Dell'Anna A M, Scolletta S, Nobile L, Taccone F S
Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium -
Minerva Anestesiol. 2014 Jun;80(6):736-43. Epub 2014 Mar 21.
Implementation of treatments able to improve survival and neurological recovery of cardiac arrest (CA) survivors is a major clinical challenge. More than ten years ago, two pivotal trials showed that application of therapeutic hypothermia (TH, 32-34 °C) to patients resuscitated from an out-of-hospital CA (OHCA) with an initial shockable rhythm significantly ameliorated their outcome. Since then, TH has been used also for non-shockable rhythms and for in-hospital CA to some extent, even if the quality of evidence supporting TH in such situations remained very low. The objective of this randomized, controlled, multicenter study (named "Targeted Temperature Management" TTM study) was to compare two different strategies of temperature control after CA; patients were randomized to be treated either at 33 °C or at 36 °C for 24 hours, while fever was accurately avoided for the first 3 days since randomization. Inclusion criteria were: Glasgow Coma Score <8, presumed cardiac origin of arrest, randomization occurring within the first 4 hours from the return of spontaneous circulation. Patients were excluded if they had an unwitnessed arrest with asystole as the initial rhythm, suspected or known acute intracranial hemorrhage or stroke, and a body temperature of less than 30 °C. A specific algorithm was used to decide for withdrawal of care in patients remaining comatose after 72 hours since normothermia was achieved. The primary outcome was 6-month mortality. After the enrollment of 939 patients, the authors did not find any significant difference between groups in primary outcome (235/473 [50%] and 225/466 [48%] of patients died in 33 °C and 36 °C group, respectively; HR for death if in the 33 °C group, 1.06 [95% CI 0.89 to 1.28; P=0.51]). Similarly, the analysis of the composite outcome of death or poor neurologic function yielded similar results between the two groups. This is the largest study evaluating the effects of two different strategies of temperature management after CA. Some important concerns have been raised on the real benefit of keeping CA patients at 33 °C and major changes in clinical practice are expected. We discussed herein the main differences with previous randomized trials and tried to identify possible explanations for these findings.
实施能够提高心脏骤停（CA）幸存者生存率和神经功能恢复的治疗方法是一项重大的临床挑战。十多年前，两项关键试验表明，对初始可电击心律的院外心脏骤停（OHCA）复苏患者应用治疗性低温（TH，32 - 34°C）可显著改善其预后。从那时起，TH也在一定程度上用于不可电击心律和院内心脏骤停患者，尽管支持TH在这种情况下应用的证据质量仍然很低。这项随机、对照、多中心研究（名为“目标温度管理”TTM研究）的目的是比较心脏骤停后两种不同的温度控制策略；患者被随机分为在33°C或36°C治疗24小时，同时在随机分组后的前3天准确避免发热。纳入标准为：格拉斯哥昏迷评分<8、推测心脏骤停起源、在自主循环恢复后的前4小时内进行随机分组。如果患者最初心律为无脉性电活动的未目击心脏骤停、疑似或已知急性颅内出血或中风以及体温低于30°C，则被排除。使用特定算法决定在达到正常体温后72小时仍昏迷的患者是否停止治疗。主要结局是6个月死亡率。在纳入939例患者后，作者发现两组在主要结局方面没有显著差异（33°C组和36°C组分别有235/473 [50%]和225/466 [48%]的患者死亡；33°C组的死亡风险比为1.06 [95% CI 0.89至1.28；P = 0.51]）。同样，对死亡或神经功能不良的复合结局分析在两组之间也得出了相似的结果。这是评估心脏骤停后两种不同温度管理策略效果的最大规模研究。对于将心脏骤停患者体温维持在33°C的实际益处已经提出了一些重要问题，预计临床实践会有重大改变。我们在此讨论了与先前随机试验的主要差异，并试图找出这些发现的可能解释。
