Trazodone increases arousal threshold in obstructive sleep apnoea.

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean+/-sd age 49+/-9 yrs, apnoea/hypopnoea index 52+/-32 events.h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) level (mean+/-sd 7.30+/-0.57 versus 6.62+/-0.64 kPa (54.9+/-4.3 versus 49.8+/-4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(2)O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO(2) levels.

Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism).

Pharyngeal collapse in obstructive sleep apnea patients is likely a product of a sleep-related decrement in pharyngeal dilator muscle activity superimposed upon abnormal airway anatomy. We postulate that during wakefulness, increased pharyngeal dilator muscle activity in apnea patients compensates for diminished airway size thus maintaining patency. We studied the waking genioglossus (GG) electromyogram (EMG) activity in 11 OSA patients and 14 age-matched controls to determine if GG activity is higher in the awake state in apnea patients than controls. To make this determination, we developed a reproducible methodology whereby true maximal GG EMG could be defined and thus basal activity quantitated as a percentage of this maximal value. Therefore, direct comparisons of basal activity between individuals was possible. We observed apnea patients to have significantly greater basal genioglossal activity compared to controls (40.6 +/- 5.6% vs. 12.7 +/- 1.7% of maximum). This difference persisted when size-matched subsets were compared. This augmented GG activity in apnea patients could be reduced with positive airway pressure. We speculate that this neuromuscular compensation present during wakefulness in apnea patients may be lost during sleep leading to airway collapse.

Outcome and function following prolonged mechanical ventilation.

Prolonged periods of mechanically assisted ventilation are reasonably common occurrences, but there are no data regarding outcome for this patient population. We retrospectively reviewed the medical records of 250 consecutive patients with a minimum of ten days of ventilatory support during a five-year period. The overall survival was 39.2% at discharge, 28.6% at one year, and 22.5% at two years. Age and functional status prior to respiratory failure were the best predictors of survival. In addition, patients with postoperative or neurologic disease as the cause of respiratory failure were found to have the highest survival rate while those with cardiac and pulmonary disease had the worst prognosis. Of those patients who survived to discharge, 39.6% were institutionalized (nursing homes) and 32.7% were confined to their homes. Prolonged mechanical ventilation is associated with a limited survival and poor functional status in many who do survive.

Central sleep apnea. Improvement with acetazolamide therapy.

Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5 +/- 0.54 mm Hg. This may be important in mediating the observed decrease in apneas.

Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome.

Obstructive Sleep Apnea (OSA) is considerably more common in men than women. Preliminary data suggest that androgens may play a role in the male predominance of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual disturbances, androgen excess, and frequently obesity. These features suggest that women with PCOS may be at increased risk for OSA. To determine whether obese women with PCOS have an increased prevalence of sleep apnea compared with age and weight-matched reproductively normal women, we performed overnight polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese women with PCOS and age and weight-matched control women. Additional measurements included waist, hip, and neck circumferences, serum total testosterone, unbound testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/- 6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that obese women with PCOS are at increased risk of OSA when compared with matched reproductively normal women. Women with PCOS should be carefully questioned regarding symptoms of sleep apnea.

Complex home monitoring.

As the demand for sleep evaluations rises, one response has been to conduct such studies in the home. In this brief review, complex home sleep monitoring systems (those recording at least four channels of physiologic data) on which there is peer-reviewed data are assessed. Four currently available systems met these criteria and are discussed. Each such system has clear strengths and weaknesses. These overall data suggest that home monitoring systems are becoming increasingly complex and more successful in monitoring, the desired variables. This trend is likely to continue.

Evaluation of a computerized polysomnographic system.

Computerized polysomnographic systems have came into common use in sleep laboratories around the world. Despite potential advantages over standard paper polysomnography, these computerized systems have been minimally evaluated as to accuracy, analysis time, or cost effectiveness when compared to paper. We evaluated the Healthdyne ALICE 3 system for comparability to paper polysomnography in sleep quantification and technician analysis time. Fifty patients were recorded simultaneously both on paper and on the ALICE 3 system and analyzed blindly with summary data from these records being quantified and compared. Five additional patients were studied for epoch-by-epoch analysis. Score-rescore assessments were accomplished for both groups. The results indicate that when allowed to autoscore, this computerized system produced substantial errors in sleep staging (REM sleep time 56.4 + 4.9 minutes vs 73.2 + 8.4 minutes for paper versus computer). This was the case for respiratory (AHI of 26.5 + 4.3 vs 15.3 + 2.6 for paper vs computer) and arousal assessment as well. However, with editing, similar results to those obtained with paper were achieved (REM sleep time -56.4 + 4.9 vs 59.0 + 4.6; AHI -26.5 + 4.3 vs 26.1 + 4.7 for paper and computer respectively), with differences rarely exceeding score-rescore discrepancies. Analysis time was substantially reduced by use of the computer (172.6 + 9.9 vs 79.7 + 4.8 minutes for paper vs computer). Epoch-by-epoch analysis revealed a trend to score toward wakefulness or lighter sleep on computer compared to paper although the differences were small. Respiratory, arousal and PLM scoring were quite similar. In conclusion, this study suggests that the ALICE 3 system with editing can produce results similar to those obtained with paper.

Evaluation of the Healthdyne NightWatch system to titrate CPAP in the home.

Although a number of devices have been developed to monitor sleep and breathing in the home, there are few publications on methodologies by which CPAP can be titrated in the home setting. This study was conducted to determine the outcome of CPAP titration in the home using the Healthdyne NightWatch (NW) system. This home sleep-evaluation system was used to diagnose sleep apnea in 30 patients using a previously described methodology. These patients subsequently underwent CPAP titration in the home using the NW system, with modem technology allowing the transfer of data from the home to the laboratory. This group was compared with 30 patients who were diagnosed with sleep apnea using standard in-lab polysomnography and had CPAP titrated on a full night in the laboratory. Both groups were subsequently placed on CPAP at the appropriate pressure for 6-8 weeks, after which a full in-lab study was completed to assess CPAP efficacy at the prescribed pressure. Compliance was also determined using a pressure-activated monitor. No differences in any variable assessed could be found between the two groups. Mean compliance was 4.6 + 0.5 (SEM) and 4.3 + 0.5 hours of CPAP use per night for the home and in-lab groups respectively. Mean AHIs on the follow-up study were 7.4 + 1.2 and 7.6 + 1.6 events per hour for the home versus in-lab groups. Sleep stage distribution was also quite comparable between groups. As a result, this study suggests that sleep apnea can be diagnosed and CPAP titrated in the home with a similar outcome, at least at 6 to 8 weeks, to standard in-laboratory testing.

Local reflex mechanisms: influence on basal genioglossal muscle activation in normal subjects.

STUDY OBJECTIVES: To define the influence of topical nasopharyngeal anesthesia on genioglossal EMG responsiveness to both negative pressure and basal muscle activity. The effects on airway mechanics (resistance and collapsibility) were also determined. PARTICIPANTS: 18 normal adult subjects (9 males and 9 premenopausal females) DESIGN AND MEASUREMENTS: Genioglossal EMG (GG EMG) was measured with intramuscular electrodes. Basal phasic and tonic GG EMG were defined, in addition to the muscle response to multiple brief applications of negative airway pressure (-10 to 12 cm H2O). Airflow resistance (at 0.2 L/second and peak flow) plus airway collapsibility were also determined. All measurements were completed with and without dense nasopharyngeal anesthesia (lidocaine). RESULTS: Following nasopharyngeal anesthesia, peak GG EMG response to negative pressure fell from 28.1+/-4.3 (SE) to 19.6+/-3.4% of maximum (p<0.01). This was associated with a significant fall in both peak phasic and tonic GG EMG under basal conditions (phasic: 20.2+/-3.2 to 15.9+/-2.7% of maximum, tonic: 13.9+/-2.5 to 9.8+/-1.8% of maximum). Falling muscle activity led to a trend of rising airflow resistance and increasing airway collapsibility. CONCLUSIONS: Local, topical receptor mechanisms located in the nasopharynx importantly modulate upper airway dilator muscle activity in humans during normal tidal breathing. Therefore, the mechanisms exist for the airway to respond to local events which would tend to compromise airway patency.

Assessment of accuracy and analysis time of a novel device to monitor sleep and breathing in the home.

Obstructive sleep apnea is increasingly recognized as a common and debilitating disorder. As a result, a variety of diagnostic technologies have evolved to potentially decrease cost and improve access and ease of assessment. In this study we compared the Healthdyne NightWatch (NW) System (a home sleep diagnostic methodology) to standard polysomnography (PSG) in two sleep centers. Two separate studies were completed. NW was compared to a simultaneously obtained PSG in 30 patients (IN-LAB study). Seventy additional patients were studied in both the home with NW and in the laboratory with PSG (HOME-LAB study). The NW system records eye movement, leg movement, SaO2, nasal-oral airflow, chest and abdominal wall motion, body position and heart rate on a solid state recorder, which permits sleep staging based on body and eye movement and standard respiratory assessment. For the PSG, standard paper recording techniques were used. The IN-LAB study revealed a correlation between NW and PSG for total sleep time of r = 0.72, with NW tending to score some awake time as nonrapid eye movement sleep. The correlation for apnea-hypopnea index (AHI) was r = 0.94 between systems, with a sensitivity of 100% and specificity of 63.6% at an AHI threshold of 10. The HOME-LAB study demonstrated understandably poor correlations between NW and PSG for most measures of sleep, which is likely a product of night-to-night variability in sleep, home versus laboratory effects and the differences in sleep staging methodology. However, the correlation for AHI was r = 0.92, with a sensitivity of 90.7% and a specificity of 70.4% at an AHI threshold of 10. Using a new methodology to assess agreement between diagnostic systems, we observed 78.6% diagnostic agreement between NW and PSG in the HOME-LAB study, with NW underestimating AHI 4.3% of the time and overestimating it in 17.1% of cases. This may relate to night-to-night variability in AHI or greater NW computer sensitivity to subtle hypopneas. We conclude that NW provides an accurate determination of AHI in both the home and laboratory, using limited instrumentation. The analysis time for NW is also reduced compared to PSG, and patients generally prefer the NW evaluation.

Ventilatory responses to sustained eucapnic hypoxia in healthy males during wakefulness and NREM sleep.

The effects of sustained eucapnic hypoxia (SEH, 20 minutes SaO2, approximately 80%) on ventilation and supraglottic airflow resistance (Rua) plus genioglossal (gg) and diaphragmatic (di) electromyograms (EMGs) were compared during wakefulness and nonrapid eye movement (NREM) sleep in six healthy normal male subjects. Early augmentation of ventilation was followed by decline or roll-off in both states. The augmentation of ventilation was less in sleep than wakefulness (e.g., after 5 minutes hypoxia, 140% and 167% of baseline, respectively, p < 0.05). This appeared to be due to three factors: 1) sleep-related increases in Rua [the ventilatory responses to SEH (sleep vs. awake) were inversely related to changes in Rua (sleep vs. awake) (p < 0.05)], 2. reduced central neural drive (inspiratory phasic EMG di after 5 minutes SEH, 111% and 121% of baseline, p < 0.05), and 3) failure to increase respiratory frequency during SEH sleep. There was also a nonsignificant trend to a biphasic response in EMG gg and a small increase in Rua during SEH.

The influence of a transmucosal cholinergic agonist on pharyngeal muscle activity.

STUDY OBJECTIVE: To assess the effect of high local oral nicotine administration on the upper airway (UA) of normal males during wakefulness. DESIGN: Nonrandomized study. SETTING: Brigham & Women's Hospital General Clinical Research Center. PARTICIPANTS: Two groups of 13 and 12 normal male subjects were evaluated. INTERVENTIONS: A "Fast acting" or "Intermediate acting" 2 mg transmucosal nicotine patch was attached to an upper molar tooth of study participants during wakefulness. MEASUREMENTS: All data were collected prior to, and at several time points after, patch placement. Data measured included serum nicotine levels, genioglossal EMG, and pharyngeal resistance during basal breathing as well as the UA muscle response and UA collapsibility during negative UA pressure pulses. RESULTS: None of the variables measured showed a statistically significant change with either nicotine patch despite a significant rise (p<0.05) in nicotine serum levels post patch placement in both groups. In several subjects, muscle activity and responsiveness to negative pressure increased after application of both patches and returned to near baseline levels at the last time point measured, a response consistent with the time course of nicotine release in both patches. CONCLUSIONS: Oral nicotine administration failed to consistently increase GG muscle activation which may be a problem of local bioavailability of nicotine in the muscle.

Evaluation of the upper airway in patients with obstructive sleep apnea.

Multiple methods have been used to study the structure and physiological behavior of the upper airway (UA) in patients with obstructive sleep apnea (OSA). Valuable information may be obtained from the physiologic measurement of pressure and resistance along the UA, as well as from imaging techniques that include: direct or fiberoptic visualization, cephalometric roentgenograms, fluoroscopy, acoustic reflection, computerized tomography, and magnetic resonance imaging. This review summarizes the information that each of these methods has contributed to our understanding of the UA. The results obtained with these different methodologies have generally been complementary with structural narrowing being identified in the majority of patients with OSA. This narrowing is usually focal and located in the velopharyngeal or retropalatal segment of the UA. This is also the predominant site of initial UA collapse. Although obesity with enlargement of soft tissue structures is considered the predominant mechanism leading to UA narrowing, abnormal craniofacial development on a genetic or developmental basis plays an important contributory role.

Breathing during sleep in stable asthmatic subjects. Influence of inhaled bronchodilators.

The bronchoconstriction of asthma displays a circadian rhythm with exacerbations often occurring in the early morning hours. Gas exchange abnormalities during sleep in patients with severe asthma have been documented; however, the influence of sleep on gas exchange in the asthmatic with few or no daytime or nocturnal symptoms is poorly understood. To determine if abnormalities in oxygenation might occur during sleep, we studied 12 stable adult asthmatic patients with reversible airflow obstruction during sleep on three consecutive nights, with night 1 being for acclimatization. On test nights 2 and 3, the subjects received, in random double-blind fashion, either inhaled fenoterol or its placebo. Spirometry was performed before and after bronchodilator treatment and on the next morning. The mean FEV1 was 63 percent predicted before treatment. There was significant (p less than 0.05) improvement in FEV1 on fenoterol night after treatment which was also present the next morning. Mean prefenoterol FEV1 was 2.04 +/- .15 (SEM) and increased to 2.61 +/- .17 after the bronchodilator. The mean morning FEV1 was 2.27 +/- .20. Mean preplacebo FEV1 was 2.07 +/- .12 and did not change significantly with placebo bronchodilator. Sleep analysis demonstrated no significant differences in total sleep time or duration of oxyhemoglobin desaturation between nights. The incidence of sleep disordered breathing was very low (0.14 apneas/hour). The frequency of apneas and hypopneas did not change significantly with treatment. Two of the 12 subjects experienced an asthma attack on placebo night which did not recur following active bronchodilator administration. We conclude that stable asthmatic patients with few nocturnal complaints have a low frequency of disordered breathing and desaturation events during sleep.

Pulmonary function in obstructive sleep apnea. Relationships to pharyngeal resistance and cross-sectional area.

Reduction in the size of the pharynx and increased pharyngeal airflow resistance have been demonstrated in patients with obstructive sleep apnea (OSA). We evaluated 15 men with severe OSA and 10 nonapneic control subjects matched for age and weight in order to determine if PCSA, inspiratory pharyngeal airflow resistance, and abnormal breathing events during sleep were associated with alterations in the flow-volume relationship and other awake PFTs. Pharyngeal cross-sectional area was determined by CT, and pharyngeal resistance between choanae and epiglottis was measured during quiet awake breathing. In patients with OSA, there was an inverse relationship between the mean cross-sectional area of the oropharynx and the ratio of FEF50%/FIF50% (rs = -0.54; p = 0.03). In all subjects, pharyngeal resistance was inversely related to percentage of predicted values for FEF25-75% (rs = -0.56; p = 0.01). The frequency of apneas during sleep was significantly (p less than 0.05) related to the percentage of predicted values for MVV, TLC, FVC, and PIF. Obesity appears to account for the strength of these relationships. Flow-volume loops and other PFTs did not distinguish patients with OSA from controls.

Upper-airway collapsibility: measurements and sleep effects.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Several techniques have been proposed to assess the collapsibility of the upper airway in awake humans, but sleep-wake comparisons have rarely been attempted and there are few studies comparing OSA patients to control subjects. We sought to compare two collapsibility measurement techniques between normal and apneic subjects, and between wakefulness and sleep. DESIGN: We conducted three studies. First, we examined whether collapsibility assessed by negative pressure pulses (NPPs) during wakefulness reflected values during sleep in 21 normal subjects. Second, we determined in these normal subjects whether collapsibility during sleep assessed by NPPs was predictive of collapsibility measured by inspiratory resistive loading (IRL). Finally, we compared upper-airway collapsibility between apnea patients (n = 22) and normal volunteers (n = 38) during wakefulness by NPPs. SETTING: Clinical and research laboratories at the Brigham and Women's Hospital. PARTICIPANTS: Two populations of normal subjects (n = 21 and n = 38) and OSA patients (n = 22). MEASUREMENTS AND RESULTS: Collapsibility during wakefulness, as measured by NPPs, correlated significantly with collapsibility during sleep (r = 0.62; p = 0.003). There was also a significant correlation between the two measures of collapsibility (IRL and NPP) during sleep (r = 0.53; p = 0.04). Both measures revealed a significant increase in pharyngeal collapsibility during sleep as compared to wakefulness. Finally, apnea patients had significantly greater pharyngeal collapsibility than control subjects during wakefulness (p = 0.017). CONCLUSIONS: These data suggest that upper-airway collapsibility measured during wakefulness does provide useful physiologic information about pharyngeal mechanics during sleep and demonstrates clear differences between individuals with and without sleep apnea.

Nocturnal nasal continuous positive airway pressure in patients with chronic obstructive pulmonary disease. Influence on waking respiratory muscle function.

Patients with COPD often have reduced inspiratory muscle strength and endurance as well as poor exercise tolerance. Increased inspiratory work during sleep (probably due to increased upper airway resistance) may further strain these compromised respiratory muscles in COPD patients. We hypothesized that nasal continuous positive airway pressure (CPAP) might reduce respiratory work during sleep in COPD patients and thereby improve waking inspiratory muscle function. To test this hypothesis, eight male COPD patients were treated with sustained nocturnal nasal CPAP. Inspiratory muscle strength (maximum inspiratory pressure) and endurance (sustained inspiratory pressure) as well as clinical performance (12-min walk) were assessed before and after therapy. We observed that compared with matched controls, COPD patients treated with nocturnal nasal CPAP had significant and substantial improvement in inspiratory muscle strength and endurance as well as functional ability as assessed by the 12-min walk. In addition, CPAP did not significantly alter sleep quality or oxygenation in the patients studied. We conclude that nocturnal nasal CPAP improves inspiratory muscle performance during wakefulness in COPD patients, which is very likely a product of the reduced work of breathing during sleep while these individuals received CPAP.

Effects of oral narcotics on sleep-disordered breathing in healthy adults.

Alcohol and benzodiazepines may increase sleep-disordered breathing by decreasing activity of pharyngeal dilating muscles, favoring the development of obstructive apneas and hypopneas. Narcotics cause greater depression of wakeful respiration than the previously mentioned drugs; however, the influence of narcotics on the upper airway and breathing during sleep has not been studied. We, therefore, examined, in 12 healthy adults, the effects of oral hydromorphone hydrochloride (2 and 4 mg) on breathing during sleep and on a variety of awake respiratory variables (minute ventilation, gas exchange, and chemoresponsiveness). In addition, awake pharyngeal inspiratory airflow resistance was determined before and after narcotic administration to assess the drug's influence on patency of the upper airway. Following both doses, minute ventilation decreased, and carbon dioxide pressure increased. The 4-mg dose of hydromorphone hydrochloride also produced a significant decrement in the hypoxic ventilatory response, whereas hypercapnic responsiveness and pharyngeal resistance did not change following either dose of the drug. Despite the respiratory depression during wakefulness described previously, no significant change was observed in any measure of sleep-disordered breathing after either dose of narcotic. We conclude that in healthy individuals without suspected sleep apnea, oral hydromorphone in standard dosages does not significantly increase sleep-disordered breathing. This result may be due to a lack of selective depression of upper-airway muscular function by the doses of narcotic used.

Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement.

We developed a short-length document that clearly delineates a prudent approach to and criteria for reimbursement of positive airway pressure (PAP) costs for the treatment of obstructive sleep apnea (OSA). Treatment modalities for OSA with PAP include continuous positive airway pressure, bilevel or variable PAP, and autotitrating PAP. This guidance on the appropriate criteria for PAP use in OSA is based on widely acknowledged peer-reviewed studies and widely accepted clinical practice. These criteria reflect current opinion on the appropriate clinical management of OSA in lieu of data pending from the Sleep Heart Health Study and upcoming outcome studies. This document is not intended to provide a complete review and analysis of the OSA clinical literature. The key to the success of this document is to foster consensus within and outside the clinical sleep community by providing a common sense and easily understood approach to the treatment of OSA with PAP.

Occlusion pressure and ventilation during sleep in normal humans.

Previous investigation in normal humans has demonstrated reduced ventilation and ventilatory responses to chemical stimuli during sleep. Most have interpreted this to be a product of decreasing central nervous system sensitivity to the normal stimuli that maintain ventilation, whereas other factors such as increasing airflow resistance could also contribute to this reduction in respiration. To improve our understanding of these events, we measured ventilation and occlusion pressures (P0.1) during unstimulated ventilation and rebreathing-induced hypercapnia during wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Eighteen subjects (10 males and 8 females) of whom seven were snorers (5 males and 2 females) were studied. Ventilation was reduced during both NREM and REM sleep (P less than 0.05), but this decrement in minute ventilation tended to be greater in snorers than nonsnorers. Unstimulated P0.1, on the other hand, was maintained or increased during sleep in all groups studied, with males and snorers showing the largest increase. The hypercapnic ventilatory response fell during both NREM and REM sleep and tended to be lower during REM than NREM sleep. However, the P0.1 response to hypercapnia during NREM sleep was well maintained at the waking level although the REM response was statistically reduced. These studies suggest that the mechanism of the reduction in ventilation and the hypercapnic ventilatory response seen during sleep, particularly NREM sleep, is likely to be multifactorial and not totally a product of decreasing central respiratory drive.