SICU Conference

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SICU Conference

• Hypertension in End-Stage Renal Disease Patient

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Hypertension and ESRD

• Hypertension is a major cause of end-stage renal
  disease(ESRD)
• Base on the 1997 United States Renal Data System
  report, the incidence rate of hypertension and
  diabetes mellitus as causes of ESRD continue to
  increase more rapidly than the other major causes
  of ESRD

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ESRD and Cardiovascular Disease

• Cardiovascular disease is the leading cause of
  death in patients undergoing dialysis and renal
  transplantation
• Atherosclerosic and cardiovascular disorders have
  been found to be more prevalent in dialysis
  patients than in the general population

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Outcomes

• A number of studies have suggested poorer
  outcomes in those patients with ESRD with
  uncontrolled hypertension
• Two Japanese studies suggested that the early
  correction of elevated systolic pressure was
  important in determining the ultimate prognosis
  of the hemodialyzed patients
• The patient groups with normal BP had better
  survival

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Low Blood Pressure

• Recent data have shown that abnormally low
  predialysis systolic blood pressure levels
  (lt110mmHg) were associated with decreased
  survival on dialysis

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Pathogenesis
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Expanded Extracellular Fluid Volume

• Volume expansion is perhaps the most important
  factor in the development and maintenance of
  hypertension in dialyzed patients
• It leads to an elevation in BP through the
  combination of an increased in cardiac output and
  an inappropriately high systemic resistance

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Increased Sympathetic Activity

• Sympathetic overactivity is a common finding in
  ESRD
• The afferent signal may arise within the kidney
  because sympathetic activation is not seen in
  aphrenic patients
• Chemoreceptors within the kidney by uremic
  metabolites may be important in generation of
  these signals

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Endogenous Digitalis-Like Substance

• It is believed to be produced in either the
  hypothalamus or adrenal cortex
• Because it inhibits Na-K ATPase activity,
  cytosolic sodium increases, inhibiting calcium
  egress, and causing increased smooth muscle
  calcium content leading to increased smooth
  muscle tone

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Endothelium-Derived Factors

• The abnormal endothelial release of
  hemodynamically active compounds
• Elevated plasma levels of endothelin-1, the
  potent vasoconstrictor, had been found in uremic
  patients
• Uremic plasma contains a higher level of an
  endogenous compound, asymmetrical
  dimethylarginine, that is an inhibitor of NO
  synthesis

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Erythropoietin

• An increased in BP of 10mmHg or more occurs in
  approximately one third of the patients with
  renal failure who are treated with erythropoietin
• Through increased total peripheral resistance
  related to increased viscosity and decreased
  hypoxic vasodilatation

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Hyperparathyroidism

• Increase in intracellular calcium induced by
  parathyroid hormone excess cause vasoconstriction
  and hypertension
• Either vitamin D administration or
  parathyroidectomy has been shown to lower blood
  pressure

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Treatment

• It has been reported that hypertension is less
  well controlled in patients undergoing dialysis
• In a large cohort of European hemodialysis
  patients treated for hypertension, it was
  reported that 87 of the patients with diabetes
  and 65 of the patients without diabetes had
  inadequate BP control

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Volume Control

• Volume control can either normalized the BP or
  make hypertension easier to control

• Salt and water balance
• Dialysis

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Dry Weight(I)

• Attaining dry weight will either normalized the
  BP or male it easier to control in 80 to 90 of
  patients
• The absence of edema does not exclude the
  hypervolemia
• It is the thorniest clinical problem of clinical
  nephrologists

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Dry Weight(II)

• Not merely the absence of edema, but the body
  sodium content and volume of body water or
  critical component thereof below which further
  reduction results in hypotension
• Volume removal to correct clinical fluid overload
  and optimized seated BP without symptomatic
  orthostatic hypotension after dialysis
• Body weight at the end of dialysis at which the
  patient can remain normotensive until the next
  dialysis without antihypertensive medication

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Salt and Water Balance

• Patient compliance is often sub-optimal

As a result, heavy reliance is placed on the
dialysis ultrafiltration capacity to remove this
excess fluid
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Lag Phenomenon

• In new patients starting dialysis, some period of
  time passes before volume is controlled, dry
  weight is achieved, and BP is controlled this
  period has been called the lag phenomenon
• This is the time required to convert the patient
  from a catabolic to an anabolic state while the
  extracellular fluid space slowly stabilized

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Dialysis

• Two crossover studies and one long-term project
  demonstrated that more frequent and longer
  hemodialysis treatment were associated with
  normal blood pressures without medications and
  with regression of left ventricular hypertrophy
• Antihypertensive drugs and rapid fluid removal
  required by shorter dialysis time may limit the
  degree of fluid removal

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Antihypertensive Drugs(I)

• Antihypertensive drugs are indicated in patients
  in whom hypertension persists, despite seemingly
  adequate volume control
• Elevated BP can usually be controlled by most
  classes of antohypertensive agents
• The selection of antohypertensive agents is
  frequently dictated by the presence of comorbid
  conditions

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Antihypertensive Drugs(II)

• One European studyCa2 channel blocker gt ACEI gt
  a blocker gt ß blocker
• These agents are often prescribed in the evening,
  especially after dialysis

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Antihypertensive Drugs(III)

• The addition of antihypertensive drugs may make
  dialysis more difficult to deliver and may lead
  to the inability to control interdialytic
  hypertension, dialysis-induced hypotension, and
  failure to achieve dry weight

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Ca2 channel blockers

• They are effective and well tolerated in dialysis
  patients
• They may be particular useful in patients with
  LVH and diastolic dysfunction
• Certain of these agents have a negative inotropic
  and negative chronotropic effect on the myocardium

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Angiotension-Conveerting Enzyme Inhibitors (I)

• Reduce the production of angiotensin II and also
  decrease degradation of vasodilating bradykinins
  and prostaglandins
• They are well tolerated and are particularly
  effective in patients with a history of heart
  failure due to systolic dysfunction and may
  induce a more rapid regression of LVH

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Angiotension-Conveerting Enzyme Inhibitors (II)

• They may aggravate anemia by reducing the action
  of erythropoietin
• They can trigger an anaphylactoid reaction in
  patients dialyzed with a PAN membrane dialyzer

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Angiotension II receptor Antagonists

• In a study of 89 patients of whom 20 were
  undergoing hemodialysis, BP responded well and no
  significant biochemical alternation were noted
• They are not associated with altered kinin
  metabolism and are not expected to elicit
  anaphylactoid reaction to PAN membrane dialyzer

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ß blockers

• They are particularly indicated in patients who
  have had a recent myocardial infarction or suffer
  from angina pectoris
• Potential side effects include CNS depression,
  bradycardia, altered lipid profiles,
  hyperkalemia, altered response to hypoglycemia,
  and bronchospasm

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a blockers

• These agents are commonly used in patients who
  also have BPH
• They have a favorable metabolic side effect
  profile
• Orthostatic symptoms may occur, especially in
  older patiemts

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Central Sympathetic Agonists

• These agents, such as clonidine and nethyldopa,
  are used less frequently because of their adverse
  effects involving the central nervous system

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Refractory Hypertension (I)

• Some dialysis patients are resistant to both
  volume control and antihypertensive medications

• Concurrent use of certain over-the-counter
  medication
• Secondary hypertension

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Refractory Hypertension (II)

• If faced with refractory hypertension, the
  clinician should redouble his efforts to
  determine whether the patient is truly at dry
  weight
• If a treatable cause cannot be found, minoxidil,
  in combination with a ß blocker may be effective
  in reducing the BP

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Blood Pressure Control

• Lowering the blood pressure too rapidly may be
  hazardous
• Blood pressure should be controlled in a gradual
  manner to allow for adaptation

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Optimal Blood Pressure Level

• The optimal blood pressure level may be best
  defined by the individual patients overall
  cardiovascular profile, including age, previous
  and concurrent complications, and comorbid
  diseases
• Blood pressure should be maintained as close to
  normal as possibleBP lt 135/85mmHg by dayBP lt
  120/80mmHg by night

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Clinical Therapeutic Conclusions

• Withdraw slowly as many antihypertensive
  medications as possible in the process of
  establishing a rational dry weight
• Set a realistic timetable for attaining dry
  weight
• Once the dry weight has been established, if BP
  remains elevated, it may be necessary to initiate
  or continue antihypertensive medication, but
  continue reassessing dry weight

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Thank You For Your Attention