Annane Djillali, Sébille Véronique, Charpentier Claire, Bollaert Pierre-Edouard, François Bruno, Korach Jean-Michel, Capellier Gilles, Cohen Yves, Azoulay Elie, Troché Gilles, Chaumet-Riffaud Philippe, Bellissant Eric
Service de Réanimation Médicale, Hôpital Raymond Poincaré, 104 Blvd Raymond Poincaré, 92380 Garches, France.
JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.
Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.
To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.
Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.
Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.
Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.
Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).
One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.
In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.
感染性休克可能与相对肾上腺皮质功能不全有关。因此，有人提出采用低剂量皮质类固醇替代疗法来治疗感染性休克。
评估低剂量皮质类固醇是否能提高感染性休克合并相对肾上腺皮质功能不全患者的28天生存率。
1995年10月9日至1999年2月23日在法国19个重症监护病房进行的安慰剂对照、随机、双盲、平行组试验。
300名符合感染性休克常规标准的成年患者在接受短促肾上腺皮质激素试验后入组。
患者被随机分配接受氢化可的松（每6小时静脉推注50毫克）和氟氢可的松（每日1次，50微克片剂）（n = 151）或匹配的安慰剂（n = 149），为期7天。
相对肾上腺皮质功能不全患者（对促肾上腺皮质激素试验无反应者）的28天生存分布。
皮质类固醇组有1名患者因撤回同意书而被排除在分析之外。促肾上腺皮质激素试验无反应者有229例（安慰剂组115例；皮质类固醇组114例），有反应者70例（安慰剂组34例；皮质类固醇组36例）。在无反应者中，安慰剂组有73例死亡（63%），皮质类固醇组有60例死亡（53%）（风险比，0.67；95%置信区间，0.47 - 0.95；P = 0.02）。安慰剂组46例患者（40%）和皮质类固醇组65例患者（57%）在28天内停用血管升压药治疗（风险比，1.91；95%置信区间，1.29 - 2.84；P = 0.001）。有反应者组间无显著差异。两组不良事件发生率相似。
在我们的试验中，低剂量氢化可的松和氟氢可的松治疗7天可显著降低感染性休克合并相对肾上腺皮质功能不全患者的死亡风险，且不增加不良事件。
