The use of high frequency oscillation in hyaline membrane disease.
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Publications and source records attributed to A C Bryan.
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The ability to maintain occlusion pressure (i.e., fatigability) during activation of the diaphragm via phrenic nerve stimulation was compared in newborn (less than 14 days old) and older (greater than 30 days old) rabbits. The younger animals had lower maximum inspiratory pressures (MIP) and markedly greater falls in pressure during sustained diaphragmatic contractions at greater than 40% MIP than did the older animals. Histological analysis showed a paucity of high-oxidative type I fibers in the diaphragms of the young animals. We therefore conclude that the newborn rabbit diaphragm is extremely susceptible to fatigue and that this susceptibility correlates with the distribution of muscle fiber types.
To determine whether surgical repair of congenital diaphragmatic hernia (CHD) results in improvement in respiratory mechanics, we measured respiratory system compliance in nine patients (five survivors and four nonsurvivors) before and after operation. In all nine infants, CHD was diagnosed within 6 hours of life, and surgical repair was through an abdominal approach after a period of stabilization. Measurements were made noninvasively, using the passive expiratory flow-volume technique. In only one of the nine infants did compliance immediately improve after surgical repair, and in another it showed no change. Both of these infants survived, with an uneventful postoperative course. In the remaining seven infants, however, postoperative compliance immediately decreased to 10% to 77% from the preoperative value. The four infants with more than 50% decrease in compliance died with increasing hypoxemia and acidosis. These results suggest that respiratory mechanics in CHD, far from improving, frequently deteriorate as a result of repair of the hernia. The role of urgent surgery in this malformation should be reevaluated.
The association between platelet counts and mechanical ventilation was assessed in 61 newborn infants with respiratory distress syndrome, 10 infants with congenital diaphragmatic hernia, and 10 infants with tracheoesophageal fistula. A significant decrease in platelet counts was observed during mechanical ventilation: (mean +/- SD) reduction of 39% +/- 5%, 42% +/- 5.6%, and 11.9% +/- 5.4% in the three groups, respectively, independent of other causes. In the group with congenital diaphragmatic hernia, there was a significant correlation between mean airway pressure and the reduction in platelet counts. In a subsequent series of experiments, platelet counts were recorded before and during ventilation in rabbits. A significant mean decrease of 37.3% in platelet counts was associated with ventilation with either air or pure oxygen. Results of these studies indicate that mechanical ventilation itself may cause a major decrease in platelet count in newborn infants.
In a previous paper Cutz, Bryan et al. showed that in rabbits after repetitive lung lavage high-frequency oscillatory ventilation maintained excellent gas exchange and did not cause hyaline membrane formation (J. Appl. Physiol. 55: 131-138, 1983). In contrast, conventional mechanical ventilation had poor gas exchange and extensive hyaline membrane formation and we attributed these differences to mechanical barotrauma. However, we completely overlooked the large number of granulocytes in the damaged lung. To investigate this using the same model we have used mechanical ventilation on two groups of rabbits, one with normal granulocytes, the other depleted of granulocytes by pretreatment with nitrogen mustard. The nondepleted rabbits had poor gas exchange, a substantial protein leak into the lung and extensive hyaline membranes. The depleted animals had good gas exchange, a very small protein leak and no hyaline membranes. Repletion of granulocytes from donor rabbits lead to poor gas exchange and hyaline membrane formation. It is concluded that lung lavage causes prompt margination of granulocytes which become activated by the ongoing epithelial barotrauma of conventional ventilation.
Present methods of assessing the work of breathing in human infants do not account for the added load when intercostal muscle activity is lost and rib cage distortion occurs. We have developed a technique for assessing diaphragmatic work in this circumstance utilizing measurements of transdiaphragmatic pressure and abdominal volume displacement. Eleven preterm infants without evidence of lung disease were studied. During periods of minimal rib cage distortion, inspiratory diaphragmatic work averaged 5.9 g X cm X ml-1, increasing to an average of 12.4 g X cm X ml-1 with periods of paradoxical rib cage motion (P less than 0.01). Inspiratory work was strongly correlated with the electrical activity of the diaphragm as measured from its moving time average (P less than 0.05). Assuming a mechanical efficiency of 4% in these infants, the caloric cost of diaphragmatic work may reach 10% of their basal metabolic rate in periods with rib cage distortion. When lung disease is superimposed, the increased metabolic demands of the diaphragm may predispose preterm infants to fatigue and may contribute to a failure to grow.
Compliance of the respiratory system (Crs) was compared using 2 previously described methods, namely, the passive expiratory flow and multiple occlusion techniques. These 2 methods have the advantage of being totally noninvasive, but both have limitations precluding their use in some circumstances. The results of this study of 10 intubated patients, who varied widely in age (premature newborn to adolescence) and diseases, showed no significant difference between the Crs obtained by the 2 methods. The Crs measurements can therefore be used interchangeably, the choice of technique being dependent on the subjects' clinical state.
We ventilated seven mongrel dogs with high frequency oscillatory ventilation (HFO) at frequencies from 3 to 30 Hz. At each frequency, the tidal volume required to achieve isocapnia (VTiso) was measured by plethysmography. In an individual dog, VTiso could be related to frequency by an equation of the form VTiso = KfA. A was similar for the seven dogs, A = -0.54 +/- 0.03. K varied from 179 to 325 cc- Hz-A, reflecting differences between the dogs in dead space, CO2 production and gradient for gas transport. This relation is consistent with that predicted from the data of previous investigators who used different ventilators, circuits and methodology. From 3 to 30 Hz, VTiso decreased from 1.2 to 0.4 times anatomic plus equipment dead space, but minute volumes required to maintain isocapnia increased from 6 to 18 times those required during conventional ventilation. We conclude that low tidal volume ventilation is also high minute volume ventilation.
Previous investigators have reported alarming gas trapping during high frequency oscillation. We have assessed trapping by measuring the difference between occlusion pressure (alveolar pressure) and measured maximal mean airway circuit pressure. Under normal operating conditions, we were unable to demonstrate trapping in normal or lung-lavaged rabbits at 15 or at 25 Hz, or in infants with infant respiratory distress syndrome, but we could produce trapping by operating at unusually low mean airway pressure. At these low pressures, lung volume is low, and we believe that choke points develop that limit maximal expiratory flow.
Previous reports indicate that apnea is induced by high frequency ventilation (HFV) in anesthetized animals. We have studied conscious dogs ventilated with HFV during sleep and wakefulness to determine if this apnea is state related. Eucapnic apnea or very low breathing frequencies were observed during quiet wakefulness, quiet sleep and tonic REM sleep. However, spontaneous breathing at nearly normal rates was invariably seen during phasic REM sleep. We conclude that HFV as administered induces apnea or near apnea in conscious animals and that the inhibitory pathways causing this apnea are probably disabled during phasic REM sleep.
The lungs of anesthetized rabbits were embolized by intravenous injection of 75 mg/kg of starch particles in divided doses. One group received high-frequency oscillatory ventilation (HFOV) at a rate of 15 Hz. Both groups were ventilated with an FIO2 of 1.0. After 3 hr of ventilation, the animals were sacrificed, and the extravascular lung water (EVLW) was determined gravimetrically. With conventional mechanical ventilation (CMV), the EVLW/body weight ratio was 4.1 +/- 1.4 g/kg (mean +/- SD) and was significantly higher than the ratio of 2.8 +/- 0.6 in animals given HFOV (P less than 0.05). In a second series of animals, 20 muCi of 125I-labeled bovine albumin was injected intravenously prior to embolization and followed by the same two types of ventilation. After the rabbits were sacrificed, the lungs were lavaged with 0.9 N saline, and the radioactivity of the fluid was measured to determine the protein leak. After CMV, 2.76 +/- 2.05% of the injected radioactivity was recovered from the fluid, significantly higher (P less than 0.01) than the amount of radioactivity recovered after HFOV, 0.3 +/- 0.28%. There also was significantly more labeled protein in the lung tissue that had been on CMV. We conclude that in this model of pulmonary edema, HFOV significantly reduces both the amount of fluid and protein leaking into the lung.
Carotid bodies from infants dying of sudden infant death syndrome contained significantly higher concentrations of dopamine (10-fold) and noradrenaline (3-fold) than those from age-matched control infants. Administration of dopamine inhibits respiration by direct action on the carotid body, and it is suggested that the elevated levels of endogenous catecholamines found in victims of sudden infant death syndrome may compromise the normal function of the carotid body, particularly the ventilatory response to hypoxia.
High-frequency ventilation (HFV) has not one but several histories. Proceeding along largely independent pathways are techniques using frequencies of 1-5 Hz and techniques using 10-40 Hz, the former being introduced by Sjostrand in 1971, the latter by Lunkenheimer in 1972. It was nearly ten years before it was recognized that these techniques must radically alter our concepts of gas transport within the lung. There has also been an unfortunate series of clinical studies purporting to show that HFV is superior to conventional ventilation in patients with lung disease. There is no doubt that nearly all reports show that HFV controls PaCO2 very easily, and that the mechanisms by which this is achieved is the primary topic of the symposium. What has not been proved is that HFV is better than conventional ventilation in increasing PaO2. The mechanisms of oxygen exchange when the lung has extensive shunts are quite different from those for CO2 exchange, and this problem has not been rigorously addressed.
The passive compliance and resistance of the respiratory system were measured in 12 spontaneously breathing newborn infants before and after endotracheal extubation. End-inspiratory airway occlusions were used to relax the respiratory muscles, allowing occlusion pressure to be measured and respiratory system compliance and resistance to be calculated from the flow volume relationship of the subsequent passive expiration. Airway pressure was measured from an endotracheal tube or a face mask, expiratory flow from a pneumotachograph, and expiratory volume from the integrated flow signal. In six of the infants, diaphragmatic electromyography was also performed before and after extubation. Resistance and EMG findings were both decreased by extubation (mean decrease 43.9%, P less than 0.001 and 27.3%, P less than 0.05, respectively), but compliance was unchanged. Thus, by substantially increasing resistance, an endotracheal tube causes the diaphragm to increase its activity to maintain ventilation.
Phrenic nerve activity was monitored in anesthetized cats during high-frequency ventilation (HFV). Rhythmic phrenic discharge disappeared during HFV in all animals at normal arterial PCO2 levels. Rhythmic activity returned after neuromuscular blockade in the vagally intact animal. Although vagotomy alone also restored phrenic discharge, this activity was further enhanced by subsequent neuromuscular blockade. Therefore we suggest that apnea during HFV results from inspiratory inhibition mediated by both chest wall and vagal afferent mechanisms.
We have measured the ventilatory response to inhaled CO2 of six newborn infants in rapid-eye-movement (REM) and non-REM (NREM) sleep. Ventilatory responses were measured using the Read rebreathing technique. The response was further partitioned into the volume contributions of the rib cage and abdominal compartment using the respiratory inductance plethysmograph. Sleep state was defined by electroencephalogram, electrooculogram, and behavioral criteria. In NREM sleep, there was a highly significant linear correlation between both tidal volume (VT) and instantaneous minute ventilation (VI) with CO2. Among infants, the slope of VT varied from 1.0 to 0.34 ml X Torr-1 X kg-1. However, these differences were largely due to differences in rib cage contribution, which varied from 0.56 to -0.08 ml X Torr-1 X kg-1. The abdominal contribution was similar among infants (0.41-0.56 ml X Torr-1 X kg-1). In REM, the slopes of VI were less steep than in NREM, with greater breath-to-breath variability. Slopes of VT also tended to be lower. The abdominal responses were similar to those in NREM, whereas the rib cage response was low and negative in three studies. We conclude that the slope of the CO2 response curve is primarily determined by the extent of rib cage recruitment.
Fundamental to the pathogenesis of obstructive sleep apnea (OSA) is the interaction of physiologic and anatomic alterations of the upper airway. However, many patients with OSA have no identifiable abnormality of the upper airway, and they have been termed idiopathic. In an attempt to find a structural deviation in upper airway anatomy, we performed acoustic echography and cephalometric roentgenograms in 9 male patients with OSA and no clinical evidence of upper airway abnormality. Mean cross-sectional area of the pharynx by acoustic reflection was less in these patients (3.7 +/- 0.8 cm2) than in subjects in a control group (5.3 +/- 0.6 cm2) (p less than 0.001). Mean glottic cross-sectional area was less in the patient group (1.5 +/- 0.5 cm2) than in the control group (2.7 +/- 0.5) (p less than 0.001). There was a significant correlation between the number of apneas per sleep hour and pharyngeal cross-sectional area (r = 0.87, p less than 0.01). Cephalometric analysis indicated that the patients had smaller mandibles by a mean of 5.4 +/- 6.6 mm (p less than 0.05). The overall posterior displacement of the mandibular symphysis, which is representative of the skeletal support of the anterior pharyngeal wall and is dependent on both mandibular size and position, was highly significant (6.4 +/- 4.7 mm) (p less than 0.01). Furthermore, there was a significant correlation between the number of apnea episodes per sleep hour and the total posterior displacement (r = 0.67, p less than 0.05). This study indicates that patients with so-called idiopathic OSA may have an anatomic predisposition to the development of upper airway occlusion that may not be detectable on clinical examination.