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]

Treat the respiratory depression and investigate the possible co-ingestion in parallel. The opioid pattern calls for ventilatory support and naloxone titrated to restore breathing rather than full consciousness.^[36][50] The paracetamol container matters even if it does not explain the presenting toxidrome: serum paracetamol and salicylate concentrations are recommended after ingestion with intent of self-harm or potentially toxic exposure to those medicines. An early paracetamol sample can be misleading; the nomogram assessment requires an appropriately timed concentration, with a different pathway when ingestion time is unknown.^[1][53]

Resuscitate and assess together — do not delay a time-critical treatment

Treat immediate threats while the toxicological risk assessment develops. Assess airway, breathing, circulation and neurological function; provide airway protection, ventilation, fluids and cardiovascular support according to clinical need. In parallel, establish what was taken, how much, when, for how long and by whom. Update the assessment as the history, investigations and clinical course evolve.^[2]

Decontamination, enhanced elimination, antidotes and supportive care are selected interventions, not compulsory sequential stations. A time-critical antidote need not wait for decontamination or completion of the history. Seek poison-centre or clinical-toxicology advice when assessing the expected course and treatment choices.^[2]

^[2]

Define the exposure before classifying it

A poison is a substance harmful to the body; excessive amounts of otherwise useful substances can also cause poisoning. Exposure may be swallowed, inhaled, injected or absorbed through skin. Effects range from transient illness to organ injury, coma and death.^[66] Clinically, specify the agent, amount, route, time course, intention and patient characteristics rather than relying on a class label alone. These details feed the evolving toxicological risk assessment.^[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. Pesticide self-poisoning accounts for an estimated 258,234 deaths a year worldwide (plausible range 233,997 to 325,907), about 30 percent (range 27 to 37 percent) of global suicides.^[28] Organophosphorus pesticide self-poisoning kills an estimated 200,000 people every year, with case fatality generally more than 15 percent.^[29] In India, aluminium phosphide is the leading cause of poisoning-related mortality, with pooled mortality 54 percent (95 percent CI 48 to 61 percent) and no definite antidote; organophosphate ingestion remains a major rural caseload.^[19][29] In high-income countries, paracetamol, opioids and psychiatric medications lead.

^[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, after the 16 September 1998 pack-size law, suicidal deaths from paracetamol and salicylates fell 22 percent (95 percent CI 11 to 32 percent) in the following year, and liver-unit admissions and transplants for paracetamol hepatotoxicity fell by around 30 percent over four years.^[27] In India and South Asia, organophosphates and carbamates, aluminium phosphide, oleander, copper sulphate and corrosives dominate; aluminium phosphide is India’s leading poisoning-related mortality, with pooled mortality 54 percent (95 percent CI 48 to 61 percent) and no definite antidote.^[19]

The anticipated severity of an exposure is weighed against the patient's status and the treatments that may be required; kidney disease is itself a risk factor for some poisonings and shapes whether enhanced-elimination techniques can be used.^[2] The high-risk special populations — children, pregnancy, and the elderly with comorbidity and co-medication — are covered at the end of this topic.

Toxidromes — read the pupils, skin, temperature and reflexes

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^{[1] [8]}

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 Hoffman’s well-defined 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. An additional GABAergic toxidrome covers the sedative-hypnotics.^[1] Serotonin toxicity is recognised separately by clonus, hyperreflexia, tremor, agitation and diaphoresis (Dunkley; Isbister).^[8][46]

^[1]

What the poison does — toxicokinetics and toxicodynamics

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^{[47] [48] [62] [63]}

Toxicokinetics concerns the movement and handling of the poison; toxicodynamics concerns its effects. Absorption, distribution, metabolism and excretion are distinct but interacting processes. Therapeutic-dose kinetics may change substantially in overdose: delayed absorption, altered protein binding or tissue distribution, enzyme saturation and organ failure can prolong toxicity. Volume of distribution matters for extracorporeal removal, but it is not the only determinant.^{[47][48][64][2]}

Absorption and bioavailability are not fixed rankings of routes. Intravenous administration delivers drug directly into systemic circulation; oral bioavailability may be reduced by intestinal and hepatic first-pass metabolism. Formulation, gastric emptying and overdose-related physiology can alter the time course. Volume of distribution is the amount of drug in the body divided by its plasma concentration: it is an apparent volume, not an anatomical compartment. Binding and tissue uptake explain why a plasma concentration need not represent all the drug in the body.^[64][47]

Dialysability is a multivariable decision. Small molecular size, water solubility, low protein binding, low endogenous clearance and a low volume of distribution favour extracorporeal clearance. Overdose can saturate protein binding, increasing the removable unbound fraction. Renal or hepatic failure may reduce endogenous clearance. Apply the poison-specific recommendation and the clinical course, rather than a universal volume-of-distribution cutoff.^[2][47]

Metabolism can detoxify or bioactivate. Phase I and phase II pathways commonly make drugs more hydrophilic for excretion, but the resulting compound is not necessarily harmless: codeine requires metabolism to active metabolites, and toxic-alcohol metabolites drive major organ injury. Methanol forms formaldehyde and then formic acid; ethylene glycol forms glycolate and oxalate among other products. Acetylcysteine supports detoxification of paracetamol's reactive metabolite through glutathione-related mechanisms. These are pathway-specific examples, not proof that all metabolism is protective.^[64][52][53]

Clearance is a volume per unit time, not an amount of drug. It is the elimination rate divided by plasma concentration, with renal, hepatic and other clearance contributions. Renal excretion may involve filtration, secretion and reabsorption; some substances also leave via the lungs or gastrointestinal tract. Which route matters depends on the compound and patient physiology.^[64][65]

First-order and zero-order elimination describe different relationships. First-order elimination removes a constant fraction per unit time; when clearance and distribution remain stable, the half-life is constant. With zero-order elimination, saturated removal mechanisms eliminate a constant amount per unit time instead. Alcohol and phenytoin are teaching examples of capacity-limited elimination; salicylate kinetics can also become saturated at higher concentrations. Do not project a therapeutic half-life unchanged into severe overdose or organ failure.^{[64][65][47][48]}

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]

Name the response endpoint before drawing a curve. LD50 is an experimental mortality endpoint: the calculated dose expected to kill half of a defined animal population. NOAEL and LOAEL identify tested doses without or with a statistically or biologically significant increase in the adverse effect being studied versus controls. They are not automatic landmarks on a mortality curve. EPA explicitly notes that dose–response relationships can differ for outcomes such as weight loss and death; an illustrative LD50 is not a patient treatment threshold.^[62][63]

Resuscitation — ABCDE and the coma cocktail

Airway intervention follows physiology and airway risk, not a GCS number alone. Assess airway protection, oxygenation, ventilation, seizures and haemodynamics while resuscitating. Provide ventilatory support for respiratory failure and cardiovascular support for shock; do not postpone these interventions to finish the diagnostic history.^[2]

The NICO trial studied a closely monitored conservative airway strategy in selected adults with suspected poisoning and GCS below 9. It excluded patients needing immediate intubation because of respiratory distress, suspected brain injury, seizure or shock; suspected cardiotropic poisoning; isolated reversible opioid or benzodiazepine poisoning; and known pregnancy. Do not generalise its findings to these excluded groups.^[51]

In its intervention arm, emergency intubation triggers included seizure, vomiting, oxygen saturation below 90 percent despite nasal oxygen, or systolic pressure below 90 mmHg despite 1 L crystalloid. A nurse or physician closely monitored vital signs and GCS for up to 4 hours or until GCS exceeded 8. This was an actively supervised trial protocol, not permission to leave a comatose patient unprotected or unobserved.^[51]

Treat the indication, not an automatic coma cocktail. Check bedside glucose and correct hypoglycaemia without delay. Thiamine may be indicated in a patient at risk of deficiency; the retrieved label indicates thiamine injection where rapid restoration is necessary, and when IV dextrose is given to patients with marginal thiamine status. Do not delay glucose correction: the retrospective veteran study found no Wernicke encephalopathy among 120 encounters in which dextrose preceded thiamine, but this does not establish that thiamine is unnecessary in a deficient patient.^[12][54]

Naloxone targets opioid respiratory depression, not every unexplained coma. Titrate it to ventilation rather than mandatory full wakefulness, with airway and ventilatory support in parallel. Published initial doses vary with context; low-dose IV titration beginning at 0.04 mg is described for opioid-dependent patients, while the 2025 AHA table lists 0.2 to 2 mg IV/IO/IM or 2 to 4 mg intranasally for adult opioid poisoning. Repeated dosing or an infusion may be needed for longer-acting opioids. Flumazenil is not an empiric coma drug: the trial meta-analysis found higher risks of adverse events (RR 2.85) and serious adverse events (RR 3.81) than placebo.^{[36][37][45][50][38]}

^{[1] [12] [1] [1]}

Sodium bicarbonate for the widened QRS

A widened QRS after a tricyclic marks fast sodium-channel cardiotoxicity that usually responds to bicarbonate; bupropion widening is different. Tricyclic poisoning responds well to sodium bicarbonate; a 1 to 2 mmol/kg bolus can be used to assess the response, targeting a serum pH of about 7.45 to 7.55.^[31] After acute tricyclic overdose, no seizures or ventricular arrhythmias occurred when the QRS was under 0.10 second; when the QRS was 0.10 second or longer, seizures occurred in 34 percent and ventricular arrhythmias in 14 percent.^[40] Bupropion widens the QRS by inhibiting cardiac gap junctions and often does not respond to alkalinisation (median QRS change minus 2 ms, not significant).^[22][31] Intravenous lipid emulsion is recommended in bupivacaine cardiac arrest; if other therapies fail, ILE is recommended for bupivacaine and suggested for other local anaesthetics, amitriptyline and bupropion — it is not first-line for amitriptyline, calcium-channel blockers or bupropion.^[42] The recommended ILE dose is a 1.5 mL/kg bolus then 15 mL/kg per hour.^[25] Superiority of lipid over alkalinisation for amitriptyline has been shown in a guinea-pig model, not in patients.^[23]

Seizures and hyperthermia

Cyclic antidepressant overdose produces life-threatening seizures, hypotension and dysrhythmias, and has accounted for a large share of overdose-related adult intensive-care admissions.^[24] Hyperthermia from serotonin syndrome is treated with the serotonin antagonist cyproheptadine — although the cyproheptadine dosing schedule is not uniform across the literature and requires clinical judgement.^[20]

Decontamination — the first pillar

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^{[2] [49] [1]}

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] [49] [5] [6]}

Know what changed. Chyka's 2005 position paper reported volunteer absorption reductions of 47.3, 40.07, 16.5 and 21.13 percent at 30, 60, 120 and 180 minutes and advised against routine charcoal. These are volunteer pharmacokinetic results, not proof of patient-outcome benefit. The 2021 review preceded the 2026 Clinical Toxicology Recommendations Collaborative guidance, which now specifies poison-dependent later windows and distinguishes additional-dose decontamination from multiple-dose enhanced elimination. Evidence remains predominantly low or very low quality.^[3][4][49]

Protect the airway, but do not intubate a low-risk patient merely to give charcoal. The 2026 guidance advises against intubation solely for charcoal when significant poisoning complications are not anticipated, and against inserting a gastric tube without intubation solely to administer charcoal. When intubation is otherwise clinically indicated, gastric-tube charcoal may be reasonable. A large ingestion with substantial life-threatening risk requires an individual risk–benefit decision, especially if other treatments are unavailable.^[49]

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 is intravenous sodium bicarbonate given to produce urine with pH 7.5 or higher, and it should be considered first-line for moderately severe salicylate poisoning that does not meet haemodialysis criteria; supplemental potassium is crucial for the regimen to work.^[39][16] In practice a blood pH around 7.5 is often targeted alongside the urine pH.^[15] Rebound after stopping bicarbonate is uncommon — 8 of 377 (2.1 percent) in one series.^[10] Intermittent haemodialysis is preferred when extracorporeal treatment is required.^[2]

^{[1] [2] [5] [32] [33] [34] [43] [44]}

Extracorporeal treatments and other elimination-enhancing techniques are chosen toxin by toxin as part of the structured risk assessment, and the nephrologist is usually involved when they are required.^[2]

Antidotes — time-critical, toxin-specific treatment

The antidote table is the single highest-yield piece of factual recall in toxicology — agent, antidote, indication. Each entry below is anchored to a source that states it, and where dosing remains unsettled the table says so.^[1]

^{[1] [14] [36] [37] [26] [30] [35] [18] [41] [31] [20] [42] [25] [50] [52] [53] [68] [69] [70] [71]}

The investigations that change the plan

Investigations follow the structured risk assessment. The approach to the poisoned patient pairs resuscitation with a risk assessment that weighs the anticipated severity of the exposure against the patient's status and the treatments that may be required — and that assessment dictates the bedside tests, the targeted drug levels and the gap calculations.^[2]

A prolonged QRS is a risk marker in TCA poisoning, not a universal sodium-channel-blocker diagnosis. In Boehnert's 49-patient study, no seizures or ventricular arrhythmias occurred when maximal QRS was below 0.10 second; seizures occurred from 0.10 second and ventricular arrhythmias only from 0.16 second. These are study findings, not stand-alone treatment or discharge rules. Bicarbonate is used for TCA cardiotoxicity, whereas bupropion-associated QRS widening may not respond in the same way.^[40][31][22]

The two gap calculations are central to toxic-alcohol reasoning. An anion-gap metabolic acidosis is the key laboratory finding in toxic-alcohol poisoning, and the osmolal gap has both utility and limitations — it must be interpreted alongside the acid-base picture rather than relied on in isolation.^[17]

Use the paracetamol nomogram only in its applicable setting. The 2023 US/Canada consensus uses the treatment line beginning at 150 micrograms/mL (150 mg/L) at 4 hours for a reliably timed acute ingestion. A concentration before 4 hours cannot be plotted for that decision. Unknown or unreliable timing, repeated ingestion over more than 24 hours, extended-release products and relevant co-ingestants need their own pathways. The consensus defines acute ingestion as a pattern completed within less than 24 hours; do not assume every ingestion involving more than one swallowing event is automatically outside its acute pathway.^[57]

Do not wait past the protective treatment window for a result. When there is strong concern for an acute ingestion exceeding 200 mg/kg or 10 g and waiting for testing would delay acetylcysteine beyond 8 hours, the consensus advises starting treatment while results are pending. With opioid or anticholinergic co-ingestion and corresponding clinical effects, a 4- to 24-hour concentration above 10 micrograms/mL but below the treatment line warrants another level 4 to 6 hours later. Extended-release preparations also require attention to repeat sampling.^[57]

State the regimen and its jurisdiction. The July 2025 US ACETADOTE label provides a three-bag regimen for patients from 5 kg: 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. For patients from 41 kg it also provides a two-bag regimen: 200 mg/kg over 4 hours, then 100 mg/kg over 16 hours. Use the label's weight-specific dilution and maximum-weight dosing tables. The label does not establish comparable efficacy of the two regimens and advises considering the three-bag regimen for early severe liver injury or a large ingestion. Do not present either regimen as the only international protocol.^[53]

The clock alone does not stop acetylcysteine. The 2023 consensus warns that a common clinical error is to administer acetylcysteine for 20 or 21 hours and then discontinue without reassessment; some patients require longer treatment, so administer it until stopping criteria are met.^[57] During treatment, monitor hepatic and renal function and fluid balance — AST, ALT, bilirubin, INR, creatinine, BUN, glucose and electrolytes — with repeat acetaminophen concentrations; when timing is uncertain, earlier concentrations can mislead.^[53] Seek clinical-toxicology advice for progressive injury, and consult a liver transplant team when AST or ALT rise progressively with coagulation abnormalities, or with encephalopathy or multisystem failure despite acetylcysteine.^[57]

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. A high anion-gap metabolic acidosis with a raised osmolal gap points to a toxic alcohol, though the osmolal gap has recognised limitations and must be read with the whole picture.^[1][17]

The three hyperthermia syndromes — the most examined differential

Do not merge these hyperthermia syndromes into one clonus-based diagnosis. Exposure, time course and neuromuscular findings help distinguish serotonin toxicity, NMS and malignant hyperthermia, but atypical presentations and overlap require clinical judgement.^{[8][46][56][61]}

^{[8] [46] [56] [61]}

The Hunter Serotonin Toxicity Criteria (Dunkley 2003) are simpler, more sensitive (84 percent versus 75 percent) and more specific (97 percent versus 96 percent) than Sternbach. Only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of serotonin toxicity as diagnosed by a clinical toxicologist; hypertonicity and maximum temperature above 38 degrees C were universal in life-threatening cases and were therefore added.^[8] Isbister describes the same triad of neuromuscular excitation, autonomic stimulation and changed mental state.^[46]

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 is metabolised through CYP2E1 to the reactive NAPQI, which depletes glutathione; most protocols apply the 150 mg/L at 4-hour Rumack-Matthew treatment line, and standard acetylcysteine — 300 mg/kg over 21 hours in divided doses — is almost universally effective when given promptly.^[13][14] Salicylate poisoning gives a mixed respiratory alkalosis with high-anion-gap metabolic acidosis; significant poisoning is treated with urine alkalinisation to a urinary pH above 7.5, and rebound toxicity is described when the infusion stops.^[15][10] Organophosphates inhibit acetylcholinesterase; atropine is titrated to muscarinic signs. Trial protocols have used atropine plus pralidoxime as background “standard care”, but current evidence is insufficient to show whether oximes are harmful or beneficial, and the WHO 30 mg/kg then 8 mg/kg/h pralidoxime regimen is not supported.^[26][30]

Tricyclic antidepressants cause fast sodium-channel blockade with QRS widening; IV sodium bicarbonate 1 to 2 mmol/kg (target pH about 7.45 to 7.55) is first-line. Lipid emulsion is not first-line for amitriptyline; guinea-pig data should not be read as a human ranking of lipid over bicarbonate.^[31][42][23]

Toxic alcohols require inhibition of toxic-metabolite formation and assessment for extracorporeal treatment. Methanol is metabolised through formaldehyde to formic acid; ethylene glycol produces glycolate and oxalate among its metabolites. Fomepizole inhibits alcohol dehydrogenase. The retrieved US label specifies 15 mg/kg IV initially, then 10 mg/kg every 12 hours for four doses, followed by 15 mg/kg every 12 hours; infuse every dose over 30 minutes. Stop only when the relevant alcohol is undetectable or below 20 mg/dL and the patient is asymptomatic with normal pH.^[17][35][52]

Adjust fomepizole around haemodialysis. During haemodialysis, dose every 4 hours. At its start, give the next scheduled dose if at least 6 hours have elapsed since the previous dose; otherwise do not add a dose. At its end, give no extra dose if less than 1 hour has elapsed since the last dose, half the next scheduled dose if 1 to 3 hours have elapsed, or the next scheduled dose if more than 3 hours have elapsed. Resume the next off-dialysis dose 12 hours after the last administered dose. Use EXTRIP's poison-specific indications for initiating extracorporeal treatment; the product label's generic concentration threshold is not a replacement for those recommendations.^[34][44][52]

Opioids give the opioid toxidrome of coma with respiratory depression and miosis; naloxone is titrated to restore respiration, not consciousness.^[1][36] Late presentations with sustained-release or enteric-coated drugs, and substantial iron, lithium or potassium ingestions, are the classic considerations for whole-bowel irrigation.^[5]

The preventable deaths — pitfalls that recur

The recurring, examiner-favoured errors trace to a short list, and most are preventable. The first is giving a decontamination measure without the indication — routine single-dose charcoal and routine ipecac are both specifically advised against by the position papers, and ipecac may delay or reduce the effectiveness of activated charcoal, oral antidotes and whole-bowel irrigation.^[3][6]

The treatment pitfalls close the list. Assuming a coma is toxic before the glucose is checked; delaying dextrose for thiamine in hypoglycaemia;^[12] relying on the osmolal gap alone to exclude a toxic alcohol when the anion gap tells the other half of the story;^[17] treating bupropion QRS widening as if it were a tricyclic bicarbonate-responsive block;^[31] and treating the WHO oxime regimen as settled evidence.^[30]

^[1]

Prognosis and disposition

Outcome is set by the agent and the dose, the time to presentation, the co-ingestants, and the availability of antidote and dialysis. Aluminium phosphide is India's leading cause of poisoning-related mortality, with pooled mortality 54 percent (95 percent CI 48 to 61 percent) and no definite antidote; prompt standard acetylcysteine almost universally prevents paracetamol hepatotoxicity except when the 4-hour level exceeds 300 mg/L; and toxic-alcohol outcome turns on early fomepizole and access to extracorporeal treatment when EXTRIP criteria are met.^[19][14][2]

^{[1] [1]}

Disposition follows the risk assessment. The exposure is judged for its anticipated severity in the context of the patient's status and the treatments that may be required — that judgement, not a clock, sets the level of observation, the need for extracorporeal treatment, and the timing of discharge.^[2] Detailed bedside guidance is available through clinical resources such as TOXBASE.^[1]

Special populations

In children, the dose is weight-based and the ingestion is often unwitnessed. Moderate paediatric salicylate poisoning has been managed with a modified bicarbonate regimen in which supplemental potassium is crucial for effective alkalinisation — the same principle as in adults.^[16] Ipecac is avoided in children as everywhere else: routine administration should definitely be avoided.^[6]

In ethylene glycol poisoning in pregnancy, treatment should be as for the non-pregnant patient and should not be withheld on account of pregnancy. When an antidote is indicated, the maternal and fetal benefits of antidote treatment outweigh the risks associated with untreated ethylene glycol poisoning, and fomepizole is preferred at all stages of pregnancy because ethanol can cause harmful fetal effects; where fomepizole is unavailable or not considered appropriate, ethanol should not be withheld on account of pregnancy.^[59] This preference is not a claim that fomepizole is proven safe in pregnancy: data on these antidotes in pregnancy are very limited, animal reproduction studies with fomepizole have not been conducted, it is not known whether fomepizole can cause fetal harm when administered to pregnant women, and the US label states it should be given to pregnant women only if clearly needed.^[52] The decision therefore remains a patient-specific risk–benefit judgement for this poisoning, with extended maternal and fetal monitoring and discussion with a teratology information service recommended in all cases.^[59]

The elderly carry more risk from the same exposure because comorbidity and co-medication compound toxicity; the structured risk assessment explicitly weighs the patient's status and the treatments that may be required before disposition.^[2]

Evidence, guidelines, and regional practice

Read the decontamination evidence chronologically. Chyka 2005 and Hoegberg 2021 inform the 2026 Clinical Toxicology Recommendations Collaborative guidance: charcoal is selective, timing is poison- and formulation-dependent, and additional-dose decontamination differs from multiple-dose enhanced elimination. Whole-bowel irrigation retains selected indications; ipecac is not routine care. The ASRA advisory and poisoning lipid-emulsion recommendations address distinct settings and must not be treated as a universal rescue algorithm.^{[3][4][49][5][6][7][42]}

Regionally, clinical resources such as TOXBASE exist to provide detailed guidance on the clinical management of poisoning.^[1] The rising cost of prescription antidotes is a global access problem formally addressed by the ACMT position statement.^[11] In India, aluminium phosphide — a pesticide with no definite antidote — is the leading cause of poisoning-related mortality.^[19]

The live controversies are the ones the position papers settled — routine ipecac and routine charcoal are out — and the ones still open: whether oximes help or harm in organophosphate poisoning,^[30] high-dose versus standard acetylcysteine when the 4-hour paracetamol level exceeds 300 mg/L,^[14] the optimal cyproheptadine schedule in serotonin toxicity,^[20] and how far lipid emulsion should extend beyond bupivacaine arrest.^[42]

^[1]

Ward-round test — four stems

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

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 — the receptor-level effects produce coma with respiratory depression and miosis.^[1] Check a capillary glucose at the bedside first to exclude hypoglycaemia. Naloxone is titrated to restore respiration, not consciousness; in opioid-dependent patients start at 0.04 mg.^[36][37]

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

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 toxicity — clonus, hyperreflexia, diaphoresis and agitation after a serotonergic exposure. Hunter criteria are more sensitive (84 versus 75 percent) and more specific (97 versus 96 percent) than Sternbach.^[8] Stop the agent, give benzodiazepines, cool, and consider cyproheptadine, recognising that its dosing schedule is not uniform.^[20][46]

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

A patient who took amitriptyline has a QRS of 150 ms and a wide-complex tachycardia. What is the treatment? Model: This is fast sodium-channel blockade from the tricyclic. Give IV sodium bicarbonate 1 to 2 mmol/kg targeting a pH of about 7.45 to 7.55 — TCA poisoning responds well to bicarbonate. ILE is not first-line for amitriptyline; if other therapies fail it can be suggested. Guinea-pig ranking of lipid over alkalinisation is not a human treatment algorithm.^[31][42][23]

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

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: Methanol or ethylene glycol is a concern, not a diagnosis established by the gaps alone. Obtain the exposure history, serial acid–base assessment and specific alcohol concentrations while treating a sufficiently suspected toxic-alcohol ingestion. The US fomepizole label specifies 15 mg/kg IV initially, then 10 mg/kg every 12 hours for four doses, followed by 15 mg/kg every 12 hours; infuse each dose over 30 minutes. Stop only when the alcohol is undetectable or below 20 mg/dL and the patient is asymptomatic with normal pH. Haemodialysis requires the separate dosing adjustments described above.^[17][52] Methanol-attributed acidaemia at this level and anion gap above 24 mmol/L meet EXTRIP indications for extracorporeal treatment; for ethylene glycol apply its distinct anion-gap, glycolate, clinical and antidote-dependent criteria.^[34][44]

References71ShowHide

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
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