Disturbed Sleep & Counting Sheep in Hospice and

Palliative MedicineAndi Chatburn, DO, MA

Fellow, University of Kansas SOM and Kansas City Hospice & Palliative Care

February 27. 2014

Emma Jane Hogbin/CC

wittecarlosanto/CC

Goals & ObjectivesReview normal sleep physiology and architectureRecognize types, causes and effects of insomniaApply diagnosis and treatment of insomnia to patients with serious illnessDiscuss general and disease specific treatment options for insomnia

Team-severus/CC

Normal Sleep PhysiologyBased on a 24.2h circadian rhythmLight-dark cycleDuration: avg. 7-8 hours per nightStructure: Onset NREM + REM Wakefulness

Peplow, M.

Stages of Sleep

Peplow, M.

Peplow, M.

Neurotransmitters Sleep onset: Serotonin and MelatoninWakefulness: Histamine, acetylcholine, dopamine, noradrenalineMelatonin, prostaglandin D2, IL-1: sleep and immune function

Neurotransmitters and Sleep

Peplow, M.

Peplow, M.

Functions of SleepRestorative/RecoveryMediating factor in pain regulationMediator of immune function

Factors needed for normal restorative sleep

TimingSleep DriveEnvironmentPhysical comfort/absence of symptomsIntact CNS functionAbsence of psychological distress

So What is Insomnia?Defined by patientUnsatisfactory sleep affecting daytime functioningInadequate/not enough/too muchMost frequent health complaint Leads to impaired daytime functioning, poor moodMay exacerbate medical or psychiatric conditions

InsomniaDisturbances:

Sleep ONSET (latency)Sleep MAINTENANCE (efficiency)Duration of sleep (OFFSET) NON-RESTORATIVE

InsomniaTransient: lasting one to several nights

Ex: Jet lagAcute/Short-term:

lasts few days to 3 weeksChronic/Long-term:

lasts for months to years, often waxes and wanes

Categories of Sleep Disorders

Diagnostic Category Common Diagnoses

Insomnia Primary insomnia, secondary insomnia due to mental disorder

Sleep related breathing disorders

Obstructive and central sleep apnea; hypoventilation/hypoxia syndromes

Hypersomnolence Narcolepsy; idiopathic hypersomnolenceCircadian rhythm disorders Delayed or advanced sleep phase; shift

work; irregular sleep-wake rhythm

Movement Disorders Restless Leg Syndrome; periodic limb movement

Parasomnias Night terrors, sleep walking, REM sleep behavior disorder

Other Environmental sleep disorder

Quantifying: Epworth Sleepiness Score

How often are you likely to fall asleep in the following situations, in contrast to feeling “just tired”?0 = would never doze1 = slight chance of dozing2 = moderate chance of dozing3 = high chance of dozing

Epworth Sleepiness Activities

Sitting and readingWatching TVSitting, inactive in a public place (theatre, meeting)As a passenger in a car for an hour without a breakLying down to rest in the afternoonSitting and talking to someoneSitting quietly after lunch without alcoholIn a car, while stopped for a few minutes in traffic

Environmental Sleep Disturbances

NoiseLightCo-sleeper/neighbor moaning, crying, snoring, movingFrequent interruptions: ex: vital signs, labs, glucose monitoringHeat/coldShift work and time zone changesMedications

Medications & Sleep Disturbances

Steroids (decreased REM)CNS stimulantsMethylxanthine bronchodilatorsMAO-I, fluoxetine, BuproprionAntihypertensives: methyldopa, propranololEtOHSelegiline, pramipexole, amantadine- can cause nightmares

Symptoms and Conditions Causing Distressed SleepPain: joint, wound, edema, nocturnal headachesNausea, Vomiting, Diarrhea, GERDDyspnea, Respiratory distressFever or hot flushesMovement disorders & neuropathyNocturiaItchingHyperarousal due to sleep deprivation itself

Psychosocial Symptoms Causing Disturbed SleepAnxietyDepressionCognitive impairment

Medication, metabolic, CNS disease, delirium

BehaviorExcessive time in bed, napping, irregular sleep/wake times. Daytime sleeping as a coping mechanism

Affects of Disturbed Sleep

Decreased quality of lifeFamily disruptions“compliance” with treatmentMoodImmune systemPain intensity

Categories of Disturbed Sleep

Unwanted Excessive Sleepiness: HypersomnolenceCan prevent patient and family from visiting with loved onesCentral sleep apnea: methadone

Disorders of Circadian Rhythm

Delayed Sleep Phase DisorderAdvanced Sleep Phase DisorderNon-24 hour sleep-wake disorder

Delayed Sleep Phase Disorder

Sleep onset and wake times much later than desiredTreatment:

Bright-Light (10K lumens) phototherapy in the morning hoursMelatonin administration in evening hours

Advanced Sleep Phase Disorder

Common in elderly patientsReport they can’t sleep past 5AMExcessive early evening sleepiness, even in social settingsOne family: Autosomal Dominant ASPD due to missence mutation in a circadian clock component PER2Bright-light photo therapy during the evening hours

Non-24h Sleep-Wake Disorder

Endogenous circadian rhythm out of sync with local environments- much longer than 24h“Days and nights reversed”Commonly blind individuals unable to perceive lightNightly low-dose melatonin (0.5mg) can synchronize circadian pacemaker

Sleep log: finding the cause

What’s keeping you awake when you want to be sleeping?What’s waking you up in the middle of sleep?What’s keeping you from falling back asleep?What’s getting you up so early in the morning?Review medication list!

Disease Specific Categories of

Disturbed Sleep

Disease specific Categories of Disturbed Sleep

ParasomniasRestless Leg SyndromeParkinsons ALSFibromyalgiaObstructive Sleep Apnea & Obesity Hypoventilation Syndrome

Parasomnias (NREM)Sleepwalking (Somnambulism, NREM 3-4)Sleep Terrors (NREM 3-4): autonomic arousalSleep Bruxism: dental guardSleep Enuresis (after age 6)Sleep-related eating disorderNocturnal leg cramps

Restless Leg SyndromeAlso: Periodic Limb Movements in Sleep (PLMS)Low ferritin (<40ng/mL): treat with iron supplementationMedical Tx:

Dopamine agonistGabapentinClonazepamOpioids

Sleep in ParkinsonsREM Sleep Behavior Disorder (RBD)Male > FemaleAgitated or violent behavior during sleepInjury to bed partner commonVivid unpleasant dream imagery“Seizure activity” absent on EEGTreatment: Clonazepam (0.5-1mg QHS)

Sleep in ParkinsonsNocturnal AkinesiaFrequent nighttime awakenings due to tremorRestless Leg SyndromesTreatment: supplemental nighttime doses of carbidopa/levodopaNighttime Urinary Urgency

Sleep in ALSChronic Nocturnal HypoventilationTreatment:

Non-Invasive Ventilation (CPAP/BiPAP) 4 hours a day, typically when sleeping

Sleep in FibromyalgiaDisruption of NREM stage 4 and repeated alpha wave intrusions

Also seen in healthy individuals with emotional distress or joint pain due to arthritis

Low levels of serotonin in CSFTheory: sleep disturbance a factor in causing fibromyalgia and pain of fibromyalgia keeps making it worse

Obstructive Sleep Apnea/Hypopnea Syndrome

Symptoms of excessive daytime sleepinessAND:

sleep breathing pauses lasting >10 sec Hypopneas >10 sec (breathing continues but ventilation reduced by >50%)Constant repetitive awakenings to open airway

Obstructive Sleep Apnea/Hypopnea Syndrome

Increased in: Obesity (>50% have BMI >30)Short Mandible/MaxillaMales, most middle age 40-65

Associated with:Tonsillar hypertrophy of AIDSPierre Robin SequenceHypothyroidismAcromegalyMyotonic dystrophyEhlers Danlos Syndrome

Sleep in Cancer/AIDSSleep deprivation altered immune function sleep deprivationImmune activation stimulates NREM stage 3 sleepNREM Stage 3 Sleep enhances immune function

Sleep in ESRDRLS and PLMS commonSleep apnea commonInsomnia caused by pain pain caused by insomnia

Sleep in ESRDCohort Study:

53% of pre-dialysis patients reported poor sleep 77% of dialysis patients had subclinical or clinical sleep disordersLab derangements not correlated with sleep quality

Sleep disturbance in Family Care Givers

Sleep disturbance common in caregiversDisruptions due to caring for loved one leads to fatigue and contributes to hopelessnessGrief, anxiety and depression are common95% of cancer caregivers report severe sleep problems

Interventions for Disturbed Sleep

Treatment for Disturbed Sleep

Treat underlying conditionTreat pain

Kinsman et al: “Pain relief is the most effective intervention for improving sleep maintenance”

Non-Pharmacologic InterventionsPharmacologic Interventions

Non-Pharmacologic Interventions

Sleep hygieneSleep log reviewMindfulness meditationCognitive Behavioral TherapyBiofeedbackProgressive muscle relaxationSleep restrictionHypnosis

Sleep HygieneTiming: same bed and wake timeAvoid nappingExercise dailyEnvironment: temperature 60-67 *F, quiet, darkComfortable mattress and pillows Avoid EtOH, cigarettes, caffeine, and heavy meals in the eveningWind down for 1 hour prior to sleepIf you can’t sleep, get up and do somethingKeep bedroom for sleep and intimacy only

Sleep Hygiene adapted for Palliative patients

Bedridden patients: provide cognitive and physical stimulation during daytime hours Nap only when absolutely necessary and avoid late afternoon/evening napsStay socially activeIdentify problems and concerns of the day before trying to sleep (problem solve while the sun shines)Avoid stimulating medication doses in the eveningMaintain adequate pain relief through the night with long acting analgesics

Pharmacologic interventions

“Z drugs”- non-benzodiazepine sedativesMelatonin AgonistsTricyclic & Tetracyclic AntidepressantsAntipsychoticsAnticholinergicsDopamine AgonistsStimulants (for hypersomnolence)Misc. Medications related to sleep

Non-Benzo GABA Agonists

“Z drugs”“Non-Benzo”- wolf in sheep’s clothing?Zolpidem (Ambien, Edular, Intermezzo, Zolpimist)Esxopiclone (Lunesta)Zaleplon (Sonata)

Benzodiazepines: Short, Mid and Long Acting

Short Acting:Alprazolam, Triazolam, Midazolam

Mid-Acting:Lorazepam, Temazepam (Restoril)

Long Acting: Chlordiazepoxide (Librium), Clonazepam, Diazepam

Melatonin AgonistsOTC MelatoninRamelteon (Rozerem): binds to melatonin MT1 and MT2 receptorsVery short acting, best for sleep latency/onset disorders

Tricyclic AntidepressantsInhibits norepi and serotonin reuptakeUsed for anticholinergic effectDespite widespread use for insomnia, evidence for efficacy in insomnia is limitedEx: Amitriptyline, Imipramine, Nortriptyline, Desipramine, Doxepin

“Tetracyclic” Antidepressants

Trazodone (Desyrel)- Serotonin reuptake inhibitor, blocks alpha-1 adrenergic & serotonin 5-HT2A receptorsMirtazapine (Remeron)- blocks alpha-2 adrenergic and serotonin 5-HT2 receptorsStudies re: sleep when used as an adjunct with another antidepressant medication

Antipsychotics (Dopamine Antagonists)

Prochlorperazine (Compazine)Haloperidol (Haldol)Chorpromazine (Thorazine)Olanzapine (Zyprexa)Risperidone (Risperdal)Quetiapine (Seroquel)

Dopamine Agonists: RLS and Sleep in Parkinson

Carbidopa/LevodopaBromocriptine (Parlodel)Pramipexole (Mirapex)Ropinirole (Requip)Rotigotine (Neupro)- transdermalGabapentin for PLMS in RLS

StimulantsMethylphenidate (Ritalin, Concerta, Daytrana, Metadate)Dextroamphetamine (Adderall, Dexedrine)Modafinil (Provigil) and Armodafinil (Nuvigil): narcolepsy, OSAHS, Shift Work Sleep Disorder, MS related fatigue

OthersPrazosin (Minipress)- nightmares related to PTSDSildenafil – jet lag

SummaryInsomnia is defined by the patientBehavioral interventions: sleep hygiene Pain makes Insomnia WorseInsomnia Makes Pain Worse

SourcesPeplow, M. Structure: The anatomy of sleep. Nature . 497, S2-S3, May 2013. Czeisler, Einkelman, Richardson. Sleep Disorders. Harrison’s Principles of Internal Medicine, 17th ed. 171-180Sateia and Byock. Sleep in Palliatinve Care. Oxford Textbook of Palliative Medicine, 4th ed. 1059-1083.National Sleep Foundation. Sleepfoundation.org. Accessed 2/2/14.