Naloxone does not alter response to hypercapnia or resistive loading in chronic obstructive pulmonary disease

To assess the role of endogenous opioid peptides in ventilatory control in patients with chronic obstructive lung disease, we measured the ventilatory and mouth occlusion pressure responses to hypercapnia and the compensatory response to an inspiratory resistive load in 11 male patients with COPD before and after intravenous administration of naloxone or placebo on 2 separate days. There were no statistically significant differences between naloxone and placebo administration in any index of ventilatory response to CO2 or resistive loading. When an inspiratory resistive load was added during CO2 rebreathing, minute ventilation at PETCO2 = 50 mm Hg in all 11 patients decreased significantly (p less than 0.05) with placebo and naloxone. In response to the inspiratory resistive load, in eight of the 11 patients mouth occlusion pressure (P0.1) did not increase; these eight subjects were classified as noncompensators. Naloxone did not affect the P0.1 response to inspiratory resistive loading, either in the group as a whole or in the subgroup of eight patients classified as noncompensators. Our study was unable to demonstrate that increased activity of endogenous opioid peptides suppresses the ventilatory response to CO2 or resistive loading in patients with chronic obstructive lung disease.     

Ventilatory and neuromuscular responses to inspiratory positive pressure during CO2 breathing

We studied the effects of assisting respiration with inspiratory positive pressure (IPP) during air and CO2 breathing by measuring ventilatory and mouth occlusion (P0.1) responses in 15 normal human subjects. Switching from spontaneous breathing to IPP without added CO2 did not cause a significant change in mean PACO2, P0.1, or V1. During CO2 breathing, switching to IPP did not significantly alter tidal volume or frequency. The mean ventilatory response to CO2 during spontaneous breathing was 1.02 liters/min/mm Hg. With IPP at pressure limits of 5 and 7 cm H2O, the mean responses were 0.93 and 0.89 liters/min/mm Hg, respectively, not significantly different from spontaneous breathing. The mean spontaneous P0.1 response to CO2 was 0.32 cm H2O/mm Hg. With IPP at 5 and 7 cm H2), the responses were 0.29 and 0.36 cm H2O/mm Hg, also not significantly different from spontaneous breathing. Reduction of muscular work of breathing by IPP in normal human subjects does not induce a measurable change in either respiratory drive or ventilation, which appears to remain dependent on chemoreceptor input. Inspiratory effort continues during IPP, even though it may be less than during spontaneous breathing.     

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.     

Effect of aging on control of breathing]

In an attempt of elucidate the effect of aging on control of breathing, we measured hypercapnic ventilatory responses (HCVR) under three different conditions in 14 elderly volunteers (mean age: 69 yrs) and in young control subjects (29 yrs). There was no significant difference in the slope value (S) of HCVR between the two groups when the test was conducted under hyperoxic conditions. However, under hypoxic conditions, the "S" was significantly increased only in the young subjects, but not so in the elderly. When an resistive load (17 cmH2O/L-sec) was added to an inspiratory line, the "S" was not changed as a result of augmented P0.1 response in the young subjects, while the "S" was significantly decreased without any increase in P0.1 response in the elderly. The dyspnea score at the end-tidal PCO2 of 50 Torr, which was evaluated by visual analogue scale, was consistently higher in the elderly than in the young under any conditions. These results suggest that hypoxic-hypercapnic interaction on ventilation and load compensation reflex to inspiratory resistive loading are impired in the elderly subjects and that these are not associated with bluntness of respiratory sensation.     

Ventilatory and arousal responses to added inspiratory resistance during sleep

Airway resistance increases during sleep. We have determined the ventilatory and arousal responses to the addition of inspiratory resistance of 4, 7, or 10 cmH2O/L/s during sleep in 10 normal men who slept wearing valved face masks. Insufficient ventilatory response data were obtained during rapid eye movement (REM) sleep to allow adequate analysis. The immediate responses to loading were decreases in tidal volume (VT), breathing frequency (f), and minute ventilation (VE), with no difference between wakefulness and Stage 2 and Stage 3/4 sleep in the effects of loading on VT and VE, but f fell more during wakefulness than during sleep (p less than 0.05) because of a greater lengthening of inspired time (TI) (p less than 0.05). During the first 10 breaths, occlusion pressure (P0.1) increased similarly in all EEG stages. Averaging responses during the 2-min periods when resistances were applied, the only variable to differ between EEG stages was TI, which increased more in wakefulness than in Stage 2 or Stage 3/4 sleep (p less than 0.01). Arousal within 2 min of application of resistance occurred less frequently from Stage 3/4 sleep than from Stage 2 or REM sleep (p less than 0.02). The study demonstrates that sleep modifies the changes in respiratory timing produced by resistive loading without having a major effect on ventilation or P0.1 responses. The low frequency of arousal from Stage 3/4 sleep with loading may explain why asthmatics rarely awaken from this stage with wheeze.     

Ventilatory control in patients with hypoxemia due to obstructive lung disease.

In 20 patients with chronic hypoxemia due to chronic obstructive pulmonary disease, we measured responses to CO2 and hypoxia in terms of ventilation and P0.1, the pressure generated by the respiratory muscles during the first 0.1 s of inspiratory effort against a closed airway at functional residual capacity. These responses were compared to those of a control group of 17 patients with similar ventilatory abnormality but without hypoxemia. Hypoxemic patients demonstrated significantly less response to hypoxia than did control subjects in terms of both ventilation and P0.1 The decreased hypoxic response might be analogous to that reported in high altitude dwellers and patients with cyanotic congenital heart disease. Ventilatory responses to CO2 were depressed in hypoxemic patients, but P0.1 responses were not significantly decreased. While breathing at rest with arterial O2 saturation of 95 per cent, hypoxemic patients demonstrated the same minute ventilation as control subjects, but tidal volume was smaller, inspiratory duration was shorter, and breathing frequency was slightly higher. This breathing pattern appeared to be independent of whether or not these patients retained CO2.     

Control of breathing in chronic obstructive pulmonary disease patients at rest and after beta-2 agonist inhalation.

Ventilatory function tests, ventilatory cycle analysis, mouth occlusion pressure (P0.1) and effective inspiratory impedance (P0.1/Vt/Ti) were measured in 11 healthy subjects and in 26 patients with chronic obstructive pulmonary disease (COPD). In COPD patients these measurements were repeated 20 min after inhalation of 400 micrograms of fenoterol. In patients we observed an increase of mean inspiratory flow (Vt/Ti), and a decrease of inspiratory time (Ti) and inspiratory duty cycle (Ti/Ttot). P0.1 and effective inspiratory impedance were significantly increased. Moreover, we found a direct correlation between forced expiratory volume in 1 s (FEV1) and ventilatory cycle components (Ti/Ttot, Ti) and an indirect correlation between FEV1 and Vt/Ti.P0.1 was directly correlated with Vt/Ti and indirectly correlated with ventilatory cycle components. These observations lead us to speculate on the possible role of two opposite mechanisms acting on the control of breathing of COPD patients. While the 'intensity' component of the ventilatory cycle would be set to maintain the tidal volume at a constant level, the 'timing' component would act in order to prevent inspiratory muscle fatigue. Furthermore, in patients responsive to beta 2-agonist drugs, fenoterol inhalation would act in synergy with the timing component of ventilatory cycle, lowering P0.1 and the effective inspiratory impedance.     

Hypnosis effect on carbon dioxide chemosensitivity

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.     

Active inspiratory impedance and neuromuscular respiratory output during halothane anaesthesia in humans

The aim of this study was to measure, in 11 patients with healthy lungs, active inspiratory impedance during anaesthesia. In addition, we recorded changes in inspiratory occlusion pressure at 100 ms (P0.1) and ventilatory pattern while awake and during anaesthesia with a mean inspiratory fraction (FI) of 0.017 halothane in O2. The total active inspiratory resistance and elastance values were 5.4 +/- 3.3 hPa.l.1.s and 29.9 +/- 6.2 hPa.l.1, respectively. P0.1 and the ratio between P0.1 and mean inspiratory flow (P0.1/(VT/TI)) increased 124% (p less than 0.001) and 68% (p less than 0.001), respectively, during anaesthesia. Respiratory frequency rose significantly from 12.2 +/- 1.5 (mean +/- SD) to 24.6 +/- 4.6 cycles.min-1, while tidal volume and inspiratory duty cycle lowered significantly from 0.599 +/- 0.195 l and 0.44 +/- 0.04 to 0.372 +/- 0.088 l (p less than 0.001) and 0.40 +/- 0.04 (p less than 0.05), respectively. Minute ventilation (VE) and VT/TI did not change significantly. During halothane anaesthesia with an FI:0.017, the increase in neuromuscular respiratory output appears to compensate for the increased mechanical load, thus resulting in maintenance of VE at levels similar to those of an awake state.     

Ventilatory responses to chemosensory stimuli in quadriplegic subjects

We tested the hypothesis that interruption of motor traffic running down the spinal cord to respiratory muscle motoneurons suppresses the ventilatory response to increased chemical drive. We compared the hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses, based on the rebreathing technique, before and during inspiratory flow-resistive loading in 17 quadriplegic patients with low cervical spinal cord transection and in 17 normal subjects. The ventilatory response was evaluated from minute ventilation (VE) and mouth occlusion pressure (P0.2) slopes on arterial oxygen saturation (SaO2) or on end-tidal PCO2 (PACO2), and from absolute VE values at SaO2 80% or at PACO2 55 mmHg. We found no difference in the unloaded HVR or HCVR between the quadriplegic and normal subjects. In the loaded HVR, the delta VE/delta SaO2 slope tended to decrease similarly in both groups of subjects. The delta P0.2/delta SaO2 slope was shifted upwards in normal subjects, yielding a significantly higher P0.2 at a given SaO2. In contrast, this rise in the P0.2 level during loaded HVR was absent in quadriplegics. Loaded HCVR yielded qualitatively similar results in both groups of subjects; delta VE/delta PACO2 decreased and delta P0.2/delta PACO2 increased significantly. The results show that the ventilatory chemosensory responses were unsuppressed in quadriplegics, although they displayed a disturbance in load-compensation, as reflected by occlusion pressure, in hypoxia. We conclude that the descending drive to respiratory muscle motoneurons is not germane to the operation of the chemosensory reflexes.     

Sleep-related changes in the human 'neuromuscular' ventilatory response to hypoxia

The ventilatory responses to hypercapnia and hypoxia are reduced during sleep compared to wakefulness. However, sleep-related increases in upper airways' resistance could reduce these ventilatory responses independently of any change in the neural output to the respiratory pump muscles. It is therefore possible that respiratory chemosensitivity, per se, is unchanged by sleep. To investigate this, four healthy male subjects were mechanically ventilated to abolish spontaneous respiratory muscle activity. The response to transient isocapnic hypoxia was quantified from the magnitude of the electromyographic activity induced in the diaphragm and from the associated reduction in peak inspiratory pressure; these indicies of respiratory motor output will not be affected by any sleep-related changes in upper airways' resistance. In all individuals, the responses to hypoxia were markedly attenuated during sleep compared to wakefulness. These observations, assessing the 'neuromuscular' ventilatory response, are consistent with a sleep-related reduction in respiratory chemosensitivity that is independent of any changes that may be due to increases in upper airways' resistance.     

Influence of progressive and of transient hypoxia on upper airway resistance in normal humans

In order to evaluate the influence of hypoxia on upper airway patency, we measured the response of upper airway resistance (UAR) to progressive (P) normocapnic hypoxia (Rebuck's method) and transient (T) hypoxia (three to five breaths to 100% N2) in 11 normal men. Breath-by-breath inspiratory UAR was calculated at isoflow during exclusive nasal breathing. The UAR response to hypoxia was characterized by the changes in nasal resistance and pharyngeal resistance (PR) as a function of SaO2, mean inspiratory flow (VT/Tl), and changes in the end-expiratory lung volume (EELV) measured with an inductance vest. The ventilatory response to hypoxia was greater during T (-0.31 +/- 0.03 L/min/%SaO2; mean +/- SEM) than during P (-0.27 +/- 0.03 L/min/%SaO2, p = 0.05). UAR decreased as SaO2 decreased; this decrease was steeper during T than during P hypoxia (delta PR/%SaO2: 3.9 +/- 0.5 during P and 2.5 +/- 0.2 during T, p = 0.05). For the whole group, there was no difference in the slope of the decrease in UAR with increasing VT/Tl between the two hypoxic tests (delta PR/delta VT/Tl: -0.85 +/- 0.1 during P and -0.70 +/- 0.1 during T, p greater than 0.05). However, in four subjects, the slope of the relationship PR/VT/Tl during T remained steeper than during P. EELV increased as SaO2 decreased, with a greater increase during progressive than during transient hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory control in presenile dementia

To evaluate the role of the cerebral cortex in the response to externally added inspiratory flow-resistive load, we studied 7 patients manifesting clinical presenile dementia of the Alzheimer's type. All subjects exhibited diffuse cerebral cortical atrophy on computerized tomography of the brain. The mean age of the group was 45.6 yr. The rebreathing technique was used to assess minute ventilation (VE) and occlusion pressure (P100) responses to progressive hypercapnia. Rebreathing runs were performed before and during the addition of an inspiratory flow-resistive load of 18 cm H2O.L-1.s. The respiratory control data of these patients were compared with data obtained by similar techniques in a matched normal volunteer control group. In the patient group, with the addition of load, the VE/PCO2 response slope decreased (p less than 0.005), whereas the P100/PCO2 response slope did not significantly change. In the control group, P100/PCO2 response slope increased with load to maintain ventilation. These results suggest that in presenile dementia, during added inspiratory load, the drop in VE is associated with an inadequate increase in respiratory neuromuscular output. This lack of load compensation in patients with presenile dementia suggests a role for the cerebral cortex in the response to externally added load.     

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

Adenosine, an endogenous nucleoside, is released by hypoxic tissue, causes vasodilation, and influences ventilation. Its effects are mediated by P1-purinoceptors. We examined to what extent the plasma adenosine concentration in the peripheral venous blood correlates with hypoxic ventilatory response (HVR) and ventilatory drive P0.1 to find out whether endogenously formed adenosine has an influence on the individual ventilatory drive under hypoxic conditions. While investigating the HVR of 14 healthy subjects, the ventilatory drive P0.1 was measured with the shutter of a spirometer. Determination of the ventilatory drive P0.1(RA) started under room air conditions (21% O₂) and then inspiratory gas was changed to a hypoxic mixture of 10% O₂in N₂to determine P0.1(Hyp). At the time of the P0.1 measurements, two blood samples were taken to determine the adenosine concentrations. After removal of cellular components and proteins, samples were analyzed by high-pressure liquid chromatography (HPLC). Both adenosine concentrations in plasma under room air (r = 0.59, p< 0.05) and adenosine concentrations under hypoxia (r = 0.75, p< 0.01) correlated significantly with the ventilatory drive P0.1. In addition, plasma adenosine concentrations during hypoxic conditions showed a significant correlation with HVR on the 0.01 level (r = 0.71, p< 0.01). The results indicate a possible role of endogenous adenosine in the regulation of breathing in humans. We assume that endogenous adenosine influences the HVR and the ventilatory drive, probably by modulating the carotid body chemoreceptor response to hypoxia.     

Breathing pattern and occlusion pressure during exercise in pre- and peripubertal swimmers

In two groups of young swimmers (prepubertal stage: group A; peripubertal stage: group B), the ventilatory response to graded exercise work with a cycle ergometer was studied. Ventilatory variables (ventilation, VE, tidal volume, VT, respiratory frequency,f, ratio between inspiratory period and total breath duration, TI/TTOT, and mean inspiratory flow, VT/TI) as well as mouth occlusion pressure measured at 100 msec (P0.1), effective impedance of the respiratory system (P0.1/VT/TI), inspiratory power for breathing (W) and O2 uptake (VO2) were measured during the third minute of each work load. At the same level of exercise both groups showed identical values of VT/TI, but VE was higher in group A individuals. This resulted from higher values of respiratory frequency with higher TI/TTOT ratios. P0.1, P0.1(VT/TI) and W were also much higher during work load in group A than in peripubertal subjects. When the above results were related to the same percentage of VO2 max, P0.1, W, respiratory frequency and duty cycle did not differ within both groups. However, VE, VT and VT/TI were lower in group A subjects with a higher P0.1/(VT/TI) ratio. Further corrections of VT, VT/TI and P0.1/(VT/TI) ratios by body weight cancelled all these differences. In conclusion, our results strongly suggest that biometric factors only determined interindividual differences in ventilatory response to exercise in prepubertal and peripubertal swimmers.     

Inspiratory neural drive response to hypoxia adequately estimates peripheral chemosensitivity in OSAHS patients.

The aim of the present study was to examine the relationships between the responses to progressive isocapnic hypoxia and hypoxic withdrawal test in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and to analyse the determinants of carotid body sensitivity in OSAHS. Nineteen consecutive OSAHS patients and 13 healthy subjects were selected. Ventilatory (delta V'I/Sa,O2/BSA) and inspiratory neural drive (delta P0.1/Sa,O2) responses to progressive isocapnic hypoxia were determined. Peripheral chemosensitivity was evaluated by the hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% oxygen (%delta V'I). Withdrawal response and ventilatory and inspiratory neural drive responses to hypoxia were lower in OSAHS patients than in control subjects. In patients with OSAHS, %delta V'I correlated significantly with delta V'I/Sa,O2/BSA and with delta P0.1/Sa,O2. On stepwise multiple linear regression analysis, a strong correlation between %delta V'I and delta P0.1/Sa,O2 was found. Moreover, %delta V'I, delta V'I/Sa,O2/BSA and delta P0.1/Sa,O2 were significantly correlated with minimum arterial oxygen saturation and with arousal index. Obstructive sleep apnoea-hypopnoea syndrome patients have a strong relationship between peripheral chemosensitivity and respiratory response to hypoxia, suggesting that hypoxic stimulation of central chemoreceptors is minimally relevant in obstructive sleep apnoea-hypopnoea syndrome. Moreover, sensitivity of the carotid body in patients with obstructive sleep apnoea-hypopnoea syndrome is related to sleep disruption and to nocturnal hypoxia.     

Ventilatory control after pulmonary resection

Because pulmonary resection decreases pulmonary compliance, the effects of resection on ventilation might be similar to the known effects of elastic loading. We evaluated the breathing pattern and ventilatory drive in 12 patients before and after pulmonary resection with mean tissue loss of 4 segments. During resting ventilation, the only significant change after resection was a decrease in inspiratory time (Tl). At a higher level of minute ventilation (VE), induced by CO2 rebreathing, significant changes included increased respiratory frequency, decreased tidal volume and Tl, and increased occlusion pressure (P0.1). Both ventilation and occlusion pressure responses to CO2 (delta VE/delta PACO2, delta P0.1/delta PACO2) were unchanged after resection. We conclude that increased ventilation induced by CO2 rebreathing unmasks a breathing pattern after pulmonary resection which is similar to that seen with breathing against an external elastic load.     

Is there central respiratory depression after intravenous administration of propranolol?

Beta-adrenergic blockers have been reported to depress central ventilatory drive. The authors investigated this possibility in a double-blind, randomized fashion in 12 healthy volunteers who received 0.1 mg.kg-1 of propranolol and normal saline intravenously at two separate study sessions. A modified Read rebreathing technique was used. Both ventilatory and occlusion pressure responses to CO2 were measured to help separate peripheral (airway) from central mechanisms. Significant beta blockade was demonstrated by statistically lower heart rate responses to CO2 rebreathing after propranolol, but not normal saline. Nevertheless, propranolol exerted no significant effect on resting end-tidal CO2 or the ventilatory and occlusion pressure responses to CO2. Although health subjects appear to have minimal alterations in their ventilatory response to CO2 after beta-adrenergic blockade, patients with airway disease may still experience significant changes in ventilation. In addition, drug interaction studies may give further insight into the presence or absence of any respiratory effects of propranolol.     

Micturitional disturbances are associated with impaired breathing control in multiple sclerosis.

STUDY OBJECTIVES: To investigate whether the localization of multiple sclerosis (MS), the duration of the disease, and the level of neurologic functioning in patients with MS predispose them to disturbed breathing control. DESIGN: Case-control study. SETTING: Outpatient pneumology department of a university hospital. PATIENTS: Twenty-three MS patients and 51 healthy control subjects. MEASUREMENTS AND RESULTS: Resting mouth occlusion pressure at 0.1 s after onset of inspiratory effort (P0.1) was measured during the hypercapnic response (HCR) and the hypoxic response (HR) in all subjects. The Kurtzke expanded disability status scale and the functional system score were used to describe the level of neurologic functioning of the MS patients. Predictors of HCR and HR were assessed by multiple regression analysis. Low maximal inspiratory pressure (MIP) values correlated with low resting P0.1 values (r = 0.44; p = 0.05), although in neuromuscular diseases, high resting P0.1 values are usually found to compensate for low MIPs. Detrusor-sphincter dyssynergia (DSD) was the only predictor for lower ventilatory HCR (p = 0.006; r2 = 0.52), lower P0.1 HCR (p = 0.004; r2 = 0.47), lower ventilatory HR (p = 0.04; r2 = 0.28), and lower P0.1 HR (p = 0.04; r2 = 0.10); low MIPs and pyramidal tract involvement had no role. CONCLUSIONS: (1) Impaired control of breathing in some MS patients is related mainly to central defects. (2) DSD is the most important predictor of disturbed ventilatory control, presumably because the micturition and pneumotaxic center are closely related and located in the rostral pons. (3) No relationship with the duration of the MS disease could be demonstrated, which can be explained by the variable course of MS itself.     

Effect of Bedtime Ethanol on Total Inspiratory Resistance and Respiratory Drive in Normal Nonsnoring Men

We have previously reported that bedtime ethanol (2.0 ml/kg of 100 proof vodka) increases upper airway closing pressure in males who habitually snored but were otherwise healthy. We also observed that some of these snorers developed obstructive apneas. To explore this phenomenon in more detail, we measured the inspiratory resistance (R_I) and respiratory drive after bedtime ethanol in 10 nonobese men (ages 23 to 33) with no history of snoring. Subjects went to bed wearing a tightly fitting valved mask over the nose and mouth that allowed measurement of inspiratory and expiratory flow, pressure in the mask, and endtidal CO₂. We measured R_I by calculating the pressure difference between the mouth and a balloon positioned in the midesophagus. Respiratory drive was quantified by the inspiratory occlusion pressure (P_0.1), the ventilatory response to hyperoxic hypercapnia (ΔV_E/ΔP_ETCO₂), and the ventilatory response to isocapnic hypoxia (ΔV_E/ΔS,O₂). Measurements were made during waking and during stage 2 NREM sleep on two nights: (1) when the subjects drank 1.5 ml/kg of 100 proof vodka in orange juice over a 30-min period 15–45 min before lights out and (2) when the orange juice contained less than 0.1 ml of vodka floating on the top. Eight of the nine men in whom we had technically adequate measurements showed a rise in R_I during NREM sleep above the waking level on both control and ethanol nights and the sleeping R_I was greater on the ethanol than on the control night. There was a tendency for P_0.1 to be higher during sleep and greater on the ethanol night, suggesting that the neural output to the respiratory muscles was not depressed and may have been stimulated by the inspiratory “loading” secondary to the increased R_I. The hypercapnic response was significantly depressed during sleep. Whereas the response tended to be less on the ethanol than on the control night, the difference was not significant. The hypoxic response showed little change from waking to sleeping and no significant change with ethanol. We speculate that inspiratory loading due to increased upper airway resistance tends to stimulate respiratory drive and thereby partially offsets the depressant effect of ethanol on the central respiratory chemoreceptors.