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decreased sleep efficiency and altered REM sleep. Antidep ressant medications can
influence sleep quality and may exacerbate or induce sleep disorders. Understanding
the effects of antidepressants on sleep is crucial for effective treatment of depression.
Different classes of antidepressants can disrupt sleep architecture and REM sleep
latency. In summary, REM sleep plays a significant role in sleep physiology and is
associated with various neurophysiological and
pathological conditions. Further
research is needed to fully understand the mechanisms and clinical implications of
REM sleep disorders.
202 A. S. BaHammam et al.
Keywords Sleep stages · REM sleep · Sleep disorders · Obstruc
tive sleep apnea
(OSA) · REM sleep behavior disorder (RBD) · Antidepressant medications
13.1 Introduction
During sleep, our body cycles through three distinct stages: rapid eye movement
(REM) and non-rapid eye movement (NREM) sleep. The body usually cycles
through these stages on average four to six times, 90 min in each stage. As the
night progresses, fewer NREM stages occur, and the duration of REM sleep episodes
increases with time (Memar and Faradji
2018). Sleep may be categorized into wake,
N1, N2, N3, and R (REM). Sleep is scored in sequential 30-s epochs, and each of
these epochs is assigned a specific sleep stage based on the American Academy of
Sleep Medicine (AASM) scoring rules. Most of the sleep is spent in the N2 stage in
normal subjects (Malik et al. 2018). REM stage is associated with active dreaming.
The EEG is like an awake individual, but the skeletal muscles are atonic and without
movement. The only exception is the eye and diaphragmatic breathing muscles,
which remain functional. The breathing rate is impaired, and more erratic and
irregular. This stage usually starts about 90 min after falling asleep, and each of
the REM cycles gets longer throughout the night. The first period typically lasts a
few minutes, and the final one can last almost an hour (Ferri et al. 2017).
13.2 AASM Scoring Criteria for Stage R (REM) Sleep
– EEG demonstrates a low-voltage, mixed EEG pattern. Sawtooth waves are
common during REM sleep; these 2–6 Hz wave patterns are sharply contoured
and occur in brief bursts.
– The characteristic that defines this stage is the rapid movement of the eyes. These
are defined on EOG by conjugate, irregular, sharply peaked eye movements with
an initial phase of fewer than 500 ms.
–
EMG demonstrates atonia, the inhibition of alpha motor neurons directly leads to
the absence of voluntary muscle activity, except for the muscles controlling eye
movement (extraocular muscles) and breathing (diaphragm) (American Academy
of Sleep Medicine
n.d.).
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13 Impact of REM Sleep on Sleep Disorders: Current Perspectives 203
13.3 Significance of REM Staging
Despite many well-done clinical and preclinical studies, the mystery regarding the
REM stage continues.
Basic science: The sleep cycle is regulated by the circadian rhythm, a process
controlled by the suprachiasmatic nucleus (SCN) of the hypothalamus (España and
Scammell
2011). The extraocular movements after which REM sleep is named are
mainly due to the cholinergic activity of the pedunculopontine tegmentum (PPT)
center and glutamatergic activity of the medial pontine reticular formation (mPRF)
(
https://www.statpearls.com/articlelibrary/viewarticle/28329/). Datta et al. showed
that “selective RSD (REM sleep deprivation) induced increased expression of
BDNF (brain-derived neurotrophic factor (BDNF) expression in the PPT
(pedunculopontine tegmentum) and SubCD (subcoeruleus nucleus) are determinant
factors in the development of the homeostatic drive for REM sleep” (Datta et al.
2015).
Many parameters are used to measure REM sleep, including the time to onset,
length of the REM stage, and amount/intensity of eye movement that occurs during
REM. REM latency refers to the time elapsed between the onset of sleep to the first
REM stage. REM density refers to the number of eye movements during REM sleep,
and changes have been associated with sleep deprivation and depression. REM sleep
is associated with more frequent and longer duration of apneas, hypopneas, and
severe hypoxemia (American Academy of Sleep Medicine n.d.; Shrivastava et al.
2014; Pirzada and BaHammam 2021).
13.4 Neurophysiological and Pathological Conditions
Concerning REM Sleep
13.4.1 REM-Predominant Obstructive Sleep Apnea
The reported prevalence of REM-related OSA is quite variable, ranging from as little
as 10% to as much as 36% of the patient population with OSA undergoing PSG
(Conwell et al. 2012). The variability in the reported prevalence is related to the lack
of an accepted definition of REM-predominant OSA. The currently accepted defi-
nition is refined by considering REM sleep duration in terms of percentage or
minutes and excluding significant NREM-OSA.
OSA can present with or provoke various psychological symptoms. BaHammam
et al. reviewed studies that have examined dreams, dream recall, and dream content
in patients with OSA. Obstructive events induce recurrent sleep fragmentation and
intermittent desaturations in patients with OSA, which may trigger different
parasomnias, including nightmares. Contradictory results have been reported
concerning dreams in patients with OSA. A clear association between post-traumatic
stress disorders, comorbid OSA, and nightmares has been reported in several studies.
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Furthermore, an improvement in nightmare frequency with continuous positive
airway pressure (CPAP) treatment has been shown. An inverse relationship between
the severity of OSA reflected by the apnea-hypopnea index and dream recall has
been demonstrated in several studies. (BaHammam and Almeneessier
2019;
BaHammam et al. 2018)
204 A. S. BaHammam et al.
REM-predominant OSA is a
sleep-breathing abnormality during which apneas
and hypopneas occur predominantly or exclusively during REM sleep periods. Body
position has an important effect on breathing abnormalities during REM sleep.
During this sleep stage, the supine posture has a worsening effect, facilitating the
occurrence of breathing abnormalities, but the duration of these events is like the
duration of events occurring in the lateral posture (Oksenberg et al.
2010). As REM
sleep is accompanied by smaller lung volumes, a decrease in airway muscle tone,
reduced hypoxic and hypercapnic ventilatory effort, and an increase in blood
pressure at the termination of the obstructive events, obstructive events tend to
worsen in REM sleep (Pirzada and BaHammam
2021).
Studies have consistently shown that REM-predominant OSA occurs more com-
monly in younger individuals, women, children, and patients with mild or moderate
OSA despite the wide variation in prevalence (Goh et al.
2000). Functional outcomes
in patients with REM OSA improve after treatment with PAP therapy comparable to
that observed in patients with OSA not restricted to REM (Su et al. 2012). The
sequelae of REM-predominant OSA are getting more clear now. Severe OSA that
occurs primarily during REM sleep is associated with a higher incidence of com-
posite cardiovascular and metabolic endpoints but in only those with preval ent
cardiovascular disease (Iannella G et al. 2020 and Aurora et al. 2018).
Despite the overwhelming research related to REM sleep behavior disorder
(RBD) and OSA as different entities, few papers paid attention to the coexistence
of RBD and OSA. The salient differences are as follows. The nadir SpO
2
of OSA
patients with RBD achieves a lower drop compared to those observed in REM-OSA
patients (Giardino et al. 2021). The improvement observed in RBD patients on OSA
severity, denoted by a lower drop in nadir SpO
2
, was named by Giardino et al. “the
respiratory RSWA (REM sleep without atonia-RSWA) benefit” (Giardino et al.
2021). These findings may sugges t that a shorter duration for sleep events and a
consequent minor reduction of nadir oxygen saturation were related to an enhance-
ment of active Pcrit (active critical closing pressure of the upper airway) in
OSA-RBD patients.
13.5 REM Sleep Behavior Disorder
REM sleep behavior disorder (RBD) is a particularly intriguing parasomnia. RBD is
a parasomnia charact erized by dream-enacting behaviors associated with REM sleep
without muscle atonia (also known as REM sleep without atonia or RSWA). These
patients have repeated episodes of sleep-rel ated vocalizati on and/or complex motor
behaviors, which may be documented by PSG. Alternatively, they may also be based
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on a clinical history of dream enactment during REM sleep (American Academy of
Sleep Medicine 2014). RBD can be isolated, also known as idiopathic (iRBD), or
comorbid (secondary) with other conditions related to neurodegenerative, autoim-
mune, or structural abnormalities or medications (Dauvilliers et al.
2018).
13 Impact of REM Sleep on Sleep Disorders: Current Perspectives 205
Muscle atonia during REM
is a protective mechanism that involves both muscle
atonia and suppression of motor-skeletal activity. This process entails active inhibi-
tion by neurons in the medulla, in addition to inhibition of the spinal motor neurons
through feedback from the forebrain and thalamus (Fraigne et al.
2015). Several
pontine regions, including the peri-locus coeruleus region, pedunculo-pontine
nucleus (PPN), and laterodorsal tegmental nucleus (LDTN) excite neurons in the
medulla, resulting in descending inhibitory projections to spinal alpha motor-
neurons causi ng hyperpolarization and muscle atonia. The disinhibition of these
neurons in RBD patients causes the appearance of muscle activity during REM
sleep.
Longitudinal studies have shown that patients diagnosed with iRBD may even-
tually be diagnosed with a neurological disorder such as Parkinson’s disease (PD),
dementia with Lewy bodies (DLB), and multisystem atrophy. Most patients are
eventually diagnosed with synucleinopathies PD, DLB, and, less frequently, MSA.
iRBD represented the prodromal period of these conditions.
In RBD, there is a predilection for the male gender, and prevalence estimates are
0.38% to 0.5% in the general population. Prevalence in patients with psychiatric
disorders is greater, related to medications prescribed for psychiatric disorders. In a
report by Olson et al. involving 93 patients with RBD, only 12 patients (13%) were
female (American Psychiatric Association 2013; Olson et al. 2000). Between 33%
and 65% of RBD patients have been reported to have had sleep-related injury to self
or bed partner (Comella et al.
1998).
Sleep clinicians should maintain an index of suspicion for RBD regardless of the
presenting sleep complaint in patients greater than 50 years of age, or those at any
age with narcolepsy and other neurological disorders (Schenck 2016; Iranzo et al.
2014). RBD in narcolepsy usually occurs in a younger age group, does not have sex
preponderance, and has fewer occurrences of complex and violent movements
(Cipolli et al. 2011 ; BaHammam et al. 2020).
All patients with RBD and their bed partners should be educated on ways to alter
the sleeping environment to prevent injury. The AASM guidelines do recommend
clonazepam for RBD treatment, but the drug should be used with caution in patients
with dementia, gait disorders, or concomitant OSA. Melatonin is also recommended
for the treatment of RBD with the advantage that there are few side effects, and this
may be a preferred medication for the elderly who may be at risk of falling with the
use of benzodiazepines. Other medication with limited evidence includes zop iclone,
benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, car-
bamazepine, and sodium oxybate (Aurora et al.
2010).
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206 A. S. BaHammam et al.
13.6 Psychiatric Disorders and REM Sleep
13.6.1 Major Depressive Disorder (MDD)
It is well known that major psychiatric disorders like MDD significantly impact sleep
architecture. MDD is correlated with a decrease in REM latency, an increase in REM
density, and a prolonged time in the first REM cycle (Anderson and Bradley
2013).
This has been confirmed in several studies that have consistently shown a reduction
in sleep efficiency, decreased slow-wave sleep (SWS), and disinhibited REM sleep
with shortened REM latency, a longer first REM cycle, and increased REM density
(the number of eye movements during REM). Many epidemiologic studies showed
poor sleep quality in 50–90% of those with depression (Riemann et al.
2001;
Kempenaers et al. 1988).
REM sleep normalizes after depression treatment, but many antidepressants are
known to lengthen REM latency and improve sleep continuity in both patients and
normal controls. Increased sleep efficiency and REM sleep improvement have also
been demonstrated after nonpharmacological therapies such as cognitive behavioral
therapy. Despite these paradoxical observations, there is a significant impact on the
sleep stages, and needs further research (Nofzinger et al.
1994; Thase et al. 1998).
13.6.2 Schizophrenia
Sleep is disturbed in 30–80% of patients with schizophrenia, depending on the
degree of psychotic symptomatology (Keshavan and Tandon 1993). Dream recall
and eye movements during sleep were studied by Dement in 1955 in patients with
schizophrenia and compared to controls. They showed a reduction in dream recall in
patients with schizophrenia and abnormal REM parameters (Dement
1955). Mem-
ory consolidation is also impaired compared to controls and positively correlated
with the amount of SWS and sleep efficiency. Manoach et al. showed that SWS and
Stage 2 sleep in the last quartile of the night (S2q4) sleep, each predicted the initial
level of overnight improvement in schizophrenia, and their product explained 77%
of the variance, suggesting that both sleep stages are necessary for consolidation
(Manoach et al. 2010).
However, the direct effect of antipsychotic medication is controversial. First-
generation or typical antipsychotics are associated with increased total sleep time,
increased sleep continuity, and REM latency, but the reported effects on other sleep
stages are variable (Cohrs
2008). However , these effects are not consistent in
subsequent studies. In contrast, studies of the effects of atypical antipsychotics
(clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and paliperidone) in
healthy controls and schizophrenia patients show a consistent effect on measures of
sleep continuity, with an increased total sleep time and/or sleep efficiency and
individually varying effects on other sleep parameters, such as an increase in REM
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Drug latency sleep action
latency. Newer antipsychotics like clozapine most frequently induce EEG slowing
and epileptiform discharges (Jackson and Seneviratne 2019).
13 Impact of REM Sleep on Sleep Disorders: Current Perspectives 207
Table 13.1 Effects of antidepressants on sleep
Sleep
architecture
disruption
Sleep-
wave
state
REM REM Mechanism of
Tricyclic
antidepressants
Increased Increase Increase Decrease Serotonin
Sedative-like Norepinephrine
Tricyclic Decrease Decrease Increase Decrease Serotonin
Antidepressants Norepinephrine
Stimulating
Mono-amine Oxidase
Inhibitors (MAOI)
Variable Variable Increase Decrease Monoamine
oxidase
SSRI Variable Variable Increase Decrease Serotonin
e.g. Fluoxetine
SNRI Decrease Variable Increase Decrease Serotonin
Venlafaxine Norepinephrine
Bupropion Variable Variable Variable Variable Norepinephrine
Dopamine
Other Increase Increase None None Norepinephrine
Antidepressants Dopamine
Schizophrenia also affects the circadian rhythm. A recent study included
prolonged actigraphy and melatonin profiles in 20 schizophrenia patients compared
to 21 unemployed controls and found marked circadian rhythm abnormalities among
patients with schizophrenia, including both delayed sleep-phase disorder and free-
running, the
non-24-h circadian rhythm in 50% of those studied, with no relationship
to the neuroleptic used (Wulff et al. 2012).
Effect of drugs on REM Sleep (Table 13.1): In order to effectively treat
depression, it is crucial to comprehend the impact of antidepressants on sleep
patterns. Certain types of antidepressant medications have the potential to exacerbate
or trigger primary sleep disorders such as restless legs syndrome, sleep bruxism,
REM sleep behavior disorder, nightmares, and sleep apnea. Patients with MDD
show abnormalities in sleep parameters. MDD has been reported to be associated
with disrupted sleep architecture, presents as a lengthened period before falling
asleep, heightened frequency and duration of waking up during sleep, and is charac-
terized by increased time awake after initially falling asleep. (WASO) time,
decreased sleep efficiency, and early morning awakenings. Early morning awaken-
ing, together with the altered distribution of REM sleep, is considered a biological
marker of circadian rhythm disturbances in depression and is a characteristic bio-
logical marker of depression with melancholic features (Wichniak et al. 2013).
Antidepressant drugs may deteriorate sleep quality due to the interaction of the
receptors with serotonin and norepinephrine reuptake inhi bitors (SNRI),
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norepinephrine reupt ake inhibitors (NRI), monoamine oxidase inhibitors (MAOI),
selective serotonin reuptake inhibitors (SSRI), and activating tricyclic
antidepressants.
208 A. S. BaHammam et al.
Tricyclic antidepressants. Most of them incre
ase total sleep time and decrease
wake time after sleep onset, while many selective serotonin reuptake inhibitors have
the opposite effect. Withdrawal from antidepressants may cause nightmares and
intensify dreaming (Wilson and Argyropoulos
2005).
Phenelzine, an MAOI drug, can safel y eliminate REM sleep in depressed patients
without altering the duration of visually scored slow-wave sleep (Landolt et al.
2001). Tolerance to the anticholinergic/sedating effects develops rapidly (usually
within a few days), while the REM-suppressing effects may persist. A REM sleep
rebound and sleep disturbance can be experienced with the abrupt discontinuation of
REM sleep-suppressing antidepressants.
In normal subjects receiving lithium for 2 weeks, total sleep time did not vary,
REM sleep decreased, and REM sleep latency increased. In depressed subjects,
either on short-term therapy or long-term therapy with lithium, sleep stages 3 and
4 increased, REM sleep decreased, REM latency increased, and REM activity/time
spent asleep (an index of REM intensity per minute of sleep) decreased (Billiard
1987).
Agomelatine is a nonsedative antidepressant drug exerting agonistic action at
melatonergic M1 and M2 receptors, and antagonistic action at serotonergic 5-HT2c
receptors. It should be considered an alternative drug of choice in treating depressed
patients with marked insomnia symptoms. In comparison to escitalopram,
agomelatine improves sleep latency after both short (after 2 weeks) and long (after
24 weeks) treatment. Both drugs differ significantly in their effect on sleep continu-
ity. In the second week, agomelatine slightly improves sleep continuity (increased
total sleep time and sleep efficiency), and escitalopram worsens it, and this effect is
not related to the suppression of REM sleep. While agomelatine has not received
approval for marketing from the U.S. Food and Drug Administration (FDA) in the
United States, it is available in other countries (Quera-Salva et al. 2011).
Central nervous system stimulants include amphetamines and related compounds
such as methylphenidate, modafinil, and pemoline. Xanthene derivatives such as
caffeine and theophylline are also considered CNS stimulants. As a rule, stimulants
increase wakefulness, decrease total sleep time and SWS, and increase sleep latency.
All of them uniformly decrease sleep continuity, SWS, and REM sleep, and increase
sleep latency (Sharma and Prasad 2015).
Opioids: In general, morphine decreases the number and duration of REM
periods, delays the onset of the first REM period, and increases the time between
REM period onsets. Many studies have shown that acute use of various opioids
results in increased REM latency, decreased REM sleep time, increased stage 1 and
stage 2 sleep, and decreased SWS. The short-term use of opioids also results in
a longer time to fall asleep, heightened wakefulness after initial ly falling asleep, and
a corresponding decrease in both the total duration of sleep and the efficiency of
sleep (Kay et al. 1969).
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13 Impact of REM Sleep on Sleep Disorders: Current Perspectives 209
Orexin receptor antagonists: The neuropeptides orexin A and orexin B (aka.
hypocretin1 and hypocretin 2) are thought to have a key role in the regulation of
sleep and wake states like narcolepsy. At least three studies administered selective
orexin receptor-2 antagonists (2-SORA) in either a healthy control (one study) or a
clinical sample (two studies). Their results show that DORAs (dual orexin receptor
antagonists) increase total sleep time primarily by prom oting REM sleep without
affecting or even decreasing non-REM sleep (Clark et al. 2020). Studies in other
species, like rats, demonstrated that intracerebroventricular injection of OX2R
antagonist (TCS-OX2–29) increased total sleep time and REM sleep. The increase
in REM sleep was due to an increase in the number of REM episodes (Kummangal
et al.
2013).
Antiseizure drugs: Older antiseizure drugs, like phenobarbital, carbamazepine,
and phenytoin, inhibit CNS activity, but the exact inhibition mechanisms are not
known. The older antiseizure drugs have varying effects on sleep architecture.
Placidi et al. study showed that the acute administration of CBZ-CR (carbamaze-
pine) increased the number of stage shifts, reduced REM sleep, and increased REM
sleep fragmentation. In the TLE (Temporal Lobe Epilepsy) group, these effects were
reversed entirely after chronic treatment. LTG increased REM sleep, reduced the
number of entries into REM sleep, decreased the number of phase shifts, and
decreased the percentage of SWS (Placidi et al. 2000c). Gabapentin (GBP) increased
REM sleep percentage, increased the mean duration of REM periods, reduced the
number of awakenings, and reduced stage 1 sleep percentage. Moreover, it has been
demonstrated that CBZ-CR disrupts REM sleep, but only during acute administra-
tion (Placidi et al. 2000a).
By attaching to the GABAA receptor and facilitating the entry of chloride ions,
PBT (phenobarbitone) promotes a decreased frequency of awakenings and a shorter
time to fall asleep. Additionally, it prolongs the duration of non-rapid eye movement
(NREM) sleep while diminishing the length of rapid eye movement (REM) sleep.
While phenytoin increases stage N1 sleep and decreases stage N3 sleep (Shvarts and
Chung
2013).
Levetiracetam (LEV): is a new generation AED used to treat both partial and
generalized epilepsy. In their study, Cicolin et al. conducted polysomnography and
Multiple Sleep Latency Tests on 14 healthy adults who received a maximum dosage
of 2000 mg/day of LEV. The results showed a notable rise in the duration of all
non-rapid eye movement (NREM) sleep stages, accompanied by a relative reduction
in the duration of rapid eye movement (REM) sleep. Overall, LEV exhibited a
tendency to enhance the consolidation of sleep without adversely affecting daytime
alertness (Cicolin et al. 2006).
Gabapentin (GBP) is an amino acid initially developed as a structural analog of
GABA, an inhibitory neurotransmitter in the adult brain. Polysomnography findings
revealed a notable increase in the proportion of REM sleep, along with an extended
average duration of REM sleep, a decrease in the frequency of arousals, as well as a
shorter duration of the initial stage of sleep (N1). Placidi et al. conducted a study to
assess 18 patients with refractory partial seizures who were receiving stable treat-
ment with a daily dosage of 1800 to 2400 mg of GBP for 4 months. The results
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showed a notabl e rise in the proportion of REM sleep and slow-wave sleep (SWS),
accompanied by a decrease in the number of awakenings and a reduction in the
duration of stage 1 sleep. Additionally, 16 patients reported experiencing enhanced
sleep quality during the study period (Placidi et al.
2000b).
210 A. S. BaHammam et al.
Melatonin and melatonin receptor
agonists: Ramelteon acts as an activator of
melatonin receptors, specifically targeting the MT1 and MT2 receptors. Inhibiting
the wakefulness-promoting activity of the suprachiasmatic nucleus. REM sleep
expression is strongly circadian modulated, and the impact of REM sleep on primary
brain functions, metabolic processes, and immune system function is significant.
Melatonin increases REM sleep percentage and causes improvements in the subjec-
tive measures of daytime dysfunction as well as clinical global impression score.
Exogenous administration of Melatonin normalizes circadian variation in human
physiology and may be helpful in elderly and shift workers (Kunz et al. 2004).
Beta-blockers: Beta-blockers are classified as lipophilic or hydrophilic. The
lipophilic agents include propranolol, metoprolol, and pindolol, while the hydro-
philic agents include atenolol and sotalol. Hydrophilic agents do not cross the blood-
brain barrier readily and, thus, have no sleep effects. Both lipophilic and hydrophilic
beta-blockers may negatively affect sleep architecture by suppressing REM sleep
(Rosen and Kostis 1985).
Benzodiazepines and nonbenzodiazepine receptor agonists: Benzodiazepines
such as diazepam, lorazepam, midazolam, and nonbenzodiazepine receptor agonists
such as zolpidem, zaleplon, eszopiclone are commonly prescribed sedative-hypnotic
medications used to treat sleep disorders. Finally, benzodiazepines and
nonbenzodiazepine receptor agonists may modestly reduce REM sleep when used
at higher than indicated doses.
13.7 Steroid and Sleep Disorders
Steroids are commonly used, and in the era of COVID-19, steroids have been
extensively used in the ICU in patients with respiratory failure. Other common
indications for steroids in the ICU include anaphylaxis, airway edema, septic
shock, asthma and COPD exacerbations, pneumocystis pneumonia, adrenal crisis,
antiemetic treatment, elevated intracranial pressure from tumors, autoimmune dis-
orders, and stress doses needed for chronic steroid users before invasive procedures.
Steroid-induced sleep disruption/psychosis: The administration of external ste-
roids is believed to induce disturbances in sleep, which can lead to additional
psychostimulant effects like changes in mood, nervousness, the onset of psychoses,
and delirium. There are three pathways responsible for the neurocognitive adverse
events (AEs) of steroids: behavior changes through modification of the HPA axis,
changes in natural sleep-wake cycles, and hyperarousal caused by modification in
neuroinhibitory pathways. In a randomized prospective crossover study involving
healthy participants, the administration of dexamethasone (3 mg every 8 h for 48 h)
led to notable alterations in sleep patterns as assessed through polysomnography.
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Compared with placebo, steroid treatment showed a significantly longer percentage
(SD) of stage 0/awake times (11.7% [11.4] vs. 2.9% [1.8]), a longer percentage
(SD) of REM sleep latency (363.8 [74.5] vs. 202.8 [79.6] min; P < 0.01), and a
reduced number (SD) of REM periods (3.8 [2.6] vs. 9.7 [3.6]; P < 0.01) (Devlin
et al.
2018).
13 Impact of REM Sleep on Sleep Disorders: Current Perspectives 211
Mitigating steroid-induced effect
s: Although steroid therapy often cannot be
altered in the critically ill population, research showed that steroid overuse is
common in the ICU setting. Minimizing dosage and duration are important ways
via which clinicians can mitigate unwanted effects. CNS AEs associated with
steroids often can be reversed once therapy is discontinued. Avoiding split-dose
administration has been proposed, given the natural diurnal production of cortisol. A
review by Flaherty discusses the importance of avoiding pharmacologic agents in
hospitalized older patients if possible due to known risks (falls, dependency, hip
fractures, rebound insomnia, and risk of delirium) (Bourne and Mills 2004; Cole
2020).
13.8 Conclusion
The increased severity of OSA during REM sleep contributes to an increased risk for
and severity of endothelial dysfunction, cardiovascular morbidity, and metabolic
disorders (Budhiraja et al.
2007; Budhiraja and Quan 2005). Dean et al. conducted a
cross-sectional analysis utilizing data from 2040 participants who participated in
polysomnography as part of the multiethnic study of atherosclerosis (MESA) during
the MESA Exam. They showed that the arousal index in REM and central apnea
indices were only higher associated with elevated DBP (Dean et al.
2015). What is
clinically significant REM OSA? At what time does REM time need to be consid-
ered in clinical evaluation? Mokhlesi et al. argue that a minimum REM sleep time
of 30 min would be required to reduce the possibility of overestimating the impact of
REM OSA in individuals with a limited duration of REM sleep. The presence of
REM OSA is linked to hypertension both in a cross-sectional and longitudinal
manner. This has significant clinical implications as the treatment of OSA typically
focuses on the first half of the sleep period, leaving a substantial portion of REM
sleep unaddressed (Mokhlesi et al.
2014).
The potential neurological implications of OSA were not recognized until
polysomnography was used to evaluate patients. It is important to conside r OSA
as a possibility in older individuals displaying common symptoms of sleep apnea
during both nighttime and daytime. Polysomnography (PSG) is an essential diag-
nostic tool for identifying OSA in elderly patients. In a recent study by Chen et al., it
was found that vertigo patients have a higher incidence of REM-related OSA, and
compliance with continuous positive airway pressure (CPAP) therapy is low in this
population. This may have practical implications in the management of elderly
patients with REM-related OSA associated with hypertension (Chen et al.
2021). Further research is needed to fully understand the mechanisms and clinical
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