PERIOPERATIVE BETA BLOCKERS

Preoperative evaluation

• Is the patient already on a beta-blocker for cardiovascular indication?  If so, then plan to continue perioperatively.
• Consider starting in vascular surgery patients with CAD or multiple clinical risk factors.  Which beta-blocker to use remains controversial.  Most likely need to start at least a week prior to surgery.

AHA guidelines (2009): (Ref 1)
Class I:	(A) Continue in those already receiving them for angina, arrhythmia, HTN.
Class IIa:	(A) Vascular surgery in patients with CAD. (B) Vascular surgery with multiple clinical risk factors.  (C) CHD or multiple clinical risk factors, undergoing intermediate to high risk procedures.

Postoperative management

• Continue beta-blockers in patients receiving them preop for cardiovascular indications.  Watch for hypotension and bradycardia.

Discussion
Our position:  In light of the current data, we do not recommend providing beta-blockers purely in an attempt to reduce perioperative cardiac complications in patients who are not already receiving them for cardiovascular indications.  There is insufficient evidence of benefit, and ample evidence of harm.  This is in line with AHA class I guidelines.  Use in class IIa situations should be considered on an individual basis. 

Which beta-blocker to use:  Most of the positive studies used bisoprolol or atenolol, and some of the negative studies used metoprolol.  However, it is difficult to draw conclusions given the different patient populations and dosing regimens.

When to start:  The POISE trial showed that a high dose beta blocker regimen started immediately before surgery increases stroke and mortality. (Ref 2) A cohort study found that patients on chronic beta blocker therapy had fewer cardiovascular events than those who only received beta-blockers postop, but this was not a randomized trial, and the indications for starting postop beta-blockers were unknown. (Ref 3) A recent analysis in vascular surgery patients suggest that benefit in a composite cardiovascular endpoint was seen if beta-blockers were started at least a week before surgery. (Ref 4)  Whether this finding remains true of solely “hard” cardiovascular endpoints, or may be generalized to other populations or with different beta-blockers, is uncertain. 

History:  There has been an evolution in the literature regarding the use of perioperative beta-blockers.

• In 1996, a study of 200 patients with known CAD or multiple CAD risk factors found that those randomized to atenolol immediately before surgery had reduced mortality at 2 years—however there were concerns at the randomization, lack of intention-to-treat analysis, and lack of early clinical outcome difference. (Ref 5)
• An unblinded 1999 study randomized patients with a positive dobutamine stress echo undergoing vascular surgery to bisoprolol versus usual care, and found a decrease in death or nonfatal MI at 30 days.  Notably, this was a high risk group of patients with a placebo rate of death or nonfatal MI of 34%. (Ref 6)
• These two studies, among others, led to the increased use of perioperative beta-blockers in both high risk patients undergoing vascular surgery, as well as patients with cardiac risk factors undergoing noncardiac surgery.
• In 2005 a retrospective cohort study examined over 600,000 patients and found that beta-blockers may cause harm in patients who were of low cardiac risk based on risk factors from the Revised Cardiac Risk Index. (Ref 7) A meta-analysis that same year was inconclusive as to whether there was any benefit to perioperative beta-blockers, but did find an increased rate of bradycardia and hypotension. (Ref 8)
• AHA guidelines as of June 2006 recommended as class I indications to continue beta-blockers in those patients already receiving them for angina, arrhythmia, or hypertension, and for vascular surgery patients with a positive preoperative stress test.  Other indications were class IIa. 
• In May 2008 the POISE trial results were published. (Ref 2) Over 8000 patients not previously on a beta blocker with CAD, PVD, stroke, CHF within 3 yrs, major vascular surgery, or 3 of 7 RFs ( intrathoracic/intraperitoneal surgery, TIA, CHF, DM, Cr >2, age >70, emergent/urgent surgery) undergoing noncardiac surgery were randomized to a regimen of high dose oral and/or IV metoprolol immediately before and after surgery.  There was a decrease in the composite end point of cardiovascular death, nonfatal MI, or nonfatal cardiac arrest (5.8% versus 6.9%) at 30 days, driven mainly by the decrease in nonfatal MI.  However, there was increased hypotension, bradycardia, stroke, and total mortality.  Some argue that the dose and dose-titration regimen of beta-blocker was too high; consider however that a lower dose regimen with negative results may have been interpreted as simply not achieving adequate beta blockade.
• In November 2008 a systematic review concluded that there was insufficient evidence to support the use of perioperative beta-blockers in patients who were not already on them for cardiovascular indications. (Ref 9) This review’s results were dominated by the POISE trial, as it was by far the largest in number of participants.
• The AHA published updated guidelines in 2009 changing the vascular surgery recommendation from class I to class IIa.  The other class IIa recommendations are unchanged.   The class IIb recommendations remain, including patients with fewer risk factors.  A class III recommendation (i.e. recommendation against) was added as follows: “Routine administration of high-dose beta-blockers in the absence of dose titration is not useful and may be harmful to patients not currently taking beta-blockers who are undergoing noncardiac surgery.” (Ref 1) Therefore, it appears that the AHA guidelines have recommended against duplicating a POISE protocol, but did not significantly expand the caution in perioperative beta-blocker use.

 

References:

• 1. Fleisher LA, Beckman JA, Brown KA, et al.  2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 2009;120;e169-e276.
• 2. POISE study group, Devereaux PJ, Yang H, et al.  Effects of Extended-Release Metoprolol Succinate in Patients Undergoing Non-Cardiac Surgery (POISE Trial): A Randomised Controlled Trial.  Lancet.  2008;371:1839-1847.
• 3. Ellenberger C, Tait G, Beattie WS.  Chronic Beta Blockade is Associated with a Better Outcome after Elective Noncardiac Surgery than Acute Beta Blockade.  Anesthesiology 2001; 114: 817-823. 
• 4. Flu WJ, van Kuijk JP, Chonchol M, et al.  Timing of Pre-Operative Beta-Blocker Treatment in Vascular Surgery Patients.  J Am Coll Cardiol 2010; 56: 1922-1929.
• 5. Mangano DT, Layug EL, Wallace A, et al.  Effect of Atenolol on Mortality and Cardiovascular Morbidity after Noncardiac Surgery.  N Engl J Med.  1996;335:1713-1720.
• 6. Poldermans D, Boersma E, Bax JJ, et al.  The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery.  N Engl J Med.  1999;341:1789-1794.
• 7. Lindenauer PK, Pekow P, Wang K, et al.  Perioperative Beta-Blocker Therapy and Mortality after Major Noncardiac Surgery.  N Engl J Med.  2005;353:349-361.
• 8. Devereaux PJ, Beattie WS, Choi PT, et al.  How Strong is the Evidence for the use of Perioperative Beta Blockers in Non-Cardiac Surgery? Systematic Review and Meta-Analysis of Randomised Controlled Trials.  BMJ.  2005;331:313-321.
• 9. Bangalore S, Wetterslev J, Pranesh S, et al.  Perioperative Beta Blockers in Patients Having Non-Cardiac Surgery: A Meta-Analysis.  Lancet.  2008;372:1962-1976.

 

 

Updated May 2011