HYPOTHESIS: Mild intraoperative hypothermia (a body temperature ~ 33° C) will improve long term neurologic outcome (as measured by Glasgow Outcome Score) in patients with recent subarachnoid hemorrhage (SAH) undergoing open craniotomies for the clipping of intracranial aneurysms, when compared with otherwise identically managed patients who are kept normothermic (~ 36.5° C) during surgery. 

DESIGN: Prospective, randomized, multicenter trial. Patients, operating neurosurgeons and the individuals responsible for all outcome assessments will be blinded. Anesthesiologists in charge of intraoperative patient management will not be blinded. Other than intraoperative temperature and planned nimodipine therapy, other aspects of perioperative care will not be controlled. 

INCLUSION: Adult (age >= 18 years) patients with recent (<= 14 days) SAH (documented by CT- or MRI- scan, or lumbar puncture) and an angiographically documented intracranial aneurysm undergoing open craniotomies for aneurysm clipping. All patients must have nimodipine planned as part of their therapy.

EXCLUSION:
1) Pre-SAH Rankin disability score of >1. 
2) Preoperative World Federation of Neurologic Surgeons (WFNS) grade IV or V. 
3) Endotracheally intubated at the time of evaluation for study eligibility 
4) Obesity (Body Mass Index > 35.0). 
5) Cold-related disorders (e.g. cryoglobulinemia) that would serve as a contraindication to cooling. 
6) Known adverse reaction to the standardized anesthetics (e.g. malignant hyperthermia). 

PRE-RANDOMIZATION: Seen in-hospital by Study coordinator of PI, after definitive diagnosis (usually post- angiography). Evaluated to establish eligibility and to obtain consent. If eligible, patient is enrolled with Clinical Trials Statistical & Data Management Center (CTSDMC) by phone. 

RANDOMIZATION: Randomization stratified by participating center (2 groups, normothermic and hypothermic). The number and color of a sealed envelope is provided to the local coordinator at time of the enrollment phone call to the CTSDMC (no more than 2 hr before surgery). The RANDOMIZATION ENVELOPE is opened (actual randomization) by the attending anesthesiologist only AFTER the patient is in the OR, anesthetized and positioned. 

ACCRUAL: Enrollment period ~ 3 years. 25-30 centers, enrolling ~ 30 patients per month total. 

TREATMENT: Standardized anesthetic. Hypothermic patients are surface cooled (using a refrigerated forced air unit) to a distal esophageal temperature of ~33.0°C prior to aneurysm clip placement. Warming is to begin immediately after clipping. Core temperature in normothermic patients is to remain at ~ 36.5°C throughout the procedure. All other aspects of surgery will remain as per local standards. 

FOLLOW-UP: Clinical course and neurologic status of patients followed in-hospital until discharge, or for 14 days after surgery (whichever comes first). Phone or clinic contacts at 3, 6 and 9 weeks after surgery, with a final follow-up visit and full neurologic evaluation at 3 months after surgery. 

ENDPOINTS:
PRIMARY: Glasgow Outcome Score (GOS) at 3 months postoperatively 
Secondary (at 3 months): NIH Stroke Score; Barthel Index (Activities of Daily Living); Rankin Disability Score; Mini-Mental State Exam (MMSE); 5-test Neuropsychology battery. 
Secondary (in hospital): Duration of intubation & ventilation; duration of critical care; duration of hospitalization; discharge destination. 

STATISTICS: Two-way alpha 0.05, Power 90% to detect absolute 10 percentage point improvement in GOS at 3 months (from 65% good outcome with normothermia to 75% good outcome with hypothermia. N=920 patients (460 each group). Accrual ~ 3 years. Randomization in permuted blocks, stratified by center. Intention-to-treat analysis. Interim analysis planned after completed 3 month follow-up of 300 and 600 patients. 

SAFETY: Immediate reporting of Deaths, Indicator Events (likely to be related to hypothermia: cardiac complications, coagulation abnormalities (clinical), infection), and severe or fatal Intercurrent Events (IE's). IE's reported to Clinical Coordinating Center for validation and verification. Summary IE reports forwarded to Performance, Safety, and Monitoring Board (PSMB) after each 60 patients (following submission of discharge data forms). PSMB will be blinded as to 3-month outcome at all times. PSMB will be blinded regarding group assignment unless unblinding requested (p<0.1 for any event, majority vote). In event of p<0.05, PSMB will report to NIH DSMC.