Safety and Outcomes of Valproic Acid in Subarachnoid Hemorrhage Patients: A Retrospective Study

Background and Purpose: Animal studies have suggested that valproic acid (VPA) is neuroprotective in aneurysmal subarachnoid hemorrhage (SAH). Potential mechanisms include an effect on cortical spreading depolarizations (CSD), apoptosis, blood–brain barrier integrity, and inflammatory pathways. However, the effect of VPA on SAH outcomes in humans has not been investigated. Methods: We conducted a retrospective analysis of 123 patients with nontraumatic SAH. Eighty–seven patients had an aneurysmal source and 36 patients did not have a culprit lesion identified. We used stepwise logistic regression to determine the association between VPA and the following: delayed cerebral ischemia (DCI), radiographic vasospasm, and discharge modified Rankin Scale (mRS) score > 3. Results: All 18 patients who received VPA underwent coil embolization of their aneurysm. VPA use did not have a significant association with DCI on adjusted analysis (Odds Ratio, OR = 1.07, 95% CI: 0.20 – 5.80). The association between VPA use and vasospasm was OR = 0.64 (0.19 – 1.98) and discharge mRS > 3 was OR = 0.45 (0.10 – 1.64). Increased age (OR = 1.04, 1.01 – 1.07) and Hunt and Hess (HH) grade > 3 (OR = 14.5, 4.31 – 48.6) were associated with an increased likelihood for poor discharge outcome (mRS > 3). Younger age (OR = 0.96, 0.93 – 0.99), mFS score = 4 (OR = 4.14, 1.81 – 9.45), and HH grade > 3 (OR = 2.92, 1.11 – 7.69) were all associated with subsequent development of radiographic vasospasm. There were no complications associated with VPA administration. Conclusion: We did not observe an association between VPA and the rate of DCI. There may have been a protective association on discharge outcome and radiographic vasospasm that did not reach statistical significance. We found that VPA use was safe and is plausible to be used in a population of SAH patients who have undergone endovascular treatment of their aneurysm. Larger, prospective studies are needed to determine the effect of VPA on outcome after SAH.