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.