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Overall, 36 studies reporting 2149 participants met the inclusion criteria, of which 11 (n = 541) have been retracted.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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    • "In recent years, a large amount of studies [3] [4] [5] [6] [7] [8] have focused on the selection of crystalloids or colloids in fluid resuscitation and many related meta-analysis [9] [10] [11] [12] [13] [14] [15] have been put forward. However, researches on the comparison between regular fluid resuscitation (RFR) and limited fluid resuscitation (LFR) were few and only one meta-analysis was found [16]. "
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    ABSTRACT: Backgrounds: The objective of this meta-analysis was to evaluate the efficacy of limited fluid resuscitation during active hemorrhage compared with regular fluid resuscitation and provide strong evidences for the improvement of fluid resuscitation strategies in uncontrolled hemorrhagic shock. Methods: Electronic searches were performed using PubMed, Medline, Embase and CNKI in accordance with pre-set guidelines. Clinical trials and observation studies were included or excluded according to the criteria. The endpoints examined were mortality, hemoglobin (Hb), platelets (PLT), hematocrit (Hct), prothrombin Time (PT), activated partial thromboplastin time (APTT), base excess (BE), blood lactic acid (BLA) and the main complications, such as multiple organ dysfunction syndrome (MODS) and acute Respiratory Distress Syndrome (ARDS). Risk ratios (RR), mean differences (MDs) and 95% confidence intervals (95% Cl) were calculated using fixed/random effect model. Results: The search indentified 11 studies including 1482 subjects. 725 hemorrhagic patients were treated with limited fluid resuscitation while 757 patients undertook regular fluid resuscitation during active hemorrhage. Limited fluid resuscitation had its advantage to reduce the mortality in hemorrhagic shock (RR = 0.67; 95% CI = 0.56-0.81; P < 0.0001) and easily controlled the blood routine index close to normal compared with regular fluid resuscitation (Hb: MD = 13.04; 95% CI = 2.69-23.38; P = 0.01. PLT: MD = 23.16; 95% CI = 6.41-39.91; P = 0.007. Hct: MD = 0.02; 95% CI = 0.02-0.03; P < 0.00001). LFR also had shorter PT and APTT compared with RFR (PT: MD = -2.81; 95% CI = -3.44--2.17; P < 0.00001 and APTT: MD = -5.14; 95% CI = -6.16--4.12; P < 0.00001). As for blood gas analysis, LFR reduced the decrease of BE (MD = 2.48; 95% CI = 1.11-3.85; P = 0.0004) and increase of BLA (MD = -0.65; 95% CI = -0.85--0.44; P < 0.00001). Besides, LFR may also reduce the occurrence of postoperative complications (MODS: RR= 0.37; 95% CI = 0.21-0.66; P = 0.0008. ARDS: RR = 0.35; 95% CI = 0.21-0.60; P < 0.0001). Conclusion: The results provide convincing evidence that support the continued investigation and use of limited fluid resuscitation during active hemorrhage in the trauma setting.
    Full-text · Article · Sep 2015 · International Journal of Clinical and Experimental Medicine
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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. "

    Full-text · Article · Mar 2015 · Injury
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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.
    Full-text · Article · Oct 2013 · Journal of critical care
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