Pulmonary Gas Exchange Measurements Research Articles

The usefulness of submaximal exercise gas exchange to define pulmonary arterial hypertension

The 6-minute walk test is widely used to characterize activity tolerance and response to therapy in pulmonary arterial hypertension (PAH) but provides little information about cardiopulmonary pathophysiology. The aim of the present study was to determine whether measures of pulmonary gas exchange during relatively light exercise could differentiate between PAH patients and healthy individuals and also stratify disease severity. The study comprised 40 PAH patients and 25 matched controls. Each completed a sub-maximal exercise test, consisting of 2 minutes of rest, 3 minutes of exercise, and 1 minute of recovery. Ventilation, pulmonary gas exchange, arterial oxygen saturation (Sao(2)), and heart rate were measured throughout using a simplified gas analysis system. A number of gas exchange variables differentiated PAH patients and controls. End-tidal CO(2) (P(ET)co(2)) and Sao(2) were lower in PAH vs controls (31 ± 7 vs 39 ± 3 mm Hg and 89% ± 5% vs 95% ± 2%, respectively, p < 0.05). Breathing efficiency (V(E)/Vco(2) ratio) was poorer in PAH vs controls (42 ± 10 vs 33 ± 5, p < 0.05). In addition, P(ET)co(2) and V(E)/Vco(2) discriminated between different severities of PAH. Gas exchange variables obtained during light sub-maximal exercise differentiated PAH patients from healthy controls and also between different severities of PAH. Sub-maximal exercise gas exchange may be a useful end point measure in a PAH population.

Influence of training and maturity status on the cardiopulmonary responses to ramp incremental cycle and upper body exercise in girls

It has been suggested that the potential for training to alter the physiological responses to exercise in children is related to a "maturational threshold". To address this, we investigated the interaction of swim-training status and maturity on cardiovascular and metabolic responses to lower and upper body exercise. Twenty-one prepubertal [Pre: 11 trained (T), 10 untrained (UT)], 30 pubertal (Pub: 14 T, 16 UT), and 18 postpubertal (Post: 8 T, 10 UT) girls completed ramp incremental exercise on a cycle and an upper body ergometer. In addition to pulmonary gas exchange measurements, stroke volume and cardiac output were estimated by thoracic bioelectrical impedance, and muscle oxygenation status was assessed using near-infrared spectroscopy. All T girls had a higher peak O(2) uptake during cycle (Pre: T 49 ± 5 vs. UT 40 ± 4; Pub: T 46 ± 5 vs. UT 36 ± 4; Post: T 48 ± 5 vs. UT 39 ± 8 ml·kg(-1)·min(-1); all P < 0.05) and upper body exercise (Pre: T 37 ± 6 vs. UT 32 ± 5; Pub: T 36 ± 5 vs. UT 28 ± 5; Post: T 39 ± 3 vs. UT 28 ± 7 ml·kg(-1)·min(-1); all P < 0.05). T girls also had a higher peak cardiac output during both modalities, and this reached significance in Pub (cycle: T 21 ± 3 vs. UT 18 ± 3; upper body: T 20 ± 4 vs. UT 15 ± 4 l/min; all P < 0.05) and Post girls (cycle: T 21 ± 4 vs. UT 17 ± 2; upper body: T 22 ± 3 vs. UT 18 ± 2 l/min; all P < 0.05). None of the measured pulmonary, cardiovascular, or metabolic parameters interacted with maturity, and the magnitude of the difference between T and UT girls was similar, irrespective of maturity stage. These results challenge the notion that differences in training status in young people are only evident once a maturational threshold has been exceeded.

The response of plasma interleukin-6 and its soluble receptors to exercise in the cold in humans

In this study, we wished to determine whether the changes in metabolism observed during exercise in the cold are associated with changes in interleukin-6 (IL-6) and/or its soluble receptors. Eight healthy male participants performed 1 h of cycling exercise at 70% [Vdot]O2max in a control (20°C) and cold (0°C) environment. Plasma concentrations of IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured before exercise, at 30 and 60 min of exercise, and 60 min after exercise. Substrate oxidation was estimated through measures of pulmonary gas exchange recorded between 50 and 55 min of cycling. Exercise in the cold resulted in an increase (P < 0.05) in carbohydrate oxidation (mean 2.58 g · min−1, s = 0.49 at 20°C vs. 2.85 g · min−1, s = 0.58 at 0°C) and a decrease (P < 0.05) in fat oxidation (0.55 g · min−1, s = 0.17 at 20°C vs. 0.38 g · min−1, s = 0.16 at 0°C) compared with the control trial. Interleukin-6 concentrations were elevated (P < 0.05) after 60 min of exercise in both the cold and control trials, with no differences between trials at any instant. Neither sIL-6R nor sgp130 was affected by exercise or the environment. The alterations in carbohydrate and fat utilization during 1 h of exercise in the cold are not paralleled by changes in plasma concentrations of IL-6 or its soluble receptors.

Effects of pre-exercise intrapulmonary blood inoculation on equine pulmonary function during supramaximal exercise

This study was designed to determine the effect of 200 ml of autologous blood instilled in the lungs of healthy horses had on gas exchange, maximal oxygen consumption and breathing mechanics during supramaximal exercise, as a model of exercise-induced pulmonary haemorrhage (EIPH). The subjects were six healthy well-conditioned Thoroughbred horses. On four occasions over a 6-week period, six horses were subjected to two bouts of exercise to fatigue per day, each at speeds equated with an oxygen requirement that was 110% of . Prior to the second bout of exercise on each day, the horses underwent bilateral bronchoscopy during which either nothing (control), or 200 ml of saline, plasma or blood was inoculated into the distal airways, divided equally between each lung. Run time to fatigue, and measurements of pulmonary gas exchange and breathing mechanics were made and analysed for the effects of the four treatments (control, saline, plasma and blood). Inoculation of blood significantly reduced pulmonary oxygen exchange, and run time to fatigue. Plasma inoculation caused intermediate effects, adversely affecting arterial oxygen tension but without significantly reducing or run time to fatigue. Saline treatment had no effect. None of the treatments had an effect on ventilatory mechanics. The results of this study suggest that volumes of blood in the order of 200 ml can impair gas exchange and interfere with the ability of horses to exercise at supramaximal intensities. Blood volumes of this magnitude are readily evident endoscopically, and probably reflect a moderate-to-severe level of EIPH, in contrast to previously published studies where the unilateral instillation of 100 ml of blood or less did not affect performance.

Comparison of metabolic monitors in critically ill, ventilated patients

Objective We compared the Deltatrac II, the M-COVX, and the Evita 4 metabolic monitoring devices under clinical conditions. Methods A prospective simultaneous clinical comparison was performed in a general intensive care department of a tertiary university hospital in 43 ventilated, critically ill patients. The monitors were compared simultaneously. After 30 min of steady state, oxygen consumption per unit time, carbon dioxide consumption per unit time, resting energy expenditure, and respiratory quotient were recorded for the Deltatrac II; the same parameters in addition to end-tidal carbon dioxide and fraction of inspired oxygen were recorded for the M-COVX; and carbon dioxide consumption per unit time, end-tidal carbon dioxide, and fraction of inspired oxygen were recorded for the Evita 4. Pulmonary gas-exchange measurements from the Deltatrac II and resting energy expenditure and respiratory quotient from the M-COVX were obtained after 30 min. The other parameters were calculated from the last five measurements obtained at the end of the study period. Results A good correlation was found between oxygen consumption per unit time and resting energy expenditure as obtained from the Deltatrac II and the M-COVX ( r = 0.76 and 0.75, respectively; P < 0.001), but the correlation was lower between carbon dioxide consumption per unit time as obtained from the Deltatrac II and the M-COVX or Evita 4 ( r = 0.67 and 0.48, respectively). Agreement between the different methods did not reach clinical acceptability, exceeding a 20% difference using the Bland-Altman statistical methods. Conclusion Poor agreement was found between the Deltatrac II and M-COVX or Evita 4 metabolic monitors, despite a good correlation between measurements, leading to the conclusion that the M-COVX and Evita 4 provide less accurate measurements of metabolic gas exchange in stable ventilated patients. These devices can be used for daily nutritional assessment and continuous monitoring, but the Deltatrac II remains the method of choice for metabolic measurement.

A new method for measurement of gas exchange during anaesthesia using an extractable marker gas

A new method for the measurement of pulmonary gas exchange during inhalational anaesthesia is described which measures fresh gas and exhaust gas flows using carbon dioxide as an extractable marker gas. The theoretical precision of the method was compared by Monte Carlo modelling with other approaches which use marker gas dilution. A system was constructed for automated measurement of uptake of oxygen, nitrous oxide, volatile anaesthetic agent and elimination of carbon dioxide by an anaesthetized patient. The accuracy and precision of the method was tested in vitro on a lung gas exchange simulator, by comparison with simultaneous measurements made using nitrogen as marker gas and the Haldane transformation. Good agreement was obtained for measurement of simulated uptake or elimination of all gases studied over a physiologically realistic range of values. Mean bias for oxygen and nitrous oxide uptake was 0.003 l min−1, for isoflurane 0.0001 l min−1 and for carbon dioxide 0.001 l min−1. Limits of agreement lay within 10% of the mean uptake rate for nitrous oxide, within 5% for oxygen and isoflurane and within 1% for carbon dioxide. The extractable marker gas method allows accurate and continuous measurement of gas exchange in an anaesthetic breathing system with any inspired gas mixture.

Breath-by-breath fluctuations of pulmonary gas exchange and ventilation in COPD patients.

The purpose of the study was to characterise statistically the inherent fluctuations in breath-by-breath measurements of pulmonary gas exchange (oxygen uptake and carbon dioxide output, V*O2 and V*CO2, respectively) and pulmonary ventilation (V*E) in patients with chronic obstructive pulmonary disease (COPD) and to compare them with those of healthy control subjects. Thirty subjects with COPD [mean (SD): 67 (6) years old; forced expiratory volume in 1 min, FEV1 1.25( 0.18) l; 42 (6)% predicted FEV1] and 12 healthy subjects [31 (3) years old; FEV1 3.62 (0.54) l; 99 (8)% predicted FEV1] performed exercise tests on a cycle ergometer at a constant work rate of moderate intensity. Steady-state exercise values for V*O2, V*CO2 and V*E were 905 (96) ml.min(-1), 847(90) ml.min(-1) and 23 (3) l.min(-1), respectively for the COPD patients and 1239(89) ml.min(-1), 1191(84) ml.min(-1)and 37(3) l.min(-1), respectively, for the healthy controls. The breath-by-breath fluctuations were well characterised by a Gaussian density-probability function with breath-to-breath autocorrelations that were not significantly different from 0, up to four subsequent breaths. Its magnitude varied among variables, but was independent of the signal amplitude for the same subject and variable. With ratios of amplitude of fluctuation:signal of around 10%, typical of the patients studied, the resolution of time constants and amplitude were congruent with 9 s and congruent with 100 ml.min(-1), respectively for V*O2 or V*CO2 with one repetition.

Isoflurane and Sevoflurane Anesthesia in Pigs with a Preexistent Gas Exchange Defect

Decreased arterial partial pressure of oxygen (PaO2) during volatile anesthesia is well-known. Halothane has been examined with the multiple inert gas elimination technique and has been shown to alter the distribution of pulmonary blood flow and thus PaO2. The effects of isoflurane and sevoflurane on pulmonary gas exchange remain unknown. The authors hypothesized that sevoflurane with a relatively high minimum alveolar concentration (MAC) would result in significantly more gas exchange disturbances in comparison with isoflurane or control. This study was performed in a porcine model with an air pneumoperitoneum that generates a reproducible gas exchange defect. After a baseline measurement of pulmonary gas exchange (multiple inert gas elimination technique) during propofol anesthesia, 21 pigs were randomly assigned to three groups of seven animals each. One group received isoflurane anesthesia, one group received sevoflurane anesthesia, and one group was continued on propofol anesthesia (control). After 30 min of volatile anesthesia at 1 MAC or propofol anesthesia, a second measurement (multiple inert gas elimination technique) was performed. At the second measurement, inert gas shunt was 15 +/- 3% (mean +/- SD) during sevoflurane anesthesia versus 9 +/- 1% during propofol anesthesia (P = 0.02). Blood flow to normal ventilation/perfusion (V(A)/Q) lung areas was 83 +/- 5% during sevoflurane anesthesia versus 89 +/- 1% during propofol anesthesia (P = 0.04). This resulted in a PaO2 of 88 +/- 11 mmHg during sevoflurane anesthesia versus 102 +/- 15 mmHg during propofol anesthesia (P = 0.04). Inert gas and blood gas variables during isoflurane anesthesia did not differ significantly from those obtained during propofol anesthesia. In pigs with an already existent gas exchange defect, sevoflurane anesthesia but not isoflurane anesthesia causes significantly more gas exchange disturbances than propofol anesthesia does.

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury

To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). Prospective, randomised, controlled study. Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.

Gas Exchange, MRS and NIRS Assessment of Metabolic Transients in Skeletal Muscle1

I.T.B.A.—National Research Council, Via F.lli Cervi 93, I-20090 Segrate (MI), Italy SYNOPSIS. The study of the kinetics of O2 consumption (VO2) at the onset and offset of constant-load submaximal exercise (VO2 on- and off-kinetics) is useful from a practical point of view (a faster adjustment of oxidative metabolism follow- ing an increased metabolic demand reduces the need for substrate level phosphor- ylation, with implications on exercise tolerance and muscle fatigue) and can give valuable insights into the regulation of oxidative metabolism in skeletal muscle. Measurements have been carried out both in man and in animals, at the tissue and at the whole body level. At the tissue level, the VO2 on- and off-kinetics were determined: a) Directly, by dynamic solution of the Fick equation throughout the transients; attempts were also made to obtain similar informations by near-infra- red spectroscopy. b) Indirectly, from the kinetics of phosphocreatine hydrolysis and resynthesis, by chemical methods or by 31 P magnetic resonance spectroscopy. At the whole body level, VO2 on- and off-kinetics are determined from breath-by- breath measurements of pulmonary gas exchange. The VO2 5 f(t) function is a complex one, particularly during the on-transient. The so-called ''phase 2'' of the VO2 on-response, as well as the VO2 off-response, yield relevant metabolic infor- mations. In muscle the VO2 on- and off-kinetics are characterized by half-times (t‰) of 15-20 sec. At the whole-body level, t‰ of the VO2 on-kinetics show a wider variability, related to the experimental protocol and to other factors. The VO2 off- phase is more constant, and its kinetic parameters appear closer to those obtained at the tissue level. The study of the VO2 kinetics is valuable for a functional eval- uation of skeletal muscle oxidative metabolism. In ordinary conditions muscle VO2 kinetics appears mainly imposed by intrinsic (metabolic) rather than extrinsic (O 2 delivery) factors.

Pulmonary abnormalities after coronary arterial bypass grafting operation: cardiopulmonary bypass versus mechanical stabilization

Background. Cardiopulmonary bypass has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting procedures. This randomized prospective study was conducted to determine whether patients undergoing coronary artery bypass grafting operations using cardiac stabilization and thereby avoiding cardiopulmonary bypass will have improved pulmonary function postoperatively.Methods. Fifty-eight patients were randomized to one of two groups: coronary artery bypass grafting operation with stabilization or coronary artery bypass grafting operation with cardiopulmonary bypass. Preoperative and postoperative pulmonary gas exchange measurements were performed on intubated patients, including the arterial partial pressure of oxygen on 100% inspired oxygen, the alveolar–arterial oxygen gradient, and pulmonary shunt. Static and dynamic lung compliance measurements were performed postoperatively. Hemodynamic variables (including creatine kinase-MB and troponin levels), intubation time, postoperative bleeding, and blood transfusions were compared.Results. Both study groups had a large decrease in arterial partial pressure of oxygen on 100% inspired oxygen (p < 0.0001) and a significant postoperative increase in the alveolar–arterial oxygen gradient (p < 0.0001). There was no statistical difference in the postoperative gas exchange between the two groups; however, the postoperative pulmonary shunt was significantly better in the stabilization group (24% versus 31%, p = 0.03). The patients were extubated in the intensive care unit earlier in the stabilization group (8.2 hours versus 9.2 hours, not significant). The mean static and dynamic lung compliance postoperatively was lower in the stabilization group, although not statistically significant (p = 0.06).Conclusions. Coronary artery bypass grafting operation using cardiac stabilization technique is safe and avoids the risk of cardiopulmonary bypass. The pulmonary gas exchange postoperatively is comparable to standard cardiopulmonary bypass procedures, but a reduced postoperative pulmonary shunt was seen in the stabilization group.

Orthostatic increase of respiratory gas exchange in hyperventilation syndrome

BACKGROUNDHyperventilation syndrome (HVS) is a common disorder which is difficult to diagnose because of somatic symptoms and its episodic nature. In previous studies respiratory alkalosis in arterial blood was often...

Blood lactate accumulation and muscle deoxygenation during incremental exercise.

Near-infrared spectroscopy (NIRS) could allow insights into controversial issues related to blood lactate concentration ([La](b)) increases at submaximal workloads (). We combined, on five well-trained subjects [mountain climbers; peak O(2) consumption (VO(2peak)), 51.0 +/- 4.2 (SD) ml. kg(-1). min(-1)] performing incremental exercise on a cycle ergometer (30 W added every 4 min up to voluntary exhaustion), measurements of pulmonary gas exchange and earlobe [La](b) with determinations of concentration changes of oxygenated Hb (Delta[O(2)Hb]) and deoxygenated Hb (Delta[HHb]) in the vastus lateralis muscle, by continuous-wave NIRS. A "point of inflection" of [La](b) vs. was arbitrarily identified at the lowest [La](b) value which was >0.5 mM lower than that obtained at the following. Total Hb volume (Delta[O(2)Hb + HHb]) in the muscle region of interest increased as a function of up to 60-65% of VO(2 peak), after which it remained unchanged. The oxygenation index (Delta[O(2)Hb - HHb]) showed an accelerated decrease from 60- 65% of VO(2 peak). In the presence of a constant total Hb volume, the observed Delta[O(2)Hb - HHb] decrease indicates muscle deoxygenation (i.e., mainly capillary-venular Hb desaturation). The onset of muscle deoxygenation was significantly correlated (r(2) = 0.95; P < 0.01) with the point of inflection of [La](b) vs., i.e., with the onset of blood lactate accumulation. Previous studies showed relatively constant femoral venous PO(2) levels at higher than approximately 60% of maximal O(2) consumption. Thus muscle deoxygenation observed in the present study from 60-65% of VO(2 peak) could be attributed to capillary-venular Hb desaturation in the presence of relatively constant capillary-venular PO(2) levels, as a consequence of a rightward shift of the O(2)Hb dissociation curve determined by the onset of lactic acidosis.

Improved oxygenation with prostaglandin F2α with and without inhaled nitric oxide in dogs

Dogs of mixed breed (n = 7) were anesthetized, right lung atelectasis was established, and the cyclooxygenase pathway was blocked with ibuprofen. Measurements of pulmonary gas exchange were performed (fractional concentration of inspired O2 = 0.95) after infusions of prostaglandin F2alpha (PGF2alpha; 2 microg . kg-1 . min-1), ventilation with nitric oxide (NO; 40 ppm), or both (PGF2alpha + NO) in random order. The arterial PO2 (PaO2) under control conditions was 117 +/- 16 Torr (shunt = 33 +/- 2.5%), was unchanged with NO alone (PaO2 = 114 +/- 17 Torr; shunt = 35.7 +/- 3. 1%), but was significantly improved with PGF2alpha alone (PaO2 = 180 +/- 28 Torr; shunt = 23.2 +/- 2.8%) and with the combination of PGF2alpha + NO (PaO2 = 202 +/- 30 Torr; shunt = 20.9 +/- 2.5%). The addition of NO did not significantly enhance the effectiveness of the PGF2alpha on PaO2. Simulation of these data in a computer model, combining pulmonary gas exchange and pulmonary blood flow, reproduced the results on the basis that vasoconstriction with PGF2alpha was maximal under hypoxia in the atelectatic lung and reduced by hyperoxia in the ventilated lung, consistent with the hypothesis of O2 dependence of PGF2alpha vasoconstriction.

Effects of Noninvasive Ventilation on Pulmonary Gas Exchange and Hemodynamics during Acute Hypercapnic Exacerbations of Chronic Obstructive Pulmonary Disease

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 +/- 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (I) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 +/- 2 cm H20, PEEP = 3 +/- 2 cm H20); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping FIO2 constant (0.23 +/- 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in Pa02 (from 50 +/- 6 to 57 +/- 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 +/- 10 to 59 +/- 10 mm Hg; p < 0.0001), but AaPO2 increased (from 39 +/- 13 to 48 +/- 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 +/- 5 to 19 +/- 3 breaths/min; p < 0.0001), tidal volume increased (from 311 +/- 42 to 520 +/- 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 +/- 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 +/- 1.6 to 5.8 +/- 1.3 L/min; p < 0.0025) with no impact on mixed venous PO2. No substantial changes in VA/Q mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 +/- 0.17 to 0.90 +/- 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in VA/Q relationships. The increase in AaPO2 was explained by the rise in R due to an increased clearance of body stores of C02 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NlPPV in this type of patient.

Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P-MRS.

Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after lung transplantation, peak VO2 was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in VO2max after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity.

A modified photo- and magnetoacoustic multigas analyzer applied in gas exchange measurements.

The feasibility of replacing a conventional mass spectrometer (MS) with a specially modified multicomponent (O2, CO2, Freon 22, and SF6) acoustic infrared and paramagnetic (IR/PM) gas analyzer in inert gas-rebreathing and metabolic gas exchange measurements has been investigated. Rebreathing variables were determined simultaneously with the MS and IR/PM analyzers in duplicate measurements at rest and during submaximal exercise in 10 subjects. The differences (means +/- SD, IR/PM - MS) were 0.028 +/- 0.048 liters [functional residual capacity (FRC)], 0.18 +/- 0.38 l/min [cardiac output (Qc)], -0.006 +/- 0.030 l/min [O2 consumption (VO2)], and -33 +/- 108 ml [combined lung tissue and capillary blood volume (Vti,c)]. The coefficients of variation on repeated estimates were 5.8% (FRC), 5.4% (Qc), 6.2% (VO2), and 17% (Vti,c) with the IR/PM analyzer and 5.9% (FRC), 4.2% (Qc), 5.0% (VO2), and 9.8% (Vti,c) with the MS. The differences (IR/PM - MS) obtained in mixed-expirate measurements were -0.006 +/- 0.020 l/min (VO2) and 0.020 +/- 0.021 l/min (CO2 production). Breath-by-breath estimates of VO2 and CO2 production with the IR/PM analyzer were, on average, 2.4 and 4.4% higher than the MS estimates, respectively. Our results demonstrate that the IR/PM gas analyzer, when appropriately modified, can substitute for a complex MS in a variety of noninvasive pulmonary gas exchange measurements.

Adult respiratory distress syndrome in children: Associated disease, clinical course, and predictors of death

The adult respiratory distress syndrome is a common cause of respiratory failure; however, its incidence, risk factors, course, and mortality rate for children remain incompletely understood. A 24-month surveillance of pediatric intensive care admissions identified 60 children with adult respiratory distress syndrome constituting 2.7% of such admissions, 8% of total days spent in a pediatric intensive care unit, and 33% of deaths. The mortality rate was 62% (confidence interval, 48.2% to 73.9%). Adult respiratory distress syndrome occurred in approximately 12% of children admitted for sepsis, viral pneumonia, smoke inhalation, or drowning. A low incidence (< 3%) was observed in children admitted with pulmonary contusion or multiple trauma. Ongoing changes in measures of pulmonary gas exchange varied with the magnitude of alveolar injury; no differences were associated with the underlying acute disease or lung injury mechanism. Efficiency of oxygenation differed among outcome groups by the second day after onset of adult respiratory distress syndrome. An alveolar-arterial oxygen tension difference > 420 was the best early predictor of death (sensitivity 80%, specificity 87%, positive predictive value 87%, negative predictive value 80%, and odds ratio 26.7). We conclude that adult respiratory distress syndrome behaves clinically as a single disease regardless of the underlying cause; its course and outcome are dependent on the magnitude of alveolar injury. We speculate that strategies for minimizing secondary lung injury may benefit all patients with adult respiratory distress syndrome.

Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency.

Insights into muscle energetics during exercise (e.g., muscular efficiency) are often inferred from measurements of pulmonary gas exchange. This procedure presupposes that changes of pulmonary O2 (VO2) associated with increases of external work reflect accurately the increased muscle VO2. The present investigation addressed this issue directly by making simultaneous determinations of pulmonary and leg VO2 over a range of work rates calculated to elicit 20-90% of maximum VO2 on the basis of prior incremental (25 or 30 W/min) cycle ergometry. VO2 for both legs was calculated as the product of twice one-leg blood flow (constant-infusion thermodilution) and arteriovenous O2 content difference across the leg. Measurements were made 3-5 min after each work rate imposition to avoid incorporation of the VO2 slow component above the lactate threshold. For all 17 subjects, the slope of pulmonary VO2 (9.9 +/- 0.2 ml O2.W-1.min-1) was not different (P greater than 0.05) from that for leg VO2 (9.2 +/- 0.6 ml O2.W-1.min-1). Estimation of "delta" efficiency (i.e., delta work accomplished divided by delta energy expended, calculated from slope of VO2 vs. work rate and a caloric equivalent for O2 of 4.985 cal/ml) using pulmonary VO2 measurements (29.1 +/- 0.6%) was likewise not significantly different (P greater than 0.05) from that made using leg VO2 measurements (33.7 +/- 2.4%). These data suggest that the net VO2 cost of metabolic "support" processes outside the exercising legs changes little over a relatively broad range of exercise intensities. Thus, under the conditions of this investigation, changes of VO2 measured from expired gas reflected closely those occurring within the exercising legs.

Breath-by-breath measurement of oxygen consumption and Fio2-Feo2with increased oxygen demand

Continuous on-line breath-by-breath measurement of pulmonary gas exchange was used to monitor the increase in oxygen uptake (VO2) and carbon dioxide excretion (VCO2) induced by the oxidative phosphorylation uncoupling agent 2, 4-dinitrophenol (DNP) in 10 dogs. With incremental doses of DNP totaling 5 mg/kg, the continuously monitored VO2 increased within 2-3 min after the first injection of the drug. VCO2 showed a similar response 4-6 min after the first injection. Temperature increase due to the pharmacological oxidative phosphorylation uncoupling required 20-30 min for a discernible change at this dose. This study also demonstrated a modified and compromised response to the drug in dogs where oxygen delivery was limited by mechanical ventilation.