What is the recommended dose and administration route for naloxone (opioid antagonist)?

Naloxone Administration: Dose and Route

For suspected opioid overdose, administer naloxone 0.4 to 2 mg IV/IM/IN as the initial dose, repeating every 2-3 minutes if inadequate response, with IV being the fastest route but IM (2 mg) and IN (2 mg) serving as equally effective alternatives when IV access is unavailable. 1, 2, 3

Route Selection Algorithm

Intravenous (IV) - Preferred When Access Available

• IV provides the most rapid onset of action and is recommended in emergency situations 2, 3
• Initial dose: 0.4 to 2 mg IV 2, 3
• For opioid-dependent patients, consider starting lower (0.04 to 0.4 mg) to minimize precipitating severe withdrawal 4
• Repeat or escalate to 2 mg every 2-3 minutes if inadequate response 5, 2, 3
• IV allows for precise titration to effect, which is critical for balancing respiratory restoration against withdrawal 1, 6

Intramuscular (IM) - When IV Unavailable

• IM is the preferred alternative when IV access is unavailable or difficult to obtain 1
• Dose: 2 mg IM, repeated in 3-5 minutes if necessary 5, 1
• IM produces longer-lasting effects than IV, which may be advantageous for prolonged opioid effects 2, 3
• Onset is slower than IV but faster than intranasal 6

Intranasal (IN) - Equally Effective for First-Line Treatment

• IN naloxone (2 mg) is equally effective as IM and particularly useful for lay rescuers, family, or bystanders in first aid settings 1
• Dose: 2 mg IN using higher concentration (2 mg/mL) formulation, repeated in 3-5 minutes if necessary 5, 1
• Nasal bioavailability is approximately 50%, with mean time to maximum concentration of 15-30 minutes 6
• Reversal of respiration may lag slightly behind IM administration 6
• Low-volume devices (0.1-0.2 mL) are superior to improvised high-volume devices and require minimal training 7

Clinical Context-Specific Dosing

Respiratory Arrest with Pulse Present

• Administer naloxone (IM or IN) in addition to standard BLS care, but prioritize bag-mask ventilation first 1, 4
• The goal is restoration of adequate ventilation, not necessarily full consciousness 5

Cardiac Arrest

• Standard resuscitative measures (high-quality CPR) take absolute priority over naloxone administration 1, 4
• Naloxone may be considered after CPR initiation if high suspicion for opioid overdose, but has no proven benefit in cardiac arrest 4
• Medications are ineffective without chest compressions for drug delivery to tissues 1

Postoperative Opioid Depression

• Use smaller incremental doses: 0.1 to 0.2 mg IV every 2-3 minutes, titrated to adequate ventilation and alertness without significant pain 2, 3
• Larger than necessary doses result in significant analgesia reversal, hypertension, and circulatory stress 4, 2, 3

Dose Escalation Strategy

• If no response after 10 mg total naloxone administered, question the diagnosis of opioid-induced toxicity 2, 3
• Fentanyl and synthetic opioid overdoses likely require higher doses than heroin overdoses 6
• The initial 0.4-0.8 mg parenteral dose is usually sufficient for heroin overdose 6

Critical Pitfalls to Avoid

Duration of Action Mismatch

• Naloxone's duration of action (30-70 minutes) is shorter than most opioids, particularly long-acting formulations like methadone or sustained-release preparations 1, 4, 6
• Patients must be observed in a healthcare setting until risk of recurrent opioid toxicity is low and vital signs normalized 1, 4
• Repeated small doses or continuous infusion (two-thirds of effective bolus dose per hour) may be necessary for recurrent toxicity 4, 8

Withdrawal Precipitation

• Use the lowest effective dose to minimize acute withdrawal syndrome in opioid-dependent patients 1, 4
• Withdrawal symptoms include hypertension, tachycardia, piloerection, vomiting, agitation, and drug cravings, but are rarely life-threatening 4
• Too rapid reversal induces nausea, vomiting, sweating, and circulatory stress 4, 2, 3

Resuscitation Priorities

• Never delay standard resuscitation measures (airway, breathing, circulation support) while waiting for naloxone to take effect 1, 4
• Provide bag-mask ventilation before naloxone administration 4

Premature Discharge

• Never discharge patients prematurely after successful reversal, as recurrent depression is common 4
• Longer observation required for long-acting opioids 4

Mixed Overdoses

• Naloxone will not reverse respiratory depression from non-opioid drugs such as benzodiazepines 4
• Recognize mixed overdoses and maintain ventilatory support regardless of naloxone response 4

Special Considerations

• Naloxone has an excellent safety profile with no known harms when administered to non-opioid intoxicated patients 4
• Nebulized naloxone (2 mg diluted in 3 mL normal saline) has been studied and well-tolerated but is less commonly used 5
• For continuous IV infusion: add 2 mg naloxone to 500 mL normal saline or 5% dextrose (concentration 0.004 mg/mL), use within 24 hours, titrate to patient response 2, 3
• Laypeople should have access to at least two dose kits for interim intervention 6