title: Inhaled nitric oxide and vasoconstrictors in acute respiratory distress syndrome.
abstract: It has been suggested that the increase in PO(2) observed with nitric oxide (NO) should be enhanced by the addition of a vasoconstrictor agent. The vasoconstrictor used in combination with NO should mimic or enhance hypoxic vasoconstriction. The aim of this study was to evaluate the respiratory and hemodynamic effects of norepinephrine (a nonspecific vasoconstrictor), almitrine bismesylate (a specific pulmonary vasoconstrictor), and inhaled NO, alone or together. During a 6-mo period, 16 patients presenting with ARDS were prospectively investigated. On inclusion, no patient was receiving cardiovasoactive drugs. The protocol consisted of seven consecutive phases: baseline, norepinephrine (in order to obtain a 3 mm Hg rise in mean pulmonary arterial pressure [Ppa]), almitrine bismesylate (16 micrograms/kg/min), inhaled NO (20 ppm delivered during inspiration), norepinephrine + inhaled NO, almitrine bismesylate + inhaled NO, almitrine bismesylate + norepinephrine + inhaled NO. General factorial analysis of variance showed that inhaled NO and almitrine bismesylate increased oxygenation (p < 0.0001). Norepinephrine had no effect on oxygenation. A synergistic effect between inhaled NO and almitrine bismesylate was found (p < 0.05), whereas norepinephrine did not affect the response to inhaled NO. Nitric oxide produced a significant decrease in Ppa and pulmonary vascular resistances (PVRI) (p < 0.0001). Both almitrine bismesylate and norepinephrine induced an increase in Ppa (p < 0.0001). Norepinephrine increased PVRI (p < 0.002), whereas almitrine bismesylate had no effect on PVRI. The present results support the hypothesis that a selective pulmonary vasoconstrictor enhances the increase in oxygenation induced by inhaled NO, whereas norepinephrine attenuates this effect.
authors.affiliation: Service de Réanimation, Service d'Information Médicale, Hôpital Sainte-Marguerite, Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Papazian
authors.forename: A
authors.initials: A
authors.lastname: Roch
authors.forename: F
authors.initials: F
authors.lastname: Bregeon
authors.forename: X
authors.initials: X
authors.lastname: Thirion
authors.forename: F
authors.initials: F
authors.lastname: Gaillat
authors.forename: P
authors.initials: P
authors.lastname: Saux
authors.forename: V
authors.initials: V
authors.lastname: Fulachier
authors.forename: Y
authors.initials: Y
authors.lastname: Jammes
authors.forename: J P
authors.initials: JP
authors.lastname: Auffray
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015765:Almitrine / Q000008:administration & dosage* / Q000009:adverse effects; D003422:Critical Care; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D009638:Norepinephrine / Q000008:administration & dosage* / Q000009:adverse effects; D010100:Oxygen / Q000097:blood; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012129:Respiratory Function Tests; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D015765:Almitrine; D010100:Oxygen; D009638:Norepinephrine