Spinal Drainage and Combined Pharmacotherapy as Potential Strategies to Improve Outcomes for Patients with Poor-Grade Subarachnoid Hemorrhage Treated with Clipping or Coiling but Not Receiving Nimodipine

Abstract

Background/Objectives: The outcome for aneurysmal subarachnoid hemorrhage (SAH) remains poor, particularly for patients presenting with World Federation of Neurological Surgeons (WFNS) grades IV-V. This study was designed to identify independent prognostic factors in this group of patients with poor-grade SAH. Methods: We prospectively analyzed 357 SAH patients with admission WFNS grades IV-V enrolled in nine primary stroke centers in Mie prefecture, Japan, from 2013 to 2022. This study compared clinical variables, including treatments for angiographic vasospasm and delayed cerebral ischemia (DCI), between patients with favorable (modified Rankin Scale [mRS] scores 0-2) and unfavorable (mRS scores 3-6) outcomes at 90 days post-onset. Multivariate analyses were then performed to identify independent determinants of favorable 90-day outcomes, followed by propensity score matching analyses. Results: The median age was 68 years, and 53.5% of patients had admission WFNS grade V. DCI occurred in 12.9% of patients, and 66.9% had unfavorable outcomes. Independent variables related to unfavorable outcomes were older age, admission WFNS grade V, ventricular drainage, edaravone administration, and delayed cerebral infarction, while those for favorable outcomes were spinal drainage (adjusted odds ratio [aOR] 6.118, 95% confidence interval [CI] 2.687-13.927, p < 0.001), modified Fisher grade 3 (aOR 2.929, 95% CI 1.668-5.143, p < 0.001), and triple prophylactic anti-DCI medication consisting of cilostazol, fasudil hydrochloride and eicosapentaenoic acid (aOR 1.869, 95% CI 1.065-3.279, p = 0.029). Nimodipine is not approved in Japan, and statin and cerebral vasospasm did not influence outcomes. As spinal drainage and the triple prophylactic anti-DCI medication were intervenable variables, propensity score matchings were performed, and they confirmed that both spinal drainage and the triple prophylactic anti-DCI medication were useful to achieve favorable outcomes. Conclusions: In poor-grade SAH, spinal drainage and the triple prophylactic anti-DCI medication may be effective in improving outcomes, possibly by suppressing DCI pathologies other than cerebral vasospasm.

Keywords: cerebral vasospasm; cerebrospinal fluid drainage; cilostazol; delayed cerebral ischemia; early brain injury; eicosapentaenoic acid; fasudil hydrochloride; outcome; subarachnoid hemorrhage.

Figure 1

Flowchart showing the included and excluded patients in this study. SAH, subarachnoid hemorrhage; mRS, modified Rankin Scale; WFNS, World Federation of Neurological Surgeons.