Early osmotherapy in severe traumatic brain injury: an international multicentre study.

Abstract

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 hours) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analysed data from 2015 from 14 tertiary ICUs in Australia, UK and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring, and compared mortality in those who received mannitol only versus HTS only. We performed multivariable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean intracranial pressure over the first 96 hours) using Cox proportional hazards regression. We collected data on 262 patients, and compared patients who received early osmotherapy with mannitol alone (n=46) with those who received HTS alone (n=46). Mannitol patients were older (median age 49.2 (19.2) versus 40.5 (16.8) years, p=0.02), with higher Injury Severity Scores (42(15.9) versus 32.1 (11.3) p=0.001)) and IMPACT-TBI predicted 6-month mortality (34.5%[23-46] versus 25% [13-38] p=0.02), but had similar APACHE-II scores, and mean and maximum intracranial pressures over the first 96 hours. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% CI 1.60-7.03, p=0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI 0.96-7.30, p=0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation. Keywords osmotherapy, traumatic brain injury, mannitol, hypertonic saline, mortality.