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J Thorac Cardiovasc Surg 2001;121:981-982
© 2001 The American Association for Thoracic Surgery

Brief Communications

Aerosolized prostacyclin (epoprostenol) as an alternative to inhaled nitric oxide for patients with reperfusion injury after lung transplantation

From the Department of Thoracic and Cardiovascular Surgery, University of Virginia Health Sciences Center, Charlottesville, Va.

Received for publication March 9, 2001. Accepted for publication March 14, 2001. Address for reprints: Curtis G. Tribble, MD, Department of Thoracic and Cardiovascular Surgery, University of Virginia Health Sciences Center, Box 3111, MR4 Building, Charlottesville, VA 22908 (E-mail: cgtuva{at}aol.com).

Treatment options for patients with severe reperfusion injury after lung transplantation often include the use of inhaled nitric oxide. However, the recent escalation in cost has made its use somewhat prohibitive. Here we describe the technique of using inhaled prostacyclin (epoprostenol), as opposed to using inhaled nitric oxide, for the treatment of lung transplant reperfusion injury. We believe this is the first reported case of its use in this setting.

Clinical summary

A 51-year-old man underwent single lung transplantation for chronic obstructive pulmonary disease. Severe reperfusion injury subsequently developed, with an oxygenation index of greater than 30. ¹ The chest radiograph showed almost complete white-out of the transplanted lung. Mean pulmonary artery pressures preoperatively were 24 mm Hg. Mean pulmonary artery pressures after lung transplantation were 35 to 40 mm Hg. This patient was subsequently treated by arteriovenous extracorporeal membrane oxygenation (ECMO). After the start of ECMO, mean pulmonary artery pressures remained at 35 to 40 mm Hg. Given this, we were concerned that the patient had ongoing reperfusion injury. We and others have thought that pulmonary vasodilators, such as inhaled nitric oxide, help to decrease reperfusion injury by decreasing pulmonary vascular resistance and increasing pulmonary artery blood flow. ² However, given the substantial cost of inhaled nitric oxide, we instead chose to administer inhaled, aerosolized prostacyclin at a rate of 50 ng · kg^–1 · min^–1 using an in-line circuit and MiniHeart nebulizer chamber (Vortran Medical Technology, Inc, Sacramento, Calif) (Table I). After institution of aerosolized prostacyclin, mean pulmonary artery pressures dropped to 25 to 30 mm Hg. After 48 hours the patient was weaned from ECMO and continued receiving inhaled prostacyclin for an additional 24 hours. This patient eventually recovered and was discharged to his home on hospital day 11.

Nitric oxide has often been used as an adjunctive measure for the treatment of reperfusion injury with some success. ² However, the recent cost increase in inhaled nitric oxide has made its use somewhat prohibitive. In this report, we demonstrate the technique of using inhaled prostacyclin in patients with reperfusion injury. We have also identified some potential advantages of inhaled prostacyclin over inhaled nitric oxide.

In this patient, inhaled prostacyclin was effective at decreasing the elevated pulmonary artery pressures associated with reperfusion injury. We and others believe decreasing pulmonary artery pressure lessens water accumulation and injury to the transplanted lung. ³ To our knowledge, no other authors have reported on the clinical use of inhaled prostacyclin for the treatment of lung transplant reperfusion injury. Some clinical studies, however, have investigated the effect of inhaled prostacyclin on acute respiratory distress syndrome. ^4,5 Van Heerden and associates ⁴ demonstrated effective use of inhaled prostacyclin in 9 patients with acute respiratory distress syndrome. Those authors demonstrated a significant dose-dependent improvement in arterial oxygenation/percent inhaled oxygen ratio after administration of inhaled prostacyclin. No significant complications resulted from the use of the drug.

Some animal studies have demonstrated the beneficial effects of intravenous prostacyclin in reducing lung transplant reperfusion injury. ^6,7 Matsuzaki and colleagues ⁶ demonstrated reduced reperfusion injury in a rabbit model after intravenous prostacyclin. Okada and coworkers ⁷ similarly demonstrated reduced reperfusion injury in a rat model after the administration of intravenous prostacyclin. Although these investigations show improvement in lung reperfusion injury after the administration of intravenous prostacyclin, to our knowledge only one animal study has shown an improvement in reperfusion injury after the administration of inhaled prostacyclin. ³

One advantage of inhaled prostacyclin is that it avoids the possible buildup of oxygen radicals associated with inhaled nitric oxide. Some authors have questioned whether or not a toxic buildup of oxygen radicals occurs with the use of nitric oxide. ^8,9 Murakami and coworkers ⁸ demonstrated improvement in reperfusion injury after administration of nitric oxide at low doses, although higher doses seemed to worsen reperfusion injury. Eppinger and coworkers ⁹ found similar results.

Another advantage of inhaled prostacyclin is that it is also less expensive than inhaled nitric oxide. Patient charges at our institution for inhaled nitric oxide are $5500 a day regardless of amount used. In comparison, inhaled prostacyclin costs $960 a day at a dosage of 50 ng · kg^–1 · min^–1, which is the recommended maximal clinical dosage.

In summary, inhaled prostacyclin appeared to be as effective as inhaled nitric oxide, may have the advantage of avoiding the potential buildup of oxygen radicals, and is cheaper than nitric oxide. Thus, inhaled prostacyclin should be considered in patients with severe reperfusion injury after lung transplantation.

References

1. Fiser SM, Kron IL, Long SM, Kaza AK, Kern JA, Tribble CG. Early intervention after severe oxygenation index elevation improves survival following lung transplantation. J Heart Lung Transplant. In press.
   
2. Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA. Inhaled nitric oxide reduces human lung allograft dysfunction. J Thorac Cardiovasc Surg 1996;111:913-9.[Abstract/Free Full Text]
   
3. Lockinger A, Schutte H, Walmrath D, Seeger W, Grimminger F. Protection against gas exchange abnormalities by pre-aerosolized PGE1, iloprost, and nitroprusside in lung ischemia-reperfusion. Transplantation 2001;71:185-93.[Medline]
   
4. van Heerden PV, Barden A, Michalopoulos N, Bulsara MK, Roberts BL. Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS. Chest 2000;117:819-27.[Abstract/Free Full Text]
   
5. Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med 1996;153:991-6.[Abstract]
   
6. Matsuzaki Y, Waddell TK, Puskas JD, Hirai T, Nakajima S, Slutsky AS, et al. Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1. Am Rev Respir Dis 1993;148(4 Pt 1):882-9.[Medline]
   
7. Okada Y, Marchevsky AM, Kass RM, Matloff JM, Jordan SC. A stable prostacyclin analog, beraprost sodium, attenuates platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation. Transplantation 1998;66:1132-6.[Medline]
   
8. Murakami S, Bacha EA, Mazmanian GM, Detruit H, Chapelier A, Dartevelle P, et al. Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group. Am J Respir Crit Care Med 1997;156(2 Pt 1):454-8.[Abstract/Free Full Text]
   
9. Eppinger MJ, Ward PA, Jones ML, Bolling SF, Deeb GM. Disparate effects of nitric oxide on lung ischemia-reperfusion injury. Ann Thorac Surg 1995;60:1169-75; discussion 1176.[Abstract/Free Full Text]
   

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Irving L. Kron John A. Kern Curtis G. Tribble Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fiser, S. M. Articles by Tribble, C. G. Search for Related Content PubMed PubMed Citation Articles by Fiser, S. M. Articles by Tribble, C. G. Related Collections Lung - transplantation