RESUMEN
PURPOSE: Conventional ventilation in the neonatal intensive care unit causes iatrogenic injury to fragile newborn lungs, especially those with preexisting pathology or prematurity. Intratracheal pulmonary ventilation (ITPV), developed by Dr Theodor Kolobow and associates at the National Institutes of Health (NIH), incorporates a continuous flow of humidified gas through a reverse thrust catheter positioned at the distal end of the endotracheal tube. In animal studies ITPV was shown to facilitate gas exchange at low peak pressures by reducing physiological dead space, facilitating exhalation, and enhancing CO2 elimination. The specific aims of this project were (1) to invent a new ITPV-specific ventilator; (2) to optimize gas exchange in a newborn animal model at low airway pressures using higher frequency ITPV; and (3) to demonstrate efficacy and improved ventilation at lower airway pressures in a prematurity model. METHODS: (1) A new ventilator had to be constructed. The first prototype is microprocessor driven, incorporating controls for flow, pressures, and concentrations of gases. The ventilator has the capability to vary Fio2, respiratory rate (0 to 15 Hz), and inspiratory-expiratory I:E ratio. (2) Prototype testing was performed. Newborn lambs (n = 3, 6 to 7 kg) underwent tracheotomy and placement of arterial and venous lines. Lambs were initially supported on conventional mechanical ventilation (CMV). Animals were allowed to achieve steady state with measurements of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted at a rate of 100 breaths per minute and flow adjusted to achieve lower peak carinal pressures than obtainable on conventional ventilation. In a stepwise fashion, respiratory rate, I:E ratio, and ITPV flows were varied while initially maintaining Paco2 constant, and then allowing improvement. (3) These experiments were repeated in preterm lambs (n = 6, 1.8 to 3.6 kg). RESULTS: At the time of transition from CMV to ITPV (rate, 100, I:E, 1:3), gas exchange was maintained despite a documented drop in average peak carinal pressure for the newborn lambs from 28.3 cm H2O on CMV to 10.3 cm H2O on ITPV (P = .028). The average peak carinal pressure fell even further at higher ITPV rates with adjustments in I:E ratio. For the premature lambs, peak carinal pressures also fell significantly on ITPV (44 to 32 cm H2O, P = .002) with corresponding significant improvement in ventilation (Paco2 from 52.2 to 31.9 mm Hg, P = .029). CONCLUSIONS: (1) Our new ITPV ventilator operates at rates and I:E ratios previously unobtainable. (2) In newborn and premature lambs ITPV functions most effectively at higher rates with higher gas flow rates and with longer exhalation, providing significantly improved gas exchange at significantly lower peak carinal pressures. (3) ITPV may prove beneficial in achieving gas exchange in newborns while avoiding barotrauma. Based on these data, we have initiated human clinical studies of ITPV in newborns with congenital diaphragmatic hernia or prematurity to improve gas exchange and reduce barotrauma in the neonatal intensive care unit.
Asunto(s)
Ventilación de Alta Frecuencia/instrumentación , Animales , Animales Recién Nacidos , Barotrauma/etiología , Barotrauma/prevención & control , Ventilación de Alta Frecuencia/efectos adversos , Ventilación de Alta Frecuencia/métodos , Humanos , Recién Nacido , Recien Nacido Prematuro , Presión , Intercambio Gaseoso Pulmonar , Ovinos , Ventiladores MecánicosRESUMEN
PURPOSE: Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. METHODS: Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. RESULTS: The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters. CONCLUSIONS: (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.