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High-dose esmolol and cardiopulmonary bypass for mitral valve replacement in the beating heart
High-Dose Esmolol and Cardiopulmonary Bypass for Mitral Valve Replacement in the Beating Heart Evan G. Pivalizza, MBChB, FFASA, and Michael S. Sweeney, MD NITIAL EXPERIENCE with high-dose esmolol administration to facilitate coronary revascularization on the nonarrested heart has been encouraging.1 In addition to the favorable effects of beta-adrenergic blockers on myocardial oxygen balance, a recent review noted accumulating evidence for the use of beta-blockers in patients with chronic heart failure (CHF). 2 The authors describe a patient presenting for mitral valve replacement (MVR), whose severe left ventricular dysfunction led to concern regarding the ability to wean from cardiopulmonary bypass (CPB). In view of the potential physiological benefits in this patient, the M V R was performed on CPB without cardiac arrest and with high-dose esmolol.
I
CASE REPORT
A 59-year-old woman (weight 110 kg, height 1.6 m) was referred for MVR. History was significant for deteriorating exercise tolerance (NYHA III), atrial fibrillation (AF), and insulin-dependent diabetes mellitus. Relevant clinical findings included AF with a ventricular rate of 90 beats/min, blood pressure of 110/60 mmHg, a 4/6 pansystolic murmur at the apex, and bibasilar crackles. The chest radiograph confirmed cardiomegaly with mild pulmonary congestion, and transthoracic echocardiograpby showed severe mitral regurgitation with an ejection fraction (EF) of 30%, and minimal improvement (EF 35%) with dobutamine (30 jag/kg/min). There was no ST-T wave change or chest pain with the stress echocardiogram. Medications included humulin insulin ( 2 0 U in the morning, and 17 U in the afternoon), digoxin (0.125 mg daily), propafenone (150 mg three times a day), captopril (I 2.5 mg twice a day), and aspirin. On the day before surgery, an intraaortic balloon pump (IABP) was placed, intravenous heparin therapy was initiated, and the patient was cardioverted to sinus rhythm. Preoperative laboratory indices (including blood urea nitrogen [12 mg/dL] and creatinine [0.8 mg/dL]) were within normal limits. On the morning of surgery, routine monitors were attached and radial and pulmonary artery catheters inserted. Anesthesia was induced with fentanyl (10 gg/kg) and sodium thiopental (2 mg/kg), intnbation facilitated with pancuronium (10 mg), and anesthesia maintained with fentanyl (total dose of 20 pg/kg) and up to 0.6% end-tidal isoflurane. Prebypass hemodynamic parameters are presented in Table 1. After heparinization, and aortic and bicaval cannulation, the left ventricular apex was vented, the patient cooled to 34°C, and a flow rate greater than 5 L/rain was maintained on bypass. An esmolol infusion was initiated at 300 pg/kg/min, with additional 250-mg boluses (to a total dose of 4.5 g) to decrease mobility and contractility of the heart. Hemodynamic parameters remained stable (Table 1), with the lowest mean arterial pressure of 44 mmHg, lowest heart rate (HR) of 50 beats/min, and lowest mixed venous oxygen saturation (SvQ) of 66%. After right atriotomy, the mitral valve was exposed through a window in the interatrial septum, and replaced with a 23-mm St. Jude prosthesis. As with the authors' previous experience in patients with significant myocardial depression, the added negative inotropy of esmolol combined with ventricular unloading led to insignificant myocardial motility that did not impede surgical access. There was no evidence of left ventricu!ar ejection on the arterial pressure line. The esmolol infusion was terminated after seating of the prosthetic valve. The left atrium was filled with blood and de-aired, the interatrial defect closed with a Dacron patch (Meadux Medical, Inc, Oakland, NJ), and the right atrium similarly filled with blood and de-aired, with the patient in the Trendelenburg position. During atrial closures, a loading dose of amrinone (1.4 mg/kg) was administered and an epinephrine infusion
initiated (maximum dose, 0.09 #g/kg/min). The IABP was restarted at a 1/1 ratio, and the patient was successfully weaned from bypass. Hemodynamics were stable (apart from intermittent AF) (Table 1), protamine was administered, and the epinephrine was weaned to 0.04 #g/kg/min before skin closure. The patient made a steady recovery, was extubated the following morning, with removal of the IABP on day 4 and weaning of inotropic support on day 5. The patient was discharged home on day 13, the AF having required pharmacological manipulation with amiodarone, diltiazero, and cardioversien. DISCUSSION
The use of high-dose esmolol has recently been reported for coronary revascularization on the beating heart, with or without ventricular assist devices,l,3 during left thoracotomy for reoperative coronary artery bypass, 4 and a combination of thoracotomy and partial CPB.2 The positive influence of beta-blocker administration on determinants of myocardial oxygen balance is well known, and avoidance of aortic cross-clamping and the attendant reperfusion injury may be beneficial in patients with poor preoperative ventricular function.l Patients for M V R often have impaired ventricular function and elevated pulmonary artery pressures. In this patient with significant myocardial dysfunction (in the absence of significant coronary artery disease), there was concern that the minimal myocardial reserve would not tolerate further deterioration after reperfusion in the presence of a competent prosthetic valve. Therefore, surgical replacement was planned On full cardiopulmonary bypass support, without cardiac arrest. A competent aortic valve was a prerequisite for the planned procedure to prevent passive left ventricular filling and potential systemic air emboli. Although the inotropy of impaired ventricles decreases significantly with the reduction in preload on initiation of CPB, cardiac activity still interferes with surgical access during coronary revascularization and MVR. Therefore, on full CPB support, esmolol was titrated to facilitate surgical exposure. As previously noted with patients for revascularization, 1 the heart rate did not fall below 40 beats/min, and there were no episodes of asystole or ventricular arrhythmia. Avoidance of the increased myocardial oxygen demand associated with ventricular distention after asystole, or ventricular tachycardia/fibrillation, is important for the success of this technique. The left ventricle was also vented to prevent increased wall tension and potential subendocardial ischemia. Mean arterial pressure was maintained without vasopressor support, and systemic oxygen
From the Departments of Anesthesiology and Thoracic and CardiovascuIar Surgery, University of Texas, Houston. Address correspondence to Evan G. Pivalizza, MBChB, FFASA, Department of Anesthesiology, University of Texas Medical School at Houston, MSB 5.020, 6431 Fannin, Houston, TX, 77030. Copyright © 1997 by W.B. Saunders Company 1053-0770/97/1104-0016503.00/0 Key words: cardiovascular anesthesia, mitral valve replacement, beta-adrenergic antagonist, esmolol, beta-blockade
Journal of Cardiothoracic and Vascular Anesthesia, Vol 11, No 4 (June), 1997: pp 485-486
485
486
PIVALIZZA AND SWEENEY
Table 1. Perioperative Hemodynamic Variables 45 Minutes 90 Minutes Pre-CPB of CPB of CPB
HR [beats/min) MAP (mmHg) MPAP ImmHg) PCWP (mmHg) CI (L/min/m) SvO2 (%)
56 66 25 14 1.3 60
58 52 6 NM NM 66
64 44 4 NM NM 77
Post-CPB
ICU
102 (AF) 66 35 25 1.9 73
106 (AF) 62 26 16 1.9 60
Abbreviations: AF, atrial fibrillation; HR, heart rate; CI, cardiac index; NM, no measure; MAP, mean arterial pressure; MPAP. mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SVO2, mixed venous oxygen saturation.
delivery was presumed adequate in the presence of bypass flows of >2.2 L/mirdm 2 and normal SvO2 measurements (although flow through the pulmonary circulation was minimal). The dose of esmolol infused over 60 minutes was simiIar to that previously reported. 1 and Cork et al6 found no evidence of esmolol effect after an average dose of 4.3 g administered over 3 hours to patients on bypass. Methanol accumulation has not been found after a calculated dose of 7.5 g administered over 6 hours (OHMEDA PPD. Inc. [Liberty Corner. NJ] package insert for esmolol hydrochloride, May 1993). With this evidence and the favorable elimination half-life of esmolol (9 minutes), significant methanol accumulation was not expected. As baseline ventricular function was impaired with elevated pulmonary artery pressure, a loading dose of amrinone was administered before termination of bypass, and weaning from CPB was
achieved with epinephrine support (0.9 pg/kg/min) and resumption of aortic balloon counterpulsation. Because the poor preoperative function dictated proactive preparation for CPB separation, the role (!f any) of residual esmolol effects is unclear. Significant short-term effects attributable to esrnolol seem unlikely in the face of the steady but protracted postoperative wean from mechanical and pharmacological support. The authors reported use of high-dose esmolol as an adjunct to CPB without Cardiac arrest in a patient undergoing MVR. Thereby, the consequences of the reperfusion injury were avoided in the presence of impaired ventricular function. Meticulous surgical technique was necessary to prevent ventricular distention (left ventricular Vent) or potential air emboli (ventricuiar decompression, careful de-airing of the atria and left ventricle in the Trendelenburg position, and the decreased inotropy of beta-blockade combined with the intrinsic myocardial dysfunctioni. In addition to the expected advantages of beta-adrenergic blockade presented in this report, use of beta-blockers in CHF is being revisited, 2 with impr0ved hemodynamics and symptoms after addition of carvedilol. 7,8 Mechanisms may include upregulation of beta-receptors, myocardial protection from elevated catecholamines, and antagonism of th e sympathetic system in CHF. Although the short-term effects of esmolol are too transient to have similar impact~ the physiological appeal of beta-adrenergic blockers in the patient with poo r ventficular function undergoing CPB suggests that further study is necessary with this novel technique.
REFERENCES
1. Abramson DC. Pivalizza EG. Gottschalk LI: Drug managemem for coronary revascularization without cardiac standstill: The use of high-dose esmolol. J Cardiothorac Vasc Anesth 9:184-188. 1995 2. Sackner-Bernstein JD. Mancini DM: Rationale for treatment of patients with chronic heart failure with adrenergic blockade. JAMA 274:1462-1467, 1995 3. Sweeney MS. Frazier OH: Device-supported myocardial revascularization: Safe help for sick hearts. Ann Thorac Surg 54:1065-1070, 1992 4. Ungerleider RM. Mills NL. Wechsler AS: Left thoracotomy for reoperative coronary artery bypass procedures. Ann Thorac Surg 40:!1-15, 1985
5. Grocon HP, Grichnik K: Partial cardiopulmonary bypass, highdose esmolol, and a left thoracotomy for reoperative coronary artery bypass graft surgery. Anesth Analg 82:SCA 129, 1996 6. Cork RC, Kramer TH, Dreischmeier B, et al: The effect of esmolol given during cardiopulmonary bypass. Anesth Analg 80:28-40, 1995 7. Olsen SL, Gilbert EM, Renlund DG, et al: Carvedilol improves left ventricular function and symptoms in chronic heart failure: A double-blind randomized study: J Am C oll Cardio125:1225-1231, 1995 8: Krum H, Sackner-Bernstein J, Goldsmith RL, et al: Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure. Circulation 92:1499-1506, 1995
I
CASE REPORT
A 59-year-old woman (weight 110 kg, height 1.6 m) was referred for MVR. History was significant for deteriorating exercise tolerance (NYHA III), atrial fibrillation (AF), and insulin-dependent diabetes mellitus. Relevant clinical findings included AF with a ventricular rate of 90 beats/min, blood pressure of 110/60 mmHg, a 4/6 pansystolic murmur at the apex, and bibasilar crackles. The chest radiograph confirmed cardiomegaly with mild pulmonary congestion, and transthoracic echocardiograpby showed severe mitral regurgitation with an ejection fraction (EF) of 30%, and minimal improvement (EF 35%) with dobutamine (30 jag/kg/min). There was no ST-T wave change or chest pain with the stress echocardiogram. Medications included humulin insulin ( 2 0 U in the morning, and 17 U in the afternoon), digoxin (0.125 mg daily), propafenone (150 mg three times a day), captopril (I 2.5 mg twice a day), and aspirin. On the day before surgery, an intraaortic balloon pump (IABP) was placed, intravenous heparin therapy was initiated, and the patient was cardioverted to sinus rhythm. Preoperative laboratory indices (including blood urea nitrogen [12 mg/dL] and creatinine [0.8 mg/dL]) were within normal limits. On the morning of surgery, routine monitors were attached and radial and pulmonary artery catheters inserted. Anesthesia was induced with fentanyl (10 gg/kg) and sodium thiopental (2 mg/kg), intnbation facilitated with pancuronium (10 mg), and anesthesia maintained with fentanyl (total dose of 20 pg/kg) and up to 0.6% end-tidal isoflurane. Prebypass hemodynamic parameters are presented in Table 1. After heparinization, and aortic and bicaval cannulation, the left ventricular apex was vented, the patient cooled to 34°C, and a flow rate greater than 5 L/rain was maintained on bypass. An esmolol infusion was initiated at 300 pg/kg/min, with additional 250-mg boluses (to a total dose of 4.5 g) to decrease mobility and contractility of the heart. Hemodynamic parameters remained stable (Table 1), with the lowest mean arterial pressure of 44 mmHg, lowest heart rate (HR) of 50 beats/min, and lowest mixed venous oxygen saturation (SvQ) of 66%. After right atriotomy, the mitral valve was exposed through a window in the interatrial septum, and replaced with a 23-mm St. Jude prosthesis. As with the authors' previous experience in patients with significant myocardial depression, the added negative inotropy of esmolol combined with ventricular unloading led to insignificant myocardial motility that did not impede surgical access. There was no evidence of left ventricu!ar ejection on the arterial pressure line. The esmolol infusion was terminated after seating of the prosthetic valve. The left atrium was filled with blood and de-aired, the interatrial defect closed with a Dacron patch (Meadux Medical, Inc, Oakland, NJ), and the right atrium similarly filled with blood and de-aired, with the patient in the Trendelenburg position. During atrial closures, a loading dose of amrinone (1.4 mg/kg) was administered and an epinephrine infusion
initiated (maximum dose, 0.09 #g/kg/min). The IABP was restarted at a 1/1 ratio, and the patient was successfully weaned from bypass. Hemodynamics were stable (apart from intermittent AF) (Table 1), protamine was administered, and the epinephrine was weaned to 0.04 #g/kg/min before skin closure. The patient made a steady recovery, was extubated the following morning, with removal of the IABP on day 4 and weaning of inotropic support on day 5. The patient was discharged home on day 13, the AF having required pharmacological manipulation with amiodarone, diltiazero, and cardioversien. DISCUSSION
The use of high-dose esmolol has recently been reported for coronary revascularization on the beating heart, with or without ventricular assist devices,l,3 during left thoracotomy for reoperative coronary artery bypass, 4 and a combination of thoracotomy and partial CPB.2 The positive influence of beta-blocker administration on determinants of myocardial oxygen balance is well known, and avoidance of aortic cross-clamping and the attendant reperfusion injury may be beneficial in patients with poor preoperative ventricular function.l Patients for M V R often have impaired ventricular function and elevated pulmonary artery pressures. In this patient with significant myocardial dysfunction (in the absence of significant coronary artery disease), there was concern that the minimal myocardial reserve would not tolerate further deterioration after reperfusion in the presence of a competent prosthetic valve. Therefore, surgical replacement was planned On full cardiopulmonary bypass support, without cardiac arrest. A competent aortic valve was a prerequisite for the planned procedure to prevent passive left ventricular filling and potential systemic air emboli. Although the inotropy of impaired ventricles decreases significantly with the reduction in preload on initiation of CPB, cardiac activity still interferes with surgical access during coronary revascularization and MVR. Therefore, on full CPB support, esmolol was titrated to facilitate surgical exposure. As previously noted with patients for revascularization, 1 the heart rate did not fall below 40 beats/min, and there were no episodes of asystole or ventricular arrhythmia. Avoidance of the increased myocardial oxygen demand associated with ventricular distention after asystole, or ventricular tachycardia/fibrillation, is important for the success of this technique. The left ventricle was also vented to prevent increased wall tension and potential subendocardial ischemia. Mean arterial pressure was maintained without vasopressor support, and systemic oxygen
From the Departments of Anesthesiology and Thoracic and CardiovascuIar Surgery, University of Texas, Houston. Address correspondence to Evan G. Pivalizza, MBChB, FFASA, Department of Anesthesiology, University of Texas Medical School at Houston, MSB 5.020, 6431 Fannin, Houston, TX, 77030. Copyright © 1997 by W.B. Saunders Company 1053-0770/97/1104-0016503.00/0 Key words: cardiovascular anesthesia, mitral valve replacement, beta-adrenergic antagonist, esmolol, beta-blockade
Journal of Cardiothoracic and Vascular Anesthesia, Vol 11, No 4 (June), 1997: pp 485-486
485
486
PIVALIZZA AND SWEENEY
Table 1. Perioperative Hemodynamic Variables 45 Minutes 90 Minutes Pre-CPB of CPB of CPB
HR [beats/min) MAP (mmHg) MPAP ImmHg) PCWP (mmHg) CI (L/min/m) SvO2 (%)
56 66 25 14 1.3 60
58 52 6 NM NM 66
64 44 4 NM NM 77
Post-CPB
ICU
102 (AF) 66 35 25 1.9 73
106 (AF) 62 26 16 1.9 60
Abbreviations: AF, atrial fibrillation; HR, heart rate; CI, cardiac index; NM, no measure; MAP, mean arterial pressure; MPAP. mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SVO2, mixed venous oxygen saturation.
delivery was presumed adequate in the presence of bypass flows of >2.2 L/mirdm 2 and normal SvO2 measurements (although flow through the pulmonary circulation was minimal). The dose of esmolol infused over 60 minutes was simiIar to that previously reported. 1 and Cork et al6 found no evidence of esmolol effect after an average dose of 4.3 g administered over 3 hours to patients on bypass. Methanol accumulation has not been found after a calculated dose of 7.5 g administered over 6 hours (OHMEDA PPD. Inc. [Liberty Corner. NJ] package insert for esmolol hydrochloride, May 1993). With this evidence and the favorable elimination half-life of esmolol (9 minutes), significant methanol accumulation was not expected. As baseline ventricular function was impaired with elevated pulmonary artery pressure, a loading dose of amrinone was administered before termination of bypass, and weaning from CPB was
achieved with epinephrine support (0.9 pg/kg/min) and resumption of aortic balloon counterpulsation. Because the poor preoperative function dictated proactive preparation for CPB separation, the role (!f any) of residual esmolol effects is unclear. Significant short-term effects attributable to esrnolol seem unlikely in the face of the steady but protracted postoperative wean from mechanical and pharmacological support. The authors reported use of high-dose esmolol as an adjunct to CPB without Cardiac arrest in a patient undergoing MVR. Thereby, the consequences of the reperfusion injury were avoided in the presence of impaired ventricular function. Meticulous surgical technique was necessary to prevent ventricular distention (left ventricular Vent) or potential air emboli (ventricuiar decompression, careful de-airing of the atria and left ventricle in the Trendelenburg position, and the decreased inotropy of beta-blockade combined with the intrinsic myocardial dysfunctioni. In addition to the expected advantages of beta-adrenergic blockade presented in this report, use of beta-blockers in CHF is being revisited, 2 with impr0ved hemodynamics and symptoms after addition of carvedilol. 7,8 Mechanisms may include upregulation of beta-receptors, myocardial protection from elevated catecholamines, and antagonism of th e sympathetic system in CHF. Although the short-term effects of esmolol are too transient to have similar impact~ the physiological appeal of beta-adrenergic blockers in the patient with poo r ventficular function undergoing CPB suggests that further study is necessary with this novel technique.
REFERENCES
1. Abramson DC. Pivalizza EG. Gottschalk LI: Drug managemem for coronary revascularization without cardiac standstill: The use of high-dose esmolol. J Cardiothorac Vasc Anesth 9:184-188. 1995 2. Sackner-Bernstein JD. Mancini DM: Rationale for treatment of patients with chronic heart failure with adrenergic blockade. JAMA 274:1462-1467, 1995 3. Sweeney MS. Frazier OH: Device-supported myocardial revascularization: Safe help for sick hearts. Ann Thorac Surg 54:1065-1070, 1992 4. Ungerleider RM. Mills NL. Wechsler AS: Left thoracotomy for reoperative coronary artery bypass procedures. Ann Thorac Surg 40:!1-15, 1985
5. Grocon HP, Grichnik K: Partial cardiopulmonary bypass, highdose esmolol, and a left thoracotomy for reoperative coronary artery bypass graft surgery. Anesth Analg 82:SCA 129, 1996 6. Cork RC, Kramer TH, Dreischmeier B, et al: The effect of esmolol given during cardiopulmonary bypass. Anesth Analg 80:28-40, 1995 7. Olsen SL, Gilbert EM, Renlund DG, et al: Carvedilol improves left ventricular function and symptoms in chronic heart failure: A double-blind randomized study: J Am C oll Cardio125:1225-1231, 1995 8: Krum H, Sackner-Bernstein J, Goldsmith RL, et al: Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure. Circulation 92:1499-1506, 1995