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, i n combination with intravenous almitrine, a selective pulmonary vasoco nstrictor, markedly improves arterial oxygenation in 50-60% of patient s with acute lung injury. The goal of this study was to assess dose re sponse of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide. M ethods: Six critically ill patients (aged 44 +/- 7 yr) were studied du ring early stage of their acute respiratory failure (Murray score: 2.6 +/- 0.1). All responded to 15 parts per million (ppm) of inhaled nitr ic oxide by an increase in Pa-O2 of at least 40 mmHg at FIO2 1. Hemody namic and respiratory parameters were recorded continuously from pulmo nary artery and systemic catheters. inspiratory, expiratory, and mean intratracheal nitric oxide concentrations were monitored continuously using a fast response time chemiluminescence apparatus (NOX 4000, Sere s, 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, an d 45 ppm to determine the dose response of inhaled nitric oxide on Pa- O2, pulmonary shunt, mean pulmonary artery pressure, and pulmonary vas cular 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 s ame protocol as during day 1. A constant FIO2 of 0.85 was used through out 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 25 1 +/- 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 dec reased pulmonary shunt (QS/QT) from 35 +/- 2 to 33 +/- 3% (P < 0.001). During almitrine combined with nitric oxide, a dose-dependent increas e in Pa-O2 was observed for inspiratory nitric oxide concentrations ra nging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm in creased Pa-O2/FIO2, from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), de creased QS/QT from 35 +/- 2 to 24 +/- 2% (Pc 0.001), pulmonary vascula r 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 respir atory 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 respo nse of nitric oxide was not changed by the administration of almitrine and a plateau effect was observed at inspiratory nitric oxide concent rations of 1.5 ppm.