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

TY - JOUR

T1 - Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

AU - Juul, Anne Benedicte

AU - Wetterslev, Jørn

AU - Gluud, Christian

AU - Kofoed-Enevoldsen, Allan

AU - Jensen, Gorm

AU - Callesen, Torben

AU - Nørgaard, Peter

AU - Fruergaard, Kim

AU - Bestle, Morten

AU - Vedelsdal, Rune

AU - Miran, André

AU - Jacobsen, Jon

AU - Roed, Jakob

AU - Mortensen, Maj-Britt

AU - Jørgensen, Lise

AU - Jørgensen, Jørgen

AU - Rovsing, Marie-Louise

AU - Petersen, Pernille Lykke

AU - Pott, Frank

AU - Haas, Merete

AU - Albret, Rikke

AU - Nielsen, Lise Lotte

AU - Johansson, Gun

AU - Stjernholm, Pia

AU - Mølgaard, Yvonne

AU - Foss, Nikolai Bang

AU - Elkjaer, Jeanie

AU - Dehlie, Bjørn

AU - Boysen, Klavs

AU - Zaric, Dusanka

AU - Munksgaard, Anne

AU - Madsen, Jørn Bo

AU - Øberg, Bjarne

AU - Khanykin, Boris

AU - Blemmer, Tine

AU - Yndgaard, Stig

AU - Perko, Grazyna

AU - Wang, Lars Peter

AU - Winkel, Per

AU - Hilden, Jørgen

AU - Jensen, Per

AU - Salas, Nader

AU - DIPOM Trial Group

AU - Juul, AB

AU - Wetterslev, J

AU - Gluud, C

AU - Jensen, Gorm

AU - Foss, Nikolai Bang

AU - Pott, Frank

AU - Zaric, Dusanka

AU - Jensen, Per

AU - DIPOM Trial Group

N1 - Keywords: Adrenergic beta-Antagonists; Adult; Aged; Delayed-Action Preparations; Diabetes Complications; Double-Blind Method; Female; Hemodynamics; Humans; Intraoperative Care; Male; Metoprolol; Middle Aged; Patient Compliance; Surgical Procedures, Operative; Treatment Outcome

PY - 2006/6/24

Y1 - 2006/6/24

N2 - Objectives To evaluate the long term effects of perioperative 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 [controlled-trials.com] .

AB - Objectives To evaluate the long term effects of perioperative 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 [controlled-trials.com] .

U2 - 10.1136/bmj.332.7556.1482

DO - 10.1136/bmj.332.7556.1482

M3 - Journal article

C2 - 16793810

SN - 0959-8146

VL - 332

SP - 1482

JO - B M J

JF - B M J

IS - 7556

ER -