The Different Faces of Hyponatremia: Multifaceted Patients and Multidisciplined Providers

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The Different Faces of Hyponatremia Multifaceted
Patients and Multidisciplined Providers

• Alpesh N. Amin, MD, MBA
• Professor of Medicine
• Chair, Department of Medicine
• Executive Director, Hospitalist Program
• University of California, Irvine School of
  Medicine
• Arthur Greenberg, MD
• Professor of Medicine
• Division of Nephrology
• Department of Medicine
• Duke University School of Medicine
• Durham, North Carolina

• Paul J. Hauptman, MD
• Professor of Internal Medicine
• Division of Cardiology
• Assistant Dean, Clinical and Translational
  Research
• St. Louis University School of Medicine
• St. Louis, Missouri
• Steven l. Zacks, MD, MPH, FRCPC
• Associate Professor of Medicine
• Division of Gastroenterology and Hepatology
• The University of North Carolina at Chapel Hill
  School of Medicine

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Prevalence and Epidemiology of Hyponatremia

• Most common disorder of electrolytes, affecting
  15 to 30 of acutely and chronically
  hospitalized patientsa
• Approximately 1 million hospitalizations per year
  are due to hyponatremia as a primary or secondary
  diagnosis
• Direct cost of managing hyponatremia is estimated
  to range from 1.6 to 3.6 billion per year in
  the United Statesb

a. From Schrier R.1 b. From Boscoe A, et al.
2
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Patients At Risk for Hyponatremia

• Primarily caused by inappropriately elevated
  plasma AVP, which is secreted in response to
  increased plasma osmolality or decreased
  volume/pressure (hypovolemia) and results in
  water reabsorption
• Etiology varies with classification
• Hypovolemia (gastrointestinal/dermal/third-space
  loss, diuretics)
• Euvolemia (SIADH, drugs diuretics, SSRIs,
  carbamazepine, TCAs, phenothiazines, etc)
• Hypervolemia (heart failure, cirrhosis, renal
  failure)
• Clinical manifestation of underlying medical
  conditions and hyponatremia may provide important
  diagnostic and prognostic information

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Treatment Challenges

• Acute, severe hyponatremia can cause substantial
  morbidity and mortality
• Mortality is higher in patients with a wide range
  of underlying diseases
• Overly rapid correction can cause severe
  neurologic deficits and death

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Definition of Hyponatremia
Hyponatremia serum sodium 135 mEq/La
Severity of Hyponatremiab Severity of Hyponatremiab Severity of Hyponatremiab
Severity Neurologic Manifestations Sodium
Mild Asymptomatic or associated with subtle changes in mental and physical function 130-135 mEq/L
Moderate Nonspecific symptoms (nausea and malaise) 125-130 mEq/L
Severe Progressive neurologic symptoms ranging from confusion to coma lt 125 mEq/L
Neurologic manifestations are also influenced by
the speed of onset of hyponatremia
a. From Adrogué HJ, Madias NE et al.3 b. From
Thompson.4
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Clinical Symptoms in Hyponatremia
More likely to occur with serum sodium lt 125 mEq/L
Common symptoms
Potential complications

• Seizures
• Coma
• Permanent brain damage
• Respiratory arrest
• Brainstem herniation
• Death

• Headache
• Nausea
• Vomiting
• Muscle cramps
• Lethargy
• Restlessness
• Depressed reflexes
• Disorientation

• Potential complications are associated with
• Severe, rapidly evolving hyponatremia
• Excessive water retention in euvolemia
• Menstruation

• From Adrogué HJ, et al.3

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Case PresentationNeurosurgical Hyponatremia

• 30-year-old man with a known third ventricle
  tumor of 8 years duration
• Intractable headaches, seizure disorder
• Medications oxycodone, levetiracetam
• Admitted for tumor resection
• BP 123/86, no JVD, clear chest, no edema, normal
  neurological exam
• Sodium 139 mmol/L, BUN 12 mg/dL, creatinine 1.0
  mg/dL, glucose 147 mg/dL

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2004
2012
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Case PresentationNeurosurgical Hyponatremia
(cont)

• Brought to the operating room
• Craniectomy, bone flap, excision of tumor from
  left lateral and third ventricles
• Pathology central neurocytoma, WHO grade III
• Returned to neurosurgical ICU
• Initially awake, but deteriorated neurologically
• CT of brain showed interval development of
  hydrocephalus
• Returned to operating room for placement of
  ventriculoperitoneal shunt
• Returned to neurosurgical ICU

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Neurosurgical HyponatremiaPostoperative Days 4
and 5

• Maintained on antibiotics, IV fluids,
  levetiracetam, IV fentanyl, high-dose
  dexamethasone
• Vital signs stable with pulse averaging 70 bpm
  range and BP in the range of 110 to 130/60 to 75
• Physical examination revealed waxing and waning
  mental status, clear chest, no edema
• Intake and output roughly balanced with 2-3 L/d
  0.9 saline or 0.45 saline in, 2-3 L/d urine out
  
• Decrease in serum sodium level from 140 to 127
  mmol/L

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Diagnostic Approach to Hyponatremia
N
Genuinely hyponatremic?
Pseudohyponatremia
Hyperglycemia Radiocontrast Mannitol
N
Genuinely hypotonic?
N
Primary polydipsia Beer potomania
Not AVP Mediated
Diluting defect?
AVP Mediated
Assess extracellular volume
Low
High
Normal
GI fluid Loss Adrenal insufficiency Diuretics Cere
bral salt wasting Burns and third space fluid
loss Marathon runners
SIADH Glucocorticoid deficiency Hypothyroidism (Re
set osmostat) NSAID

• Edema-forming states
• Heart failure
• Cirrhosis
• Nephrosis

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Case PresentationNeurosurgical Hyponatremia
(cont)

• Serum cortisol 0.8 µg/dL (normal, 5.0-25.0 µg/dL
  )
• Free thyroxine 0.68 ng/dL (normal, 0.52-1.21
  ng/dL)
• Thyroid stimulating hormone 0.23 mIU/L (normal,
  0.34-5.66 mIU/L)
• Follicle-stimulating hormone 1.0 mIU/mL (normal,
  2.5-17.7)
• Luteinizing hormone 0.3 mIU/mL (normal, 1.4-7.7
  mIU/mL)
• Sodium 127 mEq/L
• Plasma osmolality 272 mOsm/kg
• Urine osmolality 875 mOsm/kg
• Urine sodium 245 mmol/L
• Uric acid 3.6 mg/dL (normal, 4.0-8.0 mg/dL)

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Neurosurgical SIADH I
Tumor Resection
UOsm 708
Sodium, mmol/L
3 NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
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Neurosurgical SIADH II
Tumor Resection
UOsm 708
Sodium, mmol/L
3 NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
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Neurosurgical SIADH III
Tumor Resection
UOsm 708
Sodium, mmol/L
Tolvaptan, 15 mg
3 NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
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Neurosurgical SIADH IV
Tumor Resection
UOsm 708
UOsm 650
Sodium, mmol/L
Tolvaptan, 15 mg
3 NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
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Neurosurgical SIADH V
Tumor Resection
UOsm 280
UOsm 708
UOsm 650
Sodium, mmol/L
Tolvaptan, 30 mg
Tolvaptan, 15 mg
3 NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
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Hyponatremia in Heart Failure

• Increased sodium reabsorption in the kidney
• Angiotensin II Vasopressin Aldosterone

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Complicating Factors Associated With Prolonged
Length of Stay in Heart Failure

• Hyponatremia
• Volume overload
• Worsening renal failure
• Advanced age
• Comorbidities
• Marked antecedent weight gain
• Lack of (early) resolution of weight gain
• Hypotension
• Organ hypoperfusion

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ESCAPE

• Predicted probability of freedom from death and
  death or HF rehospitalization across levels of
  sodium after adjusting for important covariates

• Relationship between clinical events and patients
  with persistent hyponatremia, corrected
  hyponatremia, or normonatremia

IMAGES NO LONGER AVAILABLE
Plots are for the average patient using the
mean values of all covariates. Lighter line pairs
represent 95 CI. To convert sodium to mmol/L,
multiply by 1.0
Error brackets indicate exact binomial 95 CI
intervals
From Gheorghiade M, et al.5
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EFFECTMultivariable Predictors of Mortality

• Age
• Systolic blood pressure
• Respiratory rate
• Serum sodium
• Hemoglobin
• Blood urea nitrogen

From Lee DS, et al.8
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Hyponatremia in Patients With Cirrhosis

• Diuretics cause contraction of central blood
  volume resulting in nonosmotic release of AVP
• Patients with cirrhosis have increased
  renin-angiotensin-mediated free water
  reabsorption while diuretics block sodium
  reabsorption
• Hyponatremia is significant because
• The MELD score combined with the serum sodium
  concentration was a better predictor of death
  than the MELD score alonea
• It is associated with the development of hepatic
  encephalopathyb
• Hyponatremia is a more sensitive marker of renal
  dysfunction than creatinine in patients with
  cirrhosisc

a. From Kim WR, et al.11 b. From Häussinger D,
Schliess F.12 c. From Ruf AE, et al.13
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Serum Sodium Concentration and Relative Risk of
Death After Adjustment for MELD Score
From Kim WR, et al.11
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