Mild Hypothermia for Resuscitated Out-of-Hospital Cardiac Arrest Patients

描述（由申请人提供）：在美国，估计每年有40万至45万人在院外或急诊室经历心源性猝死。脑损伤是这些患者发病和死亡的主要原因，大多数患者无法恢复意识。目前迫切需要安全有效的治疗方法来改善心脏骤停后的预后。即使延迟4至8小时达到目标温度，院外心室颤动（VF）复苏患者诱导的轻度低温（32-34℃）也能改善神经系统恢复和生存。尽管有这些证据，诱导性低温并没有被广泛应用，其对其他初始节律患者的疗效在很大程度上还没有研究。动物模型结果表明，在恢复自然循环（ROSC）后尽快开始亚低温治疗，其疗效会有所提高。本研究的总体目标是确定现场降温策略是否能改善院外心脏骤停后的预后。为此，我们将随机分配1364名符合条件的（达到ROSC但仍处于昏迷状态）院外治疗的心脏骤停（室性心动和非室性心动）患者，接受ROSC后护理人员立即启动或不进行现场冷却的标准治疗。现场降温将通过静脉输注2升4:C生理盐水，持续20 - 30分钟，镇静，肌肉麻痹。结果将基于终点：“出院时清醒”。由于医院冷却可能潜在地改变或混淆现场冷却的效果，随机化和分析都将根据预期接收医院是否有常规冷却方案进行分层。由于美国心脏协会（AHA）的指导方针，研究地区的大多数医院通常对初始心律为VF的ROSC昏迷患者进行降温。这类医院一般不会对初始心律不是VF的类似患者进行治疗，尽管这在某种程度上是可变的。一些医院并不冷静。数据将从检查护理人员运行报告、医院记录和3个月的电话随访访谈中收集。我们提出以下具体目标：目标1：确定初始心律为VF并打算送往降温医院的符合条件的患者现场降温的结果。目的2：对初始心律非虚颤（即无脉性电活动或心脏骤停）的合格患者进行现场冷却的安全性。目的3：比较送往非降温医院的虚颤患者与送往降温医院的主要对照人群（虚颤患者）的结果差异。公共卫生相关性：据估计，美国每年有40万至45万人在院外或急诊室经历心源性猝死。脑损伤是这些患者发病和死亡的主要原因，大多数患者无法恢复意识。目前迫切需要安全有效的治疗方法来改善心脏骤停后的预后，在这项拨款申请中，我们的目标是确定使用快速输注冷生理盐水的亚低温是否会改善院外心脏骤停患者的预后。

DESCRIPTION (provided by applicant): Between 400,000 and 450,000 people are estimated to experience sudden cardiac death out of hospital or in the emergency room each year in the United States. Brain damage is a major cause of morbidity and mortality in these patients with most never regaining consciousness. Safe and effective therapies that improve outcome after cardiac arrest are urgently needed. Even with delays of 4 to 8 h to achieve target temperatures, induced mild hypothermia (32-34:C) in patients resuscitated from out-of-hospital ventricular fibrillation (VF) improved neurologic recovery and survival. Despite this evidence, induced hypothermia is not widely used, and its efficacy in patients with other initial rhythms is largely unstudied. Results from animal models suggest that efficacy of mild hypothermia would improve if initiated as soon as possible after return of spontaneous circulation (ROSC). The overall goal of this study is to determine whether a strategy of field cooling improves outcome after out-of-hospital cardiac arrest. To this end, we will randomize 1364 eligible (achieving ROSC but still comatose) patients with treated out-of-hospital for cardiac arrest (both VF and non-VF) to standard care with or without field cooling initiated immediately by paramedics following ROSC. Field cooling will be achieved with intravenous infusion of 2 liters of 4:C normal saline over 20 to 30 minutes, sedation, and muscle paralysis. Outcome will be based on the endpoint: 'awake at hospital discharge'. Since hospital cooling could potentially modify or confound the effect of field cooling, both randomization and analysis will be stratified by whether or not the intended receiving hospital has a routine cooling protocol. Because of the American Heart Association (AHA) guidelines, most hospitals in the study area routinely cool comatose patients with ROSC whose initial rhythm was VF. Such hospitals do not generally cool similar patients whose initial rhythm was not VF, though this is somewhat variable. A few hospitals do not cool. Data will be collected from review of paramedic run reports, hospital records, and 3- month telephone follow-up interview. We propose the following specific aims: Aim 1: Determine outcome of field cooling in eligible patients whose initial rhythm is VF and intended to be delivered to a cooling hospital. Aim 2: Examine safety of field cooling in eligible patients whose initial rhythm is not VF, i.e., pulseless electrical activity or asystole Aim 3: Compare the outcome differences in VF patients delivered to non-cooling hospitals with the differences found in the primary comparison population, VF patients delivered to cooling hospitals. PUBLIC HEALTH RELEVANCE: Between 400,000 and 450,000 people are estimated to experience sudden cardiac death out of hospital or in the emergency room each year in the United States. Brain damage is a major cause of morbidity and mortality in these patients with most never regaining consciousness. Safe and effective therapies that improve outcome after cardiac arrest are urgently needed and in this grant proposal we aim to determine whether the application of mild hypothermia using a rapid infusion of cold normal saline will improve outcome in patients who suffer out-of-hospital cardiac arrest.