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Department of Vascular Surgery; Erasmus MC Rotterdam; Rotterdam, The Netherlands (Schouten) Department of Anesthesiology and Critical Care; University of Pennsylvania; Philadelphia, PA (Fleisher) Department of Anesthesia; Veterans Affairs Medical Center; University of California; San Francisco, CA (London) Department of Anesthesiology; Erasmus MC Rotterdam (Feringa) Department of Cardiology; Leiden University Medical Center; Leiden (Bax) Department of Anesthesiology; Erasmus MC Rotterdam; Rotterdam, The Netherlands; d.poldermans{at}erasmusmc.nl (Poldermans)
In Response:
The issue of a possible harmful effect of ß-blockers in subgroups of patients with a low cardiac risk profile remains controversial as long as results of randomized trials are not available. Licker (1) refers to a study of Lindenauer et al. (2) to address this issue. However, in this large cohort study patients were considered to have received ß-blocker therapy for prophylaxis, whether intentionally or not, if the first record of treatment occurred on the first or second day after surgery. As the authors acknowledge, it is possible that the approach they used to identify patients taking ß-blockers was at least partially responsible for the observation that perioperative ß-blocker use is harmful for patients at low cardiac risk. ß-Blockers may have been given to many low-risk patients in response to a cardiovascular complication, rather than to prevent one (3).
There are several issues a clinician needs to be aware of when prescribing perioperative ß-blocker therapy. Dosing of ß-blockers seems to be of critical importance to prevent postoperative adverse cardiac events. It was recently shown in two studies that those taking ß-blockers have significantly less cardiac complications if ß-blockers are administered to achieve a target heart rate of 60–65 bpm (4,5). Whether these patients have an upregulation of ß-adrgenergic receptors and consequently a loss of negative chronotropic effect as suggested by Licker has only limited clinical significance as long as the dose of ß-blockers is adjusted to achieve a heart rate of 60–65 bpm. Lanfear et al. found that survival for patients receiving ß-blocker therapy after an acute coronary syndrome is affected by ß2-adrenergic receptor genotypes. It would be interesting to know whether patients with certain genotypes responded less to ß-blockade resulting in a higher heart rate when compared with patients with other genotypes. The study population consisted of patients included over 5 years ago, a time in which noncardioselective ß-blockers were used more frequently. The type of ß-blocker used, i.e., long-acting versus short acting and selective versus nonselective, needs to be considered while interpreting these study results as it is known that this also might influence outcome (6).
We agree with Licker that it is probably impossible to prevent all cardiac events in surgical patients by simply treating them with appropriate ß-blocker doses. This is related to the complex pathophysiology of perioperative myocardial infarctions. Increased stress leads to subendocardial ischemia in the presence of significant coronary artery stenosis. In these patients ß-blockers have a cardioprotective effect. However, in approximately half of the cases, a sudden rupture of an unstable coronary plaque with thrombosis is responsible for a cardiac event. The latter is unpredictable and may be the causative mechanism for postoperative cardiac events in patients without objective markers of coronary artery disease such as angina or infarction. In these cases plaque stabilization using statins could be considered and use of antiplatelet agents may also be of value (providing the increased risk of bleeding is acceptable).
In conclusion, we agree that perioperative ß-blocker therapy alone may not be enough for adequate cardioprotection. However, in selected surgical patients at increased cardiac risk, ß-blockers should be used as a part of a multimodal cardioprotective approach. Furthermore, it needs to be emphasized that adequate ß-blocker dosing is likely of pivotal importance. This should be taken into account in the interpretation of ß-blocker trials as well as in the design of future trials on the issue of perioperative ß-blockade.
REFERENCES
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