Oxygen saturation and work of breathing indices in preterm infants with bronchopulmonary dysplasia compared to healthy preterm infants at discharge.

BACKGROUND: Thoracoabdominal asynchrony (TAA) is commonly seen in preterm infants. Respiratory inductive plethysmography (RIP) is a noninvasive way to objectively assess work of breathing (WOB) indices. The impact of bronchopulmonary dysplasia (BPD) on TAA at discharge has not been established. The aim of this study is to compare WOB indices in premature infants with a diagnosis of BPD to premature infants without a diagnosis of BPD at discharge. METHODS: A prospective, observational study of premature infants (<32 weeks gestation) at discharge during quiet breathing in the supine position. RIP noninvasively measured WOB indices. A high-resolution pulse oximeter collected oxygen saturation and heart rate data. RESULTS: This study included thirty-one infants with BPD and thirty-four infants without BPD. Infants diagnosed with BPD had increased phase angle [BPD Φ = 73 . 90 (8.2) vs NoBPD Φ = 52.6 (8.2), p = 0.039]. Infants diagnosed with BPD had decreased saturations [BPD SpO2 = 96% (0.4) vs NoBPD Sp02 98% (0.3), p=<0.001], increased time with saturations less than 85% [BPD % =2.74 (0.7) vs NoBPD % =0.91 (0.4), p = .018], and increased time with saturations less than 80% [BPD % =1.57 (0.5) vs NoBPD % =0.52 (0.3), p = 0.045]. There was no difference in heart rate or breaths per minute for infants with BPD versus controls. CONCLUSION: Premature infants with BPD demonstrated increased TAA and had lower saturations compared to infants without BPD at discharge despite being chronologically older and being discharged at an older corrected gestational age. The impact of BPD on breathing patterns persists at discharge and suggests these patients may have residual lung and/or respiratory muscle dysfunction.

The impact of kangaroo mother care on work of breathing and oxygen saturation in very low birth weight infants with respiratory insufficiency.

BACKGROUND: Kangaroo mother care (KMC) is defined as prolonged skin to skin care between a mother and infant with the infant lying in prone position on mom's chest. KMC decreases morbidity and mortality and promotes physiologic stability. The aim of this study is to measure work of breathing (WOB) during KMC in very low birth weight (VLBW) infants on non-invasive respiratory support. METHODS: A prospective observational pilot study was conducted comparing WOB indices during standard care (SC) and KMC. Respiratory inductive plethysmography (RIP) measured WOB indices non-invasively: phase angle and labored breathing index. VLBW infants who were stable on non-invasive respiratory support were randomized to receive RIP measurements during KMC or during SC first. Summary statistics and mixed linear models were used to compare WOB and vital signs. RESULTS: A total of 32 infants were consented for the study, data collection and analysis was completed on 28 infants. There were no significant differences in mean phase angle during KMC or SC (73.5±4.6 SE deg vs 66.8±3.9 SE deg, p = 0.25). No differences in WOB and vital signs were detected. Controlling for respiratory support or randomization/first location did not change the results. CONCLUSION: In this pilot cohort, infants demonstrated no differences in work of breathing indices or oxygen saturation during KMC or SC while receiving non-invasive respiratory support. KMC appears to be safe and well tolerated with no worsened WOB. Larger studies should be performed to confirm our findings.

Effects of xenon gas on human airway epithelial cells during hyperoxia and hypothermia.

BACKGROUND: Hypothermia with xenon gas has been used to reduce brain injury and disability rate after perinatal hypoxia-ischemia. We evaluated xenon gas therapy effects in an in vitro model with or without hypothermia on cultured human airway epithelial cells (Calu-3). METHODS: Calu-3 monolayers were grown at an air-liquid interface and exposed to one of the following conditions: 1) 21% FiO2 at 37°C (control); 2) 45% FiO2 and 50% xenon at 37°C; 3) 21% FiO2 and 50% xenon at 32°C; 4) 45% FiO2 and 50% xenon at 32°C for 24 hours. Transepithelial resistance (TER) measurements were performed and apical surface fluids were collected and assayed for total protein, IL-6, and IL-8. Three monolayers were used for immunofluorescence localization of zonula occludens-1 (ZO-1). The data were analyzed by one-way ANOVA. RESULTS: TER decreased at 24 hours in all treatment groups. Xenon with hyperoxia and hypothermia resulted in greatest decrease in TER compared with other groups. Immunofluorescence localization of ZO-1 (XY) showed reduced density of ZO-1 rings and incomplete ring-like staining in the 45% FiO2- 50% xenon group at 32°C compared with other groups. Secretion of total protein was not different among groups. Secretion of IL-6 in 21% FiO2 with xenon group at 32°C was less than that of the control group. The secretion of IL-8 in 45% FiO2 with xenon at 32°C was greater than that of other groups. CONCLUSION: Hyperoxia and hypothermia result in detrimental epithelial cell function and inflammation over 24-hour exposure. Xenon gas did not affect cell function or reduce inflammation.

Patterns of expenditures and use of services among older adults with diabetes. Implications for the transition to capitated managed care.

OBJECTIVE: To examine health care use and expenditures among older adults with diabetes, investigate factors that are associated with higher expenditures, and describe the policy implications of caring for this population under managed care. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of expenditures for individuals with diabetes over age 65 years from a nationwide 5% random sample of Medicare beneficiaries was conducted during 1992. All components of medical care covered under Medicare were examined. Multivariate analysis was used to assess the contribution of age, race, sex, number of diabetic complications, and comorbidity (Charlson Index) on total expenditures. RESULTS: On average, individuals with diabetes (n = 188,470) were 1.5 times (P < 0.0001) as expensive as all Medicare beneficiaries (n = 1,371,960). However, there were wide variations, with the most expensive 10% of beneficiaries with diabetes accounting for 56% of expenditures for individuals with diabetes and the least expensive 50% accounting for 4%. Acute care hospitalizations accounted for the majority (60%) of total expenditures, whereas outpatient and physician services accounted for 7 and 33%, respectively. There were no differences in the number of complications for all older adults with diabetes compared with those with the highest expenditures. However, the average number of hospitalizations was 1.6 times (0.53 vs. 0.34; P < 0.0001) higher, and the average length of stay was 2 days longer, among older adults with diabetes (P < 0.0001). In the regression model, age and male sex (factors currently used to set payment rates for Medicare managed care enrollees), and number of diabetic complications, but not race, were positively related to expenditures, yet had minimal predictive power (R2 = 0.0006). The addition of the Charlson Index, also positively related to expenditures, was able to explain up to 20% of the variation in total expenditures (R2 = 0.196). CONCLUSIONS: There are large variations in expenditures among older adults with diabetes. Because elderly beneficiaries with diabetes are more expensive than the average older adult, current Medicare capitation rates may be inadequate. To avoid selection bias and under-treatment of this vulnerable population under managed care, methods to construct fair payment rates and safeguard quality of care are desirable.

Predicting expenditures for Medicare beneficiaries with diabetes. A prospective cohort study from 1994 to 1996.

OBJECTIVE: To describe health care expenditures and utilization patterns among older adults with diabetes and to examine factors associated with expenditures over a 3-year period. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of health care expenditures and utilization by diabetic patients from a random nationwide sample of aged Medicare beneficiaries from 1994 to 1996. All services covered by the Medicare program were examined. Multivariate regression was used to assess the contribution of patient characteristics in 1994 on Part B, inpatient, and total expenditures in 1995 and 1996. RESULTS: Per capita expenditures for beneficiaries with diabetes (n = 169,613) were 1.7 times greater than those for those beneficiaries without diabetes (n = 968,832) in 1994. This ratio remained fairly constant over the 2 years of follow-up. Expenditures for beneficiaries with diabetes were highly skewed. However, few of these individuals remained in the highest expenditure quintile over the 2 years of follow-up. Using multiple regression analysis to adjust for demographic and clinical characteristics, we were able to explain 7% of the variation in total expenditures in 1995 and 6% of the variation in 1996. Using the same model, we were able to explain 10.7% of the variation in Part B expenditures in 1995 and 8% in 1996. CONCLUSIONS: Beneficiaries with diabetes are consistently more expensive than beneficiaries without diabetes. Demographic and clinical factors at baseline are able to predict only a small portion of future expenditures among this population, and the most expensive patients in one year were often not the most expensive in subsequent years. More work is necessary to assure equitable risk adjustment in the calculation of capitation rates for health plans and practitioners who specialize in the care of individuals with diabetes.

High flow nasal heliox improves work of breathing and attenuates lung injury in a newborn porcine lung injury model.

BACKGROUND: High flow nasal cannula (HFNC) has been shown to improve ventilation and oxygenation and reduce work of breathing in newborns with respiratory distress. Heliox, decreases resistance to airflow, reduces the work of breathing, facilitates the distribution of inspired gas, and has been shown to attenuate lung inflammation during the treatment of acute lung injury. HYPOTHESIS: Heliox delivered by HFNC will decrease resistive load, decrease work of breathing, improve ventilation and attenuate lung inflammation during spontaneous breathing following acute lung injury in the newborn pig. METHODS: Spontaneously breathing neonatal pigs received Nitrox or Heliox by HFNC and studied over 4 hrs following oleic acid injury. Gas exchange, pulmonary mechanics and systemic inflammation were measured serially. Lung inflammation biomarkers were assessed at termination. RESULTS: Heliox breathing animals demonstrated lower work of breathing reflected by lower tracheal pressure, phase angle and phase relationship. Ventilation efficiency index was greater compared to Nitrox. Heliox group showed less lung inflammation reflected by lower tissue interleukin-6 and 8. CONCLUSION: High flow nasal Heliox decreased respiratory load, reduced resistive work of breathing indices and attenuated lung inflammatory profile while ventilation was supported at less pressure effort in the presence of acute lung injury.

Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by perfluorochemical liquid.

Although gene therapy holds great promise for the treatment of inherited and acquired diseases of the lung, a number of issues including efficient delivery and distribution of genes to pulmonary target cells must still be addressed. In this study we evaluated the use of perfluorochemical (PFC) liquid as a vehicle for delivery of recombinant adenovirus (AdCBlacZ) to lungs of juvenile rabbits. Virus was instilled into trachea of rabbits, and 4 days later the lungs were removed, cut into multiple pieces, and assayed for beta-galactosidase (beta-Gal) activity. Total lung expression of the beta-Gal reporter gene was increased two- to three-fold by instillation of the virus (10(11) particles/kg body weight) in saline (1.5 ml/kg) simultaneously with perflubron liquid (15 ml/kg) compared to virus+saline alone (control). Uniformity of beta-Gal activity between lobes was significantly improved by the PFC liquid. In perflubron-treated lungs approximately 45% of the lung pieces had beta-Gal-specific activity values within 50-150% of the mean specific activity for the total lung, compared to only approximately 15% of the pieces in control lungs. More of total lobar beta-Gal activity was recovered in the distal lung tissue (approximately two-fold greater than controls, p < 0.05). Morphological assessment of X-Gal-stained, fresh-frozen lung sections showed increased levels and more complete staining of alveolar wall cells in the PFC group. These data indicate that the PFC liquid perflubron enhances distribution of virus-mediated gene expression to the lung parenchyma in healthy rabbits. PFC liquid may be a useful treatment vehicle for accessing distal spaces of the damaged or diseased lung.

Pulmonary administration of vasoactive substances by perfluorochemical ventilation.

OBJECTIVES: Therapeutic management of respiratory distress syndrome, pneumonia, and pulmonary hypertension includes delivery of biologically active agents to the neonatal lung. However, mechanical abnormalities of the lung, intrapulmonary shunting, ventilation-perfusion mismatching, and elevated surface tension impede effective systemic or intratracheal delivery of agents to the lung during conventional gas ventilation. The objective of this study was to test the hypothesis that perfluorochemical (PFC) liquid ventilation can be used for pulmonary administration of vasoactive drugs (PAD) and to compare these responses to those elicited with intravascular (IV) administration during tidal liquid ventilation. METHODS: Cardiovascular responses of 16 preterm and neonatal lambs to randomized doses of acetylcholine, epinephrine, and priscoline were studied. Physiologic gas exchanged and acid-base balance were maintained using previously described tidal liquid ventilation techniques. In subgroups of animals, the distribution pattern of carbon 1- and choline 14-labeled dipalmitoylphosphatidylcholine (14C-DPPC) in saline and the responses to priscoline after hypoxia-induced pulmonary hypertension and hypoxemia administered during liquid ventilation were studied. RESULTS: Dose-response curves for PAD and IV administration demonstrated progressive, dose-dependent, cholinergic responses to acetylcholine (decreased mean systemic arterial pressure [MAP] and heart rate), sympathomimetic responses to epinephrine (increased MAP and heart rate), and alpha-adrenergic blockade responses to priscoline (decreased MAP and mean pulmonary arterial pressure). Compared with IV administration, PAD of priscoline resulted in a significantly greater decrease in pulmonary relative to systemic arterial pressure; this response was potentiated by hypoxia, reduced pulmonary pressures to near normal values, and improved oxygenation. The 14C-DPPC in saline was distributed relatively homogeneously throughout the lung by PAD, with 80% of the lung pieces receiving amounts of 14C-DPPC with +/-20% of the mean value. CONCLUSIONS: This study demonstrates that vasoactive agents can be delivered to the lung directly by PAD during PFC liquid ventilation. The inherent advantages of this method relate to the physical properties of PFC liquid ventilation as a vehicle (respiratory gas solubility, low surface tension-enhancing distribution, and inertness precluding interaction) and physiological properties of the lung as an exchanger.

Tracheal extubation of the neonate at 2 to 3 cm H2O continuous positive airway pressure.

To investigate the efficacy of extubation at higher levels of continuous positive airway pressure (CPAP), 49 newborns (0.95 to 4.0 kg) were extubated at 2 to 3 cm H2O following 1 to 47 days of CPAP therapy. Pre- and postextubation measurements of Po2, PCO2, pH, FiO2, and CPAP were made in all infants. No significant differences (P less than.05) were found between pre- and post-extubation arterial blood gas values for all patients. Comparison of pre- and post-extubation blood gas data with respect to birthweight (less than 2.0 kg vs greater than 2.0 kg) and intubation time (less than 8 days vs. greater than 8 days) also indicated no statistical differences. Mean alveolar-arterial oxygen differences and FiO2 for 41 infants showed progressive decreases following extubation. Six of the 49 infants required reintubation within 72 hours following extubation. The results of this study indicate that newborns with respiratory disease requiring CPAP may be extubated at 2 to 3 cm H2O with no significant changes in arterial blood gas values, thus preventing prolonged intubation associated with weaning to 0 cm H2O CPAP.

Expenditures for care of children with chronic illnesses enrolled in the Washington State Medicaid program, fiscal year 1993.

OBJECTIVE: We calculated expenditures for children with one of eight selected chronic health conditions who were enrolled in the Washington State Medicaid program and compared them with payments for all Medicaid-enrolled children. We examined variation in mean, median, and total expenditures and identified expenditure sources. METHODS: This study analyzed Medicaid claims data for 310 977 children aged 0 to 18 who were enrolled at any time in fiscal year 1993. Tracer conditions were used to examine expenditure variation within and between diagnostic groupings. A total of 18 233 children (5.9%) had at least one of the conditions. Expenditures were calculated based on payments made by the Medicaid program. RESULTS: Children with one of the eight selected conditions incurred mean expenditures of $3800, compared with $955 for all Medicaid-enrolled children. Mean payments associated with the selected conditions ranged from 2.5 times to 20 times more than payments to all children. Approximately 10% of children accounted for approximately 70% of the payments in general and in each diagnostic grouping. Variation in mean, median, and total expenditures was extensive among the conditions. For most conditions, inpatient stays accounted for the greatest proportion of expenditures; for some conditions, durable equipment, home nursing, and medication-related services accounted for substantial proportions of total expenditures. CONCLUSIONS: Medical care for children with selected chronic health conditions is 2.5 to 20 times more expensive than children in general, depending on the condition. A relatively few children account for the majority of expenditures. Extensive variation in mean, median, and total expenditures suggests that different conditions will need to be kept distinct for purposes of establishing payment rates. Children with certain conditions are vulnerable to restrictions in specific services, depending on what restrictions are imposed by a financing program. Further analyses are needed to identify risk-adjustment strategies to support delivery of high-quality services to this population of children as they migrate into managed-care environments.

Inadvertent administration of positive end-distending pressure during nasal cannula flow.

In the clinical setting, nasal cannulas are frequently used to deliver supplemental oxygen to neonates and are not believed to affect the general respiratory status. In contrast, it was hypothesized that clinical changes associated with nasal cannula gas flow may be related in part to the generation of positive end-distending pressure. To test this hypothesis, alterations in esophageal pressure were quantified as an indication of end-distending pressure and thoracoabdominal motion was quantified as an indication of breathing patterns in 13 preterm infants at gas flow levels of 0.5, 1, and 2 L/min delivered by nasal cannula with an outer diameter of either 0.2 or 0.3 cm. Changes in esophageal pressure were assessed by esophageal balloon manometry. Ventilatory patterns were assessed from thoracoabdominal motion by using respiratory inductive plethysmography. Thoracoabdominal motion was quantitated as a phase angle (theta); larger values represent greater asynchrony. The 0.2-cm nasal cannula did not deliver pressure or alter thoracoabdominal motion at any flow. In contrast, the 0.3-cm nasal cannula delivered positive end-distending pressure as a function of increasing levels of gas flow (r = .92) and reduced thoracoabdominal motion asynchrony. The mean pressure generated at 2 L/min was 9.8 cm H2O. These data demonstrate that nasal cannula gas flow can deliver positive end-distending pressure to infants and significantly alter their breathing strategy. This finding raises important concerns about the indiscriminate therapeutic use, size selection, and safety of nasal cannulas for the routine delivery of oxygen in preterm infants.

A new device for diagnosis and treatment of neonatal pneumothorax.

A new closed-system device for the diagnosis and treatment of pneumothorax was evaluated in ten New Zealand white rabbits and compared with and open-system needle. The closed-system device proved to be safe for diagnostic thoracentesis. There were no pneumothoraces as a result of the procedure with the closed-system device as confirmed by chest roentgenograms and pleural pressure measurements. In contrast, 70% of the diagnostic thoracenteses with the open-system needle were associated with pneumothorax documented by x-ray films and a significant increase in mean pleural pressure. The new apparatus was more efficacious for evacuation of pneumothoraces because complete air removal occurred in 90% of the rabbits as compared with 60% of trials with the open-system needle. If the efficacy of the new closed-system device proves to be good in human infants, the pediatrician encountering a tension pneumothorax in the newborn can use a completely assembled system that is safe for diagnosing and treating this acute life-threatening condition.

Capitation for cardiologists: accepting risk for coronary artery disease under managed care.

Patients with chronic disease may be excluded from capitated managed care plans due to higher than average expected costs. In an attempt to remedy this inequity, one type of risk adjustment technique proposes to set separate capitation rates for certain chronic illnesses, including coronary artery disease (CAD). Cardiologists, who increasingly are requested to accept capitation, will benefit from understanding the impact of using clinical factors as opposed to using demographic factors to set capitation rates. Using a 5% national random sample of the 1992 Medicare population, we determined mean annual expenditures and variation in expenditures of individuals with CAD. We compared the use of 2 demographic factors currently used for capitation rate adjustment (age and gender) with 2 factors not currently used--3-digit International Classification of Disease (ICD-9) code (a measure for severity) and Charlson index (a measure for comorbidity). Mean annual expenditures for individuals with CAD were more than double mean annual expenditures for the general Medicare population ($6,944 vs $3,247). Among individuals with CAD, mean expenditures of subgroups defined by both age and gender ranged from $6,205 to $7,724. In comparison, stratifying by measures of severity and comorbidity identified subgroups with lower and higher mean expenditures, producing a range of $1,702 to $19,959. Substantial variation of expenditures for individuals within subgroups defined by severity and comorbidity remained, with few patients having substantially higher expenditures than the rest. When capitation rates are set with the use of demographic factors alone, patients may be subjected to risk selection and physicians to financial loss. Using clinical measures may decrease the incentive for patient risk selection, but substantial financial risk to physicians would remain, because of a relatively few patients with high expenditures (or costs).

Alzheimer's disease under managed care: implications from Medicare utilization and expenditure patterns.

BACKGROUND: Little information is available about the costs, utilization patterns, and the delivery system used by Medicare beneficiaries with chronic illnesses. This information will become increasingly important as more Medicare beneficiaries with chronic illness enroll in managed care plans and delivery systems must be developed to meet their needs. OBJECTIVES: To analyze health care expenditures and utilization patterns for Medicare beneficiaries with dementia of the Alzheimer type (DAT) and compare them with those of all Medicare beneficiaries. DESIGN: A cross-sectional study. SETTING: Practices providing services to Medicare beneficiaries in the U.S. SUBJECTS: Aged Medicare beneficiaries with DAT in fiscal year (FY) 1992. MEASUREMENTS: Medical expenditures and utilization patterns. RESULTS: In FY 1992, per capita Medicare expenditures for 9323 patients with DAT were $6208, or 1.9 times the per capita expenditure for all 1,221,615 beneficiaries in our sample. Inpatient care accounted for 62.7% of expenditures. Internal medicine was the specialty identified with the largest proportion of expenditures, but no single specialty accounted for the majority of care. Payments increased with comorbid conditions such as heart failure, chronic pulmonary diseases, and cerebrovascular disease. CONCLUSION: Current Medicare capitation payments to managed care plans may not meet the higher expected annual costs of care for beneficiaries with DAT. In turn, physicians (or physician groups) who accept capitation for Medicare beneficiaries with DAT should also consider how capitation rates are established by managed care plans and should learn ways to reduce financial risk.

Pulmonary vascular resistance in the fluorocarbon-filled lung.

Pulmonary vascular resistance was investigated in the fluorocarbon-filled lung in an in situ isolated lung preparation. Lungs were perfused at constant flow (100 ml X min-1 X kg-1) with whole blood from a donor cat. left atrial pressure was held constant at zero pressure. Measurements of pulmonary arterial pressure enabled calculation of pulmonary vascular resistance. Regional changes in pulmonary blood flow were determined by the microsphere technique. During quasi-static deflation over a range of 0-30 mmHg, dependent alveolar pressure was consistently greater for a volume of fluorocarbon than for gas, with each pressure-volume curve for the fluorocarbon-filled lung shifted to the right of the curve for the gas-filled lung. In turn, pulmonary vascular resistance was found to increase linearly as a function of increasing alveolar pressure, independent of the medium in the lung. Thus, for a given volume, pulmonary vascular resistance was consistently greater in the fluorocarbon-filled lung compared with the gas-filled lung. This increase in pulmonary vascular resistance was accompanied by a redistribution of pulmonary blood flow in which blood flow to the dependent region was decreased in the fluorocarbon-filled lung compared with the gas-filled lung. Conversely, the less-dependent regions of the lung received a relatively greater percentage of blood flow when filled with fluorocarbon compared with gas. These findings suggest that pulmonary vascular resistance is increased during liquid ventilation, largely as the result of mechanical interaction at the alveolar-vascular interface.

Effect of tracheal smooth muscle tone on collapsibility of immature airways.

To test the influence of smooth muscle tone on extremely immature airways, tracheal segments (n = 19) were excised from premature lambs at 114-121 days gestation and mounted in a chamber filled with Krebs solution. Inflation (Si) and collapsing (Sc) compliance were determined by altering transmural pressure from 30 to 0 Torr and -30 to 0 Torr, respectively, both during control (C) and after acetylcholine (ACh) administration (experimental, E). Flow (V = 2-15 l/min) was then introduced through the tracheal lumen while chamber pressure (Pc) was increased from 0 to 30 Torr and driving pressure (Pd) was recorded for both C and E conditions. Tracheae were found to be extremely compliant; both Si and Sc were significantly (P less than 0.005) lower after ACh administration. Resistance to airflow (R = Pd/V) was also significantly (P less than 0.05) lower after ACh administration at each compressive pressure and each flow value. These results suggest that the highly compliant preterm trachea exhibits pressure-flow characteristics similar to a Starling resistor, and the effects of compressive pressures may be attenuated by ACh-induced smooth muscle contraction. Comparison of these results with data from adult and newborn animals suggests a developmental difference in tracheal mechanics and pressure-flow relationships, as well as in the way airway function is altered by smooth muscle stimulation.

A new experimental approach for the study of cardiopulmonary physiology during early development.

In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment.

Preterm infants: ventilation and P100 changes with CO2 and inspiratory resistive loading.

The ventilatory effects of inspiratory flow-resistive loading and increased chemical drive were measured in ten neonates during progressive hypercapnia in control and loaded states. Hypercapnia (mean increase PCO2 = 15-20) resulted from inspiring 8% CO2 in room air and inspiratory loading by a flow-resistive load = 100 cmH2O X l-1) X s. Hypercapnia produced an increase in group minute ventilation secondary to increasing tidal volumes and breathing frequencies. Loading shifted the minute ventilation-CO2 response to the right, and slopes decreased significantly (P less than 0.05) consequent to a significant decrease in the frequency-CO2 slopes (P less than 0.05), which became negative in four of the ten subjects. Mouth pressure measured at 100 ms after onset of inspiratory effort (P100) occlusion pressure-CO2 slopes measured in five subjects showed no significant increase with load application. Resistive loading produced significant increases in inspiratory time (P less than 0.02) and the inspiratory time/total breath time ratio (P less than 0.01). Airway occlusion elicited the Hering-Breuer reflex, with a significant increase in inspiratory time-to-total breath time ratio (P less than 0.01). The results show that the inspiratory resistive load produced ventilatory compromise in newborns and insufficient compensatory augmentation of central drive.

Analysis of perfluorochemical elimination from the respiratory system.

We describe a simple apparatus for analysis of perfluorochemicals (PFC) in expired gas and thus a means for determining PFC vapor and liquid elimination from the respiratory system. The apparatus and data analysis are based on thermal conduction and mass transfer principles of gases. In vitro studies were conducted with the PFC vapor analyzer to determine calibration curves for output voltage as a function of individual respiratory gases, respiratory gases saturated with PFC vapor, and volume percent standards for percent PFC saturation (%PFC-Sat) in air. Voltage-concentration data for %PFC-Sat of the vapor from the in vitro tests were accurate to within 2.0% from 0 to 100% PFC-Sat, linear (r = 0.99, P < 0.001), and highly reproducible. Calculated volume loss of PFC liquid over time correlated well with actual loss by weight (r = 0.99, P < 0. 001). In vivo studies with neonatal lambs demonstrated that PFC volume loss and evaporation rates decreased nonlinearly as a function of time. These relationships were modulated by changes in PFC physical properties, minute ventilation, and postural repositioning. The results of this study demonstrate the sensitivity and accuracy of an on-line method for PFC analysis of expired gas and describe how it may be useful in liquid-assisted ventilation procedures for determining PFC volume loss, evaporation rate, and optimum dosing and ventilation strategy.

Epithelial modulation of preterm airway smooth muscle contraction.

To determine if epithelium from immature airways can modulate the responsiveness of smooth muscle, we studied paired trachealis muscle strips from preterm sheep. The epithelium was removed from one strip and left undisturbed in the other. Concentration-effect (CE) curves to acetylcholine (ACh), KCl, and isoproterenol were obtained. To evaluate maturational effects, responses to ACh and isoproterenol were studied in trachealis strips from adult airways. Maximal stress (Po) to ACh increased after epithelium removal in preterm (P < 0.05) but not adult strips. Epithelium removal caused a leftward shift of the ACh CE curves in both preterm and adult strips (P < 0.001) and a decrease in the dose required to achieve a one-half maximal response (ED50) in both preterm (P < 0.005) and adult strips (P < 0.05). The magnitude of the change in Po as well as in the ED50 for ACh between preterms and adults was similar. Epithelium removal did not alter either the Po or the CE curves of preterm strips stimulated by KCl. Response to isoproterenol in precontracted strips was enhanced in the presence of an intact epithelium in both groups (P < 0.05). These data demonstrate that preterm airway epithelium is able to modulate the responsiveness of smooth muscle. Additionally, the magnitude of the effect is unchanged with maturation. We speculate that damage of airway epithelium from mechanical ventilation may contribute to the increased incidence of airway hyperreactivity observed in preterm infants.