Airway CO2 Research Articles

Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine.

Respiratory quotient, the ratio of CO2 production to oxygen consumption (VO2), is principally affected by the fuel source used for aerobic metabolism. Since the respiratory quotient, VO2, and CO2 production cannot be directly measured easily, indirect calorimetry is commonly used to determine the value of these variables at the airway level (i.e., airway respiratory quotient, airway VO2, and airway CO2 production). However, under nonsteady-state conditions, a variety of phenomena can alter the relationship between true metabolic activity and measurements determined by indirect calorimetry. During exercise, for example, airway respiratory quotient increases as anaerobic threshold is reached because of the disproportionate increase in airway CO2 production that results from the CO2 liberated through the buffering of excess hydrogen ions by bicarbonate. We hypothesized that hemorrhage and reinfusion might change airway respiratory quotient in a consistent manner as shock is produced and reversed. Prospective laboratory study. University animal laboratory. Eight pigs (25 +/- 2 [SD] kg), anesthetized with fentanyl and relaxed with pancuronium bromide, and mechanically ventilated on room air. The animals were sequentially hemorrhaged and then autotransfused while metabolic and hemodynamic measurements were obtained, using continuous indirect calorimetry and continuous applications of the Fick principle. Hemoglobin, arterial lactate concentration, and blood gases for calibration were measured serially. Analysis of variance was used to compare various periods in time. Between baseline and peak hemorrhage, and between peak hemorrhage and postreinfusion, all of the following variables changed significantly (p < .05): airway VO2 (baseline 6.4 +/- 0.9 mL/min/kg, peak hemorrhage 3.9 +/- 0.6 mL/min/kg, postreinfusion 7.0 +/- 1.4 mL/min/kg); airway CO2 production (baseline 5.5 +/- 0.9 mL/min/kg, peak hemorrhage 4.5 +/- 0.9 mL/min/kg, postreinfusion 6.0 +/- 1.4 mL/min/kg); airway respiratory quotient (baseline 0.87 +/- 0.07, peak hemorrhage 1.16 +/- 0.07, postreinfusion 0.87 +/- 0.05); lactate concentration (baseline 2.4 +/- 1.2 mmol/L, peak hemorrhage 6.7 +/- 1.9 mmol/L, postreinfusion 5.1 +/- 2.0 mmol/L); and delta PCO2 (venous PCO2-PaCO2) (baseline 4.5 +/- 3.6 torr [0.6 +/- 0.5 kPa], peak hemorrhage 12.1 +/- 5.3 torr [1.6 +/- 0.7 kPa], postreinfusion 2.7 +/- 2.7 torr [0.4 +/- 0.4 kPa]). Airway respiratory quotient increases in hemorrhagic shock and decreases again as shock is reversed during reinfusion. This phenomenon appears related to the buffering of excess of hydrogen ion during hemorrhagic shock.

Intra-airway CO2 distribution during airway insufflation in ventilatory failure.

Low-flow intratracheal gas insufflation is known to be an effective means of providing partial ventilatory support in respiratory failure. We studied the effects of catheter position on intraluminal CO2 concentration profiles and gas transport resistance during intra-airway insufflation at 0.15 l.kg-1.min-1 in six anesthetized paralyzed mechanically hypoventilated dogs. The two positions of the distal tip of the insufflation catheter were 0.5 cm proximal to and 4.0 cm distal to the carina. Local airway CO2 concentrations were measured via a sampling catheter passed through the tracheobronchial tree. Resistance to gas transport was calculated from the measured data. Arterial PO2 and arterial PCO2 remained constant with carinal and bronchial insufflation. Distal positioning of the insufflation tip resulted in a redistribution of ventilation between the lungs, with the ipsilateral lung being relatively hyperventilated and the contralateral lung being relatively hypoventilated. Intraluminal CO2 concentrations were markedly reduced in the ipsilateral lung compared with the profile in the contralateral lung during fresh gas delivery into the main-stem bronchus. The region of peak transport resistance was found to be in the second-generation airways during carinal insufflation and in the fourth-generation airways with intrabronchial insufflation. We conclude that gas exchange during low-flow insufflation occurs by the same mechanisms responsible for CO2 elimination in constant-flow ventilation. Overall gas exchange is not affected by position of the jet catheter.

Long‐term facilitation of inspiratory intercostal nerve activity following carotid sinus nerve stimulation in cats.

1. Repeated carotid sinus nerve (CSN) stimulation evokes a serotonin-dependent long-term facilitation (LTF) of phrenic nerve activity in cats. To determine whether CSN stimulation-evoked LTF is a general property of spinal inspiratory motoneurones, phrenic and inspiratory internal intercostal (IIC) nerve activities were recorded in nine cats (eight anaesthetized; one decerebrate), which were vagotomized, paralysed, thoracotomized and ventilated with O2; airway CO2 was controlled by means of of a servo-respirator. Baseline conditions were established by setting the arterial CO2 pressure (Pa,CO2) at approximately 2 mmHg above the threshold for IIC activity. One CSN was stimulated (3 times threshold, 25 Hz, 0.5 ms duration) with five (2 min) trains, each separated by 5 min. 2. The peak integrated phrenic activity was elevated by 33% whereas IIC activity was elevated by 226% above baseline, 90 min post-stimulation (P < 0.05). The results were similar when expressed as a percentage of the maximal neural activities (elicited by combined hypercapnia and CSN stimulation), although differences between the nerves were less pronounced. The burst frequency was not change following stimulation. 3. In five additional cats that were pretreated with the serotonin receptor antagonist, methysergide maleate (0.5-1 mg kg-1, I.V.), the CO2 thresholds of the phrenic (12 mmHg) and IIC nerves (22 mmHg) were increased (P < 0.05), and LTF could not be elicited in either neurogram. 4. Successive CSN stimulation episodes evoked a previously undescribed phenomenon. Although the peak integrated phrenic activity was unchanged (90-95% of maximal), IIC activity increased progressively during successive stimulus episodes (66-90% of maximal; P < 0.05). However, after methysergide treatment, the initial stimulus-evoked phrenic response decreased to 58% of maximal and both neurograms exhibited progressive augmentation of the stimulus-evoked response. As stimulus-evoked augmentation does not require serotonin, it is independent of LTF. 5. We conclude that CSN stimulation-evoked LTF of IIC activity exceeds that of phrenic activity. Since LTF requires the neuromodulator serotonin and is expressed predominantly by changes in burst pattern formation versus rhythm generation, serotonin may exert a greater influence on IIC relative to phrenic respiratory motor output. A unique mechanism is described whereby successive CSN stimulus episodes cause progressively increasing responses in both neurograms.

A breathing circuit alarm system based on neural networks

The objectives of our study were (1) to implement intelligent respiratory alarms with a neural network; and (2) to increase alarm specificity and decrease false-alarm rates compared with current alarms. We trained a neural network to recognize 13 faults in an anesthesia breathing circuit. The system extracted 30 breath-to-breath features from the airway CO2, flow, and pressure signals. We created training data for the network by introducing 13 faults repeatedly in 5 dogs (616 total faults). We used the data to train the neural network using the backward error propagation algorithm. In animals, the trained network reported the alarms correctly for 95.0% of the faults when tested during controlled ventilation, and for 86.9% of the faults during spontaneous breathing. When tested in the operating room, the system found and correctly reported 54 of 57 faults that occurred during 43.6 hr of use. The alarm system produced a total of 74 false alarms during 43.6 hr of monitoring. Neural networks may be useful in creating intelligent anesthesia alarm systems.

The effects of airway CO2 and cooling on ventilation and upper airway resistance in anaesthetized rats.

Upper airway (UA) luminal CO2 modulates the activity of superior laryngeal nerve afferents (Boushey et al, 1974, Bradford et al, 1990) and affects breathing and UA muscle activity through a superior laryngeal nerve-mediated reflex (Nolan et al, 1990) Therefore, airway CO2 may influence the patency of the UA, especially in obstructive apnoea and other circumstances of altered UA CO2 concentration However, the effects of UA luminal CO2 on airway patency have not been studied

The effects of airway CO2 on laryngeal pressure, 'drive' and cold receptors in spontaneously breathing cats.

We have previously demonstrated that the activity of superior laryngeal nerve afferents is affected when CO2 is applied continuously to the laryngeal lumen using an isolated, artificially ventilated upper airway (UA) preparation in anaesthetized, paralysed cats (Bradford, et al., 1990a).KeywordsLaryngeal NerveRespiratory CycleSuperior Laryngeal NervePentobarbitone SodiumNerve DischargeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The effects of laryngeal CO2 and cooling on ventilation and laryngeal resistance in the anaesthetized rat.

Superior laryngeal nerve afferent activity is altered by upper airway CO2 (Bradford et al, 1990) and cold air (Sant’ Ambrogio et al, 1986) Ventilation and upper airway muscle activity are also influenced by upper airway CO2 (Nolan et al, 1990) and cold air (Ukabam et al, 1992) through a superior laryngeal nerve-dependent reflex These responses may be important in the regulation of upper airway patency The larynx is a major site of upper airway resistance but the effects of CO2 on laryngeal resistance have not been studied The purpose of the present investigation is to compare the effects of laryngeal cooling and CO2 on ventilation and laryngeal resistance in anaesthetized rats

Practical CO2 monitoring in anaesthesia

The special value of airway CO2 monitoring is its potential to alert the clinician about a range of critical complications of anaesthesia. As a detector of several of these complications, it is both sensitive and rapidly responsive — but not specific and therefore not diagnostic by itself. Accordingly, the findings of airway CO2 monitoring (like those of all other monitoring systems)must always be interpreted in the context of clinical observation of the patient and other pertinent information.

Potentiation of exercise ventilatory response by airway CO2 and dead space loading.

We examined the effects of different modes of airway CO2 load on the ventilation-CO2 output (VE-VCO2) relationship during mild to moderate exercise. Four young and three older male subjects underwent incremental steady-state treadmill exercise while breathing a mixture of CO2 in O2 (CO2 loading) or 100% O2 with and without a large external dead space [DS loading and control (C), respectively]. During DS loading, the elevated arterial PCO2 (PaCO2) remained constant from rest to mild exercise and began to increase only at higher work rates. To achieve similar chemical drive, the same PaCO2 levels were established during CO2 loading by external PCO2 forcing. In the young group, CO2 loading resulted in a steepening of the VE-VCO2 relationship compared with C, whereas in the older group the reverse pattern was found. DS loading resulted in a consistent increase in the VE-VCO2 slope compared with C and CO2 loading [39.1 +/- 5.6 (mean +/- SD) vs. 24.9 +/- 5.0 and 26.7 +/- 4.4, respectively] in all subjects. The difference in potentiation of VE-VCO2 by CO2 and DS loading was not due to differences in mean chemical drive or changes in breathing pattern. Thus changes in the profile of airway CO2 influx may have an independent influence on ventilatory CO2-exercise interaction. Peripheral chemoreceptors mediation, although important, is not obligatory for this behavior.

Effect of changing venoarterial pH difference on in vivo arterial pH

Plasma pH has been postulated to change slowly in blood leaving the pulmonary capillaries because of the uncatalyzed dehydration of CO2. If so, there could be a difference between in vivo and in vitro arterial pH, the magnitude of which would be dependent on the venoarterial pH difference (v-aDpH). We tested this hypothesis in anesthetized dogs by changing v-aDpH by airway CO2 loading and by comparing arterial pH measured in vivo by a rapidly responding intravascular pH electrode with that measured in vitro by a conventional glass electrode. Using a multiple regression analysis, we found a small but significant contribution of venous pH to in vivo arterial pH, with a regression coefficient of 0.0718 (P less than 0.0001), suggesting a postcapillary increase of in vivo arterial pH. When carbonic anhydrase was inhibited by the administration of acetazolamide, the effect of venous pH on arterial pH was abolished, and a unique relationship between in vivo and in vitro arterial pH was established (regression coefficient 1.02; P greater than 0.05, comparison with unity). These results could be accounted for in a computer simulation of gas exchange among alveolus, plasma, and erythrocyte. We conclude that there exists a small but measurable postcapillary increase in arterial pH.

Changes in upper airway resistance during progressive normocapnic hypoxia in normal men

The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Vagal amplification of phrenic nerve activity at different levels of ventilation in spontaneously breathing cats

The vagal amplification of phrenic nerve activity (APHR) was studied as a function of minute ventilation (VE) in 12 spontaneously breathing, anaesthetized cats. Increasing levels of VE were obtained by repeated venous administrations of 2,4-dinitrophenol. The APHR was obtained from the ratio of the phrenic nerve activities in a normal and in an occluded breath. The APHR is thought to be mediated by slowly and/or rapidly adapting stretch receptors. Because airway CO2 may inhibit the discharge of these receptors, we also investigated the influence on APHR of adding 1% and 2% by volume of CO2 to inspired gas. The results showed that an increase in VE had no influence on APHR. The values of APHR ranged from 0.95 to 1.31 and were on average 1.08. Low levels of CO2 in inspired gas did not influence APHR. Our findings suggest that the vagal amplification of central inspiratory output as determined from phrenic nerve activity has a constant gain and it seems to play a relatively unimportant role in sustaining hyperpnoeic breathing.

Helium-Oxygen Mixtures in Intubated Patients with Status Asthmaticus and Respiratory Acidosis

Seven patients with status asthmaticus intubated for respiratory failure who had elevated airway pressures and persistent respiratory acidosis were successfully ventilated using a mixture of 60 percent helium and 40 percent oxygen. All patients experienced a rapid reduction in airway pressures, CO2 retention, and resolution of acidosis while breathing a helium-oxygen mixture. There were no untoward effects. Helium-oxygen mixtures improve ventilation by reducing the Reynolds number and reducing density dependent resistance. Helium's beneficial effects are due to its high kinematic viscosity, high binary diffusion coefficient for CO2, and high diffusivity. Helium-oxygen mixtures should be considered for use in mechanically ventilated asthmatics with respiratory acidosis who fail conventional therapy.

Olfactory receptor response to CO2 in bullfrogs

In vivo electrophysiological recordings of olfactory receptor cells of the bullfrog (Rana catesbeiana) exhibit a receptor response to CO2 concentrations as low as 0.5%. The amplitude of the electroolfactogram (EOG) increased with an increase in the CO2 concentration delivered to the olfactory epithelium. Likewise, there was a significant increase in the decay time (time from 90 to 10% peak EOG amplitude) with an increase in CO2. The EOG rise time (time from 10 to 90% peak EOG amplitude) and the EOG response latency (time from beginning of CO2 pulse to beginning of EOG response) significantly decreased, whereas the plateau time (time from 90% rising phase to 90% falling phase of the peak EOG amplitude) was not significantly altered by an increase in CO2. These results indicate that low concentrations of CO2, below normal end expiratory CO2 concentrations, stimulate olfactory receptor cells. These results support our proposal that the ventilatory depression observed in response to upper airway CO2 in reptiles and amphibians is mediated by CO2-sensitive olfactory receptor cells.

The responses of superior laryngeal nerve afferent fibres to laryngeal airway CO2 concentration in the anaesthetized cat

In anaesthetized cats, the isolated, in situ, larynx was subjected to a simulated respiratory cycle and the responses of fifty-six superior laryngeal nerve (SLN) afferent fibres to respiration-related stimuli were examined during changes in the fractional CO2 concentration of the laryngeal airway (Faw, CO2). Sensory SLN fibres which displayed low rates of discharge when the larynx was unventilated (quiescent fibres) and which responded to negative laryngeal airway pressure were excited by elevations in Faw, CO2 whereas quiescent fibres responsive to positive laryngeal pressure were inhibited by the same procedure. We propose that changes in airway CO2 levels may play a role in maintaining upper airway patency, especially during sleep.

The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat

In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea.

Temperature effects on pulmonary receptor responses to airway pressure and CO2 in Alligator mississippiensis

The effects of body temperature (Tb) on pulmonary stretch receptor (PSR) and CO2-sensitive intrapulmonary chemoreceptor (IPC) response characteristics may have important effects on ventilatory control in reptiles. In this study, three questions were addressed: (1) what are the effects of Tb on PSR and IPC responses to airway pressure (Paw) and lung CO2 (PCO2); (2) what are the effects of acute (<12 h) vs chronic (>1 week) changes in Tb on both receptor groups; and (3) can predicted changes in the fractional dissociation of imidazole (αim), calculated via independent changes in Tb and PCO2, explain the CO2-sensitivity of either IPC or PSR? Single fiber PSR and IPC resonses to Paw, PCO2 and Tb were determined in 11 anesthetized Alligator mississippiensis (pentobarbital; 30 mg/kg), acclimated at 20°C(N = 5) or at 30°C (N = 6). PSR activity increased as Paw increased at both Tb, but PSR activity and sensitivity to Paw were lower at 20°C. The average Q10 was 2.1. Increasing inhaled CO2 from 1 to 7% decreased PSR activity by 27 ± 6% at 20°C and 18 ± 5% at 30°C. IPC activity decreased as PCO2 increased at both Tb, but IPC activity and sensitivity were reduced at 20°C. The average Q10 was 3.2. Increasing Paw from 2 to 10 cm H2O had inconsistent effects on IPC activity. There were no differences between the effects of acute or chronic changes in Tb on either PSR or IPC responses. Predicted changes in αim could not explain the CO2-sensitivity of either IPC or PSR. We conclude that PSR and IPC adapt rapidly to Tb changes. The larger Q10 of IPC suggests that the relative role of IPC vs PSR in ventilatory control may be greater at elevated body temperatures.

A BREATHING CIRCUIT ALARM SYSTEM BASED ON NEURAL NETWORKS

Objective. The objectives of our study were (1) to implement intelligent respiratory alarms with a neural network; and (2) to increase alarm specificity and decrease false-alarm rates compared with current alarms.Methods. We trained a neural network to recognize 13 faults in an anesthesia breathing circuit. The system extracted 30 breath-to-breath features from the airway CO2, flow, and pressure signals. We created training data for the network by introducing 13 faults repeatedly in 5 dogs (616 total faults). We used the data to train the neural network using the backward error propagation algorithm.Results. In animals, the trained network reported the alarms correctly for 95.0% of the faults when tested during controlled ventilation, and for 86.9% of the faults during spontaneous breathing. When tested in the operating room, the system found and correctly reported 54 of 57 faults that occurred during 43.6 hr of use. The alarm system produced a total of 74 false alarms during 43.6 hr of monitoring.Conclusion. Neural networks may be useful in creating intelligent anesthesia alarm systems.

Effect of upper airway CO2 pattern on ventilatory frequency in tegu lizards

Nasal CO2-sensitive receptors are reported to depress ventilatory frequency in several reptilian species in response to constant low levels of inspired CO2. The purpose of this study was to determine the influence of phasic patterns of CO2 in the upper airways on ventilation. Awake lizards (Tupinambis nigropunctatus) breathed through an endotracheal tube from an isolated gas source. A second gas mixture was forced at constant flow into the external nares. A concentration of 4% CO2 was intermittently pulsed through the nares in a square-wave pattern with a frequency of 60, 12, 6, 4.2, 1.8, and 0.6 cycles/min. Concentrations of 2, 3, 4, and 6% CO2 were also pulsed through the nares at 12 cycles/min and compared with sustained levels of 1, 1.5, 2, and 3%. Additionally, 0 or 3% CO2 was forced through the upper airways with a servo system designed to mimic normal ventilatory flow and gas concentrations. No changes in breathing pattern were noted during any of the pulsing protocols, although a significant breathing frequency depression was present with sustained levels of CO2 of comparable mean concentrations. We conclude that ventilatory control is selectively responsive to sustained levels of environmental CO2 but not to phasic changes in upper airway CO2 concentration.

High-frequency ventilation-induced apnea: interaction of frequency, volume, FRC, and CO2

Apnea is often observed during high-frequency oscillatory ventilation (HFOV). This study on anesthetized dogs varied the oscillator frequency (f) and determined the stroke volume (SV) at which apnea occurred. Relaxation functional residual capacity (FRC) and the eupneic breathing end-tidal CO2 level were held constant. Airway pressure and CO2 were measured from a side port of the tracheostomy cannula. An arterial cannula was inserted for blood gas analysis. Diaphragm electromyogram (EMG) was recorded with bipolar electrodes. Apnea was defined as the absence of phasic diaphragm EMG activity for a minimum of 60 s. During HFOV, SV was increased at each f (5-40 Hz) until apnea occurred. The apnea inducing SV decreased as f increased. SV was minimal at 25-30 Hz. Frequencies greater than 30 Hz required increased SV to produce apnea. The f-SV curve was defined as the apneic threshold. Increased FRC resulted in a downward shift (less SV at the same f) in the apneic threshold. Elevated CO2 caused an upward shift (more SV at the same f) in the apneic threshold. These results demonstrate that the apnea elicited by HFOV is dependent on the interaction of oscillator f and SV, the FRC, and CO2.