Fluid and Vasopressor Resuscitation Improves Sepsis-Associated Hypotension

The use of physiologically informed fluid and vasopressor resuscitation with passive leg raise (PLR)–induced stroke volume (SV) change has been shown to be safe for guiding the personalized management of sepsis-associated hypotension and shock, according to the results of a clinical trial published in CHEST.

Researchers conducted the Fluid Responsiveness in Sepsis-Associated Hypotension (FRESH) — a prospective, multicenter, randomized, unblinded clinical trial (ClinicalTrials.gov Identifier: NCT02837731) — at a group of hospitals in the United States and the United Kingdom. Recognizing that the use of fluid and vasopressor management in patients who experience septic shock remains controversial, the investigators sought to assess the efficacy of dynamic measures, such as SV change during PLR, for guiding resuscitation and improving patient outcomes. They compared the use of PLR-guided SV responsiveness as a guide for fluid management (the intervention) vs usual care at 13 hospitals in the United States and United Kingdom.

All patients who presented to the emergency department with sepsis or septic shock were screened, which was defined as ≥2 systemic inflammatory response syndrome (SIRS) criteria and a suspected or confirmed infection, and an anticipated admission to an intensive care unit (ICU). Additional study inclusion criteria were refractory hypotension and enrollment within 24 hours of hospital arrival. Participants were randomly assigned in a 2:1 allocation to SV-guided management or usual care.

The primary study end point was the difference in positive fluid balance at 72 hours or ICU discharge, depending on which event occurred first. Predefined secondary end points included a new requirement for renal replacement therapy, a new requirement for mechanical ventilation, length of ICU stay, hours of ventilator during a 30-day period with vasopressor use, and change from baseline serum creatinine levels. The study was conducted between October 2016 and February 2019.

A total of 124 patients met the prespecified criteria for the modified intent-to-treat population: 83 in the intervention group and 41 in the usual-care group. The mean patient age was 62.1 years. The mean quick Sepsis-Related Organ Failure Assessment score, number of SIRS criteria present on admission, and baseline comorbid conditions were similar between the 2 treatment groups. Participants in both groups received a similar volume of resuscitation fluid prior to study enrollment (2.4±0.6 L in the intervention group vs 2.2±0.7 L in the usual care group).

Positive fluid balance at 72 hours or ICU discharge was significantly less in the intervention arm compared with the usual-care arm (-1.37 favoring the intervention group; P =.02). Moreover, significantly fewer patients in the intervention group than in the usual care group required renal replacement therapy (5.1% vs 17.5%, respectively; P =.04) or mechanical ventilation (17.7% vs 34.1%, respectively; P =.04). The ICU length of stay was similar between the 2 groups, and there was no major difference in hours of ventilation.

The investigators wrote that it was noteworthy that a mean difference of only 1.37 L in fluid balance during a period of 72 hours would lead to these clinical differences. “The treatment effect may be more related to timing and dosing fluid to physiologic effect, rather than fluid restriction,” the investigators suggested.

The investigators concluded that the use of PLR-induced SV change for the guidance of septic shock management is associated with lower net fluid balance, along with reductions in the risk for renal and respiratory failure. Thus, dynamic evaluations to guide the administration of fluid in such patients may improve outcomes compared with the use of usual care.

Disclosure: This clinical trial was supported by Cheetah Medical. Please see the original reference for a full list of authors’ disclosures.

Reference

Douglas IS, Alapat PM, Corl KA, et al. Fluid response evaluation in sepsis hypotension and shock: a randomized clinical trial [published online April 27, 2020]. CHEST. doi:10.1016/j.chest.2020.04.0