• Information
  1. Pathophysiology
  2. Development of Hypernatremia
  3. Causes
  4. Symptoms
  5. Evaluation of Serum Sodium
  6. Therapy

A. Pathophysiology

1. Normal serum concentration [Na+] = 138-142 mmol/L (mM)
2. Key parameters in evaluating changes in serum [Na+]
   1. Serum [Na+]
   2. Overall body volume status (hypovolemic, euvolemic, hypervolemic)
   3. Serum osmolarity (Osm)
   4. Total body [Na+] levels
3. An abnormal plasma sodium value is indicative of a disorder of water homeostasis
   1. Sodium (Na+) is a functionally impermeable solute (to cells)
   2. The [Na+] cannot be used to determine the direction of the abnormality in fluid status
   3. This is because the total body Na+ determines the patient's volume status
   4. Any abnormal serum [Na+] value may associated with high or low or normal volume
4. Serum Osmolarity
   1. Osm=2x[Na+](mM) + (urea nitrogen [mg/dL]÷ 2.8) + (glucose [mg/dL]÷ 18)
   2. Normal Osm is ~280-290 mOsm
   3. An increase in serum [Na+] (hypernatremia) always predicts a hyperosmolar state
   4. Serum Na+ levels must be corrected for hyperglycemia (and highly elevated BUN)
5. Classifying Hypernatremia
   1. With low total body Na+
   2. With normal total body Na+ (including diabetes insipidus, DI)
   3. Hypervolemia and hypernatremia (Na+ overload)
   4. All patients with hypernatremia are have hypertonic hyperosmolarity

B. Development of Hypernatremia [3]

1. The body PRIMARILY maintains osmolarity
   1. Sensors in the hypothalamus
   2. Sensors in the kidney
2. Development of hypernatremia can occur by:
   1. Inadequate intake of water
   2. Hypothalamic dysfunction: abnormal sensors, inadequate ADH production (central DI)
   3. Renal dysfunction: inability to sense ADH (nephrogenic DI), drug effects (such as lithium)
   4. Hypertonic sodium gain (usually iatrogenic)
3. Majority of patients with hypernatremia are either very young or very old

C. Causes [2]

1. Overview
   1. Net water loss (most common): pure water loss or hypotonic fluid loss
   2. Hypertonic sodium gain (less common): hypertonic saline, sodium bicarbonate
   3. Hypotonic fluid loss: renal, gastrointestinal, or cutaneous (burns, sweating)
2. Dehydration
   1. Divide into Inadequate Fluid Intake and/or Fluid Losses
   2. Fluid losses - consider dermal and respiratory
   3. Iatrogenic - most often occurs during hospitalization, not prior to it [3]
   4. Majority of hospitalizated patients lacked access to adequate free water [3]
   5. Fluid losses from osmotic diuresis or diarrhea or seizures
3. Diabetes Mellitus (DM)
   1. Initial Presentation (especially type 1 diabetes)
   2. Diabetic Ketoacidosis
4. Diabetes Insipidus (DI)
   1. Neurogenic (central) DI - failure to make (adequate) antidiuretic hormone (ADH or vasopressin)
   2. Neurogenic DI - post-traumatic, tumors, cysts, TB, sarcoidosis, aneurysms, GBS
   3. Alcohol intake causes transient neurogenic DI
   4. Nephrogenic DI - failure of kidney to respond to ADH (congenital or acquired)
   5. Acquired nephrogenic DI - renal disease, hypercalcemia, hypokalemia, drugs
   6. Drugs - lithium, demeclocycline, foscarnet, methoxyflurane, amphotericin B, vasopressin
5. Renal Failure (inability to filter Na+)
6. Coma (disordered ADH regulation; absence of thirst mechanism)
7. Hyperaldosteronism
   1. However, mineralocorticoid excess alone rarely causes hypernatremia
   2. Although total body sodium increases in this disease, volume is highly expanded

D. Symptoms

1. Polyuria (to excrete Sodium and Volume)
2. Polydipsia (to replace fluid losses)
3. Change in mental status
4. Severe hypernatremia leads to seizures
5. Most patients with hypernatremia are older
6. Overall mortality was 41% for all patients with hypernatremia [3]

E. Evaluation of Serum Sodium (Na+) With Hyperglycemia [4]

1. High levels of glucose induce hyponatremia
2. This is due primarily to extracellular shift of water since glucose is extracellular
3. Laboratory results for serum Na+ levels with hyperglycemia should be adjusted to reflect these fluid shifts (which will reverse as glucose levels drop)
4. Classically, adjustment of 1.6 meq/L decrease in Na+ for every 100mg/dL increase in serum glucose (above baseline 100mg/dL) was used
5. However, likely that adjustment factor of 2.4meq/L is more appropriate
6. For example, if serum glucose is 800mg/dL and reported serum Na+ is 132meq/L, then the corrected serum Na+ level is {(800-100)/100} x 2.4 + 132 = 149meq/L
7. The corrected serum Na+ level reflects the true state of hypovolemia

F. Therapy [2]

1. Calculate free water deficit
   1. Deficit = BW·[(Na-140)÷ 140] where BW= Body water
   2. BW = FF·Wt(Kg) where FF= fluid fraction, 0.6 for men, 0.5-0.45 for women, and elderly
   3. Change in serum [Na+] = infusate [Na+] - serum [Na+]/(total body water+1)
2. Rapid corrections of water deficits can result in neurological problems
   1. Rapid correction can induce cerebral edema with seizures and brain herniation
   2. Rapid correction (1.0mEq/hr) should be reserved only for very acute hypernatremia
   3. Safe rate of reduction in [Na+] is 0.5mM/hr or about 10mM/day
   4. For chronic hypernatremia, no more than 50% of fluid/sodium deficit should be corrected in first 24 hours [5]
   5. Electrolytes should be monitored at least every 6 hours
3. Infusate [Na+] and Extracellular Distribution
   1. 5% Dextrose in water (D5) 0mM Na+ 40% extracellular distribution
   2. 0.2% NaCl in D5 in water 34mM 55%
   3. 0.45% NaCl (1/2NS) 77mM 73%
   4. Ringer's Lactate (RL) 130mM 97%
   5. 0.9% NaCl (NS) 154mM 100%
4. Choice of Infusate
   1. Most patients have both depletion of total body water AND salt
   2. This occurs in euvolemic and hypovolemic hypernatremia
   3. Correction of problem should begin with 1/2 NS (0.45% NaCl) ± D5
   4. Normal saline (0.9% NaCl) should not be used unless hypotension is present [2]
   5. If [Na+] are very high, then consider using 0.2% NS with D5
   6. For patients with pure water deficits, D5 should generally be used
   7. If potassium (K+) has been lost, then KCl should be added to the infusate
   8. For patients without intake, daily maintenance fluid requires ADDITIONAL ~1.5L per day
   9. Maintenance fluid is RL or D5-1/2NS + 20mEq/L K+ (potassium)
5. Hypervolemic Hypernatremia
   1. Discontinue offending salt heavy agents
   2. Furosemide
   3. Dialysis as needed for renal failure
6. Care should be taken to minimize hypertonic drug and parenteral nutrition solutions
7. Treatment of Diabetes Insipidus
   1. Central DI - DDAVP (desmopressin) nasal spray
   2. Nephrogenic DI - thiaizides, amiloride, and prostaglandin inhibitors have some benefit

References

1. Kumar S and Berl T. 1998. Lancet. 352(9123):220
2. Adrogue HJ and Madias NE. 2000. NEJM. 342(20):1493
3. Palevsky PM, Bhagrath R, Greenberg A. 1996. Ann Intern Med. 124(2):197
4. Hillier TA, Abbott RD, Barrett EJ. 1999. Am J Med. 106(4):399
5. Gullans SR and Verbalis JG. 1993. Annu Rev Med. 44:289