Download AUTONOMIC FUNCTION TESTING Clinical Applications and

AUTONOMIC FUNCTION TESTING
Clinical Applications and Examples
Alejandro Ortiz-Burgos, MD
University of Miami, Internal Medicine
27 June 2006
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The Autonomic Nervous System
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ANS Overview
• ANS controls or coordinates every system
in the human body
• ANS balance is required for health
• Many “normal” people live with sub-clinical
issues or have lifestyles that adversely
effect ANS balance
• Actual normals are few
“Are you healthy or merely symptom free?”
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ANS Overview
• Physicians have been manipulating their
patients’ ANS for decades
– Cholinergic and Adrenergic Agonists and
Antagonists, Tricyclics, and SSRIs to name a
few
• Now the effects on both ANS branches
can be visualized quantitatively
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Recent Findings
• Medullary Feedback Pathway importance
– Centrally acting agents can affect proper
balance when peripheral agents cannot
• Many ANS dysfunctions tend to destabilize
a patient’s response to therapy and
disease rather than present with overt
symptoms
– Dynamic Parasympathetic imbalances
underlie many difficult to manage cases
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ANS Review
• Sympathetics Mediate
– In general, stress, “fight or flight”, and
increases metabolic activity
– Specifically, peripheral vasoconstriction,
increases HR & contractility, drives BP, dilates
pupils and bronchi, releases glucose stores
and epinephrine and norepinephrine,
decreases salivation & GI motility, relaxes
bladder
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ANS Review
• Parasympathetics Mediate
– In general, rest, relaxation, recovery, and
decreases metabolic activity
– Specifically, peripheral vasodilatation,
decreases HR & contractility, constricts pupils,
stores glucose, stimulates salivation & GI
motility, contracts bladder, and mediates
ventillation
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NON-INVASIVE TESTS
OF THE AUTONOMICS
•
•
•
•
•
Sympathetics
Hand grip
Short Valsalva
Maneuver
Postural Change
Cold Water
Sweat Response
Parasympathetics
• Deep Breathing
• Postural Change
• Long Valsalva
Maneuvers
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OTHER SOURCES OF ANS
INFO
• Q-SART (Peripheral Autonomic Neuropathy)
• Holter monitors, EKG monitors
• Hand grip, Thermoregulatory, Tilt-table, Pupil
reaction
– Qualitative, Clinical trends difficult
– Only one branch or mixed measures
– Assumptions about other branch only valid in
relatively healthy individuals
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OTHER SOURCES OF ANS
INFO
• Teaching hospitals
– Definitive work
• Requires up to two days
• Intended for most severe cases
• Current technology enables a 15.5 minute
study in the office
– Designed to test those who would otherwise not
be considered for ANS function testing – like
most diabetics
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HRV & RA = ANS
**
Normal, Healthy,
Resting Cardiogram
Slower
mHR
*
Time (sec)
FRF
Time (sec)
Faster
RSA
*RFa = Parasympathetic Measure
**LFa = Sympathetic Measure
LFa/RFa = Sympathovagal Balance
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RESPIRATION IS THE KEY
• Respiratory analysis together with HRV
analysis
– Two measures for a two component system
• Characterized systemically
• Quantified mathematically
– Respiratory analysis determines Vagal
outflow
• “Measures” Respiratory Sinus Arrhythmia to
determine systemic Parasympathetic activity
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Heart Rate Variability &
Respirations
• Heart Rate Variability (HRV) with
Respiratory Activity (RA) = ANS testing
– Consider healthy resting cardiogram:
• Faster respiratory sinus arrhythmia (RSA) =
Vagus (PSNS)
• Slower mean heart rate (mHR) changes = SNS
– Analyze separately (“peel apart”) =
independent measures of both ANS branches
• Spectral analysis is the only method
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Heart Rate Variability &
Respirations
1981
1985
HRV WITH RESPIRATIONS
1987
1988
Classical HRV
1996
RESPIRATIONS OMITTED
[Malek, Circulation]
Akselrod
at
MIT
}
}
Malek, 1996
Low, 1997
Uijtdehaage and Thayer, 2002
Williams and Lopes, 2002
Cammann and Michel, 2002
Vinik and Freeman, 2003
}
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FOR ANS MONITORING
HRV MUST INCLUDE
RESPIRATIONS
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Who To Test?
• In-office:
– Medicare pays for all chronic progressive
diseases, including Pain
• Out patient clinic:
– Medicare pays for all chronic progressive
diseases, including Pain
• In-hospital:
– Patients with acute cerebro-vascular
diseases (Stroke) and other brain injuries
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Who To Test?
• Leadership recommends* ANS
monitoring
*AHA1,2, ADA1,2,3,4, AAN5, AAFP6, JDIF1, NIH1
1. Joint Editorial Statement by the American Diabetes Association; the National Heart, Lung, and Blood Institute; the Juvenile Diabetes
Foundation International; the National Institute of Diabetes and Digestive and Kidney Diseases; and the American Heart Association.
Diabetes Mellitus: A major risk factor for cardiovascular disease. Circulation. 1999; 100: 1132-33.
2. Grundy SM, Benjamin IJ, Burke GL, Chait A. AHA Scientific Statement: Diabetes and Cardiovascular Disease, a statement for
healthcare professionals from the American Heart Association. Circulation. 1999; 100: 1134-46.
3. Boulton AJM, Vinik AI, Arrezzo JC, Bril V, Feldman EI, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D. (2005)
Diabetic Neuropathies: A statement by the American Diabetes Association. Diabetes Care. 28(4): 956-62.
4. Vinik AI, Freeman R, ErbasT. (2003) Diabetic autonomic neuropathy. Semin Neurol. 23(4): 365-72.
5. Low P and the Therapeutics and Technology Assessment Subcommittee (1996) Assessment: Clinical autonomic testing report of the
Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 46: 873-80.
6. Aring AM, Jones DE, Falko JM. (2005) Evaluation and Prevention of Diabetic Neuropathy. Am Fam Physicians. 71: 2123-30.
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Who To Test?
• ANS testing detects ANS imbalances in
asymptomatic patients BEFORE
neuropathy presents
– Imbalances, whether the primary disorder
or caused by a primary disorder, can cause
secondary disorders which can cause
further disorders and so on….
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Who To Test?
(A Partial List of ICD-9 Codes)
Neurology
314.01
ADD/ADHD
332.0
Parkinsonism
337.0
Idiopathic peripheral autonomic neuropathy
337.2
Chronic Regional Pain Syndrome
337.9
Unspecified disorder of ANS
340
Multiple sclerosis
346.0 - .9 Migraine
352.3
Disorders of Pneumogastric (10th) N.
356.4
Idiopathic progressive neuropathy
357
Polyneuropathy
358.1
Myasthenic syndromes (Eaton-Lambert)
458.0
Orthostatic hypotension
596.54
Neurogenic bladder
780.2
Syncope and collapse
780.71
Chronic fatigue syndrome
784.0
Headache
785.0
Tachycardia (postural)
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Internal Medicine
All of the rest, plus:
278.01
Morbid Obesity
279.3
AIDS
296
Depression or Bipolar Disease
300
Anxiety
307.4
Sleep Disorders
530.11
GERD
536.3
Gastroparesis
564.1
Irritable Bowel Syndrome
729.1
Fibromyalgia
780.50 Post-traumatic Stress Synd.
782.3
Edema
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Who To Test?
(A Partial List of ICD-9 Codes)
Cardiology
401.0 - 405.99 Hypertension
412
Post-MI
413
Angina
414
Atherosclerosis
424
Mitral Valve Prolapse
Syndrome
425.4 Cardiomyopathy
427
Cardiac Dysrhythmias
428
Congestive Heart Failure
Pulmonology
780.51, 780.53, 780.57 Sleep Apnea
493.90 - 493.93 Asthma
493.2 COPD
Endocrinology
244
Acquired Hypothyroidism
246
Thyroid Disorders
250.0 - 250.8
Diabetes
256.3 Premature Menopausal
Symptoms
627
Menopausal Syndromes
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Why Monitor The ANS?
• Autonomic Neuropathy signs and
symptoms are late in the progression
– Chronic Progressive Disease is the
indicator
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Why Monitor The ANS?
•
Chronic disease leads to neuropathy
– Neuropathy does not present “overnight”
– ANS dysfunction precedes neuropathy
1. Autonomic dysfunction
2. Peripheral autonomic neuropathy (PAN)
3. {Diabetic autonomic neuropathy (DAN)}
•
Loss of quality of life (eating, sleep, voiding, sex)
4. Cardiovascular autonomic neuropathy (CAN)
•
Loss of longevity
5. High risk of sudden cardiac death
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Why Monitor The ANS?
• Early detection and correction of ANS
imbalance (dysfunction) helps to:
– Protect ANS and related organs
– Keep patient stable
– Preserve quality of life
– Preserve longevity
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ANS Testing
• Fully automated, any Technician
can be trained and certified by
Ansar in an hour
• The test itself is 15.5 minutes in
duration
• Requires a plain straight-back
chair, the test equipment, and a
quiet room
• Technicians and nurses love it,
one-on-one time with the patient
and no interruptions
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ANS Testing
•
Six challenges include:
A) resting (initial) baseline,
B) the parasympathetic challenge of deep
breathing,
C) return to baseline,
D) the sympathetic challenge of a series of short
Valsalva maneuvers,
E) return to baseline, and
F) Quick postural change (seated to standing)
followed by quiet standing
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ANS Test Results
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ANS Balance
• Resting balance
– The overall effect of: Lifestyle, Disease,
History, Genetics, & Therapy
– Lifestyle and Therapy can be modified to
restore balance
• Dynamic balance
– Early indicator of disorders
• Syncope, Orthostasis, GI upset, Sex dysfunction,
Sleep disorders
– Pain indicator
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Correcting Resting Imbalance
• Establish and Maintain normal balance
Sympathetics
Parasympathetics
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Correcting Resting Imbalance
Sympathetic excess
Sym
pat
het
ics
Par
asy
mp
ath
etic
s
• Correct by reducing sympathetic levels
– Adrenergic Blockade:
• Beta-blockers,
• Angiotensin blockers,
• Calcium Channel Blockers
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Correcting Resting Imbalance
Parasympathetic excess
tics
e
h
t
a
ymp
s
a
r
Pa
tics
e
h
t
pa
Sym
• Correct by reducing parasympathetic levels
– Initiate Cholinergic Blockade, e.g., tri-cyclics
– Reduce Adrenergic Blockade
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ANS Test Results
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Correcting Resting Imbalance
Check Titration
Example:
•
Medication state indicates a net Adrenergic
antagonist level
1. Normal balance = appropriate titration for pt
2. Net excess sympathetic level, increase dosage
3. Net excess parasympathetic level, decrease
dosage
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ANS Test Results
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Dynamic ANS Imbalance
Sympathetic Withdrawal
• SW = a physiologic definition
of Orthostasis
• Upon assuming an upright posture:
– Parasympathetics withdrawal
– HR increases
– Exercise Reflex helps to maintain
vascular tone and blood flow to brain
– Exercise Reflex ends and Sympathetic surge to maintain
vascular tone and blood flow to brain
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Dynamic ANS Imbalance
Sympathetic Withdrawal
• SW can cause dizziness and precedes
abnormal changes in:
– BP, in Orthostatic Hypotension
• 20 and 10 mmHg drop in systolic and diastolic BP,
respectively
– HR, in Postural Orthostatic Tachycardia
Syndrome (POTS)
• 30 bpm increase in HR or HR in excess of 120 bpm
• Why wait for clinical symptoms?
– Earlier intervention can be lower dose and short
term
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Dynamic ANS Imbalance
Sympathetic Withdrawal
• Therapy
– Mechanical intervention, e.g., stockings
– Volume building (check resting BP)
– Pyridostigmine (reintroduced by Mayo Clinic)
– Vasopressors, e.g., Midodrine
• Start low dose, consider weaning when
reversed and stabilized (in a little as six
months if detected early)
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ANS Test Results
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Dynamic ANS Imbalance
Sympathetic Excess at Stand
Normal
Abnormal
Abnormal
• Peak sympathetic response at the beginning of
stand should be less than peak sympathetic
response to Valsalva
• Physiologically it makes no sense if more sympathetic
activity is required to stand than to perform a series of
Valsalva maneuvers
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Dynamic ANS Imbalance
Sympathetic Excess at Stand
• Sympathetic excess at stand
is associated with tilt positive
patients and Syncope
• Check HR
– If HR increases (nerves are working) Syncope is
Cardiogenic
– If HR does not increase, Syncope is Neurogenic
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Dynamic ANS Imbalance
Vagal Dominance Throughout Test
• Elderly with little responsiveness
– Vagal dominance throughout test is
associated with Vasovagal Syncope
• Therapy
– Standard for different forms
– Consider anti-cholinergics if Vagal dominance
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ANS Test Results
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Dynamic ANS Imbalance
Sympathetic Excess at Stand (Part 2)
• Double headed arrow
marks the beginning
of the stand period
• Vertical line marks
Two minutes into standing
two minutes into
standing
• Two minutes into
standing is about
when the exercise
reflex concludes
• Ectopy occurs during quiet standing, but not during Valsalva
or the gravitational response to stand?
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Dynamic ANS Imbalance
Sympathetic Excess at Stand (Part 2)
• Arrhythmia 2 to 3 minutes into standing
suggests POTS
• Therapy
– Treat for Orthostasis
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Dynamic ANS Imbalance
Parasympathetic Excess During
Sympathetic Challenge
• Sympathetics are reactionary
• Parasympathetics set metabolic threshold
• If P abnormally respond to S challenges, S
forced into greater responses
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
• PPS is the term created to label
Parasympathetic Excess During
Sympathetic Challenge
• PPS in general destabilizes the patient’s
response to disease and therapy (i.e., BP,
HR, Diabetes, Thyroid)
• Common to our Database (> 50%)
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
• A finding unique to measuring both ANS
branches simultaneously
• PPS is defined by several diffuse
symptoms including: Sleep difficulties,
GI upset, Frequent migraines or
morning headaches, evening edema or
restless leg syndrome
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
• PPS can help to differentiate CRPS
(plexus damage) from other forms of pain
• PPS associated with migraine, CFS,
ADD/ADHD, Fibromyalgia, Sleep
difficulties, Unexplained seizures,
Depression/Anxiety/Bipolar Disorders
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
• Requires centrally acting agents to
correct
– Peripherally acting agents further destabilizes
the patient
• Not all adrenergic channels are block, so pt’s
systems finds a way to defeat the therapy to
ensure proper brain perfusion
– Central agents help to settle the whole ANS
by stabilizing both branches at the central
communication point
• Effects the feedback point in the upper Medullary
brain stem nuclei where the Limbic and systemic
sympathetics input on to the nuclei that give rise to
the Vagus N.
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
• Therapy typically corrects PPS in 12-15
months, and can be weaned over 3
months (assuming no end-organ effects)
– Reset and hold ANS “set point” (nervous
system plasticity)
– Patient (ANS) drug free until some other
clinical event
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Dynamic ANS Imbalance
Paradoxic Parasympathetic Syndrome
Cingulate Gyrus
(Limbic System)
Limbic Input
Block with Tricyclics
(use for depression,
anxiety, emotional
triggers, & sleep
difficulties)
Pons
Nucleus &
Tractus
Solitarius
Systemic
Sympathetic
Input
Block with centrally acting
adrenergic-antagonists
(eg, Coreg if Diabetic or has
heart disease)
Medulla
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Systemic
Parasympathetic
Outflow
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PAIN MANAGEMENT
• Quantify patient’s relative pain levels
(relative to patient’s own baseline)
• Differentiate between Psychosomatic pain,
Somatic or Sympathetic pain and CRPS
• Assist in titration of pain medication
• Document progress in Physical Therapy
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PAIN MANAGEMENT
• ANS monitoring can quantify patient’s
relative pain levels
– Pain is a stressor
– Sympathetics respond to stress
– More or less Sympathetic activity indicates
more or less pain
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PAIN MANAGEMENT
• ANS monitoring can differentiate pain classifications
– Psychosomatic pain
• Normal to low responses
• Consider addiction
– Somatic or Sympathetic pain
• Elevated sympathetic levels either at rest (especially if medicated)
or in response to Valsalva
• Parasympathetics are normal
– Reflex Sympathetic Dystrophy as it involves a plexus crush
or restricted blood flow to a portion of the body
• Elevated sympathetic and parasympathetic levels
– Sympathetics elevated due to pain
– Parasympathetics elevated due to reduced tissue perfusion
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PAIN MANAGEMENT
• Assist in titration of pain medication
– Properly titrated medications is indicated by
normal resting (baseline) balance
• Document progress in Physical Therapy
– Normalize ANS responses to challenges
• Continuous Monitoring also possible in
hospital
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57 y/o, M Patient in ER
Blunt Trauma Pt #5568001
(Face, Chest)
120
LFa & RFa (bpm^2)
LFa
100
RFa
IHR
80
60
40
20
556
554
552
549
547
365
363
360
358
356
354
171
169
167
165
162
160
158
156
154
31
29
27
25
22
20
18
16
13
11
9
7
4
2
0
Time (minutes)
Patient coming light
Morphine injection (20% dose)
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Patient moving
Maintenance
dosing
Morphine injection (20% dose)
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General Therapy
Agent
Associated
Nervous
System
Primary
Site of
Action
Primary Effect
Beta-1 Adrenergic
Antagonists
Sympathetics
Heart
↓ Heart Rate
Beta-2 Adrenergic
Agonists
Sympathetics
Lungs
↑ Air Flow
Alpha Adrenergic
Agonists
Sympathetics
Vasculature
Constrict Vasculature
Cholinergic Antagonists
Parasympathetics
Entire Body
↓ Parasympathetic
activity
Angiotensin Blockers
Sympathetics
Kidneys
↓ Blood Pressure
Calcium-Channel
Blockers
Sympathetics
Heart
↓ Blood Pressure
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General Therapy
• Arrhythmia 2 to 3 minutes into standing
suggests POTS
• Therapy
– Treat for Orthostasis
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TESTS OF THE AUTONOMICS
• Most tests of the ANS really only test one
ANS branch at a time
• The activity of the other branch is assumed
based on the classical “push-pull”
relationship between the two
• This relationship is only valid in healthy
individuals
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Chronic Monitoring
• Provides info regarding patient stability
– Under stress
– After meals
– Before retiring
• Detects trends early
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Chronic Monitoring
• A 15 minute test to augment:
•
•
•
•
NCVS
Tilt-studies
Sleep Studies
Sex Function Tests
•
•
•
•
•
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Q-SART
Sudomotor Testing
Vestibular Tests
Stress-tests
Holter-monitoring
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Acute Monitoring
• Continuous “baseline” monitoring
– Sleep studies (Apnea or Circadian Upset)
– ER, OR, ICU
• Measures instantaneous physiologic
changes
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Normal Children
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Normals Teenagers
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Normals: The Transition Years
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Normal Adults
34 y/o
44 y/o
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Normal Adults
60 y/o
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