Hypertension epoprostenol

Intravenous epoprostenol increases exercise tolerance, improves pulmonary hemodynamics, and improves survival in patients with primary pulmonary hypertension. However, there are limitations to intravenous administration, and a significant proportion of patients develop catheter-related problems, such as thrombosis, pump failure, and catheter-related sepsis. In an attempt to improve delivery, several trials of aerosolized prostacyclin have been undertaken, primarily in patients with primary pulmonary hypertension. 

Schenk P, Petkov V, Madl C, Kramer L, Kneussl M, Ziesche R, Lang I. Aerosolized iloprost therapy could not replace long-term IV epoprostenol (prostacyclin) administration in severe pulmonary hypertension. Chest 2001 119(1) 296-300. 

Further cases of pulmonary edema have been reported during continuous intravenous epoprostenol in patients with severe pulmonary hypertension and pulmonary capillary hemangiomatosis, a rare condition characterized by proliferation of thin-walled microvessels in the alveolar walls (3). This report suggests that epoprostenol should not be used in such patients. 

A 61-year-old woman developed pulmonary edema during treatment with epoprostenol for severe pulmonary hypertension associated with limited scleroderma (5). She received an infusion of epoprostenol 1 nano-gram/kg/minute, and the dosage was increased by 1-... 

Interstitial pneumonia has been reported in a patient taking epoprostenol for primary pulmonary hypertension (6). 

Anticoagulants and continuous intravenous infusion of epoprostenol are the standard treatments for primary pulmonary hypertension. However, their combined use increases the likelihood of hemorrhagic complications, as demonstrated in a retrospective study of 31 consecutive patients with primary pulmonary hypertension (mean age, 29 years, 10 men, 21 women), nine of whom had 11 bleeding episodes nine episodes were cases of alveolar hemorrhage and two patients had severe respiratory distress (9). The mean dose of epoprostenol at the time of the first bleeding episode was 89 ng/kg/minute. More of the patients who had a bleeding episode died (67% versus 41%). 

In a double-blind, placebo-controlled study, the Bosentan Randomized trial of Endothelin Antagonist Therapy for Pulmonary Arterial I lypertension (BREATHE-2), 33 patients took epoprostenol (2 ng/kg/ min initially, increasing to a mean dosage of 14 ng/kg/min at week 16) and were then randomized for 16 weeks in a 2 1 ratio to bosentan (62.5 mg bd for 4 weeks then 125 mg bd) or placebo (11). There was a non-significant trend towards hemodynamic and clinical improvement with to the combination. There were several early and late major complications (four withdrawals with bosentan + epoprostenol two deaths due to cardiopulmonary failure, one clinical worsening, and one increase in hepatic transaminases and one withdrawal due to increased hepatic transaminases with placebo + epoprostenol. Power was the major limitation of this study, in which only 33 patients were enrolled, and the results should be interpreted with caution. Additional information is needed to evaluate the benefit to harm balance of combined bosentan + epoprostenol therapy in pulmonary arterial hypertension. 

McLaughlin VV, Genthner DE, Panella MM, Rich S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998 338(5) 273-7. 

Morimatsu H, Goto K, Matsusaki T, Katayama H, Matsubara H, Ohe T, Morita K. Rapid development of severe interstitial pneumonia caused by epoprostenol in a patient with primary pulmonary hypertension. Anesth Analg 2004 99 1205-7. 

Findlay JY, Plevak DJ, Krowka MJ, Sack EM, Porayko MK. Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension. Liver Transpl Surg 1999 5(5) 362-5. 

Myers SA, Ahearn GS, Selim MA, Tapson VF. Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy. J Am Acad Dermatol 2004 51 98-102. 

Ogawa A, Matsubara H, Fujio H, Miyaji K, Nakamura K, Morita H, Saito H, Kusano KF, Emori T, Date H, Ohe T. Risk of alveolar hemorrhage in patients with primary pulmonary hypertension—anticoagulation and epoprostenol therapy. Circ J 2005 69(2) 216-20. 

Ivy DD, Doran A, Clausen L, Bingaman D, Yetman A. Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan. Am J Cardiol 2004 93 943-6. 

Humbert M, Barst RJ, Robbins IM, Channick RN, Galie N, Boonstra A, Rubin LJ, Horn EM, Manes A, Simonneau G. Combination of bosentan with epoprostenol in pulmonary arterial hypertension BREATHE-2. Eur Respir J 2004 24 353-9. 

Prostacyclin lowers peripheral, pulmonary, and coronary resistance. It has been used to treat both primary pulmonary hypertension and secondary pulmonary hypertension, which sometimes occurs after mitral valve surgery. A commercial preparation of prostacyclin (epoprostenol) is approved for treatment of primary pulmonary hypertension, in which it appears to improve symptoms and prolong survival. However, because of its extremely short plasma half-life, the drug must be administered as a continuous intravenous infusion through a central line. Several prostacyclin analogs with longer half-lives have been developed and treprostinil was recently approved for use in pulmonary hypertension (Horn, 2002). This drug is administered by continuous subcutaneous infusion. 

PGI2 epoprostenol (inhibits platelet aggregation, used for extracorporeal circulation and primary pulmonary hypertension). 

Krowka, M.X, Frantz, R.P., McGoon, M.D., Severson, C., Plevak, D.X, Wiesner, R.H. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin) a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology 1999 30 641-648... 

Farber HW, Graven KK, Kokolski G, Korn JH. Pulmonary edema during acute infusion of epoprostenol in a patient with pulmonary hypertension and limited scleroderma. J Rheumatol 1999 26(5) 1195-6. 

Higenbottam TW, Spiegelhalter D, Scott JP, Fuster V, Dinh-Xuan AT, Caine N, WaUwork J. Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. Br Heart J 1993 70(4) 366-70. 

The cyclo-oxygenase metabolite prostacyclin is a potent, short-lived vasodilator and antithrombotic agent. Intravenous administration of the commercially available form of prostacyclin, epoprostenol, relieves the symptoms of primary pulmonary hypertension by dilating the pulmonary vasculature [99]. A stable prostacyclin analogue, iloprost, appears to be similarly effective when administered as an aerosol and obviates the logistical problems associated with maintained intravenous administration [100]. 

Secondary Pulmonary Hypertension. Secondary pulmonary hypertension is seen in some heart transplant candidates, and documenting the potential for reversibility when the primary defect is corrected is important in selecting appropriate heart transplant candidates and liver transplant patients as well. Aerosolized prostacyclin has been shown at least as effective as inhaled NO 40 ppm for this purpose in heart transplant candidates [170], while aerosolized epoprostenol has been shown similarly useful in liver transplant candidates. Delivery of iloprost was faster with an ultrasonic nebulizer but equally efficacious as compared to a jet nebulizer [171]. The role of aerosolized prostacyclin and related medications for pulmonary hypertension and for diagnostic evaluation of transplant candidates remains to be proven. Certainly, a successful aerosol treatment for pulmonary hypertension would be well received because of the inconvenience of the current method of constant infusion via an indwelling catheter. From an economic viewpoint, the market is small, so the chance of recovery of investment in new treatment would be limited. 

Epoprostenol Flolan GlaxoSmithKline Prostacyclin PGI2 Dialysis 5 ngkg min- IV Pulmonary hypertension continuous infusion after dose-ranging... 

---