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NEJM杂志昨日刊登法国P.-F. Dequin教授团队牵头的一项针对氢化可的松在严重CAP（排除感染性休克）患者中应用的一项多中心、双盲、随机对照临床研究，为糖皮质激素，尤其是氢化可的松在重症感染早期的应用提供了新的循证医学证据，或可成为脓毒症“早期预防”“早期阻断”有力武器。
 

BACKGROUND

Whether the anti-inflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear.

研究背景

糖皮质激素的抗炎和免疫调节效应是否可以降低严重社区获得性肺炎患者的死亡率尚不清楚。
 

METHODS

In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 8 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days.

方法

在这项3期、多中心、双盲、随机、对照试验中，我们将因严重社区获得性肺炎而入住重症监护病房（ICU）的成年人静脉注射氢化可的松（200 mg ivdrip qd，4天或8天，视临床改善情况而定，随后逐渐减少剂量，共8或14天）或安慰剂。所有患者均接受标准治疗，包括抗生素和支持性治疗。主要终点为28天死亡。
 

RESULTS

A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, −5.6 percentage points; 95% CI, −9.6 to −1.7; P=0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment.

结果

本研究在第二次计划的中期分析后结束，共800名患者接受了随机分组，分析了795例患者的数据。到第28天，氢化可的松组400例患者中有25例死亡，安慰剂组395例患者中有47例死亡（6.2% vs. 11.9%; P = 0.006）。在基线时未接受机械通气的患者中，氢化可的松组222例患者中有40例（18.0%）进行了气管插管，安慰剂组220例患者中有65例（29.5%）进行了气管插管（RR 0.59; 95% CI 0.40 ~ 0.86）。在基线时未接受血管升压药物的患者中，氢化可的松组359例患者中有55例（15.3%）在28天应用该种治疗，安慰剂组344例患者中有86例（25.0%）开始这种治疗（RR 0.59; 95% CI 0.43 ~ 0.82）。两组患者医院获得性感染和消化道出血的发生率相似；氢化可的松组的患者在治疗的第一周接受了更高剂量的胰岛素。
 

CONCLUSIONS

Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489. opens in new tab.)

在ICU治疗的严重社区获得性肺炎患者中，接受氢化可的松治疗的患者在第28天的死亡风险低于接受安慰剂治疗的患者。（法国卫生部资助；NCT02517489）