Hughes Adrienne, Spungen Hannah, Culbreth Rachel, Aldy Kim, Krotulski Alex, Hendrickson Robert G, Amaducci Alexandra, Judge Bryan, Meaden Christopher, Calello Diane P, Buchanan Jennie, Carpenter Joseph, Shulman Joshua, Brent Jeffrey, Wax Paul, Campleman Sharan, Levine Michael, Schwarz Evan, Manini Alex F
Oregon Health and Science University, Portland, Oregon, USA.
University of California, Los Angeles, California, USA.
Acad Emerg Med. 2025 Jul 15. doi: 10.1111/acem.70104.
Simultaneous exposure to both benzodiazepines and opioids can lead to synergistic respiratory depression, complicating overdose management. Our objective was to report on the detection of prescription and novel benzodiazepine co-exposures among patients treated in emergency departments (EDs) with suspected opioid overdoses. We aimed to describe novel benzodiazepine exposures in this population and to compare the clinical severity of co-exposure to benzodiazepines and opioids versus opioids alone.
This study utilized data from the Toxicology Investigators Consortium (ToxIC) Fentalog Study, an observational study at 10 ED sites (Sept 2020-Dec 2023). Waste serum samples were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) for the presence of over 1200 novel psychoactive substances (NPS), drugs, therapeutics, and metabolites. Analyses included demographics, clinical severity, and outcomes among those with prescription benzodiazepines, novel benzodiazepines, or no benzodiazepines.
Among the patients with opioids present (n = 1427), 29.0% of patients had detectable benzodiazepines. 20.5% of patients had detectable prescription benzodiazepines, and 8.5% of patients had detectable novel benzodiazepines. The most commonly detected prescription benzodiazepine was alprazolam (39.3%); the most common novel benzodiazepine was bromazolam (46.3% of novel benzodiazepines). The median age of those with novel benzodiazepines was 34, which was younger than those without benzodiazepines (40) and those with prescription benzodiazepines (41; p = 0.001). Patients without benzodiazepines received naloxone more frequently (p = 0.02), while novel benzodiazepine co-exposure was associated with higher naloxone nonresponse rates (p = 0.03). Patients with novel benzodiazepines (compared to the opioid-only group) had increased odds of requiring mechanical ventilation (aOR: 2.14; 95% CI: 1.07, 4.05) after adjusting for age, gender, race and ethnicity, and the presence of prescription benzodiazepines and/or fentanyl.
Nearly a third of patients with confirmed opioid overdose presenting to the ED also had concomitant benzodiazepine exposures. Those with novel benzodiazepines had significantly higher odds of intubation, suggesting greater severity of overdose.
同时接触苯二氮䓬类药物和阿片类药物可导致协同性呼吸抑制，使过量用药的管理变得复杂。我们的目的是报告在急诊科（ED）接受疑似阿片类药物过量治疗的患者中处方苯二氮䓬类药物和新型苯二氮䓬类药物共同暴露的检测情况。我们旨在描述该人群中新型苯二氮䓬类药物的暴露情况，并比较苯二氮䓬类药物与阿片类药物共同暴露与仅阿片类药物暴露的临床严重程度。
本研究利用了毒理学调查员联盟（ToxIC）芬太尼研究的数据，这是一项在10个急诊科开展的观察性研究（2020年9月至2023年12月）。使用液相色谱四极杆飞行时间质谱（LC-QTOF-MS）分析废弃血清样本中1200多种新型精神活性物质（NPS）、药物、治疗药物和代谢物的存在情况。分析包括有处方苯二氮䓬类药物、新型苯二氮䓬类药物或无苯二氮䓬类药物患者的人口统计学、临床严重程度和结局。
在检测出阿片类药物的患者（n = 1427）中，29.0%的患者可检测到苯二氮䓬类药物。20.5%的患者可检测到处方苯二氮䓬类药物，8.5%的患者可检测到新型苯二氮䓬类药物。最常检测到的处方苯二氮䓬类药物是阿普唑仑（39.3%）；最常见的新型苯二氮䓬类药物是溴替唑仑（占新型苯二氮䓬类药物的46.3%）。有新型苯二氮䓬类药物患者的中位年龄为34岁，低于无苯二氮䓬类药物患者（40岁）和有处方苯二氮䓬类药物患者（41岁；p = 0.001）。无苯二氮䓬类药物的患者更频繁地接受纳洛酮治疗（p = 0.），而新型苯二氮䓬类药物共同暴露与纳洛酮无反应率较高相关（p = 0.03）。在调整年龄、性别、种族和民族以及处方苯二氮䓬类药物和/或芬太尼的存在情况后，有新型苯二氮䓬类药物的患者（与仅阿片类药物组相比）需要机械通气的几率增加（校正优势比：2.14；95%置信区间：1., 4.05）。
到急诊科就诊的确诊阿片类药物过量患者中，近三分之一同时也暴露于苯二氮䓬类药物。使用新型苯二氮䓬类药物的患者插管几率显著更高，表明过量用药的严重程度更高。
