Therapeutic Role of Nitric Oxide in Respiratory Disease

Thomas E. Siddons, BSc, Mohammed Asif, MA, BMBCh, FRCS, and Tim W. Higenbottam, MD, MA, BSc, FRCP, University of Sheffield, Sheffield, United Kingdom

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Inhaled NO in Persistent Pulmonary Hypertension of the Neonate

During gestation, the fetus exchanges carbon dioxide for oxygen via placental gas exchange mechanisms. Only 10% of the fetal cardiac output is directed toward the pulmonary circulation because the lungs play no role in gas exchange at this stage.[13] Because pulmonary vascular resistance (PVR) is greater than systemic vascular resistance (SVR), blood from the right heart bypasses the lungs via the patent ductus arteriosus and foramen ovale. At birth, the PVR decreases to a level lower than that of the SVR, thereby allowing the lungs to take over gas exchange.In cases where the SVR does not surpass PVR, shunting of blood continues and results in persistent pulmonary hypertension of the neonate (PPHN), causing severe hypoxemia.

PPHN is associated with high morbidity and mortality rates, which are related to the severity and duration of systemic hypoxemia. Therefore,management of this condition is directed toward improving oxygenation. Conventional therapeutic regimens, such as oxygen support, mechanical ventilation, and induction of alkalosis, have not been successful in reducing mortality or the need for extracorporeal membrane oxygenation (ECMO).[14] ECMO is an invasive procedure; therefore, alternatives have been sought. The selective action, lack of systemic vascular effects, and relative simplicity of inhaled NO have led researchers to investigate whether this therapy could replace ECMO. It was recently demonstrated that, for patients with PPHN, inhaled NO is clearly beneficial and even more effective than ECMO.[15]

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