Effect of preoperative ß-blockade on perioperative mortality in coronary surgery

P. W. C. ten Broecke*, S. G. De Hert, E. Mertens and H. F. Adriaensen

Department of Anaesthesia, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium E-mail: pietertenbroeke@hotmail.com

Accepted for publication: July 27, 2002


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. Many preoperative factors can influence perioperative mortality in cardiac surgery. Because the perioperative use of ß-blocking agents may reduce perioperative cardiac complications in non-cardiac surgery, we considered the possibility that ß-blocking agents could improve survival in coronary surgery patients.

Methods. In a retrospective study on 1586 patients undergoing coronary bypass surgery, the relative risk of 30-day mortality was determined in relation to preoperative risk factors and medication. Factors included patient characteristics, pre-existing illness, specific cardiovascular risk factors, cardiac status and urgency of surgery. Treatment with ß-blocking agents, calcium antagonists, angiotensin-converting enzyme inhibitors, nitrates, anti-arrhythmic agents, diuretics and antithrombotic agents was taken into account.

Results. Sex, age, chronic obstructive pulmonary disease, urgency and the preoperative use of diuretics and chronic ß-blocking therapy were found to be linked to mortality (P<0.05). Backward stepwise regression testing identified age, urgency and ß-blocking therapy as independent factors that could predict mortality.

Conclusions. Increasing age and urgency of surgery are associated with greater mortality, whereas preoperative ß-blocking therapy is associated with less mortality. The characteristics of patients who received chronic ß-blockade did not differ significantly from those of patients who did not. The results suggest that chronic preoperative ß-blocker therapy reduces 30-day mortality in coronary surgery.

Br J Anaesth 2003; 90: 27–31

Keywords: complications, mortality; risk, assessment; surgery, cardiovascular; sympathetic nervous system, ß-blockade


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Several studies have described a number of factors that influence mortality in both cardiac and non-cardiac surgery.19 Risk factors associated with adverse outcome vary with time and differ between centres.10 Factors such as new surgical and anaesthetic techniques, changing habits, and better knowledge of the potential effects of current therapies may cause this variation.

Cardiac surgical patients often receive long-term treatment with a number of cardiovascular drugs. Although they are effective in the control of symptoms, their possible effect on perioperative mortality in cardiac surgery is unclear. Calcium antagonists can increase mortality in patients with hypertension11 and ischaemic heart disease.12 13 Weightman and colleagues14 observed that chronic nitrate therapy appeared to be associated with increased mortality after cardiac surgery and that ß-blockade had a potential beneficial effect.14 Recently, Ferguson and colleagues15 found that preoperative ß-blockade reduced 30-day mortality and morbidity in coronary artery bypass graft (CABG) surgery.15 The attitude towards ß-blocking drugs has changed over the years. These agents were often stopped before surgery because of a possible deleterious effect from their negative inotropic actions.16 17 However, evidence now suggests that perioperative ß-blocking agents may reduce perioperative cardiac complications or improve survival after vascular surgery and cardiac surgery.1822 We considered the possibility that ß-blocking agents would also improve survival in coronary surgery patients. To study this, we analysed retrospectively the effect of long-term ß-blockade on 30-day mortality in coronary surgery patients.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This retrospective study included all patients who underwent primary coronary bypass surgery between 1996 and 1999 at the University Hospital Antwerp. Data regarding risk factors commonly associated with perioperative mortality17 were collected from a database in which all patients are enrolled. These data included characteristics such as gender, age, body mass index (BMI), smoking, and conditions such as diabetes, renal insufficiency, chronic pulmonary obstructive disease, episodes of neurological transient ischaemic attack and previous stroke (Table 1). Specific cardiovascular risk factors that were recorded included a history of previous myocardial infarction, the presence of hypertension, a history of previous peripheral vascular surgery and a history of previous percutaneous coronary angioplasty. Other preoperative factors included the left ventricular ejection fraction and the degree of urgency. An urgent intervention was defined as an operation to be performed within 6 h, and other interventions were defined as elective. For the present study, regular daily use of any dose of drugs in the following categories was recorded: ß-blocking agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, nitrates, anti-arrhythmic agents, diuretics and antithrombotic agents. ß-Blocking agents were continued until the morning of surgery. In all patients (including those who did not receive ß-blocking therapy before), ß-blockers were started the day after surgery as part of routine anti-arrhythmic therapy.


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Table 1 Definitions of disease entities
 
Thirty-day mortality was used as the primary outcome. This interval was chosen because it is not subject to detection bias and because it is the standard period for the assessment of perioperative outcomes.23 All the preoperative data were entered as individual independent variables in a linear regression analysis with 30-day mortality as the dependent variable. All significant factors were then entered in a backward stepwise regression analysis to find out the independent contributions of the different risk factors to mortality. The characteristics of the patients on chronic ß-blocking therapy were compared with those of patients who were not on ß-blocking therapy, using {chi}2 analysis and the unpaired t-test as appropriate. Statistical significance was accepted if P<0.05.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
A total of 1776 patients were included in the study initially. Of these, 190 had to be excluded because of incomplete data. Finally, 1586 patients were included. Of these patients, 69 (4.3%) died within the 30-day perioperative period. Of these 69 patients, 24 died within 24 h and 22 died after 24 h and within the first 7 days. Mortality within the first 24 h was mainly from cardiac failure, whereas mortality after 24 h had several causes. Mortality was independent of surgeon and anaesthetist and did not change over the years.

By univariate regression analysis, we found that female sex, age, chronic obstructive pulmonary disease, urgency and the preoperative use of diuretics and chronic ß-blocking therapy predicted mortality (Table 2). Backward stepwise regression analysis identified age, urgency and ß-blocking therapy as independent factors that could predict mortality. Multiple logistic regression analysis gave the following equation:


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Table 2 Linear regression analysis for individual preoperative factors. Male sex coded 1, female sex 2; urgency coded 1, non-urgency 2; other factors coded 1 if present, 2 if absent
 
mortality = –0.06 + (0.002 x age) + (0.06 x urgency)– (0.05 x ß-blockade)

The coefficients for age and urgency are positive, which indicates that increasing age and urgency are associated with greater mortality. The coefficient for ß-blocking is negative, showing that preoperative use is associated with decreased 30-day mortality.

Use of chronic preoperative ß-blocking medication was not related to individual physical and cardiac status. Preoperative data for the patients on ß-blocking therapy were compared with those for patients not taking ß-blockers (Table 3). There were no significant differences in physical or cardiac status between these groups. The difference in 30-day mortality can therefore not be attributed to known differences in physical status and cardiac function in patients receiving chronic ß-blocking therapy.


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Table 3 Characteristics of ß-blocker users and non-users
 

    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Our main finding is that chronic ß-blocking therapy reduces 30-day mortality. Other independent predictors of mortality after coronary surgery are age and degree of urgency. Whereas age and degree of urgency are well-known risk factors,2 3 6 the effect of chronic ß-blocking therapy in relation to coronary surgery is less known. Kaplan and colleagues24 observed a reduction in mortality associated with preoperative propranolol medication. More recently, Weightman and colleagues14 reported reduced mortality in cardiac surgery patients on preoperative ß-blocking therapy and a positive association between in-hospital mortality and preoperative nitrate therapy. In the present study we did not observe increased mortality with nitrate therapy. Many methodological differences (such as type of operation, patient characteristics, underlying disease and cardioprotective strategies) could have caused this difference. In contrast, Sharma and colleagues25 found less mortality after percutaneous coronary intervention therapy in patients who received nitrate therapy before the procedure.

The beneficial effect of ß-blocking therapy on mortality is now generally accepted in cardiac disease and in the course of vascular surgery. Therapy with ß-blocking agents has been studied in the treatment of myocardial infarction and heart failure and in the perioperative protection of people with ischaemic cardiac disease. Many studies suggest that long-term ß-blocking therapy increases survival in patients with heart failure.26 27 Metoprolol has a protective effect on sudden death after acute myocardial infarction and data suggest a similar effect on sudden death in hypertensive patients.28 29 Gottlieb and colleagues30 found that even patients with conditions that are often considered contraindications to ß-blockade and those with non-transmural infarction benefit from ß-blocker therapy. Mangano and colleagues18 found that perioperative ß-blockade not only reduced perioperative ischaemic events, but also reduced mortality and cardiovascular complications for as long as 2 yr after the surgical procedure. Poldermans and colleagues1921 published similar findings. Other studies report beneficial effects of perioperative ß-blockade.16 31 32 Recently, Ferguson and colleagues15 published a study on the National Adult Cardiac Surgery Database of the Society of Thoracic Surgeons of North America, and they found a small but consistent survival benefit for patients on preoperative ß-blockade who were having CABG. The observed association between preoperative ß-blocker therapy and 30-day mortality is supported by our findings on a European database.

In view of all this knowledge, it is surprising that the protective effects of long-term ß-blocking therapy on mortality in coronary surgery have remained largely unexplored. The mechanisms of this protective effect remain to be established. One possible explanation is that patients on ß-blocking therapy have better cardiac function or less concomitant disease. We checked this in the present study, and preoperative ejection fraction was similar in the two groups. Concomitant diseases, such as diabetes and chronic obstructive pulmonary disease, which might be a contraindication for ß-blocking therapy, were also similar in the two groups.

One of the beneficial effects of ß-blockers is the improvement in the oxygen supply–demand balance of the myocardium from the interaction of different mechanisms.17 33 The ß-blocking agents decrease oxygen consumption by reducing heart rate and inotropic state. They may also improve myocardial metabolism independently of their effects on heart rate and arterial pressure.31 34 They also decrease any effect of increased sympathetic nervous activity by blocking the actions of catecholamines on ß-adrenergic receptors. Some ß-blockers even reduce the overall sympathetic outflow. A slower heart rate prolongs diastole and increases the time for oxygen delivery. Some ß-blocking agents may even shift the oxygen dissociation curve to the right, facilitating tissue oxygenation. Although ß-blockers are not direct vasodilators, they may increase blood supply to ischaemic myocardium by redistribution of myocardial blood flow away from normal regions to regions at risk. Suppression of dysrhythmias is another virtue of ß-blocking agents; it is not related to the oxygen supply– demand ratio but is important in relation to decreasing long-term mortality.27 3537 Other data obtained in heart failure suggest that ß-blockers may improve heart function by remodelling of the left ventricle.27 38

The sympathoadrenal tone is increased in the perioperative period for different reasons. The effects of ß-blocking therapy on the increased sympathetic tone may explain, at least in part, the observed protective effect.8

In this study, preoperative ß-blocking therapy was continued until the morning of surgery, resulting in ß-blocking effects in the perioperative period. It is not clear whether the beneficial effects of ß-blocking therapy are related to its preoperative or its perioperative effects.

In conclusion, the present study shows that chronic preoperative ß-blocking therapy is associated with reduced 30-day mortality in coronary surgery. Further research should explore whether this observation also holds for other types of cardiac surgery, with and without the use of cardiopulmonary bypass.


    References
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 Introduction
 Methods
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 Discussion
 References
 
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