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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.
Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review
- James L. Fox, Erik N. Vu, Mary Doyle-Waters, Jeffrey R. Brubacher, Riyad Abu-Laban, Zengxuan Hu
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 12 / Issue 4 / July 2010
- Published online by Cambridge University Press:
- 21 May 2015, pp. 355-364
- Print publication:
- July 2010
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Introduction:
During the past 7 years, considerable new evidence has accumulated supporting the use of prophylactic hypothermia for traumatic brain injury (TBI). Studies can be divided into 2 broad categories: studies with protocols for cooling for a short, predetermined period (e.g., 24–48 h), and those that cool for longer periods and/or terminate based on the normalization of intracranial pressure (ICP). There have been no systematic reviews of hypothermia for TBI that include this recent new evidence.
Methods:This analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the QUOROM (quality of reporting of meta-analyses) statement. We developed a comprehensive search strategy to identify all randomized controlled trials (RCTs) comparing therapeutic hypothermia with standard management in TBI patients. We searched Embase, MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, ProceedingsFirst and PapersFirst. Additional relevant articles were identified by hand-searching conference proceedings and bibliographies. All stages of study identification and selection, quality assessment and analysis were conducted according to prospectively defined criteria. Study quality was determined by assessment of each study for the use of allocation concealment and outcome assessment blinding. Studies were divided into 2 a priori–defined subgroups for analysis based on cooling strategy: short term (≤ 48 h), and long term or goal-directed (> 48 h and/or continued until normalization of ICP). Outcomes included mortality and good neurologic outcome (defined as Glasgow Outcome Scale score of 4 or 5). Pooling of primary outcomes was completed using relative risk (RR) and reported with 95% confidence intervals (CIs).
Results:Of 1709 articles, 12 studies with 1327 participants were selected for quantitative analysis. Eight of these studies cooled according to a long-term or goal-directed strategy, and 4 used a short-term strategy. Summary results demonstrated lower mortality (RR 0.73, 95% CI 0.62–0.85) and more common good neurologic outcome (RR 1.52, 95% CI 1.28–1.80). When only short-term cooling studies were analyzed, neither mortality (RR 0.98, 95% CI 0.75–1.30) nor neurologic outcome (RR 1.31, 95% CI 0.94–1.83) were improved. In 8 studies of long-term or goal-directed cooling, mortality was reduced (RR 0.62, 95% CI 0.51–0.76) and good neurologic outcome was more common (RR 1.68, 95% CI 1.44–1.96).
Conclusion:The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score ≤ 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured. Most studies report using a temperature of 32°–34°C. The maximal benefit occurred with a long-term or goal-directed cooling protocol, in which cooling was continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hours was achieved. There is large potential for further research on this therapy in prehospital and emergency department settings.