Control of breathing in patients with limb girdle dystrophy: a controlled study.

BACKGROUND--In patients with limb girdle dystrophy the relative contribution of peripheral factors (respiratory muscle weakness, and lung and/or airway involvement) and central factors (blunted and/or inadequate chemoresponsiveness) in respiratory insufficiency has not yet been established. To resolve this, lung volumes, arterial blood gas tensions, respiratory muscle strength, breathing pattern and neural respiratory drive were investigated in a group of 15 patients with limb girdle dystrophy. An age-matched normal group was studied as a control. METHODS--Respiratory muscle strength was assessed as an arithmetic mean of maximal inspiratory (MIP) and expiratory (MEP) pressures. Breathing pattern was evaluated in terms of volume (ventilation VE, tidal volume VT) and time (respiratory frequency Rf, inspiratory time TI, expiratory time TE) components of the respiratory cycle. Neural respiratory drive was assessed as the mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1) and electromyographic activity (EMG) of the diaphragm (EMGd) and the intercostal parasternal (EMGp) muscles. In 10 of the 15 patients the responses to carbon dioxide (PCO2) stimulation were also evaluated. RESULTS--Most patients exhibited a moderate decrease in vital capacity (VC) (range 37-87% of predicted), MIP (range 23-84% of predicted), and/or MEP (range 13-41% of predicted). The arterial carbon dioxide tension (PaCO2) was increased in three patients breathing room air, while PaO2 was normal in all. Compared with the control group Rf was higher, and VT, TI and TE were lower in the patients. EMGd and EMGp were higher whilst VT/TI and P0.1 were normal in the patients. Respiratory muscle strength was inversely related to EMGd and EMGp. PaCO2 was found to relate primarily to VC and duration of illness, but not to respiratory muscle strength. During hypercapnic rebreathing delta VE/delta PCO2, delta VT/delta PCO2, and delta P0.1/delta PCO2 were lower than normal, whilst delta EMGd/delta PCO2 and delta EMGp/delta PCO2 were normal in most patients. A direct relation between respiratory muscle strength and delta VT/delta PCO2 was found. CONCLUSIONS--The respiratory muscles, especially expiratory ones, are weak in patients with limb girdle dystrophy. Reductions in respiratory muscle strength are associated with increased neural drive and decreased ventilatory output (delta VT/delta PCO2). The decrease in VC, together with the duration of disease, influence PaCO2. VC is a more useful test than respiratory muscle strength for following the course of limb girdle dystrophy.     

Tidal expiratory flow patterns in airflow obstruction.

Tidal expiratory flow pattern was analysed in 99 subjects with a view to assessing it as a quantitative measurement of airflow obstruction. Fifteen normal volunteers, nine patients with dyspnoea referred for investigation in whom airway resistance was within normal limits, 24 patients with restrictive lung disorders, and 51 patients with airway obstruction were studied. The expiratory flow pattern against time had a quadrilateral configuration in airway obstruction, which differed from the more sinusoidal form that is seen in subjects without airflow obstruction. The rapid rise to tidal peak flow was analysed in two ways, percentage of volume expired at tidal peak flow (delta V/V) and percentage of expiratory time to tidal peak flow (delta t/t). Both these indices correlated significantly with conventional measurements of airway obstruction. The pattern of expiratory flow in airflow obstruction during quiet breathing resembles that of a forced expiratory maneuver at similar lung volumes. In some cases this may be caused by dynamic compression occurring during tidal breathing. In others, the pattern may result from the static recoil of the lung being permitted to drive flow freely in expiration, rather than being braked by postinspiratory contraction of inspiratory musculature.     

Effect of doxapram on control of breathing in cats.

The effects of doxapram infusion (0.25 mg.kg-1. min-1) were studied in cats anaesthetized with pentobarbitone (35 mg . kg-1 intraperitoneally). Cats were studied breathing 50 per cent oxygen and the responses to two concentrations of inspired carbon dioxide were measured. Doxapram infusion increased pulmonary ventilation by increasing both tidal volume and respiratory frequency, and also caused increases in the volume inspired in the first 0.5 second after the onset of an inspiration (V0.5) and the pressure generated in the airway 0.5 second after the onset of an inspiration when the airway had been occluded (P degrees 0.5). V 0.5, P degrees 0.5 and the mean inspiratory flow rate (VT/VI) were essentially equivalent indices of inspiratory drive. Doxapram infusion did not alter the effective impedance of the respiratory system (P degrees 0.5/V 0.5). Doxapram infusion increased the ventilatory response to carbon dioxide. The slope of the ventilatory response to carbon dioxide was increased and the response line was shifted to the left. We conclude that the increase in pulmonary ventilation caused by doxapram infusion is due almost entirely to increased inspiratory neuromuscular drive (P degrees 0.5).     

Effect of ventilatory settings on accuracy of cardiac output measurement using partial CO(2) rebreathing.

BACKGROUND: Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO(2)) rebreathing. Because this technique uses CO(2) rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement. METHODS: The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (V(T)) of 12 ml/kg; (2) volume-controlled ventilation with V(T) of 6 ml/kg; (3) pressure-controlled ventilation with V(T) of 12 ml/kg; (4) pressure-controlled ventilation with V(T) of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with V(T) set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO(2) rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis. RESULTS: When VT was set at 12 ml/kg, cardiac output with the CO(2) rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO(2) rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO(2) rebreathing technique overestimated cardiac output. CONCLUSIONS: Although cardiac output was underreported at small VT values, cardiac output measured by the CO(2) rebreathing technique correlates fairly with that measured by the thermodilution method.     

Breathing pattern and carbon dioxide retention in severe chronic obstructive pulmonary disease.

BACKGROUND: The factors leading to chronic hypercapnia and rapid shallow breathing in patients with severe chronic obstructive pulmonary disease (COPD) are not completely understood. In this study the interrelations between chronic carbon dioxide retention, breathing pattern, dyspnoea, and the pressure required for breathing relative to inspiratory muscle strength in stable COPD patients with severe airflow obstruction were studied. METHODS: Thirty patients with COPD in a clinically stable condition with forced expiratory volume in one second (FEV1) of < 1 litre were studied. In each patient the following parameters were assessed: (1) dyspnoea scale rating, (2) inspiratory muscle strength by measuring minimal pleural pressure (PPLmin), and (3) tidal volume (VT), flow, pleural pressure swing (PPLsw), total lung resistance (RL), dynamic lung elastance (ELdyn), and positive end expiratory alveolar pressure (PEEPi) during resting breathing. RESULTS: Arterial carbon dioxide tension (PaCO2) related directly to RL/PPLmin, and ELdyn/PPLmin, and inversely to VT and PPLmin. There was no relationship between PaCO2 and functional residual capacity (FRC), total lung capacity (TLC), or minute ventilation. PEEPi was similar in eucapnic and hypercapnic patients. Expressing PaCO2 as a combined function of VT and PPLmin (stepwise multiple regression analysis) explained 71% of the variance in PaCO2. Tidal volume was directly related to inspiratory time (TI), and TI was inversely related to the pressure required for breathing relative to inspiratory muscle strength (PPLsw, %PPLmin). There was an association between the severity of dyspnoea and both the increase in PPLsw (%PPLmin) and the shortening in TI. CONCLUSIONS: The results indicate that, in stable patients with COPD with severe airflow obstruction, hypercapnia is associated with shallow breathing and inspiratory muscle weakness, and rapid and shallow breathing appears to be linked to both a marked increase in the pressure required for breathing relative to inspiratory muscle strength and to the severity of the breathlessness.     

Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2 Rebreathing

Background: Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO2) rebreathing. Because this technique uses CO2 rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement.

Methods: The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (VT) of 12 ml/kg; (2) volume-controlled ventilation with VT of 6 ml/kg; (3) pressure-controlled ventilation with VT of 12 ml/kg; (4) pressure-controlled ventilation with VT of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with VT set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO2 rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis.

Results: When VT was set at 12 ml/kg, cardiac output with the CO2 rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO2 rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO2 rebreathing technique overestimated cardiac output.     

Fresh gas flow in coaxial Mapleson A and D circuits during spontaneous breathing

In a lung model simulating spontaneously breathing halothane anaesthesia, the rebreathing characteristics of the coaxial Mapleson A (Lack circuit) and D (Bain circuit) systems were tested. Using decreasing fresh gas flows (VF), the end-tidal carbon dioxide fraction (FACO2) was monitored and the point of rebreathing (R.P.) detected. The effects of changes in minute volume (VE), dead-space to tidal volume ratio (VD/VT) and carbon dioxide elimination (VCO2) were studied. The effect of increased tidal volumes (VT) on FACO2 was investigated for some different fresh gas flows (VF). The VF/VE ratio for R.P. in the Bain circuit was approximately 2 and in the Lack circuit 0.88. In both circuits an increase in VE and a decrease in the VD/VT ratio resulted in higher demands on VF if rebreathing was to be avoided. The latter effect was much more pronounced in the Lack circuit. In neither system did any changes in VCO2 affect the rebreathing characteristics. The conclusion was drawn that the Lack system is a much better choice concerning the fresh gas flows for anaesthesia with spontaneous breathing than the Bain system. It was also concluded that the fresh gas flows recommended by Humphrey for the Lack system (i.e. 51 ml X min-1 X kg b.w.-1) and by the manufacturers for the Bain system (i.e. 100 ml X min-1 X kg b.w.-1) are inadequate and should be increased if a considerable degree of rebreathing is to be avoided.     

Histamine induced changes in breathing pattern may precede bronchoconstriction in selected patients with bronchial asthma.

BACKGROUND--In asthmatic patients methacholine or histamine challenge may result in more rapid and shallow breathing. Bronchoconstriction can also be associated with changes in the pattern of breathing. However, few studies, particularly in patients with asthma, have investigated the possibility that changes in the pattern of breathing may precede the onset of bronchoconstriction. METHODS--Eight subjects were selected from 34 consecutive asthmatic patients who had previously exhibited a significant increase in respiratory frequency (Rf) and decrease in tidal volume (VT) accompanying a 20% or greater fall in FEV1 during a histamine bronchial provocation test. These patients also had bronchial hyperresponsiveness (histamine PC20FEV1 0.1-0.25 mg/ml). VT, Rf, and the ratio of VT to Rf were evaluated breath by breath under control conditions and two minutes after inhalation of either saline or each of a series of progressively increasing concentrations of histamine. In each subject the coefficient of variation (CV) for each breathing pattern variable was calculated under control conditions and at each histamine concentration over at least 30-40 breaths. For FEV1, VT and Rf step by step coefficients of variation were averaged and the mean (2SD) CV was considered to represent a threshold value in each patient. RESULTS--Histamine challenge resulted in increased Rf and Rf/VT, and decreased VT and FEV1. In all but one subject change in Rf and Rf/VT beyond the threshold value preceded change in FEV1 beyond the threshold value. The threshold concentrations of histamine for Rf and Rf/VT did not correlate with the threshold value for FEV1. CONCLUSIONS--In selected asthmatic patients a change in breathing pattern occurs prior to a change in FEV1. These results suggest that narrowing of the airways, in terms of decrease in FEV1, does not play a major part in the initial change in the pattern of breathing. This may be caused by direct stimulation of vagal airway receptors.     

Effects of an external resistance on maximum flow in chronic obstructive lung disease: implications for recognition of coincident upper airway obstruction.

To determine how the presence of generalised airflow limitation due to chronic obstructive lung disease affects the recognition of simulated upper airway obstruction, a study was carried out in 12 patients (mean (SD) age 57 (7) years) with chronic obstructive lung disease (FEV1% predicted 53 (22), range 21-70) and 12 matched control subjects. Patients and control subjects performed maximal inspiratory and expiratory flow-volume curves in a variable volume plethysmograph with and without upper airway obstruction simulated at the mouth with a series of polythene washers of internal diameter 4, 6, 8, 10, and 12 mm. In patients, as in normal subjects, peak expiratory flow (PEF) and maximum inspiratory flow at 50% of vital capacity (Vmax50) were more sensitive to upper airway obstruction than were FEV1 or maximum expiratory flow at 50% VC (VEmax50); but the reductions in all indices caused by simulated upper airway obstruction were smaller in the patients than in the controls. The fall in PEF (whether expressed in absolute units or as a percentages) consequent on severe (4 mm) upper airway obstruction became smaller with increasing severity of chronic obstructive lung disease. The subjects also produced flow-volume curves with and without 6 mm upper airway obstruction while breathing helium and oxygen (heliox). In both groups the effects of heliox on PEF and Vmax50 were increased when upper airway obstruction was simulated. It was confirmed that the functional recognition of upper airway obstruction is more difficult in patients with chronic obstructive lung disease than in normal subjects and this difficulty increases with severity of disease; an unusually large increase in PEF or Vmax50 while the patient is breathing heliox should raise the suspicion of coexisting upper airway obstruction, but such a pattern is not specific.     

Ventilatory drive and ventilatory response during rebreathing

Maranetra, N. and Pain, M. C. F. (1974). Thorax, 29, 578-581. Ventilatory drive and ventilatory response during rebreathing. The increase in inspiratory airway pressure generated against a transiently occluded airway during rebreathing is proposed as a simple index of ventilatory drive (ΔP/ΔPco₂). A study of this index in 12 normal subjects and 50 patients with chronic airways obstruction demonstrated no significant difference between normals and patients in ΔP/ΔPco₂ despite an overall reduction in the ventilatory response to carbon dioxide (ΔV̇e/ΔPco₂) in the patients. A significant association was demonstrated between the ventilatory response to carbon dioxide, ΔP/ΔPco₂ and the degree of airways obstruction. Patients with a low ΔP/ΔPco₂ showed greater hypoxaemia, hypercapnia, and polycythaemia than patients with a higher ΔP/ΔPco₂ for the same degree of airways obstruction.     

Fuzzy logic control of mechanical ventilation during anaesthesia

We have examined a new approach, using fuzzy logic, to the closed-loop feedback control of mechanical ventilation during general anaesthesia. This control system automatically adjusts ventilatory frequency (f) and tidal volume (VT) in order to achieve and maintain the end-tidal carbon dioxide fraction (FE'CO2) at a desired level (set-point). The controller attempts to minimize the deviation of both f and VT per kg body weight from 10 bpm and 10 ml kg-1, respectively, and to maintain the plateau airway pressure within suitable limits. In 30 patients, undergoing various surgical procedures, the fuzzy control mode was compared with human ventilation control. For a set-point of FE'CO2 = 4.5 vol% and during measurement periods of 20 min, accuracy, stability and breathing pattern did not differ significantly between fuzzy logic and manual ventilation control. After step-changes in the set-point of FE'CO2 from 4.5 to 5.5 vol% and vice versa, overshoot and rise time did not differ significantly between the two control modes. We conclude that to achieve and maintain a desired FE'CO2 during routine anaesthesia, fuzzy logic feedback control of mechanical ventilation is a reliable and safe mode of control.      

Pattern of breathing during exercise in patients with interstitial lung disease.

The responses to exercise were studied in 41 patients with pulmonary fibrosis, in whom vital capacity (VC) was reduced to 62% of predicted normal values. Maximum power output (POmax) was 53% predicted; there was a significant relationship between POmax and VC (r = 0.564). The maximum ventilation achieved during exercise was also related to VC (r = 0.614). Although arterial oxygen saturation (SaO2) fell by more than 5% in 13 of 31 patients, there was no relationship between either SaO2 at POmax or the exercise related fall in SaO2 and POmax. Heart rate responses were higher than normal predicted values in seven patients, all of whom showed a low POmax (36% predicted); this finding was due only in part to a fall in SaO2. The ventilatory response to exercise was within normal limits for the patients as a whole; those subjects with the lowest POmax showed relatively higher ventilatory responses to exercise but the difference was not significant. The pattern and timing of breathing was studied in 32 patients and compared with control subjects matched by sex, age, and size. Tidal volume (VT) was low in the patients; maximum VT was related to VC (r = 0.761), but at low values of VC VTmax was higher than in healthy subjects with comparable VC. The total breathing cycle time (Ttot) fell with progressive exercise in patients and controls; Ttot for a given ventilation was shorter in the patients. Inspiratory time (Ti) was shorter in patients than controls, as was Ti/Ttot. In most patients with diffuse pulmonary fibrosis exercise is limited by a reduced ventilatory capacity, despite the adoption of a short Ti and high inspiratory flow rate, both of which serve to optimise tidal volume and breathing frequency and presumably reduce both the force developed by inspiratory muscles and the sensation of breathlessness.     

Exercise responses in patients treated for pulmonary tuberculosis by thoracoplasty.

Twenty eight subjects (mean age 64 years) who had been treated for tuberculosis by thoracoplasty in the past performed an increasing work rate exercise test, from which maximum oxygen consumption (VO2max), ventilation and heart rate were measured. VO2max was significantly lower than predicted, being 0.75 l/min in 17 subjects, 1.0 l/min in 10, and 1.5 l/min in one. Only one subject achieved a heart rate of 85% of the predicted maximum. The ratio of heart rate to oxygen consumption (HR/VO2) and heart rate at standard interpolated submaximal levels of oxygen uptake at 0.75 l/min (heart rate 0.75) and 1.0 l/min (heart rate 1.0) were normal. VO2max correlated with ventilation at maximal exercise (VE max) (r = 0.87) and FEV1 (r = 0.47). It did not correlate with resting arterial oxygen or carbon dioxide tensions, FEV1, maximum inspiratory pressure, angle of scoliosis, or number of ribs resected. The relation between ventilation and oxygen consumption (VE/VO2) and VE at the submaximal levels of oxygen consumption of 0.75 l/min (VE 0.75) and 1.0 l/min (VE 1.0) were normal. In 10 subjects a plateau of breathing frequency (fmax) was reached, after which the increase in ventilation was achieved by a further increase in tidal volume (VT). These subjects showed significantly lower values for the forced expiratory ratio, VO2max, and VEmax than those with a normal relation between tidal volume and breathing frequency. VEmax was correlated with FEV1 (r = 0.61), FVC (r = 0.46), maximum VT (r = 0.55), change in VT (r = 0.52), fmax (r = 0.56), and change in breathing frequency (r = 0.72). These results indicate that exercise in patients treated for tuberculosis by thoracoplasty is limited by ventilatory capacity and that this is due to a reduction in both dynamic lung volumes and respiratory frequency.     

Pulmonary function for pectus excavatum at long-term follow-up

PURPOSE: The aim of this article was to assess whether and to what extent pulmonary function recovered to normal degree postoperatively and to investigate the changes in pulmonary function after surgical correction and the value of surgical correction. METHODS: A total of 27 patients who could be questioned and examined in person at the outpatient department of our hospital were included in this study. Of these patents, 24 were boys and 3 were girls. Their ages ranged from 3 to 16 years (mean, 8.67) at follow-up. The mean age at surgery was 4 years, and mean years of follow-up was 6.8. Pulmonary functional measurements included in vital capacity (VC), total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), RV-TLC ratio, maximal voluntary ventilation (MVV), force ventilatory capacity (FVC), forced expiratory volume in one second (FEV1), maximal midexpiratory flow curve (MMEF), maximal expiratory flow in 75% vital capacity (V75), maximal expiratory flow in 50% vital capacity (V50), maximal expiratory flow in 25% vital capacity (V25), and breathing reserve ratio (BR). RESULTS: TLC, FRC, MVV, MMEF, V75, and V50 values were not different from the normal values. IVC, FVC, FEV1, and V25 values were decreased significantly compared with the normal values. The RV and RV-TLC were high in 87.5% cases. CONCLUSIONS: Preoperative symptoms obviously improved after operation. There was little airway obstruction in the patients postoperatively. The patients with pectus excavatum should be operated on as soon as possible.     

Noninvasive cardiac output measurement using partial carbon dioxide rebreathing is less accurate at settings of reduced minute ventilation and when spontaneous breathing is present

BACKGROUND: Although evaluation of cardiac output by the partial carbon dioxide rebreathing technique is as accurate as thermodilution techniques under controlled mechanical ventilation, it is less accurate at low tidal volume. It is not clear whether reduced accuracy is due to low tidal volume or low minute ventilation. The effect of spontaneous breathing on the accuracy of partial carbon dioxide rebreathing measurement has not been fully investigated. The objectives of the current study were to investigate whether tidal volume or minute ventilation is the dominant factor for the accuracy, and the accuracy of the technique when spontaneous breathing effort is present. METHODS: The authors enrolled 25 post-cardiac surgery patients in two serial protocols. First, the authors applied three settings of controlled mechanical ventilation in random order: large tidal volume (12 ml/kg), the same minute ventilation with a small tidal volume (6 ml/kg), and 50% decreased minute ventilation with a small tidal volume (6 ml/kg). Second, when the patient recovered spontaneous breathing, the authors applied three conditions of partial ventilatory support in random order: synchronized intermittent mandatory ventilation-pressure support ventilation, pressure support ventilation with an appropriately adjusted rebreathing loop, and pressure support ventilation with the shortest available loop. After establishing steady state conditions, the authors measured cardiac output using both partial carbon dioxide rebreathing and thermodilution methods. The correlation between the data yielded by the two methods was determined by Bland-Altman analysis and linear regression. RESULTS: Cardiac output with the carbon dioxide rebreathing technique correlated moderately with that measured by thermodilution when minute ventilation was set to maintain normocapnia, regardless of tidal volumes. However, when minute ventilation was set low, the carbon dioxide rebreathing technique underreported cardiac output (y = 0.70x; correlation coefficient, 0.34; bias, -1.73 l/min; precision, 1.27 l/min; limits of agreement, -4.27 to +0.81 l/min). When there was spontaneous breathing, the correlation between the two cardiac output measurements became worse. Carbon dioxide rebreathing increased spontaneous tidal volume and respiratory rate (20% and 30%, respectively, during pressure support ventilation) when the rebreathing loop was adjusted for large tidal volume. CONCLUSIONS: During controlled mechanical ventilation, minute ventilation rather than tidal volume affected the accuracy of cardiac output measurement using the partial carbon dioxide rebreathing technique. When spontaneous breathing is present, the carbon dioxide rebreathing technique is less accurate and increases spontaneous tidal volume and respiratory rate.     

Response to tubular airway resistance in normal subjects and postoperative patients

Critically ill patients must often breathe spontaneously through an endotracheal tube that acts as a fixed inspiratory and expiratory tubular airway resistor. Although this practice is common, its effect on the pattern of breathing is not known. The mean breathing patterns of seven normal, healthy male subjects and eight male patients who had undergone upper abdominal surgery 2-4 days previously were studied breathing through a mouthpiece fitted in random order with a 5, 6, 7, 8, or 15 mm diameter (17 mm long) resistor. These diameters were selected because they simulate the pressure-flow relationships of adult endotracheal tubes. With the 15 mm aperture, the patients had a greater breathing frequency (f) than did the normal subjects (21 +/- 5 [SD] vs. 14 +/- 4 breaths/min, P less than 0.01) as well as a smaller mean tidal volume (VT). In both groups, minute ventilation (VE) and f progressively decreased as resistance was increased by decreasing the aperture size from 15 to 16 mm. In the normal subjects but not the patients, VT also progressively decreased. When the diameter was decreased from 6 mm to 5 mm, there were increases in VT and decreases in f that were more marked in the normal subjects. In both groups, the changes in VE were accompanied by decreases in mean and peak inspiratory and expiratory flow rates. Throughout the study, oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change. This, coupled with the decreases in VE resulted in decreases in the ventilatory equivalents to CO2 and O2 (VE/VCO2, VE/VO2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of posture on carbon dioxide responsiveness in patients with obstructive sleep apnoea.

BACKGROUND--It is well known that upper airway resistance increases with postural change from a sitting to supine position in patients with obstructive sleep apnoea (OSA). It is not known, however, how the postural change affects the ventilatory and occlusion pressure response to hypercapnia in patients with OSA when awake. METHODS--The responses of minute ventilation (VE) and mouth pressure 0.1 seconds after the onset of occluded inspiration (P0.1) to progressive hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) both in sitting and supine positions were measured in 20 patients with OSA. The ratio of the two (delta VE/delta P0.1) was obtained as an index of breathing efficiency. The postural changes in response to carbon dioxide (CO2) after uvulopalatopharyngoplasty (UPPP) were also compared in seven patients with OSA. RESULTS--There were no significant changes in the resting values of end tidal PCO2, P0.1, or VE between the two positions. During CO2 rebreathing, delta VE/delta PCO2 did not differ between the two positions, but delta P0.1/delta PCO2 was significantly higher in the supine than in the sitting position (supine, mean 0.67 (SE 0.09) cm H2O/mm Hg; sitting, mean 0.57 (SE 0.08) cm H2O/mm Hg), and delta VE/delta P0.1 decreased significantly from the sitting to the supine position (sitting, 4.6 (0.4) l/min/cm H2O; supine, 3.9 (0.4) l/min/cm H2O). In seven patients with OSA who underwent UPPP, delta VE/delta P0.1 improved significantly in the supine position and postural change in delta VE/delta P0.1 was eliminated. CONCLUSIONS--These results suggest that in patients with OSA the inspiratory drive in the supine position increases to maintain the same level of ventilation as in the sitting position, and that the postural change from sitting to supine reduces breathing efficiency. Load compensation mechanisms of patients with OSA appear to be intact while awake in response to the rise in upper airway resistance.     

An analysis of the ventilatory response to carbon dioxide during halothane, isoflurane, or enflurane anesthesia in humans

To analyze the effects of halothane, isoflurane, or enflurane on the ventilatory response to CO2, minute volume (VE), respiratory rate (f), occlusion pressure, mean inspiratory flow rate (VT/TI), and effective elastance (Pmax/VT) were measured in 26 patients during quiet breathing and when the respiratory system was stressed by CO2. Comparison was made at equipotent anesthetic concentration (1 MAC) and all measurements were made in the absence of surgical stimulation. Respiratory rate and Pmax/VT were unchanged in all groups after end-tidal CO2 was elevated. By contrast, VE, VT/TI, and occlusion pressure increased in all the groups when the respiratory system was stressed by CO2. Among the parameters tested delta VE/delta PaCO2 and delta VT/TI/delta PaCO2 were significantly (P less than 0.05) greater during halothane anesthesia than during isoflurane or enflurane anesthesia. We conclude that, at equipotent anesthetic concentrations, isoflurane and enflurane depress CO2 chemosensitivity more than halothane does, and that such effect is primarily related to the greater depressant effects of isoflurane and enflurane on the respiratory driving mechanisms.     

Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction.

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.     

Effect of cigarette smoking on evolution of ventilatory lung function in young adults: an eight year longitudinal study.

BACKGROUND: There are few data on the quantitative effects of cigarette smoking on lung function in young adults. These effects are important in the understanding of the early stages of chronic airflow obstruction. METHODS: A longitudinal study over eight years was carried out to estimate quantitatively the effect of cigarette smoking on ventilatory lung function in young adults and to examine the possibility that the effect is modified by other factors. The study population were 15 to 40 years of age at initial examination, when they underwent spirometry and completed an interviewer administered questionnaire on respiratory health. Eight years later 391 of the subjects were re-examined (38% response rate). The quantitative effect of cigarette smoking during the study period on the average change of forced expiratory volume in one second (FEV1) over time (delta FEV1) was estimated in two linear regression models that included potential confounders and other determinants of outcome. RESULTS: The first model showed a significant dose-response relation between the average rate of smoking during the study period and delta FEV1, giving an estimate of annual change in FEV1 of -0.42 ml for each cigarette smoked per day (-8.4 ml for each pack) (p = 0.04). In the second model, which took smoking before the study period as a potential confounder, the effect of smoking during the study period was slightly smaller (-0.33 ml/year for each cigarette smoked per day). This indicated that smoking before the study period had a marginal latent effect on delta FEV1 during the study. However, neither the effect of smoking before the study nor that of smoking during the study was significant, presumably because of collinearity. Interactions between cigarette smoking and gender, wheezing, atopy, and exposure to environmental tobacco smoke during the growth period were not significant with respect to their effect on the relation between cigarette smoking and delta FEV1. CONCLUSION: Cigarette smoking has a dose related adverse effect on the evolution of ventilatory lung function in young adulthood.