RESUMO
OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.
Assuntos
Broncodilatadores/uso terapêutico , Óxido Nítrico/uso terapêutico , Respiração com Pressão Positiva , Troca Gasosa Pulmonar/efeitos dos fármacos , Insuficiência Respiratória/terapia , Administração por Inalação , Algoritmos , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacologia , Criança , Pré-Escolar , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/fisiopatologia , Hipóxia/terapia , Lactente , Masculino , Óxido Nítrico/administração & dosagem , Óxido Nítrico/farmacologia , Oxigênio/sangue , Insuficiência Respiratória/complicações , Insuficiência Respiratória/fisiopatologia , Falha de TratamentoRESUMO
Cyclophosphamide therapy of the nephrotic syndrome has been associated with oligo- and azoospermia and with abnormalities of testicular histology in adults and pubertal boys. In 15 prepubertal boys, no abnormalities of basal serum levels of LH, FSH, or T were found when they were studied 8 months to 7 years after cyclophosphamide therapy. Five boys were pubertal during therapy were found to have elevated mean basal values of gonadotropins with normal testosterone levels and elevated LH responses to LRF; the FSH responses to LRF were elevated in four patients. One of four boys who were prepubertal during therapy but pubertal at the time of testing had an elevated basal LH and LH response to LRF. Three boys who were prepubertal at the times of therapy and testing had normal LH responses to LRF. The LRF test may provide a means of identifying the patient who has sustained testicular injury and who may require testicular biopsy.