title: Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn.
abstract: OBJECTIVE
  To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN).
  
  
  METHODS
  Prospective open observational clinical study.
  
  
  METHODS
  A regional cardiac and pediatric intensive care unit.
  
  
  METHODS
  Twenty-five consecutive near-term neonates (> 35 weeks gestation) with severe PPHN (oxygenation index [OI] > 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in PaO2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy.
  
  
  RESULTS
  Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO-one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to > 40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days--all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy.
  
  
  CONCLUSIONS
  Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.
authors.affiliation: Cardiac Unit, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: A P
authors.initials: AP
authors.lastname: Goldman
authors.forename: R C
authors.initials: RC
authors.lastname: Tasker
authors.forename: S G
authors.initials: SG
authors.lastname: Haworth
authors.forename: P E
authors.initials: PE
authors.lastname: Sigston
authors.forename: D J
authors.initials: DJ
authors.lastname: Macrae
mesh_terms: D000280:Administration, Inhalation; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D012121:Respiration, Artificial; D019141:Respiratory System Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D019141:Respiratory System Agents; D009569:Nitric Oxide