Cerebral Vasospasm After Subarachnoid Hemorrhage: Respective Short-Term Effects of Induced Arterial Hypertension and its Combination With IV Milrinone: A Proof-of-Concept Study Using Transcranial Doppler Ultrasound

Abstract

OBJECTIVES: It is unclear whether IV milrinone relaxes spasmed cerebral arteries and therefore reduces cerebral blood mean velocity (Vmean). In patients treated for cerebral vasospasm, we aimed to assess and delineate the respective impacts of induced hypertension and its combination with IV milrinone on cerebral hemodynamics as assessed with transcranial Doppler. DESIGN: Observational proof-of-concept prospective study. SETTING: ICU in a French tertiary care center. PATIENTS: Patients with aneurysmal subarachnoid hemorrhage who received induced hypertension (mean arterial blood pressure [MBP] of 100–120 mm Hg) and IV milrinone (0.5 µg/kg/min) for moderate-to-severe cerebral vasospasm. We excluded patients who underwent invasive angioplasty or milrinone discontinuation within 12 hours after the diagnosis of vasospasm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vmean was measured at vasospasm diagnosis (TDIAGNOSIS), after the induction of hypertension (THTN), and 1 (THTN+MILRINONE_H1) and 12 hours after the adjunction of IV milrinone (THTN+MILRINONE_H12). Thirteen patients were included. Median Vmean was significantly lower (p < 0.01) at THTN+MILRINONE_H1 (99 [interquartile range (IQR) 89; 134] cm.s−1) and THTN+MILRINONE_H12 (85 [IQR 73–127] cm/s) than at TDIAGNOSIS (136 [IQR 115–164] cm/s) and THTN (148 [IQR 115–183] cm/s), whereas TDIAGNOSIS and THTN did not significantly differ. In all patients but one, Vmean at THTN+MILRINONE_H1 was lower than its value at TDIAGNOSIS (p = 0.0005). Vmean-to-MBP and Vmean-to-cardiac output (CO) ratios (an assessment of Vmean regardless of the level of MBP [n = 13] or CO [n = 7], respectively) were, respectively, similar at TDIAGNOSIS and THTN but were significantly lower after the adjunction of milrinone (p < 0.01). CONCLUSIONS: The induction of arterial hypertension was not associated with a significant decrease in Vmean, whereas the adjunction of IV milrinone was, regardless of the level of MBP or CO. This suggests that IV milrinone may succeed in relaxing spasmed arteries.