22.2 Acute Poisoning: Toxidromes, Decontamination and Specific Antidotes
Key Takeaways
Supportive care (airway, breathing, circulation, glucose and temperature control) is the mainstay of treatment for most poisonings, and specific antidotes are used when indicated.
Activated charcoal (50 g in adults) is most useful within 1 hour of ingestion of a substance it binds, and must not be given to patients with an unprotected airway; it does not bind iron, lithium, alcohols or strong acids and alkalis.
Tricyclic antidepressant poisoning causes anticholinergic features, seizures and sodium channel blockade with a broad QRS; sodium bicarbonate is given for QRS above about 120 ms, arrhythmias or hypotension.
Organophosphate poisoning causes a cholinergic crisis (miosis, bradycardia, bronchorrhoea, bronchospasm, weakness); treat with large doses of atropine titrated to dry secretions, and consider pralidoxime.
Methanol and ethylene glycol cause a high anion gap metabolic acidosis with a raised osmolar gap; fomepizole (or ethanol) blocks alcohol dehydrogenase, and haemodialysis removes the parent alcohols and toxic metabolites.
22.2 Acute Poisoning: Toxidromes, Decontamination and Specific Antidotes
Approach to the Poisoned Patient
- Resuscitate: airway (intubate if GCS is low with loss of airway protection), breathing, circulation, glucose, temperature.
- History: substance, amount, time, route, intent; collateral history and packaging.
- Examination: look for a toxidrome, pupils, temperature, skin, bowel sounds, tone and reflexes.
- Investigations: ECG (QRS, QT), blood gas with lactate, anion gap and osmolar gap, paracetamol and salicylate levels in all overdoses of unknown content, specific drug levels, creatine kinase.
- Reduce absorption and enhance elimination when appropriate.
- Specific antidotes.
- Psychiatric assessment after recovery for intentional overdose.
Poison information services (for example national poison centres) give up-to-date advice.
Toxidromes
| Toxidrome | Typical agents | Features |
|---|---|---|
| Opioid | Morphine, heroin, fentanyl, methadone | Miosis, respiratory depression, reduced consciousness |
| Sedative-hypnotic | Benzodiazepines, alcohol, barbiturates | Sedation with relatively normal vital signs (benzodiazepines alone), ataxia |
| Anticholinergic | Tricyclics, antihistamines, atropine | "Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter": hyperthermia, dry skin, flushing, mydriasis, delirium, urinary retention, tachycardia |
| Cholinergic | Organophosphates, carbamates, nerve agents | Salivation, lacrimation, urination, diarrhoea, bronchorrhoea, bradycardia, miosis, fasciculation and weakness |
| Sympathomimetic | Cocaine, amphetamines, MDMA | Tachycardia, hypertension, hyperthermia, mydriasis, sweating (unlike anticholinergic), agitation, seizures |
| Serotonin syndrome | SSRIs with MAOIs, tramadol, linezolid, MDMA | Clonus (inducible, ocular), hyperreflexia, agitation, hyperthermia, diarrhoea; rapid onset |
| Neuroleptic malignant syndrome | Antipsychotics | Lead-pipe rigidity, hyperthermia, autonomic instability, raised creatine kinase; slow onset over days |
Decontamination and Enhanced Elimination
- Activated charcoal (50 g in adults, 1 g/kg in children): most useful within 1 hour of ingestion. Does not bind iron, lithium, alcohols, cyanide (poorly), strong acids or alkalis, or hydrocarbons. Contraindicated with an unprotected airway or bowel obstruction.
- Multiple-dose charcoal enhances elimination of carbamazepine, phenobarbital, dapsone, quinine and theophylline.
- Whole bowel irrigation for body packers, iron and sustained-release preparations.
- Gastric lavage is rarely indicated.
- Urinary alkalinisation (sodium bicarbonate) enhances salicylate elimination.
- Haemodialysis removes small, water-soluble, poorly protein-bound drugs: salicylates, lithium, methanol, ethylene glycol, metformin (lactic acidosis), valproate in severe cases, and theophylline.
Specific Poisonings
Paracetamol
Hepatotoxicity results from saturation of conjugation and formation of NAPQI, which depletes glutathione (see the opioid and non-opioid analgesia section). Acetylcysteine is given according to timed plasma levels plotted on a treatment nomogram, or immediately when the time of ingestion is uncertain, staggered or the dose large. Shorter regimens (for example the 12-hour SNAP regimen used in the UK) reduce adverse reactions. Markers of severe toxicity include a rising INR, acidosis and raised creatinine; the King's College criteria guide liver transplant referral.
Salicylates
Early respiratory alkalosis (direct stimulation of the respiratory centre), then high anion gap metabolic acidosis, tinnitus, vomiting, hyperthermia, hypoglycaemia and non-cardiogenic pulmonary oedema. Treat with urinary alkalinisation (target urine pH 7.5-8.5) and correct hypokalaemia. Haemodialysis for severe toxicity, renal failure, pulmonary oedema, seizures or very high levels. If intubation is needed, maintain hyperventilation, because a rise in worsens acidaemia and moves salicylate into the brain.
Tricyclic Antidepressants
- Features: anticholinergic toxidrome, seizures, hypotension (alpha-blockade), and sodium channel blockade with QRS prolongation (above about 100 ms predicts seizures; above 160 ms predicts arrhythmias), right axis deviation of the terminal QRS (R wave in aVR) and ventricular arrhythmias.
- Treatment: sodium bicarbonate 8.4% 50-100 mL boluses for QRS widening, arrhythmias or hypotension, aiming for an arterial pH of about 7.45-7.55; benzodiazepines for seizures; avoid class Ia and Ic antiarrhythmics and physostigmine; lipid emulsion in refractory cases.
Opioids
Naloxone 0.4 mg intravenously (or smaller titrated doses of about 0.1 mg in opioid-dependent patients to avoid acute withdrawal), repeated as needed. Its duration (about 30-90 minutes) is shorter than many opioids, so infusions and observation are needed for long-acting drugs such as methadone.
Benzodiazepines
Supportive care is usually enough. Flumazenil can precipitate seizures in mixed overdoses (especially with tricyclics) and in benzodiazepine-dependent patients, so it is not routinely recommended.
Toxic Alcohols
| Alcohol | Toxic metabolite | Features |
|---|---|---|
| Methanol | Formic acid | Visual disturbance, blindness, acidosis |
| Ethylene glycol | Glycolic and oxalic acids | Renal failure, calcium oxalate crystals, hypocalcaemia |
Both cause a raised osmolar gap early and a high anion gap metabolic acidosis later. Treat with fomepizole (or ethanol) to block alcohol dehydrogenase, haemodialysis, and folate (methanol) or thiamine and pyridoxine (ethylene glycol).
Carbon Monoxide
Binds haemoglobin with about 240 times the affinity of oxygen, shifts the dissociation curve to the left and inhibits cytochrome oxidase. Pulse oximetry over-reads saturation; measure carboxyhaemoglobin by co-oximetry. Treat with 100% oxygen (half-life about 4-5 hours in air, about 75 minutes on 100% oxygen); hyperbaric oxygen may be considered for severe poisoning or pregnancy.
Cyanide
Smoke inhalation (burning plastics), sodium nitroprusside and industrial exposure. Cyanide inhibits cytochrome c oxidase, causing histotoxic hypoxia, severe lactic acidosis and a high venous oxygen saturation. Treat with hydroxocobalamin 5 g intravenously (forms cyanocobalamin), or sodium thiosulphate.
Organophosphates
Inhibit acetylcholinesterase, causing a cholinergic crisis with muscarinic (bronchorrhoea, bronchospasm, bradycardia, miosis) and nicotinic (fasciculation, weakness, paralysis) effects.
- Atropine in doubling doses (start 1-2 mg) every 5 minutes until the chest is clear, heart rate above about 80/min and systolic pressure above 80 mmHg; large total doses may be needed.
- Oximes (pralidoxime) can reactivate the enzyme if given before "ageing".
- Avoid suxamethonium (prolonged block); staff should use protective equipment.
- An intermediate syndrome of proximal and respiratory weakness can occur 1-4 days later.
Cardiovascular Drugs
| Poison | Treatment |
|---|---|
| Digoxin | Digoxin-specific antibody fragments for life-threatening arrhythmias or potassium above about 5-6 mmol/L; correct hypokalaemia and hypomagnesaemia |
| Beta-blockers | Atropine, glucagon, high-dose insulin euglycaemic therapy (for example 1 unit/kg bolus then infusion with glucose), vasopressors, pacing, lipid emulsion, ECMO |
| Calcium channel blockers | Calcium, high-dose insulin euglycaemic therapy, vasopressors, lipid emulsion, ECMO |
Other Important Antidotes
| Poison | Antidote |
|---|---|
| Iron | Desferrioxamine |
| Methaemoglobinaemia (for example from dapsone, local anaesthetics) | Methylene blue 1-2 mg/kg |
| Heparin | Protamine |
| Warfarin | Vitamin K and prothrombin complex concentrate |
| Local anaesthetic toxicity | 20% lipid emulsion |
| Malignant hyperthermia, some cases of neuroleptic malignant syndrome | Dantrolene |
| Isoniazid | Pyridoxine |
A patient who took an unknown overdose has a GCS of 9, sinus tachycardia, dilated pupils, dry flushed skin and a QRS duration of 140 ms. What is the most appropriate specific treatment?
Flumazenil to reverse a possible benzodiazepine co-ingestion
Sodium bicarbonate 8.4% boluses to an arterial pH of about 7.45-7.55
Physostigmine to reverse the anticholinergic features and the delirium
Flecainide to treat the broad-complex conduction delay
A farmer presents with pinpoint pupils, profuse secretions, wheeze, bradycardia and muscle fasciculations. What is the key initial drug treatment?
Naloxone 0.4 mg intravenously
Neostigmine to improve muscle strength
Suxamethonium to facilitate rapid sequence intubation and protect the airway
Atropine in doubling doses until the chest is clear, plus an oxime
A patient has a pH of 7.08, an anion gap of 28 mmol/L, a measured osmolality 40 mOsm/kg above the calculated value, and blurred vision. What is the most appropriate treatment?
Fomepizole, haemodialysis and folate for suspected methanol poisoning
Activated charcoal 50 g and observation, because charcoal binds alcohols well in the first hours
Methylene blue 1-2 mg/kg for methaemoglobinaemia
Hydroxocobalamin 5 g for cyanide poisoning, because the osmolar gap is diagnostic of cyanide
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