title: Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery.
abstract: OBJECTIVE
  Inhaled nitric oxide (NO) is used as a therapy of pulmonary hypertension in children after cardiac surgery. Hemoglobin binds to NO with great affinity and forms methemoglobin by oxidation in the erythrocyte. Once produced, methemoglobin is unable to transport and unload oxygen in the tissues. The amount of available hemoglobin in the body for oxygen transport is thereby reduced. Anemia, acidosis, respiratory compromise and cardiac disease may render patients more susceptible than expected for a given methemoglobin level. The goal of the present study was to review the cumulative effect of inhaled NO on methemoglobin formation in critically ill children. We therefore looked for methemoglobin levels in children with congenital heart disease after cardiac surgery who were treated with inhaled NO in a range of 5-40 ppm.
  
  
  METHODS
  We retrospectively reviewed the medical charts of 38 children with congenital heart disease after cardiac surgery. We extracted demographic data and physiological measurements at the following time points: (1) T0 = before starting inhaled NO therapy, (2) T1 = 24 h after the beginning of inhaled NO therapy, (3) T2 = half-time therapy, (4) T3 = end of therapy, (5) T4 = 24 h after finishing inhaled NO therapy.
  
  
  RESULTS
  The median duration of inhaled NO therapy was 5.5 days (interquartile range 6, range 2-29), NO concentrations at T1 and T2 were 16 ppm (10, 5-40) and 12.5 ppm (12.3, 2-40), respectively. The median cumulative dose of inhaled NO was 1699 ppm (2313, 193-7018). Methemoglobin levels increased moderately, but significantly, during therapy ( T0 vs T1 p<0.05 and T0 vs T2 p<0.001). The highest methemoglobin level measured was 3.9%. Methemoglobin levels correlated positively with the inhaled NO doses applied at T1 ( r(2)=0.8376; p<0.01) and at T2 ( r(2)=0.8945; p<0.01). At T1 the methemoglobin level correlated negatively with the T1 blood pH value. The overall mortality rate was 13.2% (5 of 38 study patients died). There was no significant difference in methemoglobin levels between survivors and non-survivors.
  
  
  CONCLUSIONS
  We conclude from our data that the use of inhaled NO therapy for children with congenital heart disease after cardiac surgery in the described range of 5-40 ppm, resulting in a maximum of 4% methemoglobin blood level, is feasible and safe. However, we recommend the use of the minimal effective dose of inhaled NO and continuous monitoring of methemoglobin levels, especially in cases of anemia or sepsis in critically ill children.
authors.affiliation: Department of Neonatology and Pediatric Intensive Care, University Children's Hospital, University of Vienna, Währinger-Gürtel 18-20, 1090 Vienna, Austria. Michael.Hermon@akh-wien.ac.at
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hermon
authors.forename: Gudrun
authors.initials: G
authors.lastname: Burda
authors.forename: Johann
authors.initials: J
authors.lastname: Golej
authors.forename: Harald
authors.initials: H
authors.lastname: Boigner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stoll
authors.forename: Erwin
authors.initials: E
authors.lastname: Kitzmüller
authors.forename: Gregor
authors.initials: G
authors.lastname: Wollenek
authors.forename: Arnold
authors.initials: A
authors.lastname: Pollak
authors.forename: Gerhard
authors.initials: G
authors.lastname: Trittenwein
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D002648:Child; D006330:Heart Defects, Congenital / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008706:Methemoglobin / Q000378:metabolism*; D009569:Nitric Oxide / Q000627:therapeutic use*; D010092:Oximetry; D012189:Retrospective Studies
chemical_list: D009569:Nitric Oxide; D008706:Methemoglobin