Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial

Abstract

Balanced crystalloids may improve outcomes compared with saline for some critically ill adults. Lower tonicity of balanced crystalloids could worsen cerebral edema in patients with intracranial pathology. The effect of balanced crystalloids versus saline on clinical outcomes in patients with traumatic brain injury (TBI) requires further study. We planned an a priori subgroup analysis of TBI patients enrolled in the pragmatic, cluster-randomized, multiple-crossover Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (ClinicalTrials.gov: NCT02444988, NCT02547779). Primary outcome was 30-day in-hospital mortality. Secondary outcomes included hospital discharge disposition (home, facility, death). Regression models adjusted for pre-specified baseline covariates compared outcomes. TBI patients assigned to balanced crystalloids (n = 588) and saline (n = 569) had similar baseline characteristics including Injury Severity Score 19 (10); mean maximum head/neck Abbreviated Injury Score, 3.4 (1.0). Isotonic crystalloid volume administered between intensive care unit admission and first of hospital discharge or 30 days was 2037 (3470) mL and 1723 (2923) mL in the balanced crystalloids and saline groups, respectively (p = 0.18). During the study period, 94 (16%) and 82 (14%) patients (16%) died in the balanced crystalloid and saline groups, respectively (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.60 to 1.75; p = 0.913). Patients in the balanced crystalloid group were more likely to die or be discharged to another medical facility (aOR 1.38 [1.02-1.86]; p = 0.04). Overall, balanced crystalloids were associated with worse discharge disposition in critically injured patients with TBI compared with saline. The confidence intervals cannot exclude a clinically relevant increase in mortality when balanced crystalloids are used for patients with TBI.

Keywords: balanced crystalloids; balanced salt solutions; discharge disposition; morbidity; mortality; saline; traumatic brain injury.

FIG. 1.

Mean cumulative volume of normal saline and balanced crystalloid solutions by treatment group over the first 7 days of admission. The cumulative mean volume of intravenous balanced crystalloids (solid line) and 0.9% sodium chloride (dotted line) between admission to the intensive care unit (ICU) and hospital Day 7 is shown for patients in the balanced-crystalloids group (left) and the saline group (right). bars indicate 95% confidence intervals.

FIG. 2.

Electrolyte concentrations according to group. Mean plasma (A) sodium, (B) chloride, (C) bicarbonate, and (D) creatinine levels with 95% confidence intervals over the first 7 days of admission for Saline and Balanced Crystalloids groups. The mean and 95% confidence interval (denoted by gray shading) for plasma sodium (A), chloride (B), bicarbonate (C), or creatinine (D) concentrations on the first 7 days since admission to the intensive care unit (ICU) are shown for patients in the balanced crystalloids group and in the saline group with locally weighted scatterplot smoothing. The p value is for the interaction term between time and treatment. Color image is available online.

FIG. 3.

Probability of survival and of being discharged home during the first 30 days following intensive care unit (ICU) admission in patients in both groups. Cumulative proportion of patients surviving (dotted lines) and being discharged from the hospital alive (solid lines) for the balanced crystalloids (blue) and saline (red) groups. Patients above the dotted lines are deceased. Patients between the dotted and solid lines are alive and still in hospital. Patients below the solid lines are alive and discharged from the hospital. Color image is available online.