SLEEP SLEEP ME MEDI DICINE NE UPD UPDATE TE David Claman, MD - - PowerPoint PPT Presentation

SLEEP SLEEP ME MEDI DICINE NE UPD UPDATE TE

David Claman, MD Director, UCSF Sleep Disorders Center Professor 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

• n 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

DIFFEREN DIFFERENTIAL IAL DI DIAGNO NOSI SIS OF OF IN INSOMNIA IA

May 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 SLEEP HY HYGI GIENE ENE GUI GUIDELI ELINES

• 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”

OPTI OPTIONS ONS TO TO TA TAPER HYPNO HYPNOTICS ICS

Motivated 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. AmJPsych 2004;161:332-342

CB CBTi Ti: Cogn

gnitiv itive Beha Behavi vior

• ral

al Ther Therapy fo for In Insom somnia ia Morin 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 depression

Ashworth 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

NEUR NEUROTRANSM RANSMITTER ERS –Ar –Arousals usals & Sl Sleep eep

Saper, Scammell & Lu (2005) Nature 437:1257‐63 Sleep 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 CANNABINOIDS – min inim imal da 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 CBD FO FOR IN INSOMNIA IA

• 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

EV EVALI ALI

e‐Vaping ping Acut Acute Lun Lung Inju Injury ry: Bilateral infiltrates; Ask about Cigarettes and Vaping! LAYDEN; NEJM 2019

Lem Lembor

• rexan

ant ‐2nd

nd Or

Orexin Re Receptor An Antagoni gonist

R 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

• ver 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

RE RESTLE TLESS SS LE LEGS GS SYNDR SYNDROME ME (RLS) (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

TRE TREATM TMEN ENT OF OF RE RESTLE LESS SS LE LEGS SYNDR SYNDROME ME

RLS: 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

OBSTRUC OBSTRUCTIVE SLEEP SLEEP APNE 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

CLIN CLINIC ICAL PREDICTO PREDICTORS RS OF OF OSA OSA

ht http://www. www.st stopbang.ca

• pbang.ca/os
• sa/

a/screeni reening. g.php php

 STOPBANG – 8 Questions  High risk: yes to 5‐8 questions; Medium risk yes

• n 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 OSA and and Hypertensi Hypertension

• n
• 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 2000 Janssen C et al Journal of Hypertension 2017 Moon C et al Clinical Nurse Specialist 2016

CARDIOVASCULAR COMPLICATIONS OF OSA

JR 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 OSA and and Car Cardio iovascular scular Mor Mortal ality

Significant 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 Events

JM 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

HOM HOME TE TESTIN ING

• 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

TRE TREATM TMENT ENT

• 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 Stimulation

PJ Strollo et al. Upper-Airway Stimulation; NEJM 2014

• At 12 months: 68% reduction in AHI

CP CPAP AP

Nasal Mask, Nasal Pillows or Full Face Mask

CPAP – Site Non-specific

PREDICT PREDICTORS OF OF CP CPAP AP CO COMP MPLIANCE

• 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 Engagement

• Malhotra. Chest 2018;153:843‐850

APE: 87% adherent vs 70% Usual Care

• UCSF Data also

excellent showing 90% in pts attending CPAP Compliance clinic

CP CPAP AP Downl Download ad

Mu Must st ha have 70% 70% of

• f nigh

nights ts

• ver
• ver 4 hour

hours to to qualify qualify as as co compl mpliant during during 90 90 da day trial trial

CP CPAP AP Downl Download ad

Mu Must st ha have 70% 70% of

• f

nigh nights ts over

• ver 4 hour

hours to to qualify qualify as as co comp mpliant during during 90 90 da day trial trial

*Typically

lly, if if failin iling at at 30 30 da days, pt pts get get noti notifi fied ed by by DME DME – t – try new new mask mask or

• r pr

pressur essure?

Thanks for your attention! Questions & Comments please