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Grand Rounds John Hunter Hospital

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Has felt intermittently light-headed over a period of 12 months ... Eg Shy-Drager syndrome, Bradbury-Eggleston syndrome, Riley-Day syndrome, ... – PowerPoint PPT presentation

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Title: Grand Rounds John Hunter Hospital


1
Grand Rounds John Hunter Hospital
  • Falling Down
  • Dr William Browne
  • Advanced Trainee
  • Department Geriatric Medicine
  • 26/5/05

2
Falling Down
  • Managing a difficult and common clinical problem
  • Geriatric Medicine Service

3
Case Presentation
  • 71 year old man presented 22/1/2005 c/o feeling
    light headed.
  • Has felt intermittently light-headed over a
    period of 12 months
  • Symptoms aggravated by standing up, resolved by
    lying down

4
Presenting Complaint
  • Also complained of leg pains on walking over past
    three months
  • Had restricted walking significantly over this
    period
  • Feeling increasingly light headed over 5 days
    prior to presentation
  • Diarrhoea over three days

5
Presenting Complaint
  • On day before admission he collapsed while
    walking down steps, falling backwards injuring
    his back
  • Was out shopping on the day of presentation when
    he felt weak, light-headed, unable to walk
  • An ambulance was called by passers by and patient
    was brought to hospital

6
Past Medical History
  • Rheumatoid arthritis
  • 20 year history
  • Prolonged steroid dependence
  • Methotrexate
  • Right hallux valgus correction 10/04 at Nepean
    Hospital in Sydney
  • Failed removal of K-Wire with remnant in first
    metatarsal
  • Thought to have osteomyelitis, treated with oral
    dicloxacillin for 2 weeks

7
Past Medical History
  • Hyperlipidemia
  • TURP for benign prostatic hypertrophy
  • Right knee replacement x2

8
Medications
  • Atorvastatin 20 mg nocte
  • Perindopril/indapamide (4/1.25mg) two daily
  • Indapamide 5 mg mane
  • Prednisone 5 mg daily
  • Methotrexate 15 mg weekly
  • Dicloxacillin 500mg qid po
  • ?Allergic to penicillin

9
Social History
  • Usually lived in the Blue Mountains but was
    visiting son in Newcastle
  • Wife in nursing home in Blue Mountains, severe
    Parkinson's disease
  • Home had 5 steps
  • Usually independent with ADL's, mobility
  • Non smoker
  • Non drinker

10
Fascinating Facts In Geriatric Medicine
  • The producers of the hit TV show ER initially
    wanted to make George Clooneys character a
    geriatrician but felt this would give the
    character too much sex appeal

11
Examination Findings
  • Alert, orientated
  • Looked well
  • Large postural drop- lying 191/101 to standing
    81/64. Felt light-headed associated with this
  • HR 80 bpm, T 36ºC
  • Oxygen saturation 98 on room air

12
Examination findings continued
  • Cardiovascular-
  • Pulse 80 bpm, regular
  • JVP not raised
  • Apex undisplaced
  • HS dual with no murmurs or added sounds
  • No sacral or pedal oedema

13
Examination continued
  • Respiratory
  • Chest examination normal
  • G/I
  • Abdomen soft and non tender
  • No mass/ organomegally

14
Physical Examination Continued
  • Neurological Examination
  • GCS 15/15
  • Cranial nerves normal
  • Ocular movement normal
  • Field of vision normal
  • No nystagmus/ diplopia
  • Upper limb
  • Normal power and tone bilaterally

15
Physical Examination Continued
  • Lower Limb
  • Power 5/5 bilaterally
  • Tone normal
  • Cerebellum
  • No dysdiaochokinesis
  • Heal shin test normal
  • No intention tremor

16
Examination Continued
  • Gait
  • Felt light-headed on standing
  • Somewhat wide based
  • Able to stand on heel and toes
  • Romberg's negative
  • Sensation
  • Normal to pin

17
Examination
  • Small non discharging wound on medial aspect of
    right great toe, with mild associated swelling
  • Able to move inter-phalangeal joint without pain
  • No evidence of rheumatoid disease in the hands
  • Reduced peripheral pulses bilaterally

18
  • "Do not go gentle into that good night. Old age
    should burn and rave at close of day. Rage, rage
    against the dying of the light."

19
Initial Investigations
  • CRP 15.5
  • ESR 9
  • FBC
  • Wbc 5.8
  • Hb 136
  • MCV 99.7
  • Plat 167
  • EUC
  • Na 136
  • K 4.0
  • Cl 99
  • Bic 27
  • Urea 15.9
  • Creat 142
  • An Gap 14

20
Investigations
  • ECG-
  • Sinus rhythem
  • Normal axis
  • RBBB
  • CXR
  • Heart size normal. Lung fields clear

21
Investigations
  • X-Ray of right foot
  • K-wire remnant in head of first metatarsal

22
Admitting Diagnosis?
23
Orthopaedic Review
  • In view of history of chronic infection in right
    great toe following failed K-wire extraction an
    intitial referral was made by ED to orthopaedics
  • Plan was for medical review and to continue oral
    dicloxacillin

24
Initial Plan
  • Plan
  • IV fluids
  • Postural BPs
  • Omit diuretics and ACE inhibitor
  • Stool cultures
  • Blood cultures
  • Wound swab

25
Subsequent Progress
  • Disturbances of renal function tests largely
    resolved on repeat test following day
  • Na- 137
  • K- 3.4
  • Chloride- 1.2
  • Bicarb- 25
  • Urea- 9.4
  • Creat- 102

26
Subsequent Progress Day 2
  • Stool cultures negative
  • IV fluids ceased after 24 hours
  • Symptomatic postural drop persisted
  • TED stockings
  • Arterial doppler of right leg arranged

27
Subsequent Progress Day 3-4
  • Assessed by physiotherapist as mobilising safely
    independently
  • Serum cortisol 485
  • Coversyl Plus (inadvertently) resumed !

28
Subsequent Progress Day 5-6
  • Patient still had a large postural drop
  • Commenced on fludrocortisone 0.1mg daily
  • ID consult arranged

29
Progress Day 6-9
  • Persisting severe postural hypotension
  • Supine BP 180/100, Standing 100/70
  • Further episodes of loose stool
  • Noted to have lost 1.6 kg in weight since
    admission
  • Fludrocortisone increased to 0.2 mg mane

30
Progress Day 10-11
  • Coversyl Plus identified as still being given and
    ceased
  • Fludrocortisone dose increased to 0.3mg daily

31
Drugs that come back and bite you!
32
Drugs that come back!
  • Not ceased- withheld
  • Recharted
  • Charted at multiple sites
  • Patients secret supply
  • The post discharge return

33
Progress Day 12
  • Developed fever 37.9ºC
  • Blood cultures, bone scan and urinalysis
  • Duplex scan of lower limb arteries
  • Occlusion of both right and left anterior tibial
    arteries and peroneal arteries
  • Occlusion of left posterior tibial artery
  • An important diagnostic test was performed...

34
Progress Day 13
Procedure Date 3.2.05
35
Progress
36
Progress Day 13
  • Short synacthen test
  • Became distressed, anxious, short of breath
    within minutes of ACTH injection
  • Symptoms settled promptly with reassurance and
    did not recur
  • Baseline cortisol 266. Rise to 634 after
    synacthen
  • Low grade temperature persisted 37.6ºC
  • CRP 14, ESR 15, WBC- 6.8
  • Blood culture, MSU negative

37
Progress Day 13
  • Bone Scan
  • Recent transverse mid-sacral fracture
  • Subacute crush fracture at L4
  • Intense inflammatory arthropathy of right 1st MTP
    joint
  • Old left 9th posterior rib fracture

38
Progress Day 14
  • Persisting large postural drop
  • Diarrhoea resolved
  • Right foot ulcer, possible osteomyelitis
  • Peripheral vascular disease
  • ID/ Orthopaedic / Vascular consults

39
Progress Day 14
  • ID opinion
  • Probable osteomyelitis either
  • Remove K-wire and debride bone or..
  • Continue suppressive oral diclox 500mg BD
  • Vascular Opinion
  • Stop the TED's
  • Probably not suitable for revascularization
    (disease below knee)
  • Conservative Rx

40
Progress Day 14
  • Orthopedic opinion
  • As above- conservative Rx

41
Progress Day 15-17
  • Continued to have large symptomatic postural drop
  • Commenced on Midodrine 2.5mg bd and on two cups
    of strong coffee mane!
  • Bed tilt was arranged 15º

42
Progress Days 18-20
  • Dose of midodrine titrated up to 5mg BD
  • Dose of fludrocortisone reduced to 0.2mg
  • Patient complained of numbness in toes,
    especially great toes
  • No objective sensory/ motor loss
  • Patients postural symptoms improved
  • At discharge ( 16.2.05) however
  • Lying BP 160/102
  • Standing BP 103/71

43
Follow up
  • Postural symptoms have not returned and the
    patient remains active and independent
  • Patient continues on midodrine 5 mg BD and
    fludrocortisone 0.2 mg daily
  • At last outpatient visit patients
  • Lying BP 160/90
  • Standing BP 160/90

44
Postural Hypotension
  • There is no happiness where there is no
    wisdom No wisdom but in submission to the
    gods. Big words are always punished, And proud
    men in old age learn to be wise.
    Sophocles (496 BC - 406 BC), Antigone

45
Postural Hypotension
  • Orthostatic hypotension is a common problem
  • estimated to occur in 5 out of every 1,000
    individuals
  • 7 to 17 of patients in an acute care setting.
  • more prominent in elderly patients due to
  • the increased intake of vasoactive medications
  • concomitant decrease in physiologic function,
    such as baroreceptor sensitivity, often seen with
    aging.

46
Orthostatic Hypotension
  • Controversy exists as to the numerical markers
    responsible for symptomatology.
  • Drop in systolic BP of 20 to 30 mmHg within 3
    minutes of standing, with resulting complaints,
    is thought to be adequate for the diagnosis of
    OH.

47
Orthstatic Hypotension
  • In normal individuals, systolic BP drops no more
    than 5 to 10 mmHg on standing, pulse rate will
    increase 5 to 10 beats per minute
  • But controversial
  • Many are able to accommodate BP falls of up to
    50 mmHg without significant symptoms
  • Cerebral autoregulation, or the capacity to
    maintain constant cerebral blood flow despite
    perfusion pressure changes, was preserved in
    normal subjects until mean arterial pressure fell
    below 60 to 70 mmHg.

48
Orthostatic Hypotension
  • Setting absolute values for diagnostic criteria
    that are too tight may unnecessarily exclude
    patients from appropriate therapeutic
    interventions.

49
Causes of orthostatic hypotension
  • Autonomic Neuropathies
  • Primary (27)
  • Eg Shy-Drager syndrome, Bradbury-Eggleston
    syndrome, Riley-Day syndrome, Dopamine-beta-Hydr
    oxylase Deficiency etc.
  • Secondary (35)
  • Diabetes, Uremia, Guillane-Barre syndrome,
    amyloidosis, porphyria
  • Transient neurogenic syncope
  • Micturition syncope, vasovagal, carotid sinus
    syncope, Bezold-Jarisch reflex activation

50
Causes of orthostatic hypotension
  • Endocrine
  • Phaeochromocytoma
  • Hypo-aldosteronism
  • Reno-vascular disease
  • Vascular insufficiency/ vasodilatation
  • Varicose veins
  • Arterio-venous malformations
  • Carcinoid
  • Mastocytosis
  • Hyperbradykininism

51
Causes of Orthostatic Hypotension
  • Hypovolemic disorders
  • Anaemia
  • Decreased plasma volume
  • Hemorrhage
  • Anorexia nervosa
  • Diarrhea
  • Overdiuresis
  • Overdialysis

52
Causes of orthostatic hypotension
  • Drugs
  • Antihypertensives
  • Diuretics
  • Antidepressants (Often overlooked)
  • Pregnancy
  • Space-flight

53
Bradbury Eggleston Syndrome
  • In 1925, Bradbury and Eggleston described a
    patient with a selective neuropathy involving the
    sympathetic and parasympathetic nervous systems
  • Caused by a progressive loss of the peripheral
    preganglionic and postganglionic autonomic nerves
    for reasons not yet understood
  • The syndrome is known as the Bradbury-Eggleston
    syndrome, pure autonomic failure, or idiopathic
    OH.

54
Bradley-Eggleston Syndrome
  • This disease manifests in middle to late life and
    is five times more frequent in males.
  • The onset of this illness is insidious, occurring
    over 2 to 5 years, and sparing the adrenal
    medulla until relatively late in the disease.
  • Despite the fact that many patients are older at
    the time of diagnosis, these patients have a good
    prognosis. Many live into their late 80s
  • The most common cause of death in these patients
    is pulmonary embolus.

55
Management
  • Look for treatable causes
  • Up to 45 of reported cases of OH have been found
    to be due to drug usage
  • antihypertensive medications,
  • diuretics,
  • antianginal agents
  • antidepressants.

56
Management
  • Antihypertensives are often selectively used in
    patients with OH, as supine hypertension is a
    common component of this syndrome
  • Alcohol, nitrates, narcotics, major and minor
    tranquilizers, marijuana, and nasal sprays are
    other often-reported offending agents.
  • Patients with autonomic failure are sensitive to
    the hypertensive effects of over-the-counter
    preparations with sympathomimetic potential
    (i.e., cold remedies), and problems may also
    result from the use of topical ophthalmic
    solutions

57
Management
  • Hypovolemia
  • volume depletion from
  • haemorrhage
  • dehydration
  • anorexia nervosa
  • diarrhoea
  • excessive diuresis
  • vomiting
  • These aetiologies are typically identified in the
    course of taking a complete history.

58
Diagnosis
  • Endocrinologic disorders
  • less common
  • include
  • Pheochromocytoma
  • Renovascular disease
  • Addison disease
  • Excessive ultra filtration during dialysis
  • Mitral valve prolapse syndrome
  • May also be considered hypovolemic in nature
  • May have as much as an 8 reduction in total
    blood volume

59
Diagnostic Evaluation
  • History and examination
  • Yields a diagnosis 50 of cases
  • Tilt testing- for vasovagal syncope
  • Specificity 90, Sensitivity variable 30-80
  • Pharmacologic agents
  • Isoproterenol
  • Adenosine (vasodilatory and probable direct
    activation of sympathetic afferents)
  • Edrophonium (cholinergic action)
  • Nitroglycerin (direct vasodilatory action)

60
Diagnostic evaluation
  • Head-up tilt-table testing has become the gold
    standard for diagnosis of syncope
  • simulates conditions known to trigger syncope.
  • peripheral venous pooling brought on by upright
    posture leads to an abrupt decline in venous
    return to the heart
  • sudden decrease in ventricular volume leads to a
    much more forceful ventricular contraction and
    thereby mechanoreceptor stimulation in the
    ventricle wall
  • Surge in afferent neural traffic mimics
    conditions of hypertension, provoking an
    paradoxic sympathetic withdrawal that results in
    bradycardia and vasodilatation.

61
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62
Diagnostic Evaluation
  • Responses measured after posture change can be
    grouped into three categories according to the
    change in pulse rate
  • (1) a fall in BP with a simultaneous rise in
    pulse rate, which is a normal physiologic
    response
  • (2) a fall in BP with no rise in pulse rate or
    one which is always less than 10 bpm, which
    represents a defect in the ANS
  • (3) a fall in BP with a drop in pulse rate, which
    implies a vasovagal response

63
Diagnostic Evaluation
  • Laboratory testing includes the measurement of
    supine and upright plasma and urine
    catecholamines and dopamine
  • Basal levels of plasma norepinephrine tend to be
    normal in patients with CNS disease, whereas
    patients with peripheral autonomic disturbance
    tend to have lower levels.
  • If syncope remains unexplained, studies employing
    implantable long-term monitoring devices have
    shown bradycardia to be the most common cause

64
Non Pharmacological Intervention
  • Goal is to improve quality of life.
  • limit the number and extent of episodes of
    cerebral hypoperfusion
  • minimizing drug or alternative therapy-related
    side effects
  • Pharmacologic therapy alone is often inadequate
  • Most pressor drugs, often used in this setting,
    raise recumbent BP and increase the risk for
    cardiovascular disease while also increasing the
    risk of inadequate organ perfusion in patients
    with low BPs
  • A quality-of-life improvement can be seen in most
    patients if a nonpharmacologic treatment plan is
    effectively implemented.

65
Non Pharmacological Intervention
  • Postprandial hypotension can be minimized by
    decreasing alcohol intake, eating
    low-carbohydrate foods, and by avoiding large
    meals.
  • Meal regulation is centered on the physiologic
    principle that food evokes hypotensive responses
    secondary to postprandial shifts in blood flow to
    the splanchnic bed
  • Caffeine, which has a well-established pressor
    effect while also blocking adenosine receptors,
    should be considered as a treatment option.
    Patients are advised to consume two cups of
    coffee (240 mg caffeine) with breakfast and
    lunch.
  • Patients should avoid consuming caffeine with
    dinner, as this is when tolerance to its effects
    is most likely.

66
Non Pharmacological Intervention
  • Avoid situations that may exacerbate OH, such as
    straining, isometric exercise, and hot showers
  • If patients wish to exercise, swimming should be
    advocated as the hydrostatic pressure of the
    water opposes the gravitational effect on blood
    pooling.
  • Exercise training also has a role in the
    management of patients with syncope and poor
    orthostatic tolerance
  • Mild degree of exercise is highly desirable as it
    improves symptoms and increases orthostatic
    tolerance without increasing resting BP.

67
Non Pharmacological Intervention
  • Physical maneuvers such as leg crossing and
    squatting may allow patients with OH to increase
    their BP by as much as 13 and 44 mmHg,
    respectively.
  • These maneuvers, combined with tensing muscles at
    the onset of prodromal symptoms, have also shown
    to be effective in postponing or preventing
    vasovagal syncope
  • Postural changes serve to maximize circulating
    blood volume as can Jobst stockings, waist high
    custom-fitted elastic stockings that decrease
    splanchnic pooling and increasing interstitial
    pressure on the legs.
  • For milder forms of OH, knee-length elastic
    stockings may prove sufficient to minimize the
    orthostatic reduction in BP.

68
Non Pharmacological Intervention
  • Blood volume can also be increased by other
    methods.
  • As patients with autonomic failure have
    inadequate sodium conservation, decreased renal
    sympathetic function and decreased
    renin-angiotensin-aldosterone activity, there is
    an inappropriate wasting of sodium in the urine.
    Therefore, salt-containing foods should be
    advocated except in patients with CHF
  • Diuretics should be avoided
  • The head of the patient's bed should be raised to
    a 5 to 20 angle, which activates the
    renin-angiotensin-aldosterone system, and
    decreases both nocturnal diuresis and supine
    hypertension.

69
Pharmacologic Intervention
  • Nonpharmacologic measures alone usually benefit
    only patients with a mild form of this condition.
  • Certain patient types have been found to derive
    great benefit from drugs that are currently
    available, however, the great majority benefit
    slightly from pharmacotherapy alone.
  • Most commonly, treatment is limited by the
    development of significant supine hypertension,
    with systolic BP values above 200 mmHg, or by
    other drug-specific side effects.
  • The most beneficial approach in autonomic failure
    may be combination of fludrocortisone, midodrine,
    and erythropoietin.

70
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71
Fludrocortisone
  • Fludrocortisone (9-alpha-fluorohydrocortisone)
    is a potent mineralocorticoid with minimal
    glucocorticoid effect.
  • It is the most important agent for therapy of
    chronic OH due to its ready availability, low
    cost, and demonstrated efficacy
  • This drug increases blood volume by stimulating
    renal sodium retention. It also sensitizes the
    vasculature to circulating catecholamines. It
    requires 1 or 2 weeks for full action

72
Fludrocortisone
  • Need to provide sufficient salt load for
    maximal effect of fludrocortisone consequently,
    1 or 2 g sodium chloride may need to be
    administered on a daily basis.
  • With long-term therapy, plasma volume generally
    returns toward baseline while the increase in BP
    is maintained.
  • Orally administered fludrocortisone has a
    half-life ranging from 1.5 to 2.5 hours
    consequently, twice-daily administration may
    result in a more sustained effect at the
    mineralocorticoid receptor.

73
Fludrocortisone
  • Therapy typically begins at 0.1 mg (tablet form)
    once a day and is increased at 1- or 2-week
    intervals that allow for titration up to a total
    dosage of 1 mg/day. Most require 0.3 or 0.4 mg to
    derive greatest benefit.
  • Common side effects include
  • Decreased levels of potassium within 2 weeks of
    therapy magnesium levels are often reduced as
    well.
  • Supine hypertension may develop and limit use
  • Headache is a commonly noted side effect

74
Fludrocortisone
  • Mineralocorticoid receptor stimulation can
    adversely affect cardiovascular structure and
    function.
  • Fludrocortisone may augment cardiac hypertrophy
    in patients with autonomic failure.
  • Patients often note improvement in their standing
    time and their overall quality of life when using
    this drug. It is rare that the side effects of
    fludrocortisone are serious enough to require
    discontinuation of therapy.

75
Sympathomimetic Agents Agonists
  • The most promising agent of late is the
    alpha1-agonist, midodrine
  • Highly predictable BP responses, is well
    tolerated, and stimulates both arterial and
    venous systems without direct CNS or cardiac
    effects it does not increase heart rate

76
Midodrine
  • Improved BP control both in patients with primary
    autonomic failure and in patients with diabetic
    neuropathy.
  • In one study involving patients with neurogenic
    OH, midodrine increased systolic BP 22 mmHg on
    average (Jankovic et al)
  • Reported improvement in presyncopal/syncopal
    prodromal symptoms, energy level, feelings of
    depression, and standing time with only mild side
    effects reported
  • When compared head-to-head, these improvements,
    especially the ability to stand, are more
    significant with midodrine than with ephedrine.

77
Midodrine
  • Side effects
  • Piloerection
  • Pruritus
  • Tingling of the scalp
  • Urinary hesitancy and retention in males
  • Supine hypertension occurs in about 25 of
    patients treated with midodrine but can be
    reduced by taking the final dose of midodrine at
    least 4 hours before bedtime.

78
Antagonists.
  • Yohimbine
  • a central and peripheral alpha2-adrenoceptor
    antagonist
  • increases BP by enhancing sympathetic outflow
    centrally and augmenting norepinephrine release
    from postganglionic sympathetic neurons.
  • particularly useful in Shy-Drager syndrome or
    mild forms of the Bradbury-Eggleston syndrome.

79
Erythropoietin
  • Frequently, patients with OH in association with
    autonomic neuropathy have a decreased erythrocyte
    mass.
  • Anemia is usually proportional to plasma
    noradrenaline levels.
  • Anemia responds dramatically to recombinant
    erythropoietin administered intravenously or
    subcutaneously.
  • BP also rises an average of 10 mmHg
  • the mechanism is unclear, not believed to be due
    to an increase in blood volume or to viscosity.

80
Erythropoietin
  • Erythropoietin is administered in 25- to 75-U/kg
    doses three times per week.
  • The goal hematocrit from this treatment is poorly
    defined the suggestion is that hematocrit should
    approach but not exceed gender-specific normal
    values.
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