Comparative Effectiveness of Mannitol Versus Hypertonic Saline in Patients With Traumatic Brain Injury: A CENTER-TBI Study

Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOAs), mannitol and hypertonic saline (HTS), are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS, or their combined use translated into differences in outcome. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study is a prospective multi-center cohort study. For this study, patients with TBI, admitted to the intensive care unit (ICU), treated with mannitol and/or HTS, and aged ≥16 years were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as first administered HOA in the ICU. We assessed influence of center and patient characteristics in the choice of agent using adjusted multi-variate models. Further, we assessed the influence of HOA preference on outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS in the ICU. The first received HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, or both mannitol and HTS on the same day for 66 (13%) patients. Two unreactive pupils were more common in patients receiving both (13, 21%), compared with patients receiving HTS (40, 14%) or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA (p-value <0.05). ICU mortality and 6-month outcome were similar between patients preferably treated with mannitol compared with HTS (odds ratio [OR] = 1.0, confidence interval [CI] = 0.4-2.2; OR = 0.9, CI = 0.5-1.6, respectively). Patients who received both also had a similar ICU mortality and 6-month outcome compared with patients receiving HTS (OR = 1.8, CI = 0.7-5.0; OR = 0.6, CI = 0.3-1.7, respectively). We found between-center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a specific HOA.