Intravenous Milrinone for Delayed Cerebral Ischemia and Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Pilot Study and Protocol Development
Eveline Gutzwiller1, Amir Dehdashti2, Shayan Huda2, David Ledoux2
1Catholic Health, 2Northwell Health
Objective:

To evaluate the safety and feasibility of early intravenous (IV) milrinone therapy for delayed cerebral ischemia (DCI) and vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) and to develop a standardized clinical protocol for its implementation in neurocritical care practice. 

Background:

Intravenous milrinone, a phosphodiesterase-3 inhibitor with inotropic and vasodilatory properties, shows promise for DCI and vasospasm management; however, a standardized protocol remains lacking.

Design/Methods:

This retrospective pilot study at Staten Island University Hospital involved consecutive patients with non-traumatic SAH admitted from January 2023 to January 2025, who developed DCI or vasospasm and received early IV milrinone treatment. We established patient selection criteria, a dosing chart, monitoring parameters, and criteria for escalation or discontinuation. Outcomes assessed included milrinone side effects, vasospasm-related ischemic stroke, and rescue endovascular angioplasty rates. Descriptive statistics summarized clinical characteristics and outcomes.

Results:

Seven patients received IV milrinone upon clinical or radiographic DCI or vasospasm onset. Median age was 58.5 years; 50% were female. Most (87.5%) had Hunt-Hess grades ≥3; five had modified Fisher scale (mFS) scores of 4, two had mFS of 3. Modified Rankin Scale scores at discharge ranged from 0 (no symptoms) to 5 (severe disability). The standardized protocol parameters were:

Median starting dose: 0.125 µg/kg/min

Median maximum dose: 0.375 µg/kg/min

Median treatment duration: 8 days

No milrinone-related side effects (hypotension, arrhythmias, worsening kidney function, or electrolyte disturbances) were observed. Triggers for milrinone were predominantly new focal neurological deficits or radiographic vasospasm. Clinical and/or radiographic improvement occurred in most patients, and importantly, none required rescue intra-arterial angioplasty. These findings informed our standardized protocol, encompassing patient selection, dosing, monitoring, escalation, and discontinuation guidelines.

Conclusions:

IV milrinone appears safe and potentially effective in managing DCI and vasospasm symptoms. These promising preliminary results support implementing our standardized clinical protocol and justify further prospective randomized controlled studies.

10.1212/WNL.0000000000213076
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