加拿大渥太华大学心脏研究所George Wells团队比较了中度和轻度治疗性低温对院外心脏骤停昏迷幸存者死亡率和神经系统预后的影响。相关论文发表在2021年10月19日出版的《美国医学会杂志》上。

院外心脏骤停的昏迷幸存者死亡率高，神经损伤严重。当前指南建议在32°C至36°C温度下进行24小时的目标温度管理。然而，小规模的研究表明，以较低体温为目标有潜在益处。

为了确定中度低温（31°C）与轻度低温（34°C）相比是否能改善院外心脏骤停后昏迷幸存者的临床结局。研究组在加拿大安大略省东部某三级心脏护理中心进行了一项单中心、双盲、随机、临床优势试验。

2013年8月4日至2020年3月20日，共纳入389例院外心脏骤停患者，最终随访时间为2020年10月15日。将患者随机分配，其中193例接受目标体温为31°C的温度管理，96例接受目标体温为34°C的温度管理，持续24小时。

主要结局为180天全因死亡或神经功能预后差。神经功能预后采用残疾评定量表评估，神经功能预后差定义为得分大于5分（范围0-29，29分为最差预后[植物人状态]）。共有19个次要结局，包括180天的死亡率和重症监护病房的住院时间。

在纳入主要分析的367名患者中（平均年龄61岁；69名为女性[19%]），366名（99.7%）完成了试验。31°C组184名患者中有89名（48.4%）发生主要结局，34°C组183名患者中有83名（45.4%），组间差异不显著。

在19项次要结局中，18项无统计学意义。在目标温度为31°C和34°C的患者中，180天的死亡率分别为43.5%和41.0%。31°C组在重症监护病房的平均住院时间为10天，显著长于34°C组的7天。在31°C组和34°C组的不良事件中，深静脉血栓发生率分别为11.4%和10.9%，下腔静脉血栓发生率分别为3.8%和7.7%。

研究结果表明，在院外心脏骤停的昏迷幸存者中，与34°C的目标温度相比，31°C的目标温度并没有显著降低180天内死亡或神经功能预后较差的风险。

附：英文原文

Title: Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial

Author: Michel Le May, Christina Osborne, Juan Russo, Derek So, Aun Yeong Chong, Alexander Dick, Michael Froeschl, Christopher Glover, Benjamin Hibbert, Jean-Franois Marquis, Sophie De Roock, Marino Labinaz, Jordan Bernick, Shawn Marshall, Ronnen Maze, George Wells

Issue&Volume: 2021/10/19

Abstract:

Importance  Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures.

Objective  To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest.

Design, Setting, and Participants  Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020.

Interventions  Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n=193) or 34 °C (n=196) for a period of 24 hours.

Main Outcomes and Measures  The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit.

Results  Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P=.56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P=.63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P=.004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively.

Conclusions and Relevance  In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference.

DOI: 10.1001/jama.2021.15703

Source: https://jamanetwork.com/journals/jama/article-abstract/2785263