Ann Thorac Surg 2001;71:1004-1006
© 2001 The Society of Thoracic Surgeons
Case report
Aerosolized iloprost for severe pulmonary hypertension as a bridge to heart transplantation
Thorsten Wittwer, MDa,
Klaus Pethig, MDa,
Martin Strüber, MDa,
Marius Hoeper, MDb,
Wolfgang Harringer, MDa,
Axel Haverich, MDa,
Ulrich Franke, MDa,
Thorsten Wahlers, MDa
a Departments of Thoracic and Cardiovascular Surgery, Medical School Hannover, Hannover, Germany
b Pulmonary Medicine, Medical School Hannover, Hannover, Germany
Accepted for publication March 21, 2000.
Address reprint requests to Dr Wittwer, Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller University, 07740 Jena, Germany
e-mail: th.wittwer-md{at}t-online.de
 |
Abstract
|
|---|
Preexisting pulmonary hypertension in pediatric patients is associated with poor outcome after cardiac transplantation because of donor right ventricular dysfunction. To avoid a combined heart-lung transplantation in a 17-year-old patient, we used an intensified pretreatment with intravenous prostacyclin and dobutamine combined with an inhalative therapy with the aerosolized prostacyclin-analog Iloprost. With this regimen, the patient was hemodynamically stabilized for the waiting period of 21 days after which an uneventful cardiac transplantation was performed.
|
Introduction
|
|---|
Cardiac transplantation has become a standard therapy in end-stage heart disease, increasingly used in patients with heart failure from congenital defects [1]. Preexisting pulmonary hypertension (PHT) is frequent in this patients and remains a major risk factor for donor right ventricular dysfunction [2]. Therefore, pediatric patients with secondary PHT are usually considered for heart-lung transplantation [3], however, with impaired long-term results as compared to isolated heart transplantation [4]. We report on our experience with heart transplantation in a pediatric patient with severe PHT resulting from progressive failure of the systemic ventricle, 16 years following a Mustard correction for transposition of the great arteries (d-TGA). The patient was intensively pretreated with intravenous prostacyclin and dobutamine combined with an inhalative therapy using the aerosolized prostacyclin-analog Iloprost.
A 17-year-old boy was referred to the Department of Thoracic and Cardiovascular Surgery of the Medical School Hannover, Hannover, Germany, with end-stage heart failure and recurrent episodes of pulmonary edema. In early childhood, the patient had had a Mustard correction of d-TGA combined with a ventricular septal defect-closure. Since 18 months, a progressive deterioration of the systemic ventricular function was noticed, and serial cardiac catheterizations revealed a progressive PHT without anatomical reasons like pulmonary venous obstruction. On admission, the patient required intravenous prostacyclin (8 ng/kg/min) and dobutamine (6 µg/kg/min) to reduce PHT and to maintain sufficient cardiac output. Despite this therapy, hemodynamics revealed a severe PHT (pulmonary artery pressure [PAP] 108 mm Hg/40 mm Hg, mean: 57 mm Hg) with a pulmonary capillary wedge pressure (PCWP) of 24 mm Hg, a transpulmonary gradient (TPG = mean PAP minus PCWP) of 33 mm Hg and a cardiac output of 3.0 L/min.
In this situation, we added the aerosolized prostacyclin-analog Iloprost (Ilomedin, Schering Inc, Berlin, Germany), which was jet-nebulized with room air and delivered over 15 minutes to a spacer connected to the afferent limb of a y-valve mouthpiece 6 times a day (total nebulized dose: 100 µg/day). Doses of intravenous dobutamine and prostacyclin were kept unchanged over time. During the first administration of Iloprost, a pronounced improvement of pulmonary hemodynamics was observed (Table 1). Two hours after the first administration, the systolic PAP increased gradually to a maximum of 89 mm Hg at the time of the second Iloprost administration. After the fourth inhalative treatment, systolic PAP did not exceed 65 mm Hg at any time. Hemodynamically stabilized, the patient could be placed on the "special urgency" waiting list at Eurotransplant (Leiden, Holland) for heart transplantation. After 21 days of rather uneventful treatment, an uncomplicated standard orthotopic cardiac transplantation using a bicaval anastomotic technique was performed. Postoperatively, supported by a nitric oxide ventilation (20 ppm nitric oxide), continuation of intravenous prostacyclin and low-dose dobutamine, the patient’s hemodynamics were stable. The systolic PAP did not exceed 45 mm Hg, and extubation was performed on postoperative day (POD) 3. A routine biopsy on POD 11 revealed an International Society of Heart and Lung Transplantation (ISHLT) grade 3B rejection without hemodynamic compromise, which was treated with a standard steroid pulse therapy. As a control biopsy showed the same ISHLT grade, we initiated a 6-day course of intravenous monoclonal antibodies, which successfully terminated the rejection. The patient was discharged with normal hemodynamics 33 days postoperatively.
View this table:
[in this window]
[in a new window]
|
Table 1. Hemodynamic Improvement During First 15-Minute Inhalation Period With 15 µg of Aerosolized Iloprost and a Continuous Dose of Intravenous Prostacyclina
|
|
|
Comment
|
|---|
Heart transplantation has become an established treatment for adolescents with end-stage heart disease. Congenital cardiac defects account for an increasing percentage of indications [1]. Most of these patients had previous palliative or reparative operations with an increased operative risk from the underlying complex anatomy. Especially in severe preexisting PHT with a TPG of more than 12 mm Hg, isolated heart transplantation is associated with poor perioperative outcome [5], and combined heart-lung transplantation usually must be considered [3]. However, the long-term results of the latter procedure are lower as compared to the results obtained with uncomplicated heart transplantation [4]. Although the preoperative treatment with intravenous prostaglandins results in an improved immediate outcome after heart transplantation because of potent pulmonary vasodilating efforts and beneficial effects on myocardial contractility [6], systemic prostaglandins have major drawbacks because of severe hypotension and increased mortality in patients with heart failure [6, 7]. Recently, aerosolized prostacyclin (PGI2) has been shown to cause reversibility of PHT by selective pulmonary vasodilation without systemic hypotension [7, 8]. Especially the stable prostacyclin analog Iloprost is considered to offer a new strategy for treatment of severe PHT [8]. In our patient with rapid deterioration in clinical status, a combined heart-lung transplantation would have been associated with an unacceptable high risk because of a long waiting period and the complex anatomy with increased bleeding tendency. With an intensified regimen using aerosolized Iloprost in addition to intravenous prostacyclin, we were not only able to document the reversibility of PHT, but to stabilize the patient’s hemodynamics during the pretransplant period of 21 days. The hemodynamic benefit was achieved by a total Iloprost dose of 100 µg/d [8]. Interestingly, in contrast to the current experience with continuous prostacyclin infusion, no induction of tolerance was observed. However, a sufficient treatment with inotropics and a continuous hemodynamic monitoring are essential to avoid acute failure of the systemic ventricle from to significant reduction in PAP with subsequently increased transpulmonary blood flow. With this regimen, uncomplicated heart transplantation could be performed without any postoperative right ventricular compromise.
It is concluded that adjunct therapy with aerosolized Iloprost can offer a valuable strategy as a bridge to isolated heart transplantation especially in high-risk reoperative patients with severe PHT.
|
References
|
|---|
-
Vouhé P.R., Tamisier D., Le Bidois J., et al. Pediatric cardiac transplantation for congenital heart defects: surgical considerations and results. Ann Thorac Surg 1993;56:1239-1247.[Abstract]
-
Conte J.V., Robbins R.C., Reichenspurner H., Valentine V.G., Theodore J., Reitz B. Pediatric heart-lung transplantation: intermediate-term results. J Heart Lung Transplant 1996;15:692-699.[Medline]
-
Haverich A. Experience with lung transplantation. Ann Thorac Surg 1999;67:305-312.[Abstract/Free Full Text]
-
Hosenpud J.D., Bennett L.E., Keck B.M., Fiol B., Boucek M.M., Novick R.J. The registry of the International Society for Heart and Lung Transplantation: sixteenth official report—1999. J Heart Lung Transplant 1999;18:611-626.[Medline]
-
Erickson K.W., Costanzo-Nordin M.R., O’Sullivan E.J., et al. Influence of preoperative transpulmonary gradient on late mortality of after orthotopic heart transplantations. J Heart Lung Transplant 1990;9:526-537.
-
Montalescot G., Drobinski G., Meurin P., et al. Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure. Am J Cardiol 1998;82:749-755.[Medline]
-
Santak B., Schreiber M., Kuen P., Lang D., Radermacher P. Prostacyclin aerosol in an infant with pulmonary hypertension. Eur J Pediatr 1995;154:233-235.[Medline]
-
Olschewski H., Walmrath D., Schermuly R., Ghofrani A., Grimminger F., Seeger W. Aerosolized prostacyclin and Iloprost in severe pulmonary hypertension. Ann Int Med 1996;124:820-824.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
S. E Baker and R. H. Hockman
Inhaled Iloprost in Pulmonary Arterial Hypertension
Ann. Pharmacother.,
July 1, 2005;
39(7):
1265 - 1274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sablotzki, T. Hentschel, E. Gruenig, S. Schubert, I. Friedrich, J. Muhling, M. G. Dehne, and E. Czeslick
Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance
Eur. J. Cardiothorac. Surg.,
November 1, 2002;
22(5):
746 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
