Haloperidol Overdose

Haloperidol overdose causes sedation, extrapyramidal reactions, hypotension and QT prolongation with a risk of torsades de pointes. It can precipitate neuroleptic malignant syndrome.

Haloperidol is a high potency first generation antipsychotic used orally and by injection. Toxicity may appear above 0.5 mg/kg, and arrhythmia is more likely with intravenous use, high doses, hypokalaemia and hypomagnesaemia.

Risk factors for harm. Intravenous administration, other QT-prolonging drugs, structural heart disease, electrolyte disturbance, older age and dementia.

Course. Peak effects at 2 to 6 hours; the half life is about 20 hours, so effects last 1 to 3 days. Decanoate preparations release slowly over weeks.

Pathophysiology.

Strong dopamine D2 blockade causes extrapyramidal signs, and potassium channel (hERG) blockade prolongs repolarisation.

Alpha-1 antagonism causes hypotension.

• Drowsiness, agitation, acute dystonia (oculogyric crisis, torticollis), parkinsonism and akathisia.
• Hypotension, tachycardia, QT prolongation and torsades de pointes.
• Hypothermia or hyperthermia, seizures and coma in large ingestions.
• Neuroleptic malignant syndrome: fever, rigidity, autonomic instability and altered consciousness.

Red flags.

• QTc over 500 ms, syncope or arrhythmia.
• Fever with rigidity and raised creatine kinase.
• Laryngeal dystonia or respiratory difficulty.

• History of dose, route and other QT-prolonging drugs; paracetamol and salicylate levels.
• ECG on arrival and repeated; potassium, magnesium and calcium.
• Creatine kinase, renal function, glucose, venous gas, and full blood count.
• Clinical diagnosis of neuroleptic malignant syndrome from fever, rigidity, autonomic instability and raised creatine kinase.

Differential diagnosis. Serotonin toxicity, malignant hyperthermia, anticholinergic toxicity, other antipsychotic overdose, catatonia and encephalitis.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Continuous ECG monitoring; correct potassium to over 4.0 mmol/L and magnesium to over 1.0 mmol/L.
• Torsades de pointes: magnesium sulphate 2 g (8 mmol) intravenously over 10 minutes, repeated once if needed. Maximum 4 g in the first hour. Monitor reflexes, respiratory rate and magnesium; reduce dose in renal impairment. Use overdrive pacing or isoprenaline for recurrent torsades (specialist), and defibrillate for pulseless arrhythmia.
• Acute dystonia: procyclidine 5 mg intravenously or intramuscularly, repeated after 20 minutes if needed. Maximum 20 mg in 24 hours. Monitor heart rate, confusion and urinary retention. Avoid in glaucoma, gastrointestinal obstruction and urinary retention; use lower doses in older adults.
• Hypotension: intravenous fluids, then noradrenaline 0.05 micrograms/kg/minute intravenously, titrated to a mean arterial pressure of 65 mmHg or higher (maximum 1 microgram/kg/minute; central line; monitor blood pressure and extravasation). Avoid adrenaline and dopamine.
• Agitation: diazepam 5 to 10 mg intravenously, repeated every 5 to 10 minutes as needed. Maximum 30 mg in the first hour without specialist review. Monitor breathing, oxygen saturation and blood pressure. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• Seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if seizures continue. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• Neuroleptic malignant syndrome: stop the drug, give cooling, fluids and benzodiazepines; dantrolene 1 mg/kg intravenously, repeated every 10 minutes to a maximum of 10 mg/kg; monitor liver function, temperature and creatine kinase; avoid in hepatic impairment (use caution); bromocriptine 2.5 mg orally or by nasogastric tube three times daily, increased to a maximum of 40 mg daily (monitor blood pressure and psychosis; avoid in hypertension and pregnancy related hypertensive disorders).
• Observe for at least 6 hours (24 hours for QT prolongation or large ingestions).

Monitoring. Continuous ECG, temperature, creatine kinase, electrolytes and renal function.

Referral and escalation. Poisons information centre; intensive care for arrhythmia, neuroleptic malignant syndrome or coma.

Special groups. Older adults and people with dementia: higher risk of arrhythmia and death. Children: acute dystonia is common after small doses.