Effects of hypertonic saline versus mannitol in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings: A systematic review and meta-analysis

Background: Intracranial pressure control has long been recognized as an important requirement for patients with severe traumatic brain injury. Hypertonic saline has drawn attention as an alternative to mannitol in this setting. The aim of this study was to assess the effects of hypertonic saline versus mannitol on clinical outcomes in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings by systematically reviewing the literature and synthesizing the evidence from randomized controlled trials. Methods: We searched the MEDLINE database, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi (ICHUSHI) Web database with no date restrictions. We selected randomized controlled trials in which the clinical outcomes of adult patients with traumatic brain injury were compared between hypertonic saline and mannitol strategies. Two investigators independently screened the search results and conducted the data extraction. The primary outcome was all-cause mortality. The secondary outcomes were 90-day and 180-day mortality, good neurological outcomes, reduction in intracranial pressure, and serum sodium level. Random effects estimators with weights calculated by the inverse variance method were used to determine the pooled risk ratios. Results: A total of 125 patients from four randomized trials were included, and all the studies were conducted in the intensive care unit. Among 105 patients from three trials that evaluated the primary outcome, 50 patients were assigned to the hypertonic saline group and 55 patients were assigned to the mannitol group. During the observation period, death was observed for 16 patients in the hypertonic saline group (32.0%) and 21 patients in the mannitol group (38.2%). The risks were not significant between the two infusion strategies (pooled risk ratio, 0.82; 95% confidence interval, 0.49-1.37). There were also no significant differences between the two groups in the other secondary outcomes. However, the certainty of the evidence was rated very low for all outcomes. Conclusions: Our findings revealed no significant difference in the all-cause mortality rates between patients receiving hypertonic saline or mannitol to control intracranial pressure.