[Inhaled nitric oxide: a physiologic treatment of persistent pulmonary arterial hypertension in the newborn].
Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it.
Thébaud
B
B
Service de réanimation pédiatrique polyvalente, hôpital Robert-Debré, Paris, France.
Mercier
J C
JC
D000280:Administration, Inhalation; D006612:High-Frequency Ventilation; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000502:physiology / Q000506:poisoning / Q000627:therapeutic use*; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D011652:Pulmonary Circulation / Q000502:physiology; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy
D009569:Nitric Oxide