Characterizing the Dose-Response Relationship between Mannitol and Intracranial Pressure in Traumatic Brain Injury Patients Using a High-Frequency Physiological Data Collection System

Despite the widespread use of mannitol to treat elevated intracranial pressure (ICP), there is no consensus regarding the optimal dosage. The objective of this study was to retrospectively characterize the dose-response relationship between mannitol and ICP using data collected with a continuous high-frequency physiological data collection system. To this end, we measured ICP continuously in 28 patients with traumatic brain injury (TBI) who were given at least one dose of mannitol. Twenty TBI patients were given a total of 85 doses of 50 g of mannitol, and 18 patients were given 50 doses of 100 g. Some patients received both amounts. Cerebral perfusion pressure was maintained above 60 mm Hg. The average ICP was 22.0 +/- 10.6 mm Hg when mannitol was administered, fell immediately after dosing, and continued falling for approximately 30 min to 15.7 +/- 8.1 mm Hg across all patients. After 30 min, ICP was equal in the 100-g group (15.6 +/- 10.9) versus the 50-g group (15.7 +/- 6.3). However, at 100 min, ICP had increased in the 50-g group to nearly its initial value but was still lower in the 100-g group (18.6 +/- 7.6 vs. 14.2 +/- 6.7 mm Hg; p = 0.001). Osmotic agents such as mannitol have been used for decades to treat cerebral edema, but there has been no definitive quantitative information regarding the dosing of mannitol. In a large, retrospective study of high-frequency ICP data, we have quantitatively shown that mannitol's effect on ICP is dose-dependent and that higher doses provide a more durable reduction in ICP.