Naloxone interventions in opioid overdoses: a systematic review protocol

Area of Science:

• Emergency Medicine
• Pharmacology
• Public Health

Background:

• North America faces a severe opioid overdose epidemic driven by fentanyl and ultra-potent opioids.
• Naloxone is a crucial antidote, but optimal dosing for these potent substances is not well-established.
• Understanding naloxone's effectiveness is vital for current overdose response strategies.

Purpose of the Study:

• To determine the relationship between initial naloxone dose and toxicity reversal, adverse events, and total dose needed for opioid overdoses.
• To evaluate dose-response for naloxone in patients with undifferentiated opioid toxicity and those with suspected ultra-potent opioid toxicity.
• To inform updated clinical guidelines for naloxone administration.

Main Methods:

• Comprehensive literature search across multiple databases and trial registries.
• Inclusion of diverse study designs (interventional, observational, case reports) for suspected opioid toxicity.
• Data extraction and quality assessment by duplicate reviewers, with statistical analysis including dose-response modeling and subgroup analyses.

Main Results:

• The review synthesizes data on naloxone's efficacy and safety in various opioid overdose scenarios.
• Analysis focuses on the correlation between naloxone dosage and patient outcomes, including reversal of toxicity and adverse events.
• Dose-response relationships will be explored, considering opioid type and prevalence of ultra-potent opioids.

Conclusions:

• Findings will provide critical insights into optimal naloxone dosing strategies for the current opioid crisis.
• Results aim to address limitations in existing reviews and inform evidence-based treatment guidelines.
• Dissemination of results will support updates to overdose treatment protocols and Take Home Naloxone programs.