Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial

PurposeTo determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis.MethodsA prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100mmHg, after minimum 1000ml of IV fluid. Primary outcome was total fluid administered within 6h post randomisation.ResultsThere were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6h in the restricted volume group was 2387ml [first to third quartile (Q1-Q3) 1750-2750ml]; 30ml/kg (Q1-Q3 32-39ml/kg) vs. 3000ml (Q1-Q3 2250-3900ml); 43ml/kg (Q1-Q3 35-50ml/kg) in the usual care group (p<0.001). Median duration of vasopressor support was 21h (Q1-Q3 9-42h) vs. 33h (Q1-Q3 15-50h), (p=0.13) in the restricted volume and usual care groups, respectively. At 90-days, 4 of 48 (8%) in the restricted volume group and 3 of 47 (6%) in the usual care group had died. Protocol deviations occurred in 6/50 (12%) in restricted group and 11/49 (22%) in the usual care group, and serious adverse events in fourcases (8%) in each group.ConclusionsA regimen of restricted fluids and early vasopressor in ED patients with suspected sepsis and hypotension appears feasible. Illness severity was moderate and mortality rates low. A future trial is necessary with recruitment of high-risk patients to determine effects on clinical outcomes in this setting.