Association between continuous hyperosmolar therapy and survival in patients with traumatic brain injury - a multicentre prospective cohort study and systematic review.

BACKGROUND: Intracranial hypertension (ICH) is a major cause of death after traumatic brain injury (TBI). Continuous hyperosmolar therapy (CHT) has been proposed for the treatment of ICH, but its effectiveness is controversial. We compared the mortality and outcomes in patients with TBI with ICH treated or not with CHT. METHODS: We included patients with TBI (Glasgow Coma Scale ≤ 12 and trauma-associated lesion on brain computed tomography (CT) scan) from the databases of the prospective multicentre trials Corti-TC, BI-VILI and ATLANREA. CHT consisted of an intravenous infusion of NaCl 20% for 24 hours or more. The primary outcome was the risk of survival at day 90, adjusted for predefined covariates and baseline differences, allowing us to reduce the bias resulting from confounding factors in observational studies. A systematic review was conducted including studies published from 1966 to December 2016. RESULTS: Among the 1086 included patients, 545 (51.7%) developed ICH (143 treated and 402 not treated with CHT). In patients with ICH, the relative risk of survival at day 90 with CHT was 1.43 (95% CI, 0.99-2.06, p = 0.05). The adjusted hazard ratio for survival was 1.74 (95% CI, 1.36-2.23, p < 0.001) in propensity-score-adjusted analysis. At day 90, favourable outcomes (Glasgow Outcome Scale 4-5) occurred in 45.2% of treated patients with ICH and in 35.8% of patients with ICH not treated with CHT (p = 0.06). A review of the literature including 1304 patients from eight studies suggests that CHT is associated with a reduction of in-ICU mortality (intervention, 112/474 deaths (23.6%) vs. control, 244/781 deaths (31.2%); OR 1.42 (95% CI, 1.04-1.95), p = 0.03, I 2 = 15%). CONCLUSIONS: CHT for the treatment of posttraumatic ICH was associated with improved adjusted 90-day survival. This result was strengthened by a review of the literature.

Hypertonic saline, not mannitol, should be considered gold-standard medical therapy for intracranial hypertension.

Hyperosmolar therapy is the principal medical management strategy for elevated intracranial pressure. Mannitol has been the primary hyperosmolar agent for nearly a century and remains the de facto gold standard for medical management of intracranial hypertension. Over the past 25 years, however, hypertonic saline (HTS) has become a progressively more common alternative to mannitol, and several recent studies have suggested its relative superiority. These findings have prompted calls for large-scale comparator trials of mannitol and HTS, but such trials would only be necessary if the designation of mannitol as the gold standard is appropriate and if current evidence suggests its therapeutic equipoise with HTS. Mounting evidence supporting HTS suggests that neither of these conditions is necessarily true and, instead, mandates reassessment of the actual gold-standard agent for hyperosmolar therapy. In the present article I make the case that current evidence supports HTS, not mannitol, as the better choice for gold-standard therapy for medical management of intracranial hypertension. This is accomplished first by examining the evidence on which the apparent designation of mannitol as the presumed gold-standard is based, then by reviewing the recent comparative efficacy data for HTS versus mannitol, and finally by discussing additional clinical considerations for appropriate designation of a gold-standard agent for hyperosmolar therapy. This assessment has important implications both for patient care and for clinical trial design.