SLEEP MEDICINE UPDATE › 2020 › MDM20M20 › slides › 24_Claman_SleepMed.pdfChronic Sleep...
Transcript of SLEEP MEDICINE UPDATE › 2020 › MDM20M20 › slides › 24_Claman_SleepMed.pdfChronic Sleep...
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SLEEP MEDICINE UPDATEDavid Claman, MD
Director, UCSF Sleep Disorders CenterProfessor of Medicine
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DISCLOSURES
• No disclosures• Recommended Reading
• “Why We Sleep” by Matthew Walker• References listed in talk
• OUTLINE• Sleep Deprivation• Insomnia• Restless Legs Syndrome (RLS)• Obstructive Sleep Apnea (OSA)
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SLEEP OVER LIFESPAN
• REM sleep is preserved; REM likely involved in memory consolidation
• Deep sleep (Delta or N3) is preserved in elderly women but reduced in elderly men
• Purpose of sleep is still unknown; likely involves eliminating metabolites that accumulate during wakefulness
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Chronic Sleep Deprivation (0 v 4 v 6 v 8 hrs)Lapses in Concentration: 8 hours has fewest!
(Van Dongen Sleep 2003)
Presently Americans sleep 6 hours 51 minutes on weekdays; 7 hours 37 minutes on weekend (National Sleep Foundation poll: 23‐60 y/o)
Symptoms of sleep deprivation clearly increase if you sleep 6 hours or less
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What is your preferred sleep aid for personal use?
• A. Zolpidem• B. Melatonin• C. Diphenhydramine• D. CBD• E. Stay up later
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DIFFERENTIAL DIAGNOSIS OF INSOMNIAMay be sleep onset, sleep maintenance or early awakening
• Psychiatric / psychological• Depression or anxiety
• Medical illness – pain, nocturia, post‐nasal drip, dyspnea (heart/lungs)• Drugs in general
• Caffeine delays sleep onset• Alcohol can cause middle of the night awakenings
• Psychophysiological insomnia• Somaticized tension from anxiety causing insomnia
• Poor sleep hygiene• Maladaptive coping mechanisms are common
• Circadian rhythm issues• Jet lag, Shift work, Advanced or Delayed Sleep Phase
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SLEEP HYGIENE GUIDELINES• Keep regular bedtime and wake‐up time (even on weekends)• Keep bedroom quiet, comfortable, & dark• Relaxation technique for 10‐20 min before bed• Get regular exercise• Don’t nap ‐ if you have insomnia
• OK to nap if you are sleep deprived!
• Don’t lie in bed feeling worried, anxious, or frustrated• Don’t lie awake in bed for long periods of time• Don’t use alcohol for 3 hours before bed, & caffeine for 8 hours before bed
• Paperback self‐help book: “Say Good Night to Insomnia”
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OPTIONS TO TAPER HYPNOTICSMotivated patients can make progress!
Figure 1. 10 week Intervention. Weekly Quantity of Benzodiazepine Medication Used by Older Adults With Insomnia in a Randomized Clinical Trial of Three Interventions to Facilitate Benzodiazepine Discontinuation; 69/76 completed study; 63% drug-free at follow-up; CM Morin. AmJPsych2004;161:332-342
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CBTi: Cognitive Behavioral Therapy for InsomniaMorin CM. JAMA 2009;301:2005
• CBTi includes multiple modalities• Sleep Restriction – less hours in bed• Stimulus Control – only in bed when sleepy• Relaxation – meditation; deep breathing• Cognitive Therapy – individualized • Mindfulness – non‐judgmental awareness of moment• Sleep Hygiene – avoid naps, caffeine, alcohol
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CBTi improves both insomnia and depressionAshworth DK. J Couns Psychol 2015;62:115
• N=41;Stable on antidepressant for 6 wks
• 4 CBT sessions versus self‐help reading materials
• @3 month f/u: 61% remission of both insomnia and depression in CBTi group versus 5% in self‐help
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NEUROTRANSMITTERS –Arousals & SleepSaper, Scammell & Lu (2005) Nature 437:1257‐63Sleep Rhythms and Circadian Rhythms both affect sleep
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Medications: preferably only if necessary!• Hypnotics are usually best for sleep‐onset insomnia; GABA mechanism. These meds have no anti‐anxiety benefits. Examples: zolpidem, eszoplicone
• Sedatives: Benzodiazepines like lorazepam help with anxiety, but have longer half‐life; also GABA mechanism
• Sedating antidepressants: trazodone and mirtazapine are longer acting so often used for sleep maintenance insomnia, but can cause hangover drowsiness
• Antihistamines: diphenhydramine is sedating• Low dose Doxepin 3 or 6 mg also works thru histamine receptor
• Melatonin short‐acting approx 2 hours so for sleep onset; melatonin receptor• CBD: minimal research; cannabinoid receptor• Orexin receptor antagonists: suvorexant and lemborexant have longer half‐life
• Orexin and Hypocretin are 2 names for same hypothalamic neurotransmitter
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CANNABINOIDS – minimal data
• Over 100 cannabinoids!• CBD – Cannabidiol – sedating, reduced sleep latency; no euphoria
• From Hemp or Marijuana: legal status in flux; “Supplement” so not regulated
• CBN – Cannabinol: sedating, reduced pain, increased appetite• THC – Tetrahydrocannabinol: euphoria, reduced pain/nausea
• Variable effects on sleep stages• Dronabinol (Marinol) is synthetic analog which is FDA‐approved
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CBD FOR INSOMNIA• No good data on efficacy or sleep stages; tolerance likely develop• Established for Chronic Pain, with small effect size
• SR Snitzman et al. BMJ Supportive Palliat Care 2020;0:1‐6
• Case series from Colorado• 103 adult patients in psychiatry clinic – Anxiety or Sleep issues• Mean age 34‐36• CBD capsule 25‐75 mg• Mild improvement in anxiety and sleep scores over 1‐3 months• 79% reported improved anxiety; 15% reported worse anxiety• 66% reported improved sleep; 25% reported worse sleep
• S Shannon et al. Permanente J. 2019;23:18‐41
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EVALIe‐Vaping Acute Lung Injury:Bilateral infiltrates; Ask about Cigarettes and Vaping!LAYDEN; NEJM 2019
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Lemborexant ‐2nd Orexin Receptor AntagonistR Rosenberg et al. JAMA Network Open 2019. Lemborexant vs Zolpidem ER vs Placebo
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LEMBOREXANT Results• Placebo group improves, which is consistent with prior insomnia research, since insomnia waxes and wanes over time!
• Lemborexant superior for falling asleep and staying asleep compared to placebo
• Lemborexant half‐life 17‐19 hours; no driving impairment in testing; (Suvorexant half‐life 12 hrs)
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Which blood test is recommended for RLS?• A. TSH• B. Dopamine• C. Ferritin• D. CBC with MCV• E. Creatinine
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RESTLESS LEGS SYNDROME (RLS)• “Abnormal discomfort”
• Uncomfortable, distressing and hard to describe• Insomnia is typically present
• Urge to move• Induced by Rest• Relieved by movement• Worse at night• Causes:
• Genetic: can run in families; Autosomal dominant• Secondary: pregnancy, neuropathy; renal failure; Parkinson’s
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TREATMENT OF RESTLESS LEGS SYNDROMERLS: Wijemanne. Pract Neuro 2017;17:444‐452
• Iron deficiency may worsen RLS (serum ferritin)• If ferritin <75, give iron (with Vit C) with goal of ferritin >100
• Symptoms may worsen on antidepressants• Also avoid caffeine and alcohol
• Behavioral:• Stretch before bed; consider short bath
• Medications:• Dopaminergic agents
• Pramipexole, ropinirole, carbidopa/levodopa, rotigotine• Clonazepam• Gabapentin• Opiates
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OBSTRUCTIVE SLEEP APNEA
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KEY OSA DEFINITION• Apnea: complete cessation of airflow lasting 10 seconds or more• Hypopnea: reduced airflow (≥ 30%) for 10 seconds or more,
associated with ≥ 4% oxygen desaturation (4% is classical definition)
• Apnea‐Hypopnea Index (AHI): the number of apneas and hypopneas per hour of sleep– Normal AHI < 5– Mild 5‐14– Moderate 15‐29– Severe ≥ 30
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Which of the following is NOT in STOPBANG?
• A. Apnea (witnessed)• B. Falling asleep while driving• C. Tired (fatigue)• D. Hypertension• E. BMI>35
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CLINICAL PREDICTORS OF OSAhttp://www.stopbang.ca/osa/screening.php
STOPBANG – 8 Questions High risk: yes to 5‐8 questions; Medium risk yes on 3‐4;Low risk yes on 0‐2
Snoring Tired (fatigue) Observed Apnea Pressure (Hypertension) BMI >35 ( ≥ 30 is considered obese) Age >50 Neck size > 17 inches for men or >16 inches for women Gender male
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CLINICAL PREDICTORS OF OSA• Screening questionnaires• Epworth Sleepiness Scale: range 0‐24 for 8 questions
– Normal score < 10– In OSA population, score correlates with AHI– SLEEP 1991; 14(6):540‐5
• Berlin 10 questions validated in primary care– Snoring, apnea, fatigue, sleepiness at wheel, Hypertension– Ann Intern Med. 1999 Oct 5;131(7):485‐91
• STOP‐BANG used in Anesthesia– Snoring, Tired, Observed apnea, Pressure (HTN), BMI 35, Age 50, Neck
circumference 40 cm (15.75 inches), Gender (male)– Arch Otolaryngol Head Neck Surg. 2010 Oct: 136(10):1020‐4
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OSA and Hypertension• Numerous cohort and observational studies show strong association between OSA and HTN
• The higher AHI, the higher the likelihood of HTN (dose dependent relationship) :
• AHI 5‐15 odds ratio of HTN 2.0• AHI ≥ 15 odds ratio of HTN 2.9
• Resistant HTN (difficult to treat requiring 3 drugs at max doses) is associated with OSA in 70‐80% of patients
Peppard PE et al NEJM 2000Janssen C et al Journal of Hypertension 2017Moon C et al Clinical Nurse Specialist 2016
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CARDIOVASCULAR COMPLICATIONS OF OSAJR Tietjens J Am Heart Ass 2019
• Hypertension• CHF
• OSA can worsen CHF• Reduced LVEF can cause Cheyne‐Stokes (form of Central Sleep Apnea)
• Stroke• Pulmonary Hypertension• Atrial Fibrillation
• CPAP reduces recurrence of Afib after cardioversion• Kanagala; Circulation 2003
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CAN CPAP REDUCE CARDIOVASCULAR EVENTS?McEvoy; NEJM 2016
• RCT open label; n = 2717; Moderate‐Severe OSA (AHI 29; Epworth 7) with prior cardiovascular hx (50% CAD; 50% cerebrovascular)
• Mean age 61; 80% male; 63% Asian/25% white• Mean follow‐up = 3.7 yrs• Exclusion: severe sleepiness – at risk for falling asleep at wheel; Severe desaturation; Central apnea; advanced heart failure
• Result: no effect of CPAP treatment on Primary cardiovascular endpoints• Improvement noted in daytime sleepiness, snoring & work‐days missed
• Limitations:• Severe OSA excluded• Mean CPAP 3.3 hours per night
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McEvoy 2016
• Cumulative incidence of primary end point:
• Death from MI or stroke
• Hospitalization for CHF, unstable angina, or TIA
• Similar results for CPAP plus usual care versus usual care alone
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OSA and Cardiovascular MortalitySignificant association in Severe (AHI >30) and Mod‐Severe (AHI > 15)
U.S. Preventive Task Force 2016
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Cumulative Percentage of New Fatal (A) & non‐Fatal (B)Cardiovascular EventsJM Marin et al. Lancet. 2005 Mar 16;365(9464):1046‐53
(also see Wisconsin Mortality: Young T et al. Sleep. 2008 August 1; 31(8): 1071–107)
KEY POINTS: 1. Increased mortality seen if AHI ≥ 30 (other predictors: age, CV ds, systolic BP and smoking)
2. CPAP reduced this risk
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HOME TESTING
• Used in clinical practice for many years• Approved by Medicare in 2009
• AHI is less accurate than formal study, since actual number of sleep hours is over‐estimated, not measured
• Formal study also measures EKG, leg kicking, EEG• If +OSA, can be combined with autoCPAP• May also be useful for f/u assessment of appliance or surgery• Best validated in 2 studies of sleepy subjects
• Mulgrew Annals Int Med 2007 – highly selected cohort of moderate to severe OSA with sleepiness
• Berry Sleep 2008 – VA cohort of sleepy OSA pts
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TREATMENT• Weight loss (10% weight loss reduces AHI 25%)• Avoid alcohol and sedatives for 3+ hours before bed• Postural training (only sleep on side – Anti‐Snore shirt or tennis balls)• Nasal patency (treat allergies or obstruction)• CPAP (& Bi‐level)
• Nasal mask, nasal pillows or full‐face mask
• AutoCPAP now more common
• Oral appliances – esp for Mild or Moderate OSA• Surgery
– Nasal, palate, tongue or jaw; UPPP only has 40‐50% success– Tonsillectomy #1 pediatric treatment
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Hypoglossal Nerve StimulationPJ Strollo et al. Upper-Airway Stimulation; NEJM 2014
• At 12 months: 68% reduction in AHI
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CPAPNasal Mask, Nasal Pillows or Full Face Mask
CPAP – Site Non-specific
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PREDICTORS OF CPAP COMPLIANCE
• AR Jacobsen et al. 2017; PLoS ONE 12(12): e0189614.
• Retrospective study; n = 695• Higher ESS showed better
compliance
• Similar retrospective data from N McArdle. AJRCCM 1999
• ESS > 10 showed better use
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Active Patient EngagementMalhotra. Chest 2018;153:843‐850APE: 87% adherent vs 70% Usual Care• UCSF Data also excellent showing 90% in pts attending CPAP Compliance clinic
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CPAP Download Must have 70% of nights over 4 hours to qualify as compliant during 90 day trial
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CPAP Download Must have 70% of nights over 4 hours to qualify as compliant during 90 day trial*Typically, if failing at 30 days, pts get notified by DME – try new mask or pressure?
![Page 40: SLEEP MEDICINE UPDATE › 2020 › MDM20M20 › slides › 24_Claman_SleepMed.pdfChronic Sleep Deprivation (0 v 4 v 6 v 8 hrs) Lapses in Concentration: 8 hours has fewest! (Van DongenSleep](https://reader034.fdocuments.us/reader034/viewer/2022042402/5f123b9f5b37d7351b401b00/html5/thumbnails/40.jpg)
Thanks for your attention!Questions & Comments please