Beta-Blockers for non-cardiac surgery: a different approach after the poise data or await more information?

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Beta-Blockers for non-cardiac surgery: a different approach after the poise data or await more information?

Bruce M. Biccard

Honorary Lecturer, Nelson R Mandela School of Medicine, Private Bag 7, Congella, 4013, South Africa

Honorary Senior Clinical Lecturer, Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom

Principal Specialist, Inkosi Albert Luthuli Central Hospital, 800 Bellair Road, Mayville, 4091, South Africa

^{Correspondence to}

Recent publication of the PeriOperative ISchemic Evalution (POISE) trial has added considerable important data to our understanding of acute perioperative beta-blockade¹. Due to the number of potential triggers of perioperative cardiac events; including amongst others, inflammation, surgical stress, hypercoagulable states and hypoxia², it has been estimated, that at best, a single medical therapy could be expected to result in a relative risk reduction of 20 to 35% for the composite endpoint of cardiac death, nonfatal myocardial infarction and nonfatal cardiac arrest in the perioperative period³. As a result, before POISE, it was controversial whether perioperative beta-blockers were indeed cardioprotective². What POISE has shown is that acute perioperative beta-blockade does in fact decrease perioperative nonfatal myocardial infarction¹.

What is also now known is that there is a potential 'cost' associated with this benefit. It was appreciated prior to POISE that acute perioperative beta-blockade significantly increased drug associated bradycardia and hypotension², although clinical significance of these events was unknown. The most important data to emerge from the POISE study were that these drug associated side-effects are associated with major morbidity¹. Clinically significant hypotension and bradycardia were found to be independent predictors of mortality and clinically significant hypotension, an independent predictor of perioperative stroke¹. This clinically important data requires a change in our practice with respect to acute perioperative beta-blockade.

It is imperative that these side-effects are now actively managed in the perioperative period. In addition, it is crucial that other complications which may be exacerbated by either drug associated bradycardia or hypotension are always considered and excluded. It is possible, in fact, that a missed or delayed diagnosis of hypovolaemia, sepsis, hypoxia or anaemia may have adversely affected outcomes in the POISE trial. Indeed, there were significantly more sepsis related deaths in the metoprolol group in the POISE trial¹.

It is also imperative that we now start to reconsider our perioperative prescription of acute beta-blockade. One suggestion has been that a longer preoperative run in period is necessary, using a lower dose of beta-blocker titrated to effect over days⁴ as opposed to a higher dose, titrated over hours¹. This approach may result in less beta-blocker associated hypotension and bradycardia⁴. This certainly needs further investigation. However, it does potentially present a number of logistical problems in the initiation and titration of beta-blockers in patients being managed as outpatients at the time of beta-blocker prescription, as opposed to the simpler inpatient preoperative prescription as in the POISE trial.

The most worrying data to emerge from POISE relate to the increased all-cause mortality. Although, it is possible that attention to perioperative haemodynamic factors may decrease (or hopefully obviate) this devastating complication of perioperative beta-blockade, it is probably prudent to adopt a more conservative approach to prescription of acute perioperative beta-blockade, until this is confirmed. This begs the question; 'In which patient groups are acute perioperative beta-blockers clearly beneficial?' The POISE study suggests that vascular surgical patients and patients of intermediate cardiac risk (two cardiac clinical risk predictors⁵) benefit from perioperative beta-blockade (Figure 3 of POISE)¹. While acute perioperative beta-blockade may be reasonable in these patients, all other patients should probably have a more cautious risk-benefit analysis conducted prior to institution of perioperative beta-blockers. Importantly, there is still little data on the outcomes associated with acute perioperative beta-blockade in patients with four or more cardiac risk factors⁵, where myocardial ischaemia has not been demonstrated in response to a dynamic ventricular test^1-6, This patient group certainly needs further investigation.

Yes, a different approach to perioperative beta-blockade is advocated after publication of the POISE data¹. However, like all good research it raises further questions for which we must again gather data.

Conflict of interest: none

• 1. The POISE Investigators. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-47.
• 2. Devereaux PJ, Beattie WS, Choi PT, Badner NH, Guyatt GH, Villar JC, et al. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ. 2005;331(7512):313-21.
• 3. Devereaux PJ, Goldman L, Yusuf S, Gilbert K, Leslie K, Guyatt GH. Surveillance and prevention of major perioperative ischemic cardiac events in patients undergoing noncardiac surgery: a review. CMAJ. 2005;173(7):779-88.
• 4. Fleisher LA, Poldermans D. Perioperative beta blockade: where do we go from here? Lancet. 2008;371(9627):1813-4.
• 5. Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation .1999;100(10):1043-9.
• 6. Poldermans D, Boersma E, Bax JJ, Thomson IR, Van de Ven LL, Blankensteijn JD, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med. 1999;341(24):1789-94.

Publication Dates

• Publication in this collection
  15 Aug 2008
• Date of issue
  Aug 2008