James L. Robotham

Ventilatory management of infant baboons with hyaline membrane disease: The use of high frequency ventilation

Abstract: We tested the hypothesis that high frequency oscillatory ventilation (HFOV) would result in decreased pulmonary barotrauma in infants with hyaline membrane disease by comparing HFOV at 10 Hz to conventional positive pressure ventilation with continual distending airway pressure (PPV/PEEP) in premature baboons with hyaline membrane disease. Nineteen baboon fetuses were randomized to one of two treatment groups, delivered at 140 ± 2 days, and, after stabilization and instrumentation of PPV/PEEP, placed in their respective ventilator group. Animals on conventional ventilation were managed by adjustment of tidal volume and frequency (to 1 Hz) to keep PaCO2 below 55 and by adjustment of the mean airway pressure. One of the “HFOV” group died of cardiovascular complications before going on HFOV and was eliminated from data analysis. The remaining HFOV baboons survived the 11-day experimental period without evidence of airleak. Six of the 11 prematures treated with PPV/PEEP developed pulmonary interstitial emphysema and/or pneumothorax and five of the animals died within 48 h. The intergroup differences in airleak were significant (p < 0.05). Mean airway pressure (measured at the proximal airway) was higher initially with HFOV but then was lowered more rapidly than in the PPV/PEEP animals. The arterial to alveolar oxygen ratio rose and the FIO2 could be lowered more rapidly with HFOV than with conventional ventilation. These differences reached significance by 20 h. After 60 h there were no significant differences between HFOV and the PPV/PEEP survivors. HFOV resulted in more uniform saccular expansion, higher arterial to alveolar oxygen ratio, less oxygen exposure, and decreased acute barotrauma when compared to PPV/PEEP. Although initially mean airway pressure was in the HFOV animals this was not associated with measurable baroinjury. These data support the efficacy of HFOV in the treatment of prematures with hyaline membrane disease.

A baboon model of bronchopulmonary dysplasia. II. Pathologic features

Abstract A light microscopic (LM), transmission electron microscopic (TEM), and scanning electron microscopic (SEM) study was performed on the lungs from seven baboons delivered by cesarean section prematurely (75% of full gestation) and one at full term. Six of the seven premature baboons pursued a clinical course typical of human hyaline membrane disease (HMD) and/or bronchopulmonary dysplasia (BPD). All the animals were supported with mechanical ventilation and exposed to continuous high levels of inspired oxygen. Three animals died early (⩽3 days) of complications and two demonstrated typical light and electron microscopic lesions of hyaline membrane disease. Three baboons survived ⩾ 8 days and developed pathologically confirmed bronchopulmonary dysplasia, characterized by an altered inflation pattern of atelectasis and overdistension/“emphysema,” bronchial and bronchiolar lesions of necrosis, regenerative hyperplastic and/or squamous metaplastic changes, and peribronchiolar fibrosis and early alveolar wall fibrosis. A striking finding was a hyperplastic/obliterative respiratory bronchiolar lesion, most frequently seen in the atelectatic areas. The lungs of these animals lacked pores of Kohn; a feature shared by a study group of untreated baboons with gestation ages of 109 to 180 days. It is suggested that the lack of collateral ventilation, plus the striking hyperplastic-obliterative airway lesion might explain the characteristic feature of atelectasis. The histopathologic features of this model coincide with with those of BPD in the human neonate, with the exception of the hypertensive vascular changes, which may be a time-related lesion. The pathologic findings further support the premise that the premature baboon will be a very useful model in which the primary etiologic consideration of oxygen toxicity and barotrauma can be separated as to their roles in the causation of bronchopulmonary dysplasia.

A baboon model of bronchopulmonary dysplasia: I. Clinical features

Abstract Investigation in bronchopulmonary dysplasia (BPD) has been seriously hampered by the lack of a suitable animal model. The consistent development of BPD in preterm baboons ( Papio cynocephalus ) with hyaline membrane disease (HMD) who were treated with 95–100% inspired oxygen and supported with mechanical ventilation for more than 1 week is reported. One term (173 days) and nine preterm (134–147 days) pregnancies were delivered by cesarean section with birth weights 495–988 g. Amniotic fluid lecithin: sphingomyelin (L/S) ratios ranged from 0.47 to 1.00. The six animals with L/S ratios ⩽ 0.62 developed HMD. The clinical and radiologic course was indistinguishable from HMD in preterm humans. HMD was confirmed pathologically in two animals dying acutely. One of the remaining four was supported with supplemental oxygen as needed and remains a long-term survivor of HMD. The other three were maintained in 95–100% oxygen. A clinical and radiographic picture similar to that of human BPD developed in each and was pathologically confirmed. The preterm baboon appears to be a suitable animal model for investigation of the etiology, pathophysiology, prevention, therapy, and long-term sequelae of HMD and BPD.

A re-evaluation of the hemodynamic consequences of intermittent positive pressure ventilation

The hemodynamic effects of intermittent positive pressure ventilation (IPPV) have generally been considered straightforward, being dominated by the inspiratory reduction in systemic venous return. Paradoxically, there is considerable debate regarding the effects of PEEP. We have studied both right ventricular (RV) and left ventricular (LV) performance during a single IPPV respiratory cycle in dogs with intact circulatory systems or the right heart bypassed in open and closed chest conditions. We have found that the “reverse pulsus paradoxus” during inspiration reflects both transmission of the increased intrathoracic pressure to the thoracic aorta and an increase in LV stroke volume (SV). This inspiratory increase in LVSV has been found to be influenced by, but not dependent on: (a) respiratory variations in RVSV; (b) variations in functional residual capacity or tidal volume altering pulmonary venous return and the degree of physical compression of the heart by the lungs; (c) an inspiratory decrease in RV volume, increasing LV diastolic compliance and, thus, probably improving pulmonary venous return; (d) a decreased transmural aortic diastole pressure reflecting an effective decrease in LV afterload produced by both the general increase in intrathoracic pressure and the direct compression of the heart; and (e) variations in the pulmonary vascular volume as indicated by changes in the transmural LV end-diastolic pressure. An understanding of IPPV during a single respiratory cycle facilitates an appreciation of the steady state hemodynamic effects of IPPV with or without PEEP. Our results imply that measurements made only at endexpiration, ignoring inspiratory events, may have serious limitations. Furthermore, they suggest that IPPV with PEEP should be evaluated as a form of LV assist in LV failure.

Pulmonary interstitial emphysema in the premature baboon with hyaline membrane disease.

During experiments designed to develop an appropriate ventilatory strategy for high-frequency ventilation (HFV) in the premature baboon with hyaline membrane disease (HMD), we observed the development of pulmonary interstitial emphysema (PIE). Four study groups of 5 animals each received positive-pressure ventilation and positive end-expiratory pressure (PPV/PEEP) or HFV and 1 of 3 sighing techniques. Pathologically, all animals ventilated with PPV/PEEP or HFV with a carefully controlled intermittent sigh developed dilatation of the distal conducting airway and alveolar duct, with poorly expanded pulmonary saccules. The imposition of a sigh with inappropriate timing or excessive volume ruptured the dilated airway walls and caused interstitial air to accumulate. This was evident from the location of striking dilation of the distal airways and pseudocysts in areas of atelectasis. Thus, early in the course of HMD when saccular aeration is minimal, the pathogenesis of PIE is related to airway rather than alveolar rupture.

Cardiovascular disturbances in chronic respiratory insufficiency

The mechanical factors by which chronic respiratory insufficiency may influence right and left ventricular performance during both spontaneous and mechanical ventilation are reviewed. During a spontaneous inspiration the right heart distends because of increased inflow and increased pulmonary vascular resistance. This decreases the effective left ventricular compliance, through ventricular interdependence, reducing the gradient for pulmonary venous return. The inspiratory decrease in pleural pressure also effectively increases the impedance to left ventricular ejection. An inspiratory increase in abdominal pressure further increases the left ventricular afterload. These factors combine to impair left ventricular performance. During intermittent positive pressure ventilation, left ventricular stroke volume increases early in inspiration. This increased inspiratory flow cannot be attributed to a phase lag in the right heart output reaching the left heart chambers because, even with a constant pulmonary arterial inflow, aortic flow increases during inspiration. Several factors may act in concert to improve left ventricular performance, despite the adverse effects of intermittent positive pressure ventilation on the right ventricle. These include (1) a decrease in right heart volume, increasing left ventricular compliance and hence the gradient for pulmonary venous return; (2) anterograde emptying of the alveolar capillary bed with lung inflation; (3) the increase in pleural pressure decreasing impedance to left ventricular emptying; and (4) physical compression of the heart by the lungs.

Left ventricular geometry during intermittent positive pressure ventilation in dogs

We have analyzed how regional left ventricular (LV) performance may contribute to global LV performance during a single intermittent positive pressure ventilation (IPPV) respiratory cycle using chronically instrumented dogs with endocardial piezoelectric crystals in the three orthogonal axes, anterior-posterior (AP), septal-lateral freewall (SL), and long axis (LA) dimensions (D). Right ventricular (RV) SLD and aortic flow were also measured. Changes in LV geometry were evaluated during IPPV at two respiratory rates (10 and 20 breaths/min) and during inferior vena caval (IVC) occlusion since a change in systemic venous return is a major component of an IPPV inspiration. During an IPPV inspiration the RV SL end-diastolic D decreased, while the LV AP end-diastolic D increased (P < .01) and LV SL end diastolic D decreased (P < .001). LV end-diastolic and end-systolic volumes tended to increase during early inspiration and then diminished to an early expiratory minimum (P < .05) associated with early expiratory minimum stroke volumes and measured aortic flows (P < .02). In contrast, during IVC occlusion, the LV SL end-diastolic D initially increased while the AP end-diastolic D was falling. Thus, entirely different changes in LV end diastolic geometry result from IVC occlusion and lung inflation. These studies suggest a common factor of cardiac compression by the lung during inspiration altering diastolic intraventricular distribution of the LV preload and raise the question of whether respiratory-induced changes in LV geometry may independently modulate LV systolic pump function.

Left ventricular geometry during positive end-expiratory pressure in dogs.

We evaluated changes in left ventricular (LV) geometry in ten dogs during intermittent positive-pressure ventilation (IPPV) with and without 10 cm H2O of positive end-expiratory pressure (PEEP). The dimensions during expiration and inspiration decreased in all three orthogonal axes during PEEP, consistent with decreased LV end-diastolic (ED) and end-systolic (ES) volumes. Within a respiratory cycle, the anterior-posterior (AP) ED dimension during inspiration increased with IPPV alone but decreased when PEEP was added, consistent with presumed differences in pulmonary venous return. This caused opposite changes in AP percent regional shortening. Septal-lateral free wall (SL) percent regional shortening decreased during inspiration with both IPPV and PEEP, but the respiratory variation was significantly less during PEEP. Thus, PEEP did not simply produce a smaller version of the same events seen during IPPV alone. The larger decreases with PEEP observed in ED compared to ES – dimensions in the AP and SL axes suggest a dominant – regional preload effect, whereas the larger fall in the long axis ES compared to ED dimension suggests a primary regional decrease in afterload. Measurements of the right ventricular SL axis in three dogs showed an overall reduction with PEEP, with the inspiratory dimensions being minimal during both IPPV alone and with PEEP. Thus, ventricular interdependence cannot account for the diminished LV SL dimension with PEEP during any part of the respiratory cycle. These findings suggest that the motion of the LV free wall influenced by changes in lung volume may be at least as important as septal motion in determining LV geometry with PEEP We conclude that it is possible to consider the respiratory effects of ventilation on LV performance as the sum of multiple regions, in a manner analogous to that presently used with arteriosclerotic heart disease.

Systolic pressure amplification in pedal arteries in children

Sphygmomanometric indirect blood pressure readings on the arm were compared to direct blood pressure readings from the radial and pedal arteries in pediatric patients. The direct systolic pressure in the pedal arteries was significantly (p < 0.001) greater (25.1 ± 12.3 mm Hg) than the indirect arm systolic pressure. The direct systolic pressure from the radial artery was identical to the indirect systolic arm pressure. Although there were no statistical differences between direct and indirect diastolic pressures, correlations for diastolic pressures were relatively poor. These data indicate that (1) there is a significant and unpredictable amplification of systolic pressure in the pedal arteries which may result in erroneous diagnosis of hypertension or jeopardize early detection of circulatory shock, (2) indirect blood pressure measurement with the recommended cuff width (125% of arm diameter or 40% of arm circumference) accurately reflects direct systolic pressure in the radial artery, and (3) indirect blood pressure measurement gives a relatively poor prediction of direct diastolic pressures.

A physiological approach to hemidiaphragm paralysis.

The occurrence of unilateral phrenic nerve injury with the resultant hemidiaphragm paralysis or paresis can cause significant respiratory distress or respiratory failure in infants and children. An early bedside diagnosis of this problem will allow appropriate therapy and prevent needless diagnostic procedures. With the patient in the lateral decubitus position and the paralyzed side up, accentuated paradoxical inspiratory inward epigastric motion ipsilateral to the paralyzed hemidiaphragm can be seen. With the paralyzed hemidiaphragm down, abdominal motion appears to be normal as if the paralyzed hemidiaphragm were plicated. Thus, ventilation may be improved by changing body position as well as instituting ventilatory support while the potential for phrenic nerve recovery is evaluated.