3 results
Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review
- Jessica Moe, Jesse Godwin, Roy Purssell, Fiona O'Sullivan, Jeffrey P. Hau, Elizabeth Purssell, Jason Curran, Mary M. Doyle-Waters, Penelope M.A. Brasher, Jane A. Buxton, Corinne M. Hohl
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 22 / Issue 2 / March 2020
- Published online by Cambridge University Press:
- 20 January 2020, pp. 178-186
- Print publication:
- March 2020
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Objectives
Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses.
MethodsWe searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old.
ResultsA total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions.
ConclusionsPractitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.
LO20: Naloxone dosing for suspected opioid and ultra-potent opioid overdoses: A systematic review
- J. Moe, J. Godwin, R. Purssell, F. O'Sullivan, J. Hau, E. Purssell, J. Curran, M. Doyle-Waters, P. Brasher, J. Buxton, C. Hohl
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 21 / Issue S1 / May 2019
- Published online by Cambridge University Press:
- 02 May 2019, p. S14
- Print publication:
- May 2019
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Introduction: Optimizing naloxone dosing in the context of increasing fentanyl and ultra-potent opioid (UPO) prevalence is an important consideration for emergency health care providers. The goal of this systematic review was to evaluate the association between initial and cumulative naloxone doses on effective reversal and adverse events in undifferentiated and fentanyl/UPO overdoses. Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings from July to October 2018 and back to 1972. Our search included pertinent indexing terms for UPOs. We included interventional and observational studies reporting on naloxone administration for opioid toxicity reversal in people ≥12 years old. Additionally, we accessed non-traditional evidence sources (case reports and series) given this rapidly changing field. We conducted inclusion screens, data extraction and quality assessments in duplicate. We summarized study characteristics and where reported, analyzed number of patients with clinical response. Response was defined as not receiving further naloxone doses and remaining alive. Results: We included 174 studies (108 case reports and series, 55 observational, 9 interventional) with 26,660 subjects (median age 35.1; 74.2% male). We observed lower response among patients exposed to fentanyl/UPO versus heroin for initial naloxone doses ≤0.4mg (56.8% versus 80.2%) and > 0.4mg (27.0% versus 82.1%). Mean cumulative doses were higher for fentanyl/UPO (2.10 mg, SD 1.80 mg) versus heroin (1.48 mg, SD 1.68 mg) overdoses. In North American studies the median cumulative dose used was higher for fentanyl/UPO versus heroin overdoses. A dose-response curve for fentanyl/UPO studies showed marked variability in doses among responders, indicating heterogeneity. Adverse events reporting was inconsistent; 10% of subjects experienced withdrawal based on studies in which they were reported. Conclusion: This is the first systematic review to summarize proportion of patients with clinical response by naloxone dose provided. While variable reporting, study quality, heterogeneity, and our outcome definitions limit the conclusions we can draw, it appears that higher initial doses and in some cases, higher cumulative naloxone doses were used and may be necessary to reverse toxicity due to fentanyl/UPO compared to other opioids. High-quality prospective studies assessing effectiveness and safety are needed.
LO27: Risk factors for misuse of prescribed opioids: a systematic review and meta-analysis
- A. Cragg, S. Kitchen, J. Hau, S. Woo, C. Liu, M. Doyle-Waters, C. Hohl
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 21 / Issue S1 / May 2019
- Published online by Cambridge University Press:
- 02 May 2019, pp. S16-S17
- Print publication:
- May 2019
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Introduction: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective was to synthesize available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing opioid misuse from prescribed opioids among patients presenting with pain unrelated to cancer. Our hypothesis was that we would identify risk factors predisposing patients to developing opioid misuse. Methods: We developed a systematic search strategy and applied it to nine electronic reference databases and six clinical trial registries. We hand searched related journals and conference proceedings, the reference lists of included studies, and the top 100 hits on Google. We included studies where a medical professional exposed adults or children to an opioid through a prescription. We excluded studies with over 50% cancer patients, palliative patients, and those with illicit opioid initiation. Two reviewers independently reviewed titles, abstracts, and full texts, and extracted data using standardized forms. We assessed study quality using risk of bias. We synthesized effect sizes of dichotomous risk factors on opioid misuse using inverse variance random-effects meta-analysis, and the inverse variance-weighted mean difference between opioid misusers and non-misusers for continuously measured factors. We conducted an a priori defined subgroup analysis among opioid-naïve patients. Results: Among 9,629 studies, 67 met our inclusion criteria. Among those who had been prescribed outpatient opioids, the following factors were associated with the development of misuse: a prior history of illicit drug use (OR: 4.21, 95% CI: 2.31-7.65), recent benzodiazepine use (OR: 2.57, 95% CI: 1.23-5.38), any mental health diagnosis (OR: 2.45, 95% CI: 1.91-3.15), any short acting (IR) opioid prescription (OR: 2.40, 95% CI: 1.15-5.02), younger age (OR: 2.19, 95%CI: 1.81-2.64), and male sex (OR: 1.23, 95% CI: 1.10-1.36). Among studies limiting their population to opioid-naïve patients, younger age was the most significant risk factor for opioid misuse (OR: 5.42, 95% CI:1.51-19.43). Conclusion: Of the risk factors examined, non-cancer pain patients with a prior history of substance use or mental health diagnoses were at highest risk for prescription opioid misuse. Younger opioid-naïve patients were at highest risk of misuse. Clinicians should consider these risk factors when managing acute pain in the emergency department.