Randomized, controlled trial of low-dose inhaled nitric oxide in the treatment of term and near-term infants with respiratory failure and pulmonary hypertension.

UNLABELLED: Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear. OBJECTIVES: To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI. STUDY DESIGN: A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age <1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15). RESULTS: Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group. CONCLUSION: In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, but does attenuate the rate of clinical deterioration; and 2) at 20 ppm acutely improves oxygenation in infants initially treated with 0 ppm, but not in infants previously treated with iNO at 2 ppm. Initial treatment with a subtherapeutic dose of iNO may diminish the clinical response to 20 ppm of iNO and have adverse clinical sequelae.

Tracheal epithelial permeability to nonelectrolytes: species differences.

We developed a new excised tracheal preparation to measure the epithelial permeability of large lipid-insoluble nonelectrolytes and macromolecules. Tracheae were suspended vertically in a Ringer solution bath, and a solution containing labeled test solutes was positioned in the center of the tracheal segment, away from damaged ends. Permeability coefficients, calculated from solute fluxes into the bath, were constant for > or = 2 h at 37 degrees C, and no histological changes were observed. Measurements after epithelial removal with detergent indicate that in the intact trachea the epithelium represents > 90% of the resistance to transport. For the rat trachea, permeability coefficients for sucrose, inulin, and Dextran 20 were 9.22, 2.20, and 0.214 x 10(-7) cm/s, respectively. Values for cat tracheae were similar, those for rabbit tracheae were lower, and those for guinea pig tracheae were markedly greater. With the assumption of transport by diffusion through thin rectangular slits between epithelial cells, the rat and guinea pig data fit a slit width of 7-8 nm, whereas the rabbit and cat data cannot be explained by a model with slits of a single size.

Alterations in feline tracheal permeability after mechanical ventilation.

OBJECTIVES: Previous investigations of ventilator-induced airway injury focused on histopathologic changes associated with various ventilators and strategies for their use. We hypothesized that mechanical ventilation is associated with alterations in tracheal epithelial permeability, and designed a study using an animal model to evaluate changes in tracheal epithelial permeability after administering different types of mechanical ventilation to test this hypothesis. DESIGN: Prospective, multiple-group, controlled trial. Five groups of animals were studied and compared. Eight animals were studied without intubation or mechanical ventilation. A total of 28 animals (seven in each group) were studied after conventional mechanical ventilation, high-frequency positive-pressure ventilation, high-frequency jet ventilation, or high-frequency flow interruption at respiratory rates of 20, 150, 400, and 900 breaths/min, respectively. Comparison of data for each group was done using the Kruskall-Wallis analysis of variance. Between-group comparisons were made using standard error of the mean comparisons. For airway pressures and other physiologic data, one-way analysis of variance was performed. Between-group comparisons were made using the Student-Newman-Keuls' test. SETTING: Small animal physiology laboratory. SUBJECTS: Thirty-six adult cats. INTERVENTIONS: Mechanically ventilated animals were treated for 8 hrs and then killed. Inspired oxygen concentration, BP, and mean airway pressures were comparable in mechanically ventilated animals. Spontaneously breathing control animals were killed without endotracheal intubation or exposure to mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Permeability values in isolated tracheal segments were calculated for 14C-sucrose, 3H-inulin, and fluorescein isothiocyanate-dextran-20. Tracheal epithelial permeability to all studied molecules increased after exposure to mechanical ventilators. These different mechanical ventilators increased epithelial permeability in a progressive manner that paralleled ventilatory frequency. The changes were greatest after ventilation at the highest frequency. These observed changes in tracheal permeability are consistent with previously observed alterations in tracheal histopathology after exposure to mechanical ventilation. CONCLUSIONS: Mechanical ventilation was associated with increases in tracheal permeability to large and small nonionic molecules. These changes occurred with all studied ventilators, used as they are clinically. Permeability changes paralleled ventilatory rate changes.

Assessment of the diurnal variations in urinary homovanillic and vanillylmandelic acid excretion for the diagnosis and follow-up of patients with neuroblastoma.

The diurnal variation of urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) was studied in neuroblastoma patients and in a control group. Urinary HVA and VMA levels in four sequential 6-hour urine collections within a 24-hour period were compared. HVA and VMA levels were expressed in microgram/mg of urinary creatinine (UCr) and in mg/6h specimens. No statistically significant variations between the four time intervals were found when expressed in microgram/mg UCr or mg/6h. The small variations that exist in the excretion of HVA and VMA during different periods of the day are due to variations in renal excretion rather than variations in production. The results from this study indicate that a random urine sample should be as good as a 24-hour collection for diagnosis and follow-up of neural crest tumors.