When a skydiver is falling through the air at 50 m/s, he needs to make a snap decision: pull out the parachute now, or later? The choice needs to be made quickly and he needs to be sure about it—it’s the difference between life and death. Treating a patient with sepsis can feel like skydiving for a physician, and quick decisions need to be made that will greatly impact the outcome for the patient. In this week’s issue of NEJM, Perner et al. publish a study that will help you save some (precious) time as you decide how to treat your patients with sepsis.
When treating a patient with sepsis, one of the first decisions that needs to be made quickly is choosing a method of fluid resuscitation. Both colloids and crystalloids are reasonable choices, and among the crystalloids, Ringer’s acetate/lactate is commonly used in the US. Hydroxyethyl starch (HES) is another solution that can help increase blood volume, but HES with a high molecular weight (greater than 200 kilodaltons) and a high substitution ratio (greater than 0.4) has been shown to cause acute kidney injury in patients with severe sepsis. Recently, an HES solution with a lower molecular weight (130 kDa) and substitution ratio (0.42) has come into use. But the efficacy of using this solution (HES 130/0.42) for fluid replacement in patients with sepsis has not yet been fully explored. Although HES is commonly used in Europe for fluid replacement therapy, it has not yet been adopted by physicians in the US. These global variations in practice made it necessary to perform a clinical trial to test the efficacy of HES 130/0.42 vs. Ringer’s acetate. Knowing that this treatment is commonly used in Europe, when treating a patient with sepsis, you may pause to think: could HES 130/0.42 be better than Ringer’s acetate? Since you don’t have time for a pause, Perner et al. have made that decision a quicker one.
The authors performed a prospective, blinded clinical trial which enrolled 804 patients with severe sepsis who were randomized either to treatment with 6% HES 130/0.42 or Ringer’s acetate. The trial spanned 26 ICUs in Denmark, Norway, Finland and Iceland. 90 days after treatment, 51% of patients treated with HES 130/0.42 had died as compared with 43% of those treated with Ringer’s acetate (P=0.03), indicating a higher risk of mortality for those treated with HES 130/0.42. Although only one patient in each group had developed end-stage renal failure by day 90, patients treated with HES 130/0.42 had a higher rate of renal replacement therapy and a higher risk of severe bleeding in that time as compared to those treated with Ringer’s acetate.
Clearly, HES is not better for treatment of sepsis. “Despite that the treatment made physiological sense, it simply did not hold up in a clinical trial – again reinforcing the importance of clinical trials in determining medical practice,” said Dr. Jeffrey Drazen, NEJM editor-in-chief.
In addition to changing clinical practice in Europe, this study may change what we know about the efficacy of different types of volume expanders. It’s generally thought that HES 130/0.42 is a more potent volume expander than Ringer’s acetate, but, interestingly, no difference was seen in trial fluid volumes between the two treatment groups. Is there actually a potency difference between the two solutions?
This is the first large scale trial to show that treatment for sepsis with HES 130/0.42 causes an increased risk of death or dialysis dependency in the first 90 days of treatment. Now you can be more confident with your decision about when to pull out the parachute and help your patient with sepsis float to safety.