Sleep loss and circadian disruption in shift work: health burden and management

The endogenous circadian pacemaker located in the hypothalamic suprachiasmatic nuclei generates and maintains the timing of behavioural and physiological events according to a 24-hour rhythm. The pacemaker signals increased alertness during the day and high sleep propensity at night. Night shift and rotating or extended-duration shifts involve working at the time of the circadian nadir, when sleep propensity is maximal and consequently alertness is substantially impaired. Often complete circadian adaptation does not occur even in permanent night shift workers2 and, as a result, many night workers experience misalignment of their circadian pacemaker and the imposed sleep–wake cycle. The effects of this misalignment are exacerbated by chronic sleep restriction (see below) due to insomnia and reduced sleep duration during the day.2 Misalignment between the circadian pacemaker and the sleep–wake cycle may result in shift work disorder, defined as insomnia during daytime sleep and/or excessive sleepiness during wake episodes temporally associated with the shift schedule and occurring for at least 1 month.3

Circadian modulation of several cardiovascular risk markers (eg, circulating cortisol and catecholamines, blood pressure, cardiac vagal modulation) has been described, consistent with epidemiological studies showing a peak in adverse cardiovascular events in the morning.4 Recent laboratory studies demonstrate that circadian misalignment (such that individuals sleep 12 hours out of phase with the circadian pacemaker) leads to impaired cardiovascular and metabolic function — for example, decreased leptin levels, increased glucose levels despite increased insulin levels, reversed daily cortisol rhythm and increased mean arterial pressure.4

With increasing duration of wakefulness, the propensity for sleep increases and alertness becomes impaired. In an individual with a healthy sleep–wake cycle, alertness is maintained at a relatively stable level through interactions between the circadian pacemaker and the system that tracks how long the individual has been awake, referred to as the sleep homoeostat.2 After about 16 hours, alertness will sharply decline such that the magnitude of impairment in neurobehavioural performance after 17 hours of wakefulness is comparable to that observed at a blood alcohol concentration of 0.05%.5 After 24 hours of sleep deprivation, performance impairment is similar in magnitude to that observed at a blood alcohol concentration of 0.10%.

In laboratory studies, duration of the sleep episode shows a dose-dependent relationship with daytime neurobehavioural performance,6 reflecting the adverse impact of chronic sleep restriction on alertness level. Adverse effects of chronic sleep restriction on cardiometabolic outcomes have also been demonstrated in both laboratory and epidemiological studies.7 Although variations in intrinsic sleep need in the general population are well recognised, lifestyle factors appear to explain a substantial proportion of the variation in habitual sleep duration.8 Poor sleep quality due to a sleep disorder, other medical conditions or misalignment of sleep in shift workers results in chronic sleep restriction, which causes an even greater degree of alertness impairment overnight in shift workers.9

Alertness impairment is a hallmark symptom of many sleep disorders. Disorders such as obstructive sleep apnoea (OSA), insomnia and shift work disorder are associated with performance impairment or lost productivity, and increased risk of motor vehicle crashes and occupational injuries.6,10 Sleep disorders are more common among shift workers, exacerbating the risk of adverse safety, performance and health outcomes. A recent large survey of a broad range of Australian workers found that 32% of night workers suffered from shift work disorder, including 9% with a severe problem.11 Among United States police officers, 40.1% screened positive on a survey for at least one sleep disorder, with the most common being OSA (33.6%), followed by moderate to severe insomnia (6.5%), shift work disorder (5.4% of total, or 14.5% of those who work night shifts), restless legs syndrome (1.6%) and narcolepsy with cataplexy (0.4%).6,10

It is important to identify and address any comorbid conditions that independently cause insomnia or sleepiness further compromising alertness in the shift worker. Examples are conditions such as OSA, or mood disorders such as depression. Treatment of acute or chronic insomnia is important to maintain sleep continuity, adequate sleep length and alertness during wakefulness. Psychological approaches such as cognitive behavioural therapy are important in managing chronic insomnia.25 Limited but judicious use of sedative-hypnotic medication may help workers adapt to rotating sleep schedules but the data are controversial. Sedative-hypnotics should be used carefully owing to their potential side effects, including the carry-over of sedation to the night shift, which may negatively affect performance and safety.26 Use of alcohol, cannabis and non-medically prescribed drugs to manage sleep complaints should be discouraged.

The reality of shift work and long schedules during sustained operations, particularly in the transport industry, has resulted in even regulators considering use of medications to promote alertness under certain situations. This medicalisation of shift work to prevent human error and resulting consequences is controversial. Use of stimulants such as ephedrine or amphetamine is illegal and stigmatised. However, the availability of wakefulness-promoting agents modafinil and armodafinil (the R-enantiomer of modafinil), which improve alertness compared with placebo without much of the adverse effect profile of stimulants, has resulted in the possibility of managing alertness failure during shift work through pharmacotherapy. Based on evidence from large controlled clinical trials,27 these agents are now specifically approved by the US Food and Drug Administration for the treatment of excessive sleepiness in workers with shift work disorder. Self-limiting headache is the most commonly reported adverse event with these drugs.

Caffeine is used universally as a stimulant to maintain alertness. Caffeine improves cognitive performance in shift workers.28 A variety of doses, preparations and administration regimens are reported to be effective,28 including a single dose of 200 mg and a low-dose, repeated caffeine administration protocol (0.3 mg/kg/h). Residual effects of higher doses of caffeine on daytime sleep have been reported,29 which should be taken into consideration in caffeine administration guidelines, particularly for alertness management in night shift workers.

It should be noted that the above pharmacological strategies are aimed at managing sleepiness symptoms in shift workers. There is no evidence that these can facilitate circadian adaptation to a shift schedule or promote sleep.

Scheduled napping for shift workers may be useful in relieving excessive sleepiness during work shifts.6 However, the exact configuration of naps that maximises alertness on duty has yet to be clarified. Naps ranging from 20 to 40 minutes taken during night shifts (eg, between 2 am and 3 am)30 are beneficial, as is prophylactic napping before a night shift.6

The potential for alertness impairment due to sleep inertia should be considered and sufficient time allowed for its dissipation, particularly for naps occurring during work shifts. Sleep inertia refers to the impairment that occurs immediately on awakening and can last from minutes up to several hours. The magnitude of impairment may even be worse than that after 24 hours of sleep deprivation.31 The severity of sleep inertia varies according to the stage of sleep and circadian phase from which the awakening occurred. There is insufficient evidence to recommend how long an individual in operational settings should wait after a nap for the effects of sleep inertia to dissipate. A recent laboratory-based, simulated night shift work study in healthy male volunteers suggests that a 15-minute interval should be allowed following nap opportunities of up to 60 minutes, and also that workplace education be provided that subjective feelings of sleepiness are not a reliable indicator of performance impairments due to sleep inertia.32

Timed administration of melatonin can facilitate adaptation of the circadian pacemaker to a new sleep–wake schedule;33 however, this is not recommended for rapidly rotating shift schedules. Melatonin can also be used to promote sleep during the daytime, thereby improving sleep quality and duration in night shift workers.33 Although melatonin is safe for short-term use, long-term safety data are lacking.

For adaptation to a series of night shifts, the following is recommended: light exposure in the night and early morning hours to facilitate a circadian phase delay (ie, shift of the circadian pacemaker to a later time) and promote alertness; and shielding morning light exposure to minimise the competing circadian phase advance effect of light34 and to reduce the residual impact of the alerting effect of light on daytime sleep. However, this regimen is only suitable for a limited range of shift types. There appears to be an increase in the frequency of certain types of shift schedule that expose individuals to higher safety risks, including slow rotating, long duration (≥ 12 hours) and quick return (a break of only 8 hours when changing from one shift to another) shifts. Thus, the application of light treatment needs to be considered on a case-by-case basis, taking into account the specific characteristics of each schedule. Light is the most potent time cue for the circadian pacemaker, synchronising it to the 24-hour day. The magnitude and direction (ie, shift to an earlier or later time) of the effect critically depend on the timing of the exposure as well as the intensity, duration and wavelength. Here, timing relates to phase of the endogenous circadian pacemaker, which would ideally be measured through assessment of endogenous melatonin levels in saliva or core body temperature levels before an intervention. Timed light and darkness exposure can be used to facilitate adaptation of the circadian pacemaker to a new shift schedule.

Shift workers are at higher risk of cardiometabolic diseases and are therefore targets for closer monitoring of risk factors and avoiding unhealthy diets. High fat meals consumed during the night may produce more postprandial hypertriglyceridaemia than equivalent meals during the day.2 Promoting physical activity in the workplace and home is another countermeasure to cardiometabolic risk. Laboratory studies have shown that exercise during the night phase shifts the circadian pacemaker,35 thus potentially facilitating biological adaptation to shift work.

Shift work is commonly associated with adverse safety and health consequences (Box 2). Circadian misalignment, sleep loss and sleep disorders all contribute to these risks, and therefore should be the primary targets for clinical management approaches. Improved methods to detect those who are most vulnerable to the effects of shift work are needed. Diagnosis and management of shift work disorder is an important first step in tackling the significant health burden associated with shift work.