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Objective: This study was performed to establish whether an angiotensin II antagonist modulates daytime sleepiness or performance., Methods: The central effects of losartan (50 and 100 mg), as well as amlodipine (5 and 10 mg) and promethazine (10 mg), were studied in six healthy volunteers (aged between 20 and 27 (mean 24) yr). Digit symbol substitution, tracking, vigilance, immediate and short-term memory recall, complex reaction time, together with objective (daytime sleep latencies) and subjective measures of sleepiness, were measured 1.0 h before and 0.5, 2.0, 3.5, 5.0, 6.5, and 8.0 h after ingestion. The study was placebo-controlled and double-blind with a six-way crossover design., Results: No changes in performance or in measurements related to sleepiness were observed with losartan (50 and 100 mg). Amlodipine (10 mg) impaired immediate memory and increased subjective sleepiness at 8.0 h (p < 0.05). Promethazine (10 mg) impaired vigilance and immediate memory recall and increased reaction time (basic and complex) from 2.0 to 6.5 h after ingestion, impaired tracking from 3.5 to 6.5 h and increased subjective sleepiness from 2.0 to 8.0 h (p < 0.05)., Conclusion: The study suggests that an angiotensin II antagonist could prove useful for the treatment of hypertension in aircrew.

Introduction: The aim of this study was to establish whether fexofenadine hydrochloride, an antihistamine, modulates daytime sleepiness or performance., Methods: The effects of fexofenadine (120, 180, and 240 mg) on digit symbol substitution, tracking, and vigilance tasks, and on objective (multiple sleep latency test) and subjective sleepiness, were studied in six healthy volunteers (two males, four females, aged 20-34 [mean 26.5] yr) from 1 h pre-ingestion to 8 h post-ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. The centrally acting antihistamine, promethazine (10 mg), was used as an active control to confirm the sensitivity of the experimental procedures., Results: There were no changes in performance or sleepiness with any dose of fexofenadine at any time, compared with placebo. Promethazine, compared with both placebo and fexofenadine, impaired performance on the digit symbol substitution task (2.5 h post-ingestion), vigilance task (2.5-5h post-ingestion) and tracking task (2.5-3.5 h post-ingestion), increased objective sleepiness (1.5-2.5 h post-ingestion) and subjective sleepiness (1.5-8h post-ingestion)., Conclusion: Consideration may be given to the clinical use of currently licensed doses of fexofenadine (120-180 mg) by individuals involved in skilled activity. Fexofenadine may be potentially useful for aircrew.

Background: Intensive and sustained military operations involve long periods of overnight work and the occasional use of a stimulant to maintain performance may be beneficial. In this context a dose response study was carried out to investigate the effects of pemoline, a dopamimetic agent, on overnight work and to assess potential residual effects on subsequent sleep., Methods: Six healthy volunteers participated in a placebo-controlled, double-blind, cross-over trial involving a 12-h period of work during which subjective alertness and performance on a range of tasks were assessed at 1.5 h intervals following ingestion at 2000 hours of pemoline (10, 20, 30 and 40 mg) and, on two occasions, placebo. The work period was preceded by a 6-h sleep period with temazepam 20 mg, and followed by a 4-h recovery sleep with no medication. All sleep periods were recorded electroencephalographically., Results: There was no difference between sleep periods preceding the work period. Subjective alertness and performance on all tasks deteriorated significantly during the work period, with the earliest impairments in performance observed at 0200 hours. Pemoline increased subjective alertness and performance on all but two tasks, compared with placebo. The onset of activity was seen 4.5 h after drug ingestion and alerting effects of 30 and 40 mg pemoline persisted beyond the work period, disturbing morning recovery sleep. Doses of 10 and 20 mg pemoline had no effect on recovery sleep., Conclusion: The present studies indicate that a 20 mg dose of pemoline may be suitable for maintaining nocturnal performance without having adverse effects on recovery sleep.

Background: Effects of the H1-antihistamine, cetirizine, were studied on daytime alertness and performance to establish whether the drug would be suitable for use by air personnel and others involved in skilled activity., Methods: The investigation was carried out in six healthy volunteers, and the effects of the drug (5, 10, and 15 mg) were studied on sleep latency, subjective sleepiness, digit symbol substitution, tracking and vigilance from 0.5 h to 7.5 h after ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. Promethazine (10 mg) was used as an active control to establish the sensitivity of the experimental procedures., Results: Promethazine (10 mg) decreased the mean level of vigilance over the day, increased objective and subjective sleepiness from 1.5 to 5.5 h, and impaired tracking 5.5 h after ingestion. Cetirizine (10 and 15 mg) led to shortened sleep latencies over the day, and at 7.5 h sleep latencies were shorter with 10 mg cetirizine than with placebo. Subjective sleepiness with cetirizine was increased compared with placebo after 5 mg at 1.5 h, 10 mg at 7.5 h, and 15 mg at 5.5 h and when meaned over the day. Tracking was impaired with 5 and 15 mg cetirizine 0.5 h after ingestion., Conclusion: The study failed to establish dose-response effects of cetirizine, but it is evident that cetirizine is not free of central activity over the therapeutic range, and so its use by air personnel is not recommended.

Sleep and circadian rhythms of aircrew were studied during a 7-d polar schedule operated between London and Tokyo. Sleep, rectal temperature, and subjective alertness were recorded for 2 d before departure during the schedule, and for 10 d after the return. Changes in sleep during the early part of the trip were due to sleep loss on the outward journey, but later these changes were related to the displacement of the circadian rhythm. The acrophases of the circadian rhythms of temperature were delayed by the outward journey, and amplitudes were reduced throughout the trip. During the return, aircrew reported high levels of tiredness which persisted until the second recovery night. Though the amounts of sleep obtained during the schedule were satisfactory for the aircrew as a group, some crewmembers experienced difficulties. Realignment of circadian rhythms was attained by an advance of the circadian phase in eight aircrew and by a delay in three, and resynchronization was achieved in all cases within 6 d.

There are two overriding concerns in the design of schedules for aircrew who have to cope with irregularity of their sleep due either to work at unusual times of the day or to time zone changes. The first is that aircrew must be able to achieve an acceptable sleep pattern, and this is likely to involve short periods of sleep and naps. These, in turn, depend on limits to duty hours. The second is that the arrangement of work must bear in mind that prolonged duty and duty at certain times of the day may both involve relatively low levels of performance, and modelling can identify the adverse interactions of these influences. It is also important that the quality of the sleep of the individual pilot is taken into consideration when there are undue difficulties in coping with irregularity of work.

Performance was measured during the day (0800-1700 hours) and during the night (1700-0800 hours) of a day-night schedule, and the effect of caffeine (300 mg) was studied during the overnight periods of work. The sleep electroencephalogram was recorded together with oral temperature and urinary electrolyte excretion. Impairment of performance within 9 h after the beginning of the daytime work period was minimal, and was limited to a test of continuous performance, but impairment of performance within 9 h after the beginning of the overnight work period was more pronounced and included lowered vigilance. Impaired performance overnight was related to time on task and circadian rhythmicity, and was alleviated to some extent by the use of caffeine.

The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.

The sleep of shiftworkers in the Arctic has been investigated using electroencephalography. The subjects were studied four times a year over a 2-year period. There was a trend toward less restful sleep during the autumn and winter months, but otherwise sleep at various times of the day was similar to that of individuals elsewhere. This would suggest that sleep disturbance in polar shiftworkers can be managed in a similar way to that of shiftworkers in temperate regions.

H1-antihistamines are usually associated with impairment of central nervous functions, but unacceptable decrements in performance may not be an inevitable sequel of their use. Effects are dependent on the ability of a particular drug to cross the blood brain barrier, and so compounds which cross so slowly that tolerance of the central nervous system can develop gradually without any immediate changes in performance are of interest. However, sustained release formulations and compounds which have a selective affinity for the peripheral receptor may also have their part to play in the management of allergic states in those involved in skilled activity. As far as H2-antagonists are concerned, it is likely that as they are less liposoluble they would be free of central effects. Studies on the central effects of H1 and H2 antagonists are reviewed, and tentative recommendations are made in respect of these findings concerning the possible use of these drugs in aircrew.

The nocturnal sleep and daytime alertness of aircrew were studied by electroencephalography and the multiple sleep latency test. After a transmeridian flight from London to San Francisco, sleep onset was faster and, although there was increased wakefulness during the second half of the night, sleep duration and efficiency over the whole night were not changed. The progressive decrease in sleep latencies observed normally in the multiple sleep latency test during the morning continued throughout the day after arrival. Of the 13 subjects, 12 took a nap of around 1-h duration in the afternoon preceding the return flight. These naps would have been encouraged by the drowsiness at this time and facilitated by the departure of the aircraft being scheduled during the early evening. An early evening departure had the further advantage that the circadian increase in vigilance expected during the early part of the day would occur during the latter part of the return flight.

Adaptation to denervation of the carotid sinus region was studied on cats during hypotension induced by a controlled haemorrhage. After denervation, the fall in arterial pressure in response to haemorrhage was increased, but rhe partial recovery of blood pressure was preserved. In chronic animals, this pattern of response was also seen, but a resting hypertension developed and ensured that the minimal blood pressure and the recovery reached during the haemorrhage were similar to those of intact animals. The studies suggest that the primary role of the carotid receptors is to minimize the effect of stresses which lead to hypotension, rather than to set the level of the resting blood pressure.

The adaptation to a 9-d schedule of irregular rest and activity was studied. Sleep was recorded; patterns of oral temperature, urinary excretion, and performance at a series of tasks were measured. The relationships between circadian rhythmicity, length of time on task, and cumulative sleep loss were examined.

The effect which early evening sleep may have on overnight and subsequent daytime performance, and the effect which morning sleep may have on daytime performance after overnight sleep deprivation has been studied in six healthy male volunteers. It would appear that relatively short periods of natural and drug induced (brotizolam 0.125 mg) sleep have a beneficial effect on subsequent performance even in the absence of preceding sleep debt. In the event of disturbed sleep in shiftwork an hypnotic may be helpful, and in this context, one which is rapidly eliminated and sustains sleep is appropriate.

The currently held theory of preserved consciousness with impaired vision during positive acceleration is based on a maintained intraocular pressure and selective impairment of conduction in the peripheral visual pathway, though the experimental evidence does not wholly support this theory. During hypotension, intraocular pressure follows closely the arterial pressure, and conduction along the optic nerve is preserved as long as the electroretinogram persists. It is proposed that, though the mechanism of visual impairment during hypotension is related to events in the peripheral visual pathway, there are likely to be active forebrain events which preserve consciousness.

The findings of this cooperative study of layover sleep have direct implications for flight operations. In the consensus view of the principal investigators, these can be divided into their relevance for eastward or westward flight. Eastward flight produced more sleep disruption than westward. Different sleep and scheduling strategies are recommended for each flight direction, and the importance of individual crewmember factors is discussed in relation to age and circadian type. Despite the limitations of this study with regard to trip simplicity and the baseline data, the results for each airline are highly consistent and should be applicable to a wide range of long-haul crewmembers and carriers.