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Clinical letters

Treatment of a case of acute right heart failure by inhalation of iloprost, a long-acting prostacyclin analogue

Langer, F.1; Wendler, O.1; Wilhelm, W.2; Tscholl, D.1; Schäfers, H.-J.1

Author Information
European Journal of Anaesthesiology: November 2001 - Volume 18 - Issue 11 - p 770-773

Abstract

Introduction

Right heart failure as a result of myocardial ischaemia, reperfusion injury or elevated pulmonary vascular resistance may significantly contribute to perioperative mortality of cardiac surgery. Treatment commonly aims at the improvement of right ventricular preload, contractility and afterload. While preload is addressed by intravenous (i.v.) administration of nitrates and diuretics, contractility is generally optimized with catecholamines and phosphodiesterase inhibitors. Afterload reduction is achieved with phosphodiesterase inhibitors or intravenous prostaglandins, which are relatively unspecific as their vasodilating property affects both pulmonary and systemic vascular resistance. Selective pulmonary vasodilation with nitric oxide (NO) has been reported previously. We report an alternative selective approach using inhalation of the stable prostacyclin analogue iloprost, which may easily and effectively be applied in intubated as well as in extubated intensive care patients in perioperative right heart failure.

Presentation

A 58-year-old male patient with ischaemic cardiomyopathy and an ejection fraction of 17% was listed for cardiac transplantation. Right heart catheterization revealed a cardiac index of 1.7 L min–1 m–2 and a pulmonary artery pressure of 53/20 (mean 30) mmHg. Pulmonary vascular resistance was calculated to be 243 dyn s cm–5.

After six months on the waiting list, the patient received orthotopic heart transplantation. The organ was preserved using University of Wisconsin solution. After 141 min of ischaemia the donor heart resumed normal function in sinus rhythm. The patient was transferred to the intensive care unit in a stable condition with moderate inotropic support (epinephrine 0.12 μg kg–1 min–1). Haemodynamic monitoring included Swan-Ganz as well as a left atrial pressure catheter.

The initial perioperative course was uneventful. After the first 12 h postoperatively, mean cardiac index was 3.4 L min–1 m–2. Central venous pressure and pulmonary artery pressures were 8 mmHg and 37/15 (mean 25) mmHg, respectively. Pulmonary vascular resistance was 199.6 dyn s cm–5, systemic vascular resistance was 956.7 dyn s cm–5 with a mixed venous oxygen saturation of 72.5%. Successful weaning from mechanical ventilation was achieved overnight and the patient was extubated on the first postoperative day. Inotropic support could be gradually reduced (epinephrine 0.05 μg kg–1 min–1) with stable haemodynamics and adequate urine output.

On the second postoperative day, central venous pressure rose to 13 mmHg and pulmonary artery pressure increased to 53/15 (mean 28) mmHg with increased pulmonary vascular resistance (265.3 dyn s cm–5), while the cardiac index and mixed venous oxygen saturation decreased to 2.9 L min–1 m–2 and 58.1%, respectively. Systemic vascular resistance was calculated to be 773.0 dyn s cm–5. Transthoracic echocardiography documented impaired contractility of the right ventricle and normal left ventricular function. As left atrial pressure was normal (8 mmHg), the clinical situation was assessed as pending right heart failure: preload was lowered with a maximum nitrate dosage of 5 μg kg–1 min–1 and intensified i.v. furosemide administration (20 mg h–1). Contractility was optimized with increased inotropic support (epinephrine 0.15 μg kg–1 min–1).

Despite this treatment, the clinical condition did not resolve over the next 8 h. Thus, a trial with the nebulized prostacyclin analogue iloprost (Ilomedin®) was started (16 μg every 4 h). Inhalation was applied with a special inhalation system [1] for iloprost inhalation (Ilo-Neb®, Nebu-Tec, Elsenfeld, Germany). With this treatment central venous pressure (8 mmHg, Figure 1 b) and pulmonary artery pressure decreased [48/16 (mean 26) mmHg] as well as pulmonary vascular resistance (202.7 dyn s cm–5, Figure 1 c), while cardiac index increased (3.6 L min–1 m–2, Figure 1 a). Mixed venous saturation increased in a similar fashion (63.3%). Systemic vascular resistance remained relatively unchanged with 751.0 dyn s cm–5. Improved diuresis (> 200 mL h–1) could be established without change of diuretic dosage (Figure 1 d).

Figure 1.
Figure 1.:
Before and after iloprost: (a) mean cardiac index; (b) mean central venous pressure; (c) mean pulmonary vascular resistance; (d) mean urine output per hour.

On the third postoperative day, central venous pressure (8 mmHg), pulmonary artery pressure [41/15 (mean 25) mmHg], systemic (964.5 dyn s cm–5) and pulmonary vascular resistance (209.5 dyn s cm–5), cardiac index (3.0 L min–1 m–2) and mixed venous saturation (64.8%) were within normal ranges. Repeat echocardiography now revealed normal right ventricular performance. Thus the inhalation of iloprost was discontinued. The further clinical course was uneventful. After adequate recovery, the patient could be discharged home 23 days after heart transplantation in good clinical condition.

Discussion

Standard treatment of acute right heart failure consists of improvement of right ventricular preload, contractility and afterload. Preload is lowered with aggressive diuretic treatment and nitrates. Contractility is optimized with a tailored catecholamine regimen and phosphodiesterase inhibitors. Increased afterload is addressed with i.v. application of vasodilators, e.g. prostaglandins or phosphodiesterase inhibitors [2].

With i.v. application of vasodilators, the intended effect on the pulmonary vascular resistance is commonly limited by the concomitant vasodilating effect on the systemic vascular resistance. The decrease in systemic arterial pressure may contribute to deterioration of right ventricular contractility due to decreased coronary perfusion pressure. Thus, selective pulmonary vasodilation by airway application of vasodilators should be ideal. The concept of selective delivery of the vasodilating agent was introduced by inhalation of NO as described previously [3]. However, clinical application is mostly limited to the mechanically ventilated patient and requires specialized equipment with its financial implications. Nitric oxide application to the extubated patient remains difficult, particularly with respect to exact dosage. Rebound effects after discontinuation of the drug are commonly observed. Due to metabolism of NO to toxic NO2, this approach needs close surveillance with repeated measurements of concentrations.

A new, potent, simple and easy to use selective vasodilatation of the pulmonary circulation can also be achieved with aerosolized prostaglandins. Compared with i.v. use of prostacyclin, which is an important therapeutic tool in patients with primary pulmonary hypertension, the more selective approach of inhalative administration has been introduced recently with less effect on the systemic vascular resistance [4]. Furthermore, secondary pulmonary hypertension due to various clinical conditions (adult respiratory distress syndrome, pulmonary fibrosis, etc.) can be treated with inhalation of prostacyclin [5,6] in the intensive care unit. The intraoperative use of prostacyclin inhalation for acute right heart failure has been reported recently [7].

Iloprost has recently been propagated as a potent alternative to prostacyclin [4]. In the acute management of evident right heart failure in patients with primary pulmonary hypertension, iloprost proved to be superior to NO [8]. We have utilized aerosolized prostacyclin and iloprost in a limited number of patients with pulmonary hypertension. Both drugs appear to be effective in the pulmonary circulation and to be without relevant effect on the systemic vascular resistance. From this experience and from a practical standpoint we have completely abandoned the use of nitric oxide.

Iloprost is the first stable analogue of prostacyclin, a 5-{(E)-(1S, 5S, 6R, 7R)-7-hydroxy-6-(E)-(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-inyl]-bicyclo[3.3.0]octan 3-yliden} pentan acid. It was originally designed for i.v. use in acute ischaemia in peripheral vascular disease and especially in thromboangiitis obliterans. Iloprost is available as a 0.5-mL vial with 0.067 mg iloprost–trometamol (50 μg iloprost). For inhalation it is diluted with 4.5 mL 0.9% saline [4]. A single inhalation cycle requires 1.6 mL (16 μg iloprost) [4]. For use in ventilated patients, a common disposable nebulizer system is introduced into the inspiratory limb of the breathing system. In extubated patients inhalation is delivered with a special system [1]. The exact pharmacological half-life has not yet been investigated for the inhalation approach, but the desired haemodynamic effects return to baseline after 60–120 min [4]. In contrast to iloprost, the haemodynamic effects of prostacyclin dissipate after a few minutes, so that prostacyclin may be infused or continuously inhaled in the intubated patient, but is too short-acting for intermittent inhalation in the extubated patient. Metabolism of iloprost (molecular mass 360.5 D) occurs by b-oxidation to a nonactive metabolite, which will be cleared to 80% on the renal and 20% on the biliary pathway. Common side-effects are nausea, headache and moderate facial flush when used in extubated patients with facemasks instead of the previously mentioned dedicated system [1]. Neither possible bleeding complications due to interference with platelet function were observed in any of our surgical patients, nor possible bronchospasm.

Referring to our current patient, pulmonary hypertension due to longstanding left heart failure is common in heart transplant recipients. A pulmonary vascular resistance > 200 dyn s cm–5 is accepted as a risk factor for orthotopic heart transplantation [9]. Reversibility in response to different vasoactive drugs is crucial in recipient evaluation. Different testing procedures and a variety of drugs have been described: the drugs most commonly used are angiotensin-converting enzyme inhibitors, catecholamines, phosphodiesterase inhibitors or, most importantly, prostaglandins [2]. These drugs may also be used for perioperative management when even patients with only moderate elevation of pulmonary vascular resistance may encounter right heart failure. Aspects of preservation and ischaemia/reperfusion injury may contribute to this condition. To our knowledge, inhalation of iloprost has not been used in right heart failure after heart transplantation. This clinical condition requires highly selective pulmonary vasodilatation without decrease of mean arterial pressure and systemic vascular resistance. In our current case, reduction of pulmonary vascular resistance could be observed due to iloprost inhalation with consecutive improvement of cardiac index. Adequate diuresis could now be established with identical diuretic medication.

We conclude that inhalation of the stable prostacyclin-analogue iloprost may safely and efficiently reduce elevated pulmonary vascular resistance in acute right heart failure including heart transplantion to prevent morbidity and mortality.

Acknowledgment

This project was supported by departmental funding.

References

1 Gessler T, Schmehl T, Seeger W. Comparison of two inhalation systems for ilomedin-aerosol therapy in pulmonary hypertension. Am J Resp Crit Care Med 1999; 159: 1150–1150.
2 Kieler-Jensen N, Lundin S, Ricksten SE. Vasodilator therapy after heart transplantation: effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1 and sodium nitroprusside. J Heart Lung Transplant 1995; 14: 436–443.
3 Auler J, Oj Carmova MJ, Bocchi EA et al. Low doses of inhaled nitric oxide in heart transplant recipients. J Heart Lung Transplant 1996; 15: 443–450.
4 Olschewski H, Walmrath D, Schermuly R, Ghofrani A, Grimminger F, Seeger W. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996; 124: 820–834.
5 Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet 1993; 342: 961–962.
6 Olschewski H, Ghofrani HA, Wilkens H et al. Therapy of life threatening pulmonary hypertension with inhaled iloprost. Am J Resp Crit Care Med 1999; 159: A153–A153.
7 Schroeder RA, Wood GL, Plotkin JS, Kuo PC. Intraoperative use of inhaled PGI2 for acute pulmonary hypertension and right ventricular failure. Anesth Analg 2000; 91: 291–295.
8 Hoeper MM, Olschewski H, Ghofrani HA et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am Coll Cardiol 2000; 35: 176–182.
9 Costard-Jackle A, Fowler MB. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. J Am Coll Cardiol 1992; 19: 48–54.
Keywords:

HEART DISEASES, cardiac output, low; HEART TRANSPLANTATION; PROSTAGLANDINS, synthetic, iloprost

© 2001 European Academy of Anaesthesiology