Mortality similar with restrictive vs. liberal fluid strategies for sepsis with hypotension
A multicenter U.S. trial randomized patients with sepsis-induced hypotension to either a strategy prioritizing vasopressors and lower IV fluid volumes or a strategy prioritizing higher volumes of IV fluids before vasopressors for 24 hours after initial treatment.
Restrictive and liberal IV fluid strategies resulted in similar mortality in a trial of patients with sepsis-induced hypotension.
The unblinded Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial enrolled 1,563 patients at 60 U.S. centers. Within four hours of meeting the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 L of IV fluid, patients were randomized to either a restrictive fluid strategy, prioritizing vasopressors and lower IV fluid volumes (n=782), or a liberal fluid strategy, prioritizing higher volumes of IV fluids before vasopressors (n=781), for a 24-hour period. Results were published by the New England Journal of Medicine on Jan. 20.
During the 24 hours, the restrictive fluid group received less IV fluid (difference of medians, −2,134 mL; 95% CI, −2,318 to −1,949 mL) and had earlier, more prevalent, and longer vasopressor use than the liberal fluid group. However, the groups had similar rates of death from any cause before discharge home by day 90 (14.0% in the restrictive fluid group vs. 14.9% in the liberal fluid group; estimated difference, −0.9 percentage point [95% CI, −4.4 to 2.6]; P=0.61). Serious adverse events were similar in the two groups. Five patients in the restrictive fluid group and four patients in the liberal fluid group were lost to follow-up.
The study authors concluded that the restrictive fluid strategy used in this trial did not result in significantly lower or higher mortality than a liberal strategy. “We focused on the larger group of patients with sepsis who had hypotension, in whom the treatment approach is not clearly guided by clinical circumstances,” they said, noting that the results may not be generalizable to patients with extreme volume overload or volume depletion.
The authors reported a number of other limitations, including that the trial was unblinded and that it didn't include groups in which physicians weren't given instructions on therapy or in which different mean arterial blood pressure and lactate levels were targeted. A longer treatment period may also have produced different results, they said.
