Subarachnoid hemorrhage (SAH) is a common fetal cerebrovascular disease. Its annual incidence is 2–32 cases per 100,000 population, and contributes to 5% of stroke cases [1, 2]. More than 85% of SAH are caused by aneurysms . Poor grade aneurysmal subarachnoid hemorrhage (PGASAH) , is classified as Grade IV and V and accounts for approximately 20-40% of patients with SAH . The prognosis of PGASAH is extraordinarily poor. More than 60% patients will become dependent or will die [5, 6]. Without surgical intervention, the mortality rate of PGASAH can reach more than 90% .
Neurosurgical clipping and endovascular coiling are considered two main treatments for patients with intracranial aneurysm. Whether patients with aneurysms can benefit from surgery is still controversial, especially for those with PGASAH, which is the most critical subtype of SAH. In 2003, Maurice-Williams RS asserted the history of aneurysm surgery would end with experienced neurosurgeons is draining away as a result of death and retirement . However, the truth of the matter was quite different.
Previous trials have been performed to compare the prognosis of neurosurgical clipping and endovascular coiling. The most significant study is the International Subarachnoid Aneurysm Trial (ISAT) conducted by Molyneux et al. . Two thousand one hundred forty three patients with aSAH were randomly divided into neurosurgical clipping (n = 1070) or endovascular treatment. Outcomes at 1 year indicated that although the rebleeding rate was more common after endovascular coiling than neurosurgical clipping, endovascular coiling resulted in better clinical outcomes.
However, some flaws existed in the ISAT study. First, optimal timing of surgery may not have been considered, because a 14 hours lapse in the intervention timing of the two treatments. Second, the study excluded more cases that were suitable for neurosurgical clipping. Third, the study didn’t include middle cerebral aneurysms. Fourth, long-term follow-up outcomes were unknown. Fifth, The ISAT study ignored a selection bias, with major surgical intervention centers in the United States and Japan being excluded . Furthermore, the ISAT Collaborative Group distinctly known that the number of patients younger than 40 years or older than 70 years was small, no consistent trend for age was observed. And a limited number of patients with PGASAH were enrolled in the ISAT study . So, the conclusion that patients with aSAH who received endovascular coiling showed a better clinical outcome than those received neurosurgical clipping should be suspected.
The timing of surgical intervention for SAH has been debated worldwide. Pros and cons exist for patients with PGASAH who received different timing of surgery. PGASAH patients are more prone to encounter rebleeding than patients in good clinical condition [11–14]. Early surgery can secure the aneurysm neck to avoid rebleeding which would cause irreparable outcomes, and reduce disability rate and mortality . If the patient receives early surgery, triple-H therapy can be performed as soon as possible to avoid vasospasm postoperatively [14, 15]. However, in early surgery, serious cerebral edema may cause brain injury, postoperative hemorrhage, difficult exposure of the aneurysm intraoperatively and other operative complications . The advantages of delayed surgery include the less brain swelling and less cerebrovascular instability during the surgery. Decline in operative mortality have been associated with the operation that is relatively easy. However, the aneurysm may rupture again if surgery is delayed, thus increasing mortality .
Surgery timing for patients with PGASAH have the most uncertainty. Previous authors [5, 18–21] carried out many researches on the surgery timing of PGASAH, yet a surgery timing still remains unclear. However, till now, only one prospective randomized study has been detected. Ohman et al. randomized 216 patients with SAH in clinical Grades I to III (according to the Hunt & Hess classification) into three operation groups: acute surgery (0 to 3 days after SAH), intermediate surgery (4 to 7 days after SAH), or late surgery (after day 7). At 3 months post-SAH, clinical outcomes indicated that there was no difference in the prognosis of the three groups . In 2002, Ross et al. reported a study enrolled 1168 patients with SAH, and the outcomes indicated that there were no significant difference at discharge or 6 months between the early group (day 1–3), intermediate group (day 4–10) and late group (day 11–21). However, this study was only concerned with the prognosis of surgical patients, ignored the relationship between clinical grades, rebleeding and prognosis , the outcomes were widely suspected. Hutchinson et al.  reported their study with comparable outcomes, and their study contained similar shortfalls in analysis (as mentioned above). In 2002, de Gans et al. performed a systematic review, where only 11 studies, 1 randomized clinical trial and 10 observational studies, met the inclusion criteria . Meta-analysis showed that outcomes were better after early or intermediate surgery than after late surgery, for patients who were in good clinical condition at admission. For patients in poor clinical condition, results suggest only a trend toward a better outcome for early or intermediate surgery when compared with late surgery. In 2005, Nieuwkamp et al. reported an observational study, which included 411 patients. The study demonstrated that clinical prognosis of patients in poor clinical condition on admission who received early surgery was statistically better than late surgery . It is easy to detect that there is no randomized controlled trial concern about PGASAH.
The controversy over the optimum timing of surgery for patients with PGASAH has continued for many years, and evidence for the optimal timing of surgery in this condition is still insufficient. No randomized controlled trial specifically concerning PGASAH has currently been performed. We designed a trial to evaluate the prognosis of patients with PGASAH receiving surgery at different times, with the aim to identify optimal timing for surgical intervention.