Management of Opioid Poisoning
For suspected opioid overdose with respiratory depression or arrest, immediately administer naloxone while simultaneously providing standard airway management and ventilatory support, prioritizing high-quality CPR if cardiac arrest is suspected. 1
Immediate Resuscitation
Airway and breathing take absolute priority - establish an open airway and provide bag-mask ventilation or rescue breathing until spontaneous respirations return. 1 Standard BLS/ALS measures should continue if spontaneous breathing does not occur. 1 If cardiac arrest is suspected, focus on high-quality CPR (compressions plus ventilation) as the primary intervention, with naloxone as an adjunct rather than a replacement for resuscitation. 1
Activate emergency response systems immediately without waiting to assess the patient's response to naloxone. 1 This is a critical pitfall to avoid - never delay calling for help while attempting naloxone administration. 1
Naloxone Administration
Dosing Strategy
Titrate naloxone to restore respiratory effort, not consciousness. 2, 1 The goal is reversal of respiratory depression and restoration of protective airway reflexes, not full arousal. 2
- Adults: Initial dose 0.2-2 mg IV/IO/IM 2
- Pediatric: 0.1 mg/kg 2
- Intranasal: 2-4 mg, repeat every 2-3 minutes as needed 2
Use the lowest effective dose to minimize withdrawal symptoms. 1 In opioid-dependent patients, low-dose naloxone (0.04 mg) with appropriate titration is prudent to avoid precipitating acute opioid withdrawal syndrome. 3 Excessive doses can cause significant reversal of analgesia, agitation, nausea, vomiting, tachycardia, hypertension, seizures, ventricular arrhythmias, pulmonary edema, and cardiac arrest. 4
Route Considerations
Higher-concentration intranasal naloxone (2 mg/mL) has similar efficacy to intramuscular naloxone for reversal of opioid overdose. 5 However, nasal uptake (mean Tmax 15-30 minutes) is likely slower than intramuscular administration. 6 Nasal bioavailability is approximately 50%. 6
Special Considerations for Specific Opioids
Fentanyl overdoses likely require higher doses of naloxone than traditional opioids like heroin. 6 Initial parenteral doses of 0.4-0.8 mg are usually sufficient for heroin overdose, but synthetic opioids may need more. 6
Long-acting opioids and those with high μ-opioid receptor affinity (such as buprenorphine) are particularly resistant to naloxone effects. 7 Large doses of naloxone are required to antagonize buprenorphine due to its slow dissociation from the opioid receptor. 4 Buprenorphine antagonism is characterized by gradual onset of reversal effects and decreased duration of action. 4
Post-Naloxone Management
The duration of action of naloxone (approximately 2 hours for 1 mg IV) may be shorter than the respiratory depressive effect of the opioid. 1, 6 This creates risk for recurrent toxicity, particularly with long-acting or sustained-release formulations. 1
Observation and Monitoring
Patients must be observed in a healthcare setting until the risk of recurrent opioid toxicity is low and vital signs have normalized. 1 Tailor observation periods to the specific opioid involved:
- Shorter periods may be adequate for fentanyl, morphine, or heroin overdose 1
- Longer periods are mandatory for long-acting or sustained-release opioids 1
If recurrent opioid toxicity develops, administer repeated small doses or a continuous infusion of naloxone. 1 The maintenance infusion is two-thirds of the waking dose per hour. 2
Naloxone Infusion Preparation
For continuous infusion, titrate to reversal of respiratory depression and restoration of protective airway reflexes. 2 Monitor closely for re-sedation as naloxone is rapidly eliminated (half-life 60-120 minutes) due to high clearance. 6
Polysubstance Overdose
Non-response to naloxone strongly suggests polysubstance overdose involving non-opioid substances such as benzodiazepines or xylazine. 1 In cases of suspected combined opioid and benzodiazepine poisoning, it is reasonable to administer naloxone first (before other antidotes) for respiratory depression or respiratory arrest. 2
Never withhold naloxone when opioid overdose is suspected, even if benzodiazepine co-ingestion is present. 2 This is particularly important given the prevalence of opioid-adulterated illicit drugs. 2
Critical Pitfalls to Avoid
- Delaying emergency system activation while awaiting response to naloxone 1
- Discharging patients too early after naloxone administration, especially with long-acting opioid ingestions 1
- Failing to consider co-ingestions that may require specific management approaches 1
- Over-dosing naloxone in opioid-dependent patients, precipitating severe withdrawal 4, 3
- Assuming naloxone alone is sufficient - other resuscitative measures including maintenance of airway, artificial ventilation, cardiac massage, and vasopressor agents must be available and employed when necessary 4
Adverse Effects of Naloxone
Use naloxone with caution in patients with pre-existing cardiac disease or those who have received medications with potential adverse cardiovascular effects. 4 Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported, particularly in postoperative patients with cardiovascular disorders. 4
Naloxone-associated pulmonary edema is rare at doses consistent with labeled use for opioid overdose. 1 The pathogenesis is similar to neurogenic pulmonary edema - a centrally mediated massive catecholamine response leading to dramatic shift of blood volume into the pulmonary vascular bed. 4 This responds to positive pressure ventilation. 1
Community and Lay Responder Role
It is reasonable for lay rescuers to receive training in responding to opioid overdose, including provision of naloxone. 1 Training that includes skills practice leads to improved clinical performance compared to interventions without skills practice. 1 Intranasal naloxone is feasible for bystander administration, with studies showing successful overdose reversals and uncommon problems. 8