Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.     

Gas exchange in healthy rabbits during high-frequency oscillatory ventilation

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.     

Normocapnic high-frequency oscillatory ventilation affects differently extrapulmonary and pulmonary forms of acute respiratory distress syndrome in adults

The recently reported differences between pulmonary and extrapulmonary acute respiratory distress syndromes (ARDS(p), ARDS(exp)) are the main reasons of scientific discussion on potential differences in the effects of current ventilatory strategies. The aim of this study is to assess whether the presence of ARDS(p) or ARDS(exp) can differently affect the beneficial effects of high-frequency oscillatory ventilation (HFOV) upon physiological and clinical parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in case of failure of conventional ventilation strategy. According to the ARDS type, each patient was included either in the group of patients with ARDS(p) or ARDS(exp). Six hours after normocapnic HFOV introduction, there was no significant increase in PaO2/F(I)O2 in ARDS(p) group (from 129+/-47 to 133+/-50 Torr), but a significant improvement was found in ARDS(exp) (from 114+/-54 to 200+/-65 Torr, p<0.01). Despite the insignificant difference in the latest mean airway pressure (MAP) on conventional mechanical ventilation (CMV) between both groups, initial optimal continuous distension pressure (CDP) for the best PaO2/F(I)O2 during HFOV was 2.0+/-0.6 kPa in ARDS(p) and 2.8+/-0.6 kPa in ARDS(exp) (p<0.01). HFOV recruits and thus it is more effective in ARDS(exp). ARDS(exp) patients require higher CDP levels than ARDS(p) patients. The testing period for positive effect of HFOV is recommended not to be longer than 24 hours.     

Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation.

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VL(max) was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.     

High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability

To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.     

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.     

Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation.

This study compared pathophysiological and biochemical indexes of acute lung injury in a saline-lavaged rabbit model with different ventilatory strategies: a control group consisting of moderate tidal volume (V(T)) (10-12 ml/kg) and low positive end-expiratory pressure (PEEP) (4-5 cmH(2)O); and three protective groups: 1) low V(T) (5-6 ml/kg) high PEEP, 2-3 cmH(2)O greater than the lower inflection point; 2) low V(T) (5-6 ml/kg), high PEEP (8-10 cmH(2)O); and 3) high-frequency oscillatory ventilation (HFOV). The strategy using PEEP > inflection point resulted in hypotension and barotrauma. HFOV attenuated the decrease in pulmonary compliance, the lung inflammation assessed by polymorphonuclear leukocyte infiltration and tumor necrosis factor-alpha concentration in the alveolar space, and pathological changes of the small airways and alveoli. Conventional mechanical ventilation using lung protection strategies (low V(T) high PEEP) only attenuated the decrease in oxygenation and pulmonary compliance. Therefore, HFOV may be a preferable option as a lung protection strategy.     

Response of laryngeal mechanoreceptors to high-frequency pressure oscillation.

High-frequency pressure oscillations (HFPO) in the upper airway induce arousal, activation of genioglossus muscle, and bronchoconstriction. The present study was designed to determine the response of superior laryngeal nerve afferent fibers to HFPO. In 10 anesthetized dogs spontaneously breathing through a tracheal cannula, the upper airway was converted to a closed system. The activity of thin bundles separated from the peripheral cut end of the superior laryngeal nerve was monitored. Of 104 mechanoreceptors identified, 87 were classified as respiratory modulated and 17 as non-respiratory modulated on the basis of their response to transmural pressure change and muscle activity. The responses of these fibers to HFPO of +/- 2.5 cmH2O at 10, 20, and 30 Hz were determined. Among the respiratory-modulated receptors, 86 of 87 increased their activity in response to HFPO. Of the 17 non-respiratory-modulated receptors, 12 receptors showing a random or tonic activity did not respond to HFPO, whereas the 5 that were silent during control condition responded exclusively to HFPO. Our results show that HFPO of similar frequency but much less magnitude than snoring is capable of activating the vast majority of laryngeal mechanoreceptors. Pressure-sensitive respiratory-modulated endings appear to mediate the arousal and genioglossal response, whereas non-respiratory-modulated receptors responding to HFPO presumably mediate the bronchoconstrictive response.     

Respiratory mechanics during high-frequency oscillatory ventilation: a physical model and preterm infant study

Accurate mechanics measurements during high-frequency oscillatory ventilation (HFOV) facilitate optimizing ventilator support settings. Yet, these are influenced substantially by endotracheal tube (ETT) contributions, which may dominate when leaks around uncuffed ETT are present. We hypothesized that 1) the effective removal of ETT leaks may be confirmed via direct comparison of measured vs. model-predicted mean intratracheal pressure [mPtr (meas) vs. mPtr (pred)], and 2) reproducible respiratory system resistance (Rrs) and compliance (Crs) may be derived from no-leak oscillatory Ptr and proximal flow. With the use of ETT test-lung models, proximal airway opening (Pao) and distal (Ptr) pressures and flows were measured during slow-cuff inflations until leaks are removed. These were repeated for combinations of HFOV settings [frequency, mean airway pressure (Paw), oscillation amplitudes (ΔP), and inspiratory time (%t(I))] and varying test-lung Crs. Results showed that leaks around the ETT will 1) systematically reduce the effective distending pressures and lung-delivered oscillatory volumes, and 2) derived mechanical properties are increasingly nonphysiologic as leaks worsen. Mean pressures were systematically reduced along the ventilator circuit and ETT (Paw > Pao > Ptr), even for no-leak conditions. ETT size-specific regression models were then derived for predicting mPtr based on mean Pao (mPao), ΔP, %t(I), and frequency. Next, in 10 of 11 studied preterm infants (0.77 ± 0.24 kg), no-to-minimal leak was confirmed based on excellent agreement between mPtr (meas) and mPtr (pred), and consequently, their oscillatory respiratory mechanics were evaluated. Infant resistance at the proximal ETT (R(ETT); resistance airway opening = R(ETT) + Rrs; P < 0.001) and ETT inertance (P = 0.014) increased significantly with increasing ΔP (50%, 100%, and 150% baseline), whereas Rrs showed a modest, nonsignificant increase (P = 0.14), and Crs was essentially unchanged (P = 0.39). We conclude that verifying no-leak conditions is feasible by comparison of model-derived vs. distending mPtr (meas). This facilitated the reliable and accurate assessment of physiologic respiratory mechanical properties that can objectively guide ventilatory management of HFOV-treated preterm infants.     

Effect of the TI/TE ratio on mean intratracheal pressure in high-frequency oscillatory ventilation

In high-frequencyoscillatory ventilation (HFOV), an adequate mean airway pressure iscrucial for successful ventilation and optimal gas exchange, but airtrapping cannot be detected by the usual measurement at the y piece.Intratracheal pressures produced by the high-frequency oscillatorsHFV-Infantstar (IS), Babylog 8000 (BL), and the SensorMedics 3100A (SM)[the latter with either 30% (SM₃₀) or 50%(SM₅₀) inspiratory time] were investigated in fouranesthetized tracheotomized female piglets that were 1 day old andweighed 1.6-1.9 kg (mean 1.76 kg). The endotracheal tube wasrepeatedly clamped while the piglets were ventilated with anoscillation frequency of 10 Hz, and the airway pressure distal of theclamp was recorded as a measure of average intrapulmonary pressureduring oscillation. Clamping resulted in a significant decrease of meanairway pressure when the piglets were ventilated with SM₃₀(0.86 cmH₂O), BL (0.66 cmH₂O), and IS(0.71 cmH₂O), but airway pressure increased by a mean of0.76 cmH₂O with SM₅₀. Intratracheal pressure,when measured by a catheter pressure transducer at various oscillationfrequencies, was lower than at the y piece by 0.4-0.9cmH₂O (SM₃₀), 0.3-3 cmH₂O(BL), and 1-4.7 cmH₂O (IS) but was 0.4-0.7cmH₂O higher with SM₅₀. We conclude that theinspiratory-to-expiratory time(TI/TE) ratio influences theintratracheal and intrapulmonary pressures in HFOV and may sustain amean pressure gradient between the y piece and the trachea. ATI/TE ratio < 1:1 maybe useful to avoid air trapping when HFOV is used.

     

Effect of I/E ratio on mean alveolar pressure during high-frequency oscillatory ventilation.

This study investigated factors contributing to differences between mean alveolar pressure (PA) and mean pressure at the airway opening (Pao) during high-frequency oscillatory ventilation (HFOV). The effect of the inspiratory-to-expiratory time (I/E) ratio and amplitude of oscillation on the magnitude of - Pao (Pdiff) was examined by using the alveolar capsule technique in normal rabbit lungs (n = 4) and an in vitro lung model. The effect of ventilator frequency and endotracheal tube (ETT) diameter on Pdiff was further examined in the in vitro lung model at an I/E ratio of 1:2. In both lung models, fell below Pao during HFOV when inspiratory time was shorter than expiratory time. Under these conditions, differences between inspiratory and expiratory flows, combined with the nonlinear relationship between resistive pressure drop and flow in the ETT, are the principal determinants of Pdiff. In our experiments, the magnitude of Pdiff at each combination of I/E, frequency, lung compliance, and ETT resistance could be predicted from the difference between the mean squared inspiratory and expiratory velocities in the ETT. These observations provide an explanation for the measured differences in mean pressure between the airway opening and the alveoli during HFOV and will assist in the development of optimal strategies for the clinical application of this technique.     

Quantitative evaluation of pulmonary stretch receptor activity during high-frequency ventilation.

The purpose of this study was to determine the neural output of pulmonary stretch receptors (PSRs) in response to conditions that, in previous studies (J. Appl. Physiol. 65: 179-186, 1988 and Respir. Physiol. 80: 307-322, 1990), produced apnea in anesthetized cats. These conditions included changes in airway pressure (Paw; 2 or 6 cmH2O), stroke or tidal volume (1-4 ml/kg), frequency [conventional mechanical ventilation (CMV) vs. high-frequency ventilation (HFV) at 10, 15, and 20 Hz], and levels of inspired CO2 (0, 2, and 5%). These data were needed to assess properly the specific contribution of the PSRs to the apnea found with certain combinations of the above variables. Each PSR was subjected to HFV over a range of mechanical and chemical settings, and its activity was recorded. PSRs exhibited continuous activity associated with pump stroke in 11 of 12 fibers tested. PSRs fired more rapidly when mean Paw was 6 cmH2O [45.3 +/- 0.8 (SE) impulses/s] than when it was 2 cmH2O (31.7 +/- 0.9 impulses/s, P = 0.0001). At both pressures, PSR activity increased as the volume of inflation, or tidal volume, was increased from 1 to 4 ml/kg. At Paw of 2 cmH2O, the number of impulses per second for HFV was not different from that for CMV (averaged over the respiratory cycle), under conditions previously demonstrated as apneogenic for both modes of ventilation. Therefore the absolute amount of information being sent to the brain stem processing centers via PSRs during HFV did not differ from that during CMV. Thus any PSR contribution to HFV-induced apnea must have been the result of changes in the pattern of the signal or the central nervous system's processing of it rather than an increase in the amount of inhibitory afferent signal.     

Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18-25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas transport during high-frequency ventilation

During high-frequency small-volume ventilation (HFV), the transport rate of gas from the mouth to a lung region is a function of two conductances (conductance is the transfer rate of a gas divided by its partial pressure difference): regional longitudinal gas conductance along the airways (Grlongi) and gas conductance between lung regions (Ginter). Grlongi per unit regional lung (gas) volume [Grlongi/(Vr beta g)] was determined during HFV in 11 anesthetized paralyzed dogs lying supine. The distribution of Grlongi/(Vr beta g) was nearly uniform during HFV when stroke volumes were less than approximately two-thirds of the Fowler dead-space volume. By contrast, the distribution of Grlongi/(Vr beta g) was nonuniform when the stroke volume exceeded approximately two-thirds of the Fowler dead-space volume and the oscillation frequency was 5 Hz. Gas conductance along the airways per unit lung gas volume [average Glongi/(V beta g)], for the entire lung, increased with stroke volume at all frequencies, but for a given product of oscillation frequency and stroke volume, the average Glongi/(V beta g) was greater when stroke volume was large and oscillation frequency was low. The average Glongi/(V beta g) increased with frequency up to a maximal value; the frequency at which the maximum occurred depended on the kinematic viscosity of the inspired gas mixture.