INHALED NITRIC-OXIDE REVERSES THE INCREASE IN PULMONARY VASCULAR-RESISTANCE INDUCED BY PERMISSIVE HYPERCAPNIA IN PATIENTS WITH ACUTE RESPIRATORY-DISTRESS SYNDROME

Background: The aim of this prospective study was to determine if inha led nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permi ssive hypercapnia in patients with acute respiratory distress syndrome . Methods: In 11 critically ill patients (mean age 59 +/- 22 yr) with acute respiratory distress syndrome (Murray Score greater than or equa l to 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied : normocapnia (arterial carbon dioxide tension 38 +/- 6 mmHg, tidal vo lume 655 +/- 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia ( arterial carbon dioxide tension 65 +/- 15 mmHg, tidal volume 330 +/- 9 3 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings we re made of heart rate, arterial pressure, pulmonary artery pressure, t racheal pressure, and tidal volume (by pneumotachograph). At the end o f each condition, arterial pressure, pulmonary artery pressure, cardia c filling pressures, and cardiac output were measured. Simultaneous ar terial and mixed venous blood samples were obtained to measure arteria l oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglob in oxygen saturation, pH, and blood hemoglobin and methemoglobin conce ntrations (by hemoximeter). In addition, plasma concentrations of cate cholamines were measured with a radioenzymatic assay. In 5 patients, e nd-tidal carbon dioxide tension was measured with a nonaspirative infr ared capnometer. Calculations were made of pulmonary vascular resistan ce index, systemic vascular resistance index, true pulmonary shunt, an d alveolar dead space. Results: During hypercapnia, NO decreased pulmo nary vascular resistance index from 525 +/- 223 to 393 +/- 142 dyn . s . cm(-5) m(-2) (P < 0.01), a value similar to that measured in normoc apnic conditions (391 +/- 122 dyn . s . cm(-5) m(-2)). It also reduced mean pulmonary artery pressure from 40 +/- 9 to 35 +/- 8 mmHg (P < 0. 01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 +/- 67 to 270 +/- 87 mmHg during normocapnia and from 189 +/ - 73 to 258 +/- 101 mmHg during hypercapnia (P < 0.01). NO decreased t rue pulmonary shunt during normocapnia (from 34 +/- 3% to 28 +/- 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 /- 7% vs. 38 +/- 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 +/- 7% to 28 +/- 10% in normocapnic condi tions and from 30 +/- 3% to 22 +/- 10% in hypercapnic conditions (P < 0.05). Conclusions: Inhaled NO completely reversed the increase in pul monary vascular resistance index induced by acute permissive hypercapn ia, It only partially reduced the pulmonary hypertension induced by ac ute permissive hypercapnia, probably because the flow component of the increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxy genation after NO administration was observed during normocapnic and h ypercapnic conditions. A ventilation strategy combining permissive hyp ercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonar y circulation.