Diagnosis and Treatment of Hyponatremia

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Diagnosis and Treatment of Hyponatremia

• Acute SymptomaticChronic Asymptomatic

Thomas DuBose,M.D. Professor and Chair, Internal
Medicine Wake Forest University School of
Medicine
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Hyponatremia ICU

• Pseudohyponatremia
• Hyperglycemia, Hyperlipidemia
• Post-operative Hyponatremia
• SIADH
• Cerebral Salt Wasting
• Mechanical Ventilation
• Cirrhosis
• Congestive Heart Failure
• SIRS/MODS
• Loop diuretics with hypotonic fluid replacement
• Certain drug intoxications
• Agents that enhance ADH release or action

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Major Causes of Hyponatremia

• EIVF Depletion
• True Volume Depletion
• CHF or Cirrhosis
• SIADH
• Hormone mediated
• Adrenal Insufficiency
• Hypothyroidism
• Pregnancy
• Disorders in which ADH levels may be
  appropriately suppressed
• Advanced renal failure
• Primary polydipsia
• Beer drinkers potomania
• Pseudohyponatremia
• High plasma osmolality hyperglycemia, mannitol,
  urea
• Normal plasma osmolality hyperlipidemia,
  hyperproteinemia, glycine infusion.

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Steps in the Evaluation of Hyponatremia

• Calculate plasma osmolality
• Measure plasma osmolality
• When low defines true hypo-osmolal state or
  clinical hyponatremia
• Consider plasma glucose, protein and lipids
• Evaluate volume status of patient
• Volume depletion
• Volume expansion
• Euvolemia
• Measure urine sodium

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Estimating the Serum Osmolality

• In Spurious Hyponatremia
• Calculated OSMp lt Determined OSMp
• ? Spurious Hyponatremia (hyperlipemia,
  hyperproteinemia) is not a hypoosmolar state.

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Causes of Hypoosmolality

• Volume Depletion
• GI, lung or skin losses
• Third space sequestration
• Adrenal insufficiency
• Renal salt wasting
• Cerebral salt wasting
• Volume Expansion
• CHF, cirrhosis with ascites, nephrotic syndrome
• Euvolemic
• SIADH, water intoxication, reset osmostat, drugs

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Antidiuretic Drugs

• Antidiuretic hormones Vasopression
• Oxytocin
• Diuretics Thiazides
• Furosemide
• Ethacrynic acid
• CNS-active drugs Vincristine
• Carbamazepine
• Psychotropic drugs
• Inhibitors of prostaglandin synthesis
• Chlorpropamide
• Salicylates
• Acetaminophen
• Nonsteroidal anti-inflammatory agents
• COX 2 inhibitors
• Others Clofibrate
• Cyclophosphamide
• Somatostatin
• Ecstasy

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Syndrome of Inappropriate ADH Release (Bartters
Criteria)

• Hyponatremia and true hypoosmolality by
  definition
• Euvolemia clinical
• Urine less than maximally dilute (urinary
  osmolality usually gt 200 mOsm/kg of H2O)
• Normal renal, cardiac, hepatic, adrenal,
  pituitary, and thyroid function
• No history of antidiuretic drugs
• No emotional or physical stress
• Urinary sodium gt 20 mEq/litera

a Urinary sodium may be lt20 mEq/liter if the
patient is volume deleted or on low sodium intake.
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Disorders Associated With SIADH

• Carcinomas
• Pulmonary disorders
• Central nervous system disorders

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Most Common Causes of SIADH in Elderly (CDP and
NHR)

• Medications
• Idiopathic form
• Malignancies
• Aging Clin Exp Res 2003, 156-11.

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Disorders Associated With SIADH Carcinomas

• Small cell carcinoma of the lung
• Carcinoma of the duodenum
• Carcinoma of the pancreas
• Thymoma
• Lymphoma
• Ewings sarcoma
• Mesothelioma
• Carcinoma of the bladder
• Prostatic carcinoma
• Olfactory neuroblastoma

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Disorders Associated With SIADH Pulmonary
Disorders

• Viral pneumonia
• Bacterial pneumonia
• Pulmonary abscess
• Tuberculosis
• Aspergillosis
• Positive-pressure breathing
• Asthma
• Pneumothorax
• Cystic fibrosis
• Lung cancers

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Disorders Associated With SIADH Central Nervous
Disorders

• Encephalitis (viral or bacterial
• Meningitis (viral, bacterial, tuberculosis,
  fungal)
• Head trauma
• Brain abscess
• Brain tumors
• Guillain-Barré syndrome
• Acute intermittent porphyria
• Subarachnoid hemorrhage or subdural hematoma
• Cerebellar and cerebral atrophy

Cavernous sinus thrombosis Neonatal
hypoxia Hydrocephalus Shy-Drager syndrome Rocky
Mountain spotted fever Delirium
tremens Cerebrovascular accident (cerebral
thrombosis or hemorrhage) Acute
psychosis Peripheral neuropathy Multiple sclerosis
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Guiding Principles in the Treatment of
Hyponatremia

• 1. Neurologic disease can follow both the failure
  to promptly treat as well as injudiciously rapid
  treatment of hyponatremia.
• 2. Presence or absence of significant neurologic
  signs and symptoms must guide treatment.
• 3. Acuity or chronicity of the electrolyte
  disturbance impacts the rate at which the
  correction should be undertaken.

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A Prudent Approach to the Treatment of
Hyponatremia - 1

• Acute Symptomatic Hyponatremia (duration lt 48
  hours)
• Risk for complication of cerebral edema greater
  than risk of treatment of complication.
• Treat with hypertonic NaCl 3 NaCl _at_ 1-2
  mL/kg/hr or 2 mEq/L/hr. until convulsions
  subside. Usually means increasing Na by 10.
• Alternative furosemide and hypertonic NaCl
• Full correction is dangerous. Correct by 10 or
  to 120-122 mEq/L slowly.
• Then initiate water restriction.

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A Prudent Approach to the Treatment of
Hyponatremia - 2

• Symptomatic Hyponatremia (Chronic or Unknown
  Duration)
• 1. Increase serum sodium by 10, that is,
  approximately 10 mEq/L and then water restrict.
  Usually 1 -2 mL/kg/hr of hypertonic saline.
• 2. Do not exceed a correction rate of 1.5
  mEq/L/hr at any given time.
• 3. Do not increase serum sodium by more than
• 15 mEq/day.
• 4. Long-term
• H2O restriction
• Demeclocycline 300 - 600 mg bid
• V2 receptor antagonist? Aquaretics

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Therapeutic Strategy Based On

• Volume Status of Patient
• Presence of Absence of Symptoms
• Duration of Hypoosmolality
• Presence of absence of risk factors for
  development of neurological complication
• Osmotic demyelination is rare in patients with
  initial Na gt 120mEq/L

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A Prudent Approach to the Treatment of
Hyponatremia - 3

• Asymptomatic Hyponatremia
• 1. Almost always chronic.
• 2. Treat with water restriction regardless of how
  low the serum sodium.

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Calculating Sodium Requirement in Hyponatremia

• In correcting hyponatremia the approximate
  expansion of total body water must be determined
  first by calculating the volume of water which
  was required to dilute the serum sodium
  concentration to its observed value. For
  example, in a 70 kg patient with a serum Na
  concentration of 120 mEq/L rather than 140 mEq/L,
  this calculation is made as follows
• Body water in normal state (70 kg) (0.60) 42
  L
• Body water in abnormal state (x) (120)
  (42)(140) 49L
• Excess body water 7 L
• The amount of Na in milliequivalents required
  for correction can then be calculated again it
  is necessary to assume Na is distributed
  throughout the total body water.
• (140-patients - Na) (calculated total body
  water) total Na requirement.

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How to predict the effect of therapy on the
patients serum sodium

• The Bottle
• 0.9 154 mEq/L
• Ringers 130 mEq/L
• 0.45 77 mEq/L
• 3 513 mEq/L

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Diagnosis and Treatment of Hypernatremia
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Steps in Evaluation of Hypernatremia

• Establish history of water intake, and integrity
  of thirst mechanism
• Severe hypernatremia is unusual unless thirst
  mechanism is defective or water is not available
  to the patient.
• Determine patients volume status
• Measure urine sodium concentration

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Causes of Hypernatremia

• Volume Depletion
• Urine Na lt 20 sweating, diarrhea, burns
• Urine Na gt 20 Renal losses Hyperglycemia,
  mannitol, urea (osmotic diuresis), or intrinsic
  renal disease
• Volume Expansion
• Urine Na gt 20 Salt loading, Cushings
  syndrome, NaHCO3, hypertonic dialysis
• Eulovemic
• Urine Na lt 20 Fever, heat exhaustion,
  hypermetabolic state
• Urine Na variable or gt 20 Central DI,
  Nephrogenic DI

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Diuretic Drugs

• Alcohol
• Diphenylhydantoin
• Lithium
• Demeclocycline
• Acetohexamde
• Tolazamide

• Glyburide
• Propoxyphene
• Amphotericin
• Methoxyflurane
• Norepinephrine

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Patient Groups at Increased Risk for Hypernatremia

• Post craniotomy (sellar tumors)
• Elderly, nursing home residents
• Hypertonic infusions
• Tube feedings
• Osmotic diuretics
• Lactulose
• Mechanical ventilation
• Diabetes mellitus with poor glycemic control
• Polyuric disorders

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Diabetes Insipidus

• Central DI
• Failure to synthesize or secrete ADH
• Unable to concentrate urine with water
  deprivation (caution !)
• 3 decrease in BW or increase in Posm to 295
  normally results in increase in Uosm gt 700
• Submaximal response give ADH
• Central DI Uosm will increase by 100 or more

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Therapeutic Regimens for the Treatment of
Diabetes Insipidus
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Nephrogenic Diabetes Insipidus

• Does not respond to AVP
• Causes
• Congenital NDI - AVPR2 or AQP2 mutation
• Hypokalemia
• Hypercalcemia
• Drugs Lithium, demeclocycline, glyburide,
  colchicine, amphotericin B
• Treatment
• Thiazides
• Reduce solute intake (low Na diet)
• NSAIDS

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Treatment of Symptomatic Hypernatremia

• 1. Drop NaS by 2 mEq/L/hr.
• 2. Replace 50 of water deficit over 12-24 hrs.
• 3. Replace rest over next 24 hrs.
• 4. Perform serial neurological exams.
• 5. Decrease rate of correction when patient
  improved.
• 6. Measure Na in serum and urine q 12 hrs.