Opioid Toxicity and Overdose
Pharmacology Overview
Opioids are a drug class, not one specific drug. Common examples include: [Ref]
- Morphine
- Codeine
- Fentanyl
- Oxycodone
- Heroin (diamorphine)
MoA: [Ref]
- Primarily a μ (mu) opioid receptor agonist
- μ-receptor activation causes:
- ↓ Presynaptic Ca²⁺ influx → ↓ neurotransmitter release
- ↑ Postsynaptic K⁺ efflux → neuronal hyperpolarisation
Key opioid related medications:
- Acute opioid toxicity / overdose → naloxone (opioid receptor antagonist)
- Long-term management of opioid dependence
- Methadone = full μ-opioid receptor agonist
- Buprenorphine = partial μ-opioid receptor agonist and κ-opioid receptor antagonist
Opiates vs opioids
- Opiates = naturally derived from opium, e.g. morphine and codeine
- Opioids = broader term covering natural, semi-synthetic and synthetic opioid drugs, e.g. heroin, fentanyl, methadone
Clinical Features
Classic triad of acute opioid toxicity: [RCEM/NPIS]
- Miosis (pinpoint pupils)
- Respiratory depression (hypoventilation and ↓ respiratory rate)
- CNS depression (drowsiness, reduced GCS)
Other possible clinical features: [RCEM/NPIS]
- Hypotension
- Bradycardia
- Hypothermia
- Seizures
- Other expected effects of opioids (e.g. euphoria, nausea, vomiting, pruritus)
Commonly, opioids are co-ingested with alcohol or other CNS depressants that can further exacerbate respiratory depression, such as benzodiazepines and pregabalin. [RCEM/NPIS]
Investigation and Diagnosis
Clinical diagnosis [RCEM/NPIS]
- Urine drug screening is NOT required to diagnose acute opioid toxicity and should not delay treatment
- Naloxone may also be used diagnostically: improvement in consciousness and respiratory depression after naloxone administration supports opioid toxicity as the cause
Acute Management
Acute opioid toxicity / overdose should be approached with an A-E assessment
- Airway and breathing take priority (i.e. ventilation and oxygen)
- Naloxone for suspected opioid-induced respiratory depression
Building on the A-E approach, management is based on the patient’s clinical state: [RCEM/NPIS]
- Respiratory rate (RR), and
- SpO2 on room air
| Clinical state | Immediate airway and breathing management | Naloxone therapy |
|---|---|---|
| RR >10/min
AND SpO2 >92% on RA |
Consider discharge if the parameters are within normal limits for 6 hours after suspected time of overdose |
|
| RR 6-10/min
OR SpO2 <92% on RA |
|
1st line: IV naloxone boluses 100-200 mcg every 60 sec (maximum dose: 2,000 mcg)
RR >10 after naloxone = adequate response to naloxone
Consider discharge if RR, SpO2, ETCO2, and level of consciousness are within normal limits 4 hours after naloxone and if it has been 6 hours since time of overdose |
| Respiratory arrest
OR RR ≤5/min OR SpO2 <85% on RA |
Ventilate with BVM
|
1st line: IV naloxone bolus 400 mcg
If there is no response after the first dose
|
Naloxone = antidote for opioid toxicity / overdose
- Naloxone is used to 1) reverse respiratory depression and 2) maintain airway protective reflexes
- However, naloxone does NOT fully reverse the CNS depression