Nimodipine-induced Blood Pressure Reductions Below Personalized Limits Of Autoregulation Are Associated With Worse Outcomes After Subarachnoid Hemorrhage

Background: Impairment of cerebral autoregulation after subarachnoid hemorrhage (SAH) makes patients vulnerable to changes in blood pressure (BP). While oral nimodipine is recommended for improving neurological outcomes, its administration is frequently associated with reductions in BP. In this observational study, we examined the effect of nimodipine-induced BP reductions below personalized limits of autoregulation on outcome after aneurysmal SAH. Methods: Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used for trending the BP range at which autoregulation was most preserved. Cerebral hypoperfusion was defined as episodes with at least 30 minutes of MAP reductions below the lower limit of autoregulation (LLA) following nimodipine administration (Fig. 1). Functional outcome was measured with the modified Rankin Scale at 90 days. Results: We identified 593 occurrences of nimodipine administration with simultaneous recording of continuous physiologic data for 60 minutes before and after the intervention among 26 SAH patients (mean age 57 + 14, 21 F). Following nimodipine administration, the mean MAP decreased from 103 to 98 mmHg (p<0.001), and the time with MAP below the LLA increased from 9.5 to 21.7% (p<0.001). Moreover, the proportion of episodes with cerebral hypoperfusion was associated with worse 90-day outcomes after adjusting for age and SAH severity (OR for 10% increase 1.5, 95% CI 1.2-2.2, P=0.038). Conclusions: Nimodipine-induced BP reductions below the LLA may increase the risk of secondary brain injury and poor functional outcomes. A more personalized treatment approach accounting for cerebral autoregulation status could help identify vulnerable patients and maximize the benefit from current clinical interventions.