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

J Neurotrauma. 2022 Sep;39(17-18):1159-1167. doi: 10.1089/neu.2021.0465.


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) ( 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain Injuries, Traumatic* / etiology
  • Brain Injuries, Traumatic* / therapy
  • Crystalloid Solutions / adverse effects
  • Fluid Therapy* / adverse effects
  • Humans
  • Isotonic Solutions / therapeutic use
  • Saline Solution
  • Sodium Chloride / therapeutic use


  • Crystalloid Solutions
  • Isotonic Solutions
  • Saline Solution
  • Sodium Chloride

Associated data