Inhaled nitric oxide in adults with the acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a severe form of lung injury characterized by permeability edema and lung inflammation. The diagnostic criteria for ARDS includes the acute onset of severe hypoxemia with diffuse bilateral opacities on chest radiograph that are not due to left atrial hypertension; alveolar damage may result from either direct or indirect lung injury (1). In addition, pulmonary vascular resistance (PVR) is increased and right ventricular (RV) function impaired secondary to hypoxic and mediator induced vasoconstriction, as well as extensive endothelial damage and structural remodeling of the pulmonary vasculature (2,3). Conventional methods for optimizing oxygen delivery in ARDS include mechanical ventilation and hemodynamic support. Hypotension and progressive hypoxemia limited initial attempts to improve ventilation–perfusion matching, PVR and RV function with systemic vasodilators (4). Therapy with prostaglandin E1 and a liposomal derivative, agents with both vasoactive and anti-inflammatory properties, were also disappointing (5,6). The introduction of inhaled nitric oxide (iNO?) as a selective pulmonary vasodilator that reverses hypoxic pulmonary vasoconstriction however, renewed interest in pharmacological treatments aimed at improving ventilation–perfusion matching and reducing pulmonary hypertension in ARDS (7,8). Nitric oxide (NO?) is an endogenously formed free radical gas with numerous biological actions. It regulates or affects vascular tone, leukocyte–endothelial interactions, platelet aggregation, neurotransmission and cell-mediated immune responses through cGMP-dependent and -independent mechanisms. NO? rapidly diffuses across lipid membranes giving it access to intracellular targets, not only in the cell of origin, but also in nearby cells. In addition, NO? may form S-nitrosyl compounds and, consequently, exist in a more stable state. NO? inhalation therapy involves the addition of NO? gas to the inspiratory circuit during mechanical ventilation. The NO? gas is thought to be