Kinetics of cerebral blood flow velocities during treatment for delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage

In aneurysmal subarachnoid hemorrhage (aSAH), one of the main determinants of prognosis is delayed cerebral ischemia (DCI). Transcranial Doppler (TCD) is used to monitor vasospasm and DCI. We aimed to better understand cerebral hemodynamics response to hypertension induction (HI) with norepinephrine (NE) and inotropic therapy with milrinone so that TCD can be a bedside tool in helping to guide DCI therapies. Our primary objective was to determine TCD blood flow velocity (BFV) kinetics during HI and inotropic therapy for DCI treatment. Secondly, we performed an analysis by treatment subgroups and evaluated clinical response to therapies.

We performed a prospective observational cohort study in a Brazilian high-volume center for aSAH. Patients with aSAH admitted between 2016 and 2018 who received NE or milrinone for DCI treatment were included. TCDs were performed before therapy initiation (t0) and 45 (t1) and 90 min (t2) from the onset of therapy. For each DCI event, we analyzed the highest mean flow velocity (MFV) and the mean MFV and compared their kinetics over time. The National Institutes of Health Stroke Scale was determined at t0, t1, and t2.

Ninety-eight patients with aSAH were admitted during the study period. Twenty-one (21.4%) developed DCI, of whom six had DCI twice, leading to a total of 27 analyzed DCI events (12 treated with HI and 15 with milrinone). Patients treated with NE had their mean arterial pressure raised (85 mm Hg in t0, 112 mm Hg in t2 [p < 0.001]), whereas those treated with milrinone had a significant decrease in mean arterial pressure over treatment (94 mm Hg in t0, 88 mm Hg in t2 [p = 0.004]). Among all treated patients, there was a significant drop from t0 to t2 but not to t1 in the highest MFV and in the highest mean MFV. Among those treated with HI, there were no significant changes from t0 to t1 or t2 (highest MFV in t0 163.2 cm/s, in t1 172.9 cm/s [p = 0.27], and in t2 164 cm/s [p = 0.936]). Conversely, in those treated with milrinone, there was a significant decrease from t0 to t1 and to t2 (highest MFV in t0 197.1 cm/s, in t1 172.8 cm/s [p = 0.012], in t2 159 cm/s [p = 0.002]). Regarding clinical outcomes, we observed a significant improvement in mean National Institutes of Health Stroke Scale scores from 17 to 16 in t1 (p < 0.001) and to 15 in t2 (p = 0.002).

BFV analyzed by TCD in patients with aSAH who developed DCI and were treated with milrinone or NE significantly decreased in a time-dependent way. Milrinone effectively decrease cerebral BFV, whereas NE do not. Clinical improvement was achieved with both treatment strategies.