The parallel Lack anaesthetic breathing system

The parallel Lack system is a new modification of the Mapleson A system comprising separate inspiratory and expiratory tubes. To determine that the function of the system was that anticipated of a Mapleson A, the fresh gas flow requirements to prevent rebreathing during spontaneous ventilation were assessed in three situations: (1) a lung model (2) conscious volunteers and (3) anaesthetised patients. Two sets of criteria to define rebreathing were used; (A) those based on changes in ventilation or end-expired carbon dioxide tension and (B) minimum inspired carbon dioxide tension. Using A, rebreathing occurred at a fresh gas flow to minute ventilation ratio (VF/VE) of 0.75 for the lung model, and 0.73 for conscious volunteers. These results were comparable to those obtained for a Magill attachment. They were also close to the point at which mechanical dead space began to increase in the lung model. Criteria B gave much lower values for the onset of rebreathing. Rebreathing was present by criteria A in five of the six anaesthetised patients at a fresh gas flow of 60 ml.kg-1.min-1 (VF/VF of 0.78). The results confirm that the parallel Lack behaves as a Mapleson A system. The resistance to breathing posed by the parallel Lack was also comparable to the Magill system.     

Anesthesia equipment and respirators. Fundamentals

The decrease of functional residual capacity during anaesthesia makes mechanical ventilation mandatory. Volume- and pressure-controlled modes should both be possible. Ventilator-assisted spontaneous respiration is rarely indicated during general anaesthesia, and this mode is therefore unnecessary for anaesthesia machines. From ecological and economical points of view, modern anaesthesia machines should be equipped with a circle system enabling administration of anaesthesia under rebreathing conditions with reduced fresh gas flow. Basic requirements are low gas leakage of the system, precise gas-flow dosage, especially at low flow rates, and integrated monitoring of in- and expiratory gases. In principle, older machines may also comply with these requirements if they are appropriately upgraded and properly maintained. There is reasonable doubt whether a further reduction of flow to less than 1 l/min fresh gas is of any benefit. To maintain patient safety without compromising practicability, a tremendous surplus of technical efforts is necessary. For easier management, fresh-gas-flow-compensated circle systems facilitating adjustment of tidal volume after changes of fresh gas flow are desirable. Precautions aimed at the prevention of ventilation with hypoxic gas mixtures are still insufficient: the oxygen failure devices (nitrous oxide flow shutoff valve) are only effective if oxygen pressure from the gas supply is low. Distinct improvements have been achieved with oxygen ratio systems, preventing the administration of hypoxic gas mixtures at fresh gas flows higher than 1 l/min.     

Comparison of disposable circle and 'to-and-fro' breathing systems during anaesthesia in dogs

Low-flow anaesthesia is beneficial in terms of reducing atmospheric pollution with waste anaesthetics and improving economy. This study compared a disposable circle and a 'to-and-fro' breathing system at low fresh gas flows (10 ml/kg/minute) in 19 dogs undergoing ovariohysterectomy. Ten dogs were assigned to the circle and nine to the to-and-fro breathing system. Fractional inspired halothane, end-tidal carbon dioxide and halothane were higher and mean blood pressure was lower in dogs using the to-and-fro system, possibly indicating an increased anaesthetic depth in this group. Use of both systems resulted in an elevated inspired carbon dioxide level, although this was significantly lower in the circle system. Further work will be required to determine the clinical relevance of this difference and whether rebreathing can be eliminated by higher fresh gas flows. The disposable circle studied may be used safely in dogs.     

A computer program for automatic measurement of respiratory mechanics in artificially ventilated patients

A program for automatic and periodic determination of respiratory mechanics in artificially ventilated patients is described. Airway pressure and flow signals are obtained from the ventilator in the controlled ventilation mode with constant flow inflation and end-inspiratory pause. Periodically, the program records both signals for a given time and it delimits a ventilatory cycle and its components out of this record. Then, four mechanical parameters of the respiratory system are calculated: (1) Rinit, the resistance obtained with the end-inflation occlusion technique; (2) Ers, the elastance (inspiratory) calculated from the slope of the airway pressure profile during inflation; (3) tau, the expiratory time constant; (4) PEEP, the global positive end expiratory pressure. All parameter measurements have been evaluated in experimental conditions, and are in good agreement with reference values. The complete software includes the display of the signals and of the trends together with automatic disk file backups. An additional program allows one to display the trends again and to create table text files containing all the recorded data for further analysis. The system proved to work in ICU and anaesthesia patients with various ventilators.     

Oblique Flow over Dredged Channels.?I: Flow Description

A 3D investigation of flow across long, straight channels aligned obliquely to the flow direction has been conducted. The applied mathematical model solves the Reynolds-averaged Navier-Stokes equations using a k-ε model for turbulence closure in a curvilinear coordinate system. The uniformity along the channel alignment allows the three momentum equations to be solved in a 2D computational domain. With respect to a steady current entering a channel obliquely, two important flow features arise: (1) The flow will be refracted in the direction of the channel alignment, which may be described by depth-averaged models; and (2) a secondary flow will be introduced due to shear in the velocity profile. This can only be described using a 3D approach. The secondary flow will cause a horizontal deflection of streamlines over the vertical. Only by capturing the 3D flow behavior can the direction and magnitude of the bed shear stress be well modeled. When crossing a channel obliquely, the flow is gradually accelerated in the direction of the channel alignment. Results of the numerical flow model are compared with existing experimental data and good agreement is found.     

Respiratory gas exchange. Anesthesia with enflurane or isoflurane in nitrous oxide during spontaneous and controlled ventilation

The estimation of oxygen consumption and carbon dioxide elimination is essential for predicting the metabolic activity and needs of any patient having anaesthesia. During anaesthesia oxygen consumption can be measured and compared to a predicted value. However, oxygen uptake is affected by anaesthetic agents, which complicates the interpretation of measured oxygen uptake rate. The purpose of this study was to investigate whether there are any differences in respiratory gas exchange during anaesthesia with enflurane and isoflurane and also to assess the effects of spontaneous versus controlled ventilation. METHODS. Forty orthopedic patients were randomized to enflurane or isoflurane anaesthesia in nitrous oxide with either spontaneous or controlled ventilation. A fresh low-gas-flow technique was used. Inspiratory oxygen and end-tidal carbon dioxide concentrations and expiratory minute ventilation were measured in a circle absorber system between the y-piece and the endotracheal tube with a sampling analyser. Between the mixing box and the absorption canister, carbon dioxide concentration was continuously measured. The carbon dioxide elimination was calculated from mixed expired concentration and expiratory minute ventilation. Excess gas was collected every 10 min in a non-permeable mylar plastic bag connected to the excess valve. The excess gas flow was calculated and the oxygen uptake rate was assumed to be the difference between the oxygen fresh gas flow and the oxygen excess gas flow. RESULTS. The grand mean oxygen uptake rate was 2.5 ml.kg-1 x min-1 or 100 ml.min-1 x m-2. There were no statistically significant differences in oxygen uptake between enflurane and isoflurane anaesthesia or between spontaneous and controlled ventilation. The mean oxygen uptake rate at 10 min was between 2.0 and 2.2 ml.kg-1 x min-1 in all groups. At 30 min the mean oxygen uptake rates were 2.6 to 2.8 ml.kg-1 x min-1. Carbon dioxide elimination was closely associated with expired minute ventilation, with a carbon dioxide excretion of about 30 ml per litre gas exhaled, irrespective of ventilatory mode employed.     

Case report of severe multiple trauma. Anesthesiologic techniques

The modern anaesthetic devices have now put an end to the sixties-fashioned aphorism: "Closed circuit=open coffin". The currently renewed interest in the recirculation systems is justified by the following reasons: economic benefit; environmental advantages; clinical features, such as: 1) better humidification of gases; 2) better preservation of warmth; 3) monitoring of O2 consume; 4) gas analysis on each respiratory act. This allows the use of fresh gases at low flow without the risk of hypoxia or overdosage in patients and it guarantees for safe anaesthesia. The following clinical case clearly shows the application of the above mentioned principles. An extremely serious case of head, chest and abdominal multiple trauma, personally observed, is described. The so called technics "partial rebreathing" was adopted thanks to the availability of a device which permits a punctual monitoring of SAO2, ETCO2, FI and FET, FLO2, VM, VT, VEmin, % of N2O, invasive SAP and body temperature. These are very important parameters for a safe anaesthesia and in conditions like those of the above described clinical case.     

Effect of sucrose acetate isobutyrate (SAIB) ingestion on the hepatobiliary function of normal human male and female volunteers

Monitoring of oxygen uptake during general anesthesia would have several benefits, but unfortunately, this is usually not available in the clinical routine situation. The herein proposed formula to calculate oxygen uptake (.VO2) necessitates only the accurate measurement of FIO2 as well as fresh gas flow and composition. Additionally, this method is not affected by the presence of anesthetic gases. The calculation uses the difference in oxygen content between the delivered fresh gas and the resulting FIO2 in the anesthesia circle system. This gap originates from oxygen uptake (that is mainly caused by metabolic oxygen consumption) and is more pronounced if low fresh gas flows are administered. In order to obtain representative results, calculation of .VO2 should be performed only after achievement of respiratory steady state conditions. Due to its simplicity and wide availability, it has the potential to become a valuable extension in anesthesia monitoring during the performance of routine general anesthesia.     

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.     

Spectral properties of system I-deficient mutants of Chlamydomonas reinhardi. Possible occurrence of uphill energy transfer

The effects of end-inspiratory pause (EIP) on gas exchange were measured in 10 adult patients with acute respiratory insufficiency while maintained on mechanical ventilation. Four inspiratory patterns were studied with a constant tidal volume (10 to 15 ml/kg body weight), respiratory rate (9 to 12 breaths/min), FIO2 (0.5) and end-expiratory pressure. Inspiratory flow rate (V insp) and EIP time were varied to produce a control pattern (V insp = 60 L/min, EIP = 0), 2 EIP patterns of 0.6 and 1.2 seconds with a similar V insp and a "slow" flow pattern (V insp = 30 L/min) without EIP. The control pattern was applied before and after each study period. Arterial oxygenation was unchanged with both EIP and "slow" flow patterns when compared to control. Dead-space ventilation (VD/VT) and Paco2 were significantly decreased (p less than 0.01) as EIP was increased from 0 to 1.2 seconds, but remained unchanged with slow inspiratory flow. Thus, EIP improved the efficiency of ventilation with no apparent improvement in oxygenation in patients with acute respiratory insufficiency.     

Prolonged sevoflurane, isoflurane and halothane anaesthesia in oxygen using rebreathing or non-rebreathing system in cats

Effects of prolonged sevoflurane, isoflurane and halothane anaesthesia in oxygen on clinical, cardiopulmonary, haematologic, and serum biochemical findings were compared in healthy, premedicated cats breathing spontaneously during 6 h of anaesthesia using rebreathing (semi-closed circuit) or non-rebreathing (Bain coaxial circuit) system. Recovery from anaesthesia with sevoflurane was more rapid than that with halothane or isoflurane in both systems. Respiration and heart rates during sevoflurane anaesthesia were similar to those during isoflurane rather than halothane anaesthesia in both systems. The degree of respiratory acidosis during prolonged sevoflurane anaesthesia was similar to that during isoflurane anaesthesia, and was less than that during halothane anaesthesia in both rebreathing and non-rebreathing systems. Prolonged sevoflurane anaesthesia induced mean arterial pressure similar to isoflurane or halothane anaesthesia in the non-rebreathing system, but it depressed mean arterial pressure less than isoflurane or halothane anaesthesia in the rebreathing system. Time related increase in the arterial carbon dioxide partial pressure was observed during halothane anaesthesia especially in the rebreathing system, however, no significant time-related changes in cardiopulmonary variables were observed during either sevoflurane or isoflurane anaesthesia in both systems. There were no significant differences among sevoflurane, isoflurane and halothane anaesthesia in serum biochemical values in both systems.     

Home versus intensive care pressure support devices. Experimental and clinical comparison

A bench study using an artificial lung model and a clinical study in patients were performed to evaluate six commercially available home pressure support devices. Six devices were tested in the in vitro study, including five designed for home use and one designed for use in intensive care units. Minimal positive end-expiratory pressure (PEEP) varied across home devices, from 0.5 cm H2O to 4.3 cm H2O. Work imposed during exhalation varied up to six-fold across devices. A substantial rebreathing volume has present for the three home devices with a common inspiratory and expiratory line. This rebreathing volume decreased with increasing PEEP level, as expected, but remained substantial at the widely used PEEP level of 5 cm H2O. Use of a non-rebreathing valve increased both the work imposed by the circuit during the exhalation phase and the time required to attain the relaxation equilibrium. Except for two home devices and a bilevel positive airway pressure (BiPAP) device equipped with a non-rebreathing valve, differences in inspiratory trigger sensitivities were small between home and intensive care devices. During pressure support, the total work performed by the machines did not differ by more than 15% between devices, whereas differences of more than 300% were observed in flow acceleration. Only one home device gave a flow acceleration similar to or better than that obtained with the intensive care device. In a randomized, crossover clinical study, we compared a home device to a device specially designed for intensive care use in seven intubated patients during weaning from mechanical ventilation. The main differences between the two devices were trigger sensitivity and initial flow acceleration. For the same level of pressure support, there were no significant differences in arterial PCO2, tidal volume, respiratory rate, or minute ventilation between these two devices. However, the esophageal pressure-time product was 30% higher with the home device (165 +/- 93 versus 119 +/- 80 cm H2O/min, p < 0.05). In conclusion, differences exist between devices in terms of occurrence of rebreathing, speed of attainment of stable pressure support level, and expiratory resistance. These differences characterizing the delivery of pressure support may have clinical impact on the inspiratory effort of patients.     

Effects of three different types of management on the elimination kinetics of volatile anaesthetics. Implications for malignant hyperthermia treatment

The effectiveness of three types of management on the elimination kinetics of volatile anaesthetics was studied prospectively in 45 patients randomised to one of three groups. Patients were anaesthetised using isoflurane. Inspiratory and expiratory isoflurane concentrations were measured. After reaching a steady-state isoflurane concentration, the vaporizer was turned off. In group 1, only the fresh gas flow was increased from 40 to 120 ml.kg-1 x min-1. Patients in group 2, in addition to the increase in the fresh gas flow, had a charcoal filter connected in the inspiratory limb of the circuit. Patients in group 3 had the fresh gas flow increased and the anaesthetic machine and breathing system changed. There was a statistically significant difference in the isoflurane washout from the anaesthetic machines between group 1 (90% elimination time 39 [10] s) and group 2 (90% elimination time 25 [5] s) (p < 0.01). However, there was no significant difference in the isoflurane washout from the patients in any of the groups. Thus the use of a charcoal filter or a change of the anaesthetic machine and breathing system proved to be of no clinical advantage.     

Modeling neural mechanisms for genesis of respiratory rhythm and pattern. II. Network models of the central respiratory pattern generator

The present paper describes several models of the central respiratory pattern generator (CRPG) developed employing experimental data and current hypotheses for respiratory rhythmogenesis. Each CRPG model includes a network of respiratory neuron types (e.g., early inspiratory; ramp inspiratory; late inspiratory; decrementing expiratory; postinspiratory; stage II expiratory; stage II constant firing expiratory; preinspiratory) and simplified models of lung and pulmonary stretch receptors (PSR), which provide feedback to the respiratory network. The used models of single respiratory neurons were developed in the Hodgkin-Huxley style as described in the previous paper. The mechanism for termination of inspiration (the inspiratory off-switch) in all models operates via late-I neuron, which is considered to be the inspiratory off-switching neuron. Several two- and three-phase CRPG models have been developed using different accepted hypotheses of the mechanism for termination of expiration. The key elements in the two-phase models are the early-I and dec-E neurons. The expiratory off-switch mechanism in these models is based on the mutual inhibitory connections between early-I and dec-E and adaptive properties of the dec-E neuron. The difference between the two-phase models concerns the mechanism for ramp firing patterns of E2 neurons resulting either from the intrinsic neuronal properties of the E2 neuron or from disinhibition from the adapting dec-E neuron. The key element of the three-phase models is the pre-I neuron, which acts as the expiratory off-switching neuron. The three-phase models differ by the mechanisms used for termination of expiration and for the ramp firing patterns of E2 neurons. Additional CRPG models were developed employing a dual switching neuron that generates two bursts per respiratory cycle to terminate both inspiration and expiration. Although distinctly different each model generates a stable respiratory rhythm and shows physiologically plausible firing patterns of respiratory neurons with and without PSR feedback. Using our models, we analyze the roles of different respiratory neuron types and their interconnections for the respiratory rhythm and pattern generation. We also investigate the possible roles of intrinsic biophysical properties of different respiratory neurons in controlling the duration of respiratory phases and timing of switching between them. We show that intrinsic membrane properties of respiratory neurons are integrated with network properties of the CRPG at three hierarchical levels: at the cellular level to provide the specific firing patterns of respiratory neurons (e.g., ramp firing patterns); at the network level to provide switching between the respiratory phases; and at the systems level to control the duration of inspiration and expiration under different conditions (e.g., lack of PSR feedback).     

Sulfonamides and trimethoprim

BACKGROUND: Respiratory symptoms are important in panic disorder for frequency and intensity. Patients with this disorder are often chronic hyperventilators, and inhalation of carbon dioxide is a strong panicogenic stimulus. We tested the hypothesis of whether respiratory parameters may be used as indicators of the course of panic disorder during its treatment with fluoxetine. METHODS: Nine patients with panic disorders, previously shown to panic in response to intravenously administered lactate, and 10 control subjects underwent the Read rebreathing test by a 5-min inhalation of a 7% CO2/93% O2 mixture before and after 1 month of fluoxetine treatment. RESULTS: At baseline, patients differed from controls for higher percent value of expiratory reserve volume/vital capacity ratio and ventilatory response. Eight of the 9 patients had panic in response to the CO2 challenge. After fluoxetine, respiratory parameters decreased significatively, and only 3 patients remained hypercarbic challenge responders. CONCLUSIONS: The carbon dioxide challenge may represent a useful tool to evaluate the individual respiratory set, which may be a marker of the vulnerability to panic attack. Assessment of respiratory parameters may represent a biological marker to measure the efficacy of antipanic treatment.     

Extension of Poroelastic Analysis to Double-Porosity Materials: New Technique in Microgeomechanics

Double-porosity materials were introduced as models for oil and gas reservoirs having both storage and transport porosities, and were at first usually treated as static mechanical systems in order to study the flow patterns of fluids during reservoir pump down. Because fluid withdrawal normally increases the effective stress acting on the reservoir, it also turns out to be important to study the geomechanics of the reservoir and how changing fluid pressure affects the solid compaction and fluid permeability of these systems. At the microscale, the mechanical properties of the solid constituents and their distribution in space determine the overall macromechanics of the reservoir system. For systems containing two porosities and two types of solid constituents, exact results for all but one (which may be taken as the overall drained bulk modulus of the system) of the mechanical constants can be derived when the constitutents’ properties are known using methods developed in this paper. For multiporosity systems, closure of the system of equations remains an open question, although it is clear that the system can always be closed by the addition of further macroscale measurements.     

Horizontal Sigma Coordinate System for River-Flow Models

Because of complicated channel geometry, horizontal coordinates are important in accurate and efficient computations of river flow. We propose a simplified horizontal coordinate system for river-flow simulation, referred to here as a horizontal sigma coordinate system that uses boundary-fitted grids along river channels like a generalized curvilinear coordinate system, without losing the simplicity of Cartesian or orthogonal curvilinear coordinate systems. The proposed approach is based on a sigma coordinate system. The depth-averaged continuity and momentum equations for horizontal two-dimensional fluid motion in the Cartesian and orthogonal curvilinear coordinate systems are transformed to those in the horizontal sigma coordinate system. The form of the transformed continuity and momentum equations in the proposed system is a fairly minor modification of the form of the equations for the Cartesian and orthogonal curvilinear coordinate systems. Computational results for a straight open-channel flow with a narrow pass indicate that the horizontal sigma coordinate system is as numerically accurate as the generalized curvilinear coordinate system and that the CPU times required to calculate the horizontal sigma and Cartesian coordinate systems are comparable. We also computed flood flow in an actual river using the numerical models based on the horizontal sigma, orthogonal curvilinear, and generalized curvilinear coordinate systems. The results show that the horizontal sigma coordinate system may dramatically reduce the numerical error generated in the orthogonal curvilinear coordinate system. These facts demonstrate that the horizontal sigma coordinate system is a promising tool for numerical approximation of flow in the horizontal direction that is computationally efficient and numerically accurate.     

Tidal expired airflow patterns in adults with airway obstruction

Earlier studies have shown that time and flow indices derived from tidal expiratory flow patterns can be used to distinguish the severity of airway obstruction. This study was designed to address two aspects of tidal expiratory flow patterns: 1) how do expiratory flow patterns differ between subjects with normal and obstructed airways; and 2) can a sensitive index of airway obstruction be derived from these pattern differences? Tidal expiratory flow patterns from 66 adult subjects with varying degrees of airway obstructive disease with a forced expiratory volume in one second (FEV1) of 20-121% predicted were examined. In each subject, the expired flow pattern from each consecutive breath was scaled and then averaged together to create a single expired pattern. A detailed examination of the scaled flow patterns in 12 subjects (six with normal airways and six with airway obstruction) showed that the shape of the post-peak expiratory flow portion was different in the subjects with airway obstruction. A slope index, S, was derived from the scaled patterns and found to be sensitive to the severity of airway obstruction, correlating with FEV1 (% pred) with r2=0.74 (p<0.05, n=57). The S index also correlated (r2=0.36, p<0.05, n=47) with the functional residual capacity (FRC) (% pred) which was >100% in subjects with severe airway obstruction and lung overinflation. In subjects with normal airways, three further airflow patterns could be distinguished, which were different from the patterns seen in subjects with the severest airway obstruction. Scaled flow patterns from tidal expiration collected from uncoached subjects, can be used to derive an index of airway obstruction.     

Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal human lung

A model integrating airway/lung mechanics, pulmonary blood flow, and gas exchange for a normal human subject executing the forced vital capacity (FVC) maneuver is presented. It requires as input the intrapleural pressure measured during the maneuver. Selected model-generated output variables are compared against measured data (flow at the mouth, change in lung volume, and expired O2 and CO2 concentrations at the mouth). A nonlinear parameter-estimation algorithm is employed to vary selected sensitive model parameters to obtain reasonable least squares fits to the data. This study indicates that 1) all three components of the respiratory model are necessary to characterize the FVC maneuver; 2) changes in pulmonary blood flow rate are associated with changes in alveolar and intrapleural pressures and affect gas exchange and the time course of expired gas concentrations; and 3) a collapsible midairway segment must be included to match airflow during a forced expiration. Model simulations suggest that the resistances to airflow offered by the collapsible segment and the small airways are significant throughout forced expiration; their combined effect is needed to adequately match the inspiratory and expiratory flow-volume loops. Despite the limitations of this lumped single-compartment model, a remarkable agreement with airflow and expired gas concentration measurements is obtained for normal subjects. Furthermore, the model provides insight into the important dynamic interactions between ventilation and perfusion during the FVC maneuver.     

Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia

The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.