Macquarie Neurosurgery Debate

Leon Lai

May 2012

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

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.

Feb 2000-April 2003

Results

WELL MATCHED

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)

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.

Critiques

Originality of Study (Hindman 1999, Todd 2005, Chouhan 2006)

Participants: well matched for age, sex, WFNS and fisher grades, time to surgery, even aneurysm location

inclusion/exclusion

Objective: to address an important question

Risk of bias: low risk randomization (permuted block) allocation blinding completeness of study

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

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

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