Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Nils H. Petersen

Abstract

Background: Impaired cerebral autoregulation following aneurysmal subarachnoid hemorrhage (aSAH) increases susceptibility to secondary brain injury from systemic blood pressure (BP) fluctuations and is associated with delayed cerebral ischemia (DCI) and poor clinical outcomes. Oral nimodipine is the first-line treatment to prevent DCI after SAH but can result in BP reduction. In cases of refractory vasospasm, endovascular rescue therapy (ERT) with intra-arterial vasodilators or angioplasty may be employed. The effects of these interventions on cerebral autoregulation after aSAH are unknown.

Research Aims: To understand the impact of pharmacologic interventions on cerebral autoregulation following aSAH, we conducted two observational trials. We evaluated the relationship between nimodipine-induced BP reductions and outcome following aSAH, using patient-level autoregulatory data. We also examined the impact of ERT on cerebral hemodynamics and autoregulation.

Hypothesis: We hypothesized that nimodipine-induced BP reductions below personalized limits of autoregulation are associated with worse clinical outcomes. We further hypothesized that ERT would associate with improved cerebral autoregulation as indicated by greater time spent within autoregulatory limits.

Methods: We identified patients with aSAH from our prospectively maintained clinical and physiological data repository who received 1) nimodipine or 2) ERT for anterior circulation vasospasm. Autoregulatory function was measured continuously following aneurysm securement by correlating near-infrared spectroscopy-derived regional oxygen saturation with mean arterial pressure (MAP). The resulting autoregulatory index was used to derive lower and upper limits of autoregulation (LLA and ULA). Using linear mixed-effects models, hemodynamic and autoregulatory parameters were compared between 1) the hour before and the hour after nimodipine administration or 2) the 24-hour periods before and after ERT. For the nimodipine cohort, ordinal regression was used to assess the relationship between time with MAP below the LLA in the hour after nimodipine administration and functional outcome, as measured by modified Rankin Scale at 90 days post-discharge.

Results: Nimodipine Cohort: Analysis included 682 nimodipine administrations among 31 patients with moderate to severe aSAH (mean age 57±14 years, 71% female, median Hunt & Hess 4 [IQR 2-4], modified Fisher 4 [IQR 3-4], monitoring time 5.5±4.7 days). Following nimodipine, MAP decreased from 105.9±0.7 to 100.1±0.7 mmHg (Mean±SEM, p<0.001), resulting in increased time below the LLA from 5.3±0.5 to 13.9±0.7 minutes (p<0.001). Mean time below the LLA was significantly associated with worse functional outcome at 90 days (OR for 10-minute increase 3.6, 95% CI 1.6-8.0, p=0.0015). This association remained significant after adjusting separately for age, Hunt & Hess, modified Fisher, delayed cerebral ischemia, and the magnitude of BP response to nimodipine. ERT Cohort: Analysis included 37 patients (mean age 58±12 years, 62% female, median Hunt and Hess 4 [IQR 3-4], modified Fisher 4 [IQR 4-4]) who underwent 68 ERT sessions (mean verapamil dose 19±7 mg, 5/68 involving angioplasty in addition to verapamil). Following ERT, percent time with MAP outside the limits of autoregulation decreased (23.9±1.8% to 20.0±1.4%, p=0.006), driven by a reduction in time above the ULA from 13.4±1.2% to 9.4±0.8% (p=0.001). Neither vasospasm severity nor treatment with angioplasty significantly influenced the relationship between ERT and time above the ULA.

Statement of Scientific Impact: Nimodipine-induced BP reductions below personalized limits of autoregulation may be associated with worse functional outcome after aSAH. Further prospective studies are warranted to identify patients at risk for autoregulatory dysfunction and evaluate if nimodipine prophylaxis should be individualized based on hemodynamic response. In contrast, ERT may improve the time spent within autoregulatory limits.

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This is an Open Access Thesis.

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