Buprenorphine Overdose

Buprenorphine overdose causes sedation and respiratory depression, but a ceiling effect makes severe toxicity less likely in adults taking it alone. The risk rises sharply with co-ingested sedatives, injection use and accidental ingestion by children, in whom even small doses can cause serious toxicity.

Buprenorphine is used for opioid dependence and pain, as sublingual tablets, films, patches and long acting injections. Deaths occur mostly with benzodiazepines, alcohol or other opioids. Children may develop respiratory depression after ingesting 2 mg or more.

Risk factors for harm. Co-ingestion of benzodiazepines, alcohol or other opioids, intravenous use, children, opioid naive status and respiratory disease.

Course. Sublingual onset in 30 to 60 minutes with duration of 24 to 72 hours, so respiratory depression may be prolonged and recur after naloxone.

Pathophysiology.

Buprenorphine is a partial mu opioid agonist with very high receptor affinity and slow dissociation, giving a ceiling on respiratory depression but making it hard to reverse.

It is also a kappa antagonist and has effects at the nociceptin receptor.

• Drowsiness, miosis, nausea, vomiting, dizziness and itching.
• Respiratory depression (less than with full agonists), hypoventilation and hypoxia, especially with sedatives.
• Hypotension, bradycardia and QT prolongation (rare).
• Withdrawal on rapid reversal in dependent patients.

Red flags.

• Respiratory rate under 8 breaths/minute or hypoxia.
• Any child with an ingestion.
• Co-ingested benzodiazepine, alcohol or opioid.

• Clinical syndrome of sedation, miosis and respiratory depression; response to high dose naloxone.
• History of preparation, dose and co-ingestants; paracetamol (including combination products with naloxone) and salicylate levels.
• Blood gas, glucose, electrolytes, renal and liver function, ECG and chest imaging.
• Urine drug screen with specific buprenorphine assay; routine opiate screens do not detect it.

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

• Airway protection, oxygen and ventilation as needed; ventilation is often enough in adults with mild depression.
• Naloxone intravenously in higher doses than usual: 0.4 mg intravenously, repeated every 2 to 3 minutes and increased to 2 mg, then 4 mg, for each dose until breathing is adequate. Maximum 10 mg before reviewing the diagnosis (up to 15 mg has been used in intensive care). Monitor respiratory rate, oxygen saturation, withdrawal and re-sedation. In opioid dependent patients, titrate in smaller steps; no renal or hepatic adjustment; acceptable in pregnancy.
• Naloxone infusion if breathing falls again: 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 of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness without a protected airway, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Children: naloxone 10 micrograms/kg intravenously, repeated up to 100 micrograms/kg if no response. Maximum 2 mg for each dose. Monitor respiratory rate and re-sedation. Admit for at least 24 hours for any ingestion.
• Remove patches and wash the skin with water; observe for at least 24 hours after removal.
• Avoid flumazenil if benzodiazepine dependence is suspected (seizures); use only for confirmed benzodiazepine overdose by specialist decision.
• Long acting injection overdose: prolonged observation and supportive care.
• Observe for at least 12 hours after the last naloxone dose, and 24 hours for children.
• Psychiatric assessment in intentional ingestion; safe storage education for homes with children.

Monitoring. Respiratory rate, oxygen saturation and conscious level hourly; ECG if QT-prolonging drugs were co-ingested.

Referral and escalation. Poisons information centre; paediatric and intensive care for children or hypoventilation; addiction services after recovery.

Special groups. Children: admit with any ingestion. Pregnancy: naloxone is acceptable, with obstetric advice.