Neurogenic Orthostatic Hypotension Dr. Kurt Kimpinski Department
of Clinical Neurological Sciences University Hospital, LHSC London,
ON April 10 th, 2013 Slide 2 Disclosures Relevant Financial
Relationship(s) None Off Label Usage Pyridostigmine for treatment
of NOH Slide 3 Objectives To provide an approach to the diagnosis
of Neurogenic Orthostatic Hypotension (NOH) Review the management
of NOH with a focus on Conservative treatment measures
Pharmacotherapy Avoidance/treatment of supine hypertension Slide 4
Definitions Neurogenic Orthostatic Hypotension: a fall in postural
systolic blood pressure 30 mmHg. False positive rate = 1% Other
definitions: A fall in postural systolic blood pressure 20 mmHg or
diastolic 10 mmHg. False positive rate = 5% Slide 5 The continuum
of orthostasis Normal Orthostatic Intolerance Orthostatic
Hypotension POTS Progressive orthostatic dysfunction Slide 6 The
continuum of orthostasis Slide 7 Tilt Table: Head-up Tilt (HUT)
Orthostatic Intolerance Slide 8 HUT: Postural Tachycardia Slide 9
HUT: Orthostatic Hypotension Slide 10 Prevalence of NOH
DisorderPrevalence Aging10-30% NIDDM7.4% Parkinsons Disease37-48%
Multiple Systems Atrophy5-15 per 100 000 Pure Autonomic
Failure10-30 per 100 000 Other Autonomic Neuropathies10-50 per 100
000 Slide 11 Clinical evaluation I. Autonomic dysfunction with NOH
Presence/severity of NOH Onset/progression Associated autonomic
dysfunction Distribution Severity Slide 12 Clinical evaluation II.
Evaluation of autonomic disorders over time NOH, can be dynamic in
its presentation depending on numerous variables Evaluation of
autonomic dysfunction on other organ systems NOH can worsen
cerebral and other tissue perfusion NOH can be worsened by anemia
Evaluation of the effect of NOH on Quality of Life Slide 13
Clinical evaluation: History Orthostatic intolerance/hypotension
Gastrointestinal Upper GI dysfunction, dysmotility Genitourinary
Erectile dysfunction Distal sensory changes Sudomotor (sweating)
anhidrosis Slide 14 Symptoms: Orthostatic Hypotension
Lightheadedness.88% Weakness or tiredness.72% Blurred vision.47%
Cognitive changes..47% Headache.25-80% Vertigo37% Pallor31% Low et
al. 1995, Mayo Clin. Proc. 70:617-622. Slide 15 Diagnose and
severity of NOH Take BP supine, 1 min. and 3 min. of standing Fall
in BP by: 30 mm Hg systolic within 3 minutes of standing up
Recognize orthostatic stressors time of day (AM) warming (hot day,
bath) Meal, Water intake prolonged standing exercise Slide 16
Head-up Tilt: NOH 1. Fall in SBP 30 mmHg 2. No compensatory HR
increase on HUT 3. Prolonged HUT can increase sensitivity for
milder NOH Slide 17 NOH: differential diagnosis Hypovolemia
Endocrine abnormalities Adrenal insufficiency, hypothyroid
Electrolyte disturbances Cardiac abnormalities Arrhythmia,
restrictive diseases Medications Beta-blockers, anticholinergics,
anti-hypertensives, etc. Slide 18 Clinical evaluation: Clinical
Exam Sudomotor dry skin, regions of hyperhidrosis Gastrointestinal
- plain film, motility studies Genitourinary post void residuals
Visual pupils (Adies) Acral - small fiber neuropathy Slide 19
Orthostatic Hypotension (OH): Treatment Goals Reduce OH without
supine hypertension Increase standing time Improve ADLs Reduce
symptoms Improved ability to handle orthostatic stresses Hot days,
stressful situations, after meals etc. Slide 20 Safety Slide 21
Patient Education Recognize orthostatic symptoms Manage orthostatic
stressors Morning, meal, heat, standing, exercise Blood Pressure
log Dietary education (salt/fluids) Medications and situations to
avoid Physical counter maneuvers Postural and resistance training
Slide 22 BP & Symptom Log Supine and standing (3 min) BP After
medications Early AM and QHS Before and after meal When symptomatic
Supine BP qhs after lying for 15 minutes To detect supine
hypertension Slide 23 Orthostatic Hypotension Treatment
Conservative Measures I. High fluid intake (>40 oz/d); High salt
diet (10-20g/d) i.e. normal North American diet Plasma volume: 24
hour urinary Na +2 Volume: 1500-2500 mL/24 h Sodium: > 170
mmoL/24h Slide 24 Orthostatic Hypotension Treatment Conservative
Measures II. Physical counter maneuvers and resistance training
Focusing on lower extremity aerobic and anaerobic exercises
Compression garments Abdominal binder Elevate head of bed 4 inches
to reduce nocturnal hypertension to reduce nocturia Slide 25 Head
of Bed Elevated 4 Inches Slide 26 Physical counter maneuvers Slide
27 Pressor Effect of Water Drinking Jordan et al. Circulation 2000
101(5):504-509 Slide 28 Orthostatic Hypotension Treatment
Medications Consider pyridostigmine 30-60 mg b.i.d. or t.i.d.
Consider midodrine 5-10 mg t.i.d. last dose 6PM Consider
fludrocortisone Milder forms of NOH Slide 29 Midodrine Treatment
Avoid after 6 PM Reduce dose of fludrocortisone Tailor dose and
timing: larger dose at time of maximal need omit during periods of
reduced orthostatic stress avoid excessive hypotension Judicious
use of BP log supine/standing; orthostatic stress, avoid supine HTN
Slide 30 Midodrine: Contraindications Severe ischemia coronary,
cerebral, limb, gastrointestinal Aneurysm cerebral, aortic
Significant supine hypertension Urinary retention Slide 31
Midodrine: Effect on Standing BP; Multicenter Study Controlled
Study Low et al. JAMA 1997 277(13):1046-1050 Slide 32 Midodrine:
Effect on Standing Symptoms; Multicenter Study Controlled Study Low
et al. JAMA 1997 277(13):1046-1050 Slide 33 Pyridostigmine for OH
Enhancing ganglionic transmission by acetylcholinesterase
inhibition traffic through sympathetic ganglia modest in supine
position great increase in standing position Vasomotor effects
proportional to orthostatic needs Slide 34 Pyridostigmine for OH:
Symptoms Improvement Singer et al. JNNP 2003 74(9):1294-1298 Slide
35 Pyridostigmine for OH: Effects on Systolic Blood Pressure Singer
et al. JNNP 2003 74(9):1294-1298 Slide 36 Overall approach to
medications Individual medication profiles Side effects,
contraindications Milder NOH pyridostigmine Mild to Moderate NOH
Flourinef Midodrine pyridostigmine Severe OH or when there is
variability of the dosing schedule Midodrine Slide 37 Other drugs
with potential in NOH L-DOPS (droxidopa) Currently used in Japan,
in phase III U.S. trials Octreotide In NOH with severe GI
dysmotility Erythropoetin Correct anemia Vassopressin For AM NOH
and reduce nocturia Slide 38 Management of supine hypertension I.
In mild NOH pyridostigmine may be the best option or as an adjunct
medications Minimal effect on supine BP, may limit the necessity
for higher doses of midodrine Avoid medications after 6PM or prior
to prolonged periods of being supine midodrine Slide 39 Management
of supine hypertension II. Elevate HOB Glass of red wine
Hydralazine 25 mg qhs Slide 40 Conclusions. Patient educations is a
must. Conservative measures are as important as pharmacology in the
treatment of OH. Maximize plasma volume. Avoid or minimize supine
hypertension.
