Macquarie Neurosurgery Debate May 2012 Leon Lai
Key PointsStudy: 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 ofsurface cooling) or normothermia; target temp must reach before first clip appliedParticipants: 1001 patients 18yrs+; SAH WFNS score of I, II, or III, surgerywithin 14 days; preop Rankin score of 0 or 1.Excluded: pregnant; obese BMI>35; cold related disorder; already intubatedOutcome measure: GOS, Rankin scale, BI, NIH Stroke scale assessed at 90days after surgery
Randomisation: A permuted-block scheme; stratification according to the centreand 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 bytelephone-accessed computer system anaesthetist given opaque envelopecontaining treatment assignment. Envelope opened only after the induction.Blinding: Only the anaesthetist knows the treatment assignmentIncomplete outcome data: 1 patient lost to follow up out of 1001 patients hadlittle influence on the effect assessment.
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’ ConclusionMild hypothermia in the intraop period has no beneficial effects on patientoutcomeSubgroup analyses showed mild hypothermia is beneficial in the delayed surgicalgroup (8 to 14 days) or men, but effect is lost when adjusted to other factors.
CritiquesOriginality of Study (Hindman 1999, Todd 2005, Chouhan 2006)Objective: to address an important questionParticipants: well matched for age, sex, WFNS and fisher grades, time tosurgery, even aneurysm location inclusion/exclusionRisk of bias: low risk randomization (permuted block) allocation blinding completeness of study
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 calculationsLimitations: 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
ConclusionHigh quality study on good grade SAH patients intraop mild hypothermia doesnot show a clear benefit for patient outcomesThere is no evidence that intraop mild hypothermia is harmfulIn patients with poor grade SAH, there were insufficient data to draw anyconclusionsA study on the effect of intraop mild hypothermia in poor grade SAH patients isfeasible