Effect of continuous infusion of hypertonic saline solution on survival of patients with brain injury: a systematic review and meta-analysis

Abstract

Background: The objective was to determine the effects of continuous infusion of hypertonic saline solutions on outcomes of patients with brain injury.

Methods: Preferred Reported Items for Systemic Reviews and Meta-Analysis guidelines were followed. We searched the MEDLINE and COCHRANE clinical trials register (through December 2021) and reference lists of articles. We included all clinical trials conducted in brain-injured patients hospitalized in intensive care units evaluating continuous infusion of hypertonic saline solution (osmolarity above 308 mOsm/L). Two reviewers extracted data that were checked by two others. The primary outcome was the in-hospital mortality rate. The main secondary outcomes were the rates of intracranial hypertension, an unfavorable neurological outcome at day 90, and adverse events.

Results: We identified 23 clinical trials reporting the use of continuous infusion of hypertonic saline solution in brain-injured patients. The primary outcome was available in 10 studies (n = 1883 patients). The odds ratio (OR) for in-hospital death with the intervention was 0.68 (95% confidence interval (CI), 0.54-0.85, I² = 0%). In the subgroup of studies including only traumatic brain-injured patients (7 studies, n = 1521 patients), the OR for the primary outcome was 0.74 (95%CI 0.57-0.95) with the intervention. The OR for intracranial hypertension and unfavorable neurological outcome at day 90 were 0.66 (95%CI 0.49-0.88, I² = 42%, n = 787 patients) and 0.61 (95%CI 0.46-0.81, I² = 15%, n = 956 patients), respectively. Regarding safety, the OR of acute kidney injury and severe hypernatremia were 0.82 (95%CI 0.47-1.44, I² = 0%) and 3.38 (95%CI 2.16-5.27, I² = 24%).

Conclusions: Continuous hypertonic saline solution infusion reduced in-hospital mortality without increasing the risk of unfavorable neurological outcome at day 90 in brain-injured patients hospitalized in intensive care units. Given the inclusion of observational and heterogeneous studies, further randomized studies are needed before developing recommendations for implementation at the bedside.

Systematic review registration: PROSPERO CRD42021221367. Registered 13 May 2021.

Keywords: Brain injury; Hypertonic saline solution; Intensive care unit; Saline infusion.