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Aerosolized Prostacyclin and Iloprost in Severe Pulmonary Hypertension

Horst Olschewski, MD; Dieter Walmrath, MD; Ralph Schermuly, PhD; H. Ardeshir Ghofrani, MD; Friedrich Grimminger, MD, PhD; and Werner Seeger, MD
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From Justus-Liebig-University, Giessen, Germany. Acknowledgments: The authors thank Dr. R.H. Bodeker, Institute of Medical Statistics, for statistical discussion and Dr. R. Snipes, Institute of Anatomy, Justus-Liebig-University, Giessen, Germany, for linguistic revision of the manuscript. Requests for Reprints: Werner Seeger, MD, Department of Medicine, Justus-Liebig-University, Klinikstrasse 36, D-35392 Giessen, Germany. Current Author Addresses: Drs. Olschewski, Walmrath, Schermuly, Ghofrani, Grimminger, and Seeger: Department of Medicine, Justus-Liebig-University, Klinikstrasse 36, D-35392 Giessen, Germany.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(9):820-824. doi:10.7326/0003-4819-124-9-199605010-00006
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Objective: To compare the effects of aerosolization of prostacyclin and its stable analog iloprost with those of nasal oxygen, inhaled nitric oxide, and intravenous prostacyclin on hemodynamics and gas exchange in patients with severe pulmonary hypertension.

Design: Open uncontrolled trial.

Setting: Justus-Liebig-University, Giessen, Germany.

Patients: 4 patients with primary pulmonary hypertension and 2 patients with severe pulmonary hypertension associated with calcinosis, the Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (the CREST syndrome). All were classified as New York Heart Association class III or class IV.

Intervention: Short-term applications of O2, inhaled nitric oxide, intravenous prostacyclin, aerosolized prostacyclin, and aerosolized iloprost during repeated catheter investigation of the right side of the heart within a 1-month period. One patient had long-term therapy with inhaled iloprost.

Results: Aerosolized prostacyclin decreased pulmonary artery pressure in 6 patients from (mean ± SE) 62.3 ± 4.1 mm Hg to 50.8 ± 5.5 mm Hg and reduced pulmonary vascular resistance from 1721 ± 253 dyne/s · cm−5 to 1019 ± 203 dyne/s · cm−5, and it increased cardiac output from 2.75 ± 0.21 L/min to 4.11 ± 0.54 L/min, mixed venous oxygen saturation from 51.1% ± 3.4% to 66.3% ± 4.1%, and arterial oxygen saturation from 90.6% ± 2.7% to 93.8% ± 23% (P < 0.05 for all changes). Mean systemic arterial pressure was only slightly affected. The responses lasted for 10 to 30 minutes after inhalation was terminated. Aerosolized iloprost had an identical efficacy profile but was associated with a longer duration of the pulmonary vasodilatory effect (60 min to 120 min). In comparison, intravenous prostacyclin reduced pulmonary vascular resistance with corresponding efficacy but produced a more pronounced decline in systemic artery pressure and no clinically significant decrease in pulmonary artery pressure. Nitric oxide and O2 were less potent pulmonary vasodilators in these patients. In one patient, 1 year of therapy with aerosolized iloprost (100 µg/d in six aerosol doses) resulted in sustained efficacy of the inhaled vasodilator regimen and clinical improvement.

Conclusion: Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe pulmonary hypertension. Thus, it may offer a new strategy for treatment of this disease.


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Figure 1.
Short- and long-term effects of iloprost inhalation in one patient.Left.2O2Right.O2arrows

Example of the hemodynamic and gas exchange response to one 15-minute iloprost inhalation (white bar, ILO) in patient E, who received long-term treatment with inhalations of 100 µg of iloprost daily. During inhalation, cardiac output (CO) and venous oxygen saturation (Svo ) increased sharply. Simultaneously, mean pulmonary artery pressure (PAP) and central venous pressure (CVP) decreased. Note the almost constant mean arterial pressure (MAP) and increasing arterial oxygen saturation (Sa ) in response to inhalation. Time course of hemodynamics and arterial oxygen saturation in response to long-term iloprost aerosolization, 100 µg/d in six aerosol doses, in patient E. Baseline values (□s, assessed in the morning before daily inhalation) of Sa , pulmonary vascular resistance (PVR), PAP, and CO, and those values obtained immediately after aerosolization of the first 17 µg of the daily iloprost dose are shown. Note that the acute responses to inhalation ( ) did not decrease during long-term therapy.

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