REFACED RCT – Is Fluid Restriction in Sepsis Feasible?

November 3, 2022

Written by Alex Clark

Spoon Feed
IV crystalloid fluid restriction in the first 24-hours for ED sepsis patients without associated shock significantly reduced volumes when compared to standard of care. A larger trial investigating patient-centered outcomes is likely imminent.

Why does this matter?
Sepsis is classically treated with IV fluid, antibiotics, and source control. While the Surviving Sepsis Campaign suggests using 30 mL/kg IV of crystalloid in septic shock, there is limited data surrounding sepsis without shock. Recent trials suggest a more restrictive approach, using patient-specific hypoperfusion criteria in assessing fluid administration.

You get a liter, you get a liter, everyone gets a liter (or not)…
This multicenter, randomized, open-label study (REFACED Trial) was conducted across three Denmark EDs to assess feasibility of a 24-hour IV restrictive-fluid protocol in sepsis without shock. During this brief 6-week period, the investigators randomized 123 patients (median age 76, 58% male) to a fluid-restrictive or standard of care cohort. Those in the restrictive group were limited to 250 mL boluses only for pre-defined hypoperfusion criteria (elevated lactate, SBP < 90, mottling, severe oliguria). Inclusion criteria were (1) unplanned ED admission, (2) age ≥ 18 years, (3) sepsis defined as suspected infection, blood cultures drawn, IV antibiotics ordered or planned, and infection-related SOFA score ≥ 2, and (4) expected hospital stay > 24-hours. Excluded patients (n = 2462) received ≥ 500 mL fluids, mechanical ventilation, or vasopressors prior to enrollment. Those with low probability of survival to 24-hours or other logistical clinical barriers were also excluded.

The investigators demonstrated a statistically significant decrease in volume in the restrictive group (mean, 562 ± 1076 mL) compared to standard of care (1370 ± 1438 mL; p = 0.001). While not the primary outcome, they also highlighted no differences in secondary outcomes including feasibility measurements, use of mechanical ventilation or vasopressors, acute kidney failure, in-hospital length of stay, nor 30- or 90-day mortality. Overall, this feasibility trial supported the ED physician’s ability to adapt clinical behavior and quickly enroll patients, though there were some protocol violations (34%, n = 21). Although this study itself is not practice changing, I anticipate that the REFACED Trial will open the door for subsequent high-powered studies that will guide our management of fluids in sepsis.

Source
Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial. Acad Emerg Med. 2022 Oct;29(10):1172-1184. doi: 10.1111/acem.14546. Epub 2022 Aug 5.

Recommended Reading

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.
2. Jessen MK, Andersen LW, Thomsen MH, Kristensen P, Hayeri W, Hassel RE, Perner A, Petersen JAK, Kirkegaard H. Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)-protocol for a multicenter, randomized, clinical, proof-of-concept trial. Pilot Feasibility Stud. 2022 Mar 29;8(1):75.
3. Evans L, Rhodes A, Alhazzani W, et. al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine: November 2021 – Volume 49 – Issue 11 – p e1063-e1143.