Download sleep and pain - Memorial Physicians. Yakima medical practice

MADHUKAR KUMAR, MD.
MEMORIAL SLEEP SPECIALISTS
 Nothing to disclose
 Pain itself represents a heterogeneous group of
conditions.
 Chronic pain Vs Acute pain.
 Pain, Mood, Sleep.
 Complex relationship:
i.
Type of pain syndrome.
ii. Co – morbidities.
iii. Age & gender.
 Mainly focus on chronic pain.
 Sleep complaints are present in 67-88% of chronic
pain disorders(1) and at least 50% of individuals with
insomnia—the most commonly diagnosed disorder of
sleep impairment—suffer from chronic pain(2).
 Treatment of chronic pain is complex, sleep
disturbance often inevitable:
I. Opioids.
II. Muscle relaxants.
III. AEDs.
 Multiple consequences- insomnia, hypersomnia,
sleep related breathing disorder.
(1)
(2)
Morin CM, LeBlanc M, Daley M, Gregoire JP, Merette C. Epidemiology of insomnia: prevalence,self-help treatments, consultations, and determinants of help-seeking
behaviors. Sleep Med. 2006;7:123–30.
Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep. 2007; 30:213–8.
 Major overlap between chronic pain and other
functional disorders, and mood disorders in particular.
 Mood disorders themselves are an extremely common
cause of sleep disturbance- insomnia, hypersomnia.
 Obesity epidemic – obstructive sleep apnea syndrome.
 Most patients “All of the above.”

That pain has an arousal-enhancing consequence that prevents the initiation or
continuation of sleep, leading to daytime sleepiness and napping

That nociceptive pathways and sleep–wake pathways have common neurobiological
systems, including central serotonergic transmission. Pain and disturbed sleep could,
therefore, be the result of a common neurobiological dyfunction (1).

That poor sleep has a negative impact on pain processing, resulting in enhanced pain
sensitivity (2).

Several studies looking at the effects of partial sleep deprivation on pain or noxious
stimuli perception. Results concordant – sleep deprivation induces hyperalgesia.
(1)
(2)
Roehrs T, Roth T. Sleep and pain: Interaction of two vital functions. Semin Neurol 2005; 25: 106-16
Lautenbacher S, Kundermann B, Krieg J-C. Sleep deprivation and pain perception. Sleep Med Rev 2005;
 Sleep disturbance an inherent part of diagnosis (100 % or near).
 PSG findings are non – specific:
I.
“Alpha intrusion” - sleep, Alpha – Delta or Alpha in N1 and N2 (EEG
changes).
II.
Reduced sleep efficiency.
III.
Increased sleep fragmentation, reduction in N3.
IV.
Increased frequency of periodic limb movement (PLM Index).

UARS (upper airway resistance syndrome)- variant of OSA; normal AHI on
PSG , but symptoms of untreated OSAS; typically seen in pre-menopausal
women. Diagnosis established by Pes (esophageal pressure manometry).

Studies support improvement in functional outcome with treatment of
UARS with PAP therapy in Fibromyalgia (1).
(1) Gold AR; Dipalo F; Gold MS; Broderick J. Inspiratory airflow dynamics during sleep in women with fibromyalgia. SLEEP 2004;27(3):459-66
 “ Sleep is a behavioral state distinguishable from
wakefulness by reduced responsiveness to stimulation.”*
 Recumbent posture, closed eyes, decreased environmental
responsiveness
 Can be responsive to command, even during consolidated
sleep.
 Cetaceans – Dolphin, porpoise, whales- adaptive
evolutionary behavior of “unihemispheric” sleep from birth
e.g. baby dolphin has one eye open when swimming next to
mother.
 Invertebrates e.g. Drosophila, crayfish, roundworms – do
they sleep?
* Principles and practice of sleep medicine; Krieger, Dement, Roth.
Sudhansu Chokroverty MD, Sleep disorders medicine, Saunders, 3 e.
 Unknown.
 In Rat models, acute sleep deprivation leads to death.
 Consequences in humans more subtle.
 Evidence suggests that perhaps there is some increase
in mortality with chronic sleep deprivation, but
conflicting evidence.
 Changes in neuro – cognitive measures are better
defined versus relationship with physical disease.
 So, what is the ideal duration of sleep?
i.
ii.
iii.
iv.
v.

6 hr
8 hr
10 hr
12 hr
14 hr
Older people need less sleep?
 ACS study – self reported – 1982, 1.116 million respondents:
a) 52 % < 7.5 hrs/night
b) 20 % <6.5 hrs/night
c) 4 % < 5.5 hrs/night
d) 3 % > 9.5 hrs/night
 2005 Gallup poll, 1500 respondents, self report
a) 6.8 h on weekdays
b) 7.4 h on weekends.
 Self report is unreliable “sleep state perception.”
 EEG confirmed sleep is the gold standard, but invalidates any study

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on normal sleep duration.
Various surrogates like psychomotor vigilance, measurement of sleep
drive/homeostasis (MSLT) etc.
Normative parameters remain ill defined.
Sudhansu Chokroverty MD, Sleep disorders medicine, Saunders, 3 e.
 Rechstaffen and Kales
 Revised by AASM
 Currently:
Stage N1
ii. Stage N2
iii. Stage N3
iv. Stage REM
 Established age 2-3 months; sleep stage distribution
changes throughout life
 Primarily EEG based, EOG and EMG essential to
distinguish REM Vs NREM stages.
i.
Sudhansu Chokroverty MD, Sleep disorders medicine, Saunders, 3 e.
 Sleep stage distribution i.e. sleep architecture is critical for the
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restorative aspects of sleep.
N1N2N3REM. Cycle length is variable, but usually 2-2.5 hrs.
REM EEG activity cannot be distinguished from the wake state (EOG,
EMG).
Cortical arousals ( => 3 sec distinct and abrupt increase in EEG
frequencies during sleep) frequently seen in chronic pain, and
interfere with sleep architecture.
CAP or “cyclical alternating patterns”. Depression, pain, drugs
(benzodiazepines).
Idea of CAPs evolved from psychiatry/neurology(biological markers
for mood disorders), later applied to pain (fibromyalgia).
Remains clinically relevant, with association with sleep disordered
breathing ( Upper airway resistance syndrome).
Measures multiple parameters:
I.
4 lead EEG.
II.
Bilateral chin EMG (sub mentalis).
III.
Bilateral leg EMG (anterior tibialis).
IV.
Bilateral EOG.
V.
Single lead EKG.
VI.
Nasal pressure transducer.
VII. Oro – nasal thermistor.
VIII. Thoraco-abdominal plethysmography.
IX.
Sp O2.
X.
Technician attended, continuous video and audio recording.

Other channels like ETCO2, TCO2,P es, Ph probes, muscle leads, extended
EEG can be added.

It is the definitive standard for staging of sleep, amongst other parameters.

 The more accurate term is “cardio-respiratory monitoring.”
 Cannot distinguish sleep/wake.
 Records breathing, HR, thoraco-abdominal motion, Sp O2.
 Will almost always underestimate AHI severity (cannot
record cortical arousals).
 Useful for screening in high risk populations, but will miss
many cases of OSA.
 Single channel monitoring e.g. overnight oximetry, will also
miss cortical arousal related sleep related breathing
disorder.
 Clinically relevant aspects:
Insomnia and it’s management.
II. Sleep related breathing disorders.
III. Role of Medication(Opioids).
IV. Hypersomnia syndromes.
I.
 The most common sleep disorder.
 Headache as an example: A headache-free, population-based
British sample were significantly more likely to develop new
incident cases of headache (diagnostic type not specified) at 1year follow-up if insomnia symptoms were present at baseline. In
the same study, individuals with headache were more likely to
remit at 1 year if insomnia symptoms were absent at baseline(1).
 Huge impact on quality of life, very strong correlation with
mental illness (DSM criteria were the standard for many years).
 More acceptance of the idea of “psychophysiological insomnia”
as being independent or co-existent i.e. not all insomnia is due
to a mental illness.
 Effective management usually needs a multidisciplinary
approach.
Boardman HF, Thomas E, Millson DS, Croft PR. The natural history of headache: predictors of onset and recovery. Cephalalgia.
2006; 26:1080–8.
A complaint of difficulty initiating sleep, difficulty maintaining sleep, or waking up too
early or sleep that is chronically non - restorative or poor in quality. In children, the
sleep difficulty is often reported by the caretaker and may consist of observed bedtime
resistance or inability to sleep independently.
B.
The above sleep difficulty occurs despite adequate opportunity and circumstances to
sleep.
C.
At least one of the following forms of daytime impairment related to the nighttime
sleep difficulty is reported by the patient:
i.
Fatigue/Malaise.
ii.
Attention, Concentration or memory impairment.
iii.
Social or Vocational dysfunction or poor school performance
iv.
Mood disturbance or irritability
v.
Motivation, energy, or initiative reduction
vi.
Proneness for errors or accidents at work or while driving
vii.
Tension , headaches, or gastrointestinal symptoms in response to sleep loss
viii. Concerns or worries about sleep
A.
International classification of sleep disorders, 2nd edition, American association of sleep medicine.
 About 30 % of patient’s presenting in a primary care
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setting have prominent sleep complaints.
6- 10 % meet criteria for insomnia.
F > M.
Early adulthood typical time of onset.
Stressful life event usually identified prior to first
episode.
Older age, psychiatric disorders, family history are
additional risk factors.
Untreated insomnia – caffeine dependence, hypnotic
dependence, mood disorders, chronic pain.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Adjustment insomnia.
Psycho - physiological insomnia.
Paradoxical insomnia.
Idiopathic insomnia.
Insomnia due to a mental disorder.
Inadequate sleep hygiene.
Behavioral insomnia of childhood.
Insomnia due to drug or substance.
Insomnia due to medical condition.
Non - organic insomnia – NOS.
Organic insomnia – NOS.
International classification of sleep disorders, 2nd edition, American association of sleep medicine.
A.
B.
C.
i.
ii.
iii.
iv.
v.
The patient’s symptoms meet criteria for insomnia.
The insomnia is present for at least one month.
The patient has evidence of conditioned sleep difficulty and/ or heightened
arousal in bed as indicated by one or more of the following:
Excessive focus on and heightened anxiety about sleep.
Difficulty falling asleep in bed at the desired bed time or during planned
naps, but no difficulty falling asleep during other monotonous activities
when not intending to sleep.
Ability to sleep better away from home.
Mental arousal in bed characterized either by intrusive thoughts or
perceived inability to volitionally cease sleep – preventing mental activity
Heightened somatic tension in bed reflected by a perceived inability to relax
the body sufficiently to allow the onset of sleep.
 The sleep disturbance is not better explained by another sleep disorder,
medical or neurological disorder, mental disorder, medication use, or
substance use disorder.
International classification of sleep disorders, 2nd edition, American association of sleep medicine.
A. The patient’s symptoms meet the criteria for insomnia
B. The insomnia is present for at least one month
C. A mental disorder has been diagnosed according to standard
criteria
D. The insomnia is temporally associated with the mental
disorder; however, in some cases ,insomnia may appear a few
days or weeks before the emergence of the underlying mental
disorder
E. The insomnia is more prominent then that typically associated
with the mental disorders, as indicated by causing marked
distress or constituting an independent focus of treatment
F. The sleep disturbance is not better explained by another sleep
disorder, medical or neurological disorder, mental disorder,
medication use, or substance use disorder
International classification of sleep disorders, 2nd edition, American association of sleep medicine.
 Careful clinical evaluation.
 Important distinction between Circadian rhythm sleep disorders and

1.
2.
3.
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1.
2.
3.
insomnia (being sleepy and being unable to sleep Vs not being sleepy at
desired bed time, conforming to norms).
Tools:
Sleep diaries.
Actigraphy (Gyrometer + Photometer). Good correlation with PSG
verified sleep.
PSG – NOT routinely indicated, may be ordered for resistant or
difficult to treat insomnia.
Treatment:
Pharmacological.
Non – pharmacological / Behavioral.
Management of the underlying cause- mood, and pain disorder.
 CBT I – for Insomnia
 Most useful in Psychophysiological insomnia , where time in bed > > total sleep time.
 Good results in insomnia secondary to a mental illness.
 Sleep efficiency ( TST/TIB <= 85 % for diagnosis). Aim is to correct to 85 % or above.
 Basis being that sleep, and hence insomnia ,can be viewed as a conditioned behavior
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a.
b.
c.
d.
e.
f.
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(what is learnt can be unlearnt).
“ Stimulus control” therapy and “Sleep restriction” form the basis of this treatment.
Typically delivered in 6 – 8 sessions – can be individual, group or online formats.
End point of treatment is usually to increase Sleep Efficiency to > 85 %.
Some useful terms:
Time in bed ( TIB).
Sleep onset latency ( SOL).
Frequency of nocturnal arousals ( FNA).
Wake after sleep onset time ( WASO).
Bed time, Wake time, and Lights out ( BT/WT/LO).
Total sleep time ( TST).
Support for it’s use in chronic pain with co-morbid insomnia(1).
(1)NIH Technology Assessment Panel on Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and
insomnia. Integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. JAMA 1996; 276: 313-8
 Suvorexant (Belsomra)- novel agent approved for
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insomnia.
Orexin/Hypocretin A & B antagonist (Narcolepsy)
CYP3A4 substrate.
T ½ 10 – 12 hrs.
Good results so far. No reported cases of cataplexy, perhaps
some automatic behaviors.
 Insomnia is extremely common in the chronic pain
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population.
Sleep consolidation has been associated with decreased
sensitivity to pain, as has sleep duration.
Early intervention is essential to prevent the long term
complication of hypnotic dependence and other
complications of untreated insomnia.
Simple behavioral modification can be effective (should
be advised to all patients).
Drug choices may be informed by sleep complaints/sleep
history.
Hypnotic prescriptions need to be carefully considered in
certain population groups- elderly, women, and those
with concurrent mental illness.
 Constitute 80 % of all referrals to sleep clinics.
 Prevalence of OSA 3 – 7 % in Males; 2 – 5 % in Females(Majority of cases in post
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•
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menopausal women).
Strong correlation to obesity e.g. Prevalence is 40- 60 % if BMI >= 30, 80-90 % if BMI
>=40.
Main risk factors are weight and oro - pharyngeal anatomy. Cause is unknown; regulation
of pharyngeal muscle tone through central pathways is a plausible hypothesis.
Strong association with adverse health outcomes.
Needs treatment regardless of symptoms in many cases:
HTN
CAD
Arrythmias
Stroke
DM
Cognitive impairment
Mood disorders
Diagnostic criteria for obstructive sleep apnea-hypopnea syndrome:
Individuals must fulfill criterion A or B, plus criterion C to be diagnosed with OSAHS :
(A) Excessive daytime sleepiness that is not better explained by other factors.
(B) Two or more of the following that are not better explained by other factors:
* Choking or gasping during sleep
* Recurrent awakenings from sleep
* Unrefreshing sleep
* Daytime fatigue
* Impaired concentration
(C) Overnight monitoring demonstrates five or more obstructed breathing events per hour during sleep or 30 events per
6 hours of sleep. These events may include any combination of obstructive apnea, hypopnea or respiratory effort
related arousals.
International classification of sleep disorders, 2nd edition, American association of sleep medicine.
 Clinical presentation is characterized by consequences of
sleep fragmentation:
I.
Sleep deprivation Excessive daytime sleepiness.
II. Marked reduction in psychomotor vigilance, even in the
absence of reported sleepiness ( CDL, FAA etc.)
III. Non – restorative sleep.
IV. Cognitive problems.
V. Insomnia (maintenance Vs initial).
VI. Many patients (20-30 % ) are asymptomatic i.e. no
subjective sleep related complaints.
Epoch from an in – lab PSG demonstrating a hypopnea (decrement in
airflow signal of 30 % or more, with 3 % or greater drop in Sp O2).
Epoch from PSG for the same patient………
Hypnogram of a split night format PSG, illustrating Sp O2 channel; Note marked
change after initiation of PAP therapy (CPAP, followed by BiPAP).
Hypnogram demonstrating Sp O2 channel and sleep stages from a polysomnogram, split
night format; note reduction in sleep fragmentation, increased REM sleep duration, and
recovery in oxygenation with introduction of CPAP therapy.
 PAP therapy has the best evidence.
 Severity criteria are relevant – AHI severity(Index/hr), Sp
O2 severity.
1. 5 – 14 “Mild” OSA.
2. 15-29 “Moderate” OSA.
3. >= 30 “Severe” OSA.
 Very confusing and minimizes true complexity.
 Sp O2 summary data from PSG, Cortical arousal
summary are other factors that always need to be
considered.
 Common modalities:
1.
2.
3.
4.
5.
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CPAP/Auto CPAP or Continuous Positive Airway
Pressure.
BiPAP or Bilevel Positive Airway Pressure.
BiPAP ST where ST = Spontaneous timed mode.
ASV or Adaptive Servo-Ventilation.
AVAPS – Assured Volume and Pressure Support.
Goal is reduction of AHI to <= 5; In many instances, 0.
“Splints” the upper airway; ↑ PaO2;↓PaCO2.

Goal is usually a 50 % reduction in the AHI.
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Usually not recommended for severe OSA( AHI >=30/hr).
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Positional therapy (non – supine sleep).
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Weight loss ( 10 %  AHI ↓ 20-30 %).
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Dental device or MAD (should be avoided in obese patients, high REM AHI, and is
expensive).
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Surgical alternatives: Multi- site- DNS correction, b/l turbinate reduction,
Uvulopalatopharyngoplasty, Genioglossus advancement, and Hyoid suspension (Surgery
is painful, several week post-op recovery period, not guranteed to reduce the AHI).
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Mandibulo-Maxillary advancement (best results for severe OSA, very major surgery,
change in facies, can simultaneously correct bite and cranio-facial abnormalities).
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Tracheostomy.
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For non – PAP therapies, the argument usually holds for effectiveness, and almost never
efficacy vs PAP therapy.
 Absence of central respiratory drive, resulting in absence of respiratory airflow
and effort.
 PSG cannot accurately distinguish OSA Vs CSA in some cases.
 Clinical presentation is somewhat different, daytime sleepiness is less
prominent, many patients are non – obese, crowded oro-pharynx is not a risk
factor etc.
 Sleep fragmentation and prominent orthopnea are common (extremely
dysphoric).
 Idiopathic or primary CSA is very rare. Common causes of secondary CSA
include high altitude, systolic HF ( CSB), neurological disorders (stroke, chiari
malformation) and opiate medication.
 Opioids induce respiratory depression through stimulation of µ2 receptors.
 Rapid tolerance to respiratory depressive effects of opioids is usual. However,
response is highly individual.
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Much more commonly seen then true CSA.
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Term refers to central apnea’s seen secondary to PAP therapy.
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Prevalance and significance remain somewhat controversial, but is commonly seen.
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Longtitudinal follow up indicates this is a “PAP Adaption” phenomenon and prevalence
is eliminated over time.
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Mechanism remains unknown, but inhalation of CO2 immediately terminates this
pattern.
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This is one of the or the main problem with initiation of PAP therapy in patients on
opioids minimal data or literature, but is presumably different to complex sleep apnea
without opioids, and so cannot presume it will improve with time.

Limited literature to suggest ASV or BiPAP ST may be useful.
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Supplemental oxygen if hypoxemia reported.
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Opioid reduction maybe essential.
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There is no diagnosis code for this, so PSG report will show OSA and CSA.
 Narcolepsy w/wo cataplexy.
 Hypersomnia due to drug or substance.
 Idiopathic hypersomnia w/wo long sleep time.
 Hypersomnia not due to substance or known
physiologic condition (psychiatric diagnosis).
 Hypersomnia due to a medical condition.
 Recurrent Hypersomnia (Kleine Levine syndrome).
 US prevalence is 0.02 to 0.18 %.
 M=F.
 Cataplexy in 50 % of patients.
 “Sleep attacks”
 Sleep related hallucinations, Sleep paralysis.
 Prominent PSG changes- sleep fragmentation, early
onset REM periods, reduced sleep latency.
 Hypothalamic deficiency of Orexin/Hypocretin
receptors.
 Need the MSLT for diagnosis.
 5 nap format is standard, at 2 hr intervals, 20 min duration
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each.
EEG, EMG, EOG, EKG, Sp O2, Chest and Abdomen belts.
Preceded by overnight PSG; 6 hr TST required. Cannot be
done if SRBD,PLMD, or other pathology explaining sleep
fragmentation is observed.
Sleep diaries for 2 weeks(r/o insufficient sleep, sleep
fragmentation).
No Psychotropic medication for 2 weeks – No SSRI or REM
suppressant, no drug with hypnotic potential.
Mean sleep latency < 8 min; 2 SOREMPs or Sleep Onset
REM Periods.
 SOREMPs are not necessary for other hypersomnia
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diagnosis.
Most cases seen in clinic are “due to drug or substance.”
Pertinent- treatment of SRBD in these cases will not
necessarily eliminate sleepiness.
MSLT is not indicated in these patients.
Idiopathic hypersomnia is a diagnosis of exclusion.
Main issue is to distinguish the subjective sense of
sleepiness from fatigue/tiredness.
 Strong correlation between sleep disorders and pain conditions.
 Treatment of sleep disorder appears to improve the pain condition.
 All patients should be screened for insomnia, and sleep disordered breathing.
 Behavioral management of insomnia is effective and simple (CBT – I).
 Hypnotics may need extra care before prescription.
 Hypersomnia is commonly seen independent of a primary sleep disorder.
Evaluate for MVA risk in all patients on sedative pain medication.
 Low threshold for evaluation for sleep disordered breathing.
 Management of sleep disordered breathing is complicated by opioids(Complex
sleep apnea).