维生素C在脓毒症及脓毒性休克患者治疗中疗效的Meta分析
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摘要
目的系统评价静脉输注维生素C对脓毒症及脓毒性休克患者的疗效。方法计算机检索PubMed、EMBASE、The Cochrane Library、Web of Science、万方、CBM、CNKI电子数据库自建库至2018年8月以来关于维生素C治疗脓毒症及脓毒性休克患者的随机对照研究。由2位研究者按照纳入标准进行文献筛选、数据提取及质量评价后,采用RevMan 5.3软件进行Meta分析。结果共纳入6个随机对照试验,涉及患者318例。Meta分析结果通过随机效应模型分析得出,试验组与对照组对脓毒症及脓毒性休克患者病死率的影响,差异无统计学意义[RR=0.82,95%CI(0.48,1.38),Z=0.76,P=0.45]。漏斗图显示各研究间存在发表偏倚。结论静脉输注维生素C不能改善脓毒症及脓毒性休克患者的病死率。
Objective To systemically explore the efficacy of vitamin C intravenous infusion on patients with sepsis and septic shock. Methods A systematic search for randomized controlled trials on comparing the vitamin C treatment group and control group of patients with sepsis and septic shock was performed from PubMed, EMBASE, The Cochrane Library, Web of Science,Wanfang data, CBM, CNKI from their inception to August 2018. Two reviewers independently screened studies, extracted data and assessed methodological quality according to the inclusion criteria. Then meta-analysis was conducted using RevMan 5.3 software. Results A total of 6 studies with 318 patients were included. The random effect model in meta-analysis showed that there was no significant difference in total mortality between vitamin C treatment and control groups [RR = 0.82, 95%CI(0.48, 1.38), Z = 0.76, P = 0.45]. The funnel plot demonstrated publication bias between those studies. Conclusion Intravenous infusion of vitamin C does not reduce the mortality of patients with sepsis and septic shock.
Objective To systemically explore the efficacy of vitamin C intravenous infusion on patients with sepsis and septic shock. Methods A systematic search for randomized controlled trials on comparing the vitamin C treatment group and control group of patients with sepsis and septic shock was performed from PubMed, EMBASE, The Cochrane Library, Web of Science,Wanfang data, CBM, CNKI from their inception to August 2018. Two reviewers independently screened studies, extracted data and assessed methodological quality according to the inclusion criteria. Then meta-analysis was conducted using RevMan 5.3 software. Results A total of 6 studies with 318 patients were included. The random effect model in meta-analysis showed that there was no significant difference in total mortality between vitamin C treatment and control groups [RR = 0.82, 95%CI(0.48, 1.38), Z = 0.76, P = 0.45]. The funnel plot demonstrated publication bias between those studies. Conclusion Intravenous infusion of vitamin C does not reduce the mortality of patients with sepsis and septic shock.
引文
1 Singer M,Deutschman CS,Seymour CW,et al.The third international consensus definitions for sepsis and septic shock(sepsis-3)[J].JAMA,2016,315(8):801-810.
2 Esposito S,De Simone G,Boccia G,et al.Sepsis and septic shock:new definitions,new diagnostic and therapeutic approaches[J].J Glob Antimicrob Resist,2017(10):204-212.
3李晗宇,陈路芳,李金优,等.益生菌制剂对脓毒症小鼠生存情况的影响及机制研究[J/CD].中华危重症医学杂志(电子版),2017,10(5):289-295.
4 Wilson JX,Wu F.Vitamin C in sepsis[J].Subcell Biochem,2012(56):67-83.
5黄颖,寿松涛,王军,等.脓毒症与免疫细胞凋亡相关研究进展[J/CD].中华危重症医学杂志(电子版),2017,10(4):270-273.
6 Berger MM,Oudemans-van Straaten HM.Vitamin Csupplementation in the critically ill patient[J].Curr Opin Clin Nutr Metab Care,2015,18(2):193-201.
7 May JM,Harrison FE.Role of vitamin C in the function of the vascular endothelium[J].Antioxid Redox Signal,2013,19(17):2068-2083.
8 Mantzarlis K,Tsolaki V,Zakynthinos E.Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies[J].Oxid Med Cell Longev,2017:5985209.
9汤鲁明,王林霞,孙来芳,等.萝卜硫素对脓毒症急性肺损伤大鼠氧化损伤及脱嘌呤/脱嘧啶核酸内切酶1表达的影响[J/CD].中华危重症医学杂志(电子版),2017,10(4):246-251.
10 Wilson JX.Evaluation of vitamin C for adjuvant sepsis therapy[J].Antioxid Redox Signal,2013,19(17):2129-2140.
11王飞飞,朱晓萍,马少林.维生素C在脓毒症中的应用进展[J].中国急救医学,2017,37(11):988-991.
12 Fisher BJ,Kraskauskas D,Martin EJ,et al.Attenuation of sepsis-induced organ injury in mice by vitamin C[J].JPEN J Parenter Enteral Nutr,2014,38(7):825-839.
13 Fisher BJ,Kraskauskas D,Martin EJ,et al.Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid[J].Am J Physiol Lung Cell Mol Physiol,2012,303(1):L20-L32.
14 Fisher BJ,Seropian IM,Kraskauskas D,et al.Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury[J].Crit Care Med,2011,39(6):1454-1460.
15 Pontes-Arruda A,Aragao AM,Albuquerque JD.Effects of enteral feeding with eicosapentaenoic acid,gammalinolenic acid,and antioxidants in mechanically ventilated patients with severe sepsis and septic shock[J].Crtit Care Med,2006,34(9):2325-2333.
16 Beale RJ,Sherry T,Lei K,et al.Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis:outcome of a randomized,controlled,double-blind trial[J].Crit Care Med,2008,36(1):131-144.
17 Ferrón-Celma I,Mansilla A,Hassan L,et al.Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery[J].J Surg Res,2009,153(2):224-230.
18 Fowler AA,Syed AA,Knowlson S,et al.Phase Isafety trial of intravenous ascorbic acid in patients with severe sepsis[J].J Transl Med,2014(12):32.
19 Marik PE,Khangoora V,Rivera R,et al.Hydrocortisone,vitamin C and thiamine for the treatment of severe sepsis and septic shock:a retrospective beforeafter study[J].Chest,2017,151(6):1229-1238.
20 Galley HF,Howdle PD,Walker BE,et al.The effects of intravenous antioxidants in patients with septic shock[J].Free Radic Biol Med,1997,23(5):768-774.
21 Borrelli E,Roux-Lombard P,Grau GE,et al.Plasma concentrations of cytokines,their soluble receptors,and antioxidant vitamins can predict the development of multiple organ failure in patients at risk[J].Crit Care Med,1996,24(3):392-397.
22 Armour J,Tyml K,Lidington D,et al.Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat[J].J Appl Physiol(1985),2001,90(3):795-803.
23 Evans-Olders R,Eintracht S,Hoffer LJ.Metabolic origin of hypovitaminosis C in acutely hospitalized patients[J].Nutrition,2010,26(11-12):1070-1074.
24 Tyml K,Li F,Wilson JX.Delayed ascorbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle[J].Crit Care Med,2005,33(8):1823-1828.
25 Borrelli E,Roux-Lombard P,Grau GE,et al.Plasma concentrations of cytokines,their soluble receptors,and antioxidant vitamins can predict the development of multiple organ failure in patients at risk[J].Crit Care Med,1996,24(3):392-397.
26 De Grooth HM,Spoelstra-de Man AME,Oudemans-van Straaten HM.Early plasma vitamin C concentration,organ dysfunction and ICU mortality[J].Intensive Care Med,2014,40(1):S199-S200.
27 Carr AC,Rosengrave PC,Bayer S,et al.Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes[J].Crit Care,2017,21(1):300.
28齐艳,马培瑾,江素玲.维生素C不良反应[J].中国误诊学杂志,2005,5(9):1775-1776.
2 Esposito S,De Simone G,Boccia G,et al.Sepsis and septic shock:new definitions,new diagnostic and therapeutic approaches[J].J Glob Antimicrob Resist,2017(10):204-212.
3李晗宇,陈路芳,李金优,等.益生菌制剂对脓毒症小鼠生存情况的影响及机制研究[J/CD].中华危重症医学杂志(电子版),2017,10(5):289-295.
4 Wilson JX,Wu F.Vitamin C in sepsis[J].Subcell Biochem,2012(56):67-83.
5黄颖,寿松涛,王军,等.脓毒症与免疫细胞凋亡相关研究进展[J/CD].中华危重症医学杂志(电子版),2017,10(4):270-273.
6 Berger MM,Oudemans-van Straaten HM.Vitamin Csupplementation in the critically ill patient[J].Curr Opin Clin Nutr Metab Care,2015,18(2):193-201.
7 May JM,Harrison FE.Role of vitamin C in the function of the vascular endothelium[J].Antioxid Redox Signal,2013,19(17):2068-2083.
8 Mantzarlis K,Tsolaki V,Zakynthinos E.Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies[J].Oxid Med Cell Longev,2017:5985209.
9汤鲁明,王林霞,孙来芳,等.萝卜硫素对脓毒症急性肺损伤大鼠氧化损伤及脱嘌呤/脱嘧啶核酸内切酶1表达的影响[J/CD].中华危重症医学杂志(电子版),2017,10(4):246-251.
10 Wilson JX.Evaluation of vitamin C for adjuvant sepsis therapy[J].Antioxid Redox Signal,2013,19(17):2129-2140.
11王飞飞,朱晓萍,马少林.维生素C在脓毒症中的应用进展[J].中国急救医学,2017,37(11):988-991.
12 Fisher BJ,Kraskauskas D,Martin EJ,et al.Attenuation of sepsis-induced organ injury in mice by vitamin C[J].JPEN J Parenter Enteral Nutr,2014,38(7):825-839.
13 Fisher BJ,Kraskauskas D,Martin EJ,et al.Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid[J].Am J Physiol Lung Cell Mol Physiol,2012,303(1):L20-L32.
14 Fisher BJ,Seropian IM,Kraskauskas D,et al.Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury[J].Crit Care Med,2011,39(6):1454-1460.
15 Pontes-Arruda A,Aragao AM,Albuquerque JD.Effects of enteral feeding with eicosapentaenoic acid,gammalinolenic acid,and antioxidants in mechanically ventilated patients with severe sepsis and septic shock[J].Crtit Care Med,2006,34(9):2325-2333.
16 Beale RJ,Sherry T,Lei K,et al.Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis:outcome of a randomized,controlled,double-blind trial[J].Crit Care Med,2008,36(1):131-144.
17 Ferrón-Celma I,Mansilla A,Hassan L,et al.Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery[J].J Surg Res,2009,153(2):224-230.
18 Fowler AA,Syed AA,Knowlson S,et al.Phase Isafety trial of intravenous ascorbic acid in patients with severe sepsis[J].J Transl Med,2014(12):32.
19 Marik PE,Khangoora V,Rivera R,et al.Hydrocortisone,vitamin C and thiamine for the treatment of severe sepsis and septic shock:a retrospective beforeafter study[J].Chest,2017,151(6):1229-1238.
20 Galley HF,Howdle PD,Walker BE,et al.The effects of intravenous antioxidants in patients with septic shock[J].Free Radic Biol Med,1997,23(5):768-774.
21 Borrelli E,Roux-Lombard P,Grau GE,et al.Plasma concentrations of cytokines,their soluble receptors,and antioxidant vitamins can predict the development of multiple organ failure in patients at risk[J].Crit Care Med,1996,24(3):392-397.
22 Armour J,Tyml K,Lidington D,et al.Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat[J].J Appl Physiol(1985),2001,90(3):795-803.
23 Evans-Olders R,Eintracht S,Hoffer LJ.Metabolic origin of hypovitaminosis C in acutely hospitalized patients[J].Nutrition,2010,26(11-12):1070-1074.
24 Tyml K,Li F,Wilson JX.Delayed ascorbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle[J].Crit Care Med,2005,33(8):1823-1828.
25 Borrelli E,Roux-Lombard P,Grau GE,et al.Plasma concentrations of cytokines,their soluble receptors,and antioxidant vitamins can predict the development of multiple organ failure in patients at risk[J].Crit Care Med,1996,24(3):392-397.
26 De Grooth HM,Spoelstra-de Man AME,Oudemans-van Straaten HM.Early plasma vitamin C concentration,organ dysfunction and ICU mortality[J].Intensive Care Med,2014,40(1):S199-S200.
27 Carr AC,Rosengrave PC,Bayer S,et al.Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes[J].Crit Care,2017,21(1):300.
28齐艳,马培瑾,江素玲.维生素C不良反应[J].中国误诊学杂志,2005,5(9):1775-1776.