- Open Access
Tetrastarch in cardiac surgery: error, confounding and bias in a meta-analysis of randomized trials
© Navickis et al; licensee BioMed Central. 2015
- Published: 22 April 2015
- Blood Loss
- Hydroxyethyl Starch
- Excess Bleeding
- Reduce Blood Loss
- Test Fluid
In a meta-analysis of cardiac surgery trials, we showed that hydroxyethyl starch increases postoperative blood loss, blood product transfusion and reoperation for bleeding . Citing that meta-analysis, the US Food and Drug Administration determined excess bleeding to be a class effect of hydroxyethyl starch solutions and issued a safety warning .
Their finding of lower blood loss with tetrastarch than pentastarch is attributable to publication bias, since an unpublished trial with higher blood loss and more frequent reoperation for bleeding after tetrastarch was omitted [1,5]. The omitted trial had been submitted to the US Food and Drug Administration in a New Drug Application by the same tetrastarch manufacturer who commissioned the new meta-analysis. That trial was included in two previous meta-analyses [1,5].
The authors gratefully acknowledge the cooperation of Anne Kuitunen, Young Lan Kwak, Tomi Niemi and Alexey Schramko in furnishing blood loss data from their trials.
This work is solely that of the authors. No other individual or organization contributed substantially to the conception of the letter or to manuscript preparation and revision.
- Navickis RJ, Haynes GR, Wilkes MM. Effect of hydroxyethyl starch on bleeding after cardiopulmonary bypass: a meta-analysis of randomized trials. J Thorac Cardiovasc Surg. 2012;144:223–30.View ArticlePubMedGoogle Scholar
- Food and Drug Administration. FDA Safety Communication: boxed warning on increased mortality and severe renal injury, and additional warning on risk of bleeding, for use of hydroxyethyl starch solutions in some settings (2013). www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm358271.htm. Accessed 5 Feb 2015.
- Jacob M, Fellahi JL, Chappell D, Kurz A. The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis. Crit Care. 2014;18:656.View ArticlePubMed CentralPubMedGoogle Scholar
- Kamra C, Beney A. Human albumin in extracorporeal prime: effect on platelet function and bleeding. Perfusion. 2013;28:536–40.View ArticlePubMedGoogle Scholar
- Kozek-Langenecker SA, Jungheinrich C, Sauermann W, van der Linden P. The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood products in major surgery: a pooled analysis of randomized clinical trials. Anesth Analg. 2008;107:382–90.View ArticlePubMedGoogle Scholar
- Niemi T, Schramko A, Kuitunen A, Kukkonen S, Suojaranta-Ylinen R. Haemodynamics and acid–base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin. Scand J Surg. 2008;97:259–65.PubMedGoogle Scholar
- Choi YS, Shim JK, Hong SW, Kim JC, Kwak YL. Comparing the effects of 5% albumin and 6% hydroxyethyl starch 130/0.4 on coagulation and inflammatory response when used as priming solutions for cardiopulmonary bypass. Minerva Anestesiol. 2010;76:584–91.PubMedGoogle Scholar
- Hanart C, Khalife M, De Villé A, Otte F, De Hert S, van der Linden P. Perioperative volume replacement in children undergoing cardiac surgery: albumin versus hydroxyethyl starch 130/0.4. Crit Care Med. 2009;37:696–701.View ArticlePubMedGoogle Scholar