Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST)

Abstract

New neurologic deficits may occur after intracranial vascular surgery, even in the absence of overt complications. Consequently, several efforts have emerged in an attempt to protect the brain intraoperatively. Systemic hypothermia is one such protective adjunct that was first reported in the 1950's. Although this technique was essentially abandoned in the decades that followed, interest returned after mild hypothermia was shown to improve outcomes in experimental models of cerebral ischemia. Hypothermia has since been implemented in the treatment of head trauma, stroke, and cardiac arrest. The benefit of hypothermia during neurovascular surgery, however, remains controversial. Dr. Michael Todd and colleagues recently completed their Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) and presented their results at the Society for Neuroanesthesia and Critical Care (October 2004, Las Vegas, NV). A full scale report is expected to be published in the New England Journal of Medicine sometime in 2005. In this large, prospective, international, multicenter, and blinded study, 1001 patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) in good clinical grade (WFNS score of I, II, or III) were randomized to either intraoperative hypothermia (target temperature 33 degrees Celsius, using surface cooling techniques) or normothermia (target temperature 36.5 degrees Celsius) during aneurysm surgery. Exclusion criteria included a pre-hemorrhage Rankin Disability Score greater than 1, body mass index >35kg/m2, cold-related disorders, or endotracheal intubation at the time of enrollment. Outcome was assessed at 90 days postoperatively, primarily using the Glasgow Outcome Score (GOS). No significant differences in outcome measures was found between groups and, as a result, the authors concluded that intraoperative hypothermia does not improve neurologic outcome following craniotomy for intracranial aneurysm surgery. Furthermore, there was a suggestion that postoperative bacteremia may be more common in the hypothermic group, even though there was no difference in pneumonia, UTI, meningitis, or wound infection rate. Based on these findings, there appears to be minimal, if any, benefit to intraoperative hypothermia during aneurysm surgery. These results appear robust, considering the study design, sample size, cohort similarities, adjudicated outcomes, protocol compliance, and near-perfect follow-up. There are limitations to this investigation, however, that must be taken into account when interpreting the authors' findings. First, subgroup analysis of the data suggests a beneficial effect of intraoperative hypothermia when this technique is used in males and patients undergoing late surgery (8-14 days after initial aSAH). While these are secondary calculations without patient randomization and small sample sizes, future studies are warranted for clarification. Secondly, GOS, although widely used and universally accepted, is a relatively crude measurement of clinical outcome that may not detect subtle cognitive changes. This issue will be resolved once the outcomes from this trial's neuropsychiatric examinations are released. Furthermore, the findings of this investigation do not apply to all aSAH patients, as only those in good clinical grade were included. Closer inspection of the results reveals intraoperative hypothermia led to absolute and relative improvements in GOS 1 of 3.2% and 5.0%, respectively. This study, however, was only designed to identify absolute and relative improvements in GOS 1 of 10.0% and 15.0%, respectively. Thus, even with 1000 patients enrolled, this investigation may have been underpowered to detect the benefit of intraoperative hypothermia. To address this issue, future trials would ideally examine the effects of intraoperative hypothermia exclusively in patients with temporary clips placed for various durations, as hypothermia is intended to prolong cerebral tolerance during ischemic episodes. It is difficult, however, to endorse another expanded randomized trial, as the downside of mild intraoperative hypothermia appears trivial given the data on bleeding and cardiovascular instability from IHAST. Perhaps a more likely outcome is that surgeons will increasingly employ hypothermia in a selective manner in those cases in which prolonged ischemia is anticipated. The problem with such an approach is knowing exactly who is going to have a problem before it happens. While experience has shown that larger lesions, especially those with intraluminal thrombus or calcification, are more likely to require longer ischemia times, even the most straight-forward lesion can surprise. Without definitive data regarding the benefit of intraoperative hypothermia during aneurysm surgery, the use of this technique will continue to be determined by clinical judgment, individual case circumstances, and surgeon preference. RICARDO J. KOMOTAR, MD JESS E. JONES, BA E. SANDER CONNOLLY, JR., MD TECHNICAL & CLINICALRESEARCH