DOSE-RESPONSE CARVES OF INHALED NITRIC-OXIDE WITH AND WITHOUT INTRAVENOUS ALMITRINE IN NITRIC OXIDE-RESPONDING PATIENTS WITH ACUTE RESPIRATORY-DISTRESS SYNDROME

Background: Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50-60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide. Methods: Six critically ill patients (aged 44 +/- 7 yr) were studied during early stage of their acute respiratory failure (Murray score: 2.6 +/- 0.1). All responded to 15 parts per million (ppm) of inhaled nitric oxide by an increase in Pa-O2 of at least 40 mmHg at FIO2 1. Hemodynamic and respiratory parameters were recorded continuously from pulmonary artery and systemic catheters. inspiratory, expiratory, and mean intratracheal nitric oxide concentrations were monitored continuously using a fast response time chemiluminescence apparatus (NOX 4000, Seres, Aix-en-provence, France). On day 1, 6 inspiratory concentrations of nitric oxide were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, and 45 ppm to determine the dose response of inhaled nitric oxide on Pa-O2, pulmonary shunt, mean pulmonary artery pressure, and pulmonary vascular resistance index. On day 2, a continuous intravenous Infusion of almitrine at a dose of 16 mu g . kg(-1). min(-1) was administered and dose response to inhaled nitric oxide was repeated according to the same protocol as during day 1. A constant FIO2 of 0.85 was used throughout the study. Results:Nitric oxide induced a dose-dependent increase in Pa-O2 for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine increased Pa-O2/FIO2, from 161 +/- 30 to 251 +/- 45 mmHg (P < 0.001) and pulmonary vascular resistance index from 455 +/- 185 to 527 +/- 176 dyn . s . cm(-5). m(2) (P < 0.05), and decreased pulmonary shunt (QS/QT) from 35 +/- 2 to 33 +/- 3% (P < 0.001). During almitrine combined with nitric oxide, a dose-dependent increase in Pa-O2 was observed for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm increased Pa-O2/FIO2, from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), decreased QS/QT from 35 +/- 2 to 24 +/- 2% (Pc 0.001), pulmonary vascular resistance index from 455 +/- 185 to 385 +/- 138 dyn s cm(-5) m(2) (P < 0.05), and mean pulmonary artery pressure from 31 +/- 4 to 28 +/- 4 mmHg (P < 0.001). Conclusions: In 6 patients with early acute respiratory distress syndrome and highly responsive to inhaled nitric: oxide, the administration of intravenous almitrine at a concentration of 16 pg kg(-1) min(-1) induced an additional increase in Pa-O2. Dose response of nitric oxide was not changed by the administration of almitrine and a plateau effect was observed at inspiratory nitric oxide concentrations of 1.5 ppm.