British Journal of Anaesthesia 1996; 76: 552–559
REVIEW ARTICLE
Postoperative sleep disturbances: mechanisms and clinical
implications
S. ROSENBERG-ADAMSEN, H. KEHLET, C. DODDS AND J. ROSENBERG
Major surgery is beset by complications such as
pulmonary, cardiac, thromboembolic and cerebral
dysfunction, which cannot be attributed solely to
inadequate surgical and anaesthetic techniques, but
rather to increased organ demands caused by the
endocrine metabolic response to surgical trauma
[33]. Postoperative cerebral dysfunction comprises
delirium, confusion and milder degrees of mental
dysfunction [1, 48, 53, 62], and disturbances in the
normal sleep pattern [4, 7, 9, 13, 17, 34, 39, 42, 65].
Changes in early postoperative sleep [4, 7, 8, 13, 17,
34, 39, 42, 65] and sleep after non-surgical stress [10,
20, 24, 26, 27, 29, 60] are characterized by a decrease
in total sleep time, elimination of rapid eye move-
ment (REM) sleep, a marked reduction in the
amount of slow wave sleep (SWS) and increased
amounts of non-REM (N-REM) sleep stage 2.
Recent data have suggested that postoperative sleep
disturbances may be involved in the development of
altered mental function [27], postoperative episodic
hypoxaemia [38, 65] and haemodynamic instability
[40]. The aim of this article, therefore, is to review
the incidence and duration of postoperative sleep
disturbances, and to evaluate possible mechanisms
and potential implications for postoperative out-
come.
The normal sleep pattern
Using standardized polysomnographic recordings,
which include simultaneous electroencephalographic
(EEG), electro-oculographic (EOG) and electromyo-
graphic (EMG) recordings, sleep can be divided into
different sleep stages (see below). By questionnaire,
subjective sleep quality, which has been shown to be
related to total sleep duration and number of
awakenings [3], may be assessed.
Sleep is not homogeneous, but is divided into two
discrete forms, REM and N-REM, by their electro-
physiological characteristics [58], and each has been
subdivided further. There are striking differences
between these two sleep patterns. For example,
arousal to effective awareness depends on the
magnitude of the stimulating input and the “depth”
(Br. J. Anaesth. 1996; 76: 552–559)
Key words



of the sleep stage. Wakening from REM and stage 4
N-REM requires the greatest input, and this is as
true for external stimuli, such as noise and light, as
for internal autonomic signals, such as hypoxia or
pulmonary stretch receptor reflexes. This clearly has
an important influence on the hazards that may
accompany deep sleep after surgery (see below).
N-REM sleep is subdivided into four stages of
increasing depth or resistance to arousal, with stage
1 N-REM being light sleep and stage 4 N-REM very
deep sleep (fig. 1). The physiology of N-REM sleep
is based entirely on the autonomic medullary and
brain stem control systems. There is a reduction in
basal metabolic rate and this is associated with a
progressive decrease in oxygen requirement, heart
rate, arterial pressure, temperature and ventilation.
The decrease in arterial pressure is largely because of
peripheral vasodilatation, with cardiac output re-
maining relatively unchanged. Other physiological
variables are generally unchanged during N-REM
sleep. The tone of the anti-gravity muscles decreases
with increasing depth of N-REM sleep, but the tonic
drive to the diaphragm is maintained at all levels and
types of sleep. There is a reduction in hypoxic and
hypercapnic ventilatory responses and the response
to increasing respiratory resistive loads. The maxi-
mum decrease occurs in stages 3 and 4 N-REM (also
called slow wave sleep (SWS)), where for example
the hypoxic drive decreases by 40 %.
REM sleep is the phase most closely associated
with dreaming. It is more akin to full awareness than
sleep, in the variability and rapidity of changes in
physiological state. There are marked variations in
arterial pressure and heart rate, rate and depth of
breathing, and metabolic rate. It appears that we act
out our dreams physiologically. Major differences
from N-REM sleep are also evident in respiratory
control during REM sleep. The ␣-motor neurones
are hyperpolarized during REM, with the exception
of the facial muscle supply and that of the diaphragm.
The hypoxic ventilatory response is reduced by up to
60 % and carbon dioxide responses to between 27 %
SUSAN ROSENBERG-ADAMSEN, MD, HENRIK KEHLET, MD, PHD,
CHRIS DODDS, MB, BS, MRCGP, FRCA, JACOB ROSENBERG*, MD, DMSC,
Department of Surgical Gastroenterology 235, Hvidovre Uni-
versity Hospital, DK-2650 Hvidovre, Denmark, Department of
Anaesthesia, South Cleveland Hospital, Cleveland TS4 3BW,
England.
*Address for correspondence: Department of Surgical



 Gastroenterology 235, Hvidovre University Hospital, DK-2650
Hvidovre, Denmark.
Postoperative sleep disturbances
Figure 1 The normal sleep pattern (hypnogram).
and 0 % [15] of the awake response. The arousal
response to hypoxia requires a decrease in SpO2 to
less than 70 % for activation.
Sleep is essential and any alteration or suppression
of specific sleep stages results in a rebound response
when the inhibition is removed. The harmful effects
of prolonged REM sleep in the postoperative period
have been well documented. The time scale for these
changes has not been described fully but they are
thought to last for 1 or more weeks after surgery.
The mechanisms underlying the initiation and
maintenance of sleep and its stages are still specu-
lative, but there are some important features related
to the effects of surgery and anaesthesia on sleep. N-
REM sleep is linked closely with the central action of
serotonin (5-HT) and, to a lesser degree, the
monoamine noradrenaline. There are marked re-
ductions in the amount of deep N-REM sleep in
patients given benzodiazepines and opioids. REM
sleep can be initiated by acetylcholine agonists in
animal studies and neostigmine in human volunteers.
Atropine markedly reduces REM sleep. Also ␣2
agonists such as clonidine, or dopamine (D2) agonists
such as apomorphine, reduce REM sleep, and the
monoamine oxidase inhibitors (MAOI) can almost
abolish REM. Prazosin, an ␣1 antagonist, increases
the incidence of cataplexy, a REM-related com-
ponent of narcolepsy. It is tempting to try to isolate
key drugs as causal agents, for instance opioids, but
the same pattern is seen after regional anaesthesia
alone (see below).
Airway control during sleep
During wakefulness, the airway is maintained patent
by the action of the paired strap muscles surrounding
the oropharynx and pharyngopharynx. This pre-
vents the collapse of this part of the airway by the
subatmospheric pressures generated by the chest and
diaphragmatic action. On initiation of sleep there is
a progressive decrease in upper airway muscle tone
and maintenance of the normal action of the chest
and diaphragm. In the light stages of N-REM sleep
this disproportionate decrease in tone makes collapse
more likely. As the airway becomes progressively
narrow, airflow becomes suddenly turbulent. This
produces vibration of the upper airway or snoring.
Thus snoring is partial airway obstruction. If there is
a greater load on the airway muscles because of fatty
deposits (obesity) or increased inspiratory resistance
(such as the macroglossia of Down’s syndrome),
further collapse is likely and may culminate in
complete airway obstruction.
553
In REM sleep, atonia of the anti-gravity muscles
predisposes to instability of the airway, and most
obstructive apnoea episodes occur in this stage of
sleep. When the airway has become obstructed,
further inspiratory effort is futile because of the lack
of muscle tone during deep sleep. Vigorous para-
doxical ventilatory movements are easily visible but
ineffective. The only route to recovery of the air-
way is arousal from sleep which is usually very brief
(: 5 s) and not associated with recall. The cycle of
sleep–obstruction / hypoxia–arousal–sleep–obstruc-
tion/hypoxia may occur more than 100 times each
hour. The consequences of these episodes of obstruc-
tion are two-fold: physiological effects of the
progressive hypoxia and hypercapnia, and daytime
sleepiness from repeated life-saving arousals. These
patients are described as suffering from obstructive
sleep apnoea (OSA) syndrome [46].
The consequences of airway obstruction during
sleep may be profound and include progressive
hypoxia, bradycardia and hypercapnia. Pulmonary
artery pressure increases by hypoxic pulmonary
vasoconstriction, and there is a generalized increase
in systemic peripheral resistance. During REM sleep
this causes increased oxygen demands at a time when
hypoxia and hypertension are marked and ischaemic
injury becomes likely, particularly of the heart. If
apnoeas occur during N-REM, the association of
hypotension and hypoxia may lead to cerebral
hypoperfusion and stroke.
Function of sleep
The function of sleep is largely unknown, although
several theories have been proposed. The most
widely held theory is that sleep serves as a period of
restoration, either total body or neurological res-
toration [66]. Total or selective sleep deprivation
affects particularly the brain, with psychological and
neurological dysfunction [30], impairment in be-
havioural and psychological performance [8, 23,
30] and sleepiness [8], and impaired concentration
[30] and performance on psychometric tests [8, 23,
30]. Finally, mood is affected, with increased sadness
and irritability, and decreased vigour [30]. Selective
REM sleep deprivation produces a state of
pronounced irritability and lability, and signs of
confusion, anxiety and suspicion [2]. Deprivation of
REM sleep is followed by a significant increase
(rebound) in a recovery night [2]. SWS deprivation
produces a feeling of physical discomfort [2],
characterized by a depressive and hypochondrial
reaction [2]. Selective deprivation of SWS also
produces a rebound in SWS during a recovery night
[2, 23].
The postoperative sleep pattern
Only six studies have been performed with EEG
recording of sleep in postoperative patients after
non-cardiac surgery, including a total of 35 patients
after major abdominal surgery [4, 17, 39, 65], 18
patients after herniorrhaphy [17, 34] and 46 patients
after minor undefined surgery [42] (table 1).
 554 British Journal of Anaesthesia

patients
No. of

10

46
6

10
9

8
4
Rhythmicity

0
0
0
0

↓
↓
↓

↓
↓
↓

Figure 2 Changes in total REM sleep on pre- and

postoperative nights (based on [4, 17, 34, 39, 42, 65]).
Summary of clinical studies with EEG measured sleep after non-cardiac surgery. ↑ : Increased, ↓ : decreased, → : unchanged, 0 : not measured

arousals
No. of

→
→
→
→

0
0

↑
↑
↑
↑

After abdominal surgery all patients were sleep

deprived, as shown by total sleep time, proportion of
REM sleep and SWS on the first and second
Duration of

postoperative nights in the ICU [4] and on the ward

[17, 34, 38, 39, 65]. Total sleep time was reduced by
stage 2

up to 80 % on at least 1 of the first postoperative

→
→

→
→

nights [4, 7, 13, 17, 34], with considerable inter-

↑
↑

↑
↑
↑

↑
↑

individual variation. Throughout the operative night

↓ (entirely absent

and the subsequent 1 or 2 nights, sleep was highly

→ (in 6 of 10)
↓ (in 4 of 10)
↓ (in 8 of 10)
↑ (in 2 of 10)

fragmented with numerous movement arousals and

in 9 of 10)
Duration of

spontaneous awakenings with long wake periods [17,

34, 39], preventing the inherent rhythmicity of sleep
SWS

and the normal distribution of sleep stages [17, 39].

→
→

↓
↓
↓
↓

↓
↓

REM sleep is usually absent on the first and

sometimes the second and third postoperative nights
[4, 17, 34, 38, 39, 42, 65]. During the following 2–4
→ (in 6 of 10)
↑ (in 4 of 10)
↑ (in 7 of 10)
Duration of

nights, when other sleep abnormalities recover,

REM sleep

↑ (in all)
↑ (in all)

REM sleep reappears with increased density and

duration (rebound) in most patients [34, 38, 39, 65]
(fig. 2). In patients undergoing cholecystectomy and
↓

↓
↓
↓

↓
↓

gastroplasty, Knill and colleagues showed that

increments in REM sleep during rebound were
primarily a result of lengthening of individual REM
Total sleep

sleep periods rather than to an increased number of

↓ (in all)
↓ (in all)

periods [31]. Thus, increased total REM sleep time,

time

combined with increased REM density, results in a

→

→
→
→
→
→
→
→

↓
↓

substantial rebound in total REM activity [39]. The

increase in REM activity is associated with frequent
Postoperative

reports of distressing and vivid nightmares [39].

(3), 4, 5, 6
1, 2, (3)

1, 2, (3)
(3), 4, 5

Nightmares have been shown to be frequent (about

nights

1, (2)
(2), 3

20 %) during the first week after major non-cardiac

3, 4
1, 2
1, 2
1, 2
1–4

surgery [7, 9], with the highest incidence on the

fourth postoperative night [9], corresponding to the
Inguinal hernia repair

period of rebound REM sleep.

Major non-cardiac

Upper abdominal

Major abdominal
Cholecystectomy

On postoperative nights 1–4 there was a marked

Type of surgery

Herniorrhaphy

Minor surgery

reduction in the amount of SWS [4, 17, 34, 39, 42,

Gastroplasty

65]. In one study SWS was absent in all 10 patients

surgery
surgery

surgery

studied on the first and second nights after major

abdominal surgery [65]. An increased duration of
SWS (rebound) in the middle of the first post-
operative week may occur after initial deprivation of
Rosenberg and colleagues

Lehmkuhl and colleagues

Knill and colleagues [39]

SWS [65].
Kavey & Altshuler [34]
Aurell & Elmqvist [4]

The duration of the abnormal postoperative sleep

Ellis & Dudley [17]

pattern has been described only poorly. No studies

with EEG monitoring have been performed later
than the sixth night after abdominal surgery. Total
sleep time is gradually normalized to the pre-
Table 1

[65]

operative level within the first postoperative week

[42]

[34]. REM sleep was still increased in nine of 12

 Postoperative sleep disturbances 555

patients on the sixth night after cholecystectomy or

on the fifth night after gastroplasty [39]. In most
patients SWS gradually returned towards normal
during the third and fourth postoperative night
[34, 39, 65].
Studies based on observations by staff have shown
that during the first night in the intensive care unit
(ICU), the majority of subjects (56 %) were sleep-
Table 2 Summary of studies of postoperative sleep quality (measured by questionnaire). ↑ : Increased, ↓ : decreased, → : unchanged, 0 : not measured. *Patients were asked

deprived with respect to total sleep time [27].

patients

Similarly, the subjective feeling of sleep quality in

No. of

postoperative patients has been shown to be

8

104
4

57
157

57
100

53
10

decreased markedly during the first 1 or 2 nights

followed by recovery of sleep quality, for most
↑ (in 289 %)
Nightmares

↑ (in 12 %)
↑ (in 23 %)

↑ (in 19 %)
patients before discharge [7, 13, 17, 34] (table 2). A

↑ (in 7 %)
questionnaire study showed that approximately 23 %
of patients after elective orthopaedic, vascular or
0

0
0
0

0
0

abdominal surgery had decreased sleep quality at the

time of discharge from hospital, and about 25 % of
these patients showed changes for more than 2 weeks
Subjective sleep

after discharge [7].

↓ (in 14%)
↓ (in 24%)

↓ (in 30%)
↓ (in 55%)

In summary, profound alterations in sleep pattern

↓ (in all)
↓ (in all)

occur during the first 1–6 nights after major

quality

abdominal surgery. As previous studies have con-

0

cluded that sleep duration and the frequency and

↓
↓
↓
↓

periodicity of sleep disruption are the most im-

portant determinants for the restorative capability of
arousals/awakenings

sleep [3, 8, 23], such sleep changes may be expected

to influence restoration of body organ dysfunction
and in particular cerebral function.
↑ (in all)
↑ (in all)
No. of

Pathogenesis of postoperative sleep

disturbance
↑

↑
0

0
↑

0
↑

↑
↑

Several factors may contribute to the disturbed sleep

Total sleep

pattern in the surgical patient (fig. 3). The magnitude

↓ (in all)
↓ (in all)

of surgery is important, as the reduction in REM

retrospectively about the whole postoperative period up to 2 yr after the surgical procedure

time

sleep, SWS and the lack of inherent rhythmicity are

→

0
0
↓

0
0

more pronounced after major (gastrectomy or

↓

vagotomy) than minor (hernia repair) surgery [17].

Retrospective*
Postoperative

15 days after

In questionnaire studies, the greatest incidence of

discharge

sleep disturbances was also found after the more

nights

major surgical procedures [13, 17, 27]. The duration

3, 4
1, 2
1, 2

1, 2

1–7
Elective orthopaedic, 1, 2

1–7

1–7
3

of the operative procedure was related to the duration

of postoperative sleep disturbance [17], probably as
Inguinal hernia repair

Inguinal hernia repair

a result of more extensive surgical trauma.

Abdominal surgery

Minor orthopaedic
Major non-cardiac
Upper abdominal

Day surgery (not

In studies of patients receiving general or regional

vascular surgery
Type of surgery

Elective cardiac
abdominal and

anaesthesia for herniorrhaphy [34], minor ortho-

paedic procedures [9] or minor undefined surgery
specified)

surgery
surgery

surgery

surgery

[42], a similar degree of sleep disturbance was found,

regardless of anaesthetic technique, suggesting that
general anaesthesia per se is not an important
pathogenic factor. Furthermore, general anaesthesia
Beydon and colleagues [7]

Brimacombe & Macfie [9]

of 3 h duration in non-surgical volunteers produced

Kavey & Altshuler [34]

only a modest reduction in SWS for 1 night and no

Ellis & Dudley [17]

changes in REM sleep [51]. Furthermore, similar

changes in sleep pattern as are seen in postoperative
patients have been found in non-surgical patients
Closs [13]

with acute ischaemic stroke [24], acute myocardial

infarction [10], congestive heart failure [26] and
medical and trauma ICU patients [20, 29, 60]. Thus
general anaesthesia per se must be of minor im-
portance in the pathogenesis of postoperative sleep
disturbance, compared with the physical stress
response caused by the surgical trauma.
The injury of surgery is followed by a complex
556
Figure 3 Factors which may contribute to postoperative sleep disturbances.
stress response involving hormones and humoral
mediators of the endocrine–metabolic system,
immunosuppression and an inflammatory response
[6, 35]. The inflammatory reaction constitutes the
local response, whereas endocrine–metabolic acti-
vation with increased plasma concentrations of
catabolic hormones and reduced concentrations of
anabolic hormones, leads to hypermetabolism with
acceleration of most biochemical reactions, including
muscle protein breakdown, resulting in a negative
nitrogen balance [35]. The response may last for a
few days or even weeks, depending on the magnitude
of the surgical insult and occurrence of com-
plications.
The increased postoperative sympathetic activity
with increased catecholamines may contribute to
postoperative sleep disturbances, as high levels of
noradrenergic activity maintain wakefulness [28].
The postoperative influence of surgical trauma on
insulin is biphasic, with an impaired insulin response
to glucose during the initial phase followed by an
increased insulin response but with concomitant
increased peripheral insulin resistance (post-receptor
defect) [35]. Cortisol, another of the key mediators in
the endocrine response to surgery, causes reduction
in REM sleep and increases non-REM sleep when
administered to healthy volunteers [19, 21]. Fur-
thermore, corticotrophin-releasing hormone, which
is increased in surgical stress, decreases non-REM
sleep and increases wakefulness in a dose-dependent
manner in rabbits and rats [55, 67]. In contrast,
growth hormone releasing hormone (GHRH) may
have a sleep inducing effect [69], and is probably
increased during the postoperative period.
Administration of one of the key mediators of
injury, interleukin-1, into the lateral ventricle of
rabbits results in hyperthermia and increased non-
REM sleep, with suppression of REM sleep, thus
resembling the postoperative situation [54]. Pre-
treatment with an interleukin-1 receptor antagonist
prevented interleukin-1-induced sleep disturbances
British Journal of Anaesthesia
[54]. Endotoxin administration to healthy volunteers
[70] and intracerebroventricular injection of tumour
necrosis factor in rabbits [33] also caused deprivation
of REM sleep and an increase in non-REM sleep,
with no changes in SWS. As REM sleep is controlled
by many regions in the brain and there is a dynamic
interaction between cortex and other subcortical
systems [32], the postoperative REM sleep dis-
turbance may represent a global excitatory effect of
the entire surgical stress response on the brain,
rather than being caused by specific mediators of the
surgical stress response.
Fever, which is seen commonly in postoperative
patients, is associated with decreased REM sleep and
increased SWS in rats with fungal infections [36]. It
is not known if the fever-induced sleep disturbance
is mediated by cytokines only or if it is induced by
the increased temperature per se.
Morphine 0.1 and 0.2 mg kg91 i.m., administered
to healthy volunteers without pain, disrupted sleep
in a dose-dependent manner [52]. After a dose of
0.1 mg kg91, only SWS was reduced, whereas a
larger dose of 0.2 mg kg91 produced a marked
reduction in both REM sleep and SWS with an
increase in nocturnal awakenings [52]. There are no
data on the effect of systemic or extradural morphine
on sleep in postoperative patients.
After operation, pain is the most commonly
reported cause of night-time awakenings [13], and
based on questionnaires, provision of analgesia is the
most helpful intervention to improve sleep [13]. No
comparisons have been made between opioid and
non-opioid drugs. In patients with pain from active
rheumatoid arthritis, sleep disturbances similar to
the postoperative period have been demonstrated
[49]. The role of pain per se, that is nociceptive
stimulation vs concomitant release of inflammatory
mediators (cytokines) and stress hormones, has not
been evaluated.
The noise level in an ICU is usually greater than
is internationally recommended at all times of the
Postoperative sleep disturbances
day and night [5]. Acoustically disturbed sleep has a
decreased subjective quality, with less SWS than
undisturbed sleep [23]. Patients have reported noise
as one of the most disturbing factors of sleep in the
postoperative period on the ward [7, 13] and in the
ICU [29]. In addition, other “external” factors such
as frequent observations and therapeutic procedures
[29] and a high room temperature [43] may have a
negative effect on sleep pattern in the surgical
patient. An i.v. catheter did not affect sleep in
volunteers [37], but starvation, as seen in most
patients after major procedures, may be associated
with decreased REM sleep and increased SWS, as
shown in volunteers [45].
Obstructive sleep apnoea (OSA) syndrome
Special mention should be made of patients with the
sleep apnoea syndrome. Sleep apnoea is defined as a
pause of more than 10 s in breathing during sleep,
and OSA is defined as at least five apnoeas per hour
[48]. OSA is a common finding in non-surgical
patients, with an incidence of 1–9 % [48], although
the more severe forms are less common. It has
several major implications for anaesthesia and sur-
gery throughout the operative period. These patients
have repetitive episodes of often severe hypoxia and
may have pulmonary hypertension. They may have
impaired reflex responses to hypoxia, hypercapnia
and inspiratory loads, and may also have altered
autonomic cardiovascular reflexes [14, 71]. The
treatment of OSA with nasal continuous positive
airway pressure (CPAP) is highly effective at
preserving the airway during sleep and over several
weeks can improve the diminished reflex responses
to hypoxia and hypercapnia [44]. However, it is more
prudent to assume that they do not respond normally
to any of these challenges during anaesthesia and in
the postoperative period. They may be vulnerable to
depressant medication such as benzodiazepines and
opioids [12], and respiratory arrest can occur if these
are given. All common anaesthetic induction agents,
volatile and i.v., reduce upper airway tone in an
identical manner to deep sleep. Some of the
predisposing causes of sleep apnoea, such as a large
tongue and recessive mandible, are also associated
with difficulty in tracheal intubation and main-
tenance of a patent airway. Recovery from surgery
and anaesthesia, while the normal protective reflexes
are returning, may be a hazardous time, and
obstruction of the airway can be difficult to over-
come. This must be borne in mind after return to the
ward if sedation or opioid analgesia is given. Regional
methods of pain relief are believed to be safer than
systemic opioid analgesia [18]. If patients are treated
with CPAP, it is important that they bring their
machines into hospital as they can be used in the
recovery unit to preserve the airway until full
recovery occurs and on the ward while their sleep
returns to normal.
No data are available about postoperative sleep in
patients with sleep apnoea syndrome, but extreme
episodic oxygen desaturation in the late post-
operative period has been described in a patient with
557
the sleep apnoea syndrome [61], which may therefore
be a potential surgical risk factor.
Clinical implications of postoperative sleep
disturbances
The clinical consequences of suppression of REM
sleep and SWS with subsequent rebound in the
postoperative period remain unknown, although
there are several potentially important implications.
The postoperative rebound of REM sleep in the
middle of the first postoperative week may contribute
to the development of sleep-disordered breathing
and nocturnal hypoxaemia [38, 65]. Episodic
hypoxaemia is more frequent during periods of
REM rebound than during other sleep stages in the
postoperative period [65].
REM sleep is associated with profound sym-
pathetic activation on nights with postoperative
rebound [41] and in normal subjects [46, 68]. REM
sleep in normal subjects is associated with
haemodynamic instability [40, 47, 68], and increased
mean arterial pressure [47, 68]. In the postoperative
period these haemodynamic changes may occur with
the hypoxaemic episodes [38, 65], and following
uncomplicated abdominal surgery, episodic
hypoxaemia was associated with cardiac ischaemia
[22, 59, 64]. Sleep apnoea and episodic oxygen
desaturation may induce life-threatening cardiac
arrhythmias in non-surgical patients [25]. As the
amount of REM sleep and the intensity of its
phasic events increase in the postoperative period
with simultaneous episodic hypoxaemia and haemo-
dynamic instability, postoperative REM sleep re-
bound may be particularly dangerous and lead to
postoperative myocardial ischaemia, infarction and
eventually to unexpected postoperative death. This
hypothesis warrants further study, but is supported
by the finding that the majority of unexpected
postoperative deaths occurred at night [63].
Postoperative impairment of mental function is
a common complication in the elderly, with an
incidence of 7–77 % after major surgery and
a peak incidence in the middle of the first week
after operation [1, 48, 53, 62]. The pathogenic
mechanisms are not completely understood [1, 48,
53, 62], but factors such as hypoxaemia [1, 62] and
sleep disturbances [27] may be important. After
sleep deprivation in non-surgical volunteers, im-
paired mental performance has been demonstrated
on a simple reaction time test [8, 23], as decreased
ability for creative thinking [31], and by impaired
ability to perform other cognitive functions [31].
The performance deficit is related to age [30] and to
loss of sleep per se rather than to changes in the
composition of sleep [8, 23]. Mood is affected also by
sleep deprivation with decreased vigour and an
increase in the subjective feelings of sleepiness [2,
23, 30] and fatigue [30]. As the postoperative sleep
disturbances are pronounced and of the same
magnitude as in the above-mentioned studies in
volunteers, postoperative sleep disturbance may be
an important contributing factor in the development
of postoperative cerebral dysfunction. Furthermore,
postoperative sleep disturbance could be a con-
558
tributing factor in the phenomenon of postoperative
fatigue [11], although a direct relationship between
postoperative fatigue and sleep abnormalities re-
mains to be demonstrated.
Prevention and treatment of postoperative
sleep disturbances
As the magnitude and duration of the surgical
procedure determines the degree of postoperative
sleep disturbance [9, 17], a reduction in the surgical
stress response by minimally invasive surgery may
be effective. So far, there are no comparative studies
between sleep patterns after the same operation
performed either as a traditional open procedure or
by minimally invasive surgical techniques. Stress
reduction by neural block with local anaesthetics
[35] may be expected to improve postoperative sleep
also, but no data are available from studies using
continuous nerve block techniques. As previous
studies have suggested that pain [13, 49] and mor-
phine [52] disturb postoperative sleep, continuous
analgesic techniques with neural block using local
anaesthetics without morphine should be evaluated,
and the effect of NSAID because of their well-
documented opioid-sparing effects. Preliminary
studies with ketorolac after lower abdominal surgery
have shown decreased opioid requirements and
increased quality of sleep on the first postoperative
night [56].
Noise [7, 13, 20], nocturnal nursing procedures
[29], starvation [45] and increased room temperature
[43] are sleep disturbing factors that could be
eliminated in the postoperative period.
It has been reported that about 30 % of medical
and 88 % of surgical patients receive sedative drugs
during hospitalization [57]. Some of the most
commonly used drugs are benzodiazepines, which
have an important influence on sleep architecture
with attenuated REM sleep and SWS, and increased
stage 2 sleep [16]. Recent studies have suggested that
the newer hypnotics zopiclone and zolpidem are less
likely to alter sleep architecture [16] and that they
may increase REM sleep and SWS to a normal level
in non-surgical patients with disturbed sleep (in-
somnia) [16, 50]. The effect of these drugs on the
postoperative sleep pattern is unknown and should
be evaluated in future clinical trials.
As previously mentioned, patients with sleep
apnoea syndrome are more susceptible to respiratory
depression after sedative and narcotic administration
[12] and the significance of the sleep apnoea
syndrome as a surgical risk factor [61] should
therefore be explored in future studies.
In summary, postoperative sleep disturbances
represent an important research field, as they may
have a significant negative impact on postoperative
outcome.
References
1. Aakerlund LP, Rosenberg J. Postoperative delirium: treat-
ment with supplementary oxygen. British Journal of An-
aesthesia 1994; 72: 286–290.
2. Agnew HW, Webb WB, Williams RL. Comparison of stage
British Journal of Anaesthesia
four and 1-REM sleep deprivation. Perceptual and Motor
Skills 1967; 24: 851–858.
3. Åkerstedt T, Hume K, Minors D, Waterhouse J. The
meaning of good sleep: a longitudinal study of poly-
somnography and subjective sleep quality. Journal of Sleep
Research 1994; 3: 152–158.
4. Aurell J, Elmqvist D. Sleep in the surgical intensive care
unit: continuous polygraphic recording of sleep in nine
patients receiving postoperative care. British Medical Journal
1985; 290: 1029–1032.
5. Balogh D, Kittinger E, Benzer A, Hackl JM. Noise in the
ICU. Intensive Care Medicine 1993; 19: 43–46.
6. Beal AL, Cerra FB. Multiple organ failure syndrome in the
1990s: systemic inflammatory response and organ dysfunc-
tion. Journal of the American Medical Association 1994; 271:
226–233.
7. Beydon L, Rauss A, Lofaso F, Liu N, Cherqui D, Goldenberg
F, Bonnet F. Assessment of the quality of perioperative sleep:
study of the factors favouring insomnia. Annales Françaises
D’Anesthésie et de Réanimation 1994; 13: 669–674.
8. Bonnett MH. Performance and sleepiness following moderate
sleep disruption and slow wave sleep deprivation. Physiology
and Behavior 1986; 37: 915–918.
9. Brimacombe J, Macfie AG. Peri-operative nightmares in
surgical patients. Anaesthesia 1993; 48: 527–529.
10. Broughton R, Baron R. Sleep patterns in the intensive care
unit and on the ward after acute myocardial infarction.
Electroencephalography and Clinical Neurophysiology 1978;
45: 348–360.
11. Christensen T, Kehlet H. Postoperative fatigue. World
Journal of Surgery 1993; 17: 215–219.
12. Chung F, Crago RR. Sleep apnoea syndrome and anaesthesia.
Canadian Anaesthetists Society Journal 1982; 29: 439–445.
13. Close SJ. Patients’ night-time pain, analgesic provision and
sleep after surgery. International Journal of Nursing Studies
1992; 29: 381–392.
14. Cortelli P, Parchi P, Sforza E, Contin M, Pierangeli G,
Barletta G, Lugaresi E. Cardiovascular autonomic dysfunc-
tion in normotensive awake subjects with obstructive sleep
apnoea syndrome. Clinical Autonomic Research 1994; 4:
57–62.
15. Douglas NJ, White DP, Pickett CK, Weil JV, Zwillich CW.
Respiration during sleep in normal man. Thorax 1982; 37:
840–844.
16. Eisen J, MacFarlane J, Shapiro C. Psychotropic drugs and
sleep. British Medical Journal 1993; 306: 1331–1334.
17. Ellis BW, Dudley HAF. Some aspects of sleep research in
surgical stress. Journal of Psychosomatic Research 1976; 20:
303–308.
18. Etches RC. Respiratory depression associated with patient-
controlled analgesia: a review of eight cases. Canadian Journal
of Anaesthesia 1994; 41: 125–132.
19. Fehm HL, Benkowitsch R, Kern W, Fehm-Wolfsdorf G,
Pauschinger P, Born J. Influences of corticosteroids,
dexamethasone and hydrocortisone on sleep in humans.
Neuropsychobiology 1986; 16: 198–204.
20. Fontaine DK. Measurement of nocturnal sleep patterns in
trauma patients. Heart and Lung 1989; 18: 402–410.
21. Friess E, von Bardeleben U, Wiedemann K, Lauer CJ,
Holsboer F. Effects of pulsatile cortisol infusion on sleep-
EEG and nocturnal growth hormone release in healthy men.
Journal of Sleep Research 1994; 3: 73–79.
22. Gill NP, Wright B, Reilly CS. Relationship between
hypoxaemic and cardiac ischaemic events in the perioperative
period. British Journal of Anaesthesia 1992; 68: 471–473.
23. Gillberg M, Akerstedt T. Sleep restriction and SWS-
suppression: effects on daytime alertness and night-time
recovery. Journal of Sleep Research 1994; 3: 144–151.
24. Giubilei F, Iannilli M, Vitale A, Pierallini A, Sacchetti ML,
Antonini G, Fieschi C. Sleep patterns in acute ischaemic
stroke. Acta Neurologica Scandinavica 1992; 86: 567–571.
25. Guilleminault C, Connolly SJ, Winkle RA. Cardiac ar-
rhythmia and conduction disturbances during sleep in 400
patients with sleep apnea syndrome. American Journal of
Cardiology 1983; 52: 490–494.
26. Hanly PJ, Millar TW, Steljes DG, Baert R, Frais MA,
Kryger MH. Respiration and abnormal sleep in patients with
congestive heart failure. Chest 1989; 96: 480–488.
27. Helton MC, Gordon SH, Nunnery SL. The correlation
Postoperative sleep disturbances
between sleep deprivation and the intensive care unit
syndrome. Heart and Lung 1980; 9: 464–468.
28. Hilakivi I. Biogenic amines in the regulation of wakefulness
and sleep. Medical Biology 1987; 65: 97–104.
29. Hilton BA. Quantity and quality of patients’ sleep and sleep-
disturbing factors in a respiratory intensive care unit. Journal
of Advanced Nursing 1976; 1: 453–468.
30. Horne JA. Sleep function, with particular reference to sleep
deprivation. Annals of Clinical Research 1985; 17: 199–208.
31. Horne JA. Sleep loss and “divergent” thinking ability. Sleep
1988; 11: 528–536.
32. Jones JG, Vucevic M. Not awake, not asleep, not dead?
Intensive Care Medicine 1992; 18: 67–68.
33. Kapas L, Hong L, Cady AB, Opp MR, Postlethwaite AE,
Seyer JM, Krueger JM. Somnogenic, pyrogenic and anorectic
activities of tumor necrosis factor-alpha and TNF-alpha
fragments. American Journal of Physiology 1992; 263:
R708–R715.
34. Kavey NB, Altshuler KZ. Sleep in herniorrhaphy patients.
American Journal of Surgery 1979; 138: 682–687.
35. Kehlet H. Modification of responses to surgery by neural
blockade: Clinical implications. In: Cousins MJ,
Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia
and Management of Pain, 2nd Edn. Philadelphia: J. B.
Lippincott, 1988; 145–188.
36. Kent S, Price M, Satinoff E. Fever alters characteristics of
sleep in rats. Physiology and Behavior 1988; 44: 709–715.
37. Kerkhofs M, Linkowski P, Mendlewicz J. Effects of in-
travenous catheter on sleep in healthy men and in depressed
patients. Sleep 1989; 12: 113–119.
38. Knill RL, Moote CA, Rose EA, Skinner MI. Marked
hypoxemia after gastroplasty due to disorders of breathing in
REM sleep. Anesthesiology 1987; 67: 3A.
39. Knill RL, Moote CA, Skinner MI, Rose EA. Anesthesia with
abdominal surgery leads to intense REM sleep during the first
postoperative week. Anesthesiology 1990; 73: 52–61.
40. Knill RL, Skinner MI, Novick TV. Intense REM sleep
causes haemodynamic instability. Canadian Journal of An-
aesthesia 1991; 38: A17.
41. Knill RL, Skinner MI, Novick T, Vandenberghe HM,
Moote CA. The night of intense REM sleep after anaesthesia
and surgery increases urinary catecholamines. Canadian
Journal of Anaesthesia 1990; 37: S12.
42. Lehmkuhl P, Prass D, Pichlmayr I. General anaesthesia and
postnarcotic sleep disorders. Neuropsychobiology 1987; 18:
37–42.
43. Libert JP, Bach V, Johnson LC, Ehrhart J, Wittersheim G,
Keller D. Relative and combined effects of heat and noise on
sleep in humans. Sleep 1991; 14: 24–31.
44. Lin CC. Effect of nasal CPAP on ventilatory drive in
normocapnic and hypercapnic patients with obstructive sleep.
European Respiratory Journal 1994; 7: 2005–2010.
45. MacFadyen UM, Oswald I, Lewis SA. Starvation and human
slow wave sleep. Journal of Applied Physiology 1973; 35:
391–394.
46. McNamara SG, Grunstein RR, Sullivan CE. Obstructive
sleep apnoea. Thorax 1993; 48: 754–764.
47. Mancia G. Autonomic modulation of the cardiovascular
system during sleep. New England Journal of Medicine 1993;
328: 347–349.
48. Marcantonio ER, Goldman L, Mangione CM, Ludwig LE,
Muraca B, Haslauer CM, Donaldson MC, Whittemore AD,
Sugarbaker DJ, Poss R, Haas S, Cook EF, Orav EJ, Lee TH.
A clinical prediction rule for delirium after elective noncardiac
surgery. Journal of the American Medical Association 1994;
271: 134–139.
49. Moldofsky H, Lue FA, Smythe HA. Alpha EEG sleep and
morning symptoms in rheumatoid arthritis. Journal of
Rheumatology 1983; 10: 373–379.
559
50. Monti JM. Effect of zolpidem on sleep in insomniac patients.
European Journal of Clinical Pharmacology 1989; 36: 461–466.
51. Moote CA, Knill RL. Isoflurane anesthesia causes a transient
alteration in nocturnal sleep. Anesthesiology 1988; 69:
327–331.
52. Moote CA, Knill RL, Skinner MI, Rose EA. Morphine
disrupts nocturnal sleep in a dose-dependent fashion.
Anesthesia and Analgesia 1989; 68: S200.
53. O’Keeffe ST, Chonchubhair AN. Postoperative delirium in
the elderly. British Journal of Anaesthesia 1994; 73: 673–687.
54. Opp MR, Krueger JM. Interleukin 1-receptor antagonist
blocks interleukin 1-induced sleep and fever. American
Journal of Physiology 1991; 260: R453–R457.
55. Opp M, Obal F, Krueger JM. Corticotropin-releasing factor
attenuates interleukin 1-induced sleep and fever in rabbits.
American Journal of Physiology 1989; 257: R528–R535.
56. Parker RK, Holtmann B, Smith I, White PF. Use of ketorolac
after lower abdominal surgery. Anesthesiology 1994; 80: 6–12.
57. Perry SW, Wu A. Rationale for the use of hypnotic agents in
a general hospital. Annals of Internal Medicine 1984; 100:
441–446.
58. Rechtschaffen A, Kales A. A Manual of Standardized
Terminology, Techniques and Scoring System for Sleep Stages
of Human Subjects. Bethesda, MD: US Department of
Health, Education and Welfare, 1968.
59. Reeder MK, Muir AD, Foëx P, Goldman MD, Loh L, Smart
D. Postoperative myocardial ischaemia: temporal association
with nocturnal hypoxaemia. British Journal of Anaesthesia
1991; 67: 626–631.
60. Richards KC, Bairnsfather L. A description of sleep patterns
in the critical care unit. Heart and Lung 1988; 17: 35–42.
61. Rosenberg J, Kehlet H. Postoperative episodic oxygen
desaturation in the sleep apnoea syndrome. Acta
Anaesthesiologica Scandinavica 1991; 35: 368–369.
62. Rosenberg J, Kehlet H. Postoperative mental
confusion—association with postoperative hypoxaemia.
Surgery 1993; 114: 76–81.
63. Rosenberg J, Pedersen NH, Ramsing T, Kehlet H. Circadian
variation in unexpected postoperative death. British Journal
of Surgery 1992; 79: 1300–1302.
64. Rosenberg J, Rasmussen V, von Jessen F, Ullstad T, Kehlet
H. Late postoperative episodic and constant hypoxaemia and
associated ECG-abnormalities. British Journal of Anaesthesia
1990; 65: 684–691.
65. Rosenberg J, Wildschiødtz G, Pedersen MH, von Jessen F,
Kehlet H. Late postoperative nocturnal episodic hypoxaemia
and associated sleep pattern. British Journal of Anaesthesia
1994; 72: 145–150.
66. Shapiro CM, Flanigan MJ. Function of sleep. British Medical
Journal 1993; 306: 383–385.
67. Shibasaki T, Yamauchi N, Hotta M, Imaki T, Oda T, Ling
N, Demura H. Brain corticotropin-releasing hormone
increases arousal in stress. Brain Research 1991; 554:
352–354.
68. Somers VK, Phil D, Dyken ME, Mark AL, Abboud FM.
Sympathetic-nerve activity during sleep in normal subjects.
New England Journal of Medicine 1993; 328: 303–307.
69. Steiger A, Gukdner J, Hemmeter V, Rothe B. Wiedemann K,
Holsboer F. Effects of growth hormone-releasing hormone
and somatostatin on sleep EEG and nocturnal hormone
secretion in male controls. Neuroendocrinology 1992; 56:
566–573.
70. Trachsel L, Schreiber W, Holsboer F, Pollmächer T.
Endotoxin enhances EEG alpha and beta power in human
sleep. Sleep 1994; 17: 132–139.
71. Wilcox I, Collins FL, Grunstein RR, Hedner J, Kelly DT,
Sullivan CE. Relationship between chemosensitivity, obesity
and blood pressure in obstructive sleep apnoea. Blood Pressure
1994; 3: 47–54.