Abstract P756: Bilirubin Oxidation and Cerebral Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study

Abstract

Introduction: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high degree of morbidity and mortality. In an adequate oxidative environment, certain products of bilirubin metabolism have been hypothesized to be a cause of CV. To our knowledge no prospective CSF collection has been performed to establish a time course for their formation in the clinical context of CV. We aimed to design a pilot study assessing the feasibility of collecting and storing CSF for analysis of potential biochemical markers for CV, and to evaluate which variables can accurately and reliably be measured for a larger prospective study. Methods: Adult patients with aSAH and an external ventricular drain (EVD) were enrolled. Patients who had complications following treatment of aSAH or who developed any neurological deterioration unrelated to the aSAH were excluded. CSF was extracted from patients on the initial day of EVD placement and then daily for a total of 10 days and frozen until data analysis. Heme, Heme Oxygenase (HO-1) and Cu/Zn-Superoxide Dismutase (SOD) were measured using commercially available assay kits. Results: Patients 1, 2 and 3 had modified Fisher grades of 2, 3 and 4, respectively. Patients 1 and 3 underwent endovascular coiling and patient 2 had surgical clipping. There were no complications and no CV. Heme concentrations were 40.0 ± 8.5 μm, 55.6 ± 7.7 μm, and 64.7 ± 0.4 μm on day of bleed (day 0) for patients 1, 2, and 3, respectively, and decreased in patients 1 and 2 on day 1. SOD concentrations peaked on day 2 for patient 1 (140.2 ± 15.6 ng/mL), on day 0 for patient 2 (25.8 ± 14.9 ng/mL), and on day 1 for patient 3 (215.9 ± 24.4 ng/mL). HO-1 concentrations peaked for all three patients on day 2 (14.6 ± 0.4, 17.6 ± 12.0 and 23.6 ± 5.4 ng/mL, respectively). Conclusions: The study was successful in completing our objective of establishing a protocol for collection, storage, and measurement of three potential biochemical markers in CSF. A larger prospective study will be performed to establish the time course of bilirubin metabolism and oxidation in the CSF relative to the clinical condition of CV in patients after aSAH.