title: Inhaled nitric oxide, almitrine infusion, or their coadministration as a treatment of severe hypoxemic focal lung lesions.
abstract: BACKGROUND
  The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome.
  
  
  METHODS
  Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured.
  
  
  RESULTS
  Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia.
  
  
  CONCLUSIONS
  In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, U.F.R. de Médecine Lariboisière-Saint-Louis, Université Paris VII, France. didier.payen@hol.fr
authors.forename: D
authors.initials: D
authors.lastname: Paven
authors.forename: J
authors.initials: J
authors.lastname: Muret
authors.forename: S
authors.initials: S
authors.lastname: Beloucif
authors.forename: C
authors.initials: C
authors.lastname: Gatecel
authors.forename: N
authors.initials: N
authors.lastname: Kermarrec
authors.forename: N
authors.initials: N
authors.lastname: Guinard
authors.forename: J
authors.initials: J
authors.lastname: Mateo
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D015765:Almitrine / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008171:Lung Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012129:Respiratory Function Tests; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019141:Respiratory System Agents; D009569:Nitric Oxide; D015765:Almitrine