Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement

Abstract

IntroductionHydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.MethodsWe re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.ResultsDuration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).ConclusionsThe most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.

State of the art in fluid and volume therapy

“…On the contrary, the available studies were criticized for their lack of comparability (patient cohort, patients' status at randomization, use of volume products, maximum HES dose). Meybohm et al [63] reevaluated the prospective randomized studies and defined a six-point catalog of criteria that should be fulfilled by future studies in order to be able to be used for comparison of different infusion regimes: 4 short time interval between shock event and randomization, 4 limited use of initial fluid therapy, 4 consistent use of a fixed infusion algorithm until hemodynamic stabilization, 4 reproducible criteria for hypovolemia, 4 maximum doses of HES, 4 exclusion of patients with preexisting impaired renal function or renal replacement therapy.…”

“…The studies mentioned above only partially fulfill these criteria [63]. So far, controlled trials fulfilling all criteria mentioned above, with high case numbers and long observation period of at least 90 days, are unfortunately not available.…”

Why hydroxyethyl starch solutions should NOT be banned from the operating room

“…It seems that the debate about the place of HES in the treatment of critically ill patients is blurred by a clash of strong opinions. It is therefore essential that currently available data is evaluated in an objective manner with respect to the underlying physiology and pathophysiology of fluid treatment in various disease states [12]. Only in this way can evidence-based clinical recommendations be provided.…”

Fluid Therapy and Management

“…Bu yeni raporu takiben kritik hastalarda HES kullanı-mı ile ilgili eldeki verilerin yeniden değerlendirilmesi ve randomize kontrollü çalışmaların (RKÇ) planlaması için öneride bulunan multi disipliner bir rapor yayınlandı (31) . Bu öneri sonrasında da kritik hastalarda resüsitasyon sıvısı olarak kullanılan kristalloid ve kolloidlerin etkilerini karşılaştıran büyük kapsamlı klinik pek çok araştırma (SAFE, VISEP, CHEST, 6S, CYRISTAL, ALBIOS) yapıldı ve sonuçları değerlen-diren meta analizler yayınlandı.…”