Dr. Klein
Clinical question: Does a restrictive fluid strategy within the first 24 hours improve all-cause mortality among patients with sepsis-induced hypotension?
Background: There are limited data to guide the specific use of intravenous (IV) fluids or vasopressors in the early resuscitation of patients with sepsis-induced hypotension. Previous observational data suggested that a restrictive fluid strategy that prioritized vasopressors was potentially superior to a liberal fluid strategy. However, a recent, randomized, clinical trial in patients already admitted to the intensive care unit (ICU) showed no difference in 90-day mortality when comparing a restrictive fluid approach to unguided resuscitation.
Study design: Multicenter, randomized, unblinded, superiority trial
Setting: 60 medical centers in the U.S.
Synopsis: A total of 1,563 adult patients with suspected or confirmed sepsis-induced hypotension after administration of 1 to 3 L of IV fluid were randomized in a 1:1 ratio to either a restrictive or liberal fluid strategy protocol for a 24-hour period. The restrictive fluid protocol prioritized vasopressors. The liberal fluid protocol recommended an additional 2 L of IV fluid, followed by further boluses based on clinical triggers. Rescue fluids or vasopressors were permitted in both groups for specific parameters. Key exclusion criteria were receipt of more than 3 L of IV fluid by emergency medicine services and the presence of fluid overload.
There was no statistically significant difference in all-cause mortality before discharge by day 90 between the restrictive and liberal fluid groups (14% versus 14.9%, respectively; P=0.61). Limitations include lack of blinding, generalizability to patients with extremes of volume overload or depletion, and generalizability to patients with delayed recognition of sepsis-induced hypotension or who are in the later phases of care. These results were similar to a previous study in patients already admitted to an ICU.
Bottom line: For patients with sepsis-induced hypotension refractory to initial treatment with 1 to 3 L of IV fluid, a restrictive fluid strategy implemented within the first 24 hours did not result in significantly higher or lower mortality before discharge by day 90.
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. Klein is a hospital medicine attending physician at Maine Medicine Center, Portland, Maine, and an assistant professor at Tufts University School of Medicine, Boston.