1
GERIATRIC MEDICINE GRAND ROUNDS
January 5th, 2012
TOPIC
ORTHOSTATIC HYPOTENSION IN ELDERLY
PRESENTER
Aman Haider, MD
1st Year Fellow – Geriatric Medicine
Baylor College of Medicine
2
SECTIONS Introduction , Definitions & Background of Orthostatic Hypotension (OH)
Epidemiology of OH
Pathogenesis of OH
Etiology of OH
Clinical Presentation of OH
Evaluation of OH
Management of OH
3
INTRODUCTION ,
DEFINITION & BACKGROUND
OF
ORTHOSTATIC HYPOTENSION
4
INTRODUCTION
Orthostatic (postural) hypotension (OH) is a common disorder. Frequently under diagnosed. Frequent cause of syncope. Contributes to morbidity, disability and even mortality. It is a SYNDROME, and its prognosis depends on :
Its Specific Cause Its Severity The Distribution of its Autonomic or Non-Autonomic involvement.
5
DEFINITION ORTHOSTATIC HYPOTENSION is a reduction of …
Systolic blood pressure of at least 20 mm Hg OR Diastolic blood pressure of at least 10 mm Hg Within 3 minutes of standing.
An acceptable alternative to STANDING : Demonstration of a similar drop in blood pressure within 3 minutes Using a tilt table in the head-up position At an angle of at least 60 degrees
Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The
Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996;46:1470
6
LIMITATIONS OF DEFINITION Limitations:
Does not take into account : The possibility that different blood pressure declines may have different
clinical significance. Blood pressure changes that may occur after 3 minutes of standing.
Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The
Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996;46:1470
7
CONFOUNDING VARIABLES Should be considered before making the diagnosis :
Food ingestion Recent recumbency Time of day State of hydration Ambient temperature Postural deconditioning Hypertension and anti-hypertensive medications Gender Age
Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996;46:1470
8
EPIDEMIOLOGY
OF
ORTHOSTATIC HYPOTENSION
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PREVALENCE AMONG NURSING HOME RESIDENTS
One Study to “Determine Patterns Of Within-day Orthostatic Blood Pressure Changes” Cross Sectional study with 911 residents from 45 nursing homes . Aged 60 years or older, able to stand for at least 1 minute. Supine ,1-minute and 3-minute standing BP + HR were measured. Before and after breakfast and before and after lunch.
No OH = 48.5% Only once = 18.3% 2-3 times = 19.9% 4 or more times = 13.3% Most prevalent before breakfast, especially 1 minute after standing
(21.3%) Least prevalent after lunch, after 3 minutes of standing (4.9%)
Ooi WL, Barrett S, Hossain M, Kelley-Gagnon M, Lipsitz LA. Patterns of orthostatic blood pressure change and their clinical correlates in a frail, elderly population. JAMA. 1997 Apr 23-30; 277(16):1299-304.
10
PREVALENCE IN COMMUNITY- DWELLING ELDERLY
A study to “Assess Prevalence of Orthostatic Hypotension and its Associations”. A multicenter, observational, longitudinal study . Enrolled 5,201 men and women aged >65 yrs. Prevalence 14.8% for those age 65 to 69 and 26% for those age >85 OH was associated significantly with :
Difficulty walking (odds ratio, 1.23) Frequent falls (odds ratio, 1.52) H/o MI (odds ratio, 1.24) H/o TIA (odds ratio, 1.68) Isolated systolic hypertension (odds ratio, 1.35) Major EKG abnormalities (odds ratio, 1.21) Presence of carotid artery stenosis based on ultrasound (odds ratio, 1.67) Negatively associated with weight.
Rutan GH, et al. Orthostatic hypotension in older patients. The cardiovascular health study. CHS collaborative research group. Hypertension. 19(6 Pt 1):508-519, June 1992
11
PATHOGENESIS
OF
ORTHOSTATIC HYPOTENSION
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NORMAL POSTURAL CHANGES IN BP
Normal BP response on moving from a supine to a standing position : Small reduction (<10 mm Hg) in SBP & increase in DBP (~ 2.5 mm Hg). Gravity Induced Drop Approximately 500 to 1000 ml of blood is pooled in
the lower extremities and in the splanchnic and pulmonary circulations. Response (Baroreflex) :
Gravity Induced Drop Decreased venous return to the heart Transient reduction in CO and BP Stimulation of the baroreceptors in carotid arteries and aorta Reflexively increased sympathetic tone Increased PVR (Vasoconstriction) Inhibits parasympathetic activity Increased HR Restoration of CO and BP by an increase in HR and PVR.
13
POSTURAL CHANGES IN ELDERLY
“Age-Related Changes” that can effect normal BP Regulation :
14
ETIOLOGY
OF
ORTHOSTATIC HYPOTENSION
15
ETIOLOGY
Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007 Oct; 120 (10):841-847.
16
DRUG THAT MAY WORSEN OH
Figueroa JJ, Basford JR, Low PA, Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med, 77:2010, 298-306.
17
CLINICAL FEATURES
OF
ORTHOSTATIC HYPOTENSION
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SYMPTOMS
Symptoms that develop … On assuming erect posture, OR Following head-up tilt, and usually Resolve on resuming the recumbent position.
Symptoms include : Lightheadedness, dizziness, blurred vision, weakness, fatigue,
cognitive impairment, nausea, palpitations, tremulousness, headache, and neck ache (Coat Hanger Ache)Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996;46:1470.
In Elderly, disturbed speech, visual changes, falls, confusion, and impaired cognition are more common.
Rutan GH, Hermanson B, Bild DE, et al. Orthostatic hypotension in older adults. The Cardiovascular Health Study. Hypertension. 1992; 19:508-519.
19
OH – A PREDICTOR OF MORTALITY
Orthostatic Hypotension Predicts Mortality in Elderly Men The Honolulu Heart Program
A cohort of 3522 Japanese American men 71 to 93 years old. Total of 473 deaths in the cohort over 4 years.
52 of those who died had orthostatic hypotension 4 year all cause mortality = Relative Risk 1.64 ( 95% CI 1.19 to 2.26 ** ) ** With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes
mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer
Masaki KH, Schatz IJ and Burchfiel CM. Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart
Program. Circulation. 1998; 98: 2290-2295
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PROGNOSIS OF OH
In patients who have extrapyramidal and cerebellar disorders (eg, PD , MSA) The earlier and the more severe the involvement of the autonomic
nervous system, the poorer the prognosis - Sandroni P, Ahlskog JE, Fealey RD, Low PA. Autonomic involvement in extrapyramidal and cerebellar disorders. Clin
Auton Res 1991; 1:147–155. - Saito Y, Matsuoka Y, Takahashi A, Ohno Y. Survival of patients with multiple system atrophy. Intern Med 1994;
33:321–325.
In hypertensive patients with diabetes mellitus, the risk of death is higher if they have orthostatic hypotension.
Luukinen H, Koski K, Laippala P, Kivelä SL. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Arch Intern
Med 1999; 159:273–280.
Diastolic OH is associated with a higher risk of vascular death in older persons.
Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. N Engl J Med 1993; 329:611–615.
21
EVALUATION
OF
ORTHOSTATIC HYPOTENSION
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EVALUATION IN ER SETTING
Syncope may be the initial presentation. A study to evaluate cause of syncope in 611 patients presenting at the ER. 24 % had orthostatic hypotension.
Sarasin FP, Louis-Simonet M, Carballo D, et al. Prospective evaluation of patients with syncope: a population-based study. Am J Med. Aug 15 2001;111(3):177-84
23
EVALUATION IN INPATIENT CARE SETTING
The annual nationwide inpatient sample (NIS), sponsored by the AHRQ During 2004, 80,095 orthostatic hypotension- related hospitalizations. OH listed as the primary diagnosis in 28,073 (35%) hospitalizations. Most frequent secondary diagnoses were :
Atrial fibrillation (10.7%) Hypertension (8.9%) Syncope (8.2%) Chronic obstructive pulmonary disease (7.7%) Congestive heart failure (6.7%) Urinary tract infection (4.6%)
Shibao C, Grijalva CG, Raj SR, Biaggioni I, Griffin MR. Orthostatic hypotension-related hospitalizations in the United States.
Am J Med. 2007 Nov;120(11):975-80
24
EVALUATION IN OUTPATIENT CARE SETTING
More likely to have Chronic Etiologies
Referred from the ER or hospital upon discharge for further testing.
Usually have vague/ undifferentiated symptom description.
Discontinuing vs changing medications
MRI can be used to assess for possible etiologies of neurogenic orthostatic
hypotension.
Further testing as indicated.
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EVALUATION
Evaluation Of Suspected OH Begins by identifying reversible causes Underlying associated medical conditions.
In addition to assessing for symptoms of orthostasis Elicit symptoms of autonomic dysfunction involving the GI and GU
tract.
Detailed assessment of the motor nervous system should be performed to evaluate for signs of parkinson’s disease, as well as cerebellar ataxia.
26Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007 Oct; 120
(10):841-847.
EVALUATION OF ORTHOSTATIC HYPOTENSION
27
HISTORY
Evaluation and Management of Orthostatic Hypotension ; American Family Physician Volume 84, Number 5 ; September 1, 2011
HISTORICAL FEATURES POSSIBLE ETIOLOGY
Abnormal Uterine Bleeding, Fatigue, Rectal Bleeding Anemia
Amaurosis Fugax, Aphasia, Dysarthria, Unilateral Sensory & Motor Symptoms
Stroke
Bradykinesia, Pill-rolling Tremor, Shuffling Gait Parkinson Disease
Burns Intravascular Volume Depletion
Chest Pain, Palpitations, Shortness Of Breath CHF, MI, Myocarditis, Pericarditis
Chills, Fever, Lethargy, Nausea, Vomiting Gastroenteritis, Sepsis
Extremity Swelling CHF, Venous Insufficiency
High-risk Sexual Behavior AIDS, Neurosyphilis
Progressive Motor Weakness GBS , Multiple System Atrophy
Relapsing Neurologic Symptoms In Various Anatomic Locations Multiple Sclerosis
Symptoms After A Meal Postprandial Hypotension
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PHYSICAL EXAM
Obtain Orthostatic Vital Signs. Supine Blood Pressure and pulse after 3 minutes Standing Blood Pressure and pulse after 3 minutes
As many as 2/3rd of patients may go undetected if BP is not measured while supine.
Carlson JE. Assessment of orthostatic blood pressure:measurement technique and clinical applications. South Med J 1999; 92: 167–173.
One retrospective review of 730 patients found that vital signs had poor test characteristics when compared with tilt-table testing for the diagnosis of OH.
PPV = 61.7 % NPV= 50.2 %
Cooke J, Carew S, O’Connor M, Costelloe A, Sheehy T, Lyons D. Sitting and standing blood pressure measurements are not
accurate for the diagnosis of orthostatic hypotension. QJM. 2009;102(5):335-339.
29
PHYSICAL EXAM
Evaluation and Management of Orthostatic Hypotension ; American Family Physician Volume 84, Number 5 ; September 1, 2011
EXAMINATION FINDINGS POSSIBLE DIAGNOSIS
Aphasia, Dysarthria, Facial Droop, Hemiparesis Stroke
Cogwheel Rigidity, Festinating Gait, Lack Of Truncal Rotation While Turning, Masked Facies
Parkinson Disease
Confusion, Dry Mucous Membranes, Dry Tongue, Longitudinal Tongue Furrows, Speech Difficulty, Sunken Eyes, Upper Body Weakness
Dehydration (In Older Patients)
Decreased Libido, Impotence In Men; Urinary Retention And Incontinence In Women
Pure Autonomic Failure.
Dependent Lower Extremity Edema, Stasis Dermatitis Right-sided Congestive Heart Failure, Venous Insufficiency
Gummas, Unequal Pupils (Argyll Robertson Pupil) Loss Of Position And Vibration Senses
Tabes Dorsalis
Early Satiety, Postprandial Fullness, Constipation, Incontinence, Exercise Intolerance
Diabetic Neuropathy
Smooth Beefy Red Tongue, Lemon Pallor, Recent Loss Of Mental Capacity, Paresthesias, Ataxia
Pernicious Anemia
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ANCILLARY TESTS / IMAGING
Evaluation and Management of Orthostatic Hypotension ; American Family Physician Volume 84, Number 5 ; September 1, 2011
Ancillary Tests Conditions Suspected
BASIC METABOLIC PROFILE
BUN & Cr Intravascular volume depletion
Electrolytes
Electrolyte abnormalities from vomiting or diarrhea, or as cause of cardiac conduction abnormalities; clues to adrenal insufficiency (Dec Na & K)
Serum Glucose Hyperglycemia
IMAGING CT +/- MRI Neurodegenerative disease, stroke
COMPLETE BLOOD COUNT
White Count Infections
H&H Anemia
Platelet Count Sepsis
ECHO CHF, Structural heart disease
EKG Cardiac arrhythmia, myocardial infarction
MORNING SERUM CORTISOL LEVELS Adrenal insufficiency
SERUM VITAMIN B12 LEVEL Neuropathy from vitamin B12 deficiency
TELEMETRY MONITORING Cardiac arrhythmia
RPR/ VDRL Syphilis
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HEAD UP-TILT (HUT)
Indications for Head-up tilt testing High probability of OH despite an initial negative evaluation (e.g., PD)
Patients with significant motor impairment that precludes them from having standing vital signs obtained.
Lahrmann H.; Cortelli P.; Hilz M.; Mathias C.J.; Struhal W.; Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur. J. Neurol. 2006, 13, 930-936
To monitor the course of an autonomic disorder and its response to therapy.
Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007 Oct; 120 (10):841-847
32
PROCEDURE OF HUT
Perform tilt-table testing in a quiet room with a temperature of 68°F to
75°F.
The patient should rest while supine for 5 minutes before testing is
started.
Continuous HR monitoring and blood pressure monitoring at regular
intervals.
The table should be slowly elevated to an angle between 60 to 80 * for 3
minutes.
The test is considered Positive if systolic blood pressure falls 20 mm Hg
below baseline or if diastolic blood pressure falls 10 mm Hg below
baseline.
Measurement of plasma noradrenaline levels while supine and upright
may be of some value.
If symptoms occur during testing, the patient should be returned to the
supine position immediately.
33
EVALUATION
The procedure is generally considered safe, but serious adverse events such as syncope and arrhythmias have been reported.
34
RESPONSES TO HEAD-UP TILT TABLE TESTING
Condition Response
NormalHR increases by 10 to 15 beats per minute
DBP increases by 10 mm Hg or more
Dysautonomia No increase in heart rate
Immediate and continuing drop in
systolic and diastolic blood pressure
Neurocardiogenic syncope
( Occurs after 10 minutes or more of
testing )
Bradycardia Symptomatic, sudden
drop in blood pressure
Orthostatic hypotension
SBP decreases by 20 mm Hg or moreor
DBP decreases by 10 mm Hg or more
Postural orthostatic tachycardia syndrome
Heart rate increases by at least 30 beats/ minuteor
Persistent tachycardia of more than 120 beats/ minute
35
Management
of
Orthostatic Hypotension
36
GOALS DO NOT CHASE THE NUMBERS ….!!!!
Goals should be directed towards : Ameliorating symptoms
Relieving orthostatic symptoms Improving the patient’s functional status
Improving standing time Reducing the risk of complications.
Improving OH without excessive hypertension Correcting any underlying cause
No specific or single treatment is currently available that achieves all these
goals.
Drugs alone are never completely adequate.
37
SUPINE HYPERTENSION
Supine hypertension is a problem. Resulting from medication and/or being part of the disease. 24 h measurement of BP is best if diagnosis uncertain. After starting a new therapy.
Patients may self-monitor BP, daily at about the same time, and when they experience symptoms.
Pressor medications should be avoided after 6pm and the bed head elevated (20–30 cm).
On occasion, short acting antihypertensive drugs may be considered (e.g. Nitro-glycerine sublingual).
Lahrmann H.; Cortelli P.; Hilz M.; Mathias C.J.; Struhal W.; Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur. J. Neurol. 2006, 13, 930-936
38
MANAGEMENT PNEUMONIC
A B C D E F A Abdominal compression B Bolus of water B Bed up C Countermaneuvers D Drugs E Education E Exercise F Fluids and salt
39
NON-PHARMACOLOGIC TREATMENT
A : Abdominal and Lower Extremity Binders Podoleanu C, Maggi R, Brignole M, et al. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. J Am Coll Cardiol. 2006;48(7):1425-1432.
B : Upto 1 to 2 L of fluid/ day to balance expected 24-hour urine losses increase
standing SBP by > 20 mm hg for approx. two hours. Shannon JR, Diedrich A, Biaggioni I, et al. Water drinking as a treatment for orthostatic syndromes. Am J Med. 2002;112(5):355-360
B : Raise the head of the bed 10 to 20 degrees (~ 4 inches ) pts with autonomic
failure and supine hypertension reduce nocturnal hypertension and diuresis helps restore morning blood pressure upon standing. Van Lieshout JJ, Ten Harkel AD, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure. Clin Auton Res 2000; 10:35–42.
C : - Isometric exercises involving the arms, legs, and abdominal muscles.
- Active standing with legs crossed, with or without leaning forward. Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7(5):451-458.
40
NON-PHARMACOLOGIC TREATMENT
D : D/c culprit medications If unable to D/C culprit medications; advise patient to
take at bedtime such as anti-hypertensives. Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624.
E : Education Symptom diary avoid identified precipitating factors Avoid large carbohydrate-rich meals (to prevent postprandial
hypotension) Limit alcohol intake
Lahrmann H.; Cortelli P.; Hilz M.; Mathias C.J.; Struhal W.; Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur. J. Neurol. 2006, 13, 930-936
E : Exercise programs improves conditioning. Squatting has been used to alleviate symptomatic OH Toe raises, thigh contractions, and bending over at the waist are
recommended Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7(5):451-458
41
NON-PHARMACOLOGIC TREATMENT
F : Fluid & Salts Upto 1 to 2 L of fluid/ day increase standing SBP by > 20 mm hg.
Shannon JR, Diedrich A, Biaggioni I, et al. Water drinking as a treatment for orthostatic syndromes. Am J Med. 2002;112(5):355-360
Sodium supplementation adding extra salt to food or taking ~ 1 to 2 gms of salt tablets TID.
A 24-hour urine sodium level can aid in treatment. Value of <170 mmol per 24 hours, should be placed on 1 to 2 g of
supplemental sodium three times daily Reevaluate in one to two weeks Goal of raising urine sodium to between 150 and 200 meq. Patients should be monitored for weight gain and edema.
Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7(5):451-458
42
FLUDROCORTISONE
A synthetic mineralocorticoid. Reducing salt loss and expanding blood volume.
Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996; 76:507–509.
Sensitization of alpha-adrenoceptors. First line therapy (monotherapy) approved by FDA in 1955. Initial dose is 0.1 mg per day with increments of 0.1 mg every week. May be increased to 0.4 to 0.6 mg/day in refractory cases. Dose titration needed until :
Resolution of the symptoms OR Patient develops trace peripheral edema OR Weight gain of 4 to 8 lbs OR The maximum dose of 1 mg per day is reached.
Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007 Oct; 120 (10):841-847.
43
FLUDROCORTISONE
After oral administration,
Peak plasma levels ~ 45 min
Elimination half-life ~ 7 h.
Adverse effects include :
Headache
Supine hypertension
Congestive heart failure
Hypokalemia
Dose-dependent
In one study, hypokalemia in 24% of patients with mean onset at 8
months. Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly [published correction appears in Heart. 1997;77(3):294]. Heart. 1996;76(6):507-509.
44
MIDODRINE
Prodrug with an active metabolite, Desglymidodrine. Peripheral selective alpha-1 adrenergic agonist; cause vasoconstriction.
Absolute bioavailability ~ 93% The elimination half-life ~ 2–3 h Duration of action ~ 4 h.
First approved by FDA in 1996. Significantly increase systolic BP avoid last dose after 6 pm to avoid
supine HTN. Improve symptoms in patient with Neurogenic Hypotension. Synergistic effect when combined with fludrocortisone. Starting dose = 2.5 mg 3 times per day.
Then 2.5 mg weekly increments until a max. of 10 mg TID is reached. Before arising from bed in morning ---- Before lunch ---- Mid-afternoon
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MIDODRINE
Adverse effects : Supine Hypertension (25%) Piloerection/ goose bumps (13%) Pruritis (scalp-10% & general- 2%) Paresthesia (9%)
Contraindications : Coronary Artery Disease Urinary Retention (worsens urinary retention) Thyrotoxicosis Acute Renal Failure (Excreted in urine)
FDA has issued a recommendation to withdraw midodrine from the market because
of a lack of post-approval effectiveness data. U.S. Food and Drug Administration. Drug safety and availability. Midodrine update. September 2010.
46
PROSTAGLANDIN INHIBITORS
Block the vasodilating effects of prostaglandins raise the BP in some patients.
Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007 Oct; 120 (10):841-847.
In elderly patients, indomethacin should be avoided because of associated confusion.
All NSAIDS should be used with caution due to gastrointestinal and renal side
effects.
47
CAFFEINE
Adenosine-receptor blocker . Inhibits adenosine induced vasodilatation by blocking these
receptors.
Methylxanthine Caffeine Administered in a dose of 200 mg every morning as 2 cups of
brewed coffee or by tablet.
May attenuate symptoms in some patients. To avoid tolerance and insomnia, caffeine should not be given more
then once in the morning.
48
ERYTHROPOIETIN
Exact mechanism of action is unknown Effect is probably due to increased red cell mass and blood volume. Shown to be effective in a subgroup of patients with anemia and
autonomic dysfunction. Hoeldtke RD, Streetan DHP. Treatment of orthostatic hypotension with erythropoietin. N Engl J
Med. 1993;329:611-615.
Principal disadvantage of this drug is the Parenteral route of administration.
Serious side effects include: Hypertension Stroke Myocardial infarction
49
PYRIDOSTIGMINE
Cholinesterase inhibitor Potentiates sympathetic baroreflex pathway. Approved by FDA :
Myaesthenia Gravis (1955) Bioterrorism Increase survival after exposure to Soman "nerve gas"
poisoning (2003) Off-Label use for Orthostatic Hypotension Used for patients with mild to moderate hypotension due modest pressor
effect. Does not aggravate supine hypertension. Enhanced effect when taken with Midodrin 5 mg. Starting Dose : 30 mg TID increased to 60 mg TID. 180 mg slow release pyridostigmine (Mestinon Timespan) can be taken
once a day.
50
PYRIDOSTIGMINE
Adverse effects : Loose stools Diaphoresis Hypersalivation Fasciculations
51
OCTREOTIDE
Somatostatin Analogue
Inhibits release of gastrointestinal peptides, some of which cause vasodilation.
Administered subcutaneously starting with 25–50 mcg.
In patients with pure autonomic failures : Reduces postural, post-parandial and exertional hypotension. Does not cause or increase nocturnal hypertension.
52
OTHER AGENTS
CLONIDINE Peripheral – alpha 2-adrenergic agonist
May improve OH in patients with CNS causes of autonomic failure :• By promoting peripheral venoconstriction.• Thereby increasing venous return to the heart.
YOHIMBINE Central –alpha 2-adrenergic antagonist.
53
INDICATION FOR REFERRALReferral Specialist Indications
Geriatrician
Multiple comorbid conditions
Failure of standard therapy to alleviate symptoms
Complications, including recurrent falls, fracture, functional decline, ischemic events, decreased quality of life
Cognitive decline and confusion
Frail elderly patients
CardiologistUncontrolled supine hypertension despite standard therapy
Advanced coronary artery disease or severe ischemic symptoms
Severe left ventricular diastolic or systolic dysfunction (ejection fraction30%)
Recent onset of tachy-/bradyarrhythmia
Neurologist Specialized diagnostic testing for autonomic failure
Chronic and progressive autonomic failure
54
SUMMARY
Regardless of whether OH is symptomatic or asymptomatic, the elderly patient
remains at significant risk for future falls, fractures, TIA and MI.
The diagnostic evaluation of OH should include a comprehensive history and
physical examination, careful blood pressure measurements, and laboratory studies.
Goals of treatment in the elderly patient include ameliorating symptoms, correcting
any underlying cause, improving the patient’s functional status, and reducing the risk of complications, rather than trying to attain an arbitrary blood pressure goal.
55
SUMMARY In most cases, treatment begins with nonpharmacological interventions,
including withdrawal of offending medications (when feasible), physical maneuvers, compression stockings, increased intake of salt and water, and regular exercise.
If nonpharmacological measures fail to improve symptoms, pharmacologic agents should be initiated. Fludrocortisone, midodrine, nonsteroidal anti-inflammatory drugs, caffeine, and erythropoietin have all been used to treat orthostatic hypotension due to autonomic failure.
56
REFERENCES Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and
multiple system atrophy. The Consensus Committee of the Ameri can Autonomic Society and the American Academy of Neurology. Neurology. 1996;46(5):1470.
Ooi WL, Barrett S, Hossain M, Kelley-Gagnon M, Lip sitz LA. Patterns of orthostatic blood pressure change and their clinical correlates in a frail, elderly population. JAMA. 1997;277(16):1299-1304.
Rutan GH, Hermanson B, Bild DE, Kittner SJ, labaw F, Tell GS. Orthostatic hypotension in older adults. The Car diovascular Health Study. CHS Collaborative Research Group. Hypertension. 1992;19(6 pt 1):508-519.
Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624
Sandroni P, Ahlskog JE, Fealey RD, Low PA. Autonomic involvement in extrapyramidal and cerebellar disorders. Clin Auton Res 1991; 1:147–155.
Saito Y, Matsuoka Y, Takahashi A, Ohno Y. Survival of patients with multiple system atrophy. Intern Med 1994; 33:321–325.
Uukinen H, Koski K, Laippala P, Kivelä SL. Prognosis of Diastolic and systolic orthostatic hypotension in older Persons. Arch Intern Med 1999; 159:273–280.
Davis BR, Langford HG, Blaufox MD, Curb JD, Polk BF, Shulman NB. The association of postural changes in systolic blood pressure and mortality in persons with hypertension: the Hypertension Detection and Follow-up Program experience. Circulation 1987; 75:340–346.
57
REFERENCES Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. N Engl J
Med 1993; 329:611–615. Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, et al. Prospective
evaluation of patients with syncope. Am J Med 2001;111:177-84 Biaggioni I, Griffin MR. Orthostatic hypotension-related hospitalizations in the United States. Am
J Med. 2007 Nov;120(11):975-80 Carlson JE. Assessment of orthostatic blood pressure: measurement technique and clinical
applications. South Med J. 1999;92(2):167-173. Cooke J, Carew S, O’Connor M, Costelloe A, Sheehy T, Lyons D. Sitting and standing blood
pressure measure ments are not accurate for the diagnosis of orthostatic hypotension. QJM. 2009;102(5):335-339.
Lamarre-Cliche M, Cusson J. The fainting patient: value of the head-upright tilt-table test in adult patients with orthostatic intolerance. CMAJ. 2001;164(3):372-376.
Jamnadas-Khoda J, Koshy S, Mathias CJ, Muthane UB, Ragothaman M, Dodaballapur SK. Are current recommendations to diagnose orthostatic hypoten sion in Parkinson’s disease satisfactory? Mov Disord. 2009;24(12):1747-1751.
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