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

18

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

20

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

22

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.

25

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

28

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

31

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

45

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

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