Treatment Effect of Early Intravenous Milrinone for Cerebral Vasospasm or Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Background: This study assessed the effect of intravenous (IV) milrinone as first-line therapy for cerebral vasospasm (CVS) or delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH).

Methods: A retrospective study was performed on consecutive patients with aSAH from 2017 to 2022. We assessed the association of IV milrinone treatment with outcomes graded with modified Rankin Scale score at 6 months. We compared the use of alternative therapies for CVS or DCI between patients who received IV milrinone and those who did not. All statistical analyses were performed using STATA 18.0 (StataCorp, College Station, TX).

Results: Of 336 patients, 130 (39%) developed CVS or DCI. Seventy-three patients received IV milrinone and 57 patients did not. Among symptomatic patients, 59% showed improvement in symptoms after milrinone was started. Twenty percent of patients in the milrinone group required vasopressor therapy, whereas 84% of patients were treated with vasopressors in the nonmilrinone group (p < 0.01). Thirty one percent of patients receiving milrinone and 56% of patients in the non-milrinone group received endovascular therapy (p = 0.02). Univariate analysis showed milrinone was likely associated with good outcome (odds ratio [OR] 2.12 [95% confidence interval [CI] 0.97-4.63]; p = 0.06). Propensity score matching analysis confirmed an association between milrinone and good outcome (coefficient 0.30, standard error 0.13 [95% confidence interval [CI] 0.05-0.55]; p = 0.02).

Conclusions: Our study showed several potential benefits of early IV milrinone therapy for patients with aSAH with CVS or DCI. Patients who received IV milrinone had better outcome and required vasopressor or endovascular therapy less often. Limitations of the study included several protocol deviations, incomplete documentation of drug effect, and inconsistent assessment of CVS resolution. Early IV milrinone improved outcomes and reduced the use of other therapies to treat CVS and DCI. These results need confirmation in a large clinical trial with stratification of patients by clinical severity, indication, and optimized protocols.