Measurement of closing volume in apneic subjects

Closing volume measurement was adapted for application in apneic intubated, artifically ventilated subjects. A bolus of nitrogen was used as the marker gas. Inspiration and exhalation at a slow, uniform rate between residual volume and total lung capacity was provided by a 7000-ml syringe. Closing volumes in seven anesthetized subjects were similar to those reported for supine, conscious individuals by previous investigators. This adaptation of closing volume measurement should be useful in studying pulmonary dysfunction during anesthesia and during artificial ventilation of patients in respiratory failure.     

Lung mechanics in sitting and horizontal body positions

We measured lung compliance, pulmonary flow-resistance, and expiratory reserve volume (ERV) in ten healthy young adults in sitting, supine, and lateral positions. Average lung compliance was 0.21 in sitting, 0.19 in lateral and 0.16 L.cm H2O-1 in supine positions. The change was significant (p less than 0.01) between sitting and supine position. Flow-resistance increased from 1.78 in sitting to 2.5 cm H2O.L-1.s (p less than 0.001) in lateral positions, and did not increase further in the supine posture in spite of a 35 percent decrease in ERV (p less than 0.001). Since it is known that lower airways resistance increases with decreasing lung volume, the lack of change in flow-resistance when shifting from lateral to supine posture suggests that upper airways flow-resistance (larynx and oropharynx) is greater in the lateral decubitus than in the supine positions. The decrease of lung compliance in horizontal postures probably reflects increased pulmonary blood volume and small airways closure.     

Intraoperative autotransfusion: an underutilized technique

The effect of posture on phase III (alveolar nitrogen plateau) and phase IV (closing capacity) of the single-breath oxygen test was examined in 10 normal people. In part 1 of the study, subjects inspired and expired in the standing, supine, prone, and right lateral decubitus positions; there was no effect of posture on phase IV but slopes of phase III were higher when subjects were in the supine and lateral positions. In part 2, subjects inspired in the standing position and expired in one of the recumbent positions. Phase IV occurred infrequently except in the prone position (6 of 10 subj); slopes of phase III in part 2 were not consistently altered by changing posture. It is difficult to explain the failure of posture to alter phase IV solely on a model requiring a linear gradient of pleural pressure. The slope of phase III appears to depend more on the emptying patterns of small regions with widely varying volume-to-ventilation ratios than on gravity-dependent sequences of emptying. Finally, the data suggest a considerable similarity between the upright and prone positions in terms of lung filling and emptying.     

Lung aeration and pulmonary gas exchange during lumbar epidural anaesthesia and in the lithotomy position in elderly patients

We investigated a total of 36 subjects with a mean (SD) age of 65 (13) years, during baseline conditions (supine, before any anaesthesia), and then during one of the following protocols: (1) lithotomy positioning (n = 12), (2) epidural anaesthesia (n = 12), (3) general anaesthesia in the supine position (n = 12). Lung aeration, ventilation/perfusion matching, gas exchange and functional residual capacity were measured. Lung aeration was normal during baseline assessment with almost no regions with poor aeration and no substantial dependent densities. Shunt and perfusion of poorly ventilated regions were minor. Lithotomy positioning did not reduce functional residual capacity and did not affect aeration of the lung or ventilation/perfusion matching. Epidural anaesthesia, in general, had no effect on aeration, ventilation/perfusion matching or gas exchange, regardless of whether the patient was in the supine or lithotomy position. General anaesthesia, however, caused significant increases in poorly aerated lung regions and in dependent densities (interpreted as atelectasis). In conclusion, no or little impairment of lung aeration and ventilation/perfusion matching was caused by the lithotomy position and/or epidural anaesthesia, contrary to the effects seen during general anaesthesia. However, our findings also suggest that being overweight is a factor that may cause impairment of lung aeration.     

Gravity effects on upper airway area and lung volumes during parabolic flight

We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity ( approximately 0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1. 8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (-0.6 liter) and from microgravity to hypergravity (-0.5 liter). Laryngeal narrowing also occurred in both positions (about -15%) when gravity increased from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to explain all upper airway caliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account.     

Expiratory flow limitation in COPD patients after single lung transplantation

Expiratory flow limitation and dyspnea during resting breathing are common in patients with severe chronic obstructive pulmonary disease (COPD). Although single lung transplantation (SLT) is used to treat end-stage COPD, its effects on flow limitation and dyspnea are not well established. We assessed expiratory flow-limitation and dyspnea in 13 COPD patients after SLT at rest in the sitting and supine positions by applying negative pressure at the mouth during tidal expiration (negative expiratory pressure [NEP] technique). If NEP increases flow throughout the control tidal volume (VT), flow limitation is absent (not flow limited [NEL]). If NEP does not increase flow during part of the control VT, flow limitation is present. After SLT, lung function improved in all but one patient. Twelve patients were NFL during resting breathing in both positions studied. The patient whose lung function did not improve after SLT was flow-limited (FL) both when seated and supine. This patient also exhibited moderately severe chronic dyspnea (Medical Research Council [MRC] score = 3). In the nine other patients in whom dyspnea was assessed, it was slight (MRC score = 1). In conclusion, after SLT for end-stage COPD, expiratory flow limitation at rest is uncommon in both the seated and supine positions. This is consistent with the finding that after SLT the degree of chronic dyspnea is generally slight.     

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)     

Contributions of pulmonary perfusion and ventilation to heterogeneity in V(A)/Q measured by PET

To estimate the contributions of the heterogeneity in regional perfusion (Q) and alveolar ventilation (V A) to that of ventilation-perfusion ratio (V A/Q), we have refined positron emission tomography (PET) techniques to image local distributions of Q and V A per unit of gas volume content (sQ and sV A, respectively) and V A/Q in dogs. sV A was assessed in two ways: 1) the washout of 13NN tracer after equilibration by rebreathing (sV A(i)), and 2) the ratio of an apneic image after a bolus intravenous infusion of 13NN-saline solution to an image collected during a steady-state intravenous infusion of the same solution (sV A(p)). SV A(p) was systematically higher than sV A(i) in all animals, and there was a high spatial correlation between sQ and sV A(p) in both body positions (mean correlation was 0.69 prone and 0.81 supine) suggesting that ventilation to well-perfused units was higher than to those poorly perfused. In the prone position, the spatial distributions of sQ, sV A(p), and V A/Q were fairly uniform with no significant gravitational gradients; however, in the supine position, these variables were significantly more heterogeneous, mostly because of significant gravitational gradients (15, 5.5, and -10%/cm, respectively) accounting for 73, 33, and 66% of the corresponding coefficient of variation (CV)2 values. We conclude that, in the prone position, gravitational forces in blood and lung tissues are largely balanced out by dorsoventral differences in lung structure. In the supine position, effects of gravity and structure become additive, resulting in substantial gravitational gradients in sQ and sV A(p), with the higher heterogeneity in V A/Q caused by a gravitational gradient in sQ, only partially compensated by that in sV A.     

Factors influencing the tracheal fluctuation of inhaled nitric oxide in patients with acute lung injury

BACKGROUND: Inhaled nitric oxide (NO) improves arterial oxygenation in patients with acute lung injury (ALI) by selectively dilating pulmonary vessels perfusing ventilated lung areas. It can be hypothesized that NO uptake from the lung decreases with increasing ventilation perfusion mismatch. This study was undertaken to determine the factors influencing the fluctuation of tracheal NO concentration over the respiratory cycle as an index of NO pulmonary uptake in patients with ALI. METHODS: By using a prototype system (Opti-NO) delivering a constant flow of NO only during the inspiratory phase, 3 and 6 ppm of NO were administered during controlled mechanical ventilation into a lung model and to 11 patients with ALI. All patients had a thoracic computed tomography (CT) scan. Based on an analysis of tomographic densities, lungs were divided into three zones: normally aerated (-1.000 to -500 Hounsfield units [HU]), poorly aerated (-500 to -100 HU), and nonaerated (-100 to +100 HU), and the volume of each zone was computed. Concentrations of NO in the inspiratory limb and trachea were continuously measured by a fast-response chemiluminescence apparatus. RESULTS: In the lung model, tracheal NO concentration was stable with minor fluctuation. In contrast, in patients, tracheal NO concentration fluctuated widely during the respiratory cycle (55 +/- 10%). Because uptake of NO from the lungs was absent in the lung model but present in the patients, this fluctuation was considered as an index of pulmonary uptake of NO. This was further substantiated by (1) the coincidence of the peak and minimum tracheal NO concentration with the end-inspiratory and end-expiratory phases, respectively, and (2) continued decrease of tracheal NO concentration during prolonged expiratory phase. In patients with ALI, the fluctuation of tracheal NO concentration expressed as the difference between inspiratory and expiratory NO concentrations divided by inspiratory NO concentration was greater at 6 ppm than at 3 ppm (P < 0.01), was linearly correlated with normally aerated lung volume, inversely correlated with alveolar dead space and with poorly aerated lung volume. CONCLUSION: In patients with ALI, fluctuation of tracheal NO concentration over the respiratory cycle can be considered as an index of NO uptake from the lungs that depends on aerated lung volume and perfusion of ventilated lung areas. At bedside, it may be used to follow the evolution of ventilation-perfusion mismatch.     

FRC measurement in intensive care patients. A definition of standards

Determination of Functional Residual Capacity (FRC) can be performed through washout methods, indicator gas dilution or bodyplethysmography. Some of these techniques have been adapted for use in intensive care patients whilst being mechanically ventilated. However, most measurement setups are bulky, cumbersome to use and their running costs are high. Hence FRC measurement has not become a routine method in intensive care although it offers considerable advantages in the management of ventilated patients such as the determination of "best PEEP", the detection of progressive alveolar collapse in the course of acute lung injury and during weaning from mechanical ventilation. Up to now most efforts to improve and simplify FRC measurement were made at the expense of accuracy. An ideal method ought to be accurate, easy to handle and cost-effective. It should supply not only FRC data but also information about intrapulmonary gas distribution and dead space. These demands can be met using modern data acquisition software. The pros and cons of all methods available for FRC measurement are discussed in view of their suitability for intensive care patients. A conventional nitrogen washout using emission spectroscopy for measurement of nitrogen concentration gives satisfying exact values for the determination of the parameters mentioned above. The measurement error can be lowered under 5% by special corrections for flow and nitrogen signal (delay and rise times, changes of gas viscosity). For flow measurement a normal pneumotachograph can be used. Using a laptop computer for data acquisition the bed-side monitor fulfills most of the demands in intensive care. It is then also possible to measure indices of intrapulmonary gas distribution such as Alveolar Mixing Efficiency and Lung Clearance Index.     

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.     

A new ventilation inhomogeneity index from multiple breath indicator gas washout tests in mechanically ventilated patients

OBJECTIVES: a) To determine the validity of a new method to analyze indicator gas washout tests on mechanically ventilated patients. This method takes into account the difference between the end-expiratory gas fraction and the mean gas fraction in the lung and provides the end-expiratory lung volume and a new index of ventilation inhomogeneity called volumes regression index. b) To determine the validity of this index as a predictor of chronic obstructive pulmonary disease. c) To compare this index with the moment ratio index and Becklake index. DESIGN: Prospective study of diagnostic test. Criterium standards: Closed-circuit indicator gas dilution technique and Tiffeneau index. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: A total of 38 mechanically ventilated postoperative patients, divided into two groups: the obstructive group (n = 21) and the nonobstructive group (n = 17), based on their preoperative lung function. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: a) The mean coefficient of variation of all lung volume measurements in a group of nine healthy volunteers was 5%, and the difference between this technique and the closed-circuit helium dilution measurements was -2 +/- 5%. In patients, the mean coefficient of variation of the lung volume measurements was 3.5%. The volumes regression index was measured as 0.02 +/- 0.04 in a dummy lung, 0.37 +/- 0.08 in the healthy volunteers, 0.64 +/- 0.23 in the nonobstructive patients, and 1.1 +/- 0.3 in the obstructive patients. The volumes regression index provided a better correlation (r2 = .46) with preoperatively determined Tiffeneau index than the Becklake index (r2 = .11) or the moment ratio index (r2 = .18). CONCLUSION: The proposed technique provides a means for accurate measurement of the end-expiratory lung volume and the amount of ventilation inhomogeneity in mechanically ventilated intensive care unit patients.     

Steam volatile aroma constituents of roasted coffee: neutral fraction

A body plethysmographic technique designed to detect small degrees of uneven ventilation in the lungs is presented. The technique is based on the same theoretical model as the frequency dependence of compliance. It has the advantage of requiring little time, no cooperation by the subject and no computation. Signs of uneven ventilation were found in 3 of the 42 normal controls, in 6 of 51 light smokers and in 66 of 103 heavy smokers. The data are compared with measurements of closing volume, of the slope of phase III of the single breath nitrogen washout and of maximal mid-expiratory flow rate.     

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans

We tested the hypothesis that the slower increase in alveolar oxygen uptake (VO2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, and VO2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position (P < 0. 05) was compensated by a greater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences in VO2, MBV, or LBF between upright and supine positions. The rates of increase of VO2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [VO2 = 39.7 +/- 3.8 (SE) s, LBF = 27.6 +/- 3.9 s] than in the upright positions (VO2 = 29.3 +/- 3.0 s, LBF = 17.3 +/- 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolar VO2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.     

Continuous ambulatory radionuclide monitoring of left ventricular function: effect of body position during ergometer exercise

We assessed the reliability of a continuous ambulatory radionuclide monitoring system (the VEST system, Capintec, Inc., Ramsey, NJ) for measurement of left ventricular performance during exercise in the upright and supine positions. METHODS: Sixteen healthy male volunteers (aged 32-46 yr; mean age 37 +/- 4 yr) were studied. All volunteers underwent ergometer exercise testing in both the upright and supine positions, and left ventricular performance was determined with the VEST system. RESULTS: The resting heart rate, systolic blood pressure, pressure rate product, relative end-diastolic volume, relative end-systolic volume and left ventricular ejection fraction (LVEF) all showed no differences between the upright and supine positions. At peak exercise, the heart rate, systolic blood pressure and pressure rate product showed no differences between the upright and supine positions. In the upright position at peak exercise the relative end-diastolic volume was increased (83% +/- 9% to 91% +/- 11%, p < 0.001); the relative end-systolic volume remained unchanged (34% +/- 3% to 33% +/- 15%), and LVEF was significantly increased from 58% +/- 6% to 66% +/- 11% (p < 0.01). In the supine position at peak exercise, the relative end-diastolic volume remained unchanged (85% +/- 5 to 83% +/- 7%), the relative end-systolic volume was increased (35% +/- 5% to 43% +/- 13%, p < 0.01), and LVEF was decreased from 58% +/- 5% to 48% +/- 17% (p < 0.01). These results indicated inferior data collection by the VEST system in the supine position. CONCLUSION: Since the detector of the VEST system may be too small, the data collection is impaired during exercise in the supine position by shifting the heart with deep respiration. The VEST system is very useful for determining left ventricular performance when applied in the sitting or upright position. However, in the supine position during exercise, the use of the VEST system should be avoided because it might indicate an artifactual deterioration of left ventricular performance.     

A mathematical evaluation of the multiple breath nitrogen washout (MBNW) technique and the multiple inert gas elimination technique (MIGET)

We consider two and 50 compartment lung models for use with two techniques used to investigate the efficiency of the lungs: the Multiple Breath Nitrogen Washout (MBNW) technique used for investigating the ventilation-volume distribution; and the Multiple Inert Gas Elimination Technique (MIGET) used for investigating the ventilation-perfusion distribution. In each of these techniques pulmonary respiratory gas exchange is described by conservation of mass equations which may be written in identical form, and in each the underlying distributions of ventilation to volume and ventilation to perfusion are assumed to be continuous functions (usually assumed to be a linear sum of log-normal distributions). The mathematical models used to describe the lung have predominantly used a collection of discrete compartments to approximate these continuous distributions. The most commonly used models have used one, two or 50 compartments. In this paper, we begin by showing that in the limit as the width of the peaks of the distribution tend to zero, the continuous distributions may be replaced by a single discrete compartment placed at each peak of the distribution. We investigate the various methods used previously for parameter recovery, and show that one commonly used method for the MBNW is not suitable and suggest a modification to this recovery technique. Using simulated error-free data, we show that both the two compartment model and the 50 compartment model contain information about the ventilation-volume (or ventilation-perfusion) distribution, and investigate the extent to which this information can be used to recover the parameters which define these distributions. We go on to use Monte-Carlo methods to investigate the stability of the recovery process.     

Total lung capacity by N2 washout from high and low lung volumes in ventilated infants and children

Although there is a strong rationale for the assessment of the subdivisions of lung volume, lung function testing has focused on the measurement of FRC alone in ventilated infants and children. To assess the feasibility, reproducibility, and accuracy of measurements of total lung capacity (TLC), FRC, and their ratio, we determined both lung volumes in 50 critically ill, intubated, and paralyzed infants (mean age [SEM]), 19.9 [4.6] mo) with a variety of lung diseases, by a modified N2 washout technique from end-exhalation and from +40 cm H2O inspiratory pressure, respectively. In the same infants, we also defined TLC by adding inspiratory capacity, measured by pneumotachograph during a passive exhalation from +40 cm H2O to FRC measured by N2 washout. Respiratory mechanics were measured by single-breath occlusion, and the patients were classified according to clinical picture and lung function into groups without lung disease or with restrictive or obstructive disease. The TLC data obtained by both methods showed good agreement for the infants without lung disease or restrictive disease (limits of agreement [LOA]: -3.8/4.6 and -2.9/3.2 ml/kg, respectively). The agreement was less in the infants with airflow obstruction where the N2 washout gave slightly higher values (LOA: -7.1/11.3 ml/kg). Mean FRC/TLC was significantly elevated in the obstructive group, whereas mean FRC alone did not differ from the group without lung disease. Our results suggest that TLC can be measured by both methods in intubated infants, but with limited agreement in obstructive disease. FRC/TLC ratios allow an estimation of the degree of pulmonary hyperinflation.     

Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity

Breathing at very low lung volumes might be affected by decreased expiratory airflow and air trapping. Our purpose was to detect expiratory flow limitation (EFL) and, as a consequence, intrinsic positive end-expiratory pressure (PEEPi) in grossly obese subjects (OS). Eight OS with a mean body mass index (BMI) of 44 +/- 5 kg/m2 and six age-matched normal-weight control subjects (CS) were studied in different body positions. Negative expiratory pressure (NEP) was used to determine EFL. In contrast to CS, EFL was found in two of eight OS in the upright position and in seven of eight OS in the supine position. Dynamic PEEPi and mean transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of eight OS. In OS, PEEPi increased from 0.14 +/- 0.06 (SD) kPa in the upright position to 0.41 +/- 0.11 kPa in the supine position (P < 0.05) and decreased to 0.20 +/- 0.08 kPa in the right lateral position (P < 0.05, compared with supine), whereas, in CS, PEEPi was significantly smaller (<0.05 kPa) in each position. In OS, mean Pdi in each position was significantly larger compared with CS. Mean Pdi increased from 1.02 +/- 0.32 kPa in the upright position to 1.26 +/- 0.17 kPa in the supine position (not significant) and decreased to 1. 06 +/- 0.26 kPa in the right lateral position (P < 0.05, compared with supine), whereas there were no significant changes in CS. We conclude that in OS 1) tidal breathing can be affected by EFL and PEEPi; 2) EFL and PEEPi are promoted by the supine posture; and 3) the increased diaphragmatic load in the supine position is, in part, related to PEEPi.     

Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation

Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.     

Hypertrophic pulmonary osteoarthropathy and its occurrence with pulmonary metastases from renal carcinoma

Studies concerning the ability of an inhaled beta2-agonist to produce dose-related bronchodilatation are conflicting. In five asthmatic, five bronchitic, and five normal subjects, specific airway conductance (Gaw/VL), flow-volume curves, and single-breath nitrogen washout were recorded after noncummulative inhalation of 0.65 mg, 1.30 mg, 1.95 mg, and, in some subjects, 2.60 mg of metaproterenol sulfate. Bronchodilatation appeared to be dose-related and was best assessed by using Gaw/VL; in all but one subject with chronic bronchitis, there was a significant linear relationship between log dose and precent change in Gaw/VL. Measurements of flow rate could demonstrate significant log dose-responses in eight subjects, maximum midexpiratory flow being the most sensitive measurement of flow rate, followed in order by forced expiratory volume in one second, flow at 50 percent of forced vital capacity, peak expiratory flow rate, and flow at 75 percent of forced vital capacity. No log dose-respone curve could be observed by using the single-breath nitrogen-washout technique. This demonstration of significant log dose-responses to inhaled metaproterenol is consistent with the response to drugs acting upon receptors and suggests that patients may benefit from increasing doses of bronchodilators.