Where to Administer Naloxone
Naloxone can be administered via multiple routes—intramuscular (IM), intranasal (IN), intravenous (IV), or subcutaneous—with the choice depending on clinical setting, available access, and urgency of the situation. 1
Route Selection Algorithm
Intravenous (IV) Administration
- IV is the preferred route when venous access is available because it provides the most rapid onset of action 2
- Recommended for healthcare settings where IV access can be quickly established 2
- Initial dose: 0.4 mg to 2 mg IV, repeated at 2-3 minute intervals if needed 2
- Critical caveat: In cardiac arrest patients, medication administration is ineffective without concomitant chest compressions for drug delivery to tissues, so naloxone should only be considered after initiation of CPR 1
Intramuscular (IM) Administration
- IM is the recommended alternative when IV access is unavailable or difficult to obtain (common in chronic IV drug users) 1, 3
- FDA-approved autoinjector devices are available for both lay rescuers and healthcare providers 1
- Dose: 2 mg IM, repeated in 3-5 minutes if necessary 1
- IM administration produces longer-lasting effects compared to IV 2
- For respiratory arrest with definite pulse: It is reasonable for appropriately trained BLS healthcare providers to administer IM naloxone in addition to standard BLS care 1
Intranasal (IN) Administration
- IN is equally effective as IM for first-line treatment and is particularly useful in first aid settings by lay rescuers, family, or bystanders 1
- Dose: 2 mg IN (using higher concentration 2 mg/mL formulation), repeated in 3-5 minutes if necessary 1
- Important distinction: Higher-concentration IN naloxone (2 mg/mL) has similar efficacy to IM, while lower-concentration formulations (2 mg/5 mL) are less effective 4
- Reduces needlestick injury risk to rescuers 3
- Response time averages 3.4 minutes, with 91% of patients responding to IN alone 3
Subcutaneous Administration
Clinical Context Considerations
Respiratory Arrest (Pulse Present)
- Prioritize airway management and rescue breathing first 5, 6
- Administer naloxone (IM or IN) in addition to standard BLS/ACLS care 1, 6
- Do not delay activation of emergency response systems while awaiting naloxone response 6
Cardiac Arrest (No Pulse)
- Standard resuscitative measures take absolute priority over naloxone administration 5, 6
- Naloxone may be considered after CPR initiation if high suspicion for opioid overdose exists 1
- Remember: medications cannot reach tissues without chest compressions 1
Community/First Aid Settings
- IN or IM routes are most practical for lay rescuers 1
- Both routes have been successfully used with commercially available kits 1
Critical Pitfalls to Avoid
Duration of Action Mismatch
- Naloxone's duration (30-60 minutes) is shorter than many opioids, particularly long-acting formulations 5, 6
- Patients must be observed in a healthcare setting until risk of recurrent opioid toxicity is low 5, 6
- Monitor continuously for at least 2 hours after the last naloxone dose 6
- Repeated doses or continuous infusion may be needed for long-acting opioid overdoses 5, 6
Withdrawal Precipitation
- Using the lowest effective dose minimizes acute withdrawal syndrome in opioid-dependent patients 1, 5
- Withdrawal symptoms (hypertension, tachycardia, vomiting, agitation) are rarely life-threatening 1, 5, 6
Rescue Dose Requirements
- IN naloxone requires rescue doses 2.17 times more often than IM/IV routes 7
- Be prepared to administer supplemental naloxone regardless of initial route 8, 7
Delayed Resuscitation
- Never delay standard resuscitation measures while waiting for naloxone to take effect 5
- Airway, breathing, and circulation support remain the foundation of care 5, 6