Level 2 of 6Must-remember

Paracetamol poisoning

Assess, manage and stay safe — enough on its own

1 / 10

The card — assess, manage, caution

Assessment— look, ask, measure

Three actions precede everything else: clarify the date, time, formulation and dose taken; weigh the patient; and calculate the dose ingested in milligrams per kilogram.
Decide which of three exposure patterns this is: an acute overdose (an ingestion, or series of ingestions, within a single period of no more than one hour); a staggered overdose (taken over a period longer than one hour, for which the nomogram is invalid); or repeated supratherapeutic ingestion (accumulation over days, most often from taking two or three paracetamol-containing products together or exceeding 4 g per day for several days).
Apply the dose thresholds: treatment is considered above 150 mg/kg for a single acute ingestion (some sources 150–200 mg/kg, or 8–10 g in an average adult), and above 75 mg/kg in any 24 hours for a staggered ingestion or repeated therapeutic excess.
Expect no physical signs in the treatable phase: in Stage 1 (0–24 hours) the patient is asymptomatic or has at most anorexia, nausea, vomiting, pallor and sweating, and liver function tests, INR, creatinine and glucose are normal — a normal history, examination and blood panel at 6 hours excludes nothing.
Know the later stages so you recognise the late presenter: Stage 2 (24–72 hours) brings right upper quadrant pain and hepatic tenderness with rising aminotransferases then INR then bilirubin; Stage 3 (72–96 hours) is the peak, with jaundice, coagulopathy, encephalopathy, hypoglycaemia, lactic acidosis, acute kidney injury and haemorrhage; Stage 4 (day 4 onwards) is either regeneration over one to three weeks or multi-organ failure.
Draw the timed plasma paracetamol concentration at or after 4 hours post-ingestion and record both the time of ingestion and the time of venepuncture — concentrations taken before 4 hours are uninterpretable and a low 2-hour level has led to fatal discharge.
Measure a quantitative paracetamol level in every patient presenting with a drug overdose of any kind, including those who deny taking paracetamol, with an ethanol level and a pregnancy test where appropriate — this single test detects the occult ingestion that would otherwise present in liver failure three days later.
Send at the same time: creatinine and electrolytes, venous bicarbonate, liver function including ALT, INR, glucose, full blood count, salicylate, ethanol and an ECG.
Know when the nomogram is invalid and must not be used: presentation 15 hours or more after ingestion; a modified-release preparation; staggered ingestion or repeated therapeutic excess over more than 24 hours; co-ingestion of an anticholinergic, opioid or salicylate (delayed gastric emptying with a late secondary rise); or an unknown or unreliable time of ingestion.
Recognise the danger signs: hepatic encephalopathy of any grade; a rising INR despite acetylcysteine and vitamin K; arterial pH below 7.30; a rising lactate; hypoglycaemia; a rising creatinine with falling urine output; hyperventilation without pulmonary signs; pupillary abnormality, hypertension with bradycardia or decerebrate posturing (cerebral oedema); and a falling ALT with a rising INR.
Flag the high-risk ingestion: more than 30 g reported, or a measured concentration exceeding twice the nomogram line.
Two misleading results must never stop you treating: in established hepatotoxicity paracetamol is undetectable in plasma in 50% of cases, so an undetectable concentration in a jaundiced patient with a raised ALT means the drug has been metabolised, not that it was never taken; and beyond 12 hours a borderline concentration near the laboratory's limit of detection should be treated.
Look for co-ingestion: combination preparations mean opioid toxicity (pinpoint pupils, hypoventilation) frequently coexists, salicylate gives tinnitus and a mixed acid–base disturbance, and a tricyclic gives a broad QRS — any of these may dominate the early picture while the paracetamol goes unrecognised.
In a child, assume the worst: the amount is rarely known and must be assumed to be the maximum the container could have held — a 15 kg toddler crosses 150 mg/kg with only 2.25 g, four and a half 500 mg tablets.

Management— do this, in order

Decide on the clock and on milligrams per kilogram, never on how the patient looks — paracetamol poisoning in its treatable phase has no clinical features at all.
Acetylcysteine is time-critical: highly efficacious within 8 hours of ingestion, effective within 8–10 hours, declining steeply thereafter — so never delay it for a laboratory result in any patient presenting after 8 hours from ingestion.Doctor / Nurse
Starting the antidote unnecessarily is trivially reversible; starting it late is not — and lateness is a reason to hurry, never to withhold, since acetylcysteine reliably prevents toxicity within 12 hours, may still be beneficial up to 72 hours after ingestion, and improves outcome in established paracetamol-induced liver failure.
Intravenous acetylcysteine, adult and paediatric mg/kg identical: 150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours — a total of 300 mg/kg over 21 hours.Doctor / NurseNot available at your setup — Infusion pump.
Diluents for an adult: 200 mL of 5% glucose for the loading dose, 500 mL for the second bag and 1000 mL for the third; 0.9% sodium chloride is an accepted alternative diluent. For a 70 kg adult the doses are 10.5 g, then 3.5 g, then 7 g.
In children the mg/kg doses are unchanged but diluent volumes must be reduced in proportion to weight using a weight-banded dilution chart — adult volumes given to a small child risk fluid overload and dilutional hyponatraemia with seizures; most protocols cap the dosing weight, commonly at 110 kg.
0–8 hours since ingestion: wait until 4 hours post-ingestion, then take blood for the plasma paracetamol concentration, creatinine and electrolytes, bicarbonate, liver function and INR, and treat if the concentration lies above the treatment line — but if the result will not be available before 8 hours post-ingestion and more than 150 mg/kg has been ingested, start acetylcysteine immediately and stop it later if the level proves below the line.Doctor / Nurse
8–24 hours since ingestion: send blood urgently but commence acetylcysteine immediately if the ingested dose exceeds 150 mg/kg — do not wait for the concentration; if less is reported and the history is reliable, await the result and use the nomogram, treating any borderline level beyond 12 hours.Doctor / Nurse
More than 24 hours since ingestion: start acetylcysteine at once if the patient is jaundiced or has hepatic tenderness, and treat if the ALT is above the upper limit of normal, the INR is above 1.3 in the absence of another cause, or paracetamol is detectable; if the concentration is undetectable with normal ALT and INR in an asymptomatic patient, no antidote is indicated and any infusion already started may be stopped.Doctor / Nurse
Staggered ingestion, repeated therapeutic excess or unknown history: the nomogram does not apply — treat if more than 75 mg/kg has been ingested in 24 hours, or if the ALT or INR is abnormal; in an unconscious patient of unknown history a detectable concentration, a raised ALT or an INR above 1.3 each mandates treatment.Doctor / Nurse
Where intravenous acetylcysteine is unavailable or not tolerated, give the oral regimen: 140 mg/kg loading, then 70 mg/kg every 4 hours, diluted to about 5% with water or juice — conventionally for 72 hours (the loading dose plus 17 further doses), although 20–48 hour regimens have shown equivalent success.
Where no acetylcysteine exists at all, methionine 2.5 g orally every 4 hours for four doses is the alternative, but is probably less effective after delayed presentation.
Activated charcoal 50–100 g orally or by gastric tube in adults, or 1 g/kg (maximum 50 g) in children, within 1–2 hours of ingestion — although charcoal adsorbs oral acetylcysteine, the interaction is not clinically significant, and charcoal must never delay acetylcysteine.
For an anaphylactoid reaction (up to 15% of patients): stop the infusion; give chlorphenamine 10–20 mg intravenously in an adult for more severe cases; treat bronchospasm with oxygen-driven nebulised salbutamol 5 mg (2.5 mg under 5 years) and hypotension with 0.9% sodium chloride 500 mL in an adult or 10 mL/kg in a child; then restart at a slower rate once symptoms settle, usually within 30–60 minutes, and complete the full 300 mg/kg.Doctor / Nurse
Distinguish true anaphylaxis — stridor, tongue or lip angio-oedema with airway compromise, or profound refractory hypotension — which requires intramuscular adrenaline 0.5 mg (0.5 mL of 1 in 1000) into the anterolateral thigh, repeated after 5 minutes if necessary.Doctor / Nurse
Nausea and vomiting are common and are not a reason to stop: give ondansetron 4–8 mg intravenously 8-hourly in adults, or 0.1–0.15 mg/kg (maximum 4 mg per dose) in children; metoclopramide 10 mg intravenously is an alternative but is best avoided in children, adolescents and young adults because of acute dystonic reactions (treated with procyclidine 5–10 mg intravenously or intramuscularly).Doctor / Nurse
At the end of the 21-hour course, repeat creatinine and electrolytes, bicarbonate, liver function and INR — and if these are abnormal, particularly if the ALT or INR is still rising, continue the 16-hour infusion (100 mg/kg over 16 hours) back-to-back until recovery.Doctor / Nurse
Correct hypoglycaemia immediately (10% glucose 2 mL/kg intravenously in a child) and run a continuous glucose infusion where endogenous production fails; measure glucose 2-hourly in the acute phase and prothrombin time at least twice daily.Doctor / Nurse

Caution— what harms

Never treat a paracetamol overdose on appearance: the disease is defined by a dose, a clock and a plasma concentration, and a well patient with normal bloods is the typical patient in the treatable phase.
Never interpret a paracetamol concentration taken before 4 hours — absorption and distribution are incomplete, and a low 2-hour level is meaningless and has led to fatal discharge.
Never wait for a laboratory result before starting acetylcysteine in a patient more than 8 hours from ingestion — in that situation the antidote is started before results return, not after.Doctor / Nurse
Never use the nomogram beyond 15 hours, after a modified-release preparation, after staggered ingestion or repeated therapeutic excess over more than 24 hours, after co-ingestion of an anticholinergic, opioid or salicylate, or where the timing is unknown; when doubt remains, treat.
Never assume normal liver function tests at 6 hours mean safety: liver damage is not usually detectable by routine tests until at least 18 hours after ingestion, and peaks at 72–96 hours.
Never read a falling ALT as recovery: a falling ALT with a rising INR indicates loss of viable hepatocytes; the INR is the prognostic test and the ALT is not.
Never be reassured by a normal albumin — it stays normal unless the course is prolonged and is falsely reassuring in the first days; and bilirubin rises late.
Never abandon the course because of an anaphylactoid reaction — these reactions are histamine-mediated and dose-rate related, not allergic, are not a contraindication to future acetylcysteine, are seldom serious, and a half-delivered course is an untreated overdose.Doctor / Nurse
Never give fresh frozen plasma except in major bleeding or before an unavoidable invasive procedure, because it abolishes the prothrombin time as a prognostic instrument without improving outcome.Doctor / Nurse
Never perform a percutaneous liver biopsy — it is contraindicated by the coagulopathy; a transjugular biopsy may be performed if histology is genuinely required.Doctor
Never give charcoal to a comatose or convulsing patient unless the airway is protected by a cuffed endotracheal tube, nor in ileus, obstruction or corrosive ingestion where endoscopy is planned; beyond 1–2 hours it offers little and the aspiration risk predominates. Gastric lavage and induced emesis have no place.Doctor / NurseNot available at your setup — Endotracheal intubation kit.
Never give a rapid 15-minute loading infusion when 60 minutes is available: anaphylactoid reactions are dose-rate related and rapid loading confers no demonstrated benefit.Doctor / Nurse
Never assume a normal-looking child is safe: the usual paediatric dose is 15 mg/kg every 4–6 hours to a maximum of 60 mg/kg in 24 hours, and doubling this over several days is a recognised route to hepatotoxicity; children have smaller glycogen reserves and become hypoglycaemic earlier.
Never discharge a deliberate self-poisoning without formal psychiatric assessment of suicide risk; intentional ingestion in an adolescent should prompt consideration of unwanted pregnancy or sexual abuse, and accidental ingestion in a young child raises safeguarding questions.

Refer / escalate

Seek specialist and transplant-unit advice early — before the adverse prognostic criteria are met, since a patient who fulfils them is often too unstable to transfer safely — for hepatic encephalopathy of any grade, a rising INR despite a completed course of acetylcysteine and vitamin K, arterial pH below 7.25 at or beyond 24 hours after fluid resuscitation, a prothrombin time above 100 seconds with grade 3 or 4 encephalopathy and creatinine above 300 micromoles per litre or anuria, arterial lactate above 5 mmol/L at presentation or above 4 mmol/L at 24 hours, or a high-risk ingestion of more than 30 g or a level more than twice the nomogram line.

The card — assess, manage, caution

Paracetamol poisoning — Level 1: CorePrevious Paracetamol poisoning — Level 3: Core practiceNext

Read the full lesson free

Create a free account to unlock every page, the level exams, and progress tracking.