Opioid Overdose

Opioid overdose results from excessive agonism at mu opioid receptors, causing central respiratory depression, sedation, and, at the periphery, reduced gastrointestinal motility.

It may occur from prescription opioids, heroin, or, increasingly, illicitly manufactured fentanyl and its analogues, which are substantially more potent than heroin and have driven a marked rise in overdose mortality in many regions.

Risk is heightened after a period of reduced tolerance, such as following release from incarceration, discharge from an abstinence based treatment program, or after a period of hospitalization, since previously tolerated doses can become fatal.

The classic opioid toxidrome is a triad of:

• Reduced consciousness, ranging from drowsiness to deep coma
• Respiratory depression, with a reduced respiratory rate, shallow breathing, and, in severe cases, apnea, this being the proximate cause of death in fatal overdose
• Miosis (pinpoint pupils), though this may be absent with certain agents or in the context of significant hypoxia (which itself can cause secondary pupillary dilation)

Additional features include hypotension, bradycardia, hypothermia, and reduced bowel sounds. Non-cardiogenic pulmonary edema is a recognized complication, particularly with heroin overdose.

Diagnosis is primarily clinical, based on the toxidrome above and, where available, a history or collateral evidence of opioid use (paraphernalia, prescription history, track marks).

• A trial dose of naloxone, serves as both treatment and a diagnostic test, since a clear improvement in respiratory rate and consciousness strongly supports the diagnosis.
• Blood glucose should always be checked, since hypoglycemia can mimic or coexist with opioid toxicity.
• Paracetamol and salicylate levels should be considered given the frequency of co-ingestion in intentional overdose.
• ECG is useful given that certain opioids (notably methadone) can prolong the QT interval.

Differentials include other sedative toxidromes (benzodiazepine, alcohol), hypoglycemia, and primary CNS pathology (stroke, intracranial hemorrhage), particularly if the response to naloxone is incomplete or absent.

Airway, breathing, and circulation take priority, with bag mask ventilation providing immediate respiratory support while antidote treatment is prepared.

• Naloxone, a competitive opioid receptor antagonist, is given intravenously, intramuscularly, or intranasally. In a patient with no reason to suspect chronic opioid dependence, give 0.4 to 2 mg intravenously, repeated every 2 to 3 minutes as needed; if there is no response after a cumulative 10 mg, reconsider the diagnosis. Where chronic dependence is suspected, start at a much smaller dose, 0.04 to 0.1 mg intravenously, and titrate upward in small increments every 2 to 3 minutes to restore adequate respiration, rather than aiming for full reversal of consciousness or precipitating acute, distressing withdrawal. In children, the initial dose is 0.01 mg/kg intravenously.
• Naloxone has a shorter half life than many opioids, particularly long acting formulations and methadone, so re-sedation after initial reversal is common, and patients require an extended period of observation (generally a minimum of several hours, longer for long acting agents) even after apparently successful initial reversal.
• A naloxone infusion may be required for overdose with long acting opioids, titrated to maintain adequate respiratory function.
• Take home naloxone programs, providing naloxone kits to patients at risk of future overdose and their contacts, are an important harm reduction measure and should be discussed and facilitated where available before discharge.
• Underlying opioid use disorder should be addressed once the patient is stabilized, with referral to addiction services, and discussion of opioid substitution therapy (methadone or buprenorphine) where relevant and available, given that overdose is a critical opportunity to engage patients in longer term treatment.

Referral: addiction or substance use services for ongoing management of underlying opioid use disorder; psychiatry if the overdose was an intentional act of self harm.