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
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)
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
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
What is your preferred sleep aid for personal use?
• A. Zolpidem• B. Melatonin• C. Diphenhydramine• D. CBD• E. Stay up later
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
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”
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
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
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
NEUROTRANSMITTERS –Arousals & SleepSaper, Scammell & Lu (2005) Nature 437:1257‐63Sleep Rhythms and Circadian Rhythms both affect sleep
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
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
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
EVALIe‐Vaping Acute Lung Injury:Bilateral infiltrates; Ask about Cigarettes and Vaping!LAYDEN; NEJM 2019
Lemborexant ‐2nd Orexin Receptor AntagonistR Rosenberg et al. JAMA Network Open 2019. Lemborexant vs Zolpidem ER vs Placebo
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)
Which blood test is recommended for RLS?• A. TSH• B. Dopamine• C. Ferritin• D. CBC with MCV• E. Creatinine
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
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
OBSTRUCTIVE SLEEP APNEA
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
Which of the following is NOT in STOPBANG?
• A. Apnea (witnessed)• B. Falling asleep while driving• C. Tired (fatigue)• D. Hypertension• E. BMI>35
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
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
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
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
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
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
OSA and Cardiovascular MortalitySignificant association in Severe (AHI >30) and Mod‐Severe (AHI > 15)
U.S. Preventive Task Force 2016
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
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
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
Hypoglossal Nerve StimulationPJ Strollo et al. Upper-Airway Stimulation; NEJM 2014
• At 12 months: 68% reduction in AHI
CPAPNasal Mask, Nasal Pillows or Full Face Mask
CPAP – Site Non-specific
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
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
CPAP Download Must have 70% of nights over 4 hours to qualify as compliant during 90 day trial
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?
Thanks for your attention!Questions & Comments please