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 respons e to inhaled nitric oxide (NO) for infants and children with acute res piratory distress syndrome and pulmonary artery hypertension. Design: Prospective, clinical observational study. Setting: Thirteen-bed pedia tric intensive care unit at a 168-bed children's hospital. Patients: I nfants and children requiring mechanical ventilation with an oxygenati on index greater than 10. Methods: Children with severe acute respirat ory distress syndrome received inhalation therapy with NO after conven tional mechanical ventilation failed to result in improvement. Inhaled NO uas 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 pu lmonary artery pressure of at least 10%, or an increase in the hypoxem ia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic respo nse. After sequential titration, children who responded received conti nuous inhaled NO at the lowest dose associated with a therapeutic resp onse. Results: Fourteen children received 15 trials with inhaled NO (m edian age, 63.4 months; range, 0.4 to 201 months). One patient's condi tion deteriorated during the titration phase, unrelated to NO treatmen t, and the patient was withdrawn from the study protocol.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 pulmona ry artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI duri ng the titration phase but demonstrated an increase of more than 30% a fter NO therapy was discontinued Mean pretreatment PVRI (270 +/- 105) decreased to 207 +/- 92 dynes/sec per cubic centimeter per square mete r at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary arte ry pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhale d 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 therap y ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic h ypotension was not observed in any patient, and the maximum methemoglo bin level was 5%. Conclusion: Inhaled NO appears to be a safe, althoug h variably effective, therapy for the treatment of infants and childre n 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.