CONTRA: Hydroxyethyl starch solutions are unsafe in critically ill patients.

Hartog and Reinhart present a narrative and “Contra” review of the evidence of hydroxyethyl starch (HES) fluids in the critically ill. They suggest HES fluids should not be administered due to a lack of clinical trial evidence on important benefits and issues of potential harm (nephrotoxicity, coagulopathy, pruritis, and increased long-term mortality and morbidity).

In the same issue of Intensive Care Medicine, Boldt writes a narrative “Pro” review of HES fluids focused on the renal failure debate and argues that HES fluids differ with regard to their physiochemical properties and, as such, should not be considered the same. Boldt suggests that the first and second generation hyperoncotic HES fluids with high molecular weight (>200 kD) and high molecular substitution (>0.4) account for the renal failure seen in some studies but no studies have documented the harmful effects of modern isooncotic HES fluids (HES 6% 130/0.4) on renal function (Intensive Care Medicine, 35: 1331-1336).

Schabinski and colleagues refute this hypothesis (Intensive Care Medicine, 35: 1539-1547). They point to a large, observational study of 2911 critically ill surgical patients that showed both increased doses of the “modern” isooncotic HES fluid (HES 6% 130/0.4) and gelatin fluids were associated with an increased risk of acute renal failure. Because observational studies can suffer from bias (e.g., confounding by indication, inability to control for other unknown confounding factors, lack of standardized resuscitation approach and inability to evaluate all resuscitation endpoints), we must be cautious with our interpretation of these findings.

So what is the bottom line for treating clinicians? Unfortunately, there are no clear answers. We require rigorous and large randomized controlled trials, powered for clinically important endpoints (benefit and harm) and independent data monitoring committees in place to assure safety of enrolled patients to truly understand whether these fluids are helpful or hurtful for our critically ill patients, especially those at a high risk of death and acute renal failure. Several trials are underway (acronyms: CRISTAL; BaSES; CRYSTMAS), see clinicaltrials.gov website). The clinical evidence generated from these randomized trials will help provide needed clarity on this intense and long standing debate.

– Lauralyn McIntyre and Dean Fergusson