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

改进阿片类药物相关的院外心脏骤停的识别

基本信息

批准号：
10724213
负责人：
David G Dillon
金额：
$ 10.62万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10724213
关键词：
Accident and Emergency department Address Age Age Years American Heart Association Autopsy Blood Canada Cardiac Characteristics Clinical Clinical Treatment Clinical Trials Clinical Trials Design Coroner County Data Data Set Derivation procedure Drug usage Emergency Medicine Ethics Etiology Evaluation Event Funding Future Goals Grant Health Heart Arrest Hospitals Intervention Investigation Knowledge Medical Examiners Methods Mission Naloxone National Heart, Lung, and Blood Institute Opioid Opioid Receptor Patients Pharmaceutical Preparations Physicians Population Prevalence Probability Recommendation Recording of previous events Research Residencies Resuscitation Retrospective cohort Risk Running Safety San Francisco Scientist Secondary to Testing Time Toxicology Training United States United States National Institutes of Health Urine adjudication antagonist cohort design epidemiology study evidence base experience improved inclusion criteria innovation instrument opioid overdose opioid use disorder out-of-hospital cardiac arrest prospective randomized, clinical trials scale up screening sudden cardiac death

项目摘要

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.

项目概要/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% 2 虽然 60 岁以上患者中 99.7% 的 OHCA 在病因学上是心脏病，但 OHCA 的相当一部分是有意义的 20 至 59 岁之间的患者与药物相关。3 我们之前使用的数据来自 NHLBI 资助的心脏性猝死的尸检系统调查 (POST SCD)4 旨在调查心源性猝死的患病率我们发现 2011 年至 2016 年间，旧金山 10.3% 的 OHCA 是因药物相关的隐匿性心脏骤停。由于隐匿的阿片类药物过量5——没有吸毒史或证据的病例，否则这些病例可能会被归因于非药物过量原因，例如心源性猝死，但目前尚不清楚是否如此。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 (OA)-OHCA，美国心脏协会最近的一份科学声明确定了严格的评估纳洛酮在 OA-OHCA 中的疗效是一个重要的知识差距。1 然而，没有基于证据的方法目前已有实时识别 OA-OHCA 的技术，可以对纳洛酮的疗效进行针对性评价我们的研究团队利用 POST SCD 研究的数据来开发 NAloxone Cardiac。 ARrest Decision Instrument (NACARDI) – 两个基于考试的标准，可提高神秘学的预测试概率 OA-OHCA 从 10.3% 降至 20.6%。6 这些标准源自旧金山县死亡患者该 K38 拨款的目的是回答两个悬而未决的问题： 1) NACARDI 是吗？标准对于存活到急诊室 (ED) 的 OHCA 患者有效，并且 2) 是 NACARDI 标准我的中心假设是 NACARDI 标准是外部有效且可推广用于识别有隐匿性 OA-OHCA 风险的患者。我的长期目标是使用。该 K38 的结果可为未来多中心 NACARDI 丰富的临床制定经过验证的纳入标准在疑似 OA-OHCA 中进行纳洛酮试验本提案的目标 1 将验证 OHCA 中的 NACARDI 标准。通过计算回顾性队列中 NACARDI 的筛查特征，幸存到急诊科的患者 2011 年至 2021 年间运送至旧金山两家主要医院的所有 OHCA 患者中，使用用于识别 OA-OHCA 的血液和尿液毒理学筛查目标 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 和验尸官的网络 2018 年至 2022 年期间在加拿大多伦多现场死亡的 OHCA 患者的数据集。将通过体检医师裁决在 C-SCAN 数据集中确定 NACARDI 标准是创新，因为它们可以基于证据实时识别有隐匿性 OA-OHCA 风险的患者，而不是依赖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。拟议的研究意义重大，因为在复苏过程中识别出有隐匿风险的患者 OA-OHCA 对于在该人群中设计符合道德且成功的纳洛酮临床试验是必要的。