ARTICLES|ONLINE FIRST
Aggressive intraoperative warming versus routine thermal management during non-cardiac surgery (PROTECT): a multicentre, parallel group, superiority trial
Daniel I Sessler, Lijian Pei, Kai Li, et al
Lancet Published:April 04, 2022
DOI:https://doi.org/10.1016/S0140-6736(22)00560-8
Summary
Background
Moderate intraoperative hypothermia promotes myocardial injury, surgical site infections, and blood loss. Whether aggressive warming to a truly normothermic temperature near 37°C improves outcomes remains unknown. We aimed to test the hypothesis that aggressive intraoperative warming reduces major perioperative complications.
Methods
In this multicentre, parallel group, superiority trial, patients at 12 sites in China and at the Cleveland Clinic in the USA were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35·5°C (routine thermal management group) during non-cardiac surgery. Randomisation was stratified by site, with computer-generated, randomly sized blocks. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery expected to last 2–6 h with general anaesthesia, and were expected to have at least half of the anterior skin surface available for warming. Patients requiring dialysis and those with a body-mass index exceeding 30 kg/m2 were excluded. The primary outcome was a composite of myocardial injury (troponin elevation, apparently of ischaemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery, as assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03111875.
Findings
Between March 27, 2017, and March 16, 2021, 5056 participants were enrolled, of whom 5013 were included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients assigned to aggressive warming had a mean final intraoperative core temperature of 37·1°C (SD 0·3) whereas the routine thermal management group averaged 35·6°C (SD 0·3). At least one of the primary outcome components (myocardial injury after non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (9·9%) of 2497 patients in the aggressively warmed group and in 239 (9·6%) of 2490 patients in the routine thermal management group. The common effect relative risk of aggressive versus routine thermal management was an estimated 1·04 (95% CI 0·87–1·24, p=0·69). There were 39 adverse events in patients assigned to aggressive warming (17 of which were serious) and 54 in those assigned to routine thermal management (30 of which were serious). One serious adverse event, in an aggressively warmed patient, was deemed to be possibly related to thermal management.
Interpretation
The incidence of a 30-day composite of major cardiovascular outcomes did not differ significantly in patients randomised to 35·5°C and to 37°C. At least over a 1·5°C range from very mild hypothermia to full normothermia, there was no evidence that any substantive outcome varied. Keeping core temperature at least 35·5°C in surgical patients appears sufficient.
Funding
3M and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong.
Translation
For the Chinese translation of the abstract see Supplementary Materials section.
积极保温与常规管理对非心脏手术后心肌损伤的影响:一项多中心、平行、优效性临床试验
摘要
背景 手术患者术中出现中度低体温可能导致心肌损伤、增加手术部位感染机率和失血量。积极 保温至接近正常体温水平37°C，能否改善术后结局仍然未知。本研究旨在验证假说:术中积极 保温能够减少围术期主要并发症。
方法 这是一项临床多中心、平行、优效性随机对照试验，12家中国医疗机构和美国克利夫兰诊 所的非心脏大手术患者，按照1:1原则随机分入积极保温组(目标:终点核心体温37°C)或常规 管理组(目标:终点核心体温35.5°C)。按照医疗机构进行分层随机，通过计算机自动生成随 机号。入组标准:年龄≥45周岁，合并至少一个心血管事件危险因素，预计全身麻醉下行非心 脏大手术且手术时间约2-6小时，保温面积超过体表面积的1/2。排除标准:透析患者或身体质 量指数>30 kg/m2。主要结局指标:术后心血管事件复合终点，包括:非心脏手术后心肌损伤 (肌钙蛋白升高、症状性心肌缺血)、非致死性心脏骤停和术后30天内全因死亡，并通过意向 性分析矫正。研究注册:ClinicalTrials.gov, NCT03111875。
结果 自2017年3月27日至2021年3月16日，共入组5056例患者，其中5013例纳入最终的意向性 分析(积极保温组2507例，常规管理组2506例)。手术过程中，积极保温组的终点核心体温平 均值为37.1±0.3°C，而常规管理组的终点核心体温平均值为35.6±0.3°C。积极保温组2497例患 者中有246例(9.9%)术后出现了至少一种上述结局(非心脏手术后心肌损伤、心脏骤停、死亡)， 而常规保温组2490例患者中有239例(9.6%)。积极保温组与常规管理组比较，术后心血管事件复 合终点的相对危险度(relative risk)为1.04 (95%CI 0.87-1.24, p= 0.69)。试验过程中积极保温组报 告了39件不良事件(16件定性为严重不良事件)，常规管理组54件(30件定性为严重)。 积极 保温组中出现的1例严重不良事件，判定与加温治疗相关。
阐述 本研究证明非心脏大手术患者术中核心体温管理至37°C或35.5°C，术后30天心血管事件复 合终点发生率无显著差异。从轻度低体温到完全正常体温，超过1.5°C的差异下，没有证据表明 任何实质性结局指标间具有显著性差异。手术患者术中维持核心体温不低于35.5°C即可。
基金 3M公司及中华人民共和国香港特别行政区政府食物及卫生局 医疗卫生研究基金 。
