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Todd MM, et al. "Mild intraoperative hypothermia during surgery for intracranial aneurysm". The New England Journal of Medicine. 2005. 352(2):135-145.
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Clinical Question

In patients with recent, favorable grade subarachnoid hemorrhage undergoing aneurysm clipping, does intraoperative hypothermia to 33°C versus normothermia improve post-operative neurologic outcome?


Bottom Line

Hypothermia to 33°C during craniotomy for ruptured aubarachnoid neurysm does not improve outcome 90 days post-op when compared to intra-operative normothermia.

Major Points

A few paragraphs summarizing the clinical question, the study itself, and how to apply it to practice. A simple approach is to use the first paragraph to discuss the background, use the second paragraph to discuss the study design and outcomes, and the third paragraph for interpretation which should incorporate criticisms, meta-analyses, and review-type content.



  • Trial type: multi-center, prospective, randomized, partially blinded
    • All study personnel blinded, except the anesthesiologists involved in intraoperative care
    • Randomization stratification: time between subarachnoid hemorrhage and surgery (0 to 7 days or 8 to 14 days); center performing operation
  • N=1001
    • Experimental arm (intra-operative hypothermia, target temperature 33°C): n = 499
    • Standard (intra-operative normothermia, target temperature 36.5°C): n = 501
    • Lost to follow-up: n = 1
  • Setting: 30 centers (US, Canada, UK, Australia, New Zealand, Germany, Austria)
  • Enrollment: February 2000 - April 2003
  • Mean follow-up: intended = 90 days; actual median = 88 days
  • Analysis: intention-to-treat
  • Primary outcome: rates of "good" outcomes compared between normothermia and hypothermia groups
    • "Good outcome" = Score of 1 on Glascow Outcome Scale (mild or no disability) at 90 days post-op


Inclusion Criteria

  • 18 years of age
  • SAH demonstrated radiographically within 14 days of surgery
  • WFNS score of of I, II, or III (“good grade”)
    • WFNS = World Federation of Neurological Surgeons
    • Grade verified in operating room
  • Rankin score of 0 (no neurologic disability) or 1 (mild disability) before hemorrhage

Exclusion Criteria

  • Pregnancy
  • BMI > 35
  • Cold-related disorder
  • Endotracheal tube in place

Baseline Characteristics

  • No statistically or clinically significant differences between groups.
  • WFNS score, Fisher Grade, and hydrocephalus assessed and equivalent between groups
  • Nimodipine administered in all but one study patient

From the hypothermia group.

  • Age: 55 +/- 12 yrs
  • Race/ethnicity: 80% white
  • Current smoker: 54%
  • Time from SAH to surgery: 3 +/- 3 days (median = 2 days)


After intubation, patients assigned to the hypothermia arm were cooled to between 32.5 and 33.5 degrees Celsius by the time the first clip was applied. Rewarming of these patients was performed after the last aneurysm clip was secured. Patients assigned to the normothermia group were kept between 36 and 37 degrees Celsius.


Primary Outcome

Patients were assigned a 90-day Glasgow Outcome Scale score, and were also assessed by the Rankin scale, the Barthel index, and the NIH stroke scale, as well a battery of neuropsychological examinations.

Secondary Outcomes


Subgroup Analysis

Any differences noted originally noted in the primary analysis were no longer noted after outcomes were adjusted for differences in factors prior to randomization, covariates such as age.

Adverse Events

A total of 106 predefined adverse events or procedures were monitored. Special attention was paid to events related to neurologic injury, myocardial dysfunction, coagulation, and infection.

Higher rate of bacteremia in the hypothermic group.


  • Cooling limited to intraoperative period
  • Slow initiation/rate of cooling
  • Potential discrepancy between monitored esophageal temperature and actual brain temperature
  • Lack of control of postoperative care
  • Restriction of study to patients with good preoperative grade


Supported by a grant from the National Institute of Neurological Disease and Stroke (RO1 NS38554)

Further Reading