Upload
mark-martino
View
215
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Dr. Alan Pocinki's presentation at the 2011 EDNF Conference, "Sleep Disorders in EDS"
Citation preview
EDNF 2012 Conference August 2012
All rights reserved. 1
Alan G. Pocinki, M.D. Ehlers-‐Danlos NaBonal FoundaBon Learning Conference
August 9-‐11, 2012
Overview � Autonomic nervous system (ANS) regulates all body processes, including sleep
� ANS dysfuncBon is very common in Ehlers-‐Danlos and other hypermobility syndromes, and underlies many of their symptoms
� The most common type of sleep disorder seen in the hypermobility syndromes appears to have an autonomic basis
EDNF 2012 Conference August 2012
All rights reserved. 2
Basics of the ANS � SympatheBc nervous system: “fight or flight,” the accelerator
� ParasympatheBc nervous system: “rest and digest,” the brake
Autonomic Instability � Concept of adrenaline reserve � Central paradox: the lower the reserves, the more exaggerated your stress response, so your body “overresponds” to minor stresses
� The overresponse oWen triggers an overcorrecBon, then an overresponse…
Sympathetic and Parasympathetic Activity with Autonomic Maneuvers
Normal EDS with Dysautonomia
A B C D E F
A=Baseline, B=Deep Breathing, C=Rest, D=Valsalva, E=Rest, F=Stand
EDNF 2012 Conference August 2012
All rights reserved. 3
SympatheBc and ParasympatheBc AcBvity Before and AWer Treatment
At Diagnosis After 18 months of treatment
A=Baseline, B=Deep Breathing, C=Rest, D=Valsalva, E=Rest, F=Stand
Non-‐RestoraBve Sleep in EDS � Frequent arousals and awakenings � Li\le or no deep sleep
Normal Sleep
Non-‐Restorative Sleep
Heart Rate Variability Associated with Sleep Disruptions
Sleep Stages
Heart Rate
N3 N2
N1 REM
Awake 60
80
100
EDNF 2012 Conference August 2012
All rights reserved. 4
Heart Rate Variability-‐-‐Another Paradox � The lower sympatheBc acBvity is, the greater heart variability, or
� The more exhausted you get, the more “depleted” your energy reserves, the more exaggerated heart rate fluctuaBons will be
� The more your heart rate fluctuates, the more disrupted your sleep (not to menBon dayBme acBviBes)
� The more disrupted your sleep, the more exhausted you get—a nasty vicious cycle
EDNF 2012 Conference August 2012
All rights reserved. 5
Sleep “MispercepBon” Another Paradox
� Many EDS paBents report that they “sleep fine.” � “I’m a great sleeper. I can fall asleep any Bme, anywhere.”
� But… Do you feel rested when you get up? � “No, I never feel rested.” � “I wake up feeling like I haven’t slept.” � “I don’t think I know what feeling rested would feel like.”
� Not just a problem in EDS, e.g. 90% of people with sleep apnea are not aware of it
Non-‐RestoraBve Sleep � Frequent arousals and awakenings � Li\le or no deep sleep
Normal Sleep
Non-‐Restorative Sleep
EDNF 2012 Conference August 2012
All rights reserved. 6
SympatheBc and ParasympatheBc AcBvity Before and AWer Treatment
At Diagnosis After 18 months of treatment
A=Baseline, B=Deep Breathing, C=Rest, D=Valsalva, E=Rest, F=Stand
Treatment of Autonomic DysfuncBon � Be\er sleep � Address underlying problems:
� Pain � FaBgue � DehydraBon � Low blood sugar � EmoBonal stresses
Restoring Autonomic Balance � Be\er sleep—quanBty and quality � Adequate—really—pain control � Don’t “push through” faBgue; take breaks � Adequate salt and fluid � Avoid hypoglycemia � Minimize emoBonal stresses
EDNF 2012 Conference August 2012
All rights reserved. 7
� “Your suggesBon to ratchet down my level of ‘busy-‐ness’ [by taking frequent short breaks] to facilitate relaxaBon is great. It’s helpful and enjoyable. It’s good to have ‘doctor’s orders’ to relax and read a book for a few minutes in the middle of the day!”
EDS, Untreated (Sleep Lab)
EDS, Untreated (Same PaBent, Home Sleep Monitor)
EDNF 2012 Conference August 2012
All rights reserved. 8
EDS, AWer Treatment (Home Sleep Monitor)
Treatment of Sleep Disorders
� Don’t overlook the basics: � Good sleep hygiene � Comfortable ma\ress � Dark and quiet � Elevate head of bed (if lightheaded during the day)
� Treat sleep apnea, limb movements only if significant
EDNF 2012 Conference August 2012
All rights reserved. 9
Treatment of Sleep Disorders: MedicaBon
� Complex medicaBon “regimen” is oWen required: � MulBple medicaBons with complementary effects, e.g. one medicaBon for pain, one to reduce arousals, one to increase deep sleep
� Finding the right combinaBon can be a frustraBng trial and error process
� Home sleep monitor may be helpful (www.myzeo.com)
Treatment of Sleep Disorders: MedicaBon
� Block extra adrenaline (beta and alpha blockers, clonidine and guanfacine)
� Offset extra adrenaline (benzodiazepines, SSRI’s) � Reduce pain (analgesics, muscle relaxants, NeuronBn™, Lyrica™)
� Increase deep sleep (trazodone, amitrypBline, doxepin)
� Use “Sleeping pills” sparingly
Beta Blockers � Propranolol
� Start with 10 mg at bedBme � Increase by 10 mg every 4-‐5 days unBl fewer awakenings, side effects, or no further benefit
� Switch to long-‐acBng if needed � Take some earlier to offset “second wind” � OWen need smaller dayBme dose as well
EDNF 2012 Conference August 2012
All rights reserved. 10
Other Beta Blockers � Metoprolol
� Start with half a 25 mg tablet (metoprolol tartrate) � Increase by half a tablet every 4-‐5 days � Add long-‐acBng (metoprolol succinate) if needed
� Nadolol � Safe in asthma (Bystolic™ also safe in asthma, but once daily) � Start with 20 mg. increase by 20 every 4-‐5 days � Add smaller AM dose if needed for dayBme symptoms
� Carvedilol � Start with 3.125 mg, iIncrease by one tablet every 4-‐5 days � Add smaller AM dose if needed for dayBme symptoms
Clonidine/Guanfacine � Clonidine
� Start with 0.1 mg at bedBme � Increase by 0.1 mg no sooner than one week � No more than 0.3 mg � Usually lasts about 6 hours
� Guanfacine � Very similar to clonidine but lasts longer � Recently remarketed as Intuniv™ for ADD
Alpha Blockers � Prazosin best studied, shown to reduce nightmares in PTSD, where “a hypersensiBvity to adrenaline triggered many of their nightmares.” In a VA study, 75-‐80% of PTSD paBents stopped having nightmares.
� Usual dose is 5mg � Can worsen orthostaBc intolerance � Not clear if combinaBon alpha-‐beta blockers (e.g. carvedilol) are as effecBve, but probably not.
EDNF 2012 Conference August 2012
All rights reserved. 11
Benzodiazepines � All have beneficial properBes:
� SedaBve � AnB-‐anxiety � Muscle relaxant � AnB-‐movement, anBconvulsant � “AnB-‐adrenaline”
� But also potenBal problems: � Impair cogniBon, motor performance � Depress mood, respiraBon � Cause or worsen faBgue � Tolerance � Dependence � Withdrawal
Some Common Benzodiazepines � Clonazepam (Klonopin™)
� Longest-‐lasBng, most likely to have residual effects � Also effecBve for restless leg, PLMS
� Diazepam (Valium™) � Typically lasts about 8 hours � Probably best muscle relaxant
� Temazepam (Restoril™) � Typically lasts about 7 hours � Capsule limits dosage adjustment
� Lorazepam (ABvan™) � Typically lasts about 6 hours � Metabolized differently (less variability, interacBons)
Analgesics � AnB-‐inflammatories
� NSAID’s: Naproxen, Meloxicam, Celebrex™ � Prednisone
� Tramadol, short-‐ and long-‐acBng � NarcoBcs, short-‐, long-‐acBng; patches (fentanyl, Butrans™) � Cymbalta™, Savella™ � GabapenBn (NeuronBn™), Lyrica™ � Lidoderm™ � Flector™, Voltaren Gel™, Pennsaid™
EDNF 2012 Conference August 2012
All rights reserved. 12
Muscle Relaxants � Cyclobenzaprine
� Shown to improve sleep quality in fibromyalgia � Has analgesic, sedaBve, muscle relaxant properBes
� Soma � Less sedaBng, ? more analgesic effect, especially with narcoBcs
� Skelaxin � Less sedaBng, some can tolerate dayBme doses
� Tizanidine � More sedaBng, high margin of safety
� Baclofen � Potent, use for severe painful spasm only
Other Agents � Trazodone
� Probably most effecBve at increasing deep sleep � Low dose, 50-‐150 mg, most people take 50
� AmitrypBline � Also increases deep sleep, especially with pain � Start at 10 mg, most people take 20-‐40mg
� Doxepin � Enhances sleep more at lower doses � 10 mg tablet, liquid, or Silenor™ 3 mg, 6 mg
� DDAVP (Desmopressin)?
“Sleeping Pills” � Zolpidem, short-‐ and long-‐acBng
� Doesn’t reduce arousals or improve sleep architecture � Onset/maintenance, e.g. unBl other meds effecBve � Retrograde amnesia � Zolpidem usually lasts 5 hours, ER about 7
� Lunesta � Doesn’t reduce arousals or improve sleep architecture � Occasionally helps with sleep onset and maintenance, e.g. unBl other
medicaBons become effecBve � Usually lasts about 7 hours
� Zaleplon � Good for sleep onset, especially gewng back to sleep � Lasts 2-‐3 hours, no cogniBve impairment
� Melatonin/Rozerem � Most helpful for Circadian problems e.g. evening “second wind”
EDNF 2012 Conference August 2012
All rights reserved. 13
AnBdepressants � SSRI’s oWen cause shallower sleep, more dreams
� Prozac worst, Lexapro best � Use lowest effecBve dose, consider liquid formulaBons
� Cymbalta sleep neutral if taken in AM � Tricyclics generally improve sleep, but oWen cause dayBme sedaBon
� Wellbutrin impairs sleep if taken late in day, so take once-‐daily (XL) form early in day or consider AM only dosing of twice a day (SR) form
� Remeron generally improves sleep, can cause weight gain
DO YOU HAVE ANY DATA?
ONLY THE TWO-‐LEGGED KIND!
EDNF 2012 Conference August 2012
All rights reserved. 14
� “I am stunned, amazed, and grateful at the benefits of taking propanolol. The improvement in my sleep quality alone is fantasBc.”
� “The medicine you gave me is amazing. Two worked great but three worked even be\er. I forgot to take it one night and slept 12 hours and felt terrible. The next night I took it and slept 6 hours and felt great.”
� The metoprolol seems to help considerably with my sleep. In fact, between metoprolol, flexeril, and good old advil, I’m able to fall asleep and stay asleep. The metoprolol really seems to be parBcularly important for quality of sleep.
� Propranolol is working very well in helping me to sleep.
Summary � The most common type of sleep disorder seen in the hypermobility syndromes appears to be characterized by excessive heart rate variability at night
� MedicaBons to suppress, offset, or block this excess acBvity are effecBve in improving sleep, measured both by polysomnography and symptoms
� Improving sleep and minimizing dayBme stresses helps to replenish autonomic reserves, which in turn improves dayBme autonomic balance and also helps improve sleep, which in turn improves dayBme funcBon, which in turn improves circadian rhythms and sleep, which …..
EDNF 2012 Conference August 2012
All rights reserved. 15
EDNF (Sandy Chack) and Dr. Brad Tinkle for inviBng me Dr. Peter Rowe for encouraging me when others thought I was nuts Dr. Clair Francomano and Dr. Fraser Henderson for teaching me about EDS and sBmulaBng my interest in it All my paBents, for having the confidence in me to let me experiment on them!