User:Robinsonvaughn/Perioperative beta blockade

Perioperative Beta Blockade

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. Unfortunately, the full-text is not available for free, but would be available through the "lonesome doc" feature through Pubmed.

Overall, POISE did not show benefit for patients at reasonably high risk who got perioperative aggressive metoprolol. Some measures (stroke) were higher in the treatment group than placebo.

This article details some of the history of this clinical question. The history should serve as a cautionary tale to practitioners who do not evaluate data from publications in light of their own clinical experience. Perioperative beta blockade was advocated by non-anesthesiologists and non-surgeons as a standard of care. It was never widely adopted in the same dosing or timing as the protocols of experiments that showed benefit. Practitioners who did not routinely push atenolol before induction, and who did not generalize DECREASE to less sick patients should be congratulated for their prudence in light of POISE's results.

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).

Two other papers about the same time supported beta blockade, one running an esmolol drip on total knees (Urban), and one preventing ST depression with beta blockers on vascular patients.

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.

Right now, the most authoritative source for guidance is the AHA/ACC 2007 Update for Perioperative Evaluation. (It is currently being revised as of 6-09...twelve months after the publication of POISE, which showed no benefit of perioperative beta blockade with a total n of about twenty times the number of total patients randomized in all previous trials together that did show benefit.)

It's clear that only two groups should be mandated for beta blockade: vascular patients with recent positive provocative cardiac testing (based on the Poldermans data), and patients already taking beta blockers. Other patients are a grey area, with the AHA/ACC paper calling beta-blocking patients at high risk for perioperative cardiac events a level 2a recommendation. Here is the AHA/ACC link. Look to page e460:

http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.185699

The update again labels the evidence for the two indications mentioned in the preceding paragraph as "Class I". Importantly, the "vascular surgery" mentioned should clearly exclude carotid surgery, as perioperative beta blockade has never been shown to be beneficial in patients for carotid surgery. This is not disputed.

Several "Class IIa" recommendations are important. The word "recommendations" even deserves clarification. The exact phrasing of the ACC/AHA document is "the recommendation in favor of treatment being useful/effective; some conflicting evidence from single randomized trial or non-randomized studies; additional studies with focused objectives needed; it is reasonable to administer treatment; benefit>>risk." "It is reasonable" differs semantically from "it is recommended." It may be reasonable for citizens to stockpile gasoline during a shortage; it would not be recommended by authorities for all citizens to do so.

The indications for perioperative beta blockade in the ACC/AHA document are:

-patients for vascular surgery in which preop assessment identifies coronary heart disease, or at high cardiac risk for CAD owing to the presence of >=1 risk factors. (again, not carotids.)

-patients in which preop assessment identifies coronary heart disease, or at high risk for coronary heart disease

Importantly, this last indication would cover the large majority of patients being considered for perioperative beta blockade - namely patients with known CAD or with >=1 risk factors for CAD having vascular surgery or "intermediate risk" non-vascular surgery. The ACC/AHA paper does not have a sophisticated reference for the risk of surgery; see page e429 of the above link.

For instance, intraperotoneal surgery is classified as intermediate risk - this could include any laparoscopic surgeries, or the variety of colectomies. Orthopedic surgery is characterized as intermediate risk, this would put TKR and major spine surgery in the same catagory. Prostate surgery with the newer techniques involving laparoscopic approach with robotic assistance do not entail the same risk as open, radical prostatectomy.

(Under the side-menu "surgical risk", see a more sophisticated treatment, though by no means truly comprehensive. The references shown are several years old as of 2007.)

Therefore, the 2007 ACC/AHA reference "recommends" - again with the clear phrasing stated above - perioperative beta blockade for patients with only one risk factor for CAD having intermediate or high risk surgery as defined on page e429 in the most recent update. This recommendation stands in sharp contrast to the MVas and the DiPOM RCTs that found no benefit to perioperative beta blockade.

MVas and Dipom are two of the largest and the most recent trials, and the ACC/AHA's endorsement of the beta blockade's benefit is therefore questionable. POISE found that patients at reasonably high risk for cardiac events did not benefit from perioperative beta blockade; they may have been harmed.

Editorials have appeared that discourage the widespread use of perioperative beta blockade. These are in sharp contrast to the enthusiasm for the practice just several years ago. This recent editorial that accompanied the full publication of the MVas Trial in the American Heart Journal: (McCullough PA.  Failure of beta-blockers in the reduction of perioperative events: where did we go wrong?  Am Heart J. 2006 Nov;152(5):815-8.)

As well, the January 2007 issue of Anesthesia and Analgesia devotes several articles to this topic. Of particular interest is the editorial by London. (http://www.anesthesia-analgesia.org/)  Both of these letters predate the more definitive negative findings of POISE.

As well, editorials in American Heart Journal summarize some of the most sophisticated current thinking: on the one hand, the two recent studies finding no benefit did not beta block to a low enough heart rate or for a long enough time. On the other hand (the response by Yang), aggressive and lengthy beta blockade initiated in or well before the perioperative period carries clear risks of hypotension, or is simply impractical. The free links to these letters are:

http://download.journals.elsevierhealth.com/pdfs/journals/0002-8703/PIIS000287030700141X.pdf

http://download.journals.elsevierhealth.com/pdfs/journals/0002-8703/PIIS0002870307001408.pdf

(1) http://perioperativebetablockade.com/index.html