Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial
Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial
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DOI：
10.1016/s2213-2600(17)30046-2
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发表时间：
2017-03-01
影响因子：
76.2
通讯作者：
Radermacher, Peter
中科院分区：
文献类型：
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作者：
Asfar, Pierre;Schortgen, Frederique;Radermacher, Peter
背景对于感染性休克患者使用机械通气并增加吸入氧浓度（FiO（2））和使用高渗盐溶液进行液体复苏的研究不足。我们测试这些干预措施是否与降低mortals.Methods这两个由两个因素，多中心，随机，临床试验（HYPERS 2S）招募患者年龄在18岁及以上的感染性休克谁是机械通气从22个中心在法国。通过计算机生成的随机化列表，将患者以1：1：1：1的比例随机分配至4组，并使用随机大小的排列区组，根据研究中心和是否存在急性呼吸窘迫综合征进行分层。患者以开放标签方式接受机械通气，FiO（2）为1.0（高氧）或FiO（2）设置为目标动脉血红蛋白氧饱和度为88-95%（常氧）在第一个24小时;患者还以双盲方式接受，在前72小时内，使用280 mL推注的3.0%（高渗）生理盐水或0.9%（等渗）生理盐水进行液体复苏。主要终点是意向治疗人群随机化后第28天的死亡率。该研究注册于ClinicalTrials.gov，编号NCT 01722422。结果在2012年11月3日至2014年6月13日期间，招募了442名患者并将其分配至治疗组（常氧[n = 223]或高氧[n = 219];等渗[n = 224]或高渗[n = 218]）。由于安全性原因，试验提前停止。记录了434例患者的28天死亡率;高氧组217例患者中有93例（43%）死亡，而常氧组217例患者中有77例（35%）死亡（风险比[HR] 1.27，95% CI 0.94-1.72; p = 0.12）。高渗组214例患者中有89例（42%）死亡，而等渗组220例患者中有81例（37%）死亡（HR 1.19，0.88-1.61; p = 0.25）。我们发现，高氧组和低氧组之间严重不良事件的总体发生率有显著差异，（185 [85%]）和常氧组（165 [76%]; p = 0.02），高氧组重症监护病房获得性虚弱患者数量的临床相关性加倍（24 [11%] vs 13 [6%]; p = 0.06）和肺不张（26 [12%] vs 13 [6%]; p = 0.04）。我们发现两个生理盐水组之间的严重不良事件没有统计学差异（p = 0.23）。解释在脓毒性休克患者中，将FiO（2）设置为1.0以诱导动脉高氧可能会增加死亡风险。高渗盐水（3%）不能改善生存率。
Background There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO(2)) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality.Methods This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO(2) at 1.0 (hyperoxia) or FiO(2) set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3.0% (hypertonic) saline or 0.9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422.Findings Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia [n = 223] or hyperoxia [n = 219]; isotonic [n = 224] or hypertonic [n = 218]). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio [HR] 1.27, 95% CI 0.94-1.72; p = 0.12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1.19, 0.88-1.61; p = 0.25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 [85%]) and normoxia groups (165 [76%]; p = 0.02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 [11%] vs 13 [6%]; p = 0.06) and atelectasis (26 [12%] vs 13 [6%]; p = 0.04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p = 0.23).Interpretation In patients with septic shock, setting FiO(2) to 1.0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.