title: Are renal adverse effects of hydroxyethyl starches merely a consequence of their incorrect use?
abstract: BACKGROUND
  Clinical studies such as VISEP-study, which show a negative outcome after the administration of hydroxyethyl starch (HES), are often criticized for an "incorrect" use of HES. It is argued that HES used in these studies differed from usual practice and that recommendations for maximal dosage, duration, and creatinine values were ignored, not enough "free water" was provided and more modern HES solutions should have been used. These comments imply that renal adverse events in clinical studies are the consequence of an inappropriate use of HES. We therefore searched for evidence whether these suggested measures are beneficial.
  
  
  METHODS
  Narrative review; post hoc statistical analysis of epidemiologic data from a representative nationwide survey.
  
  
  RESULTS
  It is evident from published clinical studies that the renal risk of HES increases with cumulative dose and rising serum creatinine values, but no safe upper dose limit or creatinine threshold is known. Suggested safety measures were not able to prevent HES-induced renal failure in clinical studies. Published clinical trials with modern HES solutions are not suited to prove its assumed increased safety because of small sample sizes, low cumulative doses, short observation periods, and inadequate control fluids. Use of HES in a clinical study with negative outcomes conformed to clinical practice, indicating the generalizability of study results.
  
  
  CONCLUSIONS
  There is no evidence for the assumption that HES-associated renal impairment may be avoided by accompanying measures. Because HES use does not improve clinical outcome, the question arises whether it should be used at all in patients at risk.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Friedrich-Schiller Universität Jena, Jena, Germany.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hartog
authors.forename: Frank M
authors.initials: FM
authors.lastname: Brunkhorst
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Andreas
authors.initials: A
authors.lastname: Meier-Hellmann
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ragaller
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kuhnt
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D010952:Plasma Substitutes / Q000009:adverse effects / Q000627:therapeutic use; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes