Lehigh Valley Health Network-USF Morsani College of Medicine, Allentown, Pennsylvania.
American College of Medical Toxicology, Phoenix, Arizona.
JAMA Netw Open. 2023 Aug 1;6(8):e2331264. doi: 10.1001/jamanetworkopen.2023.31264.
Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series.
To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD.
DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis.
Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene.
The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only.
During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation.
In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.
在急诊科（ED）中，与非法阿片类药物过量（OD）相关的检测到的最快速增长的阿片类药物类型包括合成阿片类药物，如芬太尼类似物和硝甲西泮药物类别。然而，除了小型病例系列之外，新型强效阿片类药物（NPO），特别是硝甲西泮的 OD 临床结局尚不清楚。
确定与芬太尼 OD 相比，ED 中 NPO 过量患者的纳洛酮给药和临床后果。
设计、地点和参与者：这是对正在进行的全国性 ToxIC Fentalog 队列研究中 2020 年至 2022 年期间在 ED 中检测到 NPO 的成年人进行的队列研究亚组分析。纳入了在 ED 中疑似急性阿片类 OD 且残留血液样本的患者，分析了检测到 NPO 的患者。如果患者的确认性检测对布罗啡、异硝甲西泮、甲硝西泮和/或 N-哌啶基乙硝甲西泮等 NPO 分析物呈阳性，则将患者纳入本分析。对照组包括在毒理学分析中呈阳性但没有任何其他分析物的芬太尼患者。
患者接触 NPO，包括布罗啡、异硝甲西泮、甲硝西泮和/或 N-哌啶基乙硝甲西泮。
主要结局是作为 OD 后常规临床护理的一部分给予的纳洛酮总剂量和总累积纳洛酮剂量。将 NPO 阳性患者的纳洛酮需求和临床后果与仅检测到芬太尼的患者进行比较。
在研究期间，对 2298 名患者进行了筛查，其中 717 名符合纳入标准，537 名患者完成了完整的实验室检测数据，其中 11 名（2.0%）仅对芬太尼呈阳性，9 名（1.7%）对 NPO 呈阳性（布罗啡、异硝甲西泮、甲硝西泮或 N-哌啶基乙硝甲西泮）。患者年龄范围为 20 至 57 岁（4 名男性[44.4%]和 5 名女性[55.6%]）。NPO 组在医院接受的纳洛酮推注的平均（SD）数量明显高于芬太尼组（1.33 [1.50]比 0.36 [0.92]）（P =.02），这对应于中等大小的效应量（Cohen d=0.78）。甲硝西泮 OD 与心脏骤停和总体上更多的纳洛酮剂量有关。甲硝西泮病例的平均（SD）纳洛酮剂量为 3.0（0），2 例（100%）甲硝西泮 OD 患者均接受心肺复苏。
在这项对因确认的阿片类药物 OD 而入院的患者进行的队列研究中，与仅检测到芬太尼的患者相比，住院期间纳洛酮的剂量较高。需要进一步研究来证实这些初步关联。
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