Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42 Associated Excess Mortality in Septic Patients： A Systematic Review and Meta-regression

• Published in: Chinese medical journal Vol. 128; no. 17; pp. 2374 - 2382
• Main Authors: Ma, Peng-Lin, Peng, Xiao-Xia, Du, Bin, Hu, Xiao-Lan, Gong, Yi-Chun, Wang, Yu, Xi, Xiu-Ming
• Format: Journal Article
• Language: English
• Published: China Medknow Publications Pvt Ltd 05.09.2015; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; Department of Critical Care Medicine, 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China%Centre of Clinical Epidemiology and Evidence-based Medicine, Beijing Children Hospital, Capital Medical University, School of Public Health, Capital Medical University, Beijing 100069, China%Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China%Department of Critical Care Medicine, Beijing Fuxing Hospital, Capital Medical University, Beijing 100038, China; Medknow Publications & Media Pvt Ltd
• Subjects: Bias; Care and treatment; Clinical trials; Collaboration; Critical care; Drug dosages; Epidemiology; Evidence-based medicine; Fluids; Hospitals; Humans; Hydroxyethyl Starch Derivatives - therapeutic use; Intensive care; Kidneys; Management; Medicine; Meta Analysis; Mortality; Physiological aspects; Public health; Randomized Controlled Trials as Topic; Sepsis; Sepsis - mortality; Sepsis - therapy; Starch; Studies; 剂量-效应关系; 异质性; 患者; 死亡率; 羟乙基淀粉; 脓毒症; 试验报告; 随机对照试验; China; Hydroxyethyl Starch 130/0.4 or 0.42; Heterogeneity; Sepsis; Mortality
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.163387

Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group over or below control group） with the heterogeneity of risk ratio （RR） for mortality in randomized control trials （RCTs）. Methods： Three databases （PubMed, EMBASE, Cochrane） were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4＊ with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality, Results： A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of liES130/0.4＂ compared with treatment of control fluids （RR： 1.02, 95% confidence interval： 0.9-1.17; P = 0.73）. Heterogeneity was moderate across recruited trials （l^2 = 34%, P = 0.13）. But, a significant variation was demonstrated in subgroup with crystalloids as control fluids （l^2 = 42%, P 〈 0.1）. Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES 130/0.4＊ with mortality （P - 0.298）, but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4＊ （P = 0.079）.Conclusions： Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4＊ associated with excess mortality in septic patients.