated from alcoholic ketoacidosis, lactic acidosis and sepsis by the dual gap and the organ-specific clue.[1][9]

The three hyperthermia syndromes — the most examined differential

Serotonin syndrome, neuroleptic malignant syndrome and malignant hyperthermia share clonus, rigidity and fever but the antidote differs, so the discriminator is the onset and the reflexes.[1]

[1] [8]

The Hunter Serotonin Toxicity Criteria (Dunkley 2003) are more sensitive and specific than the older Sternbach criteria. Diagnosis requires a serotonergic agent in the preceding five days plus any one of: spontaneous clonus; inducible clonus plus agitation and diaphoresis; ocular clonus plus agitation and diaphoresis; tremor plus hyperreflexia; or hypertonia with a temperature above 38 degrees and ocular or inducible clonus.[8]

The agent-specific first response — in one line each

The framework applies differently to each major agent, and the modified first response is summarised here — each agent has a dedicated topic for the full depth. Know the one-line pivot for each.[1]

Paracetamol saturates conjugation and shunts through CYP2E1 to NAPQI, which depletes glutathione and causes centrilobular zone-3 necrosis; plot a 4-hour level on the Rumack-Matthew nomogram and give N-acetylcysteine if above the line, with near-100 per cent protection within 8 hours. Salicylate uncouples oxidative phosphorylation and stimulates the respiratory centre, giving the mixed respiratory alkalosis with high-anion-gap metabolic acidosis; treat severe toxicity with urine alkalinisation and haemodialysis, and watch for rebound after dialysis stops. Organophosphates inhibit acetylcholinesterase for the DUMBELSS toxidrome; decontaminate, give atropine titrated to drying of secretions, and pralidoxime before the enzyme ages.[1][10]

Tricyclic antidepressants cause fast sodium-channel blockade with QRS widening — over 100 ms predicts seizures, over 160 ms predicts ventricular dysrhythmia — treated with IV sodium bicarbonate to a pH of 7.45 to 7.55 and lipid emulsion for refractory collapse. Toxic alcohols are metabolised by alcohol dehydrogenase to formic acid or oxalate, giving a high anion gap with a high osmolal gap; block the enzyme with fomepizole, add dialysis and the cofactors — folate for methanol, thiamine and pyridoxine for ethylene glycol. Carbon monoxide binds haemoglobin with 240-fold greater affinity than oxygen and left-shifts the dissociation curve; treat with 100 per cent oxygen to cut the carboxyhaemoglobin half-life, and hyperbaric oxygen for syncope, coma, seizure, pregnancy, cardiac ischaemia or a high level.[1][9]

Opioids give pinpoint pupils and respiratory depression; titrate naloxone to the respiratory rate and plan an infusion for the long-acting agents. Body-packers swallow professionally wrapped packets for smuggling and packet rupture is lethal; whole-bowel irrigation with polyethylene glycol, surgical removal for obstruction or rupture, and antidote readiness — naloxone for heroin, N-acetylcysteine for paracetamol.[1]

The preventable deaths — pitfalls that recur

The recurring, examiner-favoured errors trace to a short list, and most are preventable. Failing to check paracetamol and salicylate levels in every overdose regardless of history is the leading one, because covert or forgotten co-ingestion is common and paracetamol has a window for the antidote. Giving flumazenil in a mixed overdose or tricyclic co-ingestion provokes refractory seizures; using the disodium EDTA salt instead of calcium disodium EDTA for lead causes fatal hypocalcaemia; and misreading the Rumack-Matthew nomogram in staggered, repeated or unknown-time ingestion — always treat empirically in these cases.[1]

The treatment pitfalls close the list. Giving amiodarone or procainamide for a tricyclic-induced wide-complex tachycardia prolongs the QRS or QT and worsens cardiotoxicity — use sodium bicarbonate. Using phenytoin for tricyclic seizures worsens cardiotoxicity because it is itself a sodium-channel blocker — use benzodiazepines. Administering succinylcholine in organophosphate poisoning produces prolonged paralysis because butyrylcholinesterase is inhibited — use rocuronium. Stopping urine alkalinisation too early in salicylate toxicity allows rebound redistribution — continue until levels and symptoms resolve. And missing an alternative diagnosis — the unexplained coma is intracranial haemorrhage, sepsis, hypoglycaemia or CNS infection until proven otherwise.[1][10]

[1]

Prognosis and disposition

Outcome is set by the toxicity and dose per kilogram, the time to presentation, the co-ingestants, the age and comorbidity, and the availability of antidote and dialysis. Aluminium phosphide carries 50 to 90 per cent mortality; paracetamol under 1 per cent with N-acetylcysteine within 8 hours; organophosphate 10 to 20 per cent even with full antidote and ICU; and toxic alcohols are good with early fomepizole but grave with severe acidosis at presentation, methanol leaving permanent blindness.[1][2]

[1] [1]

Disposition follows the agent and the severity. Discharge within 6 hours is safe for an asymptomatic patient with a low-toxicity agent, no sustained-release preparation, no delayed-toxicity agent, and psychiatric assessment done. The inpatient ward is for the symptomatic but stable under observation beyond 6 hours. HDU or ICU is for airway compromise, seizures, arrhythmia, hypotension, a QRS over 120 ms, the need for an infusion — atropine, naloxone, N-acetylcysteine, insulin euglycaemia, lipid — the need for dialysis, or a declining GCS. Every intentional overdose receives a psychiatric assessment before discharge.[1]

Special populations

In children, weight-based dosing of every antidote is the rule, and under-dosing is the classic error. Naloxone is 0.1 mg/kg up to 2 mg, N-acetylcysteine 150 mg/kg over 1 h then 50 mg/kg over 4 h then 100 mg/kg over 16 h, atropine 0.02 to 0.05 mg/kg with a minimum of 0.1 mg to avoid paradoxical bradycardia, and succimer 10 mg/kg every 8 h for 5 days then every 12 h for 14 days. Avoid ipecac, lower the threshold for whole-bowel irrigation in iron, lithium and sustained-release ingestion, and suspect non-accidental injury or neglect in any paediatric presentation.[1]

In pregnancy, stabilise the mother first — the best fetal resuscitation is maternal resuscitation. Most antidotes are safe: N-acetylcysteine crosses the placenta and protects the fetal liver; naloxone and atropine are safe; fomepizole has limited data but is used when indicated. Methylene blue is a relative contraindication for the historical association with haemolysis and methaemoglobinaemia in the G6PD-deficient fetus. Consider the teratogenic potential of the agent itself — isotretinoin, warfarin embryopathy, ACE inhibitors, methotrexate, lithium with Ebstein anomaly, sodium valproate with neural tube defects.[1]

The elderly have reduced renal and hepatic clearance that increases toxicity at lower doses, comorbidities that compound the effect, drug interactions that are common, and a blunted autonomic response — no tachycardia in an anticholinergic overdose in a patient on a beta-blocker. The high-risk agents are digoxin, warfarin, insulin, metformin, opioids and benzodiazepines; use a low threshold for admission and a longer observation. The chronic polypharmacy patient is at risk of serotonin syndrome, QT prolongation, anticholinergic load, and CYP interactions — always reconcile the medication list before discharge.[1]

Evidence, guidelines, and regional practice

The AACT and EAPCCT position papers are the evidence backbone for decontamination. Single-dose charcoal within an hour (Chyka 2005), the 2021 systematic review confirming modest benefit that falls with delayed presentation (Hoegberg), whole-bowel irrigation with narrow indications (Thanacoody 2015), and ipecac no longer recommended (Hojer 2013) frame modern practice. The EXTRIP workgroup guides extracorporeal treatment by toxin, and the ASRA practice advisory (Neal 2018) standardised lipid emulsion for local-anaesthetic systemic toxicity and its off-label extension to other lipophilic-drug cardiotoxicities.[3][4][5][6][7]

Regionally, India and South Asia run on atropine 2 mg IV every 10 to 15 min until drying of secretions, early pralidoxime before aging, and aggressive supportive ICU care, with the NIMHANS and AIIMS protocols as local references; aluminium phosphide has no antidote and is managed supportively. Australia and New Zealand use the eTG and NSW Poisoning Guidelines with species-specific antivenom. The United Kingdom uses TOXBASE as the bedside reference and the NICE mandate for psychosocial assessment before discharge. The United States runs on the AACT guidelines and the regional Poison Control Centres, with the fentanyl epidemic driving bystander naloxone distribution and very high cumulative doses. The ACMT position statement on antidote cost (Mazer-Amirshahi 2018) highlights that several life-saving antidotes — fomepizole, digoxin Fab, Crotalidae antivenom — have become prohibitively expensive, threatening access.[1][11]

The live controversies are routine ipecac and home charcoal, both abandoned; the NAC protocols — the 21-hour Prescott 300 mg/kg versus the 12-hour modified two-bag 200 mg/kg; hyperbaric oxygen for carbon monoxide, where Weaver 2002 showed benefit and a 2017 trial did not, reserving it for severe cases; and high-dose insulin euglycaemia for calcium-channel-blocker and beta-blocker overdose, an emerging standard with debated dose and timing.[1]

[1]

Ward-round test — four stems

Stem 1 — the unconscious patient with pinpoint pupils (answer)

A 24-year-old is unconscious with 1 mm pupils, a respiratory rate of 6, and needle-track marks. What is the toxidrome, the bedside test, and the treatment? Model: This is the opioid toxidrome — pinpoint pupils with respiratory depression and coma. Check a capillary glucose at the bedside first to exclude hypoglycaemia, then give naloxone 0.04 to 0.4 mg IV titrated to a respiratory rate over 12 per minute — not to full consciousness, which precipitates withdrawal. If a long-acting opioid such as methadone or fentanyl is suspected, start a naloxone infusion at two-thirds of the effective bolus per hour. Send a paracetamol and salicylate level regardless of the history, because co-ingestion is the rule, and arrange psychiatric assessment once the patient is medically stable.[1]

Stem 2 — agitation, mydriasis and ankle clonus at a party (answer)

A 19-year-old is agitated with mydriasis, heart rate 140, blood pressure 180 over 100, temperature 39.2, profuse sweating, and inducible clonus at the ankle, after taking something at a party. What is the most likely toxidrome, and what finding distinguishes it from the mimics? Model: This is serotonin syndrome — the clonus and hyperreflexia with serotonergic exposure meet the Hunter criteria, and the inducible ankle clonus is the single most specific bedside finding. It is distinguished from the sympathomimetic picture, which has no clonus, from neuroleptic malignant syndrome, which has lead-pipe rigidity and bradyreflexia over days, and from malignant hyperthermia, which follows an anaesthetic. Stop the serotonergic agent, give benzodiazepines and active cooling, and give cyproheptadine 12 mg then 2 mg every 2 h to 32 mg per 24 h.[1][8]

Stem 3 — a wide QRS after a tricyclic overdose (answer)

A patient who took amitriptyline has a QRS of 150 ms and a wide-complex tachycardia. What is the treatment, and what two drugs must you avoid? Model: This is fast sodium-channel blockade from the tricyclic — a QRS over 120 ms is the trigger. Give IV sodium bicarbonate 8.4 per cent, 1 to 2 mEq/kg as a bolus repeated to a maximum of 3 mEq/kg, titrated to a narrowing of the QRS and a plasma pH of 7.45 to 7.55, then an infusion if dysrhythmia recurs. Avoid amiodarone and procainamide, which prolong the QRS or QT and worsen cardiotoxicity, and avoid phenytoin for any seizure because it is itself a sodium-channel blocker — use a benzodiazepine. For refractory cardiovascular collapse give lipid emulsion 1.5 mL/kg as a bolus.[1][7]

Stem 4 — a high anion gap with a high osmolal gap (answer)

A disoriented patient has a pH of 7.1, an anion gap of 28, and an osmolal gap of 35 mOsm/kg. What is the diagnosis, the mechanism, and the treatment? Model: The combination of a high anion-gap metabolic acidosis with a high osmolal gap is highly specific for a toxic alcohol — methanol or ethylene glycol — both metabolised by alcohol dehydrogenase to toxic organic acids. Methanol gives visual symptoms from formic acid; ethylene glycol gives acute kidney injury with calcium oxalate crystals and hypocalcaemia from oxalate. Give fomepizole 15 mg/kg IV to block alcohol dehydrogenase, haemodialysis to remove the parent alcohol and the organic acid, and the cofactors — folate for methanol to accelerate formate metabolism, thiamine and pyridoxine for ethylene glycol to divert glyoxylate away from oxalate. Do not wait for the level; treat on the gaps.[1][9]

References

1. [1]Hoffman RJ, Nillas A Toxidromes and a general approach to poisoning Arch Dis Child, 2025.PMID 39978865
2. [2]Ghannoum M, Roberts DM Management of Poisonings and Intoxications Clin J Am Soc Nephrol, 2023.PMID 37097121
3. [3]Chyka PA, Seger D, Krenzelok EP, Vale JA; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: Single-dose activated charcoal Clin Toxicol (Phila), 2005.PMID 15822758
4. [4]Hoegberg LCG, Shepherd G, Wood DM, et al. Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose Clin Toxicol (Phila), 2021.PMID 34424785
5. [5]Thanacoody R, Caravati EM, Troutman B, et al. Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients Clin Toxicol (Phila), 2015.PMID 25511637
6. [6]Höjer J, Troutman WG, Hoppu K, et al. Position paper update: ipecac syrup for gastrointestinal decontamination Clin Toxicol (Phila), 2013.PMID 23406298
7. [7]Neal JM, Barrington MJ, Fettiplace MR, et al. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017 Reg Anesth Pain Med, 2018.PMID 29356773
8. [8]Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity QJM, 2003.PMID 12925718
9. [9]McMartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites Br J Clin Pharmacol, 2025.PMID 39234820
10. [10]O'Keefe M, Stanton M, Feldman R, et al. Incidence of rebound salicylate toxicity following cessation of urine alkalinization Clin Toxicol (Phila), 2023.PMID 37427892
11. [11]Mazer-Amirshahi M, Stolbach A, Nelson LS ACMT Position Statement: Addressing the Rising Cost of Prescription Antidotes J Med Toxicol, 2018.PMID 29185196