What is the recommended dose of naloxone (opioid antagonist) as an antidote for opioid overdose?

Naloxone Dosing for Opioid Overdose

For opioid overdose with respiratory depression, administer an initial dose of 0.4 to 2 mg naloxone intravenously, intramuscularly, or intranasally, titrating to restore adequate breathing—not full consciousness—to minimize precipitating severe withdrawal in opioid-dependent patients. 1, 2

Initial Dose Selection by Route

Intravenous Administration

• Start with 0.4 to 2 mg IV as the initial dose for suspected opioid overdose 2
• IV provides the most rapid onset of action and is recommended in emergency situations 2
• If inadequate response, repeat at 2-3 minute intervals 2
• If no response after 10 mg total, question the diagnosis of opioid toxicity 2

Intramuscular Administration

• Administer 2 mg IM when IV access is unavailable 3
• Repeat in 3-5 minutes if necessary 3
• IM administration produces a longer-lasting effect than IV 2

Intranasal Administration

• Give 2 mg IN as an effective alternative route 3
• Repeat in 3-5 minutes if needed 3
• Intranasal bioavailability is approximately 50%, with peak concentrations reached in 15-30 minutes 4
• Nasal uptake may be slower than IM, with reversal of respiration lagging behind IM naloxone 4

Critical Dosing Principles

Titrate to Breathing, Not Consciousness

• The goal is restoration of adequate ventilation, not full alertness 2
• Use the lowest effective dose to minimize withdrawal symptoms 3, 5
• For opioid-dependent patients, consider starting with lower doses (0.04-0.4 mg) to avoid precipitating severe withdrawal 6

Severity-Based Approach

• Patients with severe respiratory depression or CNS depression may require the higher end of the dosing range (2 mg) 3
• Patients with known opioid dependency benefit from lower initial doses to prevent acute withdrawal syndrome 3

Pediatric Dosing

• Initial dose: 0.01 mg/kg IV for pediatric patients 2
• If inadequate response, administer a subsequent dose of 0.1 mg/kg 2
• Use IM or subcutaneous routes if IV unavailable 2

Neonatal Dosing

• 0.01 mg/kg IV, IM, or subcutaneous for opioid-induced depression 2

Management Algorithm

Step 1: Prioritize Airway and Breathing

• Establish airway patency and provide bag-mask ventilation BEFORE naloxone 3, 5
• Do not delay standard BLS/ACLS care while awaiting naloxone response 5

Step 2: Administer Naloxone

• For patients with definite pulse but no normal breathing or only gasping, give naloxone in addition to standard resuscitation 3, 5
• In cardiac arrest, standard resuscitative measures take priority over naloxone administration 3

Step 3: Titrate and Repeat

• Reassess respiratory status every 2-3 minutes 2
• Repeat doses as needed, using incremental increases 2
• For postoperative opioid depression, use smaller increments (0.1-0.2 mg IV) every 2-3 minutes 2

Step 4: Monitor for Re-sedation

• Naloxone's duration of action (30-120 minutes) is shorter than many opioids 3, 4
• Observe patients in a healthcare setting for at least 2 hours after the last naloxone dose 5
• Repeated small doses or continuous infusion may be necessary for long-acting opioid overdoses 3, 5

Special Considerations

Fentanyl and Synthetic Opioids

• Fentanyl overdoses likely require higher doses of naloxone than heroin overdoses 4
• Initial parenteral doses of 0.4-0.8 mg are usually sufficient for heroin, but synthetic opioids may need more 4

Mixed Overdoses

• Naloxone will NOT reverse respiratory depression from benzodiazepines or other non-opioid CNS depressants 3
• Do not withhold naloxone when opioid overdose is suspected, even if benzodiazepines are also involved 1

Common Pitfalls to Avoid

Precipitating Withdrawal

• Acute opioid withdrawal syndrome can occur with excessive or rapid naloxone administration 3, 5
• Withdrawal symptoms include hypertension, tachycardia, vomiting, agitation, and drug cravings 3
• Avoid by using the lowest effective dose and titrating slowly 3, 5

Premature Discontinuation of Monitoring

• Never discharge patients immediately after naloxone response 3, 5
• Risk of recurrent respiratory depression exists as naloxone wears off 3, 5
• Continue monitoring until vital signs normalize and risk of recurrent toxicity is low 3

Delaying Standard Resuscitation

• Do not wait for naloxone to work before providing airway management and ventilation 3
• Activate emergency response systems immediately 5

Safety Profile

• Naloxone has an excellent safety profile with no known harms when administered to non-opioid intoxicated patients 3, 5
• The drug is safe over a wide dose range (up to 10 mg) 7
• Primary risk is precipitating withdrawal in opioid-dependent individuals 3, 7