Perioperative Beta Blockade – The Times have Changed
In 2003: The Agency for Healthcare Research and Quality
Patient safety practices were rated in terms of strength of the evidence supporting more widespread
implementation. Practices appear in descending order, with the most highly rated practices listed first.
Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk.
Use of perioperative beta-blockers in appropriate patients to prevent perioperative morbidity
and mortality.
3. (followed by 9 more practices involving asceptic techniques, perioperative antibiotic
prophylaxis, etc.)
1.
2.
In 2009: From the ACCF/AHA Perioperative Guidelines
In light of the POISE results, routine administration of perioperative beta blockers, particularly in
higher fixed-dose regimens begun on the day of surgery, cannot be advocated.
Introduction and Most Recent Developments
Perioperative beta blockade has been advocated for nearly fifteen years, with varying enthusiasm.
Until several years ago, the advocacy had been based on several small studies that suggested
enormous benefit. In 2008, the largest RCT was published: the POISE paper appeared in the
5/12/08 issue of Lancet.
Overall, POISE did not show benefit for patients at reasonably high risk who got an aggressive
protocol of perioperative metoprolol. Some measures (stroke) were higher in the treatment group
than placebo. Overall mortality was significantly higher in the beta-blocked group (3.1% vs. 2.3%;
p=.03.)
At present, it is still reasonable to continue to advocate perioperative beta blockade to
prevent cardiovascular events, assuming cardiovascular compromise would be very
carefully avoided -best achieved by starting weeks before surgery with oral beta blockers.
It is not, however, reasonable to mandate any protocol for perioperative beta blockade as
"best practice."
At present, the most authoritative statement on perioperative beta blockade is the American College
of Cardiology Foundation/ American Heart Association Focused Update published November, 2009.
The document is 108 pages long, including broader perioperative management, and is available on
the American Heart Association website. Importantly, the chair of the task force is Dr. Lee Fleisher,
an anesthesiologist.
http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192690
The relevant questions in 2010 remain:
1. Should my 65 year-old smoker with diabetes and known CAD having a colectomy be betablocked?
2. More importantly, in a time of increasing mandates in perioperative medicine including
thromboprophylaxis and antibiotic administration - should perioperative beta blockade be mandated?
The Focused Update answers both questions with reasonable clarity. Below are excerpts
from the Update pertaining to these questions.
The diagram on page e12 suggests that a patient with poor functional status, a history of CAD, and
diabetes having a colectomy should "proceed with planned surgery with HR control or consider noninvasive testing if it will change management." That would suggest an endorsement of HR control
with beta blockers.
However, a footnote at the bottom of the page states: “consider perioperative beta blockade (see
table 11 for populations in which this has been shown to reduce cardiac morbidity/mortality.)” That
would suggest an endorsement of careful weighing of risks and benefits before pursuing HR control.
The only class I recommendation - the only candidate for mandates, and already included
in SCIP mandates - is the continuation of beta blockers for those already taking them.
The class IIa recommendations mean that the evidence isn't clear, but the weight of the
evidence is in favor of the intervention. These should NOT be for mandated care:
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beta blockers titrated to HR and BP are probably recommended for vascular
patients with known CAD or cardiac ischemia defined in preoperative testing.
beta blockers titrated to HR and BP are reasonable for vascular patients with more
than one cardiac risk factors (CAD, CHF, CVA, DM, CRI.)
beta blockers titrated to HR and BP are reasonable for intermediate risk surgery
with more than one cardiac risk factors.
Otherwise, the usefulness is uncertain. It is noted - based on POISE's results - that
routine administration of high-dose beta blockars in the abscence of dose titration is not
useful and may be harmful to patients not currently taking beta blockers who are
undergoing noncardiac surgery. In fact, the Summary states:
"In light of the POISE results, routine administration of perioperative beta blockers,
particularly in higher fixed-dose regimens begun on the day of surgery, cannot be
advocated."
Also keep in mind that the above mentioned vascular patients DO NOT INCLUDE
PATIENTS HAVING CAROTID ENDARTERECTOMY.
So, in response to the question of whether our 65 year-old smoker with diabetes and
known CAD having a colectomy be beta blocked, the Update's answer would be: "it's
reasonable, if carefully titrated for HR and BP, but in light of the POISE results, routine
administration of perioperative beta blockers, particularly in higher fixed-dose regimens
begun on the day of surgery, cannot be advocated."
Keep in Mind that the entire goal for perioperative beta blockade is to get the patient to the
PACU with a heart rate < 80 bpm.
Background
Perioperative beta blockade was introduced in a widespread fashion in the mid-nineties with an
influential paper by Mangano in NEJM out of the VA at UCSF (n=200). The NNT to prevent a death
with a very low cost intervention was in the low double digits.
The paper was followed up by another trial - Poldermans (DECREASE- that showed that beta
blocking vascular patients with positive (reversible defect) dobutamine stress echos yielded a NNT to
prevent MI of about three. The trial was randomized but unblinded (n=100).
Review articles and meta-analyses appeared in journals from Medicine, Cardiology, Surgery,
Anesthesiology, and surgical subspecialties. The AHA/ACC adressed the issue in their 2001
recommendations for perioperative care in a careful fashion, but called the evidence for beta-blocking
patients at risk for cardiac events "Level Two A" - which is not conclusive, but the weight of the
evidence or expert opinion is in favor of the intervention.
With such impressive NNTs and such a high profile, perioperative beta blockade became an
"evidence-based" recommendation. Papers were published about the low numbers of eligible
patients who were actually getting beta-blocked. Protocols were developed.
The Agency for Healthcare Research and Quality, a part of HHS, defined perioperative beta blockade
as one of the most important best practices to reduce mortality and morbidity IN ALL OF MEDICINE:
"The use of beta-blockers to reduce perioperative cardiac events and mortality represents a major
advance in perioperative medicine for some patients at intermediate and high risk for cardiac events
during noncardiac surgery. Wider use of this therapy should be promoted and studied, with future
research focused on fine-tuning dosages and schedules and identifying populations of patients in
which its use is cost-effective."
Perioperative beta blockade was seen as one of eleven most important (of the seventy-nine practices
reviewed in detail) best practices to push for compliance to make patients safer. Their analysis and
recommendations proved wrong, and could have resulted in increased morbidity and mortality.
(ref: http://www.ahrq.gov/Clinic/ptsafety/chap25.htm and
http://www.ahrq.gov/Clinic/ptsafety/summrpt.htm)
Meanwhile, larger trials were ongoing that would drastically erode the evidence that beta blockade
had any benefit at all. As well, a Canadian anesthesiologist obtained funding to adress the issue with
a very large trial enrolling 10,000 patients (POISE.)
Two of the larger trials, MVas and DiPOM were published in 2006, along with a very large
retrospective analysis (Lindenauer.) None of these trials showed benefit, except the retrospective
analysis showed benefit in very high risk patients.
POISE was published in 2008. In POISE, metoprolol seemed to prevent non-fatal MI
(3.6% in metop, 5.1% in placebo; p=.0008). However, more beta blocked patients had a
stroke (1.0% metop, 0.5% placebo; p=.0053). This helped to drive overall mortality higher
in the beta blocked patients: 3.1% metop to 2.3% placebo; p=.0317.
In 2009, the ACCF/AHA Perioperative Guidelines were updated as above.
http://perioperativebetablockade.com/