Hostname: page-component-7c8c6479df-5xszh Total loading time: 0 Render date: 2024-03-29T00:56:06.427Z Has data issue: false hasContentIssue false

Deleterious renal effects of hydroxyethyl starch 130/0.4 and 200/0.5 solutions

Published online by Cambridge University Press:  01 October 2007

I. J. Davidson*
Affiliation:
Division of Surgical Transplantation The University of Texas Southwestern Medical Center at Dallas Dallas, TX, USA
*
Correspondence to: Ingemar J. Davidson, Division of Surgical Transplantation, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9031, USA. E-mail: Ingemar.Davidson@Utsouthwestern.Edu; Tel: +1 214 648 4823; Fax: +1 214 648 4784

Abstract

Type
Correspondence
Copyright
Copyright © European Society of Anaesthesiology 2007

EDITOR:

My recent review of 92 studies, including 23 randomized clinical trials, focused on the renal impact of colloids [Reference Davidson1]. One major conclusion from the review was that hydroxyethyl starch (HES) solutions across the full spectrum of clinically available molecular weights, substitutions and C2/C6 ratios can impair kidney function.

In comments on the review, Boldt [Reference Boldt2] recapitulates several objections previously raised about the multicentre randomized clinical trial of 129 patients with severe sepsis or septic shock by Schortgen and colleagues [Reference Schortgen, Lacherade and Bruneel3], the largest randomized trial included in the review. Those investigators had earlier rebutted the objections [Reference Schortgen and Brochard4] by noting that: (1) baseline differences affecting outcome would be unlikely due to random allocation; (2) the baseline difference in creatinine was not statistically significant; (3) the percentage of patients with renal dysfunction at baseline was actually higher in the gelatin (84%) than in the HES (75%) group, although again the difference was not statistically significant; (4) the criterion applied for acute renal failure (ARF) of a twofold serum creatinine increase might favour a group with higher baseline creatinine; and (5) ARF was the primary endpoint of the trial, which was neither designed nor powered to assess survival.

Importantly, the findings of Schortgen and colleagues [Reference Schortgen, Lacherade and Bruneel3] have now been fully confirmed by the new Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) multicentre randomized trial in 537 patients with severe sepsis or septic shock [Reference Reinhart, Bloos and Engel5]. That trial compared morbidity and mortality in patients receiving an HES solution of 200 kDa molecular weight and 0.5 M substitution (HES 200/0.5) to a maximum of 20 mL kg−1 day−1 or Ringer’s lactate control fluid. HES 200/0.5 increased both the incidence of ARF compared with that in the control group (34.9% vs. 23.2%; P = 0.003) and the frequency of renal replacement therapy (31.0% vs. 18.8%; P = 0.001). A trend towards higher mortality was also observed in the HES 200/0.5 group (41.0% vs. 33.9%; P = 0.09).

Boldt and colleagues [Reference Boldt, Brenner, Lehmann, Lang, Kumle and Werling6] also recapitulate the interpretation they had placed on their randomized trial showing renal impairment after pump priming and volume expansion with HES 130/0.4 or gelatin in elderly cardiac-surgery patients. They argued that since both groups displayed renal impairment, and gelatin is devoid of adverse effects on the kidney, the observed deleterious renal effects may have been due to cardiopulmonary bypass itself rather than due to the fluid regimen. As detailed in my review, this argument proceeds from a flawed premise, because of randomized trial evidence that in fact gelatin does impair renal function compared with albumin [Reference Himpe, van Cauwelaert and Neels7,Reference Trull, Hughes and Cooper8]. Another commentator on this trial of Boldt and colleagues has also reached the conclusion that their data demonstrate renal impairment attributable to HES 130/0.4 [Reference Wiedermann9].

Finally, Boldt contends that further reviews on volume replacement are not needed, even though he himself has been a prolific author of such reviews [Reference Boldt10Reference Boldt12]. I disagree with this. Reviews serve the valuable aim of assembling and critically appraising evidence arising from a profuse and rapidly expanding clinical research literature. Reviews can also generate testable hypotheses. For example, the Cochrane albumin meta-analysis [13] motivated the Saline vs. Albumin Fluid Evaluation (SAFE) randomized trial [Reference Finfer, Bellomo, Myburgh and Norton14]. Fluid-management strategies remain the subject of intensive investigation. Consequently, timely reviews will continue to play a key role in assimilating this growing body of evidence and in arriving at sound conclusions that can be incorporated into clinical practice.

References

[1]Davidson, IJ. Renal impact of fluid management with colloids: a comparative review. Eur J Anaesthesiol 2006; 23: 721738.CrossRefGoogle ScholarPubMed
[2]Boldt, J. Hydroxyethyl starch as a risk factor for acute renal failure in severe sepsis. Lancet 2001; 358: 581582.CrossRefGoogle ScholarPubMed
[3]Schortgen, F, Lacherade, JC, Bruneel, F et al. . Effects of hydroxyethyl starch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911916.CrossRefGoogle ScholarPubMed
[4]Schortgen, F, Brochard, L. Hydroxyethyl starch as a risk factor for acute renal failure in severe sepsis. Lancet 2001; 358: 582.CrossRefGoogle Scholar
[5]Reinhart, K, Bloos, F, Engel, C. Hydroxyethyl starch and Ringer’s lactate for fluid resuscitation in patients with severe sepsis – results from the VISEP study. The German Competence Network Sepsis. Intensive Care Med 2006; 32 (Suppl 1): 213.Google Scholar
[6]Boldt, J, Brenner, T, Lehmann, A, Lang, J, Kumle, B, Werling, C. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Intensive Care Med 2003; 29: 763769.Google Scholar
[7]Himpe, D, van Cauwelaert, P, Neels, H et al. . Priming solutions for cardiopulmonary bypass: comparison of three colloids. J Cardiothorac Vasc Anesth 1991; 5: 457466.CrossRefGoogle ScholarPubMed
[8]Trull, A, Hughes, V, Cooper, D et al. . Influence of albumin supplementation on tacrolimus and cyclosporine therapy early after liver transplantation. Liver Transpl 2002; 8: 224232.CrossRefGoogle ScholarPubMed
[9]Wiedermann, CJ. Renal impairment in cardiac surgery patients receiving hydroxyethyl starch. Intensive Care Med 2004; 30: 519520.CrossRefGoogle ScholarPubMed
[10]Boldt, J. The Holy Grail of volume resuscitation in the septic patient is…. Crit Care Med 2006; 34: 248251.CrossRefGoogle ScholarPubMed
[11]Boldt, J. Volume therapy in cardiac surgery: are Americans different from Europeans? J Cardiothorac Vasc Anesth 2006; 20: 98105.Google Scholar
[12]Boldt, J. Do plasma substitutes have additional properties beyond correcting volume deficits? Shock 2006; 25: 103116.Google Scholar
[13]Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 1998; 317: 235240.CrossRefGoogle Scholar
[14]Finfer, S, Bellomo, R, Myburgh, J, Norton, R. Efficacy of albumin in critically ill patients. BMJ 2003; 326: 559560.CrossRefGoogle ScholarPubMed