In patients with sepsis-induced hypotension refractory to initial treatment with intravenous (IV) fluid, a restrictive fluid strategy with earlier vasopressor use did not significantly change mortality before discharge compared with a liberal fluid strategy. This is among clinical trial findings published in The New England Journal of Medicine.
Although early resuscitation of patients with sepsis commonly involves IV fluids and vasopressor agents, there is a lack of research to guide their use in patients with sepsis-induced hypotension. To address this research gap, investigators conducted the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial (ClinicalTrials.gov identifier: NCT03434028), an unblinded superiority trial comparing a restrictive fluid strategy with a liberal fluid strategy.
Conducted at 60 US centers, the phase 3 CLOVERS trial randomly assigned patients for a 24-hour period to either a restrictive fluid strategy cohort (in which vasopressors and lower IV fluid volumes were prioritized) or to a liberal fluid strategy cohort (in which higher volumes of IV fluids were prioritized prior to the use of vasopressors). The primary study outcome was all-cause mortality prior to discharge home by day 90. Safety was also evaluated.
Patients were included in the trial within 4 hours after identification of sepsis-induced hypotension that was refractory to initial treatment with 1 to 3 liters of IV fluid. A total of 1563 participants were enrolled in the study — 782 to the restrictive fluid group and 781 to the liberal fluid group. The amount of resuscitation fluids given during the 24-hour protocol period differed between the restrictive and liberal fluid groups (difference of medians, -2134 mL; 95% CI, -2318 to -1949). Patients in the restrictive fluid arm also experienced earlier, more prevalent, and longer-duration vasopressor use.
Mortality from any cause prior to discharge home by day 90 was reported in 14.0% (109 of 782) of participants in the restrictive fluid group and 14.9% (116 of 781) of those in the liberal fluid group. Serious adverse events (AEs) did not differ between the 2 groups.
Limitations of this study include the receipt of more fluid than intended by some patients in the restrictive fluid group, with vasopressors administered later than intended by the protocol, and the receipt of less fluid than intended by some patients in the liberal fluid group, with vasopressors administered earlier than intended by the protocol. Further, the unblinded, group assignments may have biased results related to AEs.
The study authors concluded that “Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy.”
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This article originally appeared on Pulmonology Advisor
Shapiro NI, Douglas IS, Brower IG, et al; National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Early restrictive or liberal fluid management for sepsis-induced hypotension. N Engl J Med. Published online January 21, 2023. doi:10.1056/NEJMoa2212663