The Optimal Dose of Mannitol for Intraoperative Brain Relaxation in Aneurysmal Subarachnoid Hemorrhage: A Randomized Controlled Trial

Introduction: Elevated intracranial pressure (ICP) and cerebral edema complicate craniotomy in patients with aneurysmal subarachnoid hemorrhage (aSAH), posing challenges for achieving brain relaxation during surgery. Optimal mannitol dosing may improve surgical outcomes, but the ideal dosage for brain relaxation remains uncertain. This study aims to identify the optimal dose of mannitol to enhance intraoperative brain relaxation and assess associated clinical outcomes.

Methods: This prospective, randomized, double-blind controlled trial was conducted at Beijing Tiantan Hospital between October 2019 and November 2023. Ninety-nine adult patients (ages 18-70 years) with aSAH (Hunt-Hess grade III or lower) undergoing craniotomy were enrolled. Patients with pre-existing conditions such as heart failure or kidney insufficiency were excluded. Participants were randomly assigned to receive intravenous 20% mannitol at one of three doses: 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg, administered immediately after skin incision. The primary outcome was intraoperative brain relaxation, evaluated on a 4-point scale (1: bulging brain; 4: perfectly relaxed). Secondary outcomes included renal function, post-operative complications, and functional outcomes measured by the modified Rankin Scale (mRS) at discharge and 3-month follow-up.

Results: Among the 99 patients (mean age: 53.8 years; 53.5% male), those receiving 1.5 g/kg of mannitol achieved significantly better brain relaxation compared to the 0.5 g/kg and 1.0 g/kg groups (P < 0.001). The proportion of patients with satisfactory brain relaxation was 72.7% in the 1.5 g/kg group, compared to 30.3% and 6.1% in the 1.0 g/kg and 0.5 g/kg groups, respectively. There were no significant differences between the groups in terms of renal function or post-operative complications. Functional outcomes at discharge and 3-month follow-up were comparable across all dosing groups.

Conclusion : A mannitol dose of 1.5 g/kg provides optimal brain relaxation during aSAH craniotomy without increasing the risk of renal impairment or post-operative complications. These results suggest that higher mannitol doses can improve surgical conditions, supporting the use of 1.5 g/kg for patients undergoing craniotomy for aSAH.