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Eur J Cardiothorac Surg 2004;26:228-230
© 2004 Elsevier Science NL

Case report

Treatment of acute heart failure in an infant after cardiac surgery using levosimendan

^a Department of Anesthesiology und Intensive Care, Charité University–Hospital, Humboldt University, Schumann Str. 20-21, Berlin D-10117, Germany
^b Department of Pediatric Cardiology, Charité University–Hospital, Humboldt University, Berlin, Germany
^c Department of Cardiovascular Surgery, Charité University–Hospital, Humboldt University, Berlin, Germany

Received 18 December 2003; received in revised form 1 March 2004; accepted 24 March 2004.

^* Corresponding author. Tel.: +49-30-450-531012; fax: +49-30-450-911
e-mail: jan.braun{at}charite.de

	Abstract

Top Abstract 1. Case report 2. Discussion References

 
An infant, 2 months old, underwent cardiac surgery because of congenital heart defects and pulmonary hypertension. Surgery was performed in hypothermia and cardiac standstill. On the second day after surgery the infant had to be resuscitated due to a combination of acute left-ventricular failure, pulmonary vascular hypertension and a slight right-to-left-shunt. A breakthrough in the treatment was achieved by using levosimendan to improve left-ventricular function and to decrease vascular resistance.

Key Words: Neonatal cardiac surgery • Postoperative resuscitation • Calcium sensitizer • Levosimendan

	1. Case report

Top Abstract 1. Case report 2. Discussion References

 
A 2-month-old female infant (3400 g) with a hypoplastic aortic arch, normal left-ventricular function, multiple muscular ventricle-septum-defects (VSD), a persistent open foramen ovale and a pulmonary hypertension equivalent to the systemic blood pressure underwent cardiac surgery, which was performed in deep hypothermia, circulatory arrest, and cardiopulmonary-bypass (CPB). The aortic arch was widened using a pericardial-patch. The largest of VSDs was closed using a Gore-Tex-patch. The closure of two small muscular VSDs (smaller than 2 mm) was not possible.

Immediately after surgery transthoracic echocardiography (TTE) gave evidence of a hypocontractile and dilated left ventricle (fractional-shortening (FS) about 20%). Using the TTE the pulmonary-artery-pressure was estimated 20 mmHg lower than the systolic-blood-pressure. The left-ventricular function improved and reached nearly normal function during the next hours. With the application of intravenous nitroglycerine (0.5 µg kg^–1 min^–1) and dobutamine (5 µg kg^–1 min^–1) the patient was cardiovascular stable. It was possible to extubate the infant 18 h postoperatively. The oxygenation-saturation was 99% under the application of 0.5 l min^–1 oxygen. The baby was vigilant, the diuresis was normal and no lactatemia was observed.

Forty-eight hours following surgery and 30 min after the attempt to drink 10 ml, the infant developed a bradycardia followed by a cardiac-arrest. The infant had to be re-intubated and resuscitated for 45 min. Epinephrine was given in a cumulative dosage of 1.5 mg. The transesophageal-echocardiography (TEE) during resuscitation showed a massive dilation of the left-ventricle accompanied by complete akinesia. After the application of 3 mg enoximone a slight contraction of the left-ventricle was seen. A circulation could be achieved by the application of epinephrine 0.15 µg kg^–1 min^–1, enoximone 8 µg kg^–1 min^–1 and nitroglycerine 0.5 µg kg^–1 min^–1. The PaO₂ was about 55 mmHg (FiO₂=0.5), the arterial oxygen-saturation 92%. The baby developed lactatemia (about 7 mmol l^–1), the diuresis was supported by high dosages of frusemide.

Pulmonary artery pressures, measured by echocardiography, exceeded the systemic pressure. There was a slight right-left-shunt across the two small VSDs, a reduced left-ventricular function with a FS of 15% and a left-ventricular ejection fraction (LVEF) of 25%. After the application of epoprostenol (4 ng kg^–1 min^–1) the pulmonary artery pressure did not change. The inhalation of nitric-oxide was not possible due to a technical defect in the application system.

Within the next hours there was no improvement of the clinical situation. After a multidisciplinary discussion the decision was made to attempt improving circulation by applying levosimendan before performing any invasive interventions such as heart-catheter or surgery. Hence the infant received an intravenous bolus of levosimendan of 24 µg kg^–1 followed by an infusion of 0.2 µg kg^–1 min^–1 for the next 48 h. Immediately after application of the bolus a significant increase in left-ventricular function could be demonstrated by echocardiography. The FS and the LVEF increased from 15 to 22% and from 25 to 40%, respectively. Twelve hours after initiating treatment with levosimendan no right-left-shunt could be detected. The pulmonary pressure was half as high as the systemic-pressure as visualized by echocardiography. No adverse events were observed. The PaO₂ improved from 55 to 180 mmHg. Diuresis and lactatemia normalised within the first day of infusion. During the following 6 days the left-ventricle recovered to a fractional-shortening of 28%.

	2. Discussion

Top Abstract 1. Case report 2. Discussion References

 
We present a case history of an infant who 48 h after cardiac surgery developed an acute left-ventricular failure with pulmonary hypertension combined with right to left-shunt across small muscular VSDs. Following acute resuscitation circulation was achieved using epinephrine, enoximone, and nitroglycerine.

In this case, however, it was impossible to improve left ventricular contractility sufficiently in combination with a right to left-shunt by the use of epinephrine, enoximone, and epoprostenol alone. This treatment did not lead to a significant improvement of the patients' clinical situation, which was rapidly deteriorating in presence of low-output syndrome, acidosis and renal failure. Clinical data in adult patients with severe low-output-syndrome [1,2] and our own clinical experience in adult patients after cardiac surgery showed, that levosimendan may improve contractility, beyond the effects of catecholamines and phosphodiesterase-III-inhibitors. The decision to apply levosimendan resulted from the necessity to improve left ventricular function and to achieve a dilatation of the pulmonary vessels simultaneously. We interpreted the disappearance of the right-left-shunt during the infusion of levosimendan as a result of a combination of these effects.

The positive inotropic and the vasodilating effects of levosimendan have been published previously [1,2]. The positive effects on myocardial contractility in patients with a stunned myocardium and after cardiac surgery have been shown in animal experiments and in clinical trials [3,4]. The improved myocardial contractility after the use of levosimendan is not associated with an increase in myocardial oxygen consumption [5]. Levosimendan does not influence the intracellular calcium ion concentration and therefore does not lead to an increase in cardiac arrhythmias as a side effect [4]. In dosages above 25 µg kg^–1 an influence on the QT-time has been observed, but this was not associated with rhythmic disorders [6]. The dilating effects of this drug on blood vessels is achieved by activating the ATP-dependant potassium-channels of smooth muscle-cells and has been investigated in experimental and clinical trials [7]. The dilating effect is not selective for the pulmonary-vascular bed [8], but has also been described for the coronary vessels and the splanchnic area [9,10].

Considering the pharmacological effects and side effects of levosimendan, as in the presented case, the risk of treatment was calculated lower than the risk of any invasive interventional methods.

The instant improvement of left-ventricular function after the application of levosimendan and the reduction of the pulmonary vascular resistance in this case indicates, that levosimendan is a possible treatment option in (pediatric) patients presenting a combination of reduced myocardial function, pulmonary hypertension and the prevalence of a septal defect. Controlled clinical trials are needed to verify these observations.

	References

Top Abstract 1. Case report 2. Discussion References

 

1. Follath F., Cleland J.G., Just H., Papp J.G., Scholz H., Peuhkurinen K., Harjola V.P., Mitrovic V., Abdalla M., Sandell E.P., Lehtonen L. Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360(9328):196-202.[CrossRef][Medline]
2. Moiseyev V.S., Poder P., Andrejevs N., Ruda M.Y., Golikov A.P., Lazebnik L.B., Kobalava Z.D., Lehtonen L.A., Laine T., Nieminen M.S., Lie K.I. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 2002;23(18):1422-1432.[Abstract/Free Full Text]
3. Jamali I.N., Kersten J.R., Pagel P.S., Hettrick D.A., Warltier D.C. Intracoronary levosimendan enhances contractile function of stunned myocardium. Anesth Analg 1997;85(1):23-29.[Abstract]
4. Nijhawan N., Nicolosi A.C., Montgomery M.W., Aggarwal A., Pagel P.S., Warltier D.C. Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 1999;34(2):219-228.[CrossRef][Medline]
5. Lilleberg J., Nieminen M.S., Akkila J., Heikkila L., Kuitunen A., Lehtonen L., Verkkala K., Mattila S., Salmenpera M. Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 1998;19(4):660-668.[Abstract/Free Full Text]
6. Sundberg S., Lilleberg J., Nieminen M.S., Lehtonen L. Hemodynamic and neurohormonal effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men. Am J Cardiol 1995;75:1061-1066.[CrossRef][Medline]
7. Kersten J.R., Montgomery M.W., Pagel P.S., Warltier D.C. Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels. Anesth Analg 2000;90(1):5-11.[Abstract/Free Full Text]
8. De Witt B.J., Ibrahim I.N., Bayer E., Fields A.M., Richards T.A., Banister R.E., Kaye A.D. An analysis of responses to levosimendan in the pulmonary vascular bed of the cat. Anesth Analg 2002;94(6):1427-1433.[Abstract/Free Full Text]
9. Bowman P., Haikala H., Paul R.J. Levosimendan, a calcium sensitizer in cardiac muscle, induces relaxation in coronary smooth muscle through calcium desensitization. J Pharmacol Exp Ther 1999;288(1):316-325.[Abstract/Free Full Text]
10. Pataricza J., Hohn J., Petri A., Balogh A., Papp J.G. Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol 2000;52(2):213-217.[CrossRef][Medline]

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