title: Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are conflicting. Moreover, multiple trials from one investigator have been retracted because of scientific misconduct.
  
  
  OBJECTIVE
  To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury.
  
  
  METHODS
  Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, HealthStar, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to October 2012), reference lists of relevant articles, and gray literature.
  
  
  METHODS
  Two reviewers independently identified randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation.
  
  
  METHODS
  Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the risk of bias tool; the strength of evidence was adjudicated using the GRADE methodology.
  
  
  RESULTS
  We included 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. For the 10,880 patients in studies contributing mortality data, the risk ratio (RR) for death among patients randomized to receive hydroxyethyl starch was 1.07 (95% CI, 1.00 to 1.14; I2, 0%; absolute risk [AR], 1.20%; 95% CI, -0.26% to 2.66%). This summary effect measure included results from 7 trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. When we excluded these 7 trials that involved 590 patients, hydroxyethyl starch was found to be associated with increased mortality among 10,290 patients (RR, 1.09; 95% CI, 1.02 to 1.17; I2, 0%; AR, 1.51%; 95% CI, 0.02% to 3.00%), increased renal failure among 8725 patients (RR, 1.27; 95% CI, 1.09 to 1.47; I2, 26%; AR, 5.45%; 95% CI, 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR, 1.32; 95% CI, 1.15 to 1.50; I2, 0%; AR, 3.12%; 95% CI, 0.47% to 5.78%).
  
  
  CONCLUSIONS
  In critically ill patients requiring acute volume resuscitation, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. Moreover, after exclusion of 7 trials performed by an investigator whose research has been retracted because of scientific misconduct, hydroxyethyl starch was associated with a significant increased risk of mortality and acute kidney injury. Clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns.
authors: University of Manitoba, Department of Internal Medicine, Section of Critical Care, University of Manitoba, ON2056-675 McDermot Ave, Winnipeg, Manitoba R3E 0V9, Canada. ryan.zarychanski@cancercare.mb.ca
authors: Ryan
authors: R
authors: Zarychanski
authors: Ahmed M
authors: AM
authors: Abou-Setta
authors: Alexis F
authors: AF
authors: Turgeon
authors: Brett L
authors: BL
authors: Houston
authors: Lauralyn
authors: L
authors: McIntyre
authors: John C
authors: JC
authors: Marshall
authors: Dean A
authors: DA
authors: Fergusson
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000418:Albumins; D016638:Critical Illness / Q000401:mortality*; D000077324:Crystalloid Solutions; D005440:Fluid Therapy; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects*; D007552:Isotonic Solutions / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015532:Rehydration Solutions / Q000627:therapeutic use; D012306:Risk
chemical_list: D000418:Albumins; D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D015532:Rehydration Solutions