Morphine Overdose

Morphine overdose causes sedation, miosis and life threatening respiratory depression. It occurs through intentional or accidental ingestion, dosing errors, interactions and accumulation in renal failure, and is reversed by naloxone.

Morphine remains a major cause of drug related deaths, mainly in combination with other sedatives. A dose over 1 mg/kg orally can cause severe toxicity in the opioid naive, and 0.5 mg/kg in children.

Risk factors for harm. Opioid naive status, renal impairment (accumulation of morphine-6-glucuronide), older age, hepatic impairment, modified release preparations, co-use of sedatives and sleep apnoea.

Course. Peak effect in 1 to 2 hours orally and 20 minutes intravenously; duration of 4 to 6 hours, and 12 to 24 hours or longer for modified release preparations or renal failure.

Pathophysiology.

Morphine activates mu opioid receptors in the brainstem respiratory centres, reducing sensitivity to carbon dioxide.

Histamine release contributes to hypotension, and metabolite accumulation prolongs the effect in renal failure.

• Drowsiness, miosis, slow breathing, cyanosis and coma.
• Hypotension, bradycardia, hypothermia, pulmonary oedema and aspiration.
• Myoclonus, seizures and hyperalgesia with high doses or in renal failure.
• Intravenous use: needle marks, skin infection.

Red flags.

• Respiratory rate under 8 breaths/minute, hypoxia or apnoea.
• Renal failure with recurrent sedation.
• Modified release ingestion with a delayed peak.

• Clinical triad of reduced consciousness, miosis and respiratory depression; response to naloxone.
• History of dose, formulation and co-ingestants; paracetamol and salicylate levels.
• Blood gas, glucose, electrolytes, renal and liver function, creatine kinase and chest imaging.
• Urine opiate immunoassay confirms exposure but does not guide treatment.

Differential diagnosis. Other opioid overdose, benzodiazepine or barbiturate overdose, alcohol intoxication, hypoglycaemia, stroke and head injury.

• Airway protection, oxygen and ventilation as needed.
• Naloxone 0.4 mg intravenously, repeated every 2 to 3 minutes and increased up to 2 mg for each dose until the respiratory rate is over 10 breaths/minute and breathing is adequate (intramuscular 0.4 to 2 mg, or intranasal 4 mg). Maximum 10 mg before reviewing the diagnosis. Monitor respiratory rate, oxygen saturation, withdrawal (agitation, vomiting, pulmonary oedema) and re-sedation. In opioid dependent patients, titrate in 0.04 to 0.1 mg steps; no renal or hepatic adjustment; acceptable in pregnancy.
• Naloxone infusion for modified release preparations or renal failure: two thirds of the total bolus dose that restored breathing, given each hour in 5% glucose, titrated to a respiratory rate over 10 breaths/minute. Maximum 4 mg/hour. Monitor respiratory rate, oxygen saturation and withdrawal signs; stop after 12 hours if no re-sedation.
• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour (2 hours for modified release) 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.
• Whole bowel irrigation for large modified release ingestions with a protected airway, under specialist advice: polyethylene glycol electrolyte solution 1 to 2 litres/hour orally or via nasogastric tube (children 25 mL/kg/hour) until the rectal effluent is clear. Monitor for vomiting, aspiration and abdominal distension. Avoid in ileus, obstruction, haemodynamic instability and unprotected airway.
• Hypotension: 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. Give by central line; monitor blood pressure and extravasation.
• Renal failure: dose the opioid by creatinine clearance in future, and consider haemodialysis for recurrent toxicity from morphine metabolites.
• Observe for at least 6 hours after the last naloxone dose (12 to 24 hours for modified release).
• Psychiatric assessment in intentional ingestion; naloxone supply and overdose education after recovery.

Monitoring. Respiratory rate, oxygen saturation, conscious level and urine output hourly during treatment.

Referral and escalation. Poisons information centre for large or modified release ingestions; intensive care for hypoventilation, infusion or shock.

Special groups. Renal impairment and older adults: reduce doses. Children: calculate naloxone by weight.