DÄ internationalArchive43/2013Methodological Issues of the Studies Cited
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The doubts raised concerning the use of hydroxyethyl starch (HES) for fluid replacement in critical care (1) rely almost exclusively on data from the 6S (2) and CHEST studies (3). In both studies, central venous pressure, central venous saturation, urine output, and serum lactate concentrations were all within the ranges recommended by the Surviving Sepsis Campaign for the initial therapy of sepsis (4). This indicates that at the time of randomization these patients were already hemodynamically stabilized and normovolemic. This would not be surprising because before randomization, patients in the 6S study (2) had received on average 3.0–3.5 L of fluids, and 42% of them had received colloids. Consequently, in both studies fluid replacement with HES was contraindicated. In neither of the two studies was fluid administration standardized or goal-directed, nor were criteria for renal replacement therapy defined a priori, even though this was a secondary outcome parameter. Furthermore, the CHEST study data (3) do not provide evidence of a statistically significant increase in renal replacement therapy (relatives risk [RR], 1.20; 95% confidence interval [CI] 1.00 to 1.44; p = 0.05), and based on some of the RIFLE criteria, HES administration was even associated with less renal injury.

It is entirely incomprehensible why in the CHEST study (3) two hyperchloremic solutions were used for fluid replacement in critical care, although chloride-induced renal vasoconstriction has been known for a long time. Even in healthy individuals, the infusion of saline may result in a 40% decrease in renal perfusion (5). For these (and other unmentioned) considerable methodological issues, no conclusions can be drawn from the results of the two studies regarding the efficacy of balanced HES solutions, especially when it comes to hypovolemic, hemodynamically unstable patients in whom HES solutions are indicated.

DOI: 10.3238/arztebl.2013.0735a

Prof. em. Dr. med. Hans-Joachim Priebe

Merzhausen

hans-joachim.priebe@uniklinik-freiburg.de

1.
Hartog CS, Welte T, Schlattmann P, Reinhart K: Fluid replacement with hydroxyethyl starch in critical care—a reassessment. Dtsch Arztebl Int 2013; 110(26): 443–50 VOLLTEXT
2.
Perner A, Haase N, Guttormsen AB, et al.: Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 2012; 367: 124–34 CrossRef MEDLINE
3.
Myburgh JA, Finfer S, Bellomo R, et al.: Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367: 1901–11 CrossRef MEDLINE
4.
Chowdhury AH, Cox EF, Francis ST, Lobo DN: A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and Plasma-Lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 2012; 256: 18–24 CrossRef MEDLINE
1.Hartog CS, Welte T, Schlattmann P, Reinhart K: Fluid replacement with hydroxyethyl starch in critical care—a reassessment. Dtsch Arztebl Int 2013; 110(26): 443–50 VOLLTEXT
2.Perner A, Haase N, Guttormsen AB, et al.: Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 2012; 367: 124–34 CrossRef MEDLINE
3.Myburgh JA, Finfer S, Bellomo R, et al.: Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367: 1901–11 CrossRef MEDLINE
4.Chowdhury AH, Cox EF, Francis ST, Lobo DN: A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and Plasma-Lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 2012; 256: 18–24 CrossRef MEDLINE

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