Naloxone interventions in opioid overdoses: a systematic review protocol

Abstract

Background North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Methods To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies. Discussion Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs. Electronic supplementary material The online version of this article (10.1186/s13643-019-1048-y) contains supplementary material, which is available to authorized users.

Emergency Department–initiated Interventions for Patients With Opioid Use Disorder: A Systematic Review

“…The growing concern about the opioid crisis has stimulated research, cross‐border knowledge sharing, and health system–level initiatives 12,13 . Several literature reviews related to the opioid crisis have been recently completed to inform clinicians and decision makers on the effectiveness of different strategies and to summarize the state of knowledge in this area 13–16 . Despite the potential role of EDs, a comprehensive evaluation of the literature related to OUD interventions initiated in EDs is still lacking.…”

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

“…In clinical populations, OWS occurs after both spontaneous and naloxone-precipitated states of withdrawal. Naloxone, an opioid receptor antagonist, is a lifesaving medication used to reverse opioid-induced respiratory depression in humans and to precipitate withdrawal in animal models of OUD [4][5][6][7][8]. As the availability of increasingly potent synthetic opioids enter the illicit drug market and naloxone becomes more readily available over the counter and through Emergency Medical Services (EMS), we see increased instances of patients receiving multiple administrations of naloxone, increasing 26% from 2012-2015 [9].…”

Naloxone precipitated withdrawal increases dopamine release in the dorsal striatum of opioid dependent men

“…Acute opioid withdrawal is stressful and stimulates the hypothalamus-pituitary-adrenal (HPA) axis, leading to increases in pituitary pro-opiomelanocortin mRNA, adrenocorticotropic hormone (ACTH), and adrenal cortisol release [15]. NAL, a non-selective opioid antagonist [16,17], is used to reverse opioid overdose effects [18] and precipitates withdrawal in opioiddependent individuals. Here we aimed to study the contribution of DA to NAL precipitated withdrawal (NPW) in OUD participants.…”