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Departments of Anesthesiology and Critical Care, University of Alberta, Edmonton, Alberta Department of Anesthesiology, McGill University, Montreal, Quebec Department of Anesthesiology, University of British Columbia, Vancouver, BC Department of Anesthesiology, University of Manitoba, Winnipeg, Manitoba
To the Editor:
VanDenKerkhof et al. comment, in their survey of anesthesiologists regarding beta adrenergic blocker knowledge and practice (1), that "numerous studies have demonstrated...beta blockade to decrease cardiac complications [in] noncardiac surgery" and that "authorities have published guidelines recommending...beta adrenergic blockers for patients at risk."
While effective translation of research into current practice remains a laudable but elusive goal, the quality of the published research regarding perioperative beta-adrenergic blockade should be carefully considered prior to implying it to be the "best" practice. Auerbach and Goldman (2) in their meta-analysis recommended the "consideration" of beta blockade in patients at risk, but firmly advised that more conclusive large-scale trials were necessary prior to more definitive recommendations. Auerbach and Goldman’s recommendation was based on a meta-analysis which showed that the significance level of beta blockade in reducing cardiac event rates was only P = 0.05, and that the odds ratio for mortality did not reach statistical significance. Moreover, these summary odds ratios rely entirely upon the results of Poldermans et al.’s (3) study of bisoprolol among patients with positive dobutamine echocardiography studies undergoing vascular surgery. Poldermans et al.’s study was an unblinded trial of 112 patients and was stopped at an interim analysis for relative risk reductions of 100% for myocardial infarction and 80% for cardiac death. This small study with very few events has risk reductions that are completely inconsistent with the trials of tens of thousands of patients in acute myocardial infarction and congestive heart failure that have consistently demonstrated relative risk reductions with longer term beta-blocker therapy in the range of 25–35%. Although Poldermans et al.’s results were attributed to bisoprolol, a more valid conclusion would credit a chance finding in an unblinded trial with few events stopped at an interim analysis for effects that are too good to be true. In another trial, Mangano et al. attributed a survival benefit to perioperative atenolol use in long-term follow-up but did not include perioperative events (4). When perioperative mortality was included, no survival benefit was seen (5).
Meta-analyses have been proven to be prone to publication bias, with subsequent large randomized controlled trials often showing minimal if any effect when the same intervention is tested (6). Meta-analyses may also be frankly in error, with an excellent example being the hypothesized benefit of magnesium in myocardial infarction, initially suggested by meta-analysis (7) but subsequently repudiated and just missing conventional levels of statistical significance for harm in a large randomized trial (8).
Finally, it is important to point out that the ACC/AHA guidelines appropriately acknowledge the uncertainty surrounding the efficacy of perioperative beta-blockers to prevent serious perioperative cardiovascular outcomes as indicated by their statement, "current studies, however, suggest that appropriately administered beta-blockers reduce perioperative ischemia and may reduce the risk of MI and death in high-risk patients."
Surveying knowledge of incomplete and inadequately substantiated data lends an undeserved element of truth to the same, aiding in the progression of hypothesis to fact, transforming myth into reality, and short-circuiting establishment of "best" practice.
A large randomized controlled trial is currently ongoing worldwide to address this very issue of the effect of beta blockade perioperatively in patients at cardiac risk. It is crucial to realize that clinical equipoise remains strong on this question, and to resist admiring the clothing of a still naked emperor.
References
Department of Anesthesiology, Queen’s University, Kingston, Ontario, Canada
In Response:
We thank the authors for supporting our contention that there are many unanswered questions regarding prophylactic perioperative beta blockade, and that its routine practice remains controversial ("Although controversies remain in the literature with regard to the efficacy of this therapy...") (1). This is the reason that our center was one of three involved in a recent large study of vascular surgical patients, as well as being one of the study sites for the multinational trial currently under way, to which the authors referred. This is also the reason that our survey of Canadian anesthesiologists was just that: knowing that the issue is unresolved, yet occupies a high profile in the literature (2,3), we sought to document the knowledge and beliefs regarding the literature among practitioners, and the current clinical application of this knowledge (1). Rather than presupposing that routine prophylaxis is the "right" choice, we surveyed clinicians’ beliefs based on their own interpretation of the literature. We subsequently evaluated the frequency with which these beliefs (whether positive or negative) were put into practice and explored possible barriers to the transfer of knowledge into the clinical realm.
With regard to the controversies surrounding routine perioperative beta blockade, the final answers are yet to come from research currently in progress. Despite this, numerous authorities have recommended adopting this approach, either cautiously or liberally, on the basis that the current state of the literature, despite its limitations, has been quite consistent (4,5). The large body of data examining surrogate outcomes such as indices of hemodynamic stability and myocardial ischemia, the small body of outcome data such as mortality and major cardiac events, and the favorable safety profile of this therapy are impossible to ignore (2,3,6) and must be taken into account by all clinicians when deciding whether or not to adopt this strategy for any given patient at high risk of cardiac complications.
References
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