A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

Journal of Neurosurgery
Chad W WashingtonGregory J Zipfel

Abstract

Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an...Continue Reading

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Citations

Jun 25, 2016·Journal of Neurosurgery·Manjul TripathiKanchan Kumar Mukherjee
Nov 15, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Darcy LidingtonSteffen-Sebastian Bolz
Dec 20, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Mathilde Mh PaulsJeremy D Isaacs
Feb 23, 2020·Critical Care Nursing Quarterly·Keaton S SmetanaCasey C May

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