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CLOVERS RCT – Restrictive or Liberal Fluid Before Pressors?

March 3, 2023

Written by Millie Cosse

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This unblinded superiority trial found no significant difference in mortality among patients who were randomized to a restrictive fluid strategy with earlier use of vasopressors or liberal fluid administration for treatment of sepsis-induced hypotension.

Why does this matter?
Prior studies have evaluated standard versus restrictive fluid protocols in ICU patients, but this trial is the first to evaluate mortality difference in patients who almost exclusively presented to the emergency department with sepsis. So, which treatments should we prioritize using?

Is the juice worth the squeeze?
1,563 patients at 60 U.S. centers were randomized to restrictive or liberal fluid groups after diagnosis of sepsis-induced hypotension. Patients in the liberal fluid group were given an initial 1L IV infusion of crystalloid, followed by additional fluid boluses, with “rescue vasopressors” available. Those in the restrictive fluid group primarily received vasopressors with “rescue fluids” available. Both groups received a median 2,050mL of IV fluids before randomization. The trial was halted early due to lack of differences in primary and secondary outcomes between the groups. Authors found no significant difference in mortality: 14% in the restrictive fluid group, 14.9% in the liberal fluid group (95%CI -4.4 to 2.6, p=0.61). There were also no differences in secondary outcomes, including number of days free from ventilator or renal-replacement therapy, or number of days out of the ICU or hospital.

My takeaway: While it is possible that some subgroups may benefit from a restrictive fluid strategy, we don’t know who they are yet. For now, I’ll continue to “fill the tank” before reaching for pressors.

Source
Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. NEJM. 2023 Feb 9; 388:499-510, DOI: 10.1056/NEJMoa2212663.

What are your thoughts?