Département de Réanimation Médicale et de Médecine Hyperbare, Angers, France.
Service de Réanimation Médicale, Centre Hospitalo-Universitaire Henri Mondor, APHP, Créteil, France.
Lancet Respir Med. 2017 Mar;5(3):180-190. doi: 10.1016/S2213-2600(17)30046-2. Epub 2017 Feb 15.
There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality.
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 at 1·0 (hyperoxia) or FiO 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.
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).
In patients with septic shock, setting FiO to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.
The French Ministry of Health.
目前针对脓毒性休克患者使用高吸入氧浓度（FiO）的机械通气和高渗盐水进行液体复苏的研究还很有限。我们检测了这些干预措施是否与降低死亡率相关。
这是一项在法国 22 个中心进行的、采用双因素、多中心、随机、临床试验（HYPERS2S），纳入了年龄在 18 岁及以上、正在接受机械通气的脓毒性休克患者。通过使用大小随机排列的置换块，按照地点和是否存在急性呼吸窘迫综合征对患者进行分层，采用计算机生成的随机分组列表将患者以 1:1:1:1 的比例随机分配到四个组中。患者在接受机械通气的前 24 小时内，以开放标签的方式接受 FiO 为 1.0（高氧）或 FiO 设置为目标动脉血红蛋白氧饱和度为 88-95%（常氧）；患者在接受机械通气的前 72 小时内，还以双盲的方式接受 280 mL 3.0%（高渗）盐水或 0.9%（等渗）盐水进行液体复苏。主要终点是意向治疗人群在随机分组后第 28 天的死亡率。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT01722422。
在 2012 年 11 月 3 日至 2014 年 6 月 13 日期间，招募了 442 名患者，并将其分配到一个治疗组（常氧[223 例]或高氧[219 例]；等渗[224 例]或高渗[218 例]）。出于安全原因，该试验提前终止。434 名患者记录了 28 天的死亡率；高氧组有 217 例患者中 93 例（43%）死亡，常氧组有 217 例患者中 77 例（35%）死亡（危险比[HR]1.27，95%CI 0.94-1.72；p=0.12）。高渗组有 214 例患者中 89 例（42%）死亡，等渗组有 220 例患者中 81 例（37%）死亡（HR 1.19，0.88-1.61；p=0.25）。我们发现高氧（85%）组和常氧组（76%）之间严重不良事件的总发生率存在显著差异（p=0.02），高氧组患者在 ICU 获得性无力（24[11%]例比 13[6%]例；p=0.06）和肺不张（26[12%]例比 13[6%]例；p=0.04）的数量显著增加，与常氧组相比增加了一倍。我们没有发现两组盐水之间严重不良事件存在统计学差异（p=0.23）。
在脓毒性休克患者中，将 FiO 设置为 1.0 以诱导动脉高氧血症可能会增加死亡率。高渗（3%）盐水并不能提高生存率。
法国卫生部。
