Early Restrictive or Liberal Fluid Management for Sepsis-induced Hypotension
Clinical question: What’s the effect of restrictive versus liberal fluid resuscitation strategies in sepsis-induced hypotension on 90-day mortality?
Background: Intravenous fluid resuscitation is the mainstay therapy for sepsis despite the vasodilatory nature of septic shock, and higher volumes may be associated with higher mortality with pathological edema.
Study design: Multicenter, randomized, unblinded, superiority trial
Setting: 60 U.S. centers from March 2018 to January 2022
Synopsis: 1,563 patients were enrolled, randomized to restrictive and liberal fluid resuscitation groups in a 1:1 ratio within four hours of sepsis-induced hypotension diagnosis, and followed for 24 hours. Patients were monitored for signs of tissue hypoperfusion with vital signs, lactic acid, and bedside echocardiographic monitoring. Lactated Ringers was the most common type of fluid administered, and norepinephrine was the first-line vasopressor. 90-day mortality point estimates in two treatment groups, compared using the Z test with Greenwood’s standard error and 95% Wald confidence interval, were found to be 14% in the restrictive group and 14.9% in the liberal group. The fluid difference between the groups was 2,134 ml with 59% vasopressor use in the restrictive group compared to 37.2% in the liberal group. A similar number of serious adverse events (21 and 19) were reported in both groups, along with three instances of potential vasopressor-related extravasation among 500 patients who received peripherally administered vasopressors.
Bottom line: In patients with sepsis-induced hypotension no significant difference in 90-day mortality was found among restrictive and liberal fluid resuscitation strategies. Secondary outcomes including the number of days free from ventilator, renal replacement therapy, vasopressor use, days out of intensive care unit and out of hospital were also comparable.
Citation: National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, et al. Early restrictive or liberal fluid management for sepsis-induced hypotension. N Engl J Med. 2023;388(6):499-510.
Dr. Pannu
Dr. Pannu is a hospitalist at Atrium Health Wake Forest Baptist, and an assistant professor in internal medicine at Wake Forest University School of Medicine, both in Winston-Salem, N.C