Download - The Different Faces of Hyponatremia: Multifaceted Patients and Multidisciplined Providers
The Different Faces of Hyponatremia: Multifaceted Patients and Multidisciplined Providers
Alpesh N. Amin, MD, MBAProfessor of Medicine
Chair, Department of MedicineExecutive Director, Hospitalist ProgramUniversity of California, Irvine School of
Medicine
Arthur Greenberg, MDProfessor of MedicineDivision of Nephrology
Department of MedicineDuke University School of Medicine
Durham, North Carolina
Paul J. Hauptman, MDProfessor of Internal Medicine
Division of CardiologyAssistant Dean, Clinical and Translational
ResearchSt. Louis University School of Medicine
St. Louis, Missouri
Steven l. Zacks, MD, MPH, FRCPCAssociate Professor of MedicineDivision of Gastroenterology and
HepatologyThe University of North Carolina at
Chapel Hill School of Medicine
• 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
Prevalence and Epidemiology of Hyponatremia
a. From Schrier R.[1]
b. From Boscoe A, et al. [2]
• 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
Patients At Risk for Hyponatremia
• 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
Treatment Challenges
Definition of Hyponatremia
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
Hyponatremia: serum sodium ≤ 135 mEq/La
a. From Adrogué HJ, Madias NE et al.[3]
b. From Thompson.[4]
Clinical Symptoms in Hyponatremia
From Adrogué HJ, et al.[3]
• Seizures • Coma• Permanent brain damage• Respiratory arrest• Brainstem herniation• Death
• Headache• Nausea• Vomiting• Muscle cramps• Lethargy• Restlessness • Depressed reflexes• Disorientation
More likely to occur with serum sodium < 125 mEq/L
Potential complications
Potential complications are associated with: •Severe, rapidly evolving hyponatremia•Excessive water retention in euvolemia•Menstruation
Common symptoms
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
2004
2012
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
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
Diagnostic Approach to HyponatremiaGenuinely hyponatremic? PseudohyponatremiaN
Genuinely hypotonic?HyperglycemiaRadiocontrastMannitol
N
Diluting defect? Primary polydipsiaBeer potomania
N
Assess extracellular volume
GI fluid LossAdrenal insufficiencyDiureticsCerebral salt wastingBurns and third space fluid lossMarathon runners
SIADHGlucocorticoid deficiencyHypothyroidism(Reset osmostat)NSAID
Edema-forming states•Heart failure•Cirrhosis•Nephrosis
HighLowNormal
Not AVP Mediated
AVP Mediated
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)
Postoperative Day
Sodi
um, m
mol
/L
TumorResection
3% NaCl
Dexamethasone or Hydrocortisone
UOsm
708
Neurosurgical SIADH I
Postoperative Day
Sodi
um, m
mol
/L
TumorResection
3% NaCl
Dexamethasone or Hydrocortisone
UOsm
708
Neurosurgical SIADH II
Postoperative Day
Sodi
um, m
mol
/L
TumorResection
3% NaCl
Dexamethasone or Hydrocortisone
UOsm
708
Tolvaptan, 15 mg
Neurosurgical SIADH III
Postoperative Day
Sodi
um, m
mol
/L
TumorResection
3% NaCl
Dexamethasone or Hydrocortisone
UOsm
708
Tolvaptan, 15 mg
UOsm
650
Neurosurgical SIADH IV
Postoperative Day
Sodi
um, m
mol
/L
TumorResection
3% NaCl
Dexamethasone or Hydrocortisone
UOsm
708
Tolvaptan, 15 mg
Tolvaptan, 30 mg
UOsm
650
UOsm
280
Neurosurgical SIADH V
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
• Hyponatremia• Volume overload• Worsening renal failure• Advanced age• Comorbidities• Marked antecedent weight gain• Lack of (early) resolution of weight gain• Hypotension• Organ hypoperfusion
Predicted probability of freedom from death and death or HF rehospitalization
across levels of sodium after adjusting for important covariates
From Gheorghiade M, et al.[5]
ESCAPERelationship between clinical events and patients with persistent hyponatremia,
corrected hyponatremia, or normonatremia
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
IMAGES NO LONGER AVAILABLE
EFFECTMultivariable Predictors of Mortality• 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 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]
From Kim WR, et al.[11]
Serum Sodium Concentration and Relative Risk of Death After Adjustment for MELD Score