CHU Nantes, Pôle anesthésie réanimations, Service d'Anesthésie Réanimation chirurgicale, Nantes, France.
CHU Rennes, Service d'anesthésie réanimation 1, Université de Rennes 1, Rennes, France.
Lancet Respir Med. 2014 Sep;2(9):706-16. doi: 10.1016/S2213-2600(14)70144-4. Epub 2014 Jul 24.
Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia.
We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 μg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261.
From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio [HR] 0.75; 95% CI 0.55-1.03, p=0.07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment.
Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed.
Société Française d'Anesthésie Réanimation.
颅脑外伤后常发生医院获得性肺炎，部分原因可能是创伤性脑损伤引起的肾上腺功能不全。我们检测了小剂量氢化可的松联合氟氢可的松预防医院获得性肺炎的疗效。
我们在法国的 19 个重症监护病房进行了这项双盲、3 期、安慰剂对照试验。我们在严重颅脑损伤后 24 小时内（格拉斯哥昏迷评分≤8 分，脑 CT 扫描提示创伤相关病变）纳入年龄在 15-65 岁的患者。患者随机（1:1；固定块为 12 个，按中心和机制、格拉斯哥昏迷评分、年龄和平均动脉压[MGAP]评分分层）接受每天 200mg 逐渐减量的氢化可的松和每天 50μg 氟氢可的松（1 片）或匹配安慰剂治疗 10 天。在接受研究药物之前，通过短皮质激素试验评估肾上腺功能。如果患者没有肾上腺功能不全，则停止治疗。主要结局是随机分组后 28 天内发生医院获得性肺炎。我们进行了意向治疗分析和包括仅肾上腺功能不全患者的改良意向治疗分析（调整了依托咪酯的使用）。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01093261。
从 2010 年 9 月 1 日至 2012 年 11 月 29 日，我们共纳入 336 例患者（每组 168 例）。8 例患者撤回了同意。在第 28 天，类固醇组 165 例患者中有 74 例（45%）和安慰剂组 163 例患者中有 87 例（53%）发生了 1 次或多次医院获得性肺炎（风险比[HR]0.75；95%CI0.55-1.03，p=0.07）。在意向治疗分析中，我们记录了类固醇组 86 例和安慰剂组 110 例医院获得性肺炎（中位数 0，IQR0-1 与中位数 1，IQR0-1 例患者/例，p=0.07）。在改良意向治疗分析中，对于有肾上腺功能不全的患者，用类固醇治疗的医院获得性肺炎发生率的 HR 为 0.80（95%CI0.56-1.14，p=0.22），在一项探索性预先计划的分析中，HR 为 0.48（0.23-1.01；p=0.05），对于有正常肾上腺功能的患者。我们没有记录到与治疗相关的不良事件。
小剂量氢化可的松联合氟氢可的松并不能改善颅脑外伤患者的预后。然而，由于安慰剂组中发生医院获得性肺炎的患者比例低于预期，因此该研究的效力不足。结果在疗效方面接近统计学意义，这意味着需要进一步的研究。
法国麻醉与复苏学会。
