Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain4Unive.
Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain6Institut d´Investigació Biomèdica Sant Pau, Barcelona, Spain.
JAMA. 2015 Feb 17;313(7):677-86. doi: 10.1001/jama.2015.88.
In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial.
To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012.
Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission.
The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed.
There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34).
Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population.
clinicaltrials.gov Identifier: NCT00908713.
重要性：在患有严重社区获得性肺炎的患者中，治疗失败与过度炎症反应和较差的预后相关。皮质类固醇可能会调节这些患者的细胞因子释放，但这种辅助治疗的益处仍存在争议。
目的：评估皮质类固醇在患有严重社区获得性肺炎和高相关炎症反应的患者中的作用。
设计、地点和参与者：这是一项多中心、随机、双盲、安慰剂对照试验，在西班牙的 3 家教学医院进行，涉及严重社区获得性肺炎和高炎症反应的患者，炎症反应的定义为入院时 C 反应蛋白水平大于 150mg/L。患者于 2004 年 6 月至 2012 年 2 月期间被招募并进行随访。
干预措施：患者在入院后 36 小时内接受静脉注射 0.5mg/kg 每 12 小时甲泼尼龙（n=61）或安慰剂（n=59），疗程为 5 天。
主要结局和测量指标：主要结局是治疗失败（早期治疗失败的综合结局定义为[1]临床恶化表现为休克的发展，[2]基线时不存在需要侵入性机械通气，或[3]治疗后 72 小时内死亡；或晚期治疗失败的综合结局定义为[1]影像学进展，[2]严重呼吸衰竭持续存在，[3]休克发展，[4]基线时不存在需要侵入性机械通气，或[5]治疗开始后 72 小时至 120 小时内死亡；或两者兼有）。住院死亡率是次要结局，评估了不良事件。
结果：与安慰剂组（18 例[31%]）相比，接受甲泼尼龙治疗的患者的治疗失败率（8 例[13%]）较低（P=0.02），组间差异为 18%（95%CI，3%至 32%）。皮质类固醇治疗降低了治疗失败的风险（比值比，0.34[95%CI，0.14 至 0.87]；P=0.02）。两组的住院死亡率无差异（甲泼尼龙组 6 例[10%]，安慰剂组 9 例[15%]；P=0.37）；组间差异为 5%（95%CI，-6%至 17%）。甲泼尼龙组 11 例（18%）和安慰剂组 7 例（12%）患者出现高血糖（P=0.34）。
结论和相关性：在患有严重社区获得性肺炎和高初始炎症反应的患者中，与安慰剂相比，急性使用甲泼尼龙可降低治疗失败率。如果得到证实，这些发现将支持在这一临床人群中使用皮质类固醇作为辅助治疗。
试验注册：clinicaltrials.gov 标识符：NCT00908713。
