Opioid toxicity is an important consideration in palliative care. It may arise from dose escalation, organ failure (liver and renal), or drug interactions.
Increased risk if Morphine Equivalent Daily Dose (MEDD) > 120mg per day but can occur at much lower doses.
Incidence can be as high as 15-20%.
Red Flags
- Myoclonus (twitching muscles)
- Hallucinations
- Increased sensitivity to painful stimuli (hyperalgesia) and non-painful stimuli (allodynia)
- Slow breathing (<8 breaths/min)
Clinical Features
- CNS: increasing drowsiness, delirium, hallucinations
- Neuromuscular: myoclonus, hyperalgesia, falls
- GI: nausea, vomiting, constipation
- Respiratory: slow, shallow breathing
An initial approach to treatment
- Review opioid dose - reduce to 25% of the current dose and add in non-opioid analgesics
- Check renal/hepatic function - are there recent changes?
- Stop interacting drugs - e.g. concomitant use of pregabalin increases risk with oxycodone
- Fluids may help
Specific treatments according to symptom
| Cause | Treatment |
|---|---|
| Accumulation | Reduce or switch opioid (e.g. to fentanyl in renal failure) |
| Neurotoxicity | Reduce dose or switch opioid |
| Delirium | Reduce dose and consider haloperidol or levomepromazine |
| Respiratory depression | Rarely use naloxone (if required due to breathing compromise then titrate very carefully) |
| Myoclonus | Reduce dose, opioid switch, or add clonazepam |
| Hyperalgesia | Reduce dose or switch; add non-opioids |
When switching opioids, reduce the equianalgesic dose by 30–50% to allow for incomplete cross-tolerance.
Risk factors
Age > 65, frailty, rapid dose escalation, liver and renal failure, concomitant psychotropic drugs