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PERIOPERATIVE VENTRICULAR DYSFUNCTION : CURRENT STRATEGIES FOR MANAGING SERIES 2000 copyright Sanofi-Synthelabo, and Ventiv Healthcare.

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Presentation on theme: "PERIOPERATIVE VENTRICULAR DYSFUNCTION : CURRENT STRATEGIES FOR MANAGING SERIES 2000 copyright Sanofi-Synthelabo, and Ventiv Healthcare."— Presentation transcript:

1 PERIOPERATIVE VENTRICULAR DYSFUNCTION : CURRENT STRATEGIES FOR MANAGING SERIES 2000 copyright Sanofi-Synthelabo, and Ventiv Healthcare

2 C URRENT CONCEPTS IN CARDIAC SURGERY Changing demographics and increasing use of angioplasty, stenting, and platelet inhibitors Older patients with greater myocardial dysfunction and increased comorbidities Estafanous FG, et al. Ann Thorac Surg. 1998;65: Fontana GP. Chest Surg Clin N Am. 1998;8: Verrier ED. J Am Coll Surg. 1999;188:

3 C URRENT CONCEPTS IN CARDIAC SURGERY (CONTD) Expanding use of beating heart and minimally invasive cardiac surgical techniques Alternative surgical therapies for treating congestive heart failure (CHF) Estafanous FG, et al. Ann Thorac Surg. 1998;65: Fontana GP. Chest Surg Clin N Am. 1998;8: Verrier ED. J Am Coll Surg. 1999;188:

4 N EW Y ORK H EART A SSOCIATION (NYHA) FUNCTIONAL CLASSIFICATION Class INo symptoms or limitations on ordinary activity Class IISlight limitation of physical activity. Ordinary activity results in fatigue, dyspnea, or angina Goldman L, et al. Circulation. 1981;64:

5 NYHA FUNCTIONAL CLASSIFICATION (CONTD) Class IIIMarked limitation of physical activity. Patients are asymptomatic at rest and can carry out only very limited physical activity Class IVInability to perform any physical activity without developing symptoms. Some symptoms are present even at rest Goldman L, et al. Circulation. 1981;64:

6 M EDICAL THERAPY OF H EART F AILURE Diuretics Angiotensin-converting enzyme inhibitors  -Adrenergic–receptor blockers (mild to moderate heart failure) Digoxin Vasodilators—oral/intravenous (IV) IV inotropic/inodilator agents (acute decompensation)

7  1 - AND  2 -ADRENERGIC RECEPTOR SUBPOPULATIONS IN HUMAN VENTRICULAR MYOCARDIUM Bristow MR, et al. Circ Res. 1986;59: Receptor density (fmol/mg) Total 22 * *  1 - and  2 -receptor densities in ventricular myocardial membranes prepared from nonfailing (n = 27) and failing (n = 28) human hearts *P<.05 11

8 A NALYSIS OF  -ADRENERGIC RECEPTOR LEVELS IN HUMAN VENTRICULAR BIOPSY SPECIMENS Progressive reduction of  1 -adrenergic receptors in heart failure Engelhardt S, et al. J Am Coll Cardiol. 1996;27: Reduction in  1 Receptor Levels (%) NYHA Class II 7% NYHA Class III 26% NYHA Class IV >50%

9 D IRECT EVIDENCE OF ACUTE CARDIAC  -RECEPTOR DESENSITIZATION DURING CARDIOPULMONARY BYPASS (CPB) IN HUMANS Acute  1 -receptor desensitization—20% Proposed etiology Uncoupling of G-protein from  1 -receptor complex Impaired adenylate cyclase activity  2 -receptor density unchanged Abraham WT, et al. In: Poole-Wilson PA, et al, eds. Heart Failure. 1997: Booth JV, et al. Anesthesiology. 1998;89: Landolfo K, et al. Anesth Analg. 1997;84:SCA 6. Abstract. Schwinn DA, et al. Circulation. 1991;84: Smiley R, et al. Anesth Analg. 1992;74:

10 S YMPATHETIC DOWN-REGULATION IN HEART FAILURE* Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine. 1992: *NE indicates norepinephrine; E, epinephrine; AC, adenylate cyclase; cAMP, cyclic adenosine monophosphate. Normal NE 11 11 E +++ AC +++ cAMP +++ Contractility Down-regulated 11 + AC + cAMP + Contractility NE E

11  -BLOCKADE IN CHRONIC HEART FAILURE Previous thinking: contraindicated Short-term adverse effects Current thinking: indicated in stable mild to moderate heart failure Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997;349: Colucci WS, et al. Circulation. 1996;94: Packer M, et al. Circulation. 1996;94: Packer M, et al. N Engl J Med. 1996;334:

12 E FFECTS OF  -BLOCKADE IN CHRONIC HEART FAILURE Improves cardiac function  ejection fraction (EF)  left ventricular (LV) end-diastolic volume  LV end-systolic volume Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997;349: CIBIS-II Investigators and Committees. Lancet. 1999;353:9-13. Colucci WS, et al. Circulation. 1996;94: Merit HF Study Group. Lancet. 1999;353: Packer M, et al. Circulation. 1996;94: Packer M, et al. N Engl J Med. 1996;334:

13 E FFECTS OF  -BLOCKADE IN CHRONIC HEART FAILURE (CONTD) Reduces symptoms and improves functional class Slows disease progression Reduces risk of hospitalization Improves survival Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997;349: CIBIS-II Investigators and Committees. Lancet. 1999;353:9-13. Colucci WS, et al. Circulation. 1996;94: Merit HF Study Group. Lancet. 1999;353: Packer M, et al. Circulation. 1996;94: Packer M, et al. N Engl J Med. 1996;334:

14 C ARDIAC SURGERY IN PATIENTS WITH DIABETES Diffuse multivessel coronary artery disease Increased preoperative and perioperative myocardial infarction rate Less distensible ventricle due to interstitial glycoprotein Potential for autonomic dysfunction Factor SM, et al. N Engl J Med. 1980;302: Hiramatsu K, et al. Am J Cardiol. 1992;70:

15 C ARDIAC SURGERY IN PATIENTS WITH DIABETES (CONTD) Catecholamines worsen hyperglycemia Increased renal insufficiency, sternotomy complications, and sepsis Increased peripheral vascular disease and intra-aortic balloon pump complications Increased hospital stay and costs Factor SM, et al. N Engl J Med. 1980;302: Hiramatsu K, et al. Am J Cardiol. 1992;70:

16 I MPLICATIONS OF B EATING-HEART SURGERY Beating heart with controlled myocardial ischemia Hemodynamic instability produced by mechanical stabilizers and manipulation Vasoactive and inotropic support may be required during acute periods of surgical revascularization

17 A CUTE MYOCARDIAL DYSFUNCTION AND RECOVERY AFTER CORONARY SURGERY LVEF = left ventricular ejection fraction RVEF = right ventricular ejection fraction Breisblatt WM, et al. J Am Coll Cardiol. 1990;15: Percentage RVEFLVEF Preop Immed postop Nadir (~4 h) Recovery (6-7 h)

18 R ISK FACTORS FOR LOW CARDIAC OUTPUT AFTER CPB Preoperative LV dysfunction Long aortic cross-clamp time and total CPB time Incomplete cardiac surgical revascularization Emergency surgery Persistent ischemia Reperfusion injury and inflammatory changes Hardy JF, et al. J Cardiothorac Vasc Anesth. 1993;7:33-39.

19 R ISK FACTORS FOR LOW CARDIAC OUTPUT AFTER CPB (CONTD) Dysrhythmias Pulmonary hypertension and right ventricular (RV) failure Hardy JF, et al. J Cardiothorac Vasc Anesth. 1993;7:33-39.

20 P REOPERATIVE AND INTRAOPERATIVE PREDIC- TORS OF INOTROPIC SUPPORT AND LONG- TERM OUTCOME IN PATIENTS HAVING CABG Lower preoperative EF Older age Cardiac enlargement on chest x-ray Female sex Higher baseline and postcontrast LV end-diastolic pressure Prolonged bypass or ischemic time Royster RL, et al. Anesth Analg. 1991;72:

21 F ACTORS THAT PREDICT THE NEED FOR INOTROPIC DRUG SUPPORT DURING CARDIAC VALVE SURGERY Increased age History of CHF Increased length of CPB Decreased LVEF Pulmonary hypertension Concurrent coronary artery bypass graft (CABG) Butterworth JF, et al. Anesth Analg. 1998;86:

22 C ONSEQUENCES OF “FAILED WEAN” FROM CPB Ventricular distention  ischemia   contractility Added pump time Increased risk of coagulopathy, pulmonary dysfunction, and neurological injury Greater risk of atrial and ventricular dysrhythmias Lewis KP. J Cardiothorac Vasc Anesth. 1993;7: Parr GVS, et al. Circulation. 1975;51:

23 C ONSEQUENCES OF “FAILED WEAN” FROM CPB (CONTD) Systemic hypotension and organ injury Subsequent need for mechanical support Additional operating room time and costs Lewis KP. J Cardiothorac Vasc Anesth. 1993;7: Parr GVS, et al. Circulation. 1975;51:

24 P OTENTIAL ROLE OF EARLY INOTROPIC THERAPY FOR WEANING FROM CPB Reduced incidence of Ventricular distention Need for mechanical assist devices Multiorgan dysfunction Decreased time on CPB Decreased cost Doolan LA, et al. J Cardiothorac Vasc Anesth. 1997;11:37-41.

25 A DVANTAGES OF INTRAOPERATIVE ECHOCARDIOGRAPHY Systolic and diastolic function LV volume Regional wall motion Direct valve assessment Assessment of the aorta

26 P ERIOPERATIVE ECHOCARDIOGRAPHY: D IAGNOSTIC INDICATIONS Hemodynamic instability of uncertain etiology Valve anatomy and function Aortic assessment Valve repair or replacement Congenital heart surgery Aortic dissection or aneurysm High-risk myocardial revascularization

27 P ERIOPERATIVE ECHOCARDIOGRAPHY: D IAGNOSTIC INDICATIONS (CONTD) Ventricular assist devices Endocarditis Intracardiac air or mass Assessment of myocardial infarction complications Assessment during beating-heart and minimally invasive cardiac surgery

28 A DVANTAGES OF INTRAOPERATIVE ECHOCARDIOGRAPHY Transesophageal echocardiography (TEE) can measure cardiac output and indicate why it is low Global LV and RV dysfunction Regional LV dysfunction (ischemia) LV volume Valvular dysfunction

29 I NTRAOPERATIVE ECHOCARDIOGRAPHIC ASSESSMENT OF AORTA TEE Dissection Type I, II, or III, AR, hemopericardium Aneurysm Location, size, thrombus Epiaortic echo Identifies atherosclerosis of the ascending aorta Risk factor for perioperative CNS injury Wareing TH, et al. Ann Thorac Surg. 1993;55:

30 I NTRAOPERATIVE ECHOCARDIOGRAPHY: H IGH-RISK CORONARY BYPASS Major management alteration Surgical (33%) Pharmacologic therapy (51%) Reduced morbidity and mortality (retrospective) Myocardial infarction (1.2% vs 3.8%) In-hospital CNS morbidity (1.2% vs 3.3%) Hospital mortality (1.2% vs 3.8%) Savage RM, et al. Ann Thorac Surg. 1997;64:

31 S YSTOLIC AND DIASTOLIC FAILURE Pressure Volume Normal CHF (systolic failure) Compliance (diastolic failure) Normal

32 U SE OF IV POSITIVE INOTROPIC DRUGS IN CARDIAC SURGERY Incidence of drug usage varies widely Administered in response to ventricular dysfunction during weaning from bypass Therapy usually continued to the ICU Additional therapy may be required in ICU; however, consider other reversible causes Clinical Process Improvement Program. Clinical Process Improvement: Coronary Artery Bypass Graft (CABG) Clinical Benchmarking Database. Report #2, Royster RL. J Cardiothorac Vasc Anesth. 1993;7:19-25.

33 C OMPLICATIONS OF SYMPATHOMIMETIC THERAPY Dysrhythmias Altered systemic and pulmonary vascular resistance Myocardial ischemia Electrolyte disturbances Hyperglycemia

34 U SE OF INOTROPIC AGENTS AND DYSRHYTHMIAS Any inotropic agent may exert proarrhythmic effects by increasing intracellular cAMP Patients with LV dysfunction may be more prone to nonsustained ventricular tachycardia with any inotropic therapy The incidence of dysrhythmias attributable to all inotropic agents is similar and relatively low Naccarelli GV, et al. Am J Cardiol. 1989;63:35A-40A.

35 G OALS OF THERAPY Maintain organ perfusion pressure Maintain myocardial O 2 supply Optimize O 2 delivery Optimize ventricular loading conditions Optimize pulmonary and systemic arterial afterload conditions

36 P HARMACOLOGIC APPROACHES FOR PERIOPERATIVE BIVENTRICULAR DYSFUNCTION Vasodilator therapy Inotropic agents Catecholamines Phosphodiesterase inhibitors Digoxin, calcium , T 3   Not within product labeling currently approved by the USFDA.  Not currently approved by the FDA for use in the United States. Bailey JM, et al. Adult Cardiac Surgery. 1997: Levy JH. J Cardiothorac Vasc Anesth. 1993;7(suppl): Bennett-Guerrero E, et al, for the Duke T 3 Study Group.Royster RL, et al. Cardiovasc Anesth. 1992;74:3-13. JAMA.1996;275: Pulmonary vasodilators Phosphodiesterase inhibitors Inhaled nitric oxide  Prostaglandins  New agents

37 V ASODILATOR THERAPY Arterial vasodilation decreases ventricular wall stress Venodilation decreases venous return and preload Multiple mechanisms for improving systolic and diastolic dysfunction Nitrate tolerance (chronic use) Therapy may be limited by hypotension Kikura M, et al. Curr Opin Anesth. 1994;7:42-52.Munzel T, et al. Am J Cardiol. 1996;77:24C-30C. Levy JH, et al. Calcium Antagonists in Clinical Medicine Munzel T, et al. J Am Coll Cardiol. 1996;27: Levy JH. J Cardiothorac Vasc Anesth. 1993;7(suppl):46-51.

38 C ATECHOLAMINES: SELECTIVITY OF SYMPATHOMIMETIC DRUGS Alpha Phenylephrine Norepinephrine Epinephrine Dopamine Dobutamine Dopexamine  Isoproterenol Beta  Not currently approved by the FDA for use in the United States. Bailey JM, et al. Adult Cardiac Surgery. 1997: Levy JH. J Cardiothorac Vasc Anesth. 1993;7(suppl):46-51.

39 P ARENTERAL PHOSPHODIESTERASE INHIBITORS Methylxanthines (aminophylline) Bipyridines (milrinone and amrinone) Imidazolones (enoximone  ) Benzylisoquinolines (papaverine)  Not currently approved by the FDA for use in the United States. Bailey JM, et al. Adult Cardiac Surgery. 1997: Levy JH. J Cardiothorac Anesth. 1993;7(suppl):46-51.

40 I NOTROPIC EFFECTS OF PHOSPHODIESTERASE INHIBITORS* Colucci WS, et al. N Engl J Med. 1986;314: *ATP indicates adenosine triphosphate; AMP, adenosine monophosphate; PDE, phosphodiesterase.  -adrenergic agonists Adenylyl cyclase Increased contractility Calcium channel Ca ++ ATP Phosphorylated active kinase Ca ++ cAMP Phosphodiesterase Mg ++ Intracellular PDE inhibitors Inactive protein kinase Extracellular Cell membrane 5' AMP

41 P ERIOPERATIVE DOSING AND ADMINISTRATION OF MILRINONE Loading dose of 50 mcg/kg over 10 min followed by an infusion of 0.5 mcg/kg/min Titrate ( mcg/kg/min) depending on effect Weaning protocols vary Half-life may increase with renal and prolonged administration

42 B ENEFITS OF EARLY PHOSPHODIESTERASE INHIBITOR ADMINISTRATION Increased inotropy (LV and RV) Pulmonary vasodilation Possible avoidance of mechanical pumps Dilation of internal mammary artery (IMA) Possible prevention of a “failed wean” Doolan LA, et al. J Cardiothorac Vasc Anesth. 1997;11:37-41.Hardy JF, et al. J Cardiothorac Vasc Anesth. 1993;7: Doyle AR, et al. Ann Thorac Surg. 1995;59:S3-S11. Lobato EB, et al. Br J Anaesth. 1998;81:

43 M ILRINONE EFFECTS ON LV END-DIASTOLIC PRESSURE AND D P /DT Baim DS, et al. N Engl J Med. 1983;309: ECG dP/dt LV Baseline mm Hg Milrinone

44 M ILRINONE CONCENTRATION AND CARDIAC INDEX (CI) IN CARDIAC SURGICAL PATIENTS Bailey JM, et al. Anesthesiology. 1994;81: % Change in CI Milrinone Concentration (ng/mL)

45 T HE EFFECT OF MILRINONE ON CI AFTER EMERGENCE FROM CPB Changes in CI (mean ± SD)  Not within product labeling currently approved by the USFDA. Kikura M, et al. Anesth Analg. 1997;85: MIL 50 MIL MIL 75  Control *† * * * Time (min) CI (L/min/m 2 )

46 T HE EFFECT OF MILRINONE ON LV FUNCTION AFTER EMERGENCE FROM CPB Changes in velocity of circumferential fiber shortening corrected for heart rate (Vcfc) (mean ± SD)  Not within product labeling currently approved by the USFDA. Kikura M, et al. Anesth Analg. 1997;85: Vcfc (circ/sec) Time (min) MIL 50 MIL MIL 75  Control *†

47 T HE EFFECT OF MILRINONE ON CI AND V CFC AFTER EMERGENCE FROM CPB CI and Vcfc significantly increased from baseline at 5 and 10 min in all milrinone groups CI and Vcfc were significantly higher at 5 and 10 min than in control group No significant changes in CI and Vcfc were observed in control group Kikura M, et al. Anesth Analg. 1997;85:16-22.

48 C AVEATS OF MILRINONE THERAPY Milrinone is a potent venodilator, therefore give cautiously in the hypovolemic patient If patient has LV outflow tract obstruction and mitral regurgitation due to systolic anterior motion of the mitral valve, milrinone should not be administered Hypotension can be attenuated with slower administration, volume administration, and/or concomitant catecholamines

49 A COMPARISON OF MILRINONE LOADING DOSES IN PATIENTS UNDERGOING CARDIAC SURGERY  Not within product labeling currently approved by the USFDA. Butterworth J, et al. Anesth Analg. 1995;81: CI (L/min/m 2 ) Elapsed Time (min) B1B mcg/kg  50 mcg/kg 75 mcg/kg 

50 I N VITRO EFFECTS OF PHOSPHODIESTERASE INHIBITORS ON HUMAN IMA RELAXATION  Not currently approved by the FDA for use in the United States. Salmenpera M, Levy, JH. Anesth Analg. 1996;82: % Relaxation Concentration (mcmol) M P A E A=amrinone E =enoximone  M=milrinone P=papaverine

51 IMA FLOW AFTER MILRINONE AND EPINEPHRINE Lobato EB, et al. J Cardiothorac Vasc Anesth. In press. IMA Flow (mL/min) Before M After M Before E After E *P<.05 compared with pretreatment Values are mean ± SD M = milrinone 50 mcg/kg E = epinephrine 0.03 mcg/kg/min *

52 M ILRINONE IN THE CARDIAC TRANSPLANT SETTING Use to test reversibility of elevated pulmonary vascular resistance  Continuation depends on predrug and postdrug hemodynamics List as status Ia or lb and continue agent(s) until transplant Minimal problems with thrombocytopenia  Not within product labeling currently approved by the USFDA. Givertz MM, et al. J Am Coll Cardiol. 1996;28: Skoyles JR, et al. J Cardiothorac Vasc Anesth. 1993;6:

53 M ILRINONE IN THE CARDIAC TRANSPLANT SETTING (CONTD) Continue agent(s) as a “tune-up” for days to weeks Optimize oral agents and send home as status II Intraoperative and postoperative use to prevent or treat RV failure Givertz MM, et al. J Am Coll Cardiol. 1996;28: Skoyles JR, et al. J Cardiothorac Vasc Anesth. 1993;6:

54 P ERIOPERATIVE VENTRICULAR DYSFUNCTION IN PEDIATRIC PATIENTS Incomplete repair Prolonged CPB and ischemic time Immature myocardium (very calcium-dependent) Afterload sensitivity Pulmonary hypertension

55 H EMODYNAMIC EFFECTS OF MILRINONE IN NEONATES  Increased cardiac output (47%) Decreased systemic vascular resistance (36%) Decreased pulmonary vascular resistance (30%) Decreased right and left atrial pressure  Not within product labeling currently approved by the USFDA. Chang AC, et al. Crit Care Med. 1995;23:

56 H EMODYNAMIC EFFECTS OF A LOADING DOSE (50 MCG/KG) OF MILRINONE IN INFANTS AND CHILDREN  Increased cardiac output (18%) Decreased blood pressure (12%) Decreased systemic vascular resistance (25%)  Not within product labeling currently approved by the USFDA. Bailey JM, et al. Anesthesiology. 1999;90:

57 P HARMACOKINETICS AND DOSING OF MILRINONE IN PEDIATRIC PATIENTS  Larger volume of distribution and clearance than adults Clearance is lower in infants than children A 50 mcg/kg loading dose is therapeutic— an additional loading dose may be needed to maintain therapeutic levels  Not within product labeling currently approved by the USFDA. Bailey JM, et al. Anesthesiology. 1999;90: Ramamoorthy C, et al. Anesth Analg. 1998;86:

58 P HARMACOKINETICS AND DOSING OF MILRINONE IN PEDIATRIC PATIENTS  (CONTD) A 0.5 mcg kg -1 min -1 infusion will maintain therapeutic levels  Not within product labeling currently approved by the USFDA. Bailey JM, et al. Anesthesiology. 1999;90: Ramamoorthy C, et al. Anesth Analg. 1998;86:

59 C OMPARISON OF MILRINONE VERSUS AMRINONE Shorter context-sensitive half-life More titratable Less adverse effects on platelets Similar pharmacodynamic profiles Bailey JM, et al. Anesthesiology. 1994;81: Kikura M, et al. Int Anesthesiol Clin. 1995;33: Kikura M, et al. Anesth Analg. 1995;81: Rathmell JP, et al. Anesth Analg. 1998;86: Salmenpera M, et al. Anesth Analg. 1996;82:

60 S URGICAL APPROACHES TO HEART FAILURE High-risk myocardial revascularization Mitral valve reconstruction Orthotopic heart transplantation (OHT) Ventricular assist devices (as a bridge to OHT, in lieu of OHT  ) Partial left ventriculectomy  Cardiomyoplasty   Not currently approved by the FDA for use in the United States.

61 S URGICAL APPROACHES TO HEART FAILURE: MITRAL VALVE RECONSTRUCTION Preservation of annular-chordal-papillary muscle continuity Maintenance of ellipsoidal chamber geometry Maintenance of LV systolic function Lower LV volume Less end-systolic wall stress Bolling SF, et al. J Thorac Cardiovasc Surg. 1998;115:

62 P ARTIAL LEFT VENTRICULECTOMY WITH MITRAL VALVE REPAIR   Not currently approved by the FDA for use in the United States.

63 M ECHANICAL CIRCULATORY SUPPORT Intra-aortic balloon pump Abiomed BVS 5000 Bio-Medicus Thoratec Farrar DJ, et al. Ann Thorac Surg. 1996;61: Noon GP, et al. Ann Thorac Surg. 1996;61: Frazier OH, et al. Ann Surg. 1995;222: Torchiana DF, et al. J Thorac Cardiovasc Surg. Jett GK. Ann Thorac Surg. 1996;61: ;113: McCarthy PM, et al. Sem Thorac Cardiovasc Surg. 1994;6: TCI HeartMate left ventricular assist device (LVAD) Novacor LVAD Axial flow pumps


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