Red flags
- GCS <=8 - airway protection required
- Pinpoint pupils + respiratory depression - opioid toxidrome, give naloxone
- Hypoglycaemia - reversible, check immediately
- Asymmetric pupils/focal signs - structural cause, not pure toxic
- Hyperthermia + coma - sympathomimetic/serotonergic/anticholinergic toxicity or environmental
- QRS widening/arrhythmia with coma - sodium channel blocker toxicity
Differential by mechanism
Toxidrome-based
- Opioid: miosis, resp depression, reduced bowel sounds - reverses with naloxone
- Sedative-hypnotic (benzodiazepine, alcohol, GHB, barbiturate): normal/small pupils, resp depression, hypotonia
- Anticholinergic: mydriasis, dry/flushed skin, urinary retention, tachycardia, hyperthermia ("mad as a hatter")
- Cholinergic (organophosphate): miosis, salivation, lacrimation, bradycardia, fasciculations
- Sympathomimetic: mydriasis, tachycardia, hyperthermia, agitation preceding coma
Metabolic
- Hypoglycaemia, hyponatraemia, hepatic/uraemic encephalopathy, hypercapnia, myxoedema coma, Addisonian crisis
Structural
- Intracranial haemorrhage, large infarct, mass lesion, raised ICP, status epilepticus (non-convulsive)
Infective
- Meningitis/encephalitis, sepsis-associated encephalopathy
Other toxic
- CO poisoning, serotonin syndrome (late stage), lithium toxicity, baclofen overdose
Focused history
- Collateral history - found where, empty packets/containers, suicide note, time last seen well
- Known medications, illicit drug use, psychiatric history, previous overdoses
- Diabetes, liver/renal disease, recent infection, head injury
Focused examination
- Glucose immediately (bedside)
- GCS, pupils (size, symmetry, reactivity), temperature
- Toxidrome features (skin, bowel sounds, tone, reflexes)
- Signs of trauma, needle marks, chronic liver/renal disease
Investigation strategy
- Glucose, VBG/ABG, UEC, LFT, calcium, ammonia if hepatic cause suspected
- Paracetamol and salicylate levels in every case of unexplained coma/overdose
- ECG (QRS, QTc)
- CT brain if focal signs, trauma, no clear toxic/metabolic cause, or failure to improve as expected
- Urine/serum tox screen - limited sensitivity/specificity, rarely changes acute management
Management
1. Airway, breathing, circulation first
- Protect airway if GCS <=8 or losing airway reflexes
2. Reversible causes - treat empirically while awaiting results
- Glucose if hypoglycaemic or glucose unknown/unavailable immediately
- Naloxone if opioid toxidrome suspected (titrate to reverse respiratory depression, not to full wakefulness - avoids precipitating withdrawal)
- Thiamine before/with glucose if alcohol/malnutrition risk
3. Specific antidotes as indicated by toxidrome/history
- Flumazenil - avoid routinely; risk of seizures in mixed OD/chronic benzodiazepine use, reserved for isolated iatrogenic benzodiazepine sedation
- Sodium bicarbonate for sodium channel blocker toxicity
4. Supportive care
- Temperature control, seizure management, ICU if refractory/ventilated
Traps
- Flumazenil is not routine in undifferentiated coma - can precipitate seizures in TCA co-ingestion or chronic benzodiazepine dependence
- Naloxone should be titrated to adequate respiration, not full arousal - avoids acute opioid withdrawal in dependent patients
- A urine drug screen rarely changes management and commonly gives false positives/negatives - do not delay treatment waiting for it
- Always check glucose before attributing coma entirely to a known overdose
Talk track
1. Reversible causes first, always
- "Glucose and naloxone can be given empirically before any other workup - both cheap, both potentially curative."
2. Flumazenil is the exception, not the rule
- "I don't reach for flumazenil in undifferentiated coma - the seizure risk in mixed overdose outweighs the benefit."
8 of 8 sections written · drafted 2026-09-13