Prolonged Intracisternal Papaverine Toxicity: Index Case Description and Proposed Mechanism of Action

BACKGROUND: Intracisternal papaverine (iPPV) is a vasodilator used for prophylaxis of intraoperative vasospasm during aneurysmal clipping. Postoperative side effects of iPPV include transient cranial nerve palsies, most commonly mydriasis owing to oculomotor nerve involvement, with rapid resolution. METHODS: We critically reviewed current literature on the adverse effects of iPPV in aneurysmal surgery with a focus on oculomotor nerve involvement. We also present the index case of prolonged bilateral mydriasis secondary to iPPV irrigation toxicity and its putative underlying mechanism. RESULTS: Papaverine toxicity occurs in the setting of its antimuscarinic action and blood-cerebrospinal fluid and blood-brain barrier compromise owing to acute subarachnoid hemorrhage and direct effect of papaverine. Our patient also experienced severe vasospasm and a minor stroke, both contributing to further blood-brain barrier disruption, and relatively acidic pH of the subarachnoid hemorrhage milieu. CONCLUSIONS: We propose that these factors perpetuate phase dynamics of papaverine crystals and facilitate a sustained slow release of papaverine within the cisternal system. Were it indicated, 0.3% iPPV would reasonably diminish the risk for neurotoxicity.