Improving the Identification of Opioid-Associated Out-of-Hospital Cardiac Arrest

项目摘要/摘要 美国每年发生超过356,000例院外心脏骤停，其中近90% 在60岁以上的患者中，99.7%的HC A在病因上是心脏的，但有相当大的比例 年龄在20岁到59岁之间的患者与毒品有关。3我们之前使用的数据来自NHLBI资助的 心脏性猝死的死后系统调查(4) 与神秘药物有关的心脏骤停。我们发现，2011-2016年间，旧金山10.3%的uchA是 由于隐匿的阿片类药物过量5--没有吸毒史或药物使用证据的病例 归因于非过量原因，如心源性猝死。虽然目前还不清楚 纳洛酮-一种阿片受体竞争性拮抗剂-对经历阿片类药物相关的患者有益 美国心脏协会最近的一份科学声明确定了对 纳洛酮治疗骨性关节炎的疗效是一个重要的知识空白1.然而，没有循证的方法来 实时识别目前存在的OA-uchA，对纳洛酮在这方面的疗效进行有针对性的评价 组队难。我们的研究小组利用SCD后研究的数据开发了纳洛酮心脏 逮捕决定仪(NACARDI)--两个基于考试的标准，可提高潜伏症的预测概率 从10.3%到20.6%。6这些标准来源于旧金山县死亡的患者 在田野中发现的。这笔K38拨款的目的是回答两个悬而未决的问题：1)NACARDI 对于存活到急诊科(ED)的uchA患者有效的标准，以及2)NACARDI标准 是否可在旧金山以外的地区推广？我的中心假设是NACARDI的标准是 外部有效和可推广用于识别隐匿性OA-uchA风险的患者。我的长期目标是利用 这项K38的结果为未来的多中心NACARDI强化临床制定了有效的纳入标准 纳洛酮治疗疑似骨性关节炎的临床试验。该提案的目标1将验证联合国儿童基金会的NACARDI标准 在回顾性队列中通过计算NACARDI筛查特征存活到ED的患者 在2011-2021年间被送往旧金山两家主要医院的所有uchA患者中，使用 血液和尿液毒理学检查以确定OA-uchA。AIM 2将完善和外部验证NACARDI 标准使用来自加拿大心脏骤停网络(C-SCAN)的数据，该网络是以EMS和验尸官为基础的 2018-2022年间在加拿大多伦多现场死亡的uchA患者的数据集。隐匿性阿片类药物过量 将通过法医裁决在C扫描数据集中确定。NACARDI的标准是 创新是因为它们允许基于证据的实时识别存在隐匿性OA-uchA风险的患者， 而不是依赖于目前通过尸检或逮捕后毒理学测试进行追溯评估的做法。 这项拟议的研究具有重要意义，因为在复苏过程中确定了哪些患者存在隐匿性风险 对于在这一人群中设计一项合乎道德和成功的纳洛酮临床试验来说，OA-uchA是必要的。

PROJECT SUMMARY/ABSTRACT Over 356,000 cases of out-of-hospital cardiac arrest (OHCA) occur in the US each year, nearly 90% of which are fatal.2 While 99.7% of OHCA in patients over age 60 are cardiac in etiology, a meaningful proportion of OHCA for patients between 20 and 59 years of age are drug-related.3 We previously used data from the NHLBI-funded Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD)4 to investigate the prevalence of occult drug-related cardiac arrest. We found that 10.3% of OHCA in San Francisco between 2011-2016 were due to occult opioid overdose5 – cases without a history or evidence of drug use that would otherwise have been attributed to a non-overdose cause, such as sudden cardiac death. While it is currently unknown whether naloxone – an opioid receptor competitive antagonist – is beneficial to patients experiencing opioid-associated (OA)-OHCA, a recent American Heart Association scientific statement identified the rigorous evaluation of naloxone’s efficacy in OA-OHCA as an important knowledge gap.1 However, no evidenced-based method to identify OA-OHCA in real-time currently exists, making the targeted-evaluation of naloxone’s efficacy in this group difficult. Our study team leveraged data from the POST SCD study to develop the NAloxone Cardiac ARrest Decision Instrument (NACARDI) – two exam-based criteria that improve the pre-test probability of occult OA-OHCA from 10.3% to 20.6%.6 These criteria were derived from patients in San Francisco County who died of OHCA in the field. The objective of this K38 grant is to answer two outstanding questions: 1) Are the NACARDI criteria valid in OHCA patients who survive to the emergency department (ED), and 2) Are the NACARDI criteria externally generalizable outside of San Francisco? My central hypothesis is that the NACARDI criteria are externally valid and generalizable for identifying patients at risk for occult OA-OHCA. My long-term goal is to use the results of this K38 to develop validated inclusion criteria for a future multi-center NACARDI-enriched clinical trial of naloxone in suspected OA-OHCA. Aim 1 of this proposal will validate the NACARDI criteria in OHCA patients who survived to the ED by calculating screening characteristics for NACARDI in a retrospective cohort of all OHCA patients who were transported to two major hospitals in San Francisco between 2011-2021, using blood and urine toxicology screens to identify OA-OHCA. Aim 2 will refine and externally validate the NACARDI criteria using data from the Canadian Sudden Cardiac Arrest Network (C-SCAN), an EMS- and coroner-based dataset of OHCA patients who died in the field in Toronto, Canada between 2018-2022. Occult opioid overdose will be identified in the C-SCAN dataset through medical examiner adjudication. The NACARDI criteria are innovative because they allow for evidence-based real-time identification of patients at risk for occult OA-OHCA, instead of relying on the current practices of retrospective evaluation via autopsy or post-arrest toxicology testing. The proposed research is significant because identifying patients during a resuscitation who are at risk for occult OA-OHCA is necessary to design an ethical and successful clinical trial of naloxone in this population.