Impact of Nimodipine-Induced Blood Pressure Reductions on Cerebral Autoregulation and Functional Outcome After...

Impairment of cerebral autoregulation following aneurysmal subarachnoid hemorrhage (aSAH) increases susceptibility to secondary injury from blood pressure (BP) fluctuations. Although nimodipine is recommended to improve neurological outcomes, it is frequently associated with BP reduction. In this observational cohort study, we examined the effect of nimodipine-induced BP reductions that exceed autoregulatory capacity on functional outcome following aSAH.

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 the lower and upper limits of autoregulation (LLA and ULA). Physiologic parameters were compared between the hour before and the hour after nimodipine administration using linear mixed-effects models. Ordinal regression was used to assess the relationship between time with MAP below the LLA and functional outcome, as measured by the modified Rankin scale at 90 days post discharge.

Analysis included 682 nimodipine administrations among 31 patients with moderate to severe aSAH (mean age 57 ± 14 years, 71% female, median Hunt & Hess score 4 [interquartile range (IQR) 2-4], modified Fisher grade 4 [IQR 3-4], monitoring time 5.5 ± 4.7 days). Following nimodipine, MAP decreased from a mean ± SEM of 105.9 ± 0.7 to 100.1 ± 0.7 mm Hg (p < 0.001), resulting in increased time below the LLA from a mean ± SEM of 5.3 ± 0.5 to 13.9 ± 0.7 min (p < 0.001). Mean time below the LLA was significantly associated with worse functional outcome at 90 days (odds ratio for 10-min increase 3.6, 95% confidence interval 1.6-8.0, p = 0.0015). This association remained significant after adjusting separately for age, Hunt & Hess score, modified Fisher grade, delayed cerebral ischemia, and the magnitude of BP response to nimodipine.

Nimodipine-induced BP reductions below personalized limits of autoregulation may be associated with worse functional outcome after aSAH. Further prospective studies are warranted to explore how autoregulatory sensitivity to nimodipine can be used to identify vulnerable patients and maximize benefits from current clinical interventions.