Fentanyl Overdose

Fentanyl overdose causes rapid onset, profound respiratory depression, often with chest wall rigidity. It is a leading cause of overdose deaths in North America and is increasingly seen in other regions, including through illicit counterfeit tablets and contaminated drug supplies.

Fentanyl is 50 to 100 times as potent as morphine, and synthetic opioid involvement now accounts for most opioid overdose deaths in the United States. Transdermal patches, lozenges and nasal sprays are prescribed, and illicit powder contains unknown concentrations.

Risk factors for harm. Opioid naive status, illicit supply of unknown strength, co-use of benzodiazepines, xylazine or alcohol, heat exposure with patches, and use of damaged or multiple patches.

Course. Intravenous or inhaled use acts within seconds to minutes; patches release for 72 hours and a depot remains in the skin for 24 hours or more after removal.

Pathophysiology.

Fentanyl is a highly lipophilic mu opioid agonist that rapidly crosses the blood brain barrier, suppressing respiration and consciousness.

Rigid chest wall and vocal cord closure result from effects on brainstem and spinal motor circuits.

• Sudden unresponsiveness, pinpoint pupils, slow or absent breathing and cyanosis.
• Chest wall rigidity (wooden chest) that impairs ventilation.
• Bradycardia, hypotension, pulmonary oedema and seizures or myoclonus.
• Coadministration signs: xylazine causes skin ulcers and prolonged sedation.

Red flags.

• Apnoea or respiratory rate under 8 breaths/minute.
• Chest wall rigidity or difficulty with bag mask ventilation.
• Recurrent respiratory depression after naloxone.

• Clinical triad of unresponsiveness, miosis and respiratory depression; response to naloxone.
• Routine urine opiate screens do not detect fentanyl; use specific fentanyl immunoassay or confirmatory testing when available.
• Blood gas, glucose, creatine kinase, renal function, paracetamol level, ECG and chest imaging.
• Examine the skin for patches and remove them.

Differential diagnosis. Other opioid overdose, benzodiazepine overdose, xylazine intoxication, hypoglycaemia, stroke and alcohol intoxication.

• Airway, ventilation and oxygen first; bag mask ventilation with an airway adjunct.
• 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. Higher or repeated doses may be needed because of fentanyl potency. In opioid dependent patients, titrate in 0.04 to 0.1 mg steps; no renal or hepatic adjustment; acceptable in pregnancy.
• Naloxone infusion: 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.
• Chest wall rigidity not responding to naloxone: rocuronium 1 mg/kg intravenously once with intubation and ventilation. Maximum 1 mg/kg for each dose. Monitor neuromuscular blockade and ventilation; reduce dose in hepatic impairment; use caution in pregnancy. Avoid suxamethonium if hyperkalaemia is suspected.
• Patch exposure: remove all patches, wash the skin with water (not alcohol, which increases absorption), avoid heat, and observe for at least 24 hours after removal because of the skin depot.
• Pulmonary oedema: oxygen, positive airway pressure and ventilation; avoid diuretics unless fluid overloaded.
• Observe for at least 6 hours after the last naloxone dose (24 hours for patches, lozenges or large ingestions).
• Xylazine co-exposure: supportive care for sedation, bradycardia and hypotension; naloxone does not reverse xylazine; wound care for ulcers.
• Overdose education, take home naloxone and referral to addiction services after recovery.

Monitoring. Respiratory rate, oxygen saturation, conscious level and cardiac rhythm continuously until stable for 6 hours.

Referral and escalation. Intensive care for hypoventilation, rigidity or infusion; addiction services and harm reduction after recovery.

Special groups. Children: strict observation after any exposure to patches, which can be fatal. Pregnancy: naloxone is acceptable.