Naloxone Infusion Protocol for Adult Opioid Overdose
For adult opioid overdose requiring continuous naloxone infusion, prepare 2 mg naloxone in 500 mL normal saline or D5W (concentration 0.004 mg/mL) and infuse at two-thirds of the effective bolus dose per hour after initial resuscitation. 1
Initial Bolus Dosing
Start with 0.4-2 mg IV naloxone as the initial bolus dose 1. The FDA label is clear on this range, and recent research confirms that lower doses (0.4 mg) are equally effective as higher doses (1-2 mg) for time to recurrence of toxicity 2.
- Administer IV for fastest onset (recommended in emergencies)
- Repeat every 2-3 minutes if inadequate response
- If no response after 10 mg total, question the diagnosis of opioid toxicity 1
Critical pitfall: Titrate to adequate ventilation, not full consciousness. Over-reversal causes withdrawal symptoms, hypertension, tachycardia, and patient agitation 1.
Continuous Infusion Setup
When repeat boluses are needed or long-acting opioids are involved:
Standard concentration: Add 2 mg naloxone to 500 mL normal saline or 5% dextrose = 0.004 mg/mL (4 mcg/mL) 1
Infusion rate calculation: Use two-thirds of the effective bolus dose per hour 3. For example:
- If 2 mg bolus reversed overdose → infuse at ~1.3 mg/hour
- If 0.4 mg bolus worked → infuse at ~0.27 mg/hour
The pharmacokinetic basis: naloxone has a short half-life (60-120 minutes) with rapid clearance 4. The two-thirds rule maintains plasma levels equal to or greater than what existed 30 minutes post-bolus 3.
Monitoring and Duration
- Continuous surveillance is mandatory - opioid duration often exceeds naloxone's effect 1
- Titrate infusion rate to patient response (adequate respirations, not full alertness) 1
- Most infusions run 4-5 hours (median 284 minutes in real-world data) 5
- Discard unused mixture after 24 hours 1
Key consideration: With fentanyl and synthetic opioids dominating current overdoses, higher naloxone doses may be required 4, 6. The traditional 0.4 mg dose was established in the heroin era. Start conservatively but be prepared to escalate quickly if inadequate response.
Practical Considerations
- Stability: Do not mix with bisulfite, metabisulfite, long-chain anions, or alkaline solutions 1
- Waste: Real-world data shows median 8 mg wasted per infusion 5 - prepare only what's needed
- Disposition: Most patients (45%) were discharged from ED, but 41% required admission (14% to ICU) 5
- Repeat dosing: Expect need for re-dosing around 70 minutes regardless of initial bolus size 2
Special Populations
Children: 0.01 mg/kg IV initial dose, may repeat with 0.1 mg/kg if inadequate response 1
Neonates: 0.01 mg/kg IV, IM, or SC 1
Postoperative patients: Use smaller increments (0.1-0.2 mg) every 2-3 minutes to avoid reversing analgesia and causing hypertension 1
The 2023 AHA guidelines emphasize that suspected opioid overdose should not delay naloxone administration, even in mixed overdoses with benzodiazepines 7. This is particularly critical given opioid-adulterated illicit drug supplies.