• B B Abdelmalak, A Bonilla, E J Mascha, A Maheshwari, W H Wilson Tang, J You, M Ramachandran, Y Kirkova, D Clair, R M Walsh, A Kurz, and D I Sessler.
• Department of General Anaesthesiology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44102, USA. abdelmb@ccf.org. www.OR.org
• Br J Anaesth. 2013 Aug 1;111(2):209-21.

BackgroundThe inflammatory response to surgical tissue injury is associated with perioperative morbidity and mortality. We tested the primary hypotheses that major perioperative morbidity is reduced by three potential anti-inflammatory interventions: (i) low-dose dexamethasone, (ii) intensive intraoperative glucose control, and (iii) lighter anaesthesia.MethodsWe enrolled patients having major non-cardiac surgery who were ≥40 yr old and had an ASA physical status ≤IV. In a three-way factorial design, patients were randomized to perioperative i.v. dexamethasone (a total of 14 mg tapered over 3 days) vs placebo, intensive vs conventional glucose control 80-110 vs 180-200 mg dl(-1), and lighter vs deeper anaesthesia (bispectral index target of 55 vs 35). The primary outcome was a collapsed composite of 15 major complications and 30 day mortality. Plasma high-sensitivity (hs) C-reactive protein (CRP) concentration was measured before operation and on the first and second postoperative days.ResultsThe overall incidence of the primary outcome was about 20%. The trial was stopped after the second interim analysis with 381 patients, at which all three interventions crossed the futility boundary for the primary outcome. No three-way (P=0.70) or two-way (all P>0.52) interactions among the interventions were found. There was a significantly smaller increase in hsCRP in patients given dexamethasone than placebo [maximum 108 (64) vs 155 (69) mg litre(-1), P<0.001], but none of the other two interventions differentially influenced the hsCRP response to surgery.ConclusionsAmong our three interventions, dexamethasone alone reduced inflammation. However, no intervention reduced the risk of major morbidity or 1 yr mortality. TRIAL REGISTRATION IDENTIFIER: NCT00433251 at www.clinicaltrials.gov.

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