Clazosentan Administration Was Not Associated with Intracranial Pressure Elevation in Aneurysmal Subarachnoid...

Background/Objectives: Clazosentan reduces cerebral vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH). However, concerns that clazosentan may cause cerebral edema and increase intracranial pressure (ICP) have discouraged its use in patients with poor-grade aSAH. Methods: This single-center retrospective study included 59 patients with aSAH who underwent continuous direct ICP monitoring, of whom 23 received clazosentan and 24 received fasudil. Most clazosentan-treated patients had poor-grade aSAH (WFNS 4-5, 95.7%). The primary outcome was the change in mean daily ICP in the clazosentan group between the pre-treatment and full treatment periods, with a secondary analysis restricted to the first 7 days and stratified by the presence of intracerebral hematoma (ICH). Cerebral perfusion pressure (CPP) changes were assessed as secondary outcomes, and the fasudil group served as an exploratory comparator. Results: Among 21 clazosentan-treated patients available for primary analysis, median ICP did not change significantly between the pre-treatment and treatment periods (6.4 vs. 8.4 mmHg; median ΔICP +0.5 mmHg, 95% CI -1.74 to +2.64; p = 0.708), a finding consistent in the first 7 days and across subgroups by ICH status. In contrast, CPP increased significantly between the pre-treatment and treatment periods (69.1 vs. 84.5 mmHg; median ΔCPP +14.0 mmHg, 95% CI +8.93 to +17.44; p < 0.001). Conclusions: In this retrospective single-center cohort, no statistically significant ICP elevation was observed during clazosentan administration under standard neurosurgical management. Although the small sample size limits statistical power and a false-negative result cannot be excluded, these findings may help inform clinical decision-making regarding clazosentan use in patients with poor-grade aSAH.