Fluid Resuscitation with 6% Hydroxyethyl Starch (130/0.4) in Acutely Ill Patients: An Updated Systematic Review and Meta-Analysis

Critical Care & Trauma Division, The George Institute for Global Health, University of Sydney, Australia. .a
Anesthesia and analgesia (Impact Factor: 3.47). 01/2012; 114(1):159-69. DOI: 10.1213/ANE.0b013e318236b4d6
Source: PubMed


Recent research suggests that 6% hydroxyethyl starch (HES) 130/0.4 is one of the most frequently used resuscitation fluids worldwide. The retraction of studies evaluating its use necessitates a reevaluation of available evidence regarding its safety and efficacy.
We performed a systematic review and meta-analysis of unretracted randomized controlled trials comparing the effects of 6% HES 130/0.4 with other colloid or crystalloid solutions on mortality, acute kidney injury/failure, and bleeding in acutely ill or perioperative patients. A sensitivity analysis including the data from retracted studies was also conducted.
Overall, 36 studies reporting 2149 participants met the inclusion criteria, of which 11 (n = 541) have been retracted. Of the remaining 25 studies, there was a high risk of bias in 17 studies; 19 studies (n = 1246) were conducted in perioperative patients and 6 (n = 362) in critically ill patients. Sixteen studies reported mortality: 104 deaths in 1184 participants. The relative risk of death was 0.95 (95% confidence interval 0.64-1.42, I(2) = 0%, P = 0.73); including the retracted studies added a further 14 deaths and the relative risk was 0.92 (95% confidence interval 0.63-1.34, I(2) = 0%, P = 0.95). The data reporting acute kidney injury, red blood cell transfusion, and bleeding were of insufficient quantity and quality and not amenable to meta-analysis.
Published studies are of poor quality and report too few events to reliably estimate the benefits or risks of administering 6% HES 130/0.4. This same conclusion is reached with or without the retracted studies. Given the widespread use of 6% HES 130/0.4, high-quality trials reporting a large number of events are urgently required.

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    • "This limitation of their study will further confound interpretation of their results. Thus, we would like to echo the conclusion of a systematic review by Gattas et al. [6] that there is no convincing evidence that the third-generation HES 130/0.4 is safe in surgical, emergency or intensive-care patients despite the publication of numerous clinical studies. "

    Injury 03/2015; 46(8). DOI:10.1016/j.injury.2015.03.011 · 2.14 Impact Factor
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    • "o r g Please cite this article as: Serpa Neto A, et al, Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney..., J Crit Care (2013), 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]. "
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    ABSTRACT: 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. 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. 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]). 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.
    Journal of critical care 10/2013; 29(1). DOI:10.1016/j.jcrc.2013.09.031 · 2.00 Impact Factor
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    • "There is a controversy about the safety of HES, particularly regarding its effects on coagulation [37]. These concerns could prove to be important in the setting of brain-injured patients. "
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    ABSTRACT: IntroductionWe sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury.MethodsWe conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours.ResultsForty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387).ConclusionsThis study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint, intracranial pressure did not appear different between groups.Trial registrationEudraCT 2008-004153-15 and NCT00847977The work in this trial was performed at Nantes University Hospital in Nantes, France.
    Critical care (London, England) 04/2013; 17(2):R77. DOI:10.1186/cc12686 · 4.48 Impact Factor
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