Systemic Cardiovascular Responses to Clazosentan as Potential Indicators of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Background Clazosentan, an endothelin A receptor antagonist, reduces angiographic vasospasm after subarachnoid hemorrhage (SAH); however, delayed cerebral ischemia (DCI) can still develop. We investigated whether the systemic cardiovascular responses to clazosentan could predict the occurrence of DCI. Methods We retrospectively analyzed 48 patients with aneurysmal SAH treated with clazosentan. Cardiac output (CO) and systemic vascular resistance (SVR) were measured using a non-invasive finger-cuff hemodynamic monitor. Changes in CO and SVR (ΔCO and ΔSVR) were defined as differences between post- and pre-clazosentan administration. Results DCI occurred in seven patients (14.6%). Patients with DCI showed significantly lower ΔCO (-0.4 L/min vs 0.7 L/min, p = 0.014) and higher SVR (454 mmHg·min/L vs. -242 mmHg·min/L, p = 0.008) than those without DCI. Receiver operating characteristic analysis revealed an area under the curve of 0.817 (95% confidence interval (CI), 0.660–0.974) for ΔCO and 0.794 (95% CI, 0.591–0.998) for ΔSVR. In multivariate logistic regression, the combined pattern of negative ΔCO and positive ΔSVR was independently associated with DCI after age adjustment (odds ratio 11.03, 95% CI 1.34-90.75, p = 0.026). Conclusions These exploratory findings raise the possibility that non-invasive monitoring of systemic hemodynamic responses may help identify the patients at high risk of DCI after SAH during clazosentan therapy.