Con: inhaled prostaglandin as a pulmonary vasodilator instead of nitric oxide.

C a m NHALED NITRIC OXIDE (iNO) achieved favored status as a pulmonary vasodilator principally because of its remarkble pulmonary selectivity. Previously available methods for educing pulmonary vascular resistance (PVR) were all accomanied by the risk of systemic hypotension. However, because NO is immediately bound by hemoglobin, its vasodilatory ffects are limited to the pulmonary vasculature at any dose. lthough the only Food and Drug Administration (FDA)pproved indication for the use of iNO is in the setting of espiratory failure of the newborn, iNO has been used off-label n a wide range of patients and clinical settings and with several ery different objectives.1 For example, iNO is used to test ascular reactivity in pulmonary hypertensives,2,3 to reduce the ncidence or severity of lung reperfusion injury after lung ransplantation,4 to improve oxygenation in the setting of acute ung injury,5 and to either prevent or treat right heart failure.6-8 n fact, iNO was considered a true breakthrough in the treatent of perioperative right heart failure because maintenance f coronary perfusion pressure is so critical when reducing ight ventricular afterload in this setting.9 In addition, because NO preferentially dilates well-ventilated regions of the lung nd thereby improves ventilation/perfusion matching and arteial oxygenation, iNO is used to correct life-threatening hypoxmia; this is despite the disappointing finding that iNO did not mprove survival in patients with the acute respiratory distress yndrome.10,11 However, the improvement in oxygenation in ypoxic neonates and the resultant reduction in the need for xtracorporeal membrane oxygenation12 was the breakthrough hat won FDA approval for iNO therapy. After obtaining FDA approval in 1999, the cost of adminisration of iNO was set at what most clinicians (and hospital dministrators) considered exorbitant ($3,000/day with a 12,000 cap). Understandably, this generated great interest in nding a less expensive alternative.13 Consequently, a wide ariety of intravenous vasodilators were tested via the inhaled oute with the expectation that maximizing drug levels at the arget organ would minimize their systemic effects. In addition o prostacyclin (prostaglandin I2 [PGI2], which is discussed in etail later), clinical studies report selective pulmonary vasoilation by inhaled milrinone,14 NO adducts,15 nitroglycerin,16 odium nitroprusside,17 prostaglandin E1,18 and a more stable nalog of PGI2, iloprost.19 Based on a number of encouraging reports, numerous centers and the accompanying “pro” paper) are now advocating that PGI2 should be used instead of iNO. They argue that the ctions of iPGI2 are equivalent to iNO, and iPGI2 is safer, asier, and less costly to administer than iNO. The purpose of his “con” section of the debate is to present evidence to the ontrary. This article argues that (1) the appropriate studies ave not yet been done to affirm equivalency of these 2 drugs; 2) assertions of the lack of systemic effects of iPGI2 represent verzealous interpretations of limited or poorly controlled studes; (3) the safety profile of iNO is quite good, whereas iPGI2 as a number of concerning safety issues; (4) the administration ystem for iPGI2 has a number of important limitations; and (5) he fact that a day’s supply of iPGI2 costs less than a day’s