Toxicology sits in SLO1 (complex, stable patients) and SLO3, and the unknown overdose is a classic FRCEM Final scenario: a sick patient, no clean history, and a decision that hangs on reading the signs correctly. The April 2025 RCEM poisoning guideline (Management of Patients with Suspected but Unidentified Poisoning in the Emergency Department) gives you a toxidrome-led structure for exactly that — with the reminder that not every undifferentiated patient is poisoned, so the other causes (sepsis, stroke, metabolic) still need excluding.

Please note: this guideline is for the individual patient with an unknown poison — it is explicitly not for CBRN, HAZMAT or mass-casualty chemical releases.

It presents an undifferentiated overdose and asks you to identify the toxidrome and act. Common presentations:

• Pinpoint pupils, sweating, bradycardia, bronchorrhoea → cholinergic crisis (organophosphate) — atropine, not naloxone.
• Drowsy after a suspected overdose, broad QRS on the ECG → sodium-channel blockade — sodium bicarbonate.
• Agitated, dry, hot, dilated pupils, urinary retention → anticholinergic — supportive care ± benzodiazepines.
• Any deliberate overdose, history unclear → send a paracetamol level regardless of the story.

The discriminating findings are usually in the examination, the venous gas and the ECG, read together with the relevant details in the history — the background, the medications available to them, and the circumstances of the presentation — which point towards the likely agent.

RCEM provides a useful structure, in flow-chart form, for approaching the undifferentiated poisoned patient. In the exam, the stem can drop you in at any point — so knowing the detail under each step is crucial:

The principle is simple: treat the life-threatening problems as you find them, working through the usual ABCDE, whilst you try to identify the poison. Identifying the agent must never delay the emergency treatment that stabilises breathing, circulation or the brain. But notice that many of those immediate interventions are poison-specific in themselves — atropine for the cholinergic crisis, bicarbonate for sodium-channel blockade, high-dose insulin for beta-blocker or calcium-channel-blocker toxicity — so reading the toxidrome and resuscitating the patient happen together, not one after the other.

A few points worth remembering:

• TOXBASE and the NPIS are your source for up-to-date, poison-specific guidance.
• Poisoning may be implicated whenever there is diagnostic uncertainty in the undifferentiated patient — and traumatic injury may need ruling out in the potentially poisoned.
• ECGs and blood gases may need repeating several times as the picture evolves.
• Illicit and internet-bought drugs may not contain what they claim — expect adulterants and multiple substances.

The next step is toxicokinetics. Once you have a likely agent, ask yourself: when was the exposure, and is it still being absorbed; has the peak plasma concentration been reached; what is the half-life; is the patient likely to deteriorate, and what should I pre-empt? This is how you distinguish the patient who looks well now but will deteriorate later from the one who has already peaked.

Points in the history worth noting — each will aid your management decisions, and in a stem they are usually there as a clue to the agent:

• What, how much, and when — and over how long: a single dose and a staggered ingestion are managed completely differently.
• Their own medicines — prescribed (antidepressants, opioids, cardiac drugs like beta-blockers and digoxin) and over-the-counter (paracetamol, NSAIDs, antihistamines).
• What else they could reach — a partner’s or parent’s medication, and herbal, Ayurvedic or traditional remedies.
• Recreational — alcohol, illicit drugs, and new psychoactive substances (‘legal highs’, which often aren’t what they claim to be).
• Natural toxins — plants, mushrooms, venomous animals.
• Occupation & environment — farm chemicals (organophosphates), industrial solvents, fumes.
• Anyone else affected? — suggests a shared source: carbon monoxide, a contaminated supply, a deliberate release.
• Forensic context — a history of political or criminal activity raises the possibility of deliberate poisoning.

So if a stem mentions other people affected, or an occupational or forensic detail, don’t skim past it — it is usually pointing you towards the agent: a shared carbon monoxide source, organophosphate exposure, or deliberate poisoning.

Work through ABCDE, treating what you find as you go. Run it as consider / investigate / intervene at each step:

Several of these points are commonly tested:

• The GCS must never be used for prognosis in the poisoned patient — most patients in a toxic coma recover fully with good supportive care. It is a snapshot, not a prediction.
• Pulse oximetry is unreliable in carbon monoxide poisoning, methaemoglobinaemia, sulfhaemoglobinaemia and after methylthioninium — use a blood gas with co-oximetry.
• Seizures → benzodiazepines first; phenytoin is contraindicated because it is itself a sodium-channel blocker.
• Correct the cause before the antiarrhythmic. Bicarbonate (for QRS prolongation) or magnesium (for QT prolongation), plus electrolyte correction, come before amiodarone — and toxic arrhythmias may be refractory to cardioversion without the antidote.
• High-dose insulin euglycaemia therapy is the circulation intervention to remember for severe beta-blocker or calcium-channel-blocker toxicity.

Other complications to note — the kind of small detail the exam likes to test:

• Rhabdomyolysis — from seizures, agitation or pressure necrosis; maintain hydration and urine output.
• Urinary retention — from anticholinergic toxicity or atropine treatment; catheterise early.
• Pharmacobezoar — a mass of tablets that delays absorption, then breaks down to release a bolus, causing sudden, unexpected deterioration hours later. Sustained-release preparations behave similarly: prolonged absorption, longer half-life, later peak.

A toxidrome is a cluster of signs that points to a class of poison — and often you have to treat on the toxidrome alone, before anyone can tell you what was taken.

RCEM uses the CRESS mnemonic to tell them apart — five signs you check together at the bedside, ideally alongside the airway assessment:

• Consciousness — depressed, or agitated and delirious?
• Respiration — depressed, or driven up?
• Eyes — pinpoint or dilated pupils?
• Secretions — wet (sweating, salivation, bronchorrhoea) or bone dry?
• Skin — sweaty, or dry, hot and flushed?

Read those five signs together and the toxidrome usually becomes clear:

When it’s the biochemistry rather than the toxidrome that gives it away, think of the organ syndromes: acute liver failure (paracetamol, Amanita, iron), acute kidney injury (ethylene glycol, methanol, NSAIDs), and a raised-anion-gap metabolic acidosis (ethylene glycol, methanol, aspirin, iron, cyanide, carbon monoxide, metformin).

Many overdoses are diagnosed from the ECG. Seek the changes early and treat them as soon as you see them, and repeat the ECG because the picture can change:

Some investigations are baseline for everyone: an ECG, a venous gas (lactate, chloride, sodium, potassium, glucose) and laboratory FBC, renal function, LFTs, magnesium, creatine kinase and INR. Then tailor the rest based on your suspicions:

• Paracetamol in every case of possible self-harm — and considered in all unknown poisoning. Salicylate, toxic-alcohol and ethanol levels are added case-by-case or on NPIS advice.
• The two gaps. If a toxic alcohol is suspected, calculate the osmolar gap on admission and the anion gap, and recalculate the anion gap after a few hours to catch a rise as the parent alcohol is metabolised to its acid. Anion gap = (Na + K) − (HCO₃ + Cl), normal 12–16; osmolar gap = measured − calculated osmolarity, normal < 10.
• Specific assays — iron, lithium, digoxin, phenytoin, carbamazepine, valproate, theophylline, methanol, ethylene glycol — when the history points to them and the result changes management. Carboxyhaemoglobin and methaemoglobin are on most ED gas analysers.
• Ethanol isn’t routine, but measure it urgently in undiagnosed coma, a widened osmolar gap, suspected severe ethanol or toxic-alcohol poisoning, and children with unexplained acidosis.
• Imaging — CT head for reduced consciousness or focal signs; a low-dose CT abdomen/pelvis if internal drug packets are suspected; CT to exclude non-toxic diagnoses and trauma.

Decontamination runs alongside resuscitation, never instead of it. It reduces the absorbed dose, but must not delay time-critical treatments that may be lifesaving. The method depends on the route:

• Single-dose activated charcoal — consider orally or by NG tube if a potentially toxic amount of a charcoal-bound substance was taken within the last hour. It is contraindicated if the airway is unprotected (and the patient isn’t intubated) or where aspiration risk is high (e.g. hydrocarbons).
• Skin / surface — remove clothing and dry decontaminate with absorbent material, then wash with water and soap, taking care to protect staff from the agent and its vapours.
• Eyes — irrigate with crystalloid for a minimum of 10–15 minutes, then check the corneal pH.
• Gastric lavage is not routine and may harm — a rare, NPIS-discussed option in life-threatening ingestion not amenable to charcoal.

Charcoal doesn’t bind everything — it is ineffective against:

Enhanced elimination — multiple-dose activated charcoal, urinary alkalinisation, renal replacement therapy and whole-bowel irrigation — is agent-specific; the indications come from TOXBASE/NPIS rather than a generic threshold.

Antidotes are often the key to treating a poisoning, and using them early — matched to the toxidrome, or better still a confirmed agent — is actively encouraged. One caution: some are themselves harmful if given without their target poison, so confirm with TOXBASE or the NPIS. Hospitals stock them by how quickly they might be needed — some kept immediately in resus (Category A), some elsewhere in the hospital within an hour (Category B), and some held supra-regionally and released through NPIS (Category C). Here are the common ones you’re likely to reach for — doses from TOXBASE/BNF:

Paracetamol is the overdose every candidate must own, pitched at consultant level — not “give NAC”, but the timing decisions and the transplant criteria.

• Single acute ingestion, known time: a 4-hour (or later) level on the single UK treatment line (the MHRA “100” line; risk stratification was abolished in 2012) decides treatment.
• Staggered ingestion or uncertain timing: the nomogram doesn’t apply — treat with NAC and use levels, LFTs and INR to guide duration.
• Regimen — the two-bag SNAP protocol. NAC is weight-based, dosed to a maximum of 110 kg, giving a 300 mg/kg total over 12 hours in two consecutive infusions: bag 1 — 100 mg/kg over 2 hours, then bag 2 — 200 mg/kg over 10 hours. This shorter schedule causes far fewer anaphylactoid reactions than the old three-bag, ~21-hour regimen; if a reaction does occur, pause or slow the infusion, treat it, and restart at a lower rate.

A patient who’s been poisoned by an unknown agent is safe to discharge once they are physiologically and biochemically stable, have returned to their baseline cognitive function, and no further deterioration is anticipated — with the observation period set by the toxidrome and likely poison, checked against TOXBASE. There’s no universal “six hours and home”; the safe window is agent-specific.

• Modified- and sustained-release preparations (and the pharmacobezoar) cause delayed, prolonged toxicity — observe longer, per TOXBASE, and beware sudden late deterioration.
• Agents with late toxicity — paracetamol (hepatic, days), iron (after a quiescent phase), sulfonylureas (recurrent hypoglycaemia), modified-release calcium-channel blockers — are dangerous precisely because the early picture reassures.

Two non-clinical points that also earn marks:

• Capacity. Many intoxicated patients lack capacity to decline care or self-discharge; assess it, record the rationale clearly, and manage under the Mental Capacity Act (per the RCEM MCA guideline).
• Mental health & safeguarding. Anyone who has self-harmed — by overdose or otherwise — needs a mental-health assessment before discharge, separate from medical clearance. In children, consider deliberate poisoning as a form of non-accidental injury.

The unknown poison rewards a structured approach, not a memorised drug list. Resuscitate as you go; take the five CRESS signs and identify the toxidrome; read the ECG for sodium-channel blockade or a long QT; send a paracetamol level on everyone; work out whether the patient has peaked yet or is still to deteriorate; decontaminate alongside treatment, never before it; and set the observation period by the agent, not the clock. Learn the few numbers that matter — 50–100 mL of 8.4% bicarbonate for a broad QRS, magnesium 2 g for a long QT, atropine doubled to dry secretions in a cholinergic crisis, the King’s criteria for paracetamol.

Because the April 2025 guideline is recent and detailed, it is likely to feature in the next few sittings. For more on what the exam prioritises, see our FRCEM Final high-yield topics for 2026, and for the poisoned arrest specifically, the toxins section of our cardiac arrest in special circumstances guide.

Sources: RCEM Best Practice Guideline, Management of Patients with Suspected but Unidentified Poisoning in the Emergency Department (April 2025); TOXBASE and the National Poisons Information Service; MHRA paracetamol guidance and the SNAP regimen; the King’s College Hospital criteria for paracetamol-induced acute liver failure; BNF. Drug doses are for reference only — always check TOXBASE and the BNF.