Kirkegaard Hans, Søreide Eldar, de Haas Inge, Pettilä Ville, Taccone Fabio Silvio, Arus Urmet, Storm Christian, Hassager Christian, Nielsen Jørgen Feldbæk, Sørensen Christina Ankjær, Ilkjær Susanne, Jeppesen Anni Nørgaard, Grejs Anders Morten, Duez Christophe Henri Valdemar, Hjort Jakob, Larsen Alf Inge, Toome Valdo, Tiainen Marjaana, Hästbacka Johanna, Laitio Timo, Skrifvars Markus B
Research Center for Emergency Medicine and Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.
Department of Anesthesiology and Intensive Care, Stavanger University Hospital, Stavanger, Norway3Department of Clinical Medicine, University of Bergen, Bergen, Norway.
JAMA. 2017 Jul 25;318(4):341-350. doi: 10.1001/jama.2017.8978.
International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.
To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.
DESIGN, SETTING, AND PARTICIPANTS: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.
Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.
The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.
In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group.
In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.
clinicaltrials.gov Identifier: NCT01689077.
国际复苏指南建议，院外心脏骤停后昏迷的患者应进行目标温度管理（TTM），体温维持在33°C至36°C至少24小时，但TTM的最佳持续时间尚不确定。
确定与目前推荐的标准24小时TTM相比，33°C的TTM持续48小时是否能带来更好的神经学预后。
设计、地点和参与者：这是一项由研究者发起的国际、结局评估者设盲、平行、实用、多中心随机临床优效性试验，在6个欧洲国家的10所大学医院的10个重症监护病房（ICU）进行。2013年2月16日至2016年6月1日，共纳入355例院外心脏骤停后昏迷的成年患者，最终随访时间为2016年12月27日。
患者被随机分为48小时（n = 176）或24小时（n = 179）的TTM（33±1°C），随后以每小时0.5°C的速度逐渐复温直至达到37°C。
主要结局为6个月时的神经学预后，采用脑功能分类（CPC）评分为1或2来定义良好预后。次要结局包括6个月时的死亡率，包括死亡时间、不良事件的发生情况以及ICU资源使用情况。
在355例随机分组的患者（平均年龄60岁；295例[83%]为男性）中，351例（99%）完成了试验。在这些患者中，48小时组69%（120/175）的患者在6个月时预后良好，而24小时组为64%（112/176）（差异为4.9%；95%CI，-5%至14.8%；相对风险[RR]，1.08；95%CI，0.93 - 1.25；P = 0.33）。48小时组6个月时的死亡率为27%（48/175），24小时组为34%（60/177）（差异为-6.5%；95%CI，-16.1%至3.1%；RR，0.81；95%CI，0.59 - 1.11；P = 0.19）。48小时组和24小时组之间的死亡时间无显著差异（风险比，0.79；95%CI，0.54 - 1.15；P = 0.22）。48小时组的不良事件（97%）比24小时组（91%）更常见（差异为5.6%；95%CI，0.6% - 10.6%；RR，1.06；95%CI，1.01 - 1.12；P = 0.04）。48小时组的ICU住院时间中位数（151小时对117小时；P < 0.001）比24小时组长，但住院时间（11天对12天；P = 0.50）无差异。
在入住ICU的院外心脏骤停昏迷幸存者中，与33°C的TTM持续24小时相比，33°C的TTM持续48小时并未显著改善6个月时的神经学预后。然而，该研究检测临床重要差异的能力可能有限，可能需要进一步研究。
clinicaltrials.gov标识符：NCT01689077。
