Gen Thorac Cardiovasc Surg (2008) 56:563–565 DOI 10.1007/s11748-008-0301-4
CASE REPORT
Levosimendan and severe pulmonary hypertension during open heart surgery Ferit Cicekcioglu, MD · Ali Ihsan Parlar, MD Ozgur Ersoy, MD · Kerem Yay, MD · Alaa Hijazi, MD S. Fehmi Katircioglu, MD
Received: 28 November 2007 / Accepted: 2 July 2008 © The Japanese Association for Thoracic Surgery 2008
Abstract Weaning from cardiopulmonary bypass is the most important stage during mitral valve surgery, especially in patients with severe pulmonary hypertension. We report two patients with severe pulmonary hypertension who were operated on because of valvular heart disease. To reduce the pulmonary artery pressure, levosimendan was used because of its vasodilatory and cytoprotective effects. All patients tolerated the operation and levosimendan administration. Their postoperative course was uneventful. Levosimendan can be used to treat pulmonary hypertension during operations for heart valve disease. Patients clearly benefit from the vasodilator action of the drug for reducing pulmonary artery pressure.
levosimendan was used in patients with various conditions—e.g., myocardial protection, difficulty weaning from cardiopulmonary bypass (CPB). Levosimendan is a calcium sensitizer that enhances myocardial contractility and produces both coronary and peripheral vasodilatation. Its vasodilatatory effect is related to activation of ATP-sensitive potassium channels.2 We selected levosimendan for use in two patients with seriously high PAP because it is a vasodilatator and cytoprotective agent that increases contractility without increasing oxygen consumption.2,3
Key words Levosimendan · Preconditioning · Pulmonary hypertension · Valve repair/replacement
A 54-year-old woman was seen in a hospital with dyspnea. She was classified as having New York Heart Association (NYHA) class III disease. Her electrocardiogram (ECG) showed an atrial fibrillation rhythm. Transthoracic echocardiography revealed mitral stenosis (21/10 mmHg peak/mean gradient), third-degree aortic insufficiency, aortic stenosis (60/30 mmHg peak/ mean gradient), ejection fraction 60%, and 120 mmHg systolic PAP. Coronary angiography and catheterization were performed, and we found normal coronary artery anatomy and 120 mmHg systolic PAP (sPAP). The other patient, a 64-year-old woman was admitted to our clinic with symptoms of dyspnea, orthopnea, and stable angina pectoris. She was classified as NYHA class III and had risk factors such as hypertension and diabetes mellitus. Her ECG showed sinus rhythm. Transthoracic echocardiography revealed fourth-degree mitral insufficiency, ejection fraction 50%–55%, and 95 mmHg sPAP. Coronary angiography and catheterization revealed proximal left anterior descending coronary
Introduction Pulmonary hypertension is the result of critical mitral valve stenosis, and elevated pulmonary artery pressure (PAP) is a risk factor for postoperative recovery.1 Various agents have been used to reduce the morbidity and mortality risk of pulmonary hypertension,1 with the main aim of this therapy being to reduce the PAP. Recently,
F. Cicekcioglu · A.I. Parlar · O. Ersoy · K. Yay · A. Hijazi · S.F. Katircioglu (*) Kalp ve Damar Cerrahisi Klinigi (Cardiovascular Surgery Clinic), Turkiye Yuksek Ihtisas Hastanesi, Sihhiye, Ankara 06100, Turkey Tel. +90-312-306-1188; Fax +90-312-229-5868 e-mail:
[email protected]
Case report
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Gen Thorac Cardiovasc Surg (2008) 56:563–565
Table 1 Test results for cases 1 and 2 Measurement
CI (l/min) PCWP (mmHg) MAP (mmHg) MPAP (mmHg) RAP (mmHg) SVRI (dyne s/cm5/m2) PVRI (dyne s/cm5/m2)
Case 1
Case 2
Preop
After Levo
Postop —6 h
Postop —12 h
Postop —24 h
Preop
After levo
Postop —6 h
Postop —12 h
Postop —24 h
2.17 13 100 80 12 1365 1046
3.45 15 57 58 6 495 418
3.61 14 60 60 6 503 377
3.93 17 70 55 9 523 320
4.19 26 70 60 7 507 269
1.58 21 78 75 5 1263 935
2.51 17 80 63 4 836 500
2.98 15 81 50 3 723 321
3.33 18 80 52 0 723 278
3.74 15 61 50 6 491 255
Levo, levosimendan; CI, cardiac index; PCWP, pulmonary capillary wedge pressure; MAP, mean arterial pressure; MPAP, mean pulmonary arterial pressure; RAP, right atrial pressure; SVRI, systemic vascular resistance index; PVRI, pulmonary vascular resistance index; Preop, preoperatively; Postop, postoperatively
artery (LAD) 70% stenosis, proximal circumflex artery (CX) 95% stenosis, right coronary artery (RCA) 20% stenosis, and 115 mmHg sPAP. The changes in the following measurements for both patients before, during, and after levosimendan administration are detailed in Table 1: cardiac index, pulmonary capillary wedge pressure, mean arterial pressure, mean pulmonary arterial pressure, right atrial pressure, systemic vascular resistance index, and pulmonary vascular resistance index.
Surgical Technique After induction of general anesthesia, levosimendan was administered to decrease the preload and afterload during surgery. We administered levosimendan with a bolus dose of 12 μg/kg/min for 10 min and then instituted an infusion at a rate of 0.1 μg/kg/min.4 After median sternotomy aortic and bicaval cannulation were performed, CPB (2.5 l/m²) was initiated, the aorta was cross-clamped, and crystalloid cardioplegia was introduced antegradely and retrogradely. Cold blood cardioplegia was used retrogradely every 20 min through the coronary sinus. The patient’s temperature was reduced to 31°C. In the first patient, the mitral and aortic valves were replaced with 29 mm and 21 mm mechanical prostheses, respectively; and tricuspid annuloplasty was performed. The cross-clamp and CPB times were 66 and 98 min, respectively. In the second patient, left internal thoracic artery (LITA) to the LAD (LITA–LAD), saphenous vein graft to the diagonal artery (D) from the aorta (Ao–saphenous vein–D), and saphenous vein graft to the CX posterolateral branch (Ao–saphenous–CXPL) bypass grafting were performed. Then the mitral valve was repaired with the Wooler annuloplasty technique. The cross-clamp and CPB times were 47 and 94 min, respectively. Warm blood cardioplegia was instituted
before releasing the cross-clamp terminal. The patients were weaned from CPB without difficulty. The patients were then transferred to the intensive care unit (ICU), where the levosimendan infusion was continued for 24 h. The duration of the ICU stay was 24 h for the first patient, who was discharged from the hospital on postoperative day (POD) 10. Before discharge, control echocardiography showed a normal functional prosthesis, 60% ejection fraction, and 60 mmHg sPAP. An intraaortic balloon pump (IABP) was inserted in second patient in the ICU because of hypotension and bradycardia. The IABP was removed on POD 6, and the patient was discharged from the hospital on POD 11. Before discharge, control echocardiography showed a normal functional mitral valve with minimal insufficiency, ejection fraction 50%–55%, and 45 mmHg sPAP.
Discussion During and after cardiac surgery various agents, such as prostaglandins and nitrates, have been introduced to reduce an elevated PAP with varying degrees of success.1 Levosimendan has been used for various indications, such as poor left ventricular function.2,3 The effect of levosimendan on vascular bed is vasodilatation and this can be seen in many of the coronary and pulmonary vessels.4,5 Although this vasodilatation effect of levosimendan has not been detailed, it is known that an important pathway is ATP-sensitive potassium (KATP) channels in small resistance vessels and calciumactivated potassium- and voltage-dependent potassium channels in large conductance vessels.6,7 The vasodilatation effect of levosimendan on pulmonary arteries seems to be related to this pathway. When the pathway is working, it ends with the decrease of intracellular calcium
Gen Thorac Cardiovasc Surg (2008) 56:563–565
that produces pulmonary vessel vasodilatation. A second mechanism of this pathway is that the decreased sensitivity of vascular smooth muscle contractile proteins against calcium may play a role in vasodilatation.8 Beyond these two mechanism, especially at higher doses of levosimendan, vasodilatation occurs by the inhibition of phosphodiesterase (PDE) in vascular smooth muscle.9 Inhibition of PDE by levosimendan creates an increased concentration of cAMP in the vascular smooth muscle of pulmonary vessels and cascade that ends in vasodilatation. In the two patients described herein, we were able to demonstrate that excessively high PAP can be controlled by levosimendan, an inodilator agent. PAP >50 mmHg is referred to as pulmonary hypertension. In this report we selected two patients whose sPAP was >100 mmHg. We assumed that the level of sPAP is associated with varying degrees of right and left ventricular failure. Major determinants of ventricular performance are preload, afterload, and contractility. The right ventricle works in a volume-dependent manner and is susceptible to changes in afterload. In contrast to the left ventricle, a small increase in afterload leads to a significant reduction in right ventricular function, which later leads to left ventricular failure. Levosimendan has a vasodilatator effect and can cause systemic hypotension in some patients. We observed this hypotensive effect of levosimendan in our second patient. Despite the hypotension, we did not terminate the levosimendan infusion because of its benefits of contractility and lowering pulmonary hypertension. To provide hemodynamic stability and increase coronary perfusion, we used an IABP instead of other inotropic agents, which can increase oxygen consumption of myocardium. The therapeutic target of this problem is to reduce PAP and increase right ventricular contractility without causing systemic hypotension. Thus, levosimendan has become the focus of our interest for treating this type of disorder.
Conclusion Levosimendan is a new drug that is currently being introduced into clinical use. Its widely accepted indica-
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tions are acute postinfarction cardiac failure, diastolic cardiac failure, and low-cardiac-output syndrome following coronary artery bypass grafting.3 On searching in the medical literature, we found limited trials that used levosimendan to reduce high pulmonary pressure in patients with right ventricular failure.10 We used levosimendan during mitral valve surgery in patients who had seriously high PAP. There is a clear benefit achieved by the vasodilator characteristics of the drug for reducing high PAP and for protecting right ventricular contractility. We think that preconditioning with levosimendan in patients who have seriously high PAP is an attractive subject to investigate. Clinical and randomized trials should be carried out.
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