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Review
. 2021 Jul 1;33(3):195-202.
doi: 10.1097/ANA.0000000000000755.

Treatment of Subarachnoid Hemorrhage-associated Delayed Cerebral Ischemia With Milrinone: A Review and Proposal

Thomas D Bernier  1 , Michael J Schontz  1 , Saef Izzy  2   3 , David Y Chung  3   4   5 , Sarah E Nelson  6 , Thabele M Leslie-Mazwi  3   5 , Galen V Henderson  2   3 , Hormuzdiyar Dasenbrock  7   8 , Nirav Patel  9   3 , Mohammad A Aziz-Sultan  9   3 , Steven Feske  2   3 , Rose Du  9   3 , Yasser B Abulhasan  10   11 , Mark R Angle  10
Affiliations
Review

Treatment of Subarachnoid Hemorrhage-associated Delayed Cerebral Ischemia With Milrinone: A Review and Proposal

Thomas D Bernier et al. J Neurosurg Anesthesiol. .

Abstract

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multifactorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single-center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multicenter, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.

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Conflict of interest statement

D.Y.C. has received grant funding from the National Institutes of Health (KL2TR002542 and K08NS112601), the American Heart Association and American Stroke Association (18POST34030369), the Andrew David Heitman Foundation, the Aneurysm and AVM Foundation, and the Brain Aneurysm Foundation. S.E.N. has received grant funding from the Brain Aneurysm Foundation as well as personal fees from Springer Nature. The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Search strategy
DCI, delayed cerebral ischemia; IA, intraarterial; IV, intravenous
Figure 2
Figure 2. Proposed protocol for the use of intravenous milrinone infusion in the treatment of delayed cerebral ischemia
The figure shows a proposed step-wise approach to the initiation and titration of milrinone following the onset of aSAH-related DCI. aSAH, aneurysmal subarachnoid hemorrhage; DCI, delayed cerebral ischemia; IA, intraarterial; IV, intravenous
See this image and copyright information in PMC

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