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

项目总结/摘要 美国每年发生超过356，000例院外心脏骤停（OHCA）病例，其中近90% 虽然60岁以上患者中99.7%的OHCA是心脏病因，但OHCA中有意义的比例 年龄在20 - 59岁之间的患者中， 心源性猝死的尸检系统调查（POST SCD）4调查以下疾病的患病率： 与药物有关的心脏骤停我们发现，2011-2016年间，弗朗西斯科10.3%的OHCA是 由于隐匿性阿片类药物过量5例-没有药物使用史或证据的病例， 归因于非过量的原因，例如心脏性猝死。虽然目前尚不清楚是否 纳洛酮--一种阿片受体竞争性拮抗剂--有益于经历阿片相关性 （OA）-OHCA，最近美国心脏协会的科学声明确定了对 纳洛酮在OA-OHCA中的疗效是一个重要的知识缺口。1然而，没有循证方法来 实时识别OA-OHCA目前存在，使纳洛酮的疗效有针对性的评价， 组困难。我们的研究团队利用来自POST SCD研究的数据开发了NAloxone Cardiac ARrest决策工具（NACARDI）-两个基于考试的标准，可提高隐匿性的预测试概率 OA-OHCA从10.3%到20.6%。6这些标准来自旧金山弗朗西斯科县死亡的患者 OHCA在外地。这项K38赠款的目的是回答两个悬而未决的问题：1）NACARDI 标准在存活到急诊科（艾德）的OHCA患者中有效，以及2）NACARDI标准 在弗朗西斯科以外的地方推广吗我的中心假设是，NACARDI标准是 外部有效，可用于识别具有隐匿性OA-OHCA风险的患者。我的长期目标是利用 该K38的结果为未来的多中心NACARDI富集临床研究制定了经验证的入选标准 纳洛酮治疗疑似OA-OHCA的试验。本提案的目标1将验证OHCA中的NACARDI标准 通过计算回顾性队列中NACARDI的筛选特征存活至艾德的患者 在2011-2021年间被送往旧金山弗朗西斯科两家大医院的所有OHCA患者中， 血液和尿液毒理学筛查以识别OA-OHCA。目标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，这是一个基于EMS和验尸官的 2018-2022年间在加拿大多伦多现场死亡的OHCA患者数据集。隐匿性阿片类药物过量 将通过医学检查员裁定在C-SCAN数据集中识别。NACARDI标准是 具有创新性，因为它们允许基于证据的实时识别具有隐匿性OA-OHCA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回顾性评估的做法。 这项拟议的研究意义重大，因为在复苏过程中识别出有隐匿性心脏病风险的患者 OA-OHCA是必要的，以设计一个道德和成功的纳洛酮在这一人群中的临床试验。

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.