The use of meta-analyses for benefit/risk re-evaluations of hydroxyethyl starch
Critical Care volume 19, Article number: 240 (2015)
Whether hydroxyethyl starch (HES) is safe for perioperative use is not known. Evaluating HES in cardiac surgery, Jacob and colleagues suggested conclusion was of a more favorable safety profile for HES 130/0.4 . The authors, however, wrongly stated that they followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines because the meta-analysis lacked a table of included study characteristics, an assessment of bias, identification of any pre-specified subgroup analyses, and tests of interaction to compare different HES solutions. In many included studies, the control group received HES, patients with heavy bleeding were excluded post hoc, and anti-fibrinolytic drugs were used to minimize bleeding. For instance, in two included trials the group assigned to gelatin actually received significantly more postoperative HES 130/0.4 than the group allocated to HES 130/0.4 [2,3]. In an included trial of HES 130/0.4, the results from one of the four study centers were excluded post hoc without explanation . Other sources of bias were aggregation of intra- with postoperative blood loss and preferential use of calculated rather than measured blood loss. Furthermore, no tests of interaction were presented even to address the question of whether HES 130/0.4 differs from other HES solutions in its effect on bleeding risk after cardiac surgery.
Between-study heterogeneity was shown to considerably affect the use of meta-analyses for drug-safety alert issues . Even though meta-analyses may help predict iatrogenic risks, in the field of perioperative volume resuscitation with HES quality of meta-analytic evidence is still too poor to reliably inform drug-regulatory authorities. This technique should not replace further assessments during benefit/risk ratio re-evaluations of HES for perioperative use.
Jacob M, Fellahi JL, Chappell D, Kurz A. The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis. Crit Care. 2014;18:656.
Boks RH, Wijers MJ, Hofland J, Takkenberg JJ, Bogers AJ. Low molecular starch versus gelatin plasma expander during CPB: does it make a difference? Perfusion. 2007;22:333–7.
Vanhoonacker J, Ongenae M, Vanoverschelde H, Donadoni R. Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for cardiopulmonary bypass priming: the effects on postoperative bleeding and volume expansion needs after elective CABG. Acta Anaesthesiol Belg. 2009;60:91–7.
Ertmer C, Wulf H, Van Aken H, Friederich P, Mahl C, Bepperling F, et al. Efficacy and safety of 10% HES 130/0.4 versus 10% HES 200/0.5 for plasma volume expansion in cardiac surgery patients. Minerva Med. 2012;103:111–22.
Alves C, Marques FB, Macedo AF. Drug-safety alerts issued by regulatory authorities: usefulness of meta-analysis in predicting risks earlier. Eur J Clin Pharmacol. 2014;70:745–56.
This letter is solely the work of the author. No other individual or organization made any substantial contribution to the creation and revision of the letter.
CJW has received fees for speaking and travel reimbursements from manufacturers of plasma-derived therapies (Grifols, Kedrion, CSL Behring, Baxter).
See related article by Jacob et al., http://ccforum.com/content/18/6/656
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Wiedermann, C.J. The use of meta-analyses for benefit/risk re-evaluations of hydroxyethyl starch. Crit Care 19, 240 (2015). https://doi.org/10.1186/s13054-015-0940-7
- Included Study
- Bleeding Risk
- Prefer Reporting Item
- Hydroxyethyl Starch