Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial

Abstract

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 SMART (Isotonic Solutions and Major Adverse Renal Events Trial) admitted to the medical ICU with an International Classification of Diseases, 10th Edition, Clinical Modification System 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 ICU 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 [aOR], 0.74; 95% confidence interval [CI], 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; 95% CI, 1.08-1.69) compared with 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 with use of saline.Clinical trial registered with www.clinicaltrials.gov (NCT02444988).

Keywords: balanced crystalloids; lactated Ringer’s; saline; sepsis; septic shock.

Figure 1.

Derivation of the study cohort. Among 15,802 patients in SMART (Isotonic Solutions and Major Adverse Renal Events Trial), 1,641 were admitted to the medical ICU with a diagnosis of sepsis and were included in the primary analysis for the current study.

Figure 2.

Relationship between baseline chloride and bicarbonate concentration, study groups, and 30-day in-hospital mortality. The mean and 95% confidence interval (denoted by gray shading) for the probability of 30-day in-hospital mortality is displayed for patients in the balanced crystalloids group (blue) and in the saline group (red) relative to (A) baseline plasma chloride concentration and (B) baseline bicarbonate concentration, with locally weighted scatterplot smoothing. Although 30-day in-hospital mortality overall was lower in the balanced crystalloids group than the saline group, neither baseline chloride nor baseline bicarbonate concentration modified the effect of study group on in-hospital mortality.

Figure 3.

Vasopressor dose and plasma lactate concentration according to study group. The mean and 95% confidence interval (denoted by gray shading) for (A) dose of vasopressor in micrograms per kilogram per minute in norepinephrine equivalents for patients receiving vasopressors and (B) measured plasma lactate concentration for those with a measured value for the balanced crystalloids group (blue) and the saline group (red) for the first 5 days following ICU admission are displayed using locally weighted scatterplot smoothing. The number of patients with a measured value on each day is displayed for each group.