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☆
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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2022, Annals of Medicine and SurgeryCitation Excerpt :Additionally, the total amount of HES 130/0.4 used in our study was relatively small (28 mL/kg), and the preoperative and postoperative urine output was sufficient, indicating that HES 130/0.4 was rapidly excreted and that it may have had little impact on the renal function. Using HES as intravenous fluid resuscitation in critically ill patients leads to an increase in the rate of renal replacement therapy [5,6,24] and in the mortality rate [6,24]. This could be because most patients had hypotension and a decreased circulating blood volume, which caused a decrease in GFR.
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No financial support. The authors declare that they have no competing interests.