他汀类药物辅助治疗肺炎或脓毒症疗效的Meta分析

doi:10.13481/j.1671-587x.20160228

摘要/Abstract

摘要：

目的: 系统评价他汀类药物治疗肺炎或脓毒症的效果,为他汀类药物治疗肺炎或脓毒症提供相关的循证医学依据。方法: 应用PubMed、EMbase、Cochrane Library、中国生物医学文献数据库、万方数据库和中国知网等数据库检索从建库至2015年1月31日发表的关于他汀类药物的临床随机对照研究。由2位研究者分别按照纳入及排除标准独立进行文献筛查、数据提取及质量评价后进行检索结果汇总,使用Cochrane协作网提供的软件Review Manager 5.3对纳入文献进行数据的处理及统计分析。结果: 有9项研究共1227例患者纳入研究。①共纳入6项研究对住院期间死亡率进行Meta分析,他汀类药物较对照组未能降低肺炎或脓毒症患者住院期间死亡率;相对危险度(RR)=0.83,95%CI(0.63,1.08),P=0.17。②共纳入7项研究对机械通气及入住ICU的需求进行Meta分析,他汀类药物较对照组在改善细菌感染患者机械通气及入住ICU方面未见明显效果;RR=0.99,95%CI(0.96,1.03),P=0.62。③共纳入4项研究对超敏C反应蛋白(CRP)水平进行Meta分析,与安慰剂组比较,他汀类药物可明显降低CRP水平;均数差(MD)=-8.30mg·L^-1,95%CI(-12.13,-4.47),P<0.0001。结论: 他汀类药物不能降低肺炎或脓毒症患者住院期间死亡率及机械通气或入住ICU次数,但可以降低肺炎或脓毒症患者的CRP水平并减轻全身炎症反应。

关键词: 他汀类, 肺炎, 脓毒症, Meta分析

Abstract:

Objective: To systematically review the effects of statins in the treatment of the patients with pneumonia or sepsis, and to provide evidence-based basis for the using of statin in treatment of pneumonia or sepsis.Methods: PubMed, Embase, The Cochrane Library, CNKI, WanFang Data and VIP were searched for randomized placebo-controlled trials of statins published from the establishment time of datebases to January 31, 2015.The qualities of the included studies were independently assessed by two reviewers and the relevant data was extracted for analysis using Review Manager 5.3.Results: Nine trails involving a total of 1227 patients were included.①A total of 6 studies about the mortality of hospitalized patients were included in the Meta-analysis;compared with placebo group, statins didn't improve the mortality of hospitalized patients with pneumonia or sepsis; risk ratio (RR)=0.83, 95%CI(0.63, 1.08), P=0.17.②A total of 7 studies about the rates of mechanical ventilation usage or ICU admission of the patients were included in the Meta-analysis.Compared with placebo group, statins didn't improve the rates of mechanical ventilation usage or ICU admission of the patients with bacteria infection; RR=0.99, 95% CI(0.96, 1.03), P=0.62.③A total of 4 studies about the levels of C reaction protein (CRP) were included in the Meta-analysis.Compared with placebo group, statins significantly reduced the levels of CRP; mean differences(MD)=-8.30mg·L^-1, 95%CI(-12.13, -4.47), P<0.0001.Conclusion: Statins can not significantly reduce both the in-hospital mortality and the rates of mechanical ventilation usage or ICU admission, but can significantly reduce the plasma CRP levels, and reduce the inflammation.

Key words: statins, pneumonia, sepsis, Meta-analysis

中图分类号:

R563.1

邱立洁, 张也, 张文静, 钱东华. 他汀类药物辅助治疗肺炎或脓毒症疗效的Meta分析[J]. 吉林大学学报(医学版), 2016, 42(02): 336-344.

QIU Lijie, ZHANG Ye, ZHANG Wenjing, QIAN Donghua. Meta-analysis on curative effects of statins in treatment of pneumoniaor or sepsis[J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 336-344.

参考文献

[1] De Loecker I,Preiser JC.Statins in the critically ill[J].Ann Intensive Care,2012,2(1):19.

[2] Abeles AM,Pillinger MH.Statins as antiinflammatory and immunomodulatory agents:a future in rheumatologic therapy?[J].Arthritis Rheum,2006,54(2):393-407.

[3] Khan AR,Riaz M,Bin Abdulhak AA,et al.The role of statins in prevention and treatment of community acquired pneumonia:a systematic review and meta-analysis[J].PLoS One,2013,8(1):e52929.

[4] Kwok CS,Yeong JK,Turner RM,et al.Statins and associated risk of pneumonia:a systematic review and meta-analysis of observational studies[J].Eur J Clin Pharmacol,2012,68(5):747-755.

[5] Wan YD,Sun TW,Kan QC,et al.Effect of statin therapy on mortality from infection and sepsis:a meta-analysis of randomized and observational studies[J].Crit Care,2014,18:R71.

[6] 郑辉烈,王忠旭,王增珍.Meta分析中发表偏倚的Begg's检验,Egger's检验及Macaskill's检验的SAS程序实现[J].中国循证医学杂志,2009,9(8):910-916.

[7] Sterne JA,Gavaghan D,Egger M.Publication and related bias in meta-analysis:power of statistical tests and prevalence in the literature[J].J Clin Epidemiol,2000,53(11):1119-1129.

[8] Papazian L,Roch A,Charles PE,et al.Effect of statin therapy on mortality in patients with ventilator-associated pneumonia:a randomized clinical trial[J].JAMA,2013,310(16):1692-1700.

[9] 孙广信,李国燕,李振华.阿托伐他汀辅助治疗重症社区获得性肺炎的临床探索[J].中国卫生产业,2012,9(19):78.

[10] Novack V,Eisinger M,Frenkel A,et al.The effects of statin therapy on inflammatory cytokines in patients with bacterial infections:a randomized double-blind placebo controlled clinical trial[J].Intens Care Med,2009,35(7):1255-1260.

[11] Kruger PS,Harward ML,Jones MA,et al.Continuation of statin therapy in patients with presumed infection:a randomized controlled trial[J].Am J Respir Crit Care Med,2011,183(6):774-781.

[12] Viasus D,Garcia-Vidal C,Simonetti AF,et al.The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia:a randomised,double-blind,placebo-controlled trial[J].BMJ Open,2015,5(1):e006251.

[13] Kruger P,Bailey M,Bellomo R,et al.A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis[J].Am J Respir Crit Care Med,2013,187(7):743-750.

[14] Patel JM,Snaith C,Thickett DR,et al.Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)[J].Crit Care,2012,16(6):R231.

[15] Makris D,Manoulakas E,Komnos A,et al.Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality:Open-label,randomized study[J].Crit Care Med,2011,39(11):2440-2446.

[16] 舒平,周慧云,黄志刚,等.阿托伐他汀对脓毒症患者急性肾损伤的保护作用[J].中华危重症医学杂志:电子版,2013,6(2):5-9.

[17] Xing XQ,Duan S,Wu XW,et al.Atorvastatin reduces lipopolysaccharide-induced expression of C-reactive protein in human lung epithelial cells[J].Mol Med Rep,2011,4(4):753-757.

[18] Iwata A,Shirai R,Ishii H,et al.Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells[J].Clin Exp Immunol,2012,168(2):234-240.

[19] Troeman DP,Postma DF,van Werkhoven CH,et al.The immunomodulatory effects of statins in community-acquired pneumonia:a systematic review[J].J Infect,2013,67(2):93-101.

[20] Merx MW,Liehn EA,Graf J,et al.Statin treatment after onset of sepsis in a murine model improves survival[J].Circulation,2005,112(1):117-124.