Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial

Abstract

Background Fluid treatment in sepsis is a challenge and clinical equipoise exists regarding intravenous (IV) volumes. We aimed to determine whether a 24‐h protocol restricting IV fluid was feasible in adult patients with sepsis without shock presenting to the emergency department (ED). Methods The REFACED Sepsis trial is an investigator‐initiated, multicenter, randomized, open‐label, feasibility trial, assigning sepsis patients without shock to 24 h of restrictive, crystal IV fluid administration or standard care. In the IV fluid restriction group fluid boluses were only permitted if predefined criteria for hypoperfusion occurred. Standard care was at the discretion of the treating team. The primary outcome was total IV crystalloid fluid volumes at 24 h after randomization. Secondary outcomes included total fluid volumes, feasibility measures, and patient‐centered outcomes. Results We included 123 patients (restrictive 61 patients and standard care 62 patients) in the primary analysis. A total of 32% (95% confidence interval [CI] 28%–37%) of eligible patients meeting all inclusion criteria and no exclusion criteria were included. At 24 h, the mean (±SD) IV crystalloid fluid volumes were 562 (±1076) ml versus 1370 (±1438) ml in the restrictive versus standard care group (mean difference –801 ml, 95% CI −1257 to −345 ml, p = 0.001). Protocol violations occurred in 21 (34%) patients in the fluid‐restrictive group. There were no differences between groups in adverse events, use of mechanical ventilation or vasopressors, acute kidney failure, length of stay, or mortality. Conclusions A protocol restricting IV crystalloid fluids in ED patients with sepsis reduced 24‐h fluid volumes compared to standard care. A future trial powered toward patient‐centered outcomes appears feasible.

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis

“…Additional data and clarifications were provided by the authors of 12 trials. 10 , 11 , 12 , 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 …”

“… 9 Hence, the strategies for IV fluid management in sepsis have been dominated by clinical equipoise. Several RCTs of fluid therapy in sepsis have been published, 10 , 11 , 12 , 13 which substantially increases the quantity of evidence. Therefore, we conducted an updated systematic review with meta-analysis to provide a summary of the available evidence on patient-important outcomes of lower vs higher IV fluid volumes in adult patients with sepsis.…”

Precision fluid and vasoactive drug therapy for critically ill patients

“…Fluids Versus Standard Care in Adults with Sepsis in the Emergency Department (REFACED) trial was recently published that lends support to a future adequately powered trial to detect a between-group mortality difference <5%. 70 Although large-scale randomized investigations have not demonstrated a survival advantage for restricted compared to liberal fluid regimens, there remain concerns regarding excessive fluid administration. These concerns have prompted calls for resuscitation based on precision care for individual patients rather than a simple restricted versus liberal dichotomous breakdown.…”

“…Similarly, no significant between‐group differences were detected for serious adverse events, days alive without life support, or days alive and out of hospital. Another multicenter feasibility study known as the Restrictive Fluids Versus Standard Care in Adults with Sepsis in the Emergency Department (REFACED) trial was recently published that lends support to a future adequately powered trial to detect a between‐group mortality difference <5% 70 …”

Challenges With Using a Weight-Based Approach to Bolus Fluid Dosing in Obese Critically Ill Patients

“…Similarly, a feasibility study for a trial known by the acronym REFACED Sepsis reported that of the 383 patients screened as eligible, 32% were included and protocol violations occurred in 34% of patients in the restrictive strategy. 31…”