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Pharmacological Prevention of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

  • Practice Guidance for Critical Care Management of SAH
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Abstract

Background

Causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH) include early brain injury and delayed neurologic deterioration, which may result from delayed cerebral ischemia (DCI). Complex pathophysiological mechanisms underlie DCI, which often includes angiographic vasospasm (aVSP) of cerebral arteries.

Methods

Despite the study of many pharmacological therapies for the prevention of DCI in aSAH, nimodipine—a dihydropyridine calcium channel blocker—remains the only drug recommended universally in this patient population. A common theme in the research of preventative therapies is the use of promising drugs that have been shown to reduce the occurrence of aVSP but ultimately did not improve functional outcomes in large, randomized studies. An example of this is the endothelin antagonist clazosentan, although this agent was recently approved in Japan.

Results

The use of the only approved drug, nimodipine, is limited in practice by hypotension. The administration of nimodipine and its counterpart nicardipine by alternative routes, such as intrathecally or formulated as prolonged release implants, continues to be a rational area of study. Additional agents approved in other parts of the world include fasudil and tirilazad.

Conclusions

We provide a brief overview of agents currently being studied for prevention of aVSP and DCI after aSAH. Future studies may need to identify subpopulations of patients who can benefit from these drugs and perhaps redefine acceptable outcomes to demonstrate impact.

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  1. Department of Pharmacy, Temple University Hospital, Philadelphia, PA, USA

    Meghan M. Caylor

  2. Community Neurosciences Institute, Community Health Partners, 7257 North Fresno Street, Fresno, CA, 93720, USA

    R. Loch Macdonald

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Caylor contributed to the article outline, wrote some parts of the original manuscript, reviewing necessary literature, interpreting the literature, and then approved of the final manuscript and agreed to be accountable for all aspects of the work. Macdonald wrote the initial article outline, wrote some parts of the original manuscript, reviewed necessary literature, interpreted the literature, revised the paper, approved the final manuscript, and agreed to be accountable for all aspects of the work.

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Correspondence to R. Loch Macdonald.

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RLM reports consulting fees from Acasti Pharma US, CSL Behring and Idorsia Pharmaceuticals. MMC reports no conflicts of interests for this publication nor any disclosures.

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Caylor, M.M., Macdonald, R.L. Pharmacological Prevention of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 40, 159–169 (2024). https://doi.org/10.1007/s12028-023-01847-6

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