Timing of Intervention

Aneurysms are at highest risk for re-rupture in the first 24 hours following the initial hemorrhage. Consequently, the natural instinct has been to exclude aneurysms from the systemic circulation as early as possible to prevent rebleeding and allow aggressive treatment of vasospasm. However, early surgery is complicated by theoretical concerns of increased surgical morbidity and mortality due to the edematous and inflamed state of the brain and the presence of diffuse, thick blood in the operative field. Clinical trials, therefore, have sought to determine whether the timing of surgery affects outcomes (1).

In the only randomized, prospective trial of the timing of aneurysmal surgery (2), 216 patients with anterior circulation aneurysms and Hunt and Hess Grades I to III were assigned to either early (zero to three days), intermediate (four to seven days), or late (more than seven days) surgery. The researchers reported significantly better clinical outcomes (functional and mortality) in the early-surgery group than in the intermediate- and late-surgery groups. Even though mortality was 5.6% in the early-surgery group, it was 12.9% in the late-surgery group. Likewise, those who underwent early surgery had a higher rate of functional independence at three months than did other patients. Unfortunately, the number of patients studied was small and did not include all SAH patients. Therefore, some view these results with reservation.

The International Cooperative Study on the Timing of Aneurysm Surgery is the largest clinical trial to date addressing this issue. It was an international prospective, observational clinical trial that observed 3521 patients who had either early or late surgery (0-3 or 11-14 days, respectively) (3). Despite theories of the benefit of early surgery to prevent rebleeding, the results indicated no significant differences in functional outcomes or death between early and late surgery; the risks of early surgery were equivalent to the risks of rebleeding and vasospasm that are associated with late surgery. However, a subanalysis of the North American patients in this trial (772 patients) suggested an improved rate of good clinical outcomes in the early-surgery group and nearly twice the mortality in the late-surgery group (4). The lack of randomization in these trials calls into question the possibility of selection bias in the observed outcomes. Nevertheless, for a combination of reasons, early surgery or endovascular coiling has been adopted as the preferred contemporary management plan to prevent early rebleeding. The true benefit of early surgery might never be clarified, as further randomized clinical trials to study the timing of aneurysmal surgery are unlikely for ethical considerations (1 ).

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