Dose-response curves 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 Pao2 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, Sérès, 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 Pao2, 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 micrograms.kg-1.min-1 was administered and dose response to inhaled nitrix 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 Pao2 for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine increased Pao2/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.m2 (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 Pao2 was observed for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm increased Pao2/FIo2 from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), decreased Qs/QT from 35 +/- 2 to 24 +/- 2% (P < 0.001), pulmonary vascular resistance index from 455 +/- 185 to 385 +/- 138 dyn.s.cm-5.m2 (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 nitrix oxide, the administration of intravenous almitrine at a concentration of 16 micrograms.kg-1.min-1 induced an additional increase in Pao2. 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.
D000280:Administration, Inhalation; D000328:Adult; D015765:Almitrine / Q000008:administration & dosage*; D003422:Critical Care / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D011175:Positive-Pressure Respiration; D012119:Respiration / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D019141:Respiratory System Agents / Q000008:administration & dosage*
D019141:Respiratory System Agents; D009569:Nitric Oxide; D015765:Almitrine