The controversy over perioperative use of beta blockers just won’t go away. We’ve addressed the issue of perioperative beta blocker use in multiple columns (see Patient Safety Tips of the Week for November 20, 2007 “New Evidence Questions Perioperative Beta Blocker Use” and November 4, 2008 “Beta Blockers Take More Hits” and our December 2009 What’s New in the Patient Safety World column “Updated Perioperative Beta Blocker Guidelines”).
After several years in which we pushed for almost universal use of beta blockers perioperatively, publication of the POISE trial significantly changed things. You’ll recall that the POISE trial showed that, though preoperative beta blockers prevented 15 MI’s for every 1000 patients treated, there was an increased risk of stroke and an excess of 8 deaths per 1000 patients treated.
But critics of POISE were quick to point out that the dosage and timing of beta blockade in POISE were not reflective of the optimal way to use perioperative beta blockers. Proponents of their use (eg. Poldermans et al 2009) continue to focus on the need for careful titration of dose, timing, specific beta blocker, and issues such as withdrawal of beta blockers. Those critics have argued that beta blockers should be started well in advance of planned surgery and in low doses that are then titrated upward to meet specific heart rate targets. On the other hand, in POISE the beta blockers were started in most cases IV in relatively high doses on the day of surgery.
Now a new look at some observational data (Wallace 2010) suggests that perioperative beta blockade reduces mortality at both 30 days and one year. And that data reinforces that perioperative withdrawal of beta blockers increases mortality. A protocol for perioperative beta blockers was implemented at the San Francisco VAMC in 1998 after some of the early studies had demonstrated a reduction in cardiac events by use of perioperative beta blockers. That protocol has largely remained in place at that medical center since 1998, though physician compliance with it is purely voluntary. So the authors took a retrospective look at the outcomes in surgery there, comparing patients in whom the protocol was followed to those in which it was not. Their database included over 20,000 patients who had almost 40,000 operations. Those patients who had a beta blocker added had significantly reduced 30-day and one-year mortality rates, as did those in whom pre-operative beta blockers were continued. But those in whom beta blockers were withdrawn had significantly increased risks of death at 30 days and one year. The effects were seen in most types of surgery (cardiac and non-cardiac) though there was no reduction in mortality when beta blockers were added or continued in low-risk patients. The average doses of beta blockers in this study were considerably lower than the equivalent doses used in POISE.
But this was not a randomized controlled trial. It was a retrospective analysis of data and occurred at a medical center where it was widely accepted that perioperative beta blockers are a good thing and activities promoting perioperative beta blocker use were continued throughout the study period. And the reasons why a physician might opt not to use beta blockers was not obvious in their data.
The accompanying editorial by Foex and Sear (Foex 2010) also notes that blood pressure may be important. In the Wallace study a systolic arterial pressure of 120 mm Hg was required before the next dose of beta blocker could be given. Foex and Sear also note that there are really no good studies that address how much in advance of surgery beta blockers should be started.
The Wallace paper showed that beta blocker withdrawal almost quadrupled the 30-day mortality rate and almost doubled the 1-year mortality rate. A similar retrospective analysis of patients undergoing arthroplasty (van Klei 2009) had also shown that withdrawal of beta blockers roughly doubled the postoperative MI rate and mortality rate. The editorial accompanying the van Klei study (London 2009) also summarizes multiple prior studies assessing the effect of beta blocker withdrawal perioperatively. These studies confirm the continuation of beta blockers in patients who are already taking them is important. They confirm the 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade’s only remaining Class I recommendation that beta blockers be continued in patients already taking them for angina, arrhythmias, hypertension or other ACC/AHA class I guideline indications.
A very thoughtful article on the physiological rationale for perioperative beta blockers, the studies done and the reasons for the controversy was published by Chopra and colleagues (Chopra 2009) in 2009. They stress that careful attention to both patient risk and beta-blocker profile is critical to the safe and effective implementation of this therapy.
The controversy is not likely to be resolved until a study like POISE is repeated, using the titrated dose approach to perioperative beta blockers.
Poldermans, Don; Schouten, Olaf; van Lier, Felix; Hoeks, Sanne E.; van de Ven, Louis; Stolker, Robert Jan; Fleisher, Lee A. Perioperative Strokes and Beta Blockade. Anesthesiology 2009. 111(5): 940-945, November 2009.
Wallace AW, Au S, Cason BA. Association of the Pattern of Use of Perioperative ß-Blockade and Postoperative Mortality. Anesthesiology 2010; 113(4): 794-805
Foëx P, Sear JW. Challenges of ß-Blockade in Surgical Patients. Anesthesiology 2010; 113(4): 767-771
van Klei WA, Bryson GL., Yang H, Forster AJ. Effect of [beta]-blocker Prescription on the Incidence of Postoperative Myocardial Infarction after Hip and Knee Arthroplasty. Anesthesiology 2009; 111(4): 717-724
Fleisher LA, Beckman JA, Brown KA, et al.for the American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine, Society for Vascular Surgery. 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. J. Am. Coll. Cardiol. 2009, first published on Nov 2, 2009 as doi: doi:10.1016/j.jacc.2009.07.010
London, MJ. Perioperative [beta]-Blockade, Discontinuation, and Complications: Do You Really Know It When You See It? Anesthesiology 2009; 111(4): 690-694