Ventilation and ventilatory response to carbon dioxide during caudal anaesthesia with lidocaine or bupivacaine in sedated children

Resting ventilation, arterial blood-gas tensions and the ventilatory response to carbon dioxide were measured in sedated children before and after caudal anaesthesia using 10 mg.kg-1 of 1.5% lidocaine or 3.3 mg.kg-1 of 0.5% bupivacaine. Expired minute volume decreased slightly after both caudal blocks but end-tidal Pco2 increased slightly after caudal block with lidocaine. No clinical changes in Paco2 and Pao2 were observed in either group. The slope of the CO2 response curves increased significantly after both caudal blocks. The mean plasma levels of lidocaine and bupivacaine were 3.95 +/- 0.64 (s.d.) and 1.33 +/- 0.29 micrograms.ml-1, respectively. These results indicate that the ventilatory response to hypercapnia is markedly improved by the two caudal blocks, but resting ventilation is slightly impaired by caudal block with lidocaine, and from the aspect of pulmonary ventilation bupivacaine is better than lidocaine for caudal anaesthesia.     

Ventilatory and circulatory responses to carbon dioxide and high level sympathectomy induced by epidural blockade in awake humans

In order to examine the effects of cervico-thoracic epidural block with 1.5% lidocaine on ventilatory and circulatory responses to carbon dioxide, the authors studied the CO2-ventilatory response curves and the changes in heart rate (HR) and blood pressure (AP) to rebreathing of exhaled gas before and after the block in healthy volunteers. Neither resting ventilation nor ventilatory response to CO2 was affected by the epidural block (mean analgesic level extended from C4 to T7); the slope of the CO2-ventilatory response curve averaged 2.38 +/- 0.81 L X min-1 X mm Hg-1 (mean +/- SD) before and 2.32 +/- 0.82 L X min-1 X mm Hg-1 after the block. Resting HR and AP decreased significantly (P less than 0.01) after the block, but responses in HR and AP to CO2 rebreathing were not significantly changed by the block. Plasma concentrations of norepinephrine and epinephrine were similar before and after the block both with and without CO2 rebreathing. These results indicate that high levels of sympathetic denervation induced by epidural block do not impair circulatory and ventilatory responses to carbon dioxide in awake, healthy humans.     

VENTILATORY RESPONSE TO CARBON DIOXIDE DURING EXTRADURAL ANAESTHESIA WITH LIGNOCAINE AND FENTANYL

Twenty-seven patients undergoing extracorporeal shock-wave lithotripsyor knee arthroscopy received extradural anaesthesia with 2%lignocaine plus adrenaline 1 in 200000. They were allocatedrandomly to three groups, one receiving no fentanyl (n = 6),the two others receiving fentanyl 50 µg either extradurally(n = 15) or i.v. (n = 6). Three tests of sensitivity to carbondioxide (Read's method) were performed successively on eachpatient: before operation and at 1 and 2 h after the extraduralinjection. Whereas lignocaine and adrenaline alone had no significanteffects on basal ventilation and the ventilatory response tocarbon dioxide, extradural fentanyl caused a slight reductionin resting ventilatory rate and ventilation at 1 and 2 h withno change in resting end-tidal carbon dioxide concentration.In addition, the slope of the ventilatory response to carbondioxide was reduced slightly at 1 h and ventilation at end-tidalnCO₂ of 7.3 kPa was reduced also at 1 and 2 h. Conversely, thesame dose of fentanyl i.v. had lesser and shorter effects onventilation at rest and during carbon dioxide rebreathing. Ourresults show that fentanyl 50 µg given extradurally causedslight ventilatory depression which is probably clinically unimportant.     

Activation of opioid mu receptors in caudal medullary raphe region inhibits the ventilatory response to hypercapnia in anesthetized rats

BACKGROUND:: Opioids, extensively used as analgesics, markedly depress ventilation, particularly the ventilatory responsiveness to hypercapnia in humans and animals predominantly via acting on mu receptors. The medullary raphe region (MRR) contains abundant mu receptors responsible for analgesia and is also an important central area involving carbon dioxide chemoreception and contributing to the ventilatory responsiveness to hypercapnia. Therefore, the authors asked whether activation of mu receptors in the caudal, medial, or rostral MRR depressed ventilation and the response to hypercapnia, respectively. METHODS:: Experiments were conducted in 32 anesthetized and spontaneously breathing rats. Ventilation and it response to progressive hypercapnia were recorded. The slopes obtained from plotting minute ventilation, respiratory frequency, and tidal volume against the corresponding levels of end-tidal pressure of carbon dioxide were used as the indices of the respiratory responsiveness to carbon dioxide. DAMGO ([d-Ala2, N-Me-Phe4, Gly-ol]-enkephalin), a mu-receptor agonist, was systemically administered (100 mug/kg) before and/or after local injection of CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (100 ng/100 nl), a mu-receptor antagonist, into the caudal MRR, or locally administered (35 ng/100 nl) into the MRR subnuclei. RESULTS:: The authors found that systemic DAMGO significantly inhibited ventilation and the response to carbon dioxide by 20% and 31%, respectively, and these responses were significantly diminished to 11% and 14% after pretreatment of the caudal MRR with CTAP. Local administration of DAMGO into the caudal MRR also reduced ventilation and the response to carbon dioxide by 22% and 28%, respectively. In sharp contrast, these responses were not observed when the DAMGO microinjection was made in the middle MRR or rostral MRR. CONCLUSIONS:: These results lead to the conclusion that mu receptors in the caudal MRR rather than the middle MRR or rostral MRR are important but not exclusive for attenuating the hypercapnic ventilatory response.     

Activation of Opioid μ Receptors in Caudal Medullary Raphe Region Inhibits the Ventilatory Response to Hypercapnia in Anesthetized Rats

Background: Opioids, extensively used as analgesics, markedly depress ventilation, particularly the ventilatory responsiveness to hypercapnia in humans and animals predominantly via acting on [mu] receptors. The medullary raphe region (MRR) contains abundant [mu] receptors responsible for analgesia and is also an important central area involving carbon dioxide chemoreception and contributing to the ventilatory responsiveness to hypercapnia. Therefore, the authors asked whether activation of [mu] receptors in the caudal, medial, or rostral MRR depressed ventilation and the response to hypercapnia, respectively.

Methods: Experiments were conducted in 32 anesthetized and spontaneously breathing rats. Ventilation and it response to progressive hypercapnia were recorded. The slopes obtained from plotting minute ventilation, respiratory frequency, and tidal volume against the corresponding levels of end-tidal pressure of carbon dioxide were used as the indices of the respiratory responsiveness to carbon dioxide. DAMGO ([d-Ala2, N-Me-Phe4, Gly-ol]-enkephalin), a [mu]-receptor agonist, was systemically administered (100 [mu]g/kg) before and/or after local injection of CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (100 ng/100 nl), a [mu]-receptor antagonist, into the caudal MRR, or locally administered (35 ng/100 nl) into the MRR subnuclei.

Results: The authors found that systemic DAMGO significantly inhibited ventilation and the response to carbon dioxide by 20% and 31%, respectively, and these responses were significantly diminished to 11% and 14% after pretreatment of the caudal MRR with CTAP. Local administration of DAMGO into the caudal MRR also reduced ventilation and the response to carbon dioxide by 22% and 28%, respectively. In sharp contrast, these responses were not observed when the DAMGO microinjection was made in the middle MRR or rostral MRR.     

The chemoreflex control of breathing and its measurement

The chemoreflex control of breathing is described in terms of a graphical model. The central chemoreflex, the ventilatory response to carbon dioxide mediated by the central chemoreceptors, is modelled as a straight-line relation between the ventilatory response and the arterial level of carbon dioxide. The peripheral chemoreflex, the ventilatory response to carbon dioxide and hypoxia mediated by the peripheral chemoreceptors, is broken into two relations. First, a straight-line relation between the ventilatory response and the arterial level of carbon dioxide whose slope (sensitivity) increases as the oxygen level varies from hyperoxic to hypoxic. Second, a rectangular hyperbolic relation between the ventilatory response and the arterial level of oxygen with ventilation increasing with increasing hypoxia. The three ventilatory response relations (one central and two peripheral) add to produce the total chemoreflex ventilatory response which forms the feedback part of the respiratory regulator. The forward part consists of the relation between the arterial level of carbon dioxide and ventilation when ventilation is controlled (the metabolic hyperbola). The forward and feedback parts of the respiratory regulator can be combined so as to predict resting ventilation and carbon dioxide levels under a number of circumstances. Methods of measurement of these chemoreflex ventilatory responses are also described so as to illustrate the physiological principles involved in the model.     

Mixed-effects modeling of the intrinsic ventilatory depressant potency of propofol in the non-steady state

BACKGROUND: Despite the ubiquitous use of propofol for anesthesia and conscious sedation and numerous publications about its effect, a pharmacodynamic model for propofol-induced ventilatory depression in the non-steady state has not been described. To investigate propofol-induced ventilatory depression in the clinically important range (at and below the metabolic hyperbola while carbon dioxide is accumulating because of drug-induced ventilatory depression), the authors applied indirect effect modeling to Paco2 data at a fraction of inspired carbon dioxide of 0 during and after administration of propofol. METHODS: Ten volunteers underwent determination of their carbon dioxide responsiveness by a rebreathing design. The parameters of a power function were fitted to the end-expiratory carbon dioxide and minute ventilation data. The volunteers then received propofol in a stepwise ascending pattern with use of a target-controlled infusion pump until significant ventilatory depression occurred (end-tidal pressure of carbon dioxide > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 microg/ml. Propofol pharmacokinetics and the Paco2 were determined from frequent arterial blood samples. An indirect response model with Bayesian estimates of the pharmacokinetics and carbon dioxide responsiveness in the absence of drug was used to describe the Paco2 time course. Because propofol reduces oxygen requirements and carbon dioxide production, a correction factor for propofol-induced decreasing of carbon dioxide production was included. RESULTS: The following pharmacodynamic parameters were found to describe the time course of hypercapnia after administration of propofol (population mean and interindividual variability expressed as coefficients of variation): F (gain of the carbon dioxide response), 4.37 +/- 36.7%; ke0, CO2, 0.95 min-1 +/- 59.8%; baseline Paco2, 40.9 mmHg +/- 12.8%; baseline minute ventilation, 6.45 l/min +/- 36.3%; kel, CO2, 0.11 min-1 +/- 34.2%; C50,propofol, 1.33 microg/ml +/- 49.6%; gamma, 1.68 +/- 21.3%. CONCLUSION: Propofol at common clinical concentrations is a potent ventilatory depressant. An indirect response model accurately described the magnitude and time course of propofol-induced ventilatory depression. The indirect response model can be used to optimize propofol administration to reduce the risk of significant ventilatory depression.     

Enflurane requirement and ventilatory response to carbon dioxide during lidocaine infusion in dogs.

Arterial plasma lidocaine concentration of 1 to 3.5 microgram/ml produced dose-related decreases in enflurane requirement (MAC) ranging from 15 to 37 per cent in dogs. The ventilatory responses to carbon dioxide at comparable depths of anesthesia with enflurane alone and the enflurane-lidocaine combination were measured in each animal and compared. With both anesthetic regimens there were increases in resting arterial carbon dioxide tension (mean maximal increase = 18 torr) and a 69 per cent decrease in the slope of the ventilatory response as depth of anesthesia increased. The effect of the drug interaction appears to be additive, since the ventilatory depression produced by the enflurane-lidocaine combination was no greater than that produced by enflurane alone at equivalent levels of anesthesia.     

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.     

Influences of Morphine on the Ventilatory Response to Isocapnic Hypoxia

Background: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops.

Methods: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (PET CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold).

Results: At constant PET CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher PET CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084).     

Respiratory effects of spinal anesthesia: resting ventilation and single-breath CO2 response

The effects of spinal anesthesia with bupivacaine or lidocaine on resting pulmonary ventilation and on the response to the single-breath carbon dioxide test were studied in 11 unpremedicated patients. Resting end-tidal PCO2 decreased from 34.8 +/- 4.5 (mean +/- SD) to 31.6 +/- 4.6 mm Hg after induction of spinal anesthesia (P = 0.002). The decrease in end-tidal PCO2 correlated negatively with patient age (r = -0.67, P = 0.02) and positively with spinal analgesic level (r = 0.58, P = 0.06). Breath-to-breath variability of ventilation increased during spinal anesthesia. Spinal anesthesia was not associated with statistically significant changes in tidal volume, respiratory rate, minute ventilation, mean inspiratory flow rate, inspiratory duty cycle duration, or the response to the single-breath CO2 test.     

Ventilatory response to carbon dioxide after intramuscular and epidural fentanyl

The authors compared the effects of administration of fentanyl 200 micrograms on the ventilatory response to carbon dioxide in two groups of nine healthy unpremedicated subjects: one group received fentanyl as an intramuscular injection; in the other group, fentanyl was injected into the epidural space. In the intramuscular group, the slope of the ventilatory response to CO2 did not decrease significantly. In the epidural group, the slope of the ventilatory response to CO2 decreased significantly from 2.48 +/- 1.05 to 1.77 +/- 0.7, 1.74 +/- 0.7, and 2.07 +/- 0.74 L X min-1 X mm Hg-1 at 30, 60, and 120 min after injection (chi +/- SD, P less than or equal to 0.05), respectively. At each time of the study, plasma fentanyl levels were significantly lower in the epidural group than in the intramuscular group (P less than or equal to 0.05). These results suggest that epidural fentanyl induces a nonsystemic ventilatory depression that may be due to the rostral spread of the drug.     

Mixed-effects Modeling of the Intrinsic Ventilatory Depressant Potency of Propofol in the Non-steady State

Background: Despite the ubiquitous use of propofol for anesthesia and conscious sedation and numerous publications about its effect, a pharmacodynamic model for propofol-induced ventilatory depression in the non-steady state has not been described. To investigate propofol-induced ventilatory depression in the clinically important range (at and below the metabolic hyperbola while carbon dioxide is accumulating because of drug-induced ventilatory depression), the authors applied indirect effect modeling to Paco2 data at a fraction of inspired carbon dioxide of 0 during and after administration of propofol.

Methods: Ten volunteers underwent determination of their carbon dioxide responsiveness by a rebreathing design. The parameters of a power function were fitted to the end-expiratory carbon dioxide and minute ventilation data. The volunteers then received propofol in a stepwise ascending pattern with use of a target-controlled infusion pump until significant ventilatory depression occurred (end-tidal pressure of carbon dioxide > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 [mu]g/ml. Propofol pharmacokinetics and the Paco2 were determined from frequent arterial blood samples. An indirect response model with Bayesian estimates of the pharmacokinetics and carbon dioxide responsiveness in the absence of drug was used to describe the Paco2 time course. Because propofol reduces oxygen requirements and carbon dioxide production, a correction factor for propofol-induced decreasing of carbon dioxide production was included.

Results: The following pharmacodynamic parameters were found to describe the time course of hypercapnia after administration of propofol (population mean and interindividual variability expressed as coefficients of variation): F (gain of the carbon dioxide response), 4.37 +/- 36.7%; ke0, CO2, 0.95 min-1 +/- 59.8%; baseline Paco2, 40.9 mmHg +/- 12.8%; baseline minute ventilation, 6.45 l/min +/- 36.3%; kel, CO2, 0.11 min-1 +/- 34.2%; C50,propofol, 1.33 [mu]g/ml +/- 49.6%; [gamma], 1.68 +/- 21.3%.     

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).     

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).     

The effects of intravenous clonidine on ventilation

The effects of clonidine, an alpha 2 adrenergic agonist, on ventilation were studied in a group of adult volunteers. The ventilatory variables measured were minute ventilation, respiratory rate, end-tidal carbon dioxide tension and the response to carbon dioxide challenge. We found no differences in minute ventilation, respiratory rate and end-tidal carbon dioxide tension, before and after clonidine administration. However, the ventilatory response to carbon dioxide was significantly attenuated following clonidine, suggesting that clonidine has respiratory depressant effects.     

Ventilatory response to CO2 following intravenous ketamine in children

The effects of intravenous ketamine (bolus of 2 mg.kg-1 followed by a continuous infusion at a rate of 40 micrograms.kg-1.min-1) on ventilatory response to carbon dioxide were studied in nine children ranging in age from 6 to 10 yr and in weight from 20 to 48 kg. Ketamine did not affect resting respiratory rate, tidal volume, end-tidal CO2 tension (PETCO2), or minute ventilation. Five minutes after the ketamine bolus, the slope VE/PETCO2 decreased significantly (P less than 0.05) from 1.71 +/- 0.47 to 1.05 +/- 0.23 1.min-1.mmHg-1 (mean +/- SD). After 30 min of continuous iv ketamine infusion, the slope returned to 1.65 +/- 0.44 1.min-1.mmHg-1, a significantly higher value (P less than 0.05) compared with the nadir and not significantly different from control. The minute ventilation at a PETCO2 of 60 mmHg decreased from 824 +/- 98 to 626 +/- 26 ml.kg-1.min-1 5 min after iv ketamine, and remained depressed (640 +/- 125 ml.kg-1.min-1 P less than 0.05) throughout the 30-min ketamine infusion. In addition, the slope VT/PETCO2 and the VT 60 did not change during the study; nonetheless, the slope f/PETCO2 and the f 60 decreased significantly following iv bolus ketamine, and the f 60 remained significantly decreased following ketamine infusion. The authors conclude that clinically useful doses of iv ketamine significantly alter ventilatory control in children.     

Ventilatory response to CO2 following intravenous and epidural lidocaine

The authors determined the effects of intravenous infusion and epidural administration of lidocaine on the control of ventilation in two groups of eight healthy unpremedicated subjects. In the intravenous group, an injection of 1.5 mg/kg lidocaine was followed by an infusion at a rate of 60 micrograms X kg-1 X min-1 for 30 min. The slope of the ventilatory response to CO2 was significantly increased (P less than 0.05) from its control value (2.65 +/- 1.22 1 X min-1 X mmHg-1 [mean +/- SD]) at the end of the infusion (58%), while plasma lidocaine level was at 3.14 +/- 0.82 microgram/ml. The correlation between individual plasma lidocaine levels and the changes in the slope of the ventilatory response to CO2 was significant (r = 0.58, n = 24, P less than 0.01). In the epidural group, after the administration of 5 mg/kg of lidocaine, the slope of the ventilatory response to CO2 increased significantly (P less than 0.05) from its control value (1.52 +/- 0.75 1 X min-1 X mmHg-1) at 15 (+22%) and 25 min (+42%), while plasma lidocaine levels were at 1.79 +/- 0.42 and 2.22 +/- 0.47 microgram/ml, respectively. In both groups, resting minute ventilation and end-tidal CO2 values remained unchanged. These results suggest that epidural lidocaine has a stimulating effect on the ventilatory control mechanisms that results from the systemic effect of the drug.     

THE VENTILATORY RESPONSE TO CARBON DIOXIDE DURING PARTIAL PARALYSIS WITH TUBOCURARINE

The ventilatory response to carbon dioxide of five normal subjectswas measured at two levels of partial paralysis of the respiratoryand peripheral muscles with tubocurarine. During mild paralysisthe mean reduction of vital capacity was 14 per cent, maximumpleural pressure 19 per cent and grip strength 55 per cent ofmeasurements before curarization. With moderate paralysis, meanreduction of vital capacity was 34 per cent, maximum pleuralpressure 28 per cent and grip strength 94 per cent of controlmeasurements. There was no change in the ventilatory responseto carbon dioxide during mild or moderate paralysis.     

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.