Alternating Hyperosmolar Therapy in Patients With Elevated and Refractory Intracranial Pressure

Introduction: Elevated intracranial pressure (ICP) remains a challenge and immediate danger in patients with acute brain injury. Current literature supports the use of a single hyperosmolar agent, primarily hypertonic saline or mannitol, to reduce the ICP. However, the efficacy and safety of alternating hyperosmolar agents has not been evaluated. The objectives of this study are to analyze the ICP lowering effects and evaluate the safety profile of alternating hyperosmolar therapy.


Methods: This was a single-center, retrospective study of adults (≥ 18 years old) with acute brain injury admitted to the Neurosciences Intensive Care Unit between May 7, 2018, and September 6, 2024. Patients with intracranial hypertension refractory to a single hyperosmolar agent who received alternating doses of mannitol and hypertonic sodium approximately every 3 hours with an ICP monitor were included in the study. We evaluated the impact of alternating hyperosmolar therapy on ICP. Safety was assessed by measuring the frequency of acute kidney injury, electrolyte disturbances, and changes in volume status.


Results: A total of 46 patients were included in this study with 29 (63%) males and a median (IQR) age of 46.5 (35.9, 62.4) years. Traumatic brain injury and intracranial hemorrhage were the most frequently reported brain injuries accounting for 17 (37%) and 12 (26%) patients, respectively. The median (IQR) dose of mannitol was 40.1 (34.6, 50.0) grams while the median (IQR) dose of hypertonic sodium was 120 (90, 125) milliequivalents. The median (IQR) duration of alternating hyperosmolar therapy was 14.0 (7.8, 37.3) hours. Eighty-six percent of patients experienced a decrease in ICP after initiation of alternating hyperosmolar therapy with a median (IQR) baseline ICP of 12 (6, 21) mmHg and a median (IQR) trough ICP of 2 (0, 8) mmHg. Seven acute kidney injuries occurred, and 7 patients experienced pulmonary edema. Median (IQR) peak sodium, chloride, and osmolar gap values were 149 (144, 155) mEq/L, 115 (111, 119) mEq/L, and 5.7 (0.7, 9.0) mOsm/kg, respectively, while receiving alternating hyperosmolar therapy.


Conclusions: Alternating hyperosmolar therapy may provide a transient ICP reduction without a substantial increase in adverse effects in patients with refractory ICP to a single hyperosmolar agent.