Chant Clarence, Leung Ann, Friedrich Jan O
Crit Care. 2013 Nov 29;17(6):R279. doi: 10.1186/cc13134.
The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods.
We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models.
Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, -1.5; 95% CI, -2.8 to -0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I2 = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054).
Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance.
本研究旨在确定与传统给药方法相比，在重症患者中使用基于药效学的抗菌药物给药方式（如延长/持续输注）是否能改善预后。
我们检索了Medline、HealthStar、EMBASE、Cochrane临床试验注册库和CINAHL，检索时间从建库至2013年9月，不限语言，以查找比较延长/持续输注与传统给药方式的研究。两位作者独立选择研究、提取方法学和预后数据，并进行质量评估。采用随机效应模型进行荟萃分析。
在1319篇被引文献中，13项随机对照试验（RCTs）（n = 782例患者）和13项队列研究（n = 2117例患者）符合纳入标准。与传统的非基于药效学的给药方式相比，持续/延长输注的RCTs显著降低了临床失败率（相对危险度（RR）0.68；95%置信区间（CI）0.49至0.94，P = 0.02）和重症监护病房住院时间（平均差值，-1.5；95% CI，-2.8至-0.2天，P = 0.02），但未降低死亡率（RR，0.87；95% CI，0.64至1.19；P = 0.38）。这些分析未发现显著的试验间异质性（I2 = 0）。当汇总所有纳入研究（RCTs和队列研究）的结果时，死亡率降低几乎达到统计学显著性（RR，0.83；95% CI，0.69至1.00；P = 0.054）。
小型RCTs的汇总结果表明，在重症患者中使用抗生素持续/延长输注可降低临床失败率和重症监护病房住院时间。当RCTs结果与队列研究结果合并时，死亡率降低几乎达到统计学显著性。这些结果支持开展有足够效力的RCTs，以更好地确定持续/延长输注在抗生素耐药时代的效用。
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