What about HES in burn patients ?

Following the 2013 alert by the European Medicines Agency (EMA) discouraging the use of hydroxyethyl-starch solutions (HES) in critically ill and burn patients [1], most specialized units treating burn victims have stopped using HES in this population. But, how well-founded was the EMA alert in this specific type of patient? A major burn patient is defined as one with burn injury affecting at least 20% or 30% of the body surface area (BSA). At this percentage, the patient experiences a systemic impact, characterized by an inflammatory response with microvascular changes that lead to altered capillary permeability, and hypovolemic and cell shock, commonly known as burn shock [2]. It is recognized that intravenous fluid resuscitation is essential to improve survival in major burn patients, as they are in an exceptionally severe clinical state. In addition to the above-mentioned systemic changes, they may experience massive bleeding when undergoing surgical treatment for their injuries and are highly susceptible to the development of infection. But not all victims of burn injury are major burn patients, and not all develop sepsis or have the same systemic repercussions. The different etiologies and severity of the lesions makes this a very heterogeneous patient population, and it is surprising that the European Medicines Agency considers them all in the same manner with respect to HES administration. We believe that the alert emitted, which explicitly says “Hydroxyethyl-starches (HES) should no longer be used in patients with sepsis, burn injuries or critically ill patients” [1] lacks specific information. Given that there is considerable variability in the characteristics of burn patients and that these require advanced fluid therapy management [2], data are needed on the severity of the injury, the affected BSA, systemic involvement, and the time during which this recommendation should be applied. Several questions come to mind in relation to this recommendation: Should solar burns or 1% burns be taken into account in a trauma patient with bleeding? Is it only appropriate for major burns? How long should it be applied? During the first 24h, as is done with the remaining colloids in patients with burns? One week? One month? And what is quite important: on what basis did this specific recommendation for burn patients emerge? When the alert was communicated, it was based on a series of large, recently published studies: 6S [3], CRYSTMAS [4], CHEST [5], CRISTAL [6], and VISEP [7]. But, were burn patients actually included in these studies? To answer our concerns about the current recommendations for these patients, we set out to review the methods used in these studies, and here we present our results. The 6S study [3], involving 798 patients and excluding those with burns affecting >10% BSA, compared mortality and acute kidney injury after initial resuscitation with Ringer’s acetate (RA) versus HES 130/0.42. It is surprising that only burns involving <10% BSA were accepted, when these patients are not usually considered critically ill and are unlikely to develop severe sepsis. The study concluded that patients with severe sepsis or septic shock receiving HES had a higher risk of death and renal replacement requirement at 90days than those given RA. Of note, patients were randomized after the first 24h, once they had been stabilized and when they may already have received 1liter of synthetic colloids, as in the majority of these studies [3,5,8]. Furthermore, 38 patients in the RA group received synthetic colloids without being excluded from the statistical analysis. As to the results, there were no significant differences in mortality at 28 days, but differences were seen at 90 days. Mortality was related to the requirement for renal replacement therapy (RRT), but the indications for this therapy were not defined in the study protocol and were left to the discretion of the attending physician. The number of patients with a definite RRT requirement was exactly the same in the two groups. There were no significant differences between the groups for the authors’ defined measure of renal failure, for the urinary output (UO) values, or for patients with doubling of plasma creatinine levels. With regard to the RIFLE score, the raw data were given in an appendix, but statistical significance was not calculated. No significant differences were seen for the overall SOFA score, but the renal subscore data were not provided; instead, they were combined with those of patients undergoing RRT.