Esmolol

This prospective study was done to compare the control of heart rate and haemodynamics during coronary artery revascularisation without cardiopulmonary bypass using either esmolol or diltiazem. Sixty adult patients with one or two vessel coronary artery disease, were randomly divided into 2 equal groups. Group A received a 500 (mu)g/kg loading dose of esmolol followed by a 100 (mu)g/kg/h infusion, for control of heart rate during surgical anastomosis of the coronary vessel. While Group B received 0.15 mg/kg diltiazem as a loading dose followed by a 5 mg/h infusion for heart rate control, during the anastomosis. It was seen that heart rate control was better in Group A, 51.4 (+/-1.3) beats/min, than in Group B, 69.6 (+/-3.9) beats/min but the decrease in heart rate was significant in both the groups at peak effect compared to respective predrug values. Group A patients had unchanged systemic resistance and pulmonary artery wedge pressure but mean pulmonary artery pressure and pulmonary vascular resistance were significantly raised. Group B patients had decreased systemic resistance, mean pulmonary artery pressure and pulmonary artery wedge pressure, and reduced right ventricular stroke work index. We concluded that although esmolol provided dramatically slower heart rates, during surgery, the resulting elevations in mean pulmonary artery pressure and pulmonary vascular resistance would require caution if used in patients with underlying right ventricular dysfunction from ischaemia or infarction. Diltiazem by virtue of its effects on systemic vascular resistance, cardiac output, and lowering of mean arterial pressure may be a better choice in hypertensive patients.

Key words Beta-blockers - calcium channel blockers - cardiac surgery without bypass - diltiazem - esmolol

Avoidance of hypotension and tachycardia are the basic tenets of anaesthesia for patients with coronary artery disease (CAD)1. The 3 major determinants of myocardial oxygen consumption are heart rate, myocardial contractility and wall stress. An increase in heart rate reduces subendocardial perfusion by shortening diastole2. In dogs with moderate to severe coronary stenosis, systolic shortening was best with high pressures and slow heart rates and worst with low pressures and high heart rates3. Heart rate also has an effect on coronary autoregulation. The effect of heart rate on sub-endocardial autoregulation is due to the increase in myocardial oxygen consumption because of tachycardia and the decrease in diastolic time and diastolic perfusion. This results in a decrease in coronary vascular reserve, earlier failure of autoregulation and subendocardial ischaemia. So tachycardia, because of its effect on both demand and supply is deleterious in the presence of CAD, where perfusion pressure beyond an epicardial arterial obstruction are unknown. Apart from the advantages of avoiding tachycardia, attaining slow heart rates becomes a surgical necessity when coronary artery bypass is done on a beating heart for single vessel or two vessel disease.

Two drugs commonly used for heart rate control are esmolol and diltiazem. Esmolol is an intravenous short acting, cardioselective Beta1 antagonist. It is rapidly metabolised by an aryl esterase present in red blood cells, by hydrolysis of the methyl ester linkage. Esmolol has a half-life of 9 min. Esmolol is in common use clinically for heart rate control in patients undergoing coronary revascularisation without bypass, without use of cardioplegia on cardiopulmonary bypass and for ministernotomy and minithoracotomy procedures4. Diltiazem is a calcium channel blocker of the benzothiazepine group. Diltiazem suppresses sinoatrial node automaticity, atrioventricular conduction and cardiac contractility. The drug also causes moderate coronary vasodilatation, causing increased coronary blood flow5. Intravenous diltiazem is used to control ventricular response in atrial fibrillation and flutter, as prophylaxis for supra ventricular tachycardia making it suitable for heart rate control in patients with CAD undergoing revascularisation6. Although esomolol and diltiazem are the most commonly used drugs for heart rate control in patients with CAD undergoing coronary revascularisation both with and without cardiopulmonary bypass, we were unable to find any study comparing the relative merits of these two drugs in this surgical situation. We, therefore decided to compare the relative efficacy of esmolol and diltiazem for heart rate control in patients undergoing coronary revascularisation on the beating heart.

Material & Methods

After approval by the Institute's ethics committee and informed patient's consent, this prospective study was conducted at the Cardiothoracic Centre of All India Institute of Medical Sciences, New Delhi between March 1997 and July 1998 on 60 adult patients with single or two vessel CAD undergoing coronary revascularisation, on the beating heart without cardiopulmonary bypass but through a midline sternotomy. Patients with asthma, chronic obstructive pulmonary disease (COPD), preoperative arrhythmias, poor left ventricular function (EF

In the operation theatre under local anaesthesia intravenous and radial intra arterial monitoring lines were started and a continuous cardiac output pulmonary artery catheter (Vigilance, Baxter Edwards Critical care, Irvine, CA, USA) was introduced through the right internal jugular vein. Anaesthesia was induced with midazolam 0.1 mg/kg and fentanyl 10 (mu)g/kg with vecuronium 0.1 mg/kg to facilitate tracheal intubation. Anaesthesia was maintained with nitrous oxide in oxygen (50%) with 0.4-0.6 per cent halothane and supplemental fentanyl and vecuronium. After measuring base-line haemodynamic parameters including heart rate, mean blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac output, and computing derived parameters including systemic vascular resistance, pulmonary vascular resistance, stroke volume, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, right ventricular stroke work index, and stroke volume index, the patients were randomly divided into two groups of 30 patients each and received either Esmolol 500 (mu)g/kg loading dose followed by an infusion 100 (mu)g/kg/h (Group A), or diltiazem 0.15 mg/kg loading dose followed by a 5 mg/h infusion (Group B).

Haemodynamic parameters were again recorded at the time of distal coronary anastomosis, by which time peak drug effect was assumed to have been achieved. The study drug infusions were discontinued on completion of the distal anastomosis. Results were analysed by the analysis of variance (ANOVA). P values of

Results

A total of 60 adult patients with 1 or 2 vessel CAD, undergoing coronary revascularisation on the beating heart, without use of cardiopulmonary bypass and cardioplegic arrest were studied. Demographic values were similar in both groups. The two groups of patients were similar in respect to their preoperative anti-anginal and anti-hypertensive medication, as seen by comparable base-line haemodynamic parameters. Age of the patients ranged from 39 to 64 yr, mean 49.76 (+/-6.9) yr: There were 16 female and 44 male patients. A mean of 1.5 (+/-0.6) vessels were grafted in Group A, and 1.3 (+/-0.9) in Group B. Left internal mammary artery was used in 29 of the 30 patients in Group A and 28 of the 30 patients in Group B. The other conduit used was the radial artery of the non dominant hand in 16 of Group A and 14 of Group B. Base-line haemodynamics were comparable in the two groups. Haemodynamic parameters at peak drug effect at the start of distal coronary anastomosis, with infusion running are shown in the Table.

Heart rate control was better in Group A, 51.4 (+/-1.3) beats/min, at peak effect compared to base-line values of 80.6 (+/-12.1) beats/min (P

Mean arterial pressures decreased significantly in Group B at peak drug effect compared to base-line (P

Discussion

Single or two vessel CAD, not amenable to percutaneous angioplasty (PTCA) is frequently treated by grafting without the use of cardiopulmonary bypass, or in haemodynamically unstable patients, on bypass without the use of cardioplegia. Control of heart rate is an important aid to the surgical technique on the beating heart allowing precise suture placement during the distal coronary anastomoses.

Although various agents have been advocated for heart rate control including esmolol, diltiazem, metoprolol, atenolol, labetolol, neostigmine and adenosine7, we studied two of the most commonly used drugs esmolol and diltiazem. Diltiazem reduced systemic vascular resistance and afterload, increasing cardiac output slightly. Mean pulmonary artery pressure, pulmonary vascular resistance and pulmonary artery wedge pressures were not significantly affected. Left and right ventricular stroke work index was decreased or unaltered. Use of esmolol in asthmatic patients has been reported to cause only a slight increase in airway pressures and is hence considered safe in patients with COPD8, however we excluded such patients from this study. Although higher than recommended doses of esmolol have been used in some studies9, we found the recommended doses quite adequate if volume status, ventilation and anaesthetic depth were kept adequate. We found heart rate control to be more dramatic with esmolol. Slower heart rates could be achieved with esmolol with quicker return to base-line values on stopping the infusion as compared to diltiazem where the drug effect was more prolonged.

Esmolol did not affect systemic vascular resistance and pulmonary artery wedge pressure significantly but mean pulmonary artery pressure and pulmonary vascular resistance were significantly raised. Right ventricular stroke work index increased significantly. Right ventricular strain is possible with esmolol, and while it may not affect patients with good right ventricular function it may worsen preexisting poor right heart function due to ischaemia or infarction. Esmolol should be cautiously used in such patients for heart rate control. Diltiazem by virtue of its effects on systemic vascular resistance, cardiac Output, and lowering of mean arterial pressure may be a better choice in hypertensive patients.

Recently, the introduction of various tissue stabilisers such as the Octopus stabiliser (Medtronic Corporation, Minneapolis, MN, USA) have reduced the requirement for induced bradycardia to provide a non-moving surgical field. The tissue stabiliser keeps the artery to be bypassed immobile while surgical anastomosis is carried out. Heart rate control is however still desirable in the patient with CAD in order to prevent ischaemia.

References

1.Kaplan JA. Anaesthesia for myocardial revascularisation. In: Kaplan JA (ed): Cardiac Anesthesia (ed3) Philadelphia, PA. WB Saunders: 1991 pp. 689-726.

2. Marcus ML. Metabolic regulation of coronary blood flow. InMarcus ML (ed): The coronary circulation in health and discase. New York, McGraw Hill, 1983;63:651-92.

3. Buffington CW. Haemodynarnic determinants of ischacmic myocardial dysfunction in the presence of coronary stenosis in dogs Anesthesiology 1985;63: 651-612.

4. Gayes JM. Emery RW, Nissen MD. Anaesthetic considerations for patients undergoing minimally invasive coronary artery bypass surgery: Ministernotomy and minithoracotomy approaches. J Cardiothorac Vasc Anesth 1996; 10.531-5.

5. McAllister RG Jr, Hamann SR, Blouin RA. Pharmacokinetics of calcium-entry blockers. Am J Cardiol 1985;55: 30B-40B.

6. Yusuf S. Calcium antagonists in coronary artery disease and hypertension. Time for reevaluation? Circulation 1995;92. 1079-82.

7. Belardineli L, Linden J, Berne RM. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989: 32: 71-97.

8. Menkhaus PG, Reves JG, Kisssin I, Alvis JM. Govier AV. Samuelson PN, et al. Cardiovascular effects of esmolol in anaesthetized humans. Anesth Analg 1985;64: 327-34.

9. Abramson DC, Pivalizza EG, Gottschalk LI. Drug management for coronary revascularisation without cardiac standstill: flic use of high-dose esmolol. J Cardiothorac Vasc Anesth 1994; 9: 184-8.

Sandeep Chauhan, Nita Saxena, B.H. Rao, R.S.K. Singh & Anil Bhan

Cardiothoracic Centre, All India Insttitute of Medicine Sciences, New Delhi

Accepted November 22, 1999

Reprint request: Dr Sandeep Chauhan. Assistant Professor. Department of Cardiac Anaesthesia, Cardiothoracic Centre All India Institute of Medical Sciences, Ansari Nagar, New Dehli 110029

Copyright Indian Council of Medical Research Nov 1999
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