Among the many variables that influence outcomes in acute subarachnoid hemorrhage resulting from a ruptured cerebral aneurysm (aSAH), the three most consistent predictors of a dismal outcome are poor initial clinical presentation, advanced age, and aneurysm rebleeding . As a result, the management of aSAH is focused largely on securing the culprit aneurysm from future rehemorrhage. Craniotomy with clipping and endovascular coil embolization (embosurgery) are both effective in this regard, although the landmark International Subarachnoid Aneurysm Trial demonstrated superior short- and long-term outcomes for embosurgery .
Because rebleeding represents the major preventive cause of death and disability, obliterating the aneurysm in a timely fashion would therefore appear prudent. Unfortunately, unfavorable cofactors often exist to delay surgery, including worsening clinical grade and developing hydrocephalus. Most surgeons are loath to operate on patients who are likely to die despite their efforts; therefore, waiting a day or more to stabilize the patient is a common reason frequently invoked for delaying surgery, especially in the elderly and poorer clinical grade patients with aSAH. Compounding this clinical caveat, a substantial body of research has repeatedly found that the timing of clipping surgery is critical in avoiding additional patient morbidity . Specifically, clipping during days 0–2 or after day 10 following aSAH has better outcomes compared to surgery performed between days 4–6. This reflects the influence of cerebral arterial vasospasm, which typically occurs in the 4- to 10-day window, and which exacerbates operative ischemia because of retraction and anesthesia. Because of this temporal nuance, important questions are raised in the post-International Subarachnoid Aneurysm Trial era. First, does the timing of embosurgery improve patient outcomes by eliminating aneurysm rebleeding if performed within 24 hours? Second, could the timing of embosurgery introduce an unanticipated risk parameter for the patient?
The article by Gu et al in this issue contributes important data to the quite limited understanding of the timing of embosurgery . Gu et al identified slightly improved outcomes for patients older than 69 years who had embosurgery within 24 hours of aSAH compared to embosurgery after this time. The significance between these two groups of patients was admittedly marginal ( p = .032), corresponding to a 1 in 31 probability that the findings were due to chance. Had only one patient from either group crossed over, the study’s conclusion would be quite different, showing no statistical difference between the two groups ( p > .05). Recently, Phillips et al likewise found a borderline credible ( p = .04) improvement in adults (mean age, 52 years) with aSAH who had ultra-early embosurgery within 24 hours compared to patients treated on days 1–3 .
The apparent association of improved outcomes for ultra-early embosurgery noted by the Gu and Phillips teams should be considered in light of the findings of similar sized cohort studies by Baltsavius et al and Lawson et al . Lawson evaluated outcomes after embosurgery on days 0–3 and days 4–10, whereas Baltsavius compared embosurgical results for days 0–2, days 3–10, and days 11–30. Neither Baltsavius nor Lawson detected any difference in outcomes for patients with aSAH and the timing of embosurgery; however, the ultra-early subgroup analysis of embosurgery was not addressed. Nevertheless, in considering all four of these observational, nonrandomized cohorts that included elderly patients, one can reasonably suggest that a trend may exist for improved outcomes of ultra-early embosurgery in patients with aSAH.
Selection bias most assuredly impacts the validity of these investigations by Gu and the others. Although this problem is acknowledged by the authors, its significance cannot be discounted. The used clinical grades are neurologic scores, and though they appear fairly distributed among the ultra-early and delayed embosurgery groups, other unassessed, independent predictors of poor outcomes can both directly contribute to a worse outcome while effectively delaying the clinical team from securing the aneurysm within 24 hours. These important comorbidities represent unavoidable selection biases and include deteriorating clinical grade, aneurysm rehemorrhage, seizures, uncontrolled hypertension, intraparenchymal hemorrhage, cardiac dysfunction, respiratory failure, hyperglycemia, intraventricular hemorrhage, and hydrocephalus . Acutely managing one or more of these problems can easily delay embosurgery beyond the initial 24-hour window. Any resulting adverse outcome might very well be due to the delaying factor itself, and not caused by delayed embosurgery, per se. The work by Gu and associates has succeeded in drawing attention to the need for definitive, randomized, prospective evidence in the timing of embosurgery for aSAH.
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