TOPLINE

In a randomized trial of patients with septic shock in the emergency department (ED), early vasopressor therapy with restricted fluid administration did not increase the number of days alive and out of the hospital through 90 days compared with greater fluid volumes with later vasopressor use.

METHODOLOGYResearchers conducted a multicenter, open-label, randomized trial of 963 adults (median age, 69 years; 60.6% men) with septic shock presenting to the ED across Australia, New Zealand, and Ireland between 2021 and 2025. Eligible patients had clinically suspected infection, hypotension despite at least 1 L of fluid, a lactate level > 2.0 mmol/L, and were receiving antimicrobial treatment.Patients were randomly assigned to receive restricted fluid administration with early vasopressor therapy (vasopressor group; n = 481) or greater fluid volumes with later vasopressor therapy (fluid group; n = 482) for up to 24 hours.The primary outcome was days alive and out of hospital from randomization to day 90. The secondary outcomes included mortality at 28 and 90 days, survival time at 90 days, the number of days patients were alive and at home through 90 days, and safety outcomes.TAKEAWAYThe median number of days patients were alive and out of the hospital through 90 days was identical between the vasopressor and fluid groups (76 days vs 76 days; P = 1.00).Patients in the vasopressor group received less intravenous fluid during the first 24 hours than those in the fluid group (1140 mL vs 2248 mL); they were also more likely to receive vasopressors than those in the fluid group (86.5% vs 67.6%).Mortality at 90 days was similar between the vasopressor and fluid groups (16.4% vs 14.4%; relative risk [RR], 1.14; 95% CI, 0.85-1.54), and other secondary outcomes did not differ significantly.Adverse events were few and similar between the two groups; however, pulmonary edema occurred less frequently in the vasopressor group than in the fluid group (0.6% vs 5.0%; RR, 0.12; P < .001).IN PRACTICE

“Among patients presenting to the emergency department with early septic shock, administration of restricted volumes of fluids and early vasopressors as compared with greater volumes of fluids and later vasopressors did not increase the days alive and out of the hospital from randomization to day 90,” the authors of the study concluded.

SOURCE

The study was led by Sandra L. Peake, MD, PhD, Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. It was published online on June 11, 2026, in The New England Journal of Medicine.

LIMITATIONS

The trial was limited by its open-label design, lack of control over treatments administered after the 24-hour intervention period, exclusion of patients with treatment limitations or substantial prerandomization fluid exposure, potential attenuation of treatment separation because some patients did not receive protocol-guided therapy or received the intervention for less than 24 hours, and limited generalizability to patients requiring fluid restriction and those in resource-limited healthcare settings.

DISCLOSURES

The study was funded by the Australian National Health and Medical Council Medical Research Future Fund and the New Zealand Health Research Council. Several authors reported receiving research grants or funding from national research agencies, including the National Health and Medical Research Council, the Health Research Council of New Zealand, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.