An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage

ABSTRACT

Introduction: Survival from aneurysmal subarachnoid hemorrhage has increased in the past few decades. However, functional outcome after subarachnoid hemorrhage is still suboptimal. Delayed cerebral ischemia (DCI) is one of the major causes of morbidity.

Areas covered: Mechanisms underlying vasospasm and DCI after aneurysmal subarachnoid hemorrhage and pharmacological treatment are summarized in this review.

Expert opinion: Oral nimodine, an L-type dihydropyridine calcium channel blocker, is the only FDA-approved drug for the prevention and treatment of neurological deficits after aneurysmal subarachnoid hemorrhage. Fasudil, a potent Rho-kinase inhibitor, has also been shown to improve the clinical outcome and has been approved in some countries for use in patients with aneurysmal subarachnoid hemorrhage. Although other drugs, including nicardipine, cilostazol, statins, clazosentan, magnesium and heparin, have been expected to have beneficial effects on DCI, there has been no convincing evidence supporting the routine use of those drugs in patients with aneurysmal subarachnoid hemorrhage in clinical practice. Further elucidation of the mechanisms underlying DCI and the development of effective therapeutic strategies for DCI, including combination therapy, are necessary to further improve the functional outcome and mortality after subarachnoid hemorrhage.

KEYWORDS:

• Aneurysmal subarachnoid hemorrhage
• delayed cerebral ischemia
• vasospasm
• pharmacotherapy

Article highlights

• Although survival from aneurysmal subarachnoid hemorrhage has increased in the past few decades, functional outcome after subarachnoid hemorrhage is still suboptimal in part due to delayed cerebral ischemia (DCI).

• Not only angiographic vasospasm (large artery vasospasm) but also disturbed microcirculation due to microvasospasm, microthrombosis, impaired autoregulation, cortical spreading ischemia, and blood-brain barrier disruption may contribute to the development of DCI.

• Although the majority of current drug therapies targeting DCI have been focused on preventing and treating angiographic vasospasm, neuroprotective treatment aimed at preventing or treating various types of DCI are of current interest.

• Nimodipine and fasudi have been shown to improve DCI, neurological outcome, and mortality after aneurysmal subarachnoid hemorrhage.

• There has been no convincing evidence supporting the use of cilostazol, statins, clazosentan, magnesium, and heparin for patients after aneurysmal subarachnoid hemorrhage.

This box summarizes key points contained in the article.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The authors are funded by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (18590815 and 21590898 to Y Higashi) and a Grant in Aid from the Japanese Arteriosclerosis Prevention Fund (to Y Higashi).