Level Of Alveolar Ventilation Research Articles

Arterial Blood Gases in Normal Subjects at 2240 Meters Above Sea Level: Impact of Age, Gender, and Body Mass Index.

The values of arterial blood gases (ABG) change with altitude above sea level; empirical verification is essential because ventilatory acclimatization varies with ethnicity and a population's adaptation. The aim of the study was to describe ABG in a healthy population residing at 2,240 meters above sea level, to identify the mean level of alveolar ventilation (PaCO2), and to know whether a progressive increase in PaCO2 occurs with age and the impact of increasing body mass index (BMI). We conducted a cross-sectional study in a referral center for respiratory diseases in Mexico City. Associations among variables with correlation coefficient and regression models of PaO2, SaO2, and P(A-a)O2 as dependent variables as a function of age, BMI, minute ventilation, or breathing frequency were explored. Two hundred and seventeen healthy subjects were evaluated with a mean age of 40 ± 15 years, mean of the PaO2 was 71 ± 6 mmHg, SaO2 94% ± 1.6%, PaCO2 30.2 ± 3.4 mmHg, HCO3 20 ± 2 mmol/L, BE-2.9 ± 1.9 mmol/L, and the value of pH was 7.43 ± 0.02. In a linear regression, the main results were PaO2 = 77.5-0.16*age (p < 0.0001) and with aging P(A-a)O2 tended to increase 0.12 mmHg/year. PaCO2 in women increased with age by 0.075 mmHg/year (p = 0.0012, PaCO2 =26.3 + 0.075*age). SaO2 and PaO2 decreased significantly in women with higher BMI 0.14% and 0.52 mmHg per kg/m2, (p = 0.004 and 0.002 respectively). Mean PaCO2 was 30.7 mmHg, implying a mean alveolar ventilation of around 30% above that at sea level.

Effect of respiratory effort on target minute ventilation during Adaptive Support Ventilation.

Background: Adaptive support ventilation (ASV) is an intelligent mode of mechanical ventilation protocol which uses a closed-loop control between breaths. The algorithm states that for a given level of alveolar ventilation, there is a particular respiratory rate and tidal volume which achieve a lower work of breathing. The mode allows the clinician to set a desired minute ventilation percentage (MV%) while the ventilator automatically selects the target ventilatory pattern base on these inputs and feedback from the ventilator monitoring system. The goal is to minimize the work of breathing and reduce complications by allowing the ventilator to adjust the breath delivery taking into account the patient’s respiratory mechanics (Resistance, and Compliance). In this study we examine the effect of patients’ respiratory effort on target tidal volume (VT) and Minute Ventilation (V̇e) during ASV using breathing simulator. Methods: A bench study was performed by using the ASL 5000 breathing simulator to compare the target ventilator to actual VT and V̇e value in simulated patients with various level of respiratory effort during ASV on the Hamilton G5 ventilator. The clinical scenario involves simulated adult male with IBW 70kg and normal lung mechanics: respiratory compliance of 70 mL/cm H2O, and airway resistance of 9 cm H2O/L/s. Simulated patients were subjected to five different level of muscle pressure (Pmus): 0 (Passive), -5, -10, -15, -25 (Active) cm H2O at a set respiratory rate of 10 (below targeted VT) set at three different levels of minute ventilation goals: 100%, 200%, and 300%, with a PEEP of 5 cm H2O. Fifty breaths were analyzed in every experiment. Means and standard deviations (SD) of variables were calculated. One way analysis of variants was done to compare the values. Pearson correlation coefficient test was used to calculate the correlation between the respiratory effort and the VT, V̇e, and peak inspiratory pressure (PIP). Results: The targeted VT and V̇e were not significant in the passive patient when no effort was present, however were significantly higher in the active states at all levels of Pmus on the 100%, 200% and the 300 MV%. The VT and V̇e increase correlated with the muscle effort in the 100 and 200 MV% but did not in the 300%. Conclusions: Higher inspiratory efforts resulted in significantly higher VT and V̇e than targeted ones. Estimating patients’ effort is important during setting ASV. Keywords: Mechanical ventilation, ASV, InteliVent, Pmus, tidal volume, percent minute ventilation

Hypoventilation syndromes.

In patients with impaired inspiratory muscle function or altered respiratory system mechanics, an imbalance between load and capacity can arise. The ventilatory control system normally compensates for this by increasing drive to maintain adequate alveolar ventilation levels, thereby keeping arterial CO2 within its normal range. To reduce work of breathing, a pattern of reduced tidal volume and increased respiratory rate occurs. This pattern itself may eventually reduce effective ventilation by increasing dead space ventilation. However, the impact of sleep on breathing and its role in the development of diurnal respiratory failure is often overlooked in this process. Sleep not only reduces respiratory drive, but also diminishes chemoresponsiveness to hypoxia and hypercapnia creating an environment where significant alterations in oxygenation and CO2 can occur. Acute increases in CO2 load especially during rapid eye movement sleep can initiate the process of bicarbonate retention which further depresses ventilatory responsiveness to CO2. Treatment of hypoventilation needs to be directed toward factors underlying its development. Nocturnal noninvasive positive pressure therapy is the most widely used and reliable strategy currently available to manage hypoventilation syndromes. Although this may not consistently alter respiratory muscle strength or the mechanical properties of the respiratory system, it does appear to reset chemosensitivity by reducing bicarbonate, resulting in a more appropriate ventilatory response to CO2 during wakefulness. Not only is diurnal hypoventilation reduced with noninvasive ventilation, but quality of life, functional capacity and survival are also improved. However, close attention to how therapy is set up and used are key factors in achieving clinical benefits.

Cardiorespiratory responses to prolonged normobaric inhalatory hypoxia in healthy men

Changes in the cardiorespiratory indicators due to the prolonged (25 min) inhalation of a respiratory mixture with an exponentially falling (from 20.9% to 10%) oxygen concentration were studied in healthy young men. The efficiency of oxygen uptake (as the ventilatory equivalent of O2) in the lungs has been shown to fall particularly promptly (within the first 2–5 min). Individual manifestations of this fall were variable (ranging from 22 to 84% of the baseline data) and driven, to a considerable degree, by the subject’s current level of alveolar ventilation, mobilizing its urgent reserve to improve the ventilation-perfusion relations in the lungs. The subsequent response as a growth in the heart rate (HR) recorded in 100% of cases was delayed relative to the start of hypoxic exposure and combined with increased hypoxemia marked as a decrease in the blood oxygen saturation of hemoglobin. The individual HR growth in response to hypoxia ranged from 8 to 43% of the baseline level and was significantly related to the current level of diastolic arterial blood pressure. The hypoxic ventilatory response was expressed only in 71% of cases, including the 15% when it was reversed (decreased) against the background of a concomitant decrease in the respiratory frequency.

Hyperventilation accelerates rise in arterial blood concentrations of sevoflurane in gynecologic patients

We investigated whether ventilation volumes affected arterial blood sevoflurane concentration (A (sev)) and its uptake into the body during general anesthesia. Thirty female patients undergoing elective gynecologic surgery were randomly allocated into three groups: hyperventilation, normal ventilation, and hypoventilation. Inspiratory (CI(sev)) and end-tidal ((sev)) sevoflurane concentrations were routinely measured by infrared analysis, and A (sev) were analyzed by gas chromatography for 40 min after intubation. Cardiac index and total peripheral vascular resistance were measured with a Finometer. During the first 10 min after sevoflurane administration, A (sev) in the hyperventilation group was the highest and differed significantly from those in the normal ventilation group, followed by those in the hypoventilation group. In addition, hyperventilation significantly increased the slope of A (sev) over time in the first 5 min, but there were no differences in slopes in the 5-10, 10-20, and 20-40 min periods, which indicates no difference in sevoflurane bodily uptake among the three groups after 5 min. Hyperventilation accelerated the rate of A (sev) increase immediately after sevoflurane administration, which was time dependent with respect to different alveolar ventilation levels.

Initiating inspiration outside the medulla does produce eupneic breathing

ARTERIAL PCO2 IS DICTATED by the ratio between the level of pulmonary gas exchange and alveolar ventilation (VA), not minute ventilation. If so, how could isocapnia be maintained if only the magnitude (tidal volume, VT) and duration (TI and TTOT) of the neural output produced by the central pattern generator of breathing (CPG) can be altered? In other words, what is the strategy used by the respiratory control system to match its output to the level of pulmonary gas exchange to keep arterial blood gas homeostasis if this neural output con- tributes to dead space ventilation? In this Viewpoint, we will show that when the spontaneous breathing is replaced by a cortically triggered breathing pattern at various breathing frequencies (we will name this new rhythm an "ecto-rhythm"), the relationship between TTOT and VT has a positive intercept that averages the pulmonary dead space. As a result, the coupling between ventilation and the pulmonary gas exchange becomes possible (17). We will present the idea that whenever isocapnia is maintained during spontaneous or automatic breathing, the magnitude and dura- tion of breath cycles must display the same relationship as during an ecto-rhythm (15). Conversely, we will discuss the implications of the observation that breathing can display the same essential regulatory properties whether generated outside or within the pontomedullary CPG area (7). Ecto-rhythm, breathing pattern, and gas exchange: the re-

Central CO2chemoreception in cardiorespiratory control

Central CO₂chemoreception in cardiorespiratory control

Effects of ventilation, humidity and temperature on airway responsiveness to methacholine in rats.

Exercise-induced bronchoconstriction is associated with heat and water loss from the airways. It is not known whether these conditions can influence the response to bronchoactive agonists. The effects of different degrees of alveolar ventilation on the pulmonary response to methacholine and the role of humidity and temperature in this response were evaluated. Wistar rats were anaesthetized, tracheostomized and mechanically ventilated. Increasing doses of methacholine were infused intravenously and respiratory system resistance (Rrs) and elastance (Ers) were measured. The rats were ventilated with dry air at 13 degrees C, dry air at 37 degrees C, humid air at 13 degrees C and humid air at 37 degrees C. These four groups were further divided into three subgroups with a respiratory frequency adjusted to reach a carbon dioxide tension in arterial blood of 30, 40 and 50 mmHg. Temperature, humidity and level of alveolar ventilation did not influence the position of the dose/response curve to methacholine. However, the maximal changes in Ers were significantly lower in the rats ventilated with humid air. In addition, maximal changes in Ers were significantly higher in the rats with lower alveolar ventilation. These differences were not observed for maximal values of Rrs. The pulmonary response to methacholine in normal rats is significantly affected by the humidity of inspired air and the level of alveolar ventilation. This influence is more intense in the small airways and/or distal airspaces. This suggests that exercise or hyperventilation can change the behaviour of airway smooth muscle.

Continuous Noninvasive Ventilation for Patients with Neuromuscular Disease and Spinal Cord Injury

Patients with a variety of neuromuscular diseases including quadraplegia due to high spinal cord lesions can be managed with full-time noninvasive ventilation instead of intermittent positive pressure ventilation (IPPV) via a tracheostomy. This approach is not suitable for patients with severe bulbar involvement. To be successful with full-time noninvasive IPPV, the ventilator user must realize three goals. First, respiratory system compliance should be optimized and maintained by frequent full inflations delivered by stacking breaths from a volume-cycled ventilator or by insufflating air at adequate pressures using a mechanical insufflator-exsufflator. Second, normal levels of alveolar ventilation are sustained using a variety of noninvasive approaches, including nasal, oronasal, or mouthpiece interfaces. Third, patients must be taught to use techniques and devices to enhance cough, particularly the mechanical insufflator-exsufflator. When these goals are met, noninvasive NPPV can offer patients greater comfort, simpler and more convenient ventilator use, and reduced rates of infections, complications, and hospitalizations as compared with tracheostomy IPPV.

Intermittent CPAP during General Anesthesia

Department of Anesthesiology, MDC 59; University of South Florida; College of Medicine; 12901 Bruce B. Downs Boulevard; Tampa, Florida;jdowns@com1.med.usf.eduIn Reply:-We appreciate Dr. Fletcher's careful review of our article and considerate comments. We considered the ratio PaCO(2):minute ventilation to be a simple calculation of ventilatory efficiency in the restrictive setting of cardiopulmonary and metabolic stability with "…relatively constant PaCO(2) and carbon dioxide production…" [1] We did not and would not advise use of the calculation in a setting of variable CO2production, alveolar ventilation, or PaCO(2). As a separate measure, we calculated the P(a-et)CO(2) and confirmed that intermittent CPAP results in more efficient ventilation than traditional controlled mechanical ventilation (CMV). Fletcher also referred to an increase in alveolar ventilation, which was precluded by study design. We produced equivalent levels of alveolar ventilation during CMV and intermittent CPAP, as evidenced by similar PaCO(2) values, but with significantly less total ventilation during the latter. Using the calculation P(a-et)CO(2)/PaCO(2) as an indication of the fraction of unperfused, but ventilated alveoli [2] we found a mean alveolar deadspace of 4% during intermittent CPAP and 17% during CMV.It is well known that an inspiratory pause applied during CMV may result in a smaller calculated physiologic deadspace. [3] It is less apparent that "conducting airways," which define the "anatomic" deadspace, are reduced in volume by an end-inspiratory pause. It also is not clear that CPAP will have a pulmonary effect similar to that observed with conventional positive pressure ventilation with an inspiratory plateau. Our data clearly support a significant decrease in alveolar deadspace during intermittent CPAP. To test Fletcher's hypothesis that a decrease in anatomic deadspace might account for the observed increase in efficiency of ventilation during intermittent CPAP, we calculated the difference in mean anatomic and alveolar deadspace (VD) volumes during CMV and intermittent CPAP, using data in the manuscript [1] and standard equations. [4] We assumed a normal anatomic deadspace of 194 ml during CMV. During intermittent CPAP alveolar V (D) was 15 ml, anatomic VD139 ml, and total physiologic VD153 ml. During CMV alveolar VDwas 74 ml, anatomic VD194 ml, as assumed, and total physiologic VD268 ml. We observed that intermittent CPAP caused modest decrease in calculated anatomic VDcompared with CMV, of 28%. More important however, was the fivefold increase in alveolar deadspace generated by controlled ventilation. Overall physiologic VDwas 74% higher during CMV than during intermittent CPAP, emphasizing our conclusion that intermittent CPAP provides more efficient ventilation.John B. Downs, M.D.Department of Anesthesiology, MDC 59; University of South Florida; College of Medicine; 12901 Bruce B. Downs Boulevard; Tampa, Florida;jdowns@com1.med.usf.edu(Accepted for publication December 17, 1998.)

Airway Pressure Release Ventilation in Severe Acute Respiratory Failure

Airway pressure release ventilation (APRV), a new ventilatory support technique, was compared with conventional intermittent positive-pressure ventilation plus PEEP (CPPV) in 18 patients with severe acute respiratory failure. Patients were initially stabilized on CPPV and then switched to APRV. The APRV provided effective ventilatory support in 17 of 18 patients; APRV achieved similar levels of alveolar ventilation as CPPV (for APRV, mean PaCO2 = 45.0 +/- 6.2 mm Hg; vs for CPPV, mean PaCO2 = 43.3 +/- 5.7 mm Hg), with significantly lower mean maximum airway pressures (38.9 +/- 10.1 cm H2O vs 64.6 +/- 15.4 cm H2O; p = 0.0001) and mean VT (0.79 +/- 0.11 L vs 1.05 +/- 0.15 L; p = 0.0002). No significant differences in mean airway pressure, end-expiratory pressure, FIO2, ventilator rate, arterial blood gas levels, and hemodynamic function were noted between APRV and CPPV.

After phrenicotomy the rat alters the output of the remaining respiratory muscles without changing its sleep-waking pattern

The respiratory activity of selected rib cage and abdominal wall muscles was studied in intact and bilaterally phrenicotomized (PNX) rats during non-rapid eye movement sleep (nREMS) and REMS. The polygraphic method was used to identify the animal's sleep-waking states before and after PNX. Electromyographic (EMG) recordings were made from the following muscles: the parasternals of the 1st, 3rd, and 5th interspaces; the external and internal intercostals of the 1st, 6th and 10th interspaces; the levator costae attaching to the 10th rib; the scalenus medius; and, the abdominal wall muscles, teh external and internal obliques and rectus abdominis. Afte PNX, all rib cage muscles contracted exclusively during inspiration and all but one increased their activity. The exception was the internal intercostal muscl of the 10th interspace; its activity decreased. The external and internal oblique muscles, both of which were active during expiration in nREMS, also increased their output after PNX: rectus abdominis became an inspiratory muscle. The persistence of phasic activity of respiratory muscles during REMS varied not only from muscle to muscle but from one REMS epoch to another. The sleep-waking pattern of the PNX rat differed in only a minor way from that of the intact rat. Therefore, we conclude that the rat with total paralysis of its diaphragm uses mainly its neurometabolic mechanisms to achieve an adequate level of alveolar ventilation and not neurobehavioral mechanisms.

New drugs and new understandings of paediatric pharmacology

lnhalational anaesthetic agents The uptake and elimination of the inhaled anaesthetic agents in infants and children have been extensively studied. The high level of alveolar ventilation compared to the functional residual capacity, the larger proportion of vessel rich tissues, and a lower blood gas solubility coefficient all contribute to the rapid induction and recovery phases which occur in the infant. Inhalation anaesthetic agents are probably metabolized less in infants than in older patients; serum bromide levels are lower following halothane in infants than in adults. Serum inorganic fluoride levels are lower following enflurane anaesthesia, but this may also be due to increased bone deposition of fluoride in paediatric patients. The effects of the volatile anaesthetics on the cardiorespiratory system of infants and chidren are now more fully documented, lsoflurane causes an increase in heart rate and halothane slows the heart. At equal levels of anaesthesia, halothane and isoflurane cause a similar degree of hypotension which is dose-related. Isoflurane, however, causes less depression of myocardial contractility but more afterload reduction than halothane. Cardiac output is better maintained with isoflurane provided fluid is administered to maintain preload. 2 The addition of nitrous oxide to the inspired gas mixture results in cardiovascular effects which are similar to those produced by equianaesthetic dose levels of the volatile agents in oxygen. 3 While the volatile anaesthetics all cause similar increases in end-tidal carbon dioxide levels in spontaneously breathing children the patterns of ventilation differ. Depression of the ventilatory response to carbon dioxide is dose-dependent. Halothane causes tachypnoea, isoflurane causes little change in rate, and enflurane tends to slow ventilation. 4 Intercostal muscle activity is suppressed by haiothane, paradoxical breathing occurs at end-tidal concentrations above one per cent. 5 Intravenous anaesthetics and analgesics The dose requirements of thiopentone in infants and children of various ages show wide variation. Newborn infants require 3-4 mg.kg -I while those of 1-6 mo require 7-8 mg.kg-~. 6 In healthy children 5-6 mg. kg-i is the dose required for rapid reliable induction of anaesthesia. 7 The pharmacokinetics of thiopentone in paediatric patients have been studied and show a shorter elimination time in infants and children than in adults) The narcotic analgesics have been widely used in infants, especially for major surgical procedures, fentanyl being the most commonly used drug. The dose response of neonates to fentanyl indicate that a dose 10-12.5 I~g kg -I will prevent any response to surgical stimulation and provide anaesthesia for 60-90 min. 9 Older infants may require higher doses. I~ The pharmacokinetics of fentanyl depend upon age. Neonates show wider variation and slower clearance rates than older infants, who may demonstrate clearance rates higher than those of adults. ~ Preterm infants and neonates with increased intraabdominal pressure predictably demonstrate a prolonged elimination half-life of the drug. J2 Some infants demonstrate secondary peaks in plasma levels of the drug and these may be associated with respiratory depression in patients not on mechanical ventilation. The cardiovascular system is little affected by even large doses of fentanyl, but a useful effect in blunting the neonatal pulmonary vascular responses to stress has been noted. Chest wall compliance is significantly reduced by fentanyl in children.

Artificial ventilation by means of electrical activation of the intercostal/accessory muscles alone in anesthetized dogs.

We have previously shown that large inspired volumes can be achieved in phrenicotomized animals by intercostal/accessory muscle activation via spinal cord stimulation. In the present study, we evaluated the utility of this technique to provide complete ventilatory support for prolonged time periods (6 to 8 h, selected arbitrarily). In 10 deeply anesthetized dogs, a single electrode was introduced onto the epidural surface of the spinal cord and positioned at the T2-T3 spinal level. Bilateral phrenicotomy was performed in all animals to prevent possible diaphragm activation. The spinal cord was rhythmically stimulated approximately 13 times/min with trains of 15- to 20-Hz impulses of sufficient amplitude to achieve inspired volumes of 13 to 15 ml/kg and pressure-time index (product of duty cycle and delta P/Pmax) of less than 0.15 with each contraction. Level of alveolar ventilation was monitored by end-tidal PCO2 and intermittent arterial blood gas measurements. Mean inspired volume and minute ventilation were 236 +/- 7.84 (SE) ml and 3.12 +/- 0.13 (SE) L/min, respectively, and not significantly different between the first and sixth hours of continuous stimulation. Mean duty cycle (Ti/Ttot) was 0.26 +/- 0.01. Mean airway pressure (delta P) during prolonged electrical stimulation under conditions of airway occlusion was 8.05 +/- 0.61 (SE) cm H2O. Mean ratio of delta P/Pmax was 0.47 +/- 0.03 (SE) cm H2O; mean pressure-time index was 0.12 +/- 0.01 (SE). There was no evidence of system fatigue, as evidenced by the lack of any significant shift in the pressure frequency curve over a 6-h time period.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of cardiogenic oscillations to gas exchange in constant-flow ventilation.

The contribution of cardiogenic oscillations to gas exchange during constant-flow ventilation was examined in 11 dogs. With the use of two variations of cardiopulmonary bypass to maintain the systemic and pulmonary circulation, the influence of cardiogenic oscillations was removed by arresting the heart. Cardiac arrest by ventricular fibrillation was associated with a mean decrease in alveolar ventilation of 43% in five dogs on right and left heart bypass. However, successful defibrillation and return of the prearrest level of alveolar ventilation could not be achieved; thus we studied six dogs on left heart bypass. Alveolar ventilation decreased an average of 37% with cardiac arrest, and defibrillation resulted in a return of alveolar ventilation to 81% of the prearrest value. These results are consistent with previous predictions that cardiogenic oscillations are an important mechanism of gas transport during constant-flow ventilation.

AN EXPERIMENTAL STUDY OF GASEOUS HOMEOSTASIS AND THE MAGILL CIRCUIT USING LOW FRESH GAS FLOWS

Gas concentrations and ventilation levels have been measured within a conventional Magill circuit when conscious volunteers breathed a non-narcotic gas mixture at varying fresh gas flows. When evidence of rebreathing of alveolar gas was detected, the fresh gas flow was kept constant until a steady state developed. All subjects showed evidence of rebreathing when the fresh gas flow approached the predicted alveolar ventilation levels. A variety of subject-circuit interactions was seen and shown to be precipitated by naturally occurring breath-to-breath variations in ventilation. A single large breath could perturb the system. This could have a temporary effect, when the fresh gas flow was sufficient to wash the increased aliquot of expired carbon dioxide from the circuit. At other times a progressive response occurred as ventilatory stimulation as a result of the increased inspired carbon dioxide concentrations caused alveolar gas to reach the reservoir bag and converted the system behaviour from that of a simple added deadspace to that of a total mixing device. Whilst marked changes occurred commonly in both ventilation and inspired gas concentrations, only slight changes in end-tidal gas concentrations occurred.

An Arterial Blood Gas Diagram for Clinical Use

A simple diagram for arterial blood gas tensions was constructed from values obtained from normal volunteers at rest, during voluntary breath-holding and during maximal voluntary hyperventilation. Thus, an appropriate arterial oxygen tension (PaO2) was established for any physiologic level of alveolar ventilation, as reflected by the arterial carbon dioxide tension (PaCO2). Blood gas tensions of 177 ambulatory patients with differing clinical types of pulmonary insufficiency were plotted against the diagram and the magnitude of the observed deviations from the normal range were compared to selected pulmonary function test results. The vast majority of test results exhibited lower oxygen tensions than predicted from the observed PaCO2. This actual-predicted PaO2 difference was directly related to the severity of airways obstruction in chronic obstructive pulmonary disease and to the severity of restriction in interstitial lung diseases. Patients in the early stages of lung disease had resting hypocarbia before the onset of hypoxemia or of significant pulmonary function test abnormality. The diagram provides a simple, rapid clinical method of diagnosing and estimating the severity of the blood gas disturbances which reflect V ˙ / Q ˙ mismatching at any physiologic level of alveolar ventilation.

The measurement of ventilatory response to CO 2

Summary The interpretation of the measurements of ventilatory response to CO 2 has been shown to involve assumptions made about the P co 2 at receptor sites such as the carotid bodies and the motor output from the central controlling sites in the mid-brain. The influences which play upon these central areas, which are best thought of in terms of the central excitatory state, must also be considered. A steady state and a rebreathing method have been described which provide an estimate of the ventilatory response to CO 2 . The steady state method requires considerable attention to detailed theoretical points if it is to provide meaningful information. The rebreathing method is of particular value in studies performed on patients as it is brief and bloodless and causes less distress. Both methods reveal CO 2 responsiveness to be very variable from subject to subject and in the same subject from time to time, and this variability is in contrast with the stability of the arterial P co 2 at rest. If such correlation as does exist between the ventilatory response to CO 2 and the arterial P co 2 is causal, it remains uncertain which component initiates the changes which can occur in both. It is likely that the P co 2 of the respiratory centre is but one of the factors which affect its motor output and hence the level of alveolar ventilation, and more attention needs to be paid to wakefulness and conditioning, and to the interrelationship between all the influences.

Changes in alveolar-arterial oxygen tension difference (A-aDO2) during variations in alveolar ventilation.

AbstractThe alveolar‐arterial PO2 difference (A—aDO2) was determined at various levels of alveolar ventilation in anesthetized, tracheotomized dogs, ventilated with room air by means of a volume cycled respirator; the ventilation being changed by varying the tidal volume, keeping the respiratory rate constant.—A decrease in ventilation was accompanied by a marked decrese in A—aDO2, and vice versa: At PaCO2≤30 mm Hg (mean 25.5 mm Hg) A—aDO2 was 28.3 mm Hg (range 18—42 mm Hg), at PaCO2 31–50 mm Hg (mean 41.5 mm Hg) A—aDO2 was 19.3 mm Hg (range 13—30 mm Hg); at PaCO2≥51 mm Hg (mean 60.5 mm Hg).A—aDO2 was 9.7 mm Hg (range 5—14 mm Hg).—Assuming an arterio‐venous difference in hemoglobin O2 saturation of 20% and 40%, respectively, the A—aDO2 for the 3 PCO2 intervals were calculated as venous admixture, being 7.1, 10.4 and 23.0%, and 3.7, 5.5 and 13.0%, respectively.—This indicates that reduction of the alveolar ventilation is accompanied by increasing disturbances of the alveolar‐arterial gas exchange,—of the nature uneven distribution of ventilation and perfusion, and/or venous admixture.The inverse relationship between the extent of the disturbances of alveolar‐arterial gas exchange and A—aDO2 in these studies show that A—aDO2 should only be used for the evaluation of changes in the alveolar‐arterial gas exchange when the alveolar ventilation remains unchanged.

The effects of voluntarily controlled alveolar hyperventilation on carbon dioxide excretion.

Four subjects hyperventilated at three carefully controlled alveolar ventilation levels. It was found that carbon dioxide excretion and the rate of change of alveolar carbon dioxide tension were related to the alveolar ventilation.Three exponential components were recognized in the carbon dioxide excretion curves and their time constants determined. These were related to the body stores from which carbon dioxide was removed.The slope of the whole body carbon dioxide dissociation curve was found to be related to the alveolar ventilation level and ranged from 1·17–2·03 ml./mm. Hg./min,