Management of Suspected Opioid Overdose with Naloxone by Emergency Medical Services Personnel [Entered Retrospectively]

Project Summary Title and Description

Title
Management of Suspected Opioid Overdose with Naloxone by Emergency Medical Services Personnel [Entered Retrospectively]
Description
Objectives. To compare different routes, doses, and dosing strategies of naloxone administration for suspected opioid overdose by emergency medical services (EMS) personnel in field settings, and to compare effects of transport to a health care facility versus nontransport following successful reversal of opioid overdose with naloxone. Methods. Four databases were searched through March 2017. Additional studies were identified from reference lists and technical experts. We included randomized controlled trials (RCTs) and cohort studies comparing different naloxone routes of administration, doses, or dosing strategies and on effects of transport or nontransport following successful reversal of opioid overdose with naloxone. Two investigators independently applied prespecified criteria to rate study quality. The strength of evidence was determined based on the overall risk of bias, consistency, directness, precision, and reporting bias. Results. Twelve studies met inclusion criteria. Three RCTs and four cohort studies compared different routes of administration. Two trials compared intranasal (IN) with intramuscular (IM) naloxone administration (strength of evidence [SOE] for all outcomes: low). While 2 mg of a higher-concentration formulation of IN naloxone (2 mg/1 mL) is similar in efficacy to 2 mg of IM naloxone, 2 mg of a lower-concentration formulation of IN naloxone (2 mg/5 mL formulation) is less effective than the same dose IM but associated with decreased risk of agitation and/or irritation. The 2 mg/5 mL formulation of IN naloxone studied in this trial is lower than concentrations used in the United States. In both trials, IN naloxone was associated with increased likelihood of rescue naloxone use. Although one RCT and two observational studies evaluated intravenous (IV) versus IN naloxone, evidence was insufficient to determine comparative benefits and harms, due to methodological limitations and poor applicability to U.S. EMS settings (SOE: insufficient). There was insufficient evidence from two observational studies to compare parenteral routes of administration (IM, IV, or subcutaneous [SQ]). No study compared outcomes of patients transported versus not transported following successful reversal of opioid overdose with naloxone. Five studies reported low rates of deaths and serious adverse events (0% to 1.25%) in patients not transported to a hospital after successful naloxone treatment, but used an uncontrolled design and had other methodological limitations (SOE: insufficient). Limitations. Few studies met inclusion criteria, all studies had methodological limitations, and no study evaluated naloxone auto-injectors or IN naloxone formulations recently approved by the US Food and Drug Administration (FDA). Conclusions. Low-strength evidence suggested that higher-concentration IN naloxone (2 mg/1 mL) is similar in efficacy to IM naloxone (2 mg), with no difference in adverse events. Research is needed on the comparative effectiveness of the FDA-approved naloxone auto-injectors (0.4 mg and 2 mg) and highly concentrated (4 mg/0.1 mL and 2 mg/0.1 mL) IN naloxone reformulation, different doses, and dosing strategies. Uncontrolled studies suggested that nontransport of patients following successful reversal of naloxone overdose might be associated with a low rate of serious harms, but patients were probably at low risk for such events, and there was insufficient evidence to determine risk of transport versus nontransport.
Attribution
N/A
Authors of Report
N/A
Methodology description
Four databases were searched through March 2017. Additional studies were identified from reference lists and technical experts. We included randomized controlled trials (RCTs) and cohort studies comparing different naloxone routes of administration, doses, or dosing strategies and on effects of transport or nontransport following successful reversal of opioid overdose with naloxone. Two investigators independently applied prespecified criteria to rate study quality. The strength of evidence was determined based on the overall risk of bias, consistency, directness, precision, and reporting bias.
PROSPERO
CRD42016053891
DOI
10.23970/AHRQEPCCER193
Notes
The data for this project was entered retrospectively. Project data can be found in the following uploaded documents: Data Abstraction contains PMID; Key Question; Country, Setting, Study Years; Eligibility Criteria; Intervention Characteristics; Number of Treatment and Control Subjects; Population Characteristics; Exposure Characteristics; Results; Duration of Followup; Adverse Events; Funding Source; and Comments for all included studies. Risk of Bias contains PMID; Randomization, Allocation Concealment; Groups at baseline; Outcome Assessor, Care Provider, and Patient masking; Attrition, Crossovers, Adherence, and Contamination information; Loss to followup; Intention to Treat Analysis; Post-randomization exclusions; Outcomes pre-specified; Funding Source; and overall Risk of bias.
Funding Source
Prepared by The Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD

Key Questions

1. 1. What is the comparative benefit and harms of out-of-hospital administration of naloxone by EMS personnel using intravenous, intramuscular, subcutaneous, and intranasal routes of administration?
2. 1A: What are the comparative benefits and harms of different intravenous, intramuscular, subcutaneous, or intranasal doses of naloxone?
3. 2: What is the comparative benefit and harms of titration of naloxone administered by EMS personnel until the patient resumes sufficient spontaneous respiratory effort versus until the patient regains consciousness?
4. 3: For patients with confirmed or suspected opioid overdose in out-of-hospital settings treated with multiple doses of naloxone (including patients who do not improve after an initial dose of intranasal naloxone), what are the effects on benefits and harms of differences in timing of repeat dosing?
5. 4: For patients with confirmed or suspected opioid overdose in out-of-hospital settings who regain sufficient spontaneous respiratory effort and are alert and oriented after naloxone administration by EMS personnel, what are the benefits and harms of transporting patients to a healthcare facility versus non-transport?

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