Abstract
This thesis has investigated the effects of a number of environmental factors on sleep and explored the amelioration of such effects by pharmacological interventions. The presence of changes in sleep was measured by recordings of the electrical activity of the brain (electroencephalogram, EEG), eye movements (electroocculogram, EOG) and muscle activity (electromyogram, EMG). The pharmacological interventions were not only tested for their efficacy in ameliorating sleep deprivation or sleep disturbance but also far any residual effects on performance. The environmental factors studied were those that are likely to be encountered by occupational groups such as shiftworkers, aircrew and mountain guides. Any disturbance of sleep in these groups may lead to episodes of drowsiness and performance impairments when they are carrying out skilled tasks. It is therefore important to investigate safe treatments to ameliorate the sleep disturbances. Shift work and jet lag do not have direct effects on sleep rather it is the requirement to sleep at times in the circadian cycle that are not conducive to sleep that causes problems. The morning sleep after the night shift is shorter than night sleep and adaptation of the circadian rhythm confers little benefit in those workers whose shifts rotate rapidly. Cumulative sleep deprivation and a low alertness at night lead to performance impairments. Early morning shifts also cause problems as workers find it difficult to retire early at a time of peak alertness. Jet lag leads to difficulties with sleep depending on the direction of travel. Westward travel causes similar problems to night work: difficulties in maintaining sleep. Eastward travel is associated with difficulties in falling asleep as the traveller attempts to sleep early in the circadian cycle. The drug investigated for the treatment of shift work and jet lag was melatonin. Melatonin has been advocated for the treatment of such conditions. The usefulness of melatonin depends on its ability to be effective at all times in the circadian cycle. A dose response study (0.5 to 10mg) on its effects on nocturnal and evening sleep was compared with a benzodiazepine (temazepam 20mg) which is often used by individuals coping with irregular patterns of work. Melatonin had little effect on nocturnal sleep. Hypnotic activity of melatonin (0.5 to 10 mg) in the evening was similar to 20 mg temazepam. Sleep is disturbed in those who ascend to altitude with periodic breathing and many awakenings, this may lead to daytime drowsiness and impaired performance. Sleep disturbance at two altitudes, 3500m, in the Italian Alps, and 5400m, in the Karakorum mountains in Pakistan, were studied. The effects of 20mg temazepam at the lower altitude and the effects of 10mg temazepam together with 500mg acetazolamide daily were studied in two groups of climbers. In addition a dose response study of the effects of temazepam (10 to 30 mg) and diazepam 10mg on sleep at ‘altitude’ was carried out in a decompression chamber at a simulated altitude of 3810m. Sleep during the alpine expedition was limited to reductions in sleep efficiency and increases in awake activity. Delays and reductions in rapid eye movement sleep were seen at the beginning of the stay at altitude. No overall benefit of temazepam was seen at this lower altitude although some benefit was seen in older subjects who had more disturbed sleep. No relationships between hypoxic ventilatory responses and behaviour at altitude were established. In the Karakorum expedition sleep at around 5,400m was very disturbed in spite of prophylactic treatment with acetazolamide. Total sleep time was lower and sleep onset lengthened linearly during the six nights at 5,400m. Similar reductions in sleep efficiency and stage 4 sleep were also observed. The number of respiratory pauses greater than 5 seconds at 5,400 ranged from 700 per night in one subject to less than 20 in another. There was no effect of temazepam on the number of these events. The beneficial effects of temazepam (10mg) on sleep seen previously at around 4900m were not evident at this increased altitude. The detailed analysis of the respiratory data in the decompression chamber study showed no evidence of respiratory depression with up to 30 mg temazepam. Although there was an increase in end tidal PCO2 with diazepam (10mg). Both 20 and 30 mg temazepam improved sleep at the simulated altitude without any evidence of respiratory depression. Two separate experiments were carried out; one of which investigated the effect of light, the other the effect of noise on sleep during the day after a reduced night of sleep at home. The levels of light were chosen based on 300 lux, which is roughly equivalent to moderate interior lighting. The brightest condition was 2400 lux, which is approximately equivalent to interior light levels on a sunny day. The conditions investigated were dark, 300, 600, 1200, and 2400 lux. Prior to the second experiment, a pilot study was used to identify the noise level most likely to cause sleep disturbance. Based on this study, sounds at approximately 55dB(A) were presented to subjects via loudspeakers whilst they were in bed. To put this in perspective, noise levels of 35 dB(A) are approximately equivalent to that heard in a library, 65dB(A) to office noise and 125dB(A) to a jet aircraft taking off. Eight different noise stimuli were used and were randomly presented, with a maximum of eight events per hour and a maximum duration of 10 seconds/event. Each subject performed the trial on 6 occasions, corresponding to 6 different conditions. With the exception of a no-noise condition, the conditions varied according to the timing of the noise stimuli during the sleep period. Light had only a small effect on the quality of daytime sleep. The main disturbance occurred when sleeping in the brightest condition (24001ux). Slow wave sleep (SWS), was reduced. In addition, total sleep time was reduced during the second 100-minute period, and individuals reported that their sleep had been disturbed. Some changes were also seen at lower light levels: at 1200 lux more awakenings occurred compared with sleeping in the dark, and at 600 lux there was a reduction in total sleep time during the second 100-minute period. Noise commencing at or soon after falling asleep reduced the amount of SWS by approximately 50%. This reduction was associated both with the overall sleep period and with the first 100 minutes of sleep, which is roughly equivalent to the first sleep cycle. The time taken to enter SWS after sleep onset also increased when the noise began at lights out. There was no evidence that performance during the 4 hours after rising was affected by exposure to noise, and subjects did not report any differences in the quality of their sleep under the different noise conditions. The final experiment studied the effect of a novel zaleplon on sleep in a noisy environment. The effectiveness and residual effects of zaleplon, 10 and 20mg, zopiclone 7.5 mg in promoting sleep after middle of the night administration were compared with placebo. The residual effects 4 hours after administration were also compared. Zaleplon 10 and 20 mg reduced the time taken to return to sleep after awakening in the middle of the night and was free of effects on psychomotor performance the next morning. The control drug, zopiclone, impaired performance in the morning. In summary, the diverse environmental factors considered here are all associated with some degree of sleep disturbance and potentially impaired performance. Pharmacological interventions are useful in some instances.