title: Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure.
abstract: OBJECTIVE
  To describe the effects of inhaled nitric oxide on oxygenation and ventilation in patients with acute, hypoxic respiratory failure and to characterize those who respond to low doses with a significant improvement in PaO2.
  
  
  METHODS
  Prospective dose response trial of inhaled nitric oxide. Patients who demonstrated a > or =15% improvement in PaO2 were randomized to receive conventional mechanical ventilation with or without prolonged inhaled nitric oxide.
  
  
  METHODS
  Pediatric intensive care unit of a tertiary care children's hospital serving as a regional referral center for respiratory failure.
  
  
  METHODS
  Pediatric patients with an acute parenchymal lung disease requiring mechanical ventilation, an F(IO2) of > or =0.5, a positive end-expiratory pressure of > or =7 cm H2O, and whose PaO2/FIO2 ratio was < or =160.
  
  
  METHODS
  PaO2, PaCO2, pH, heart rate, blood pressure, and methemoglobin were recorded at baseline and after inhaling 1, 5, 10, and 20 ppm of nitric oxide. Peak expiratory flow rate and mean airway resistance were measured while subjects received 0 and 20 ppm of inhaled nitric oxide. Patients were followed up until extubation or death.
  
  
  RESULTS
  Twenty-six patients (median age, 2.6 yrs [range, 1 mo-18.2 yrs]) were enrolled in the study. PaO2 increased (p< .001) and Pa(CO2) fell (p< .0001) from baseline with the administration of inhaled nitric oxide. There was no statistical difference among 1, 5, 10, and 20 ppm with regard to effects on oxygenation. Sixteen patients (62%) responded to inhaled nitric oxide with a > or =15% improvement in PaO2; 14 of these responses occurred at a dose of 1 or 5 ppm. Response to inhaled nitric oxide was not associated with age, length of intubation, presence of primary lung disease, chest radiograph, or illness severity. Among patients weighing < or =20 kg, responders showed a greater fall in mean airway resistance (p < .05) than nonresponders. Mortality was not influenced by prolonged inhaled nitric oxide when analyzed by intention to treat. Patients receiving prolonged inhaled nitric oxide at doses of < or =20 ppm maintained methemoglobin levels of <3.0% and circuit concentrations of NO2 of <1 ppm.
  
  
  CONCLUSIONS
  Inhaled nitric oxide at doses of < or =5 ppm improves the oxygenation and (to a lesser extent) ventilation of most children with acute, hypoxic respiratory failure. The unpredictable response of patients necessitates individualized dosing of inhaled nitric oxide, starting at concentrations of < or =1 ppm. Inhaled nitric oxide at < or =20 ppm may exert a small salutary effect on bronchial tone. The benefits of prolonged inhaled nitric oxide remain unknown.
authors.affiliation: Department of Pediatrics, Saint Louis University, Cardinal Glennon Children's Hospital, St. Louis, MO 63104, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Ream
authors.forename: J F
authors.initials: JF
authors.lastname: Hauver
authors.forename: R E
authors.initials: RE
authors.lastname: Lynch
authors.forename: B
authors.initials: B
authors.lastname: Kountzman
authors.forename: G B
authors.initials: GB
authors.lastname: Gale
authors.forename: R B
authors.initials: RB
authors.lastname: Mink
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000293:Adolescent; D000403:Airway Resistance / Q000187:drug effects; D001784:Blood Gas Analysis; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007223:Infant; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011446:Prospective Studies; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D008706:Methemoglobin; D010100:Oxygen