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 / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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).</p><p><b>METHODS</b>Three databases (PubMed, EMBASE, Cochrane) were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES130/0.4* 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.</p><p><b>RESULTS</b>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 HES130/0.4* compared with treatment of control fluids (RR 1.02, 95% confidence interval 0.90-1.17; P = 0.73). Heterogeneity was moderate across recruited trials (I2 = 34%, P = 0.13). But, a significant variation was demonstrated in subgroup with crystalloids as control fluids (I2 = 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 HES130/0.4* 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).</p><p><b>CONCLUSIONS</b>Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES130/0.4* associated with excess mortality in septic patients.</p>