title: Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group.
abstract: Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.
authors.affiliation: Unité de Réanimation Chirurgicale (Department of Anesthesiology), Hôpital de la Pitié-Salpétrière, University of Paris VI, France.
authors.forename: L
authors.initials: L
authors.lastname: Gallart
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
authors.forename: L
authors.initials: L
authors.lastname: Puybasset
authors.forename: G S
authors.initials: GS
authors.lastname: Umamaheswara Rao
authors.forename: P
authors.initials: P
authors.lastname: Coriat
authors.forename: J J
authors.initials: JJ
authors.lastname: Rouby
mesh_terms: D000280:Administration, Inhalation; D015765:Almitrine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007773:Lactates / Q000097:blood; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011175:Positive-Pressure Respiration; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012772:Shock, Septic / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007773:Lactates; D019141:Respiratory System Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D015765:Almitrine; D010100:Oxygen