Con: Inhaled Prostaglandin as a Pulmonary Vasodilator instead of Nitric Oxide

Abstract

INHALED NITRIC OXIDE (iNO) achieved favored status as a pulmonary vasodilator principally because of its remarkable pulmonary selectivity. Previously available methods for reducing pulmonary vascular resistance (PVR) were all accompanied by the risk of systemic hypotension. However, because iNO is immediately bound by hemoglobin, its vasodilatory effects are limited to the pulmonary vasculature at any dose. Although the only Food and Drug Administration (FDA)-approved indication for the use of iNO is in the setting of respiratory failure of the newborn, iNO has been used off-label in a wide range of patients and clinical settings and with several very different objectives. 1 Ichinose F. Roberts Jr, J.D. Zapol W.M. Inhaled nitric oxide: A selective pulmonary vasodilator: Current uses and therapeutic potential. Circulation. 2004; 109: 3106-3111 Crossref PubMed Scopus (223) Google Scholar For example, iNO is used to test vascular reactivity in pulmonary hypertensives, 2 Balzer D.T. Kort H.W. Day R.W. et al. Inhaled nitric oxide as a preoperative test (INOP Test I): The INOP Test Study Group. Circulation. 2002; 106: I76-I81 PubMed Google Scholar , 3 Sitbon O. Humbert M. Jagot J.L. et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J. 1998; 12: 265-270 Crossref PubMed Scopus (261) Google Scholar to reduce the incidence or severity of lung reperfusion injury after lung transplantation, 4 Cornfield D.N. Milla C.E. Haddad I.Y. et al. Safety of inhaled nitric oxide after lung transplantation. J Heart Lung Transplant. 2003; 22: 903-907 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar to improve oxygenation in the setting of acute lung injury, 5 Rossaint R. Falke K.J. Lopez F. et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993; 328: 399-405 Crossref PubMed Scopus (1560) Google Scholar and to either prevent or treat right heart failure. 6 Argenziano M. Choudhri A.F. Moazami N. et al. Randomized, double-blind trial of inhaled nitric oxide in LVAD recipients with pulmonary hypertension. Ann Thorac Surg. 1988; 65: 340-345 Abstract Full Text Full Text PDF Scopus (178) Google Scholar , 7 Oz M.C. Ardehali A. Collective review Perioperative uses of inhaled nitric oxide in adults. Heart Surg Forum. 2004; 7: E584-E589 Crossref PubMed Scopus (5) Google Scholar , 8 Ardehali A. Hughes K. Sadeghi A. et al. Inhaled nitric oxide for pulmonary hypertension after heart transplantation. Transplantation. 2001; 72: 638-641 Crossref PubMed Scopus (106) Google Scholar In fact, iNO was considered a true breakthrough in the treatment of perioperative right heart failure because maintenance of coronary perfusion pressure is so critical when reducing right ventricular afterload in this setting. 9 Vlahakes G.J. Turley K. Hoffman J.I. The pathophysiology of failure in acute right ventricular hypertension Hemodynamic and biochemical correlations. Circulation. 1981; 63: 87-95 Crossref PubMed Scopus (434) Google Scholar In addition, because iNO preferentially dilates well-ventilated regions of the lung and thereby improves ventilation/perfusion matching and arterial oxygenation, iNO is used to correct life-threatening hypoxemia; this is despite the disappointing finding that iNO did not improve survival in patients with the acute respiratory distress syndrome. 10 Taylor R.W. Zimmerman J.L. Dellinger R.P. et al. Inhaled nitric oxide in ARDS Study GroupLow-dose inhaled nitric oxide in patients with acute lung injury A randomized controlled trial. JAMA. 2004; 291: 1603-1609 Crossref PubMed Scopus (425) Google Scholar , 11 Dellinger R.P. Zimmerman J.L. Taylor R.W. et al. Inhaled Nitric Oxide in ARDS Study GroupEffects of inhaled nitric oxide in patients with acute respiratory distress syndrome Results of a randomized phase II trial. Crit Care Med. 1998; 26: 15-23 Crossref PubMed Scopus (673) Google Scholar However, the improvement in oxygenation in hypoxic neonates and the resultant reduction in the need for extracorporeal membrane oxygenation 12 Hoffman G.M. Ross G.A. Day S.E. et al. Inhaled nitric oxide reduces the utilization of extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn. Crit Care Med. 1997; 25: 352-359 Crossref PubMed Scopus (67) Google Scholar was the breakthrough that won FDA approval for iNO therapy.