Balanced Crystalloids Versus Saline in Sepsis: A Secondary Analysis of the SMART Trial

Ryan M Brown, Li Wang, Taylor D Coston, Nathan I Krishnan, Jonathan D Casey, Jonathan P Wanderer, Jesse M Ehrenfeld, Daniel W Byrne, Joanna L Stollings, Edward D Siew, Gordon R Bernard, Wesley H Self, Todd W Rice, Matthew W Semler
American Journal of Respiratory and Critical Care Medicine 2019 August 27

RATIONALE: Administration of intravenous crystalloid solutions is a fundamental therapy for sepsis, but the effect of crystalloid composition on patient outcomes remains unknown.

OBJECTIVES: To compare the effect of balanced crystalloids versus saline on 30-day in-hospital mortality among critically ill adults with sepsis.

METHODS: Secondary analysis of patients from the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) admitted to the medical intensive care unit with an ICD-10-CM code for sepsis, using multivariable regression to control for potential confounders.

MEASUREMENTS AND MAIN RESULTS: Of 15,802 patients enrolled in SMART, 1,641 patients were admitted to the medical intensive care unit with a diagnosis of sepsis. A total of 217 patients (26.3%) in the balanced crystalloids group experienced 30-day in-hospital morality, compared with 255 patients (31.2%) in the saline group (adjusted odds ratio, 0.74; 95% confidence interval, 0.59 - 0.93; P = 0.01). Patients in the balanced group experienced a lower incidence of major adverse kidney events within 30 days (35.4% vs 40.1%; aOR 0.78; 95% CI 0.63 - 0.97) and a greater number of vasopressor-free days (20 ± 12 vs 19 ± 13; aOR 1.25; 95% CI 1.02 - 1.54) and renal replacement therapy-free days (20 ± 12 vs 19 ± 13; aOR 1.35 [1.08 - 1.69]), compared to the saline group.

CONCLUSIONS: Among patients with sepsis in a large randomized trial, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality compared to use of saline. Clinical trial registration available at, ID: NCT02444988.


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