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Effect of perioperative β blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

BMJ 2006; 332 doi: (Published 22 June 2006) Cite this as: BMJ 2006;332:1482
  1. Anne Benedicte Juul, research fellow (anne.j{at},
  2. J⊘rn Wetterslev, chief physician1,
  3. Christian Gluud, head of department1,
  4. Allan Kofoed-Enevoldsen, chief physician in endocrinology2,
  5. Gorm Jensen, head of department3,
  6. Torben Callesen, consultant in anaesthesiology4,
  7. Peter N⊘rgaard, consultant in anaesthesiology5,
  8. Kim Fruergaard, consultant in anaesthesiology5,
  9. Morten Bestle, consultant in anaesthesiology5,
  10. Rune Vedelsdal, consultant in anaesthesiology6,
  11. André Miran, registrar in anaesthesiology6,
  12. Jon Jacobsen, consultant in anaesthesiology7,
  13. Jakob Roed, consultant in anaesthesiology7,
  14. Maj-Britt Mortensen, senior registrar in anaesthesiology7,
  15. Lise J⊘rgensen, senior registrar in anaesthesiology4,
  16. J⊘rgen J⊘rgensen, senior registrar in anaesthesiology8,
  17. Marie-Louise Rovsing, senior registrar in anaesthesiology8,
  18. Pernille Lykke Petersen, senior registrar in anaesthesiology8,
  19. Frank Pott, senior registrar in anaesthesiology8,
  20. Merete Haas, senior registrar in anaesthesiology8,
  21. Rikke Albret, senior registrar in anaesthesiology8,
  22. Lise Lotte Nielsen, senior registrar in anaesthesiology8,
  23. Gun Johansson, consultant in anaesthesiology9,
  24. Pia Stjernholm, consultant in anaesthesiology7,
  25. Yvonne M⊘lgaard, senior registrar in anaesthesiology7,
  26. Nikolai Bang Foss, senior registrar in anaesthesiology3,
  27. Jeanie Elkjær, senior registrar in anaesthesiology3,
  28. Bj⊘rn Dehlie, senior registrar in anaesthesiology3,
  29. Klavs Boysen, consultant in anaesthesiology10,
  30. Dusanka Zaric, consultant in anaesthesiology10,
  31. Anne Munksgaard, senior registrar in anaesthesiology10,
  32. J⊘rn Bo Madsen, chief physician in anaesthesiology4,
  33. Bjarne Øberg, consultant in anaesthesiology4,
  34. Boris Khanykin, senior registrar in anaesthesiology4,
  35. Tine Blemmer, senior registrar in anaesthesiology11,
  36. Stig Yndgaard, consultant in anaesthesiology4,
  37. Grazyna Perko, senior registrar in anaesthesiology4,
  38. Lars Peter Wang, consultant in anaesthesiology4,
  39. Per Winkel, consultant statistician1,
  40. J⊘rgen Hilden, statistician12,
  41. Per Jensen, statistician12,
  42. Nader Salas, data manager, DIPOM Trial Group1
  1. 1 Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet, Copenhagen University Hospital, Denmark
  2. 2 Department of Internal Medicine, Kolding Fredericia Hospital, Denmark
  3. 3 Department of Cardiology and Anaesthesiology, H:S Hvidovre Hospital Copenhagen University Hospital, Denmark
  4. 4 Department of Anaesthesiology, H:S Rigshospitalet, Copenhagen University Hospital, Denmark
  5. 5 Department of Anaesthesiology, KAS Gentofte, Copenhagen University Hospital, Denmark
  6. 6 Department of Anaesthesiology, KAS Herlev Hospital, Copenhagen University Hospital, Denmark
  7. 7 Department of Anaesthesiology, KAS Glostrup, Copenhagen University Hospital, Denmark
  8. 8 Department of Anaesthesiology, H:S Bispebjerg Hospital, Copenhagen University Hospital, Denmark
  9. 9 Department of Anaesthesiology, Amager Hospital, Copenhagen University Hospital, Denmark
  10. 10 Department of Anaesthesiology, H:S Fredriksberg Hospital, Copenhagen University Hospital, Denmark
  11. 11 Department of Anaesthesiology, FAC Hiller⊘d, Hiller⊘d, Denmark
  12. 12 Department of Biostatistics, Faculty of Health Sciences, Copenhagen University, Denmark
  1. Correspondence to: A B Juul
  • Accepted 13 March 2006


Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery.

Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat.

Setting University anaesthesia and surgical centres and one coordinating centre.

Participants 921 patients aged > 39 scheduled for major non-cardiac surgery.

Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days.

Main outcome measures 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.

Trial registration Current Controlled Trials ISRCTN58485613 [


  • Contributors The DIPOM Trial Group consists of investigators from public hospitals in the greater Copenhagen area. Principal investigators were PN, KF, JW, RV, JJ, YM, PS, TC, LJ, JJ, GJ, NBF, KB, JBM, TB, and SY. Clinical investigators were MB, ABJ, AM, JR, M-BM, M-LR, PLP, RA, FP, MH, LLN, JE, BD, DZ, AM, BØ, LPW, BK, GP, JW, and PW. NS developed the data management systems and was responsible for data management. PJ and JH carried out statistical analyses. ABJ (coordinating investigator and guarantor), CG, JW, AKE, GJ, and TC formed the steering committee.

  • Funding AstraZeneca, Danish Heart Foundation, Danish Diabetes Foundation, Copenhagen Hospital Corporation's Research Council, Danish Medical Research Council's “Program for Strengthening Regional Collaboration within Medical Health Research,” and Copenhagen Hospital Corporation.

  • Competing interests None declared.

  • Ethical approval The trial was approved by the local ethics committee (journal No AGF/USS KA 99077ms), the Danish Medicines Agency (journal No AD-MET-0003), and the Danish Data Protection Agency.

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