A cohort study found that an initial fluid administration of 30 mL/kg or more was associated with lower mortality rates in patients with community-onset sepsis. This benefit was observed not only in patients experiencing hypoperfusion but also in those with specific cardiac and renal comorbidities.1
Guidelines currently recommend administering at least 30 mL/kg of initial fluid to patients with sepsis-induced hypoperfusion. However, trial-level evidence is lacking. While landmark fluid trials like CLASSIC and CLOVERS shaped modern fluid management in critical care, they included patients who had already received 2 to 3 liters before enrollment.2,3 Furthermore, uncertainty remains about the benefits of fluids in patients with severe comorbidities and intermediate lactate elevation.
Published in JAMA Network Open, the recent cohort study evaluated data from 25,481 adult patients hospitalized for community-onset sepsis that had an indication for fluid resuscitation. The study, which included patients from 67 hospitals in the Michigan Hospital Medicine Safety Consortium, evaluated the association between administering 30 mL/kg or more of fluid within six hours of hospital arrival and 30-day mortality.
Administration of 30 mL/kg or more of fluid compared with less was associated with a 4.4 percentage point reduction in 30-day mortality in patients with hypoperfusion (defined as MAP <65 mm or lactate >4 mmol/L) and a 1.8 percentage point reduction in patients with intermediate lactate elevation (defined as lactate of 2 to 4 mmol/L) without severe comorbidities.
“We found that there’s a broader population of patients who might benefit from 30 mils per kilogram than currently targeted by sepsis initiatives and guidelines,” said study lead author Elizabeth Munroe, MD, Assistant Professor at Intermountain Medical Center.
The study also evaluated several commonly used approaches to calculating weight-based fluid dosing and found that, regardless of the approach, getting 30 mL/kg was associated with reduced mortality.
“Though the study expands and provides more support for using the sepsis guideline recommendation of 30 mL/kg, it can’t prove causation,” said Anna Duchnowska, DNP, ACNP-BC, CCAPP, a critical care nurse practitioner at the University of Illinois Hospital in Chicago.“However, I thought it was an interesting start that can lead to further randomized trials and research based on the findings in terms of benefits in mortality for a wider group than we initially assumed based on the guidelines, including patients with renal impairment or heart failure.”
Dr. Duchnowska also highlighted that including the intermediate lactate elevation group raises the question of whether resuscitation should be considered earlier for patients who are not in overt shock but exhibit this lower threshold, with the goal of potentially preventing clinical decompensation to overt shock.
However, she also pointed out several limitations of the study.
Although the study attempted to improve validity by using records from both community and medical centers for better external validation, the geographic region covered was quite limited, she said. Additionally, the study focused solely on community-onset sepsis, raising questions about whether these findings can be generalized to patients with hospital-onset sepsis who were already hospitalized.
References
1. Munroe ES, Walzl E, Seelye S, et al. Comorbidities, weight-based initial fluid resuscitation, and mortality in patients with sepsis. JAMA Netw Open. 2026;9(6):e2618232. doi:10.1001/jamanetworkopen.2026.18232
2. Sivapalan P, Meyhoff TS, Hjortrup PB, et al. Conservative vs. liberal fluid therapy in septic shock – protocol for secondary Bayesian analyses of the CLASSIC trial. Acta Anaesthesiol Scand. 2022;66(6):767-771. doi:10.1111/aas.14058
3. Lanspa MJ, Khan A, Lyons PG, et al. Crystalloid liberal or vasopressors early resuscitation in sepsis-study of treatment’s echocardiographic mechanisms (CLOVERS-STEM). Crit Care Explor. 2024;6(12):e1182. doi:10.1097/CCE.0000000000001182
