Evaluation of big endothelin–1 concentrations in serum and ventricular cerebrospinal fluid after early surgical compared with nonsurgical management of ruptured intracranial aneurysms

Object Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post–subarachnoid hemorrhage (SAH) vasospasm. Methods Serum and CSF concentrations of big endothelin (ET)–1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET–1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET–1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET–1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgery-treated, 1.84 ± 0.83 pg/ml; and embolization-treated 2.19 & plusmn; 0.54 pg/ml) and without (microsurgery-treated 1.76 & plusmn; 0.61 pg/ml; and embolization-treated 2.01 ± 0.48 pg/ml) delayed infarctions. Conclusions Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET–1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET–1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.

Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy

✓ Previous studies on the initial nonoperative management of aneurysmal subarachnoid hemorrhage (SAH) demonstrated that antifibrinolytic therapy reduced the risk of rebleeding by approximately 50%; however, prolonged antifibrinolytic treatment was associated with an increase in the incidence of hydrocephalus and delayed ischemic deficit. When early surgical intervention became routine for ruptured aneurysms, the use of antifibrinolytic therapy diminished. However, early surgery is generally performed in the first several days after SAH and the risk of rebleeding remains until the aneurysm is obliterated. Based on a review of the literature, the authors formed two hypotheses: 1) the high-dose intravenous administration of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, might reduce the risk of recurrent hemorrhage in the interval between SAH and early surgical intervention, and 2) a short course of EACA might not produce the increase in complications previously associated with its prolonged administration. The use of preoperative high-dose EACA therapy was evaluated in 307 patients to determine its safety and efficacy in reducing the incidence of rebleeding before early aneurysm surgery. All patients were admitted within 3 days of their SAH and were classified as Hunt and Hess Grades I to III. Only four patients (1.3%) suffered a recurrent hemorrhage. This compares favorably to the rebleeding rate of 5.7% reported for the early surgery group in the International Cooperative Study on the Timing of Aneurysm Surgery. The incidence of hydrocephalus or symptomatic vasospasm was not unduly elevated in patients receiving preoperative EACA. Thirty-five patients (11.4%) needed temporary cerebrospinal fluid drainage during their hospitalization and, overall, 8.8% required a ventriculoperitoneal shunt. The mean age of the patients who required a shunt was nearly 10 years older than the general study population. Seventy-one patients (23%) developed symptomatic vasospasm and 8.1% suffered a stroke. This study indicates that a brief course of high-dose EACA is safe and may be beneficial in diminishing the risk of rebleeding in good-grade patients prior to early surgical intervention. Further investigation is planned based on these promising results.