title: Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.
abstract: OBJECTIVE
  To evaluate the long term effects of perioperative beta blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery.
  
  
  METHODS
  Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat.
  
  
  METHODS
  University anaesthesia and surgical centres and one coordinating centre.
  
  
  METHODS
  921 patients aged > 39 scheduled for major non-cardiac surgery.
  
  
  METHODS
  100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days.
  
  
  METHODS
  The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity.
  
  
  RESULTS
  Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (- 0.8% to 5.6%).
  
  
  CONCLUSIONS
  Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN58485613.
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet, Copenhagen University Hospital, Denmark. anne.j@ctu.rh.dk
authors.forename: Anne Benedicte
authors.initials: AB
authors.lastname: Juul
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.forename: Allan
authors.initials: A
authors.lastname: Kofoed-Enevoldsen
authors.forename: Gorm
authors.initials: G
authors.lastname: Jensen
authors.forename: Torben
authors.initials: T
authors.lastname: Callesen
authors.forename: Peter
authors.initials: P
authors.lastname: Nørgaard
authors.forename: Kim
authors.initials: K
authors.lastname: Fruergaard
authors.forename: Morten
authors.initials: M
authors.lastname: Bestle
authors.forename: Rune
authors.initials: R
authors.lastname: Vedelsdal
authors.forename: André
authors.initials: A
authors.lastname: Miran
authors.forename: Jon
authors.initials: J
authors.lastname: Jacobsen
authors.forename: Jakob
authors.initials: J
authors.lastname: Roed
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Mortensen
authors.forename: Lise
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jørgensen
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Rovsing
authors.forename: Pernille Lykke
authors.initials: PL
authors.lastname: Petersen
authors.forename: Frank
authors.initials: F
authors.lastname: Pott
authors.forename: Merete
authors.initials: M
authors.lastname: Haas
authors.forename: Rikke
authors.initials: R
authors.lastname: Albret
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Nielsen
authors.forename: Gun
authors.initials: G
authors.lastname: Johansson
authors.forename: Pia
authors.initials: P
authors.lastname: Stjernholm
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Mølgaard
authors.forename: Nikolai Bang
authors.initials: NB
authors.lastname: Foss
authors.forename: Jeanie
authors.initials: J
authors.lastname: Elkjaer
authors.forename: Bjørn
authors.initials: B
authors.lastname: Dehlie
authors.forename: Klavs
authors.initials: K
authors.lastname: Boysen
authors.forename: Dusanka
authors.initials: D
authors.lastname: Zaric
authors.forename: Anne
authors.initials: A
authors.lastname: Munksgaard
authors.forename: Jørn Bo
authors.initials: JB
authors.lastname: Madsen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Øberg
authors.forename: Boris
authors.initials: B
authors.lastname: Khanykin
authors.forename: Tine
authors.initials: T
authors.lastname: Blemmer
authors.forename: Stig
authors.initials: S
authors.lastname: Yndgaard
authors.forename: Grazyna
authors.initials: G
authors.lastname: Perko
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Wang
authors.forename: Per
authors.initials: P
authors.lastname: Winkel
authors.forename: Jørgen
authors.initials: J
authors.lastname: Hilden
authors.forename: Per
authors.initials: P
authors.lastname: Jensen
authors.forename: Nader
authors.initials: N
authors.lastname: Salas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D048909:Diabetes Complications; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010349:Patient Compliance; D013514:Surgical Procedures, Operative; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol