Elsevier

Journal of Critical Care

Volume 29, Issue 1, February 2014, Pages 185.e1-185.e7
Journal of Critical Care

Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature

https://doi.org/10.1016/j.jcrc.2013.09.031Get rights and content

Abstract

Purpose

Fluid resuscitation is a key intervention in sepsis, but the type of fluids used varies widely. The aim of this meta-analysis is to determine whether resuscitation with hydroxyethyl starches (HES) compared with crystalloids affects outcomes in patients with sepsis.

Materials and Methods

Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 2013. Studies that compared resuscitation with HES versus crystalloids in septic patients, and reported incidence of acute kidney injury (AKI), renal replacement therapy (RRT), transfusion of red blood cell (RBC) or fresh frozen plasma and/or mortality. Three investigators independently extracted data into uniform risk ratio measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence.

Results

Ten trials (4624 patients) were included. An increased incidence of AKI (risk ratio [RR], 1.24 [95% Confidence Interval {CI}, 1.13-1.36], and need of RRT (RR, 1.36 [95% CI, 1.17-1.57]) was found in patients who received resuscitation with HES. Resuscitation with HES was also associated with increased transfusion of RBC (RR, 1.14 [95% CI, 1.01-1.93]), but not fresh frozen plasma (RR, 1.47 [95% CI, 0.97-2.24]). Furthermore, while intensive care unit mortality (RR, 0.74 [95% CI, 0.43-1.26]), and 28-day mortality (RR, 1.11 [95% CI, 0.96-1.28]) was not different, resuscitation with HES was associated with higher 90-day mortality (RR, 1.14 [95% CI, 1.04-1.26]).

Conclusions

Fluid resuscitation practice with HES as in the meta-analyzed studies is associated with increased an increase in AKI incidence, need of RRT, RBC transfusion, and 90-day mortality in patients with sepsis. Therefore, we favor the use of crystalloids over HES for resuscitation in patients with sepsis.

Introduction

Fluid resuscitation is essential in the management of patients with sepsis. The Surviving Sepsis Campaign guidelines strongly recommends early and aggressive fluid resuscitation in these patients to maintain adequate mean arterial pressures and to improve and secure blood flow [1]. Surprisingly, there is a wide variation in the type of fluid used for resuscitation in patients with sepsis worldwide, which is primarily the result of personal preferences, local availability, and probably also marketing [2], [3]. Indeed, in Australia, more than half of all fluid resuscitations are with colloids, mainly albumin, and in European countries, nearly half of all fluid resuscitations are with colloids, mainly hydroxyethyl starches (HES) [3]. By contrast, in the United States crystalloids are preferred [3]. Colloid solutions, including HES, are suggested to result in a more rapid and lasting circulatory stabilization than crystalloids, but there are limited studies that support these potentially beneficial effects [4].

Use of colloids, especially HES, may be not without risks. Randomized controlled trials suggest use of HES to be associated with coagulation alterations, allergic reactions, increased incidence of acute kidney injury (AKI) and need of renal replacement therapy (RRT), and higher overall mortality [5], [6], [7]. While it was believed that harm was only found with use of HES solutions with higher molecular weights and higher substitution ratios [8], recent trials suggest harm from HES solutions with a lower molecular weight and a lower substitution ratio as well [8], [9], [10], [11], [12], [13], [14], [15]. One recent meta-analysis comparing resuscitation with HES and resuscitation with albumin in patients with sepsis confirms earlier findings of harm from HES [16], as do other meta-analyses comparing resuscitation with HES with resuscitation with other fluids in critically ill patients [2], [17]. Notably, these meta-analyses did not focus on patients with sepsis, but included studies of unselected critically ill patients [2], [17].

We aimed to determine whether there is a difference in the incidence of AKI, need of RRT, red blood cell (RBC) and fresh frozen plasma (FFP) transfusion, and overall mortality in patients with sepsis receiving HES for fluid resuscitation compared with fluid resuscitation with crystalloids.

Section snippets

Search methods to identify studies

Studies were identified by 2 authors through a computerized blinded search of Medline (1966-2013), EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) using a sensitive search strategy combining the following Medical Subject Headings and keywords: (colloid [MeSH Terms] OR albumin [MeSH Terms] OR starch [MeSH Terms] OR dextran [MeSH Terms] OR gelatin [MeSH Terms] OR plasma [MeSH Terms]) AND (sepsis [MeSH Terms] OR septic shock [MeSH Terms]). Then, reviewed articles and

Literature search

The search strategy retrieved 2423 unique citations. Of these citations, 2368 were excluded after the first screening based on the abstracts or titles, leaving 55 articles for a full-text review (Fig. 1). Forty five articles were further excluded for the following reasons: no data on outcome of interest (n = 19); comparison with other type of colloid (n = 12); retracted articles (n = 6); data on septic patients not available (n = 4); same cohort previously analyzed (n = 2); and other reason (n

Discussion

We found an association between fluid resuscitation with HES and increased incidence of AKI, RRT, RBC transfusions, and 90-day mortality compared with resuscitation with any type of crystalloid in patients with sepsis. Also, the meta-analysis suggests neither a difference in the amounts of fluids used on the first day nor during follow-up between patients resuscitated with HES and patients resuscitated with saline.

Recently, 2 meta-analyses of studies of fluid resuscitation with HES in

Conclusions

In conclusion, resuscitation practice with HES as used in meta-analyzed studies in patients with sepsis is associated with an increase in AKI incidence, need of RRT, RBC transfusion, and 90-day mortality. Taken together with the results of recently published well-powered randomized controlled trials, HES as used in the fluid resuscitation protocols in the meta-analyzed studies of patients with sepsis can no longer be recommended.

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