BARCELONA — Hydroxyethyl starch solutions can't be recommended for fluid resuscitation in patients with severe sepsis or septic shock, or in those at risk of renal problems, researchers said at the annual congress of the European Society for Intensive Care Medicine.
The starch solutions are associated with higher rates of acute renal failure and increased 90-day mortality in these patients, especially in those who receive more than the highest recommended dosage of 22 mL/kg of body weight, said Dr. Frank Brunkhorst of the Friedrich Schiller University of Jena (Germany).
Dr. Brunkhorst, who also manages the German Sepsis Society, reported the interim results of the Influence of Colloid vs. Crystalloid Volume Resuscitation in Patients with Severe Sepsis and Septic Shock (VISEP) study.
VISEP, a phase III trial, randomized patients to volume replacement with either 10% hydroxyethyl starch (HES) 200/0.5 solution (10% Hemohes) or Ringer's lactate solution.
The study was powered for 1,200 patients, but it was suspended after the first interim analysis of 600 showed trends of increased renal failure and mortality in the HES group, Dr. Brunkhorst said.
All patients in the study had either severe sepsis or septic shock; their mean age was 64 years. The mean Acute Physiology and Chronic Health Evaluation II score was 20, and the mean Simplified Acute Physiology Score (version II) was 53.
Hemodynamic stabilization occurred significantly faster in the HES group. Mortality at 28 days was slightly but not significantly higher in the HES group, compared with the Ringer's lactate group (27% vs. 24%), a trend repeated for 90-day mortality (41% HES vs. 34% Ringer's lactate).
There were no significant differences in the Sequential Organ Failure Assessment scores overall.
However, the coagulation and renal subscores were significantly higher in the HES group, Dr. Brunkhorst said. In addition, almost twice as many HES as Ringer's patients needed hemodialysis during their treatment (31% vs. 19%), with a total of 650 days of dialysis in the HES group and 321 days in the Ringer's group.
Acute renal failure rates were also significantly higher in the HES group (35% vs. 23%).
The highest recommended dosage of HES (22 mL/kg) was exceeded in 99 patients. A subanalysis of this group identified an increase in dose-dependent mortality at 90 days: 75% of those who exceeded the dosage and 49% of those who did not died. “This was highly statistically significant,” Dr. Brunkhorst said.
No previous study has identified this significantly increased mortality risk in patients who receive high doses of HES, he said—probably because the observation period was too short. “All the other studies had a follow-up of only a few days. This was a phenomenon observed only after 3 weeks,” Dr. Brunkhorst said.
In 2003, when the VISEP study began, 10% HES was the lightest molecular weight and most rapidly degrading colloidal fluid replacement solution available, said Dr. Konrad Reinhart, a coinvestigator of the VISEP trial. Since then, lighter solutions have come to market.
However, he said, no studies have demonstrated enough treatment superiority to convince him to use any colloidal solution instead of Ringer's.
There are many case reports of pruritic dermatitis associated with starch deposits in the dermis.
Autopsy reports have also shown starch deposits in kidney and liver that persisted for more than 10 years after HES treatment, said Dr. Reinhart, director of the department of anesthesiology and intensive care medicine at the University Hospital of the Friedrich Schiller University of Jena.
Dr. Reinhart is also not convinced that acute renal failure is the only factor involved in the increased risk of death in HES patients.
“Several case reports have looked at foamy macrophage syndrome in these patients,” he said (Ann. Int. Med. 2002;137:1013–4), adding that his institution has restricted the use of starch solutions. “We have stopped using them in our unit, and I won't use them at all in sepsis patients,” Dr. Reinhart said.
“No data have ever demonstrated a beneficial effect [over Ringer's], but a lot have demonstrated harm.”