This document summarizes a study on the effects of intraoperative mild hypothermia in patients undergoing neurosurgery for subarachnoid hemorrhage. The study was a prospective randomized controlled trial including 1001 patients from 30 centers. Patients were randomly assigned to receive either intraoperative hypothermia at 33°C or normothermia at 36.5°C. The study found that mild hypothermia provided no overall benefit to patient outcomes at 90 days post-surgery compared to normothermia. However, a subgroup analysis found hypothermia may be beneficial for patients undergoing surgery 8-14 days after hemorrhage or for male patients, but these effects were lost after adjusting for other factors.

1. Macquarie Neurosurgery Debate
May 2012
Leon Lai

2. Key Points
Study: Partially blinded prospective RCTs (30 centers across USA, UK, AUS, NZ,
Canada)
Objective: to determine whether the use of intraoperative mild hypothermia (33ºC)
was associated with better outcomes, compared to normothermia (36.5ºC)
Method: Patients were randomly assigned to intraop hypotheramia (with use of
surface cooling) or normothermia; target temp must reach before first clip applied
Participants: 1001 patients 18yrs+; SAH WFNS score of I, II, or III, surgery
within 14 days; preop Rankin score of 0 or 1.
Excluded: pregnant; obese BMI>35; cold related disorder; already intubated
Outcome measure: GOS, Rankin scale, BI, NIH Stroke scale assessed at 90
days after surgery

3. Randomisation: A permuted-block scheme; stratification according to the centre
and the time between SAH and surgery (0 to 7 days or 8 to 14 days)
Allocation: patients evaluated and enrolled <2 hours before surgery; done by
telephone-accessed computer system  anaesthetist given opaque envelope
containing treatment assignment. Envelope opened only after the induction.
Blinding: Only the anaesthetist knows the treatment assignment
Incomplete outcome data: 1 patient lost to follow up out of 1001 patients had
little influence on the effect assessment.

4. Results
Feb 2000-April 2003
ED
H
ATC
M
E LL
W

7. Subgroup Analysis of Good Outcome
Hypothermia Normothermia OR (95CI)
(%) (%)
Surgery within 7 days 64 63 1.06 (0.81 to 1.40)
Surgery 8 to 14 days 83 61 2.70 (1.00 to 7.30)
Men 69 57 1.78 (1.12 to 2.84)

9. Authors’ Conclusion
Mild hypothermia in the intraop period has no beneficial effects on patient
outcome
Subgroup analyses showed mild hypothermia is beneficial in the delayed surgical
group (8 to 14 days) or men, but effect is lost when adjusted to other factors.

10. Critiques
Originality of Study (Hindman 1999, Todd 2005, Chouhan 2006)
Objective: to address an important question
Participants: well matched for age, sex, WFNS and fisher grades, time to
surgery, even aneurysm location
 inclusion/exclusion
Risk of bias: low risk
 randomization (permuted block)
 allocation
 blinding
 completeness of study

11. Statistical Methods:
 sample size (1000 patients to detect a 10% improvement)
 planned interim analyses for 357 and 655 patients
 primary outcome measure well defined
 appropriate statistical calculations
Limitations:
 Exclusion of grade IV and V WFNS SAH
 No control over postoperative period
 is mild hypothermia (33ºC) good enough?
 discrepancy between oesophageal temp and brain temp not known
 participant flow diagram

12. Conclusion
High quality study on good grade SAH patients  intraop mild hypothermia does
not show a clear benefit for patient outcomes
There is no evidence that intraop mild hypothermia is harmful
In patients with poor grade SAH, there were insufficient data to draw any
conclusions
A study on the effect of intraop mild hypothermia in poor grade SAH patients is
feasible