Efficacy of controlled-release papaverine pellets in preventing symptomatic cerebral vasospasm

Object. Vasospasm as a complication of subarachnoid hemorrhage is a major c oncern in clinical practice. The systemic drugs in current use are of limit ed value. Topical, intrathecal, or intraarterial papaverine administered du ring surgical or angiographic procedures is a potent vasodilating drug; how ever, hypotension limits its systemic application. Local application of pap averine in a biodegradable controlled- or sustained-release matrix is prepo sed for vasospasm prophylaxis to be used in patients scheduled for aneurysm surgery. Methods. Controlled-release papaverine (PapaCR) drug pellets were prepared using the biodegradable aliphatic polyester poly(DL-lactide-co-glycolide) a s the carrier matrix. In vitro tests were performed to determine drug kinet ics. One hundred seventeen patients, 73 assigned to the control group and 4 4 assigned to the PapaCR-treated group, participated in this study. Patient s who were deemed to be at high risk for the development of vasospasm were selected to participate in the study. During aneurysm surgery, drug pellets were placed in cisterns over arterial segments. In two patients, cerebrosp inal fluid was sampled every 6 hours for the first 5 days through a lumbar catheter that had been inserted at the beginning of aneurysm surgery. The i ncidence of clinical vasospasm and Glasgow Outcome Scale scores in the pati ents were evaluated statistically. The results of in vitro studies showed that effective local concentrations of papaverine could be maintained for more than 10 days. The first-degree d rug-release profile was demonstrated using this design. In clinical studies no adverse effects due to the drug were seen. The PapaCR effectively preve nted development of clinical vasospasm, and outcome scores were significant ly better in patients in the treated group. Conclusions. Local application of controlled- or sustained-release papaveri ne can be safely used in preventing vasospasm.