Effect of frequency and tidal volume on pleural pressure in rabbits during high frequency ventilation.

Regional effects of the chest wall on airway pressure transmission were studied during high frequency ventilation in anesthetized rabbits. We measured airway pressure (Paw), esophageal pressure (Pes), and costal pleural pressure (Ppl) by a rib capsule and flow and volume with a calibrated pneumotachograph. Using a closed circuit, pressures and flow were measured at varying frequencies (2-80 Hz) and tidal volumes (2-20 ml). Mean Pes and Ppl increased with flow amplitude above 100-250 ml/s, whereas mean Paw decreased, consistent with air trapping. Paw, Pes, and Ppl amplitudes increased monotonically with flow amplitude except above 400-500 ml/s, where the Ppl amplitude decreased suddenly. The latter occurring simultaneously with a sudden fall in mean Paw indicated airway flow limitation in costal regions. Flow instabilities during flow limitation were consistent with the large increase in the phase difference between Paw and Ppl and its variability, with frequency. By contrast, the phase difference between Paw and Pes and its variability were relatively small. These differences in Pes from Ppl responses might be caused by a difference in the impedance of the airway-mediastinum pathway or a direct transmission of tracheal pressure oscillations to the esophagus. The former suggests that constraints offered by the mediastinum and rib cage resulted in nonuniform ventilation during high frequency ventilation.

Persistent pulmonary hypertension of the newborn infant. Comparison of conventional versus extracorporeal membrane oxygenation in neonates fulfilling Bartlett's criteria.

Persistent pulmonary hypertension of the newborn (PPHN) is a challenge for the neonatologist and a common indication for treatment with extracorporeal membrane oxygenation (ECMO) when medical management fails. We observed 132 neonates born between January 1985 and December 1988 with the diagnosis of persistent pulmonary hypertension of the newborn: 73 (55%) met the Bartlett criteria for treatment with ECMO with 80% predicted mortality; 21 (29%) deteriorated despite conventional medical treatment, were thought to be dying, and were sent for ECMO. Among the 52 patients who were medically treated 40 (77%) survived, a marked difference compared with a predicted 20% survival. All ECMO-treated neonates survived. Although conventionally treated infants showed a trend toward less dependence on supplemental oxygen at > 28 days of life, this study failed to detect a significant difference between those two groups. We conclude that mortality was lower for ECMO-treated infants than for those who were medically treated (0 of 21 vs 12 of 52, p < 0.05); mortality for infants with persistent pulmonary hypertension of the newborn who met Bartlett's criteria and were medically treated was lower than published data; and there was no significant difference in oxygen dependence at > 28 days between the survivors who received ECMO and those who received medical therapy.

Pleural pressure measured in the zone of apposition of diaphragm to rib cage in rabbits.

In 10 anesthetized adult rabbits, we studied the effect of spontaneous breathing and positive pressure ventilation on pleural pressure on the costal lung surface (Ppl) and in the zone of apposition of the rib cage to the diaphragm (Papp). Ppl and Papp were measured by rib capsules installed in the 5th or 6th rib and 11th or 12th rib, respectively. Esophageal (Pes) and gastric (Pga) pressures were measured with air-filled balloons. At end expiration (functional residual capacity), Ppl was subatmospheric (-2.5 +/- 1.4 cm H2O), decreased during spontaneous inspiration, and was in phase with Pes. In contrast, Papp was above atmospheric pressure (2.1 +/- 1.8 cm H2O), increased during inspiration, and was in phase with Pga. Papp lagged Ppl by 180 degrees during spontaneous inspiration but was in phase with Ppl during mechanical ventilation. Changes in Ppl (delta Ppl) during inspiration were greater in magnitude than either delta Papp or delta Pga. Changes in transdiaphragmatic pressure in the zone of apposition (delta Pga-delta Papp) were near zero (-0.4 +/- 0.3 cm H2O), much smaller in magnitude than those (delta Pga-delta Ppl) associated with the lung (3.0 +/- 1.5 cm H2O). These results are consistent with the concept that during breathing, abdominal pressure is transmitted to the zone of apposition of the rib cage to the abdomen. During spontaneous breathing at rest, the pleural space in the zone of apposition is mechanically independent of the pleural space associated with the lung.

Mechanical coupling of the rib cage, abdomen, and diaphragm through their area of apposition.

Although volumetric displacements of the chest wall are often analyzed in terms of two independent parallel pathways (rib cage and abdomen), Loring and Mead have argued that these pathways are not mechanically independent (J. Appl. Physiol. 53: 756-760, 1982). Because of its apposition with the diaphragm, the rib cage is exposed to two distinct pressure differences, one of which depends on abdominal pressure. Using the analysis of Loring and Mead as a point of departure, we developed a complementary analysis in which mechanical coupling of the rib cage, abdomen, and diaphragm is modeled by a linear translational transformer. This model has the advantage that it possesses a precise electrical analogue. Pressure differences and compartmental displacements are related by the transformation ratio (n), which is the mechanical advantage of abdominal over pleural pressure changes in displacing the rib cage. In the limiting case of very high lung volume, n----0 and the pathways uncouple. In the limit of very small lung volume, n----infinity and the pathways remain coupled; both rib cage and abdomen are driven by abdominal pressure alone, in accord with the Goldman-Mead hypothesis. A good fit was obtained between the model and the previously reported data for the human chest wall from 0.5 to 4 Hz (J. Appl. Physiol. 66:350-359, 1989). The model was then used to estimate rib cage, diaphragm, and abdominal elastance, resistance, and inertance. The abdomen was a high-elastance high-inertance highly damped compartment, and the rib cage a low-elastance low-inertance more lightly damped compartment. Our estimate that n = 1.9 is consistent with the findings of Loring and Mead and suggests substantial pathway coupling.

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.

Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits.

We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (Ptr) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. PaO2, PaCO2, Ptr, and Palv were measured at the following settings: FiO2 = 0.5, frequency 2-28 Hz, Vt 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H2O. Many combinations of frequency and Vt resulted in the same PaO2 and PaCO2. Paw had a large effect on Palv and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f x Vt2 described the trends in Palv and blood gas tensions. As the product of f x Vt2 increased, PaO2 initially increased and then decreased, whereas PaCO2 decreased and Palv increased. No single combination of frequency, Vt and Paw simultaneously provided the lowest Palv and physiologic blood gas tensions. Adequate blood gas tensions and low Palv were obtained at frequencies less than 12 Hz, a Vt of 2 mL/kg and a Paw of 10 cm H2O. In healthy and lavaged rabbits PaO2 increased and PaCO2 decreased as frequency increased at lower Vt.PaO2 decreased as frequency increased at higher Vt in lavaged rabbits only. Palv tended to be greater in lavaged rabbits.

Rib cage vs. abdominal displacement in dogs during forced oscillation to 32 Hz.

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that during oscillatory forcing the base of isolated canine lungs distends preferentially relative to the apex as frequency and tidal volume increase. The tendency toward such nonuniform phasic lung distension might influence phasic displacement of the rib cage (RC) relative to the abdomen (ABD). To test this hypothesis we measured RC and ABD displacement in four anesthetized dogs during forced oscillation. Sinusoidal volume changes were delivered through a tracheostomy at 1-32 Hz and measured by body plethysmography. RC and ABD displacements were measured by inductive plethysmography. During oscillation with air at fixed tidal volumes (10-80 ml) RC, normalized to unity at 1 Hz, increased to 2.06-2.22 at 8 Hz (P less than 0.001) and then decreased to 1.06-1.35 (P less than 0.0025) at 32 Hz. ABD, normalized to unity at 1 Hz, was 1.12-1.16 at 4 Hz (P less than 0.001) and decreased to 0.12-0.14 at 32 Hz (P less than 0.001). Displacement of ABD relative to RC did not increase systematically with increasing tidal volume during sinusoidal forcing at any frequency. Thus we found no discernible influence of nonuniform phasic lung distension on chest wall behavior. We infer that in the dog the nonuniform mechanical behavior of the chest wall dominates the nonuniform (but opposing) mechanical tendency of the lung.

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.

Rib cage versus abdominal displacement in rabbits during forced oscillations to 30 Hz.

We measured relative displacement of the rib cage (RC) and abdomen (ABD) in 12 anesthetized rabbits during forced oscillations. Sinusoidal volume changes were delivered through a tracheostomy at frequencies from 0.5 to 30 Hz and measured by body plethysmography. Displacements of the RC and ABD were measured by inductive plethysmography. During oscillation at fixed tidal volume (VT = 1.3 ml/kg) the ratio ABD/RC, normalized to unity at 0.5 Hz, was 0.88 +/- 0.06 at 2 Hz and increased to 1.28 +/- 0.13 at 6 Hz (P less than 0.01). As frequency increased further ABD/RC fell sharply but between 20 and 30 Hz reached a plateau of 0.17 +/- 0.02 (P less than 0.001). Displacements of RC and ABD were nearly synchronous from 0.5 to 2 Hz, but as frequency increased ABD lagged RC progressively, reaching a phase difference of 90 degrees between 6 and 8 Hz and 180 degrees between 16 and 20 Hz. In six additional rabbits we measured chest wall displacements while varying VT from 0.5 to 3.7 ml/kg. ABD/RC was independent of VT at low frequencies (less than or equal to 6 Hz) but fell sharply with increasing VT at the higher frequencies. We interpreted these findings using a chest wall model having an RC compartment whose displacements are governed primarily by a nonlinear compliance, in parallel with an ABD compartment whose displacements are governed by a series resistance, inertance, and in addition a nonlinear compliance. The experimental findings are in large measure accounted for by such a model if the degree of nonlinearity of ABD and RC compliances are comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing mechanical performance of neonatal high-frequency ventilators.

Factors influencing the mechanical performance of neonatal high-frequency ventilators of diverse design were assessed under controlled conditions. Each of eight ventilators was coupled to in vitro models of the neonatal respiratory system simulating disease of varying severity. The principal performance characteristics examined were frequency dependence and load dependence of tidal volume delivered, peak inspiratory flow rate, and waveforms of pressure at either end of the endotracheal tube. Despite wide diversity of ventilator designs, including jets, flow interrupters, and oscillators, common features emerged. In almost all devices tidal volume increased with endotracheal tube size, was invariant with respiratory system compliance, and decreased with frequency of oscillation. Peak inspiratory flow rates for a given tidal volume and frequency were smallest in the group of oscillators compared with jets and flow interrupters. Proximal pressure was a poor indicator of distal pressure. These findings suggest that delivered tidal volume may be sensitive to endotracheal tube size and airway patency but relatively insensitive to changes in lung tissue or chest wall mechanical properties. In these regards high-frequency ventilation differs from pressure-limited conventional mechanical ventilation. Comparison of data obtained at different clinical centers using high-frequency ventilators of varying design may be possible by taking these factors into account.

Severe intracranial hemorrhage and hydrocephalus in low-birthweight infants treated with CSF shunts.

The high-risk low-birth-weight newborn not uncommonly develops intracranial hemorrhage and intraventricular hemorrhage (ICH/IVH) from the immature state of the germinal matrix. Posthemorrhagic hydrocephalus may develop. Infants with small hemorrhages (grades I, II of Papile), with or without hydrocephalus have been shown to develop normally in 80%-90% of cases. There is limited information in the literature about the management and outcome of infants with more severe hemorrhages (grades III, IV of Papile), due to the dismal outlook as to their outcome in most centers. The current status and concerns as to the management of these infants is reviewed, and the aspects of neurosurgical and neonatal follow-up and outcome are described. A significant number of these infants have severe handicaps, which are primarily motor. However, a group of infants is noted who have normal intellectual performance despite varying degrees of motor handicaps: 18% have normal intellectual and motor development. In the current series predictors of poorest outcome are the presence of grade IV hemorrhage and/or seizures. The vast majority of the grades III and IV hemorrhages develop hydrocephalus that is a complex management issue for the neurosurgeon.

A system for high-frequency oscillatory ventilation and intermittent mandatory ventilation in neonates.

We combined high-frequency oscillatory ventilation and intermittent mandatory ventilation, using a system composed of an Emerson airway vibrator, a Babybird 1 ventilator, and rate/pressure monitors. The Emerson device, a modified air compressor with rate controller, oscillated a small volume of gas at the airway. This device was coupled to the bird unit through a circuit of our design. Humidified fresh gas and pressure-relief valves were provided by the bird ventilator, and mean airway pressure was adjusted by its expiratory-limb venturi device or by the end-expiratory pressure control. The volume of gas delivered by the oscillator to various sites was measured with a plethysmograph tuned to high frequencies. At frequencies of 20 to 30 Hz, a 27-ml volume from the oscillator decreased to between 7 and 14 ml at the proximal airway, and to between 0.1 and 2.3 ml at the distal tip of the endotracheal tube. The magnitude of this decrease depended on the size of the endotracheal tube, the circuit resistance of the ventilator, oscillation frequency, and the position of the oscillator's expansion-chamber valve. We have used this system for over 3 yr to ventilate sick neonates safely and effectively.

Ventriculoperitoneal shunts in low birth weight infants with intracranial hemorrhage: neurodevelopmental outcome.

Fifty preterm infants (mean birth weight, 1266 +/- 303 g; mean gestational age, 30 +/- 2 weeks) who required a ventriculoperitoneal (VP) shunt for posthemorrhagic hydrocephalus (92% with Grade III or IV hemorrhage) were followed for neurodevelopmental problems. VP shunts were placed at a median age of 29 days (range, 18 to 87 days) after serial lumbar punctures failed to control progressive and symptomatic ventriculomegaly. A total of 34 infants (68%) required one shunt revision or more, and the overall infection rate per patient was 50%. Seven infants died, 2 from shunt infections. The infants were evaluated with audiological, ophthalmological, and neurodevelopmental examinations. Of the survivors, 11 (28%) have severe visual loss and 10 (24%) have hearing impairment. Of the infants, 21 (49%) have severe motor handicaps and 19 (38%) have seizure disorders. Developmental and motor scores were obtained using the Bayley or Knobloch-Gesell scales. Seven infants (18%) have normal developmental outcomes; 26 (60%) have multiple handicaps. Grade IV hemorrhage or the occurrence of seizures was a predictor of poor neurodevelopmental outcome. We conclude that progressive posthemorrhagic hydrocephalus in low birth weight infants is associated with multiple handicaps despite early VP shunt placement.

Respiratory distress syndrome treated with human surfactant: radiographic findings.

Chest radiographs of 18 newborns treated with endotracheal instillation of human surfactant for respiratory distress syndrome (RDS) were compared with those of 18 similar but untreated infants. In the treated infants, severity of RDS significantly improved after surfactant administration. Most treated infants (16/18) exhibited a left-to-right shunt, presumably through a patent ductus arteriosus; similar findings were noted in untreated infants (17/18). Complications of respiratory assistance in the treated infants included transient pulmonary interstitial emphysema (n = 1), pneumothorax (n = 1), and mild (n = 4) to moderate (n = 2) bronchopulmonary dysplasia; the incidences of these complications did not exceed those in untreated infants. In three treated infants, a transient interstitial lung disease developed 3-4 days after surfactant administration.

Combined high-frequency oscillatory ventilation and intermittent mandatory ventilation in critically ill neonates.

Combined high-frequency oscillatory ventilation (HFOV) and intermittent mandatory ventilation (IMV) was used in 12 neonates with inadequate gas exchange with conventional IMV. Diagnoses included diaphragmatic hernia with hypoplastic lungs, pneumonia, persistent fetal circulation, and severe respiratory distress syndrome. In most patients there was severe air leak. Within 10 hours of beginning HFOV-IMV the mean arterial PCO2 fell from 60 +/- 5 (means +/- SEM) to 38 +/- 2 mm Hg (P less than 0.01) and the mean IMV rate was reduced from 96 +/- 8 to 17 +/- 4 breaths per minute (P less than 0.001). The mean arterial-alveolar oxygen tension ratio rose from 0.05 +/- 0.01 to 0.09 +/- 0.01 (P less than 0.005). Mean airway pressure in the trachea was reduced from 16 +/- 2 to 10 +/- 3 cm H2O (P less than 0.05). Four patients died, three of whom had diaphragmatic hernias with hypoplastic lungs. Five of the eight survivors had mild bronchopulmonary dysplasia requiring supplemental oxygen. These studies demonstrate that in some neonates with respiratory failure who fail to respond to conventional IMV, combined HFOV-IMV can be successful.