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Chapter 8

Perioperative Beta-Blockers

Paul B. Cornia and Christopher J. Wong

PREOPERATIVE EVALUATION Is the patient already on a beta-blocker? If so, then plan to ■

continue perioperatively. Consider starting in vascular surgery patients with CAD. ■

Whether any one beta-blocker is superior is not de fi nitively known. If prophylactic beta- blockade is started, begin well in advance of surgery ( ³ 1 week) and titrate to heart rate (60–70 bpm) while avoiding hypotension. See Table ■ 8.1 for class I and IIa indications for perioperative beta-blockers [ 1 ] .

POSTOPERATIVE MANAGEMENT Continue beta-blockers in patients receiving them preop. Watch ■

for hypotension and bradycardia.

DISCUSSION Our position : In light of the current data, we do not recommend starting a beta blocker routinely before surgery purely in an attempt to reduce perioperative cardiac complications. There is insuf fi cient evidence of bene fi t, and ample evidence of harm. This is in line with AHA class I guidelines. Use in class IIa situations should be consid-ered on an individual basis.

C.J. Wong and N.P. Hamlin (eds.), The Perioperative Medicine Consult Handbook, DOI 10.1007/978-1-4614-3220-3_8, © Springer Science+Business Media New York 2013

54 THE PERIOPERATIVE MEDICINE CONSULT HANDBOOK

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 dif fi cult to draw de fi nitive conclusions given the differ-ent patient populations and dosing regimens used in the randomized trials. Dose titration, as opposed to fi xed dose regimens, may be a more important factor than the speci fi c agent used.

When to start : The POISE trial showed that a high-dose beta-blocker regimen started immediately before surgery reduces post-op cardiac events, but increases stroke and mortality [ 2 ] . A cohort study found that patients on chronic beta-blocker therapy had fewer cardiovascu-lar events than those who only received beta-blockers post-op, but this was not a randomized trial, and the indications for starting post-op beta-blockers were unknown [ 3 ] . An analysis in vascular surgery patients suggests that bene fi t in a composite cardiovascular endpoint was seen if beta-blockers were started at least a week before surgery [ 4 ] . Whether this fi nding remains true of solely “hard” cardiovascular endpoints, or may be generalized to other populations or with differ-ent 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 regarding the randomization,

TABLE 8.1 INDICATIONS FOR PERIOPERATIVE BETA-BLOCKERS, FROM THE ACCF/AHA GUIDELINES [ 1 ]

Class I Continue in those already receiving them for angina, arrhythmia, and hypertension

Class IIa Titrate to heart rate and blood pressure in the following situations: (A) Vascular surgery in patients with CAD

(“probably recommended”) (B) Vascular surgery in patients with

multiple clinical risk factors (“reasonable”)

(C) Intermediate- to high-risk procedures in patients with CAD or multiple clinical risk factors (“reasonable”)

Adapted with permission from [ 1 ]

55CHAPTER 8: PERIOPERATIVE BETA-BLOCKERS

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lack of intention-to-treat analysis, and lack of early clinical out-come difference [ 5 ] . An unblinded 1999 study randomized patients with a positive ■

dobutamine stress echo undergoing vascular surgery to biso-prolol 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 % [ 6 ] . These two studies, among others, led to the increased use of ■

perioperative beta-blockers in both high-risk patients undergo-ing 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 at low cardiac risk based on risk factors from the Revised Cardiac Risk Index [ 7 ] . A meta-analysis that same year was inconclusive as to whether there was any bene fi t to perioperative beta-blockers, but did fi nd an increased risk of bradycardia and hypotension [ 8 ] . ACC/AHA guidelines published the following class I indications ■

in June 2006: 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 [ ■ 2 ] . Over 8,000 patients not previously on a beta-blocker with CAD, PVD, stroke, CHF within 3 years, major vascular surgery, or three of seven risk factors (intrathoracic/intraperitoneal surgery, TIA, CHF, DM, creatinine >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 endpoint 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, bra-dycardia, stroke, and total mortality. Some argue that the dose and dose-titration regimen of beta-blocker was too aggressive. Consider however that a lower dose regimen with negative results may have been interpreted as simply not achieving ade-quate beta-blockade. In November 2008 a systematic review concluded that there ■

was insuf fi cient evidence to support the use of perioperative beta-blockers in patients who were not already on them for

56 THE PERIOPERATIVE MEDICINE CONSULT HANDBOOK

cardiovascular indications [ 9 ] . This review’s results were dominated by the POISE trial, as it had the largest number of participants by far. 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.” [ 1 ] Therefore, the updated AHA guidelines recommend against duplicating the POISE protocol in practice, but did not otherwise signi fi cantly 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 cardiovascu-lar 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:e169–276.

2. POISE study group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol suc-cinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371:1839–47.

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;114:817–23.

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;56:1922–9.

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;335:1713–20.

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;341:1789–94.

7. Lindenauer PK, Pekow P, Wang K, et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005;353:349–61.

8. Deveraux PJ, Beattie WS, Choi PT, et al. How strong is the evidence for the use of periopera-tive beta blockers in non-cardiac surgery? Systematic review and meta-analysis of random-ized controlled trials. BMJ. 2005;331:313–21.

9. Bangalore S, Wetterslev J, Pranesh S, et al. Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis. Lancet. 2008;372:1962–76.