Cerebral blood flow monitoring predicts response to intrathecal nicardipine treatment for vasospasm

Introduction: A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia, a predictor of poor functional outcome. Intrathecal administration of nicardipine upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of intrathecal nicardipine on microvascular cerebral blood flow (CBF). Methods: In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who required an external ventricular drain to treat obstructive hydrocephalus and who were treated with intrathecal nicardipine as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of delayed cerebral ischemia on imaging. Results: CBF increased significantly over the 90 min of monitoring after the first dose (p< 0.001) in the absence of systemic hemodynamic changes. CBF also increased on average in response to repeated doses on days 2 and 3, although the magnitude of this response decreased with successive treatment day. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of delayed cerebral ischemia was 5/6 in class 1 and 0/13 in class 2 (p< 0.001). Similar significant differences in CBF response in patients with and without delayed cerebral ischemia were also observed on days 2 and 3 (both p< 0.001). Conclusions: These results suggest that the CBF response to intrathecal nicardipine reaches a therapeutic steady state with successive treatment days. Moreover, the CBF response may provide a valuable biomarker for treatment responsiveness.