Download Hyponatremia

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
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]
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
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
Definition of Hyponatremia
Hyponatremia: serum sodium ≤ 135 mEq/La
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
< 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]
Clinical Symptoms in Hyponatremia
More likely to occur with serum sodium < 125 mEq/L
Common symptoms
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Headache
Nausea
Vomiting
Muscle cramps
Lethargy
Restlessness
Depressed reflexes
Disorientation
Potential complications
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Seizures
Coma
Permanent brain damage
Respiratory arrest
Brainstem herniation
Death
Potential complications are associated
with:
• Severe, rapidly evolving hyponatremia
• Excessive water retention in euvolemia
• Menstruation
From Adrogué HJ, et al.[3]
Case Presentation
Neurosurgical 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
2004
2012
Case Presentation
Neurosurgical 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
Neurosurgical Hyponatremia
Postoperative 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
Diagnostic Approach to Hyponatremia
Genuinely hyponatremic?
Genuinely hypotonic?
Not
AVP Mediated
Diluting defect?
N
N
N
Pseudohyponatremia
Hyperglycemia
Radiocontrast
Mannitol
Primary polydipsia
Beer potomania
AVP Mediated
Assess extracellular volume
Low
GI fluid Loss
Adrenal insufficiency
Diuretics
Cerebral salt wasting
Burns and third space fluid loss
Marathon runners
High
Normal
SIADH
Glucocorticoid deficiency
Hypothyroidism
(Reset osmostat)
NSAID
Edema-forming states
• Heart failure
• Cirrhosis
• Nephrosis
Case Presentation
Neurosurgical 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)
Neurosurgical SIADH I
Sodium, mmol/L
Tumor
Resection
UOsm
708
3% NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
Neurosurgical SIADH II
Sodium, mmol/L
Tumor
Resection
UOsm
708
3% NaCl
Dexamethasone or Hydrocortisone
Postoperative Day
Neurosurgical SIADH III
Sodium, mmol/L
Tumor
Resection
UOsm
708
3% NaCl
Tolvaptan,
15 mg
Dexamethasone or Hydrocortisone
Postoperative Day
Neurosurgical SIADH IV
Sodium, mmol/L
Tumor
Resection
UOsm
708
3% NaCl
UOsm
650
Tolvaptan,
15 mg
Dexamethasone or Hydrocortisone
Postoperative Day
Neurosurgical SIADH V
Sodium, mmol/L
Tumor
Resection
UOsm
708
3% NaCl
UOsm
650
Tolvaptan,
15 mg
UOsm
280
Tolvaptan,
30 mg
Dexamethasone or Hydrocortisone
Postoperative Day
Hyponatremia in Heart Failure
Increased sodium reabsorption in the kidney
Angiotensin II
Vasopressin
Aldosterone
Complicating Factors Associated With
Prolonged Length of Stay in Heart Failure
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Hyponatremia
Volume overload
Worsening renal failure
Advanced age
Comorbidities
Marked antecedent weight gain
Lack of (early) resolution of weight gain
Hypotension
Organ hypoperfusion
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]
EFFECT
Multivariable Predictors of Mortality
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Age
Systolic blood pressure
Respiratory rate
Serum sodium
Hemoglobin
Blood urea nitrogen
From Lee DS, et al.[8]
Hyponatremia in Patients With Cirrhosis
• Diuretics cause contraction of central blood volume
resulting in nonosmotic release of AVP
• Patients with cirrhosis have increased reninangiotensin-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]
Serum Sodium Concentration and Relative
Risk of Death After Adjustment for MELD
Score
From Kim WR, et al.[11]