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.     

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.     

Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation

BACKGROUND: Nocturnal non-invasive ventilation (NIV) is an effective treatment for hypercapnic respiratory failure in patients with restrictive thoracic disease. We hypothesised that NIV may reverse respiratory failure by increasing the ventilatory response to carbon dioxide, reducing inspiratory muscle fatigue, or enhancing pulmonary mechanics. METHODS: Twenty patients with restrictive disease were studied at baseline (D0) and at 5-8 days (D5) and 3 months (3M). RESULTS: Mean (SD) daytime arterial carbon dioxide tension (Paco(2)) was reduced from 7.1 (0.9) kPa to 6.6 (0.8) kPa at D5 and 6.3 (0.9) kPa at 3M (p = 0.004), with the mean (SD) hypercapnic ventilatory response increasing from 2.8 (2.3) l/min/kPa to 3.6 (2.4) l/min/kPa at D5 and 4.3 (3.3) l/min/kPa at 3M (p = 0.044). No increase was observed in measures of inspiratory muscle strength including twitch transdiaphragmatic pressure, nor in lung function or respiratory system compliance. CONCLUSIONS: These findings suggest that increased ventilatory response to carbon dioxide is the principal mechanism underlying the long term improvement in gas exchange following NIV in patients with restrictive thoracic disease. Increases in respiratory muscle strength (sniff oesophageal pressure and sniff nasal pressure) correlated with reductions in the Epworth sleepiness score, possibly indicating an increase in the ability of patients to activate inspiratory muscles rather than an improvement in contractility.     

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.     

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.     

Diphenhydramine Increases Ventilatory Drive during Alfentanil Infusion

Background: Diphenhydramine is used as an antipruritic and antiemetic in patients receiving opioids. Whether it might exacerbate opioid-induced ventilatory depression has not been determined.

Methods: The ventilatory response to carbon dioxide during hyperoxia and the ventilatory response to hypoxia during hypercapnia (end-tidal pressure of carbon dioxide [PETCO2] [almost equal to] 54 mmHg) were determined in eight healthy volunteers. Ventilatory responses to carbon dioxide and hypoxia were calculated at baseline and during an alfentanil infusion (estimated blood levels [almost equal to] 10 ng/ml) before and after diphenhydramine 0.7 mg/kg.

Results: The slope of the ventilatory response to carbon dioxide decreased from 1.08 +/- 0.38 to 0.79 +/- 0.36 l [middle dot] min-1 [middle dot] mmHg-1 (x +/- SD, P < 0.05) during alfentanil infusion; after diphenhydramine, the slope increased to 1.17 +/- 0.28 l [middle dot] min-1 [middle dot] mmHg-1 (P < 0.05). The minute ventilation (VE) at PETCO2 [almost equal to] 46 mmHg (VE 46) decreased from 12.1 +/- 3.7 to 9.7 +/- 3.6 l/min (P < 0.05) and the VE at 54 mmHg (V (E) 54) decreased from 21.3 +/- 4.8 to 16.6 +/- 4.7 l/min during alfentanil (P < 0.05). After diphenhydramine, VE 46 did not change significantly, remaining lower than baseline at 9.9 +/- 2.9 l/min (P < 0.05), whereas VE 54 increased significantly to 20.5 +/- 3.0 l/min. During hypoxia, VE at Sp O2 = 90% (VE 90) decreased from 30.5 +/- 9.7 to 23.1 +/- 6.9 l/min during alfentanil (P < 0.05). After diphenhydramine, the increase in VE 90 to 27.2 +/- 9.2 l/min was not significant (P = 0.06).     

Respiratory depression following diazepam: reversal with high-dose naloxone

The authors compared the effects of naloxone and saline solution on the respiratory changes following diazepam in a double-blind crossover trial in six subjects. Following baseline measurements of respiration, each subject was given diazepam, 15 mg, intravenously. Sixty and ninety-five minutes later each subject received either two doses of naloxone, 15 mg, intravenously, or two doses of the equivalent volume of saline solution. Forty-five minutes after diazepam administration the slopes of the curves of the ventilatory responses to rebreathing carbon dioxide (VE/PETCO2) were depressed to 53 per cent of control (P < 0.05). Following the two doses of naloxone, the slopes of VE/PETCO2 recovered, until, 120 minutes after the second dose of naloxone, slopes had returned to control values. After saline solution, however, slopes remained depressed at 68 per cent of control (P < 0.05). A similar recovery following naloxone was observed in the PETCO2 intercept of the VE/PETCO2 response curve and in the slope of the mouth-occlusion-pressure response curve to rebreathing carbon dioxide. End-tidal carbon dioxide during quiet breathing and during inspiratory resistive-loaded breathing (80 cm H2O/l/s) showed small increases after diazepam, which were not significantly reduced by naloxone. The results of this study show that diazepam produces respiratory depression, and that this may be relieved by large doses of naloxone.     

Effects of fenoterol on ventilatory response to hypercapnia and hypoxia in patients with chronic obstructive pulmonary disease

BACKGROUND: It has previously been shown that fenoterol, a beta 2 adrenergic agonist, increases the ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) in normal subjects. The effects of beta 2 adrenergic agonists on chemoreceptors in patients with chronic obstructive pulmonary disease (COPD) remain controversial. This study was designed to examine whether fenoterol increases the HVR and HCVR in patients with COPD. METHODS: The HCVR was tested in 20 patients using a rebreathing method and the HVR was examined using a progressive isocapnic hypoxic method. The HCVR and HVR were assessed by calculating the slopes of plots of occlusion pressure (P0.1) and ventilation (VE) against end tidal carbon dioxide pressure (PETCO2) and arterial oxygen saturation (SaO2), respectively. Spirometric values, lung volumes, and respiratory muscle strength were also measured. The HCVR and HVR were examined after the oral administration of fenoterol (15 mg/day) or placebo for seven days. RESULTS: Fenoterol treatment increased the forced expiratory volume in one second (FEV1) and inspiratory muscle strength. In the HCVR the slope of P0.1 versus PETCO2 was increased by fenoterol from 0.35 (0.23) to 0.43 (0.24) (p < 0.01). Moreover, the P0.1 at PETCO2 of 8 kPa was higher on fenoterol than on placebo (p < 0.05) and the VE was also greater (p < 0.01). In the HVR fenoterol treatment increased the P0.1 at 80% SaO2 from 0.90 (0.72) to 0.97 (0.55) kPa (p < 0.05) while the slopes of the response of P0.1 and VE were not changed. CONCLUSIONS: Fenoterol increases the ventilatory response to hypercapnia in patients with COPD, presumably by stimulation of the central chemoreceptor. The hypoxic ventilatory response is only slightly affected by fenoterol.


     

Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline.

Methylxanthines are known to be respiratory stimulants and are thought by some to augment hypercapnic and hypoxic ventilatory drive and improve respiratory muscle strength. Hypoxic and hypercapnic ventilatory responses were measured in 10 normal subjects before, during, and after administration of theophylline for three and a half days. Pulmonary function, carbon dioxide production, and mouth pressures during maximal static inspiratory and expiratory efforts were also measured. The mean (SD) serum theophylline concentration was 13.8 (3.2) mg/l. Lung volumes and flow rates did not change significantly with theophylline. The mean (SD) values for maximum static inspiratory pressure were 152 (27), 161 (25), and 160 (24) cm H2O, respectively before, during, and after theophylline. Neither these values nor peak expiratory pressure measurements were significantly changed. The slopes of the hypercapnic ventilatory responses were 2.9 (0.9), 3.3 (1.2), and 3.3 (1.4) l/min/mm Hg carbon dioxide tension (PCO2) respectively before, during, and after theophylline administration. The respective values for the slopes of the hypoxic response were -1.4 (0.9), -1.3 (0.8), and -1.1 (0.9) l/min/1% oxyhaemoglobin saturation. None of these values changed significantly with theophylline. Theophylline, however, increased carbon dioxide production (200 to 236 ml/min) and alveolar ventilation (4.7 to 5.7 l/min) significantly, with a concomitant fall of end tidal PCO2 (35.5 to 32.9 mm Hg). It is concluded that in man oral theophylline at therapeutic blood concentrations increases carbon dioxide production and ventilation without changing pulmonary function, respiratory muscle strength, or the hypoxic or hypercapnic ventilatory response significantly.     

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.     

Effects of subanaesthetic sevoflurane on ventilation. 1: Response to acute and sustained hypercapnia in humans

We have determined the influence of 0.1 minimum alveolar concentration (MAC) of sevoflurane on ventilation, the acute ventilatory response to a step change in end-tidal carbon dioxide and the ventilatory response to sustained hypercapnia in 10 healthy adult volunteers. Subjects undertook a preliminary 10-min period of breathing air without sevoflurane to determine their normal ventilation and natural end-tidal PCO2. This 10-min period was repeated while breathing 0.1 MAC of sevoflurane. Subjects then undertook two procedures: end-tidal PO2 was maintained at 13.3 kPa and end-tidal PCO2 at 1.3 kPa above the subject's normal value for 30 min of data collection, first with and then without 0.1 MAC of sevoflurane. A dynamic end-tidal forcing system was used to generate these gas profiles. Sevoflurane did not significantly change ventilation: 10.1 (SEM 1.0) litre min-1 without sevoflurane, 9.6 (0.9) litre min-1 with sevoflurane. The response to acute hypercapnia was also unchanged: mean carbon dioxide response slopes were 20.2 (2.7) litre min-1 kPa-1 without sevoflurane and 18.8 (2.7) litre min-1 kPa-1 with sevoflurane. Sustained hypercapnia caused a significant gradual increase in ventilation and tidal volume over time and significant gradual reduction in inspiratory and expiratory times. Sevoflurane did not affect these trends during sustained hypercapnia. These results suggest that 0.1 MAC of sevoflurane does not significantly affect the acute ventilatory response to hypercapnia and does not modify the progressive changes in ventilation and pattern of breathing that occur with sustained hypercapnia.      

Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects.

BACKGROUND--The effects of beta 2 adrenergic agonists on chemoreceptors remain controversial. This study was designed to examine whether fenoterol, a beta 2 adrenergic agonist, increases the ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) in normal subjects. METHODS--HCVR was tested with a rebreathing method and HVR was examined with a progressive isocapnic hypoxic method in 11 normal subjects. Both HCVR and HVR were assessed by the slope of occlusion pressure (P0.1) or ventilation (VE) plotted against end tidal carbon dioxide pressure and arterial oxygen saturation, respectively. Respiratory muscle strength, spirometric values and lung volume were measured. After a single oral administration of 5 mg fenoterol or placebo HCVR and HVR were evaluated. RESULTS--Fenoterol treatment did not change the specific airway conductance or forced expiratory volume in one second. Respiratory muscle strength did not change. Fenoterol increased the slope of the HCVR of both P0.1 (from 0.251 (0.116) to 0.386 (0.206) kPa/kPa, average increase 71%) and VE (from 10.7 (3.4) to 15.1 (4.2) l/min/kPa, average increase 52%), and shifted the response curves to higher values. For the HVR fenoterol increased the slopes of both P0.1 and VE (from -4.06 (2.00) x 10(-3) to -7.99 (4.29) x 10(-3) kPa/%, an average increase of 83%, and from -0.221 (0.070) to -0.313 (0.112) l/min/%, a 44.5% increase, respectively), and shifted the response curves to higher values. CONCLUSION--Acute administration of fenoterol increases the ventilatory responses to both hypercapnia and hypoxia in normal subjects.     

The pharmacodynamic effect of a remifentanil bolus on ventilatory control

BACKGROUND: In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously. METHODS: In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PET(CO2)) at approximately 46 or 56 mm Hg (alternate subjects). After 6 min of equilibration, subjects received 0.5 microg/kg remifentanil over 5 s, and minute ventilation (V(E)) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mm Hg). The V(E) data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (k(eo)), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration-response curve (gamma). RESULTS: The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l x min(-1) x mm Hg(-1) [-0.12 to 0.66] 2 min after remifentanil (P<0.001); within 5 min, it recovered to approximately 0.6 l x min(-1) x mm Hg(-1), and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mm Hg (VE50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P<0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of VE50 included k(eo) = 0.24 min(-1) (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and gamma = 1.74. CONCLUSIONS: After administration of 0.5 microg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.     

Interaction of extradural morphine and lignocaine on ventilatory response

We have evaluated the effects of lumbar extradural morphine and lignocaine on the ventilatory response to carbon dioxide. Twenty-four female patients were allocated randomly to receive extradural morphine 2 mg (group M), 2% lignocaine 10 ml (group L) or a combination of morphine 2 mg and 2% lignocaine 10 ml (group ML). On the day before surgery, resting ventilatory values including minute volume (VE) and tidal volume (VT), and ventilatory response to progressive hyperoxic hypercapnia (VE/PE'CO2) were measured. On the day of surgery, the same measurements were repeated 30 min after extradural injection. Ventilatory values at rest were not altered after extradural injection. Mean VE/PE'CO2 decreased significantly after extradural morphine (P = 0.002) and increased (P = 0.011) after extradural lignocaine. Mean VE 7.3 (VE at PE'CO2 7.3 kPa) decreased significantly after extradural morphine (P < 0.001) and increased after extradural lignocaine (P = 0.047). Extradural morphine and lignocaine did not significantly alter mean VE/PE'CO2 and mean VE 7.3: 14.6 (95% confidence intervals 12.1- 17.1) to 15.3 (13.1-17.6) litre min-1 kPa-1 and 22.8 (18.1-27.5) to 22.8 (17.3-28.3) litre min-1, respectively. We conclude that extradural co-administration of morphine and lignocaine did not increase the risk of respiratory depression associated with morphine.      

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)     

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 dopamine on hypoxic-hypercapnic interaction in humans

To investigate the effect of intravenous dopamine on the chemical regulation of ventilation, we studied the ventilatory responses to hypercapnic hypoxia during dopamine infusion. Intravenous dopamine (3 micrograms X kg-1 X min-1) was administered to six healthy human subjects. Two hypoxic challenges (PETO2 = 52.5 +/- 2.5 mm Hg, SaO2 = 88.8 +/- 2.2%; mean +/- SD) were administered at three CO2 levels (PETCO2 = 40.8 +/- 0.5, 45.6 +/- 0.2, 49.8 +/- 0.3 mm Hg) to each subject. The ventilatory responses were quantified by calculation of slopes and intercepts of the relationship between minute exhaled ventilation (VE) and arterial hemoglobin saturation (SaO2), and by the relationship between this slope (delta VE/delta SaO2) and carbon dioxide tension. Dopamine caused a 77% reduction in delta VE/delta SaO2 (hypoxic sensitivity) during eucapnia, a 39.5% reduction in hypoxic sensitivity at PETCO2 = 46 mm Hg, and 38% reduction at PETCO2 = 50 mm Hg (P less than 0.05). Dopamine also reduced normoxic ventilation at all carbon dioxide levels. There was a greater depression in VE during hypercapnia (25.7% reduction) than during eucapnia (12% reduction). This indicates that dopamine depresses the normoxic ventilatory response to carbon dioxide. Intravenous dopamine reduces the ventilatory response to both hypoxia and hypercapnia but preserves the augmentation of hypoxic ventilatory drive by hypercapnia.     

Effect of CPAP on intrinsic PEEP,inspiratory effort,and lung volume in severe stable COPD

BACKGROUND: Intrinsic positive end expiratory pressure (PEEPi) constitutes an inspiratory threshold load on the respiratory muscles, increasing work of breathing. The role of continuous positive airway pressure (CPAP) in alleviating PEEPi in patients with severe stable chronic obstructive pulmonary disease is uncertain. This study examined the effect of CPAP on the inspiratory threshold load, muscle effort, and lung volume in this patient group. METHODS: Nine patients were studied at baseline and with CPAP increasing in increments of 1 cm H(2)O to a maximum of 10 cm H(2)O. Breathing pattern and minute ventilation (I), dynamic PEEPi, expiratory muscle activity, diaphragmatic (PTPdi/min) and oesophageal (PTPoes/min) pressure-time product per minute, integrated diaphragmatic (EMGdi) and intercostal EMG (EMGic) and end expiratory lung volume (EELV) were measured. RESULTS: Expiratory muscle activity was present at baseline in one subject. In the remaining eight, PEEPi was reduced from a mean (SE) of 2.9 (0.6) cm H(2)O to 0.9 (0.1) cm H(2)O (p<0.05). In two subjects expiratory muscle activity contributed to PEEPi at higher pressures. There were no changes in respiratory pattern but I increased from 9.2 (0.6) l/min to 10.7 (1.1) l/min (p<0.05). EMGdi remained stable while EMGic increased significantly. PTPoes/min decreased, although this did not reach statistical significance. PTPdi/min decreased significantly from 242.1 (32.1) cm H(2)O.s/min to 112.9 (21.7) cm H(2)O.s/min). EELV increased by 1.1 (0.3) l (p<0.01). CONCLUSION: High levels of CPAP reduce PEEPi and indices of muscle effort in patients with severe stable COPD, but only at the expense of substantial increases in lung volume.     

Ventilatory responses to hypercapnia during tetracaine spinal anesthesia

The effect of spinal anesthesia with hyperbaric tetracaine with epinephrine on resting ventilation and on ventilatory responsiveness to CO2 rebreathing was studied in 10 unpremedicated patients. Resting end-tidal PCO2 (PETCO2) decreased from 37 +/- 3 mmHg (mean +/- SD) to 34 +/- 2 mmHg after induction of spinal anesthesia (p less than 0.05). Minute ventilation (VE) and occlusion pressure (P0.1) at PETCO2 = 55 mmHg increased during spinal anesthesia from 32.0 +/- 12.9 to 40.2 +/- 17.0 l/min and from 5.0 +/- 1.8 to 8.6 +/- 4.7 cmH2O, respectively. The magnitude of the increase in VE during spinal anesthesia correlated inversely with age. Spinal anesthesia was not associated with significant changes in vital capacity, maximal inspiratory pressure, or the slopes of the lines relating VE or P0.1 to PCO2. These results show increased ventilatory responsiveness to CO2 (a parallel leftward shift of the CO2 response curve) with tetracaine spinal anesthesia.     

The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease

Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 +/- 2.60 vs 8.70 +/- 2.10 L/min; P = 0.04) by means of increased tidal volume (0.46 +/- 0.16 vs 0.53 +/- 0.14 L/breath; P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 +/- 0.17 vs 0.55 +/- 0.14 L/s; P = 0.02) and a decrease in pulmonary resistance (20.7 +/- 9.9 vs 16.6 +/- 8.1 cm H(2)O. L(-1). s(-1); P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, PaO(2), and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients. IMPLICATIONS: Thoracic epidural anesthesia with bupivacaine 0.25% does not impair ventilatory mechanics and inspiratory respiratory muscle strength in severely limited chronic obstructive pulmonary disease patients. Thus, thoracic epidural anesthesia can be used safely in patients with end-stage chronic obstructive pulmonary disease.