Evaluation of Intravenous Milrinone in the Treatment of Vasospasm following an Aneurysmal Subarachnoid Hemorrhage

Introduction: Delayed cerebral ischemia due to cerebral vasospasm (CV) is a complication of aneurysmal subarachnoid hemorrhage (aSAH). Systemic and intra-arterial (IA) hyperdynamic therapy (HYP) are treatment options and milrinone has been suggested as adjunctive therapy for inotropic and vasodilatory effects. Vasospasm monitoring includes transcranial Dopplers (TCDs) for cerebral blood flow velocity (CBFV) and rates greater than 120 cm/second suggest CV. 

Objectives: Compare median CBFV on hyperdynamic therapy plus IV milrinone (MIL) versus HYP alone (CONT). Secondary outcomes include severity of CV, rate and duration of milrinone infusion, and modified Rankin scores (mRS) on discharge. 

Study Design: Retrospective, review of aSAH patients (n=9) post IA for CV receiving milrinone versus control (n=9), a matched cohort based on aSAH, IA and HYP for CV, age, gender, Glasgow Coma Scale (GCS), and Fisher grade on admission.

Methods: Screened discharge diagnosis of aSAH, age ≥18 years, surgically clipped / coiled within 72 hours,  with CV and baseline TCD measurements prior to IA. Exclusion criteria < 24 hours of milrinone. 

Results: Mean age was 53 ± 8.5 in MIL and 52 ± 7.1 in CONT. Median GCS on admission MIL 13 (IQR=13-14) vs. CONT  9 (IQR: 8-12). The majority with admission Fischer grade 3. Median CBFV ranged from 79 to 147.5 cm/second MIL compared to 85 to 212 cm/second CONT (p=0.052). Treatment patients averaged 10 ± 3.42 days on MIL at 0.23 ± 0.11 mcg/kg/min. CV severity did not differ between groups (p=1). 89% of MIL vs 66% CONT were discharged with moderate to severe disability and dependence (mRS ≥3) (p=0.17). 

Conclusions: No difference was detected between groups in baseline characteristics or outcomes. A larger randomized prospective clinical trial is required to assess effectiveness (initiated 11/2015). Limitations of this study include lack of safety data, limited patient documentation, and retrospective design.