Dose response to inhaled nitric oxide in pediatric patients with pulmonary hypertension and acute respiratory distress syndrome.
OBJECTIVE
To determine the pulmonary vascular functional dose response to inhaled nitric oxide (NO) for infants and children with acute respiratory distress syndrome and pulmonary artery hypertension.


METHODS
Prospective, clinical observational study.


METHODS
Thirteen-bed pediatric intensive care unit at a 168-bed children's hospital.


METHODS
Infants and children requiring mechanical ventilation with an oxygenation index greater than 10.


METHODS
Children with severe acute respiratory distress syndrome received inhalation therapy with NO after conventional mechanical ventilation failed to result in improvement. Inhaled NO was sequentially titrated from 10 parts per million to 20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary artery pressure of at least 10%, or an increase in the hypoxemia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic response. After sequential titration, children who responded received continuous inhaled NO at the lowest dose associated with a therapeutic response.


RESULTS
Fourteen children received 15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months). One patient's condition deteriorated during the titration phase, unrelated to NO treatment, and the patient was withdrawn from the study protocol. The mean (+/- SD) pretreatment oxygenation index was 35 +/- 15, which decreased to 32 +/- 20 at 80 ppm of inhaled NO (p = 0.01). Ten children had pulmonary artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI during the titration phase but demonstrated an increase of more than 30% after NO therapy was discontinued. Mean pretreatment PVRI (270 +/- 106) decreased to 207 +/- 92 dynes/sec per cubic centimeter per square meter at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary artery pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhaled NO (p = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic hypotension was not observed in any patient, and the maximum methemoglobin level was 5%.


CONCLUSIONS
Inhaled NO appears to be a safe, although variably effective, therapy for the treatment of infants and children with acute respiratory distress syndrome. The maximum dose response occurs between 20 and 40 ppm of inhaled NO. Systemic side effects did not occur in any child who received NO therapy.
Nakagawa
T A
TA
Division of Pediatric Critical Care Medicine, Children's Hospital, King's Daughters, Norfolk, VA 23607, USA.
Morris
A
A
Gomez
R J
RJ
Johnston
S J
SJ
Sharkey
P T
PT
Zaritsky
A L
AL
D000280:Administration, Inhalation; D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects; D002407:Catheterization, Swan-Ganz; D002648:Child; D002675:Child, Preschool; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000188:drug therapy; D007223:Infant; D008168:Lung / Q000098:blood supply; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects; D011669:Pulmonary Wedge Pressure; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D015996:Survival Rate; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D008706:Methemoglobin; D010100:Oxygen