Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Toxidromes - opioid

Description

Triad: miosis + resp depression (dec RR) + dec GCS
- +/- hypotension, dec bowel sounds, hypothermia
Causes: heroin, morphine, oxycodone, fentanyl (+ analogues), codeine, methadone, tramadol
- Tramadol/pethidine also cause seizures + serotonin toxicity - not a pure opioid picture
- Buprenorphine - partial agonist, ceiling effect on resp depression, but still fatal with co-depressants

Epidemiology

Leading cause of drug-induced death in Australia
inc driven by illicit fentanyl contamination of heroin/counterfeit pills
Also iatrogenic - postoperative, opioid-naive patients after dose escalation, chronic pain patients

Aetiopathogenesis

Mu-opioid receptor agonism
- Brainstem resp centre: dec sensitivity to CO2 -> hypoventilation, apnoea
- Edinger-Westphal nucleus stimulation -> pupillary constriction
- CNS depression -> dec GCS
- dec GI motility -> constipation, dec bowel sounds
- Histamine release (esp. morphine) -> flushing, pruritus, hypotension

Diagnosis

Clinical triad + response to naloxone = diagnostic
Normal/dilated pupils do NOT exclude opioid toxicity - mixed ingestion, hypoxia, meperidine/tramadol
ECG - QT prolongation with methadone
Paracetamol level in all deliberate self-poisoning (co-ingestion common)

Management

Airway and breathing first

Bag-mask ventilation if apnoeic - before naloxone

Naloxone

Titrate to adequate respiration, not full consciousness - avoid precipitating acute withdrawal/agitation
IV in small increments (e.g. 100 mcg), or IM/intranasal, titrated to RR >=10-12
Shorter-acting than most opioids -> re-sedation risk, esp. with methadone or sustained-release preparations -> observe or infusion

Disposition

Observe until GCS/RR remain normal off naloxone, for a period matching the opioid's duration of action
Take-home naloxone + counselling before discharge - every survived overdose is an opportunity

Associations

Co-ingestants: benzodiazepines, alcohol - synergistic resp depression, commonest combination in fatal overdose
Aspiration pneumonitis
Non-cardiogenic pulmonary oedema (esp. heroin)
Rhabdomyolysis/compartment syndrome from prolonged immobility

Natural history & complications

Death from resp arrest -> hypoxic brain injury
Recurrent overdose common - tolerance lost after abstinence (release from custody, rehab, detox) -> fatal miscalculation of usual dose
Every overdose survived is a trigger for OAT referral and take-home naloxone

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