Effects of an early restrictive versus liberal fluid strategy on long-term patient-centered outcomes in sepsis-induced hypotension (SHAMROC): An open-label, randomized controlled trial

RATIONALE: The impact of fluid resuscitation strategies on patient-centered outcomes of sepsis survivors is unknown.

OBJECTIVES: To assess the effect of an early restrictive or liberal fluid resuscitation strategy on long-term functional outcomes in patients with sepsis-induced hypotension.

METHODS: SHAMROC (Sepsis-induced Hypotension: Assessing effect of Method of Resuscitation On patient-Centered outcomes) prospectively assessed the impact of random assignment to a restrictive or liberal fluid resuscitation strategy for sepsis-induced hypotension outcomes at 6 and 12 months after randomization in the NIH NHLBI PETAL Network’s CLOVERS trial (NCT03434028). The pre-specified analyses used trimmed means at 50% to prevent informative censoring of deceased patients.

MEASUREMENTS AND MAIN RESULTS: Of the 1563 participants included in the CLOVERS trial, 898 (57%) were included in the SHAMROC trial. As 196 were lost to follow-up, 702 participants were analyzed at 6 months (431 survivors and 271 non-survivors). Baseline characteristics were similar between the groups. At 6 months, no group differences were observed in cognitive function (restrictive versus liberal; trimmed mean difference in Montreal Cognitive Assessment-Blind Score, 0.11, 95% CI -1.44-1.70), executive function (trimmed mean difference in Hayling Sentence Completion Test, 0.38, 95% CI -0.97-1.76), disability status (trimmed mean difference in Activity of Daily Living Score, 0.03, 95% CI -0.84-0.90), mobility (trimmed mean difference in PROMIS Mobility Score, 0.72, 95% CI -2.20-3.64), and health-related quality of life (trimmed mean difference in EQ-5D-5L, -0.01, 95% CI -0.07-0.06). Outcomes also did not differ at 12 months.

CONCLUSIONS: In this long-term follow-up of a randomized controlled trial of patients with sepsis-induced hypotension, the restrictive fluid strategy used in this study resulted in similar cognitive and physical function at 6 and 12 months, compared to a liberal fluid strategy.

National Heart, Lung, and Blood Institute

Anselm Jorda, Georg Gelbenegger, Nathan I Shapiro, Ivor S Douglas, Casey Whitman, Zhe Chen, Joseph A Hippensteel, Lee A Kamphuis, Robert J Flick, Michael O Harhay, Ellen Caldwell, Markus Zeitlinger, Bernd Jilma, Theodore J Iwashyna, Catherine L Hough, Catherine L Auriemma