Written by Elizabeth Cairns, Mobilize Recovery Special Projects and Michael Masiowski, MD, reviewed by Code Recover Clinician Advisors, August 2026

The primary goal of overdose resuscitation is the restoration of adequate spontaneous ventilation. While the "ABCs" remain the gold standard (airway, breathing, circulation), the surge in high-potency synthetics like fentanyl may require higher initial doses of naloxone or repeated administration. However, clinicians should aim for "low and slow" dosing (0.04mg to 0.1mg IV), titrating to restore adequate ventilation rather than to full arousal. A patient who is somnolent but ventilating adequately may not need naloxone at all, and may be better served by close observation while the opioid metabolizes. (source)

In cases of total respiratory arrest, naloxone should be administered without delay (source); standard initial dosing is 0.4mg to 2mg. Providers should be prepared for the "naloxone gap," where the opioid's half-life exceeds that of the antagonist, potentially leading to re-sedation. (source) This is particularly common with long-acting formulations or massive ingestions found in modern street supplies.

Beyond the immediate reversal, the post-arrest period is a critical window for stabilization. The HOUR rule (Hospital Observation Upon Reversal) holds that a patient may be safely discharged one hour after naloxone administration if all six of the following are met: ambulates as usual, oxygen saturation above 95% on room air, respiratory rate between 10 and 20, temperature between 35.0°C and 37.5°C, heart rate between 50 and 100, and a Glasgow Coma Scale of 15. (source) Meeting these criteria establishes medical readiness for discharge — but discharge should not occur without a connection to a peer with lived experience and a dispensed naloxone kit.

Care After an Overdose Reversal

The first hour following an overdose reversal is a high-risk, high-opportunity period. Physically, the patient may be experiencing the trauma of precipitated withdrawal or the lingering effects of hypoxia. Clinically, the assessment must focus on pulmonary complications (like non-cardiogenic pulmonary edema) and the risk of secondary "stacking" overdoses as the naloxone wears off. (source)

Psychologically, this is when a patient is most vulnerable. This is the optimal time to introduce a peer with lived experience. While the clinician handles the medical stabilization, the peer provides the "social stabilization" that prevents the patient from fleeing the ED out of shame or fear of withdrawal.

This patient population, the non-fatal overdose, has the highest risk of subsequent overdose death — 5.5% die within one year, 1.1% within one month, and 0.25% within two days. (source) It is the standard of care to initiate or offer MOUD. (source) Any reluctance on the part of the ED provider is outdated and opens the possibility to the increasing legal liability of not providing adequate care and stabilization. (source)

Documentation for post-overdose care should include the patient's mental status, oxygen saturation on room air, and their ability to ambulate. A standardized "discharge bundle" including overdose prevention education, a peer handoff, and a bridge prescription for MOUD is the current best practice for reducing subsequent overdose risk.

Fentanyl and Multi-substance Overdose Care

The opioid landscape has shifted from prescription pills to heroin, and now commonly includes fentanyl and synthetic analogues. Fentanyl is 50-100 times more potent than morphine and has a rapid onset. (source) Understanding this typology is crucial for adjusting resuscitation and induction protocols. With these synthetic opioids, multiple doses of naloxone are sometimes required for effective resuscitation.

The emergence of nitazenes and non-opioid additives like xylazine (a veterinary sedative) may also complicate overdose resuscitation. Xylazine does not respond to naloxone and causes severe necrotic skin ulcers and prolonged sedation. (source) When a patient does not fully wake up after naloxone, clinicians should suspect these adulterants — and should avoid attributing the incomplete response to "naloxone-resistant fentanyl," which is a common misreading of xylazine co-exposure. (source)

The clinician should be aware of the possibility of multi-substance overdose and/or long acting opioid analogues and adjust treatment accordingly.