Written by Jason Lesnick
Spoon Feed
This retrospective analysis found an increased rate of repeat naloxone administration in US EDs from 2016–2022.
Needing naloxone to navigate new novel narcotics…
This retrospective claims-based cohort study analyzed naloxone use in U.S. EDs and looked for changes in the rate of multiple naloxone administrations over time.
Using a retrospective, claims-based cohort design with MarketScan (2016–2022) and NEDS (2016–2021) databases, investigators analyzed over 2.3 million ED visits looking at the percentage of patients who received multiple doses of naloxone during their ED visit and the percentage of ED visits with multiple naloxone administrations.
They found that among naloxone-treated ED patients, multiple administrations increased from 10.1% to 17.4% in MarketScan (72.8% relative increase) and from 3.0% to 7.3% of visits in NEDS (146.7% increase), respectively (p < 0.01).
When counting all ED visits in this sample, 11.8% of patients received 2 naloxone doses, and 3.7% received 3 or more administrations. This analysis found that the adjusted odds of receiving multiple administrations of naloxone increased by 10–13% per year.
The authors note a few significant limitations with their data—they were unable to determine how naloxone infusions were classified and unable to determine what percent of patients in each database received naloxone by EMS.
How will this change my practice?
This study reinforces my practice of having a low threshold to give additional naloxone in patients currently experiencing opiate overdose who have not had an adequate response. This study also suggests to me that prolonged observation periods (i.e. 6 hours) after a patient has required naloxone for opiate reversal should be considered if one suspects synthetic opiates as the cause—especially in cases where patients required multiple administrations.
Editor’s note: The rise of new, super-potent synthetic opioids—nitazenes—may be driving renarcotization. Watch patients with opioid overdose at least 6 hours if you can. ~Clay Smith
Source
Use of Multiple Naloxone Administrations in the Emergency Department: A Retrospective Claims-Based Analysis. J Emerg Med. 2025 Dec;79:111-122. doi: 10.1016/j.jemermed.2025.04.022. Epub 2025 May 8. PMID: 41129837.
View JournalFeed Critical Appraisal
Critical Appraisal
Study Identification
Background
Study Question
Study Design & Conduct
Prospective / Retrospective: Retrospective
Multicenter: Yes
Unit of Allocation: Not applicable
Unit of Analysis: ED visits
Randomization Method: Not applicable
Allocation Concealment: Not applicable
Blinding: Not applicable
Follow-up Duration: Not applicable
Population
- At least one ED claim for opioid overdose
- Adults (≥18 years)
- Complete age and sex data
- Incomplete age or sex data
Number Enrolled: 335,846
Number Analyzed: 335,846
Key Baseline Characteristics
Sex: 50% male
Disease Severity: Not reported
Care Setting Distribution: Emergency Departments
Additional Baseline Characteristics
- Insurance type distribution
- Overdose substance recorded
Exposures / Interventions
Description: Multiple naloxone administrations
Definition / Dose: Not applicable
Timing: During ED visit
Classification Method: HCPCS code J2310
Protocolized / Discretionary: Not reported
Description: Single naloxone administration
Definition: Not applicable
Outcomes & Results
Primary Outcomes
Definition: Percentage of patients receiving multiple naloxone administrations
Time Point: During ED visit
Measurement Method: Claims data analysis
Results: Market Scan: 14.7%; NEDS: 6.3%
Secondary Outcomes
Definition: Not applicable
Time Point: Not applicable
Measurement Method: Not applicable
Results: Not applicable
Risk of Bias
Risk of Bias - ROBINS-I
- Bias due to confounding (Some concerns): Confounding factors such as pre-hospital naloxone use not fully accounted for.
- Bias in selection of participants (Low): Participants selected based on clear inclusion criteria from large databases.
- Bias in classification of interventions (Low): Naloxone administration was clearly defined using HCPCS codes.
- Bias due to deviations from intended interventions (Low): Intervention was consistently applied as per protocol.
- Bias due to missing data (Some concerns): Missing data on naloxone dose strengths and routes of administration.
- Bias in measurement of outcomes (Some concerns): Outcome measurement relied on claims data, which may lack precision.
- Bias in selection of the reported result (Low): All relevant outcomes were reported.
Transparency
COI Statement Present: TRUE
Prehospital use has seen a huge increase in naloxone use, but that’s directly related to the amount of police cars on scene. My usual observation time in the ED rarely went past 2 hours, so I really appreciate this data.
It’s hard to get people to stay. My colleague, Matt Lipton, mentioned using nalmefene nasal spray since it lasts longer. I thought this was genius! I don’t have any experience with nalmefene, but I like the idea of giving a longer acting agent to patients who won’t stay for a period of observation.