Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities in postmenopausal women.

OBJECTIVE: To study the association of climacteric vasomotor symptoms and nocturnal breathing abnormalities in a sample of healthy postmenopausal women. METHODS: Out of 71 postmenopausal women who took part in a large sleep study, 65 women were included into the present study. Sleep was monitored with polysomnography and nocturnal breathing with a static-charge sensitive bed and a pulse oximeter. Climacteric vasomotor symptoms were scored daily for 14 days and levels of oestradiol and FSH were measured in the serum. RESULTS: Altogether 21 (32.3%) women had some degree of breathing abnormalities during the study night. The occurrence of clinically significant sleep apnoea was low (1.5%) and of moderate type (OP-2). In contrast, increased respiratory resistance pattern, typical for partial upper airway obstruction, was frequent (16.9%). Seventy-eight per cent of the women had arterial oxyhaemoglobin desaturation events, but only in 4.6% of the women these events occurred more than 5 times/h of time in bed. Older women had more simple periodic breathing (P-1) and lower mean arterial oxyhaemoglobin saturation (SaO(2)). Body mass index (BMI) correlated with the apnoea frequency (OP-2) and inversely with the mean SaO(2). The severity of climacteric vasomotor symptoms or serum oestradiol concentration did not correlate with nocturnal breathing abnormalities. CONCLUSIONS: Nocturnal breathing abnormalities, especially partial upper airway obstruction, are common in postmenopausal women, but climacteric vasomotor symptoms do not predict their occurrence or severity. Increasing age and high BMI are important determinants of nocturnal breathing abnormalities.     

Effect of 2000 m descent simulated in a hyperbaric chamber on arterial blood oxygen saturation and sleep quality in workers of a gold mine situated at an altitude of 3800-4200 m above sea level

Acute mountain sickness can become life threatening to people traveling at high altitude. Simulated descent with a hyperbaric chamber is a widely accepted way to treat this condition. The aim of this study was to analyze the influence of simulated descent to 2000 m on arterial oxygen saturation (SaO2), periodic breathing and sleep quality in a group of workers of a gold mine situated at 3800 m. Sleep studies were performed twice in stationary hyperbaric chamber with a portable system--MESAM IV in 20 workers. During the first study the chamber was not pressurized and on the second night the barometric pressure was set to mimic descent to 2000 m. During second study, a significant decrease in ODI (Oxygen Desaturation Index), from 9.7 +/- 6/h to 1.8 +/- 3.4/h (p < 0.0001), was noticed; mean SaO2 increased from 84.3 +/- 3.2% do 92.7 +/- 2.8% (p < 0.0001), significant changes in percentage of study time in individual SaO2 ranges were also noticed. The number (12.7 +/- 8.4 vs. 7.5 +/- 5; p < 0.05) and index of changes in body position were decreased (2.0 +/- 1.5 vs. 1.2 +/- 0.9/h; p < 0.05) as well. CONCLUSION: Simulated descent to 2000 m causes a decrease in number of desaturations, improvement in mean SaO2 during sleep, decrease in heart rate and these data suggest a decrease in periodic breathing during sleep. A decrease in number and index of body position changes suggests improved sleep quality.     

Sleep and breathing at altitude of 3800 m--the acclimatization effect

Periodic breathing (PB) is a very common phenomenon occurring during sleep at high altitude. It consists of repetitive apneas or hypopneas of central origin and clusters of hyperpneic breaths. The aim of this study was to analyze sleep structure and periodic breathing in shift workers of a gold mine situated in Tien-Schan Mountains at 3800 m. In 12 subjects aged 36.1 +/- 9.3 yrs, polysomnography (PSG) was performed twice, on the night after the first working shift or during the day following first night shift, and the second PSG at the end of the first week of work. After one week, significant increase in REM sleep was noticed (5.2 +/- 4.0% vs. 12.0 +/- 6.7%, p < 0.05). There were no differences in sleep pattern between night sleep and sleep during daytime. During first PSG periodic breathing was seen in all subjects and occupied 14.7 +/- 16.6% of total sleep time. After one week PB decreased in 8 subjects however, in 4 subjects an increase in PB was observed (15.4 +/- 11.2 vs. 29.0 +/- 11.8% of sleep time). CONCLUSIONS: Sleep at altitude is characterized by reduction of REM sleep, which improves after a week of acclimatization. There are great individual variations in duration of periodic breathing; in some subjects an increase in PB can be seen.     

Zaleplon and zolpidem objectively alleviate sleep disturbances in mountaineers at a 3,613 meter altitude

STUDY OBJECTIVES: To assess the effects of zolpidem and zaleplon on nocturnal sleep and breathing patterns at altitude, as well as on daytime attention, fatigue, and sleepiness. DESIGN: Double-blind, randomized, placebo-controlled, cross-over trial. SETTING: 3 day and night alpine expedition at 3,613 m altitude. PARTICIPANTS: 12 healthy male trekkers. PROCEDURE: One week spent at 1,000 m altitude (baseline control), followed by 3 periods of 3 consecutive treatment nights (N1-3) at altitude, to test 10 mg zolpidem, 10 mg zaleplon, and placebo given at 21:45. MEASURES: Sleep from EEG, actigraphy and sleep logs; overnight arterial saturation in oxygen (SpO2) from infrared oximetry; daytime attention, fatigue and sleepiness from a Digit Symbol Substitution Test, questionnaires, and sleep logs; acute mountain sickness (AMS) from the Lake Louise questionnaire. RESULTS: Compared to baseline control, sleep at altitude was significantly impaired in placebo subjects as shown by an increase in the amount of Wakefulness After Sleep Onset (WASO) from 17 +/- 8 to 36 +/- 13 min (P<0.05) and in arousals from 5 +/- 3 to 20 +/- 8 (P<0.01). Slow wave sleep (SWS) and stage 4 respectively decreased from 26.7% +/- 5.8% to 20.6% +/- 5.8% of total sleep time (TST) and from 18.2% +/- 5.2% to 12.4% +/- 3.1% TST (P<0.05 and P<0.001, respectively). Subjects also complained from a feeling of poor sleep quality combined with numerous 02 desaturation episodes. Subjective fatigue and AMS score were increased. Compared to placebo control, WASO decreased by approximately 6 min (P<0.05) and the sleep efficiency index increased by 2% (P<0.01) under zaleplon and zolpidem, while SWS and stage 4 respectively increased to 22.5% +/- 5.4% TST (P<0.05) and to 15.0% +/- 3.4% TST (P<0.0001) with zolpidem only; both drugs further improved sleep quality. No adverse effect on nighttime SpO2, daytime attention level, alertness, or mood was observed under either hypnotic. AMS was also found to be reduced under both medications. CONCLUSIONS: Both zolpidem and zaleplon have positive effects on sleep at altitude without adversely affecting respiration, attention, alertness, or mood. Hence, they may be safely used by climbers.     

High‐altitude hypoxia and periodic breathing during sleep: gender‐related differences

High‐altitude exposure is characterized by the appearance of periodic breathing during sleep. Only limited evidence is available, however, on the presence of gender‐related differences in this breathing pattern. In 37 healthy subjects, 23 male and 14 female, we performed nocturnal cardio‐respiratory monitoring in the following conditions: (1) sea level; (2) first/second night at an altitude of 3400 m; (3) first/second night at an altitude of 5400 m and after a 10 day sojourn at 5400 m. At sea level, a normal breathing pattern was observed in all subjects throughout the night. At 3400 m the apnea–hypopnea index was 40.3 ± 33.0 in males (central apneas 77.6%, central hypopneas 22.4%) and 2.4 ± 2.8 in females (central apneas 58.2%, central hypopneas 41.8%; P < 0.01). During the first recording at 5400 m, the apnea–hypopnea index was 87.5 ± 35.7 in males (central apneas 60.0%, central hypopneas 40.0%) and 41.1 ± 44.0 in females (central apneas 73.2%, central hypopneas 26.8%; P < 0.01), again with a higher frequency of central events in males as seen at lower altitude. Similar results were observed after 10 days. With increasing altitude, there was also a progressive reduction in respiratory cycle length during central apneas in males (26.9 ± 3.4 s at 3400 m and 22.6 ± 3.7 s at 5400 m). Females, who displayed a significant number of central apneas only at the highest reached altitude, were characterized by longer cycle length than males at similar altitude (30.1 ± 5.8 s at 5400 m). In conclusion, at high altitude, nocturnal periodic breathing affects males more than females. Females started to present a significant number of central sleep apneas only at the highest reached altitude. After 10 days at 5400 m gender differences in the apnea–hypopnea index similar to those observed after acute exposure were still observed, accompanied by differences in respiratory cycle length.     

Sleep structure and periodic breathing in Tibetans and Han at simulated altitude of 5000 m

Tibetans are the oldest population living permanently at high altitude. They possess several adaptations to low oxygen pressure that improve oxygen transport. We hypothesised that native Tibetans have mechanisms allowing them to maintain a better sleep structure and oxygenation during sleep at high altitude than newcomers from lower altitudes acclimatised to living at high altitude. We studied eight healthy young Tibetans, aged 26+/-7 years, and six healthy young Han aged 30.5+/-4 years. All subjects were living on the Tibetan plateau at an altitude of around 4000 m. Investigations were performed in Xining at an altitude of 2261 m, PB=581 mmHg. Two full polysomnographies (PSG) were performed in a hypobaric chamber, one at the ambient altitude, the second during acute exposure to the simulated altitude of 5000 m (PB=405 mmHg). Both PSG were done on the same night using split night design. At 2261 m no differences in sleep structure, breathing pattern during sleep or oxygenation were found, except a higher number of arousals and awakenings in Han (P<0.002). At 5000 m Tibetans had a longer sleep time (P=0.002), shorter stage 1 non-REM sleep (P<0.001) and longer stage 2 non-REM sleep than Han (P<0.001). Tibetans showed a trend to have more periodic breathing (PB) and higher mean arterial blood saturation than Han (NS). Our data suggest that Tibetans preserved better sleep structure and arterial blood oxygenation than Han during acute exposure to the simulated altitude of 5000 m.     

Acclimatisation in trekkers with and without recent exposure to high altitude

In mountaineers, recent altitude exposure has been shown to improve climbing performance and clinical outcomes during re-exposure to high altitude. However, the timing of previous altitude exposure has not been clearly reported and previous findings might be driven by individuals who were still acclimatised at the time of re-exposure. Our goal was to determine whether recent altitude exposure would confer an advantage even in individuals who had de-acclimatised for ≥ 1 week before being re-exposure. Low-altitude natives kept a daily trekking log throughout 7- to 8-day trek from Lukla (2,840 m) to Gokyo Ri (5,360 m). Trekkers with recent altitude exposure (re-acclimatisers, RA; n = 20) walked 20% faster (p < 0.01), reported lower acute mountain sickness scores (9 ± 8 vs. 15 ± 13; p = 0.02), and used less medication to treat headache (p < 0.05) compared to trekkers with no recent altitude exposure (initial acclimatisers, IA; n = 30). On Gokyo Ri, S(p)O(2) was significantly higher in RA than IA trekkers (85 ± 6 vs. 78 ± 6; p = 0.01). These data indicate improved functional outcomes and physiological compensation for hypoxia in RA. However, even after de-acclimatisation for 7-30 days, it is possible that RA trekkers began the trek in a more acclimatised state than IA trekkers. RA trekkers might represent a self-selected group that has previously tolerated altitude well and has therefore opted to return. Some findings might also reflect improved psychological altitude tolerance in RA. A direct comparison of the functional and physiological responses to hypoxia throughout an initial and re-acclimatisation to high altitude is needed.     

Efficacy and safety of as-needed, post bedtime dosing with indiplon in insomnia patients with chronic difficulty maintaining sleep

OBJECTIVE: To evaluate the efficacy and tolerability of immediate release indiplon capsules in patients with chronic insomnia using an "as-needed" dosing strategy in response to difficulty falling back to sleep following a middle of the night, nocturnal awakening. METHODS: Adult outpatients (N=264; 71% female; age, 46 years) who met DSM-IV criteria for primary insomnia, with average total sleep time (TST) < 6.5 hours and >8 nights in the past month with nocturnal awakenings, were randomized to 4 weeks of double-blind treatment with 10 mg or 20 mg indiplon capsules, or placebo. The primary endpoint was latency to sleep onset post-dosing after a middle of the night awakening (LSOpd). Secondary endpoints included patients' subjective assessment of total sleep time (sTSTpd). Next day residual effects were evaluated by a 100 mm Visual Analog Scale (VAS) rating of sleepiness. RESULTS: Both doses of indiplon significantly reduced LSOpd at all time-points. Compared to placebo (45.2 min), the 4-week least squares (LS) mean LSOpd was 36.5 min in the indiplon 10 mg group (P = 0.0023) and 34.4 min in the indiplon 20mg group (P < 0.0001). The 4-week LS mean sTSTpd was higher in the indiplon 10 mg group (253 min) and 20mg group (278 min) compared to placebo (229 min; P < 0.01 for both comparisons). There was no increase observed in VAS ratings of next-day sleepiness for either dose of indiplon when compared to placebo. Indiplon was well-tolerated at both doses. CONCLUSIONS: Patients with chronic insomnia with nocturnal awakenings achieved significant and sustained improvement in sleep parameters while utilizing an as-needed post bedtime dosing strategy with indiplon capsules. Indiplon was well-tolerated, with no self-rated, next-day residual effects.     

The acute effects of uvulopalatopharyngoplasty on breathing during sleep in sleep apnea patients

Uvulopalatopharyngoplasty (UPPP) is frequently employed in the treatment of obstructive sleep apnea (OSA). Despite anecdotal reports of early post-UPPP deaths and the recommendation by some authors to perform a prophylactic tracheotomy for selected patients at the time of UPPP, there has been no systematic examination of breathing during sleep in the early post-UPPP period. In order to evaluate the early postoperative risk and the need for prophylactic tracheotomy in UPPP patients, we conducted polysomnograms (PSGs) on eight obese OSA patients on the second post-UPPP night and on another obese OSA patient on the fifth night after surgery. Postoperatively during wakefulness there was a significant increase in the alveolar-arterial oxygen gradient (p less than 0.05); in three individuals, the PaO2 was sufficiently reduced to warrant supplemental oxygen. For the group of nine patients there were no differences between the pre- and post-UPPP apnea index (AI), hypopnea index (HI), or apnea plus hypopnea index during non-rapid eye movement sleep. In individual patients, the pattern of sleep-disordered breathing events was variably altered, but there was a reciprocal relationship between the changes in AI and HI (r = 0.75; p less than 0.02). The duration of apnea in non-rapid eye movement sleep was shorter in four patients and unchanged in five patients postoperatively. Although the mean nadir of hemoglobin saturation was unchanged before and after UPPP, one patient desaturated to dramatically low levels in association with several excessively prolonged apneas post-UPPP. Desaturation was probably minimized in the three patients receiving supplemental oxygen. There were no serious adverse effects resulting directly from sleep-disordered breathing or nocturnal hemoglobin oxygen desaturation following UPPP. Our data suggest that performing a tracheotomy in a nonselective fashion in OSA patients undergoing UPPP is not warranted. In lieu of this, these individuals should be carefully monitored following surgery. In addition, patients with severe OSA and/or moderate-to-severe nocturnal hemoglobin oxygen desaturation should be considered for early postoperative PSGs as should those individuals who are more hypoxemic while awake following surgery. Patients who require supplemental oxygen postoperatively should also be studied to ensure adequate oxygenation and to monitor for acute, oxygen-related prolongation of apnea.     

Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure

OBJECTIVE: The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. INTERVENTIONS: Oxygen. MEASUREMENTS AND RESULTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). CONCLUSION: In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.     

Short-term effects of normobaric hypoxia on the human spleen

Spleen contraction resulting in an increase in circulating erythrocytes has been shown to occur during apnea. This effect, however, has not previously been studied during normobaric hypoxia whilst breathing. After 20 min of horizontal rest and normoxic breathing, five subjects underwent 20-min of normobaric hypoxic breathing (12.8% oxygen) followed by 10 min of normoxic breathing. Ultrasound measurements of spleen volume and samples for venous hemoglobin concentration (Hb) and hematocrit (Hct) were taken simultaneously at short intervals from 20 min before until 10 min after the hypoxic period. Heart rate, arterial oxygen saturation (SaO(2)) and respiration rate were recorded continuously. During hypoxia, a reduction in SaO(2) by 34% (P < 0.01) was accompanied by an 18% reduction in spleen volume and a 2.1% increase in both Hb and Hct (P < 0.05). Heart rate increased 28% above baseline (P < 0.05). Within 3 min after hypoxia SaO(2) had returned to pre-hypoxic levels, and spleen volume, Hb and Hct had all returned to pre-hypoxic levels within 10 min. Respiratory rate remained stable throughout the protocol. This study of short-term exposure to eupneic normobaric hypoxia suggests that hypoxia plays a key role in triggering spleen contraction and subsequent release of stored erythrocytes in humans. This response could be beneficial during early altitude acclimatization.     

Hypnotic activity of melatonin

OBJECTIVE: To establish the effect of melatonin upon nocturnal and evening sleep. METHODS: Experiment I: The effect of melatonin (0.1, 0.5, 1.0, 5.0, and 10 mg), ingested at 23:30, was studied on nocturnal sleep (23:30-07:30) and core body temperature in 8 healthy volunteers. Performance was measured 8.5 h post-ingestion. On completion of the experiment dim light melatonin onsets (DLMO) were determined. Experiment II: The effect of melatonin (0.5, 1.0, 5.0, and 10 mg), ingested at 18:00, was studied on evening sleep (18:00-24:00) and core body temperature in 6 healthy volunteers. Performance was measured 6.5 h post-ingestion. Each experiment was placebo-controlled and double-blind with a cross-over design with temazepam (20 mg) as an active control. RESULTS: Experiment I: Melatonin (5 mg) reduced the duration of stage 3 in the first 100 min of sleep. Melatonin (0.1 mg) reduced body temperature 6.5 to 7 h post-ingestion. Temazepam increased stage 2, reduced wakefulness and stage 1, and increased the latency to REM sleep. Temazepam reduced body temperature 4.5 to 6.5 h post-ingestion. There were no changes in performance compared with placebo. DLMO occurred between 20:40 and 23:15. Experiment II: Melatonin (all doses) increased total sleep time (TST), sleep efficiency index (SEI) and stage 2, and reduced wakefulness. Temazepam increased TST, SEI, stage 2 and slow-wave sleep, and reduced wakefulness. There were no changes in body temperature or performance compared with placebo. CONCLUSION: Melatonin given at 23:30 has no significant clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of melatonin when given in the early evening (presumably in the absence of endogenous melatonin) is similar to 20 mg temazepam.     

Oxygenation and breathing pattern during phasic and tonic REM in patients with chronic obstructive pulmonary disease

Oxygen desaturation in chronic obstructive pulmonary disease (COPD) occurs during sleep and is most marked in REM sleep. REM is not a homogeneous state, consisting of phasic REM (PREM) (REMs, myoclonic twitches) and tonic REM (TREM) (muscle atonia, desynchronized electroencephalogram). In normals, onset of PREM produces transient changes in breathing pattern with a decrease in respiratory amplitude and an increase in frequency, which produce reductions in oxygen saturation (SaO2). Because it is reasonable to expect such breathing pattern changes to cause more desaturation in COPD, and because systematic all-night studies of PREM and TREM have not been reported, we studied 18 patients with severe COPD [Forced expiratory volume in one second (FEV1) = 25.7 +/- 3.5 (SEM) % predicted] during sleep and monitored SaO2 and breathing pattern in PREM and TREM. PREM made up 19.7% of total REM (4.6% total sleep time) but was associated with 81.7% of the total REM desaturations of greater than 5% (57.9% of all sleep desaturations of greater than 5%). With PREM onset, breathing pattern changed 72.5% of the time, most often with a transient decrease in amplitude and increase in frequency. Even though 27.5% of PREM was not associated with changes in breathing pattern and many PREM segments were very short, we were still able to show highly significant SaO2 differences between PREM and TREM. Mean TREM SaO2 was 88.0 +/- 1.2%; mean PREM SaO2 was 86.6 +/- 1.4%, with mean nadir SaO2 for individual PREM segments falling to 84.8 +/- 1.5%. Mean awake SaO2 was 89.7 +/- 0.8%. We conclude that in COPD the transition from TREM to PREM is associated with breathing pattern changes and oxygen desaturation. Differences in breathing pattern with PREM onset may be related to different effects of PREM processes on respiratory neurons and diaphragm motor neurons.     

Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

Centrally active agents have a variable impact in patients with obstructive sleep apnoea (OSA) that is unexplained. How to phenotype the individual OSA response is clinically important, as it may help to identify who will be at risk of respiratory depression and who will benefit from a centrally active agent. Based on loop gain theory, we hypothesized that OSA patients with higher central chemosensitivity have higher breathing instability following the use of a hypnosedative, temazepam. In 20 men with OSA in a double‐blind, placebo‐controlled cross‐over trial we tested the polysomnographically (PSG) measured effects of temazepam 10 mg versus placebo on sleep apnoea. Treatment nights were at least 1 week apart. Ventilatory chemoreflexes were also measured during wakefulness in each subject. The patients (mean ± standard deviation; 44 ± 12 years) had predominantly mild‐to‐moderate OSA [baseline apnoea–hypopnoea index (AHI) = 16.8 ± 14.1]. Patients’ baseline awake central chemosensitivity correlated significantly with both the change of SpO₂ nadir between temazepam and placebo (r = ?0.468, P = 0.038) and oxygen desaturation index (ODI; r = 0.485, P = 0.03), but not with the change of AHI (r = 0.18, P = 0.44). Peripheral chemosensitivity and ventilatory recruitment threshold were not correlated with the change of SpO₂ nadir, ODI or AHI (all P > 0.05). Mild–moderate OSA patients with higher awake central chemosensitivity had greater respiratory impairment during sleep with temazepam. Relatively simple daytime tests of respiratory control may provide a method of determining the effect of sedative–hypnotic medication on breathing during sleep in OSA patients.     

Assessing nighttime vigilance through a three-letter cancellation task (3-LCT): effects of daytime sleep with temazepam or placebo

Nocturnal sleepiness is a common complaint suffered by night-shift workers, especially in conditions of an abrupt shift of the wake-sleep cycle. Alertness management strategies can minimize the adverse effects of sleep loss and circadian rhythm desynchronization and promote optimal vigilance in operational settings. Within these strategies. one possibility is to use short periods of "prophylactic sleep" (before long periods of work), which can be facilitated by hypnotics. Vigilance can be evaluated by means of several tests which, sometimes, imply procedures and devices not easily employable in operational settings. In such conditions pencil and paper tests of vigilance can be very useful in the assessment of attentional performance degradation due to sleep loss and/or inversion of the sleep-wake cycle. In this study we evaluated the sensitivity of a three-Letter Cancellation Task (3-LCT) in revealing nighttime variations of vigilance in a laboratory simulation of acute night shift, after a diurnal sleep with placebo (PLC) or temazepam (TMZ). Nocturnal levels of vigilance were also assessed using the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT). All tests were administered four times at 2-h intervals during nighttime after a daytime sleep. Results show that the 3-LCT is sensitive to variations of vigilance occurring during a laboratory simulation of acute night shift. We also found some effects of TMZ, which in the first nocturnal session caused a slowing down of visuoattentive performance. Nocturnal variations of vigilance detected through the 3-LCT were similar to those revealed by means of MSLT, while the ability to maintain wakefulness was substantially spared during the night.     

Auditory evoked responses upon awakening from sleep in human subjects

The hypothesis that a state of hypoarousal upon awakening should lead to a decrease in amplitude and an increase in latency of the N1-P2 components of the Auditory Evoked Potentials (AEPs) as compared to presleep wakefulness levels, was evaluated after two nocturnal awakenings and after the final morning awakening from a 7.5-h night of sleep. The amplitude of the N1-P2 complex was reduced upon awakening as compared to presleep wakefulness levels, but only following the first nocturnal awakening, scheduled after the first 2 h of sleep. This result is interpreted as indicating a link between slow wave sleep amount, mainly present during the first part of the night, and lowered levels of brain activation upon awakening. The reaction times, recorded concomitantly to AEPs, were more sensitive to the negative effects of sleep inertia.     

Fasting glycemia in sleep disordered breathing: lowering the threshold on oxyhemoglobin desaturation

STUDY OBJECTIVES: Commonly used definitions of sleep-disordered breathing (SDB) are based on identifying discrete events of breathing abnormalities during sleep that are accompanied by an oxyhemoglobin desaturation (delta SaO2) of at least 4%. However, it is not known whether disordered breathing events with oxyhemoglobin desaturation less than 4% are associated with clinical sequelae such as abnormalities in fasting glycemia. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: Participants from the Sleep Heart Health Study (SHHS) with a fasting glucose measurement made within a year of the baseline polysomnogram. MEASUREMENTS AND RESULTS: SDB severity was defined using the apnea-hypopnea index (AHI) and the hypopnea index (HI) by counting events with different levels of oxyhemoglobin desaturation (0.0%-1.9%, 2.0%-2.9%, 3.0%-3.9%, > or = 4.0%). Fasting glucose levels were used to classify individuals into normal (<100 mg/dL), impaired (100-125 mg/dL), and diabetic (> or = 126 mg/dL) groups. Ordinal logistic regression was used to determine the adjusted relative odds of an abnormal glucose value across quartiles of the hypopnea index, independent of factors such as age, body mass index, waist circumference, and usual sleep duration. The prevalence of impaired and diabetic fasting glucose in the analytical sample was 32.9% and 5.8%, respectively. The covariate-adjusted relative odds of impaired or diabetic fasting glucose in the highest versus the lowest AHI quartile was 1.35 (95% CI: 1.04-1.76) for events with a delta SaO2 > or = 4.0%, 1.72 (95% CI: 1.20-2.48) for events with a delta SaO2 between 3.0%-3.9%, 1.41 (95% CI: 1.07-1.86) for events with a delta SaO2 between 2.0%-2.9%, and 1.07 (95% CI: 0.84-1.37) for events with a delta SaO2 between 0.0%-1.9%. The corresponding odds ratios for the HI were 1.47 (95% CI: 1.13-1.92), 2.25 (95% CI: 1.59-3.19), 1.44 (95% CI: 1.09-1.90), and 1.15 (95% CI: 0.90-1.47), respectively. CONCLUSIONS: The results of this study indicate that SDB events accompanied by oxyhemoglobin desaturation of between 2% to 4% are associated with fasting hyperglycemia. These findings suggest that milder degrees of SDB may predispose to adverse metabolic outcomes.     

Comparison between ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia in healthy sleeping man

Ventilatory and mouth occlusion pressure (P0.1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (VE), tidal volume (VT), 'duty cycle' (TI/TT), mean inspiratory flow rate (VT/TI) and P0.1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at 'equivalent' levels of hypoxia and hypercapnia, i.e., at levels which produced the same P0.1 during wakefulness: an oxyhaemoglobin saturation (Sao2) of 94% during the isocapnic-hypoxic tests (PETCO2 = 42.5 +/- 1.2 mmHg) was found to be equivalent to a PETCO2 of 47.4 +/- 3.7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P0.1 were similar in all sleep stages. Sleep did not significantly modify P0.1 or breathing pattern responses to hypoxia (Sao2 = 94%). In contrast, at the 'equivalent' level of hypercapnic stimulation, P0.1 (P less than 0.05) and VE (P less than 0.01) responses were significantly impaired, particularly in REM sleep, with a decrease in VT (P less than 0.01) and VT/TI (P less than 0.05) responses. The results suggest that CO2 intracranial receptor mechanisms are more affected by sleep than the O2 peripheral receptor activity.     

A theoretical study of the effect of circadian rhythms on sleep-induced periodic breathing and apnoea

This study employed a mathematical model of the respiratory control system to test the plausibility of the hypothesis that circadian rhythms in respiratory control can significantly influence respiratory stability at sleep onset. Computer simulations utilized a standardized "normal" sleep onset effect, superimposed upon systematic changes in chemoreflex parameters that mimicked the peaks and troughs of normal and high amplitude circadian rhythms. The analysis predicted that circadian influences may augment sleep-induced periodic breathing in nocturnal sleep compared with daytime naps. Furthermore, increased circadian amplitude of chemoreflex threshold, or absence of a circadian rhythm in peripheral chemosensitivity, each acted to stabilize respiration during daytime sleep onset and promote periodic breathing during nocturnal sleep onset. High amplitude circadian rhythms in respiratory control were predicted to cause an increasing number and duration of obstructive apnoeas from early to late night. It is suggested that the circadian timing system creates a nocturnal window of respiratory vulnerability and that abnormal circadian rhythms could potentially induce nocturnal sleep apnoea, even in individuals with normal sleep mechanisms.     

Ear oximetry studies during sleep in patients with severe chronic obstructive pulmonary disease in a stable state

Changes in ear oxygen saturation (SaO2) during the night were measured in 12 elderly patients (mean age = 63.4 +/- 6.7 years) with stable severe chronic obstructive pulmonary disease. The mean FEV1 was 0.84 L (range = 0.45 to 1.30 L) and the mean SaO2 daytime value was 94.4% (range = 93% to 96%). The mean maximal decrease in SaO2 from daytime to sleep was 2.3% (range = 0% to 4%). There was no correlation between the decrease in SaO2 during sleep and the degree of airways obstruction, or the daytime SaO2. In contrast to published data, our 12 patients did not have a significantly lower mean minimum SaO2 than those without chronic obstructive pulmonary disease.