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."

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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

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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

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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

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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

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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

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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

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Progress Day 10-11

• Coversyl Plus identified as still being given and
  ceased
• Fludrocortisone dose increased to 0.3mg daily

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Drugs that come back and bite you!
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Drugs that come back!

• Not ceased- withheld
• Recharted
• Charted at multiple sites
• Patients secret supply
• The post discharge return

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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...

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Progress Day 13
Procedure Date 3.2.05
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Progress
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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

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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

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Progress Day 14

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

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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

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Progress Day 14

• Orthopedic opinion
• As above- conservative Rx

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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

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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

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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

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Postural Hypotension

• There is no happiness where there is no
  wisdomNo 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

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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.

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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.

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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.

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Orthostatic Hypotension

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

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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.

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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.

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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.

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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.

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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

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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)

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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.

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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

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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

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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.

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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.

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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.

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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.

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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

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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.

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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

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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.

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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.

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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.

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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.

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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.