AUTONOMIC FUNCTION TESTING Clinical Applications and Examples

Transcription

1 AUTONOMIC FUNCTION TESTING Clinical Applications and Examples Alejandro Ortiz-Burgos, MD University of Miami, Internal Medicine 27 June

2 The Autonomic Nervous System 2

3 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? 3

4 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 4

5 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 5

6 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 6

7 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 7

8 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 8

9 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 9

10 OTHER SOURCES OF ANS Teaching hospitals Definitive work Requires up to two days INFO 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 10

11 HRV & RA = ANS Normal, Healthy, Resting Cardiogram Slower mhr ** * Time (sec) Time (sec) Faster RSA FRF *RFa = Parasympathetic Measure **LFa = Sympathetic Measure LFa/RFa = Sympathovagal Balance 11

12 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 12

13 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 13

14 Heart Rate Variability & Akselrod at MIT Classical HRV [Malek, Circulation] Respirations } HRV 1996 } Malek, 1996 Low, 1997 Uijtdehaage and Thayer, 2002 Williams and Lopes, 2002 Cammann and Michel, 2002 Vinik and Freeman, 2003 WITH RESPIRATIONS RESPIRATIONS OMITTED }FOR ANS MONITORING HRV MUST INCLUDE RESPIRATIONS 14

15 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 15

16 Who To Test? Leadership recommends* ANS monitoring *AHA 1,2, ADA 1,2,3,4, AAN 5, AAFP 6, JDIF 1, NIH 1 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: 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: 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): Vinik AI, Freeman R, ErbasT. (2003) Diabetic autonomic neuropathy. Semin Neurol. 23(4): 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: Aring AM, Jones DE, Falko JM. (2005) Evaluation and Prevention of Diabetic Neuropathy. Am Fam Physicians. 71:

17 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. 17

18 Who To Test? (A Partial List of ICD-9 Codes) Neurology ADD/ADHD Parkinsonism Idiopathic peripheral autonomic neuropathy Chronic Regional Pain Syndrome Unspecified disorder of ANS 340 Multiple sclerosis Migraine Disorders of Pneumogastric (10 th ) N Idiopathic progressive neuropathy 357 Polyneuropathy Myasthenic syndromes (Eaton-Lambert) Orthostatic hypotension Neurogenic bladder Syncope and collapse Chronic fatigue syndrome Headache Tachycardia (postural) Internal Medicine All of the rest, plus: Morbid Obesity AIDS 296 Depression or Bipolar Disease 300 Anxiety Sleep Disorders GERD Gastroparesis Irritable Bowel Syndrome Fibromyalgia Post-traumatic Stress Synd Edema 18

19 Who To Test? (A Partial List of ICD-9 Codes) Cardiology Hypertension 412 Post-MI 413 Angina 414 Atherosclerosis 424 Mitral Valve Prolapse Syndrome Cardiomyopathy 427 Cardiac Dysrhythmias 428 Congestive Heart Failure Pulmonology , , Sleep Apnea Asthma COPD Endocrinology 244 Acquired Hypothyroidism 246 Thyroid Disorders Diabetes Premature Menopausal Symptoms 627 Menopausal Syndromes 19

20 Why Monitor The ANS? Autonomic Neuropathy signs and symptoms are late in the progression Chronic Progressive Disease is the indicator 20

21 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 21

22 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 22

23 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 23

24 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 24

25 ANS Test Results 25

26 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 26

27 Correcting Resting Imbalance Establish and Maintain normal balance Sympathetics Parasympathetics 27

28 Correcting Resting Imbalance Sympathetic excess Sympathetics Parasympathetics Correct by reducing sympathetic levels Adrenergic Blockade: Beta-blockers, Angiotensin blockers, Calcium Channel Blockers 28

29 Correcting Resting Imbalance Parasympathetic excess Sympathetics Parasympathetics Correct by reducing parasympathetic levels Initiate Cholinergic Blockade, e.g., tri-cyclics Reduce Adrenergic Blockade 29

30 ANS Test Results 30

31 Correcting Resting Imbalance Example: Check Titration 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 31

32 ANS Test Results 32

33 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 33

34 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 34

35 Therapy Dynamic ANS Imbalance Sympathetic Withdrawal 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) 35

36 ANS Test Results 36

37 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 37

38 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 38

39 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 39

40 ANS Test Results 40

41 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? 41

42 Dynamic ANS Imbalance Sympathetic Excess at Stand (Part 2) Arrhythmia 2 to 3 minutes into standing suggests POTS Therapy Treat for Orthostasis 42

43 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 43

44 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%) 44

45 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 45

46 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 46

47 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. 47

48 Dynamic ANS Imbalance Paradoxic Parasympathetic Syndrome Therapy typically corrects PPS in 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 48

49 Dynamic ANS Imbalance Paradoxic Parasympathetic Syndrome Cingulate Gyrus (Limbic System) Limbic Input Nucleus & Tractus Solitarius Pons Block with Tricyclics (use for depression, anxiety, emotional triggers, & sleep difficulties) Systemic Sympathetic Input Medulla Systemic Parasympathetic Outflow Block with centrally acting adrenergic-antagonists (eg, Coreg if Diabetic or has heart disease) 49

50 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 50

51 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 51

52 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 52

53 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 53

54 57 y/o, M Patient in ER Blunt Trauma Pt # (Face, Chest) LFa & RFa (bpm^2) LFa RFa IHR Time (minutes) Patient coming light Morphine injection (20% dose) Maintenance dosing Morphine injection (20% dose) Patient moving 54

55 General Therapy Agent Beta-1 Adrenergic Antagonists Beta-2 Adrenergic Agonists Alpha Adrenergic Agonists Associated Nervous System Primary Site of Action Primary Effect Sympathetics Heart Heart Rate Sympathetics Lungs Air Flow Sympathetics Vasculature Constrict Vasculature Cholinergic Antagonists Parasympathetics Entire Body Parasympathetic activity Angiotensin Blockers Sympathetics Kidneys Blood Pressure Calcium-Channel Blockers Sympathetics Heart Blood Pressure 55

56 General Therapy Arrhythmia 2 to 3 minutes into standing suggests POTS Therapy Treat for Orthostasis 56

57 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 57

58 Chronic Monitoring Provides info regarding patient stability Under stress After meals Before retiring Detects trends early 58

59 Chronic Monitoring A 15 minute test to augment: NCVS Tilt-studies Sleep Studies Sex Function Tests Q-SART Sudomotor Testing Vestibular Tests Stress-tests Holter-monitoring 59

60 Acute Monitoring Continuous baseline monitoring Sleep studies (Apnea or Circadian Upset) ER, OR, ICU Measures instantaneous physiologic changes 60

61 Normal Children 61

62 Normals Teenagers 62

63 Normals: The Transition Years 63

64 Normal Adults 34 y/o 44 y/o 64

65 Normal Adults 60 y/o 65