Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest
Bruno François, Alain Cariou, Raphaël Clere-Jehl, et al
N Engl J Med 2019; 381:1831-1842
DOI: 10.1056/NEJMoa1812379
BACKGROUND 背景
Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown.
因可除颤心律导致院外心跳骤停且接受目标性体温管理的患者发生呼吸机相关肺炎的风险增加。短期预防性抗生素的益处尚不明确。
METHODS 方法
We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin–clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia.
我们进行了一项多中心、双盲、随机、安慰剂对照试验，入选因可除颤心律导致院外心跳骤停的成年 (>18 岁)患者，收入ICU，接受目标体温(32 to 34°C)管理且应用机械通气。已接受抗生素治疗、多重耐药菌长期定植或临终状态患者排除。在心跳骤停后6小时内，患者分别接受静脉阿莫西林-克拉维酸(剂量分别为1 g 和 200 mg)或安慰剂，每日3次，疗程2天。主要预后指标为早期呼吸机相关性肺炎(在住院最初7天内发生)。由一个独立的评估委员会确定呼吸机相关性肺炎的诊断。
RESULTS 结果
A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P=0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups.
共有198名患者接受随机分组，194名患者纳入分析。经过判断，共确诊60名呼吸机相关性肺炎患者，包括51例早期呼吸机相关肺炎。与安慰剂相比，抗生素预防组早期呼吸机相关肺炎发生率较低(19 [19%] vs. 32 [34%]; 风险比, 0.53; 95% 可信区间, 0.31 to 0.92; P=0.03)。抗生素组与对照组晚期呼吸机相关肺炎发生率(4% vs. 5%)，无机械通气天数 (21 vs. 19 天)，ICU住院日 (存活患者 5 vs. 8 天，死亡患者 7 vs. 7 天)，及28天病死率 (41% vs. 37%)并无差异。
CONCLUSIONS 结论
A 2-day course of antibiotic therapy with amoxicillin–clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28.
对于因可除颤心律导致院外心跳骤停且接受目标体温(32 to 34°C)管理的患者，收入ICU，与安慰剂相比，2天疗程的阿莫西林-克拉维酸能够能够降低早期呼吸机相关肺炎的发生率。其他主要临床指标如无机械通气天数及28天病死率两组间无显著差异。
(Funded by the French Ministry of Health; ANTHARTIC ClinicalTrials.gov number, NCT02186951. opens in new tab.)
评论[仅代表个人观点]
- 老调重弹：多种非手术情况下的预防性抗生素是很久以来临床研究的话题，如多发创伤患者医院获得性肺炎的预防，免疫功能抑制患者PCP的预防等，沉寂一段时间后又出现了新的研究结果
- 关注的短期指标：如果仅仅关注早期呼吸机相关肺炎而言，这个研究的结果应当认定为阳性，支持使用预防性抗生素。然而，如果关注迟发性肺炎或耐药菌感染导致的迟发性肺炎（既往研究发现，预防性抗生素增加耐药菌导致的迟发性医院获得性肺炎风险增加），又当如何？样本量是否足够说明这一点呢？
- 关注的远期指标：如果考虑到预防性抗生素对整体环境中细菌耐药的影响，是否又会得到不同结果？
- 我个人不会因为这个研究应用预防性抗生素
