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Management of ischemic priapism with high-dose intracavernosal phenylephrine: from bench to bedside.

INTRODUCTION
Ischemic priapism is associated with cavernosal acidosis, which decreases the efficacy of adrenergic agonists. We determined the effect of acidosis on ligand dissociation from adrenergic receptors and assessed the efficacy of high-dose phenylephrine in treating patients with acute ischemic priapism.


METHODS
Dissociation rates of [3H]prazosin were determined at pH 7.2 and 6.9 in membrane preparations of rabbit penile cavernosal tissue. Vital signs were recorded from patients before injection, and at 1 minute and 5 minutes after injection of high-dose phenylephrine (1,000 mg q 5 minutes) for 17 consecutive cases of iatrogenic ischemic priapism that occurred after vascular assessment. We also provide two case reports of prolonged ischemic priapism successfully managed with high-dose phenylephrine.


RESULTS
Dissociation rates of [3H]prazosin were greater at pH 6.9 (K (-1) = 0.23/minute) than at pH 7.2 (K (-1) = 0.10/minute), suggesting decreased receptor affinity at acidic pH. Intracavernosal therapy with high-dose phenylephrine (mean dose 2,059 +/- 807 microg) was 100% effective with no adverse events or significant changes in vital signs. In addition, two patients with ischemic priapism for > or =36 hours were successfully treated with high-dose intracavernosal phenylephrine (mean dose 45,000 microg) without any adverse event. Both patients are currently potent.


CONCLUSIONS
Acidic pH may decrease the binding affinity of adrenergic ligands to their receptors. Phenylephrine at doses higher than previously reported may be necessary to overcome this decreased affinity in acidosis associated with ischemic priapism. High-dose intracavernosal phenylephrine administration is safe and effective in the management of ischemic priapism. Continuous cardiovascular monitoring is advised.