Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.
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.
Juul
Anne Benedicte
AB
Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet, Copenhagen University Hospital, Denmark. anne.j@ctu.rh.dk
Wetterslev
Jørn
J
Gluud
Christian
C
Kofoed-Enevoldsen
Allan
A
Jensen
Gorm
G
Callesen
Torben
T
Nørgaard
Peter
P
Fruergaard
Kim
K
Bestle
Morten
M
Vedelsdal
Rune
R
Miran
André
A
Jacobsen
Jon
J
Roed
Jakob
J
Mortensen
Maj-Britt
MB
Jørgensen
Lise
L
Jørgensen
Jørgen
J
Rovsing
Marie-Louise
ML
Petersen
Pernille Lykke
PL
Pott
Frank
F
Haas
Merete
M
Albret
Rikke
R
Nielsen
Lise Lotte
LL
Johansson
Gun
G
Stjernholm
Pia
P
Mølgaard
Yvonne
Y
Foss
Nikolai Bang
NB
Elkjaer
Jeanie
J
Dehlie
Bjørn
B
Boysen
Klavs
K
Zaric
Dusanka
D
Munksgaard
Anne
A
Madsen
Jørn Bo
JB
Øberg
Bjarne
B
Khanykin
Boris
B
Blemmer
Tine
T
Yndgaard
Stig
S
Perko
Grazyna
G
Wang
Lars Peter
LP
Winkel
Per
P
Hilden
Jørgen
J
Jensen
Per
P
Salas
Nader
N
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
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol