Preoperative Beta-blockade: Unanswered Questions

Steven L. Cohn, Medical Director-UHealth Preoperative Assessment Center,
August 02, 2013

While I agree for the most part with the comments of Bouri et al[1] in their recent meta-analysis of preoperative beta-blockade, I believe the answers to a number of questions are not in, and the authors failed to highlight some important points. None of the "secure" trials started beta- blockers more than a day before surgery nor did they titrate the dose to control heart rate. The authors did not focus on the timing aspect, the type of beta-blocker, or the dosing and heart rate control. I agree that there is no evidence to support their use less than 1 week preoperatively, but beta-blockers do decrease perioperative ischemia and non-fatal myocardial infarctions. We don't really know whether or not mortality or stroke is increased if beta-blockers are started more than a week preoperatively and titrated to heart rate control. We do know that there appears to be a difference in beta-blockers, with metoprolol potentially being worse than bisoprolol or atenolol, in part due to different metabolism and cardioselectivity,[2] and when given shortly before surgery, metoprolol is more likely to have either no effect in rapid metabolizers or excess bradycardia and hypotension in slow metabolizers. Furthermore, the authors incorrectly described the dose of metoprolol-ER in POISE,[3] stating it was similar to the shorter acting doses of other drugs in other studies. While they gave 100 mg preoperatively, they followed that with another 100 mg within 6 hours of surgery and then another 200 mg dose 12 hours later - a total of up to 400 mg in a 24-36 hour period - much more than in the other studies. Patients on chronic beta-blockers do not appear to have an increased risk of perioperative stroke. Additionally, all meta-analyses on perioperative beta-blockade are dominated by the POISE trial, and when this study is eliminated, there is inadequate evidence for or against beta-blockers. The authors also stated that beta-blockers "caused" an increase in mortality rather than saying "were associated with" and increase in mortality. I am not aware of a proven cause and effect relationship. Ultimately it comes down to two points - 1) preoperative beta-blockade, when started shortly before surgery, reduced non-fatal MI at the expense of increased strokes and overall mortality and therefore should not be used; 2) new randomized controlled trials need to be done to evaluate the effect of preoperative beta-blockade started at least a week before surgery and titrating the dose to heart rate control. ---------------------------------------------------- 1 Bouri S, Shun-Shin MJ, Cole GD et al. Meta-analysis of secure randomized controlled trial of beta-blockade to prevent perioperative death in non- cardiac surgery. Heart Published Online First: July 31, 2013; doi:10.1136/heartjnl-2013-304262.

2 Badgett RG, Lawrence VA, Cohn SL. Variations in pharmacology of beta-blockers may contribute to heterogeneous results in trials of perioperative beta-blockade. Anesthesiology. 2010 Sep;113(3):585-92. PMID: 20693881.

3 POISE Study Group, Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. PMID: 18479744. ----------------------------------------------------

Steven L. Cohn, MD, FACP, SFHM Medical Director-UHealth Preoperative Assessment Center Director - UMH Medical Consultation Service Professor of Clinical Medicine University of Miami Miller School of Medicine Email: scohn@med.miami.edu

Conflict of Interest:

None declared

Conflict of Interest

None declared