Hypernatremia is defined as a plasma sodium concentration >145 mEq/L. It is usually caused by a water deficit rather than sodium gain. Common causes include impaired thirst, diarrhea, insensible losses from fever/ventilation, and renal losses from osmotic diuresis or diabetes insipidus. Symptoms range from none in chronic cases to neurologic issues like altered mental status. Treatment involves gradually correcting the sodium level by about 10-12 mEq/L/day using oral or IV water while monitoring for complications like cerebral edema. Replacing volume deficits and identifying underlying causes are also important.
4. • Hypernatremia is seen in about 1% of
hospitalized patients and is more common
(7%) in intensive care unit patients.
• Mortality rate as high as 40% is reported with
hypernatremia, though it is uncommonly
identified as the primary cause of death.
• Palevsky PM, Bhagrath R,GreenbergA. Hypernatremia in hospitalized patients.
Ann Intern Med 1996;124:197-203.
• Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an
independent risk factor for mortality. Am J Kidney Dis 2007;50:952-7.
5. Etiology
• Hypernatremia may be caused by a primary
Na gain or a water deficit, the latter being
much more common.
• Normally, this hyperosmolar state stimulates
thirst and the excretion of a maximally
concentrated urine.
For hypernatremia to persist, one or both of
these compensatory mechanisms must also
be impaired.
6. • Impaired thirst response may occur in
situations where access to water is limited,
often due to physical restrictions
(institutionalized, handicapped, postoperative,
or intubated patients) or the mentally
impaired (delirium, dementia).
• Elderly individuals with reduced thirst and/or
diminished access to fluids are at the highest
risk of developing hypernatremia.
Palevsky PM. Hypernatremia. Semin Nephrol. Jan 1998;18(1):20-30.
7. • Hypernatremia due to water loss
The loss of water must occur in excess of
electrolyte losses in order to raise [Na].
Nonrenal water loss may be due to
evaporation from the skin and respiratory
tract (insensible losses) or loss from the GI
tract.
Diarrhea is the most common GI cause of
hypernatremia.
8. • Osmotic diarrhea (induced by lactulose,
sorbitol, or malabsorption of carbohydrate)
and viral gastroenteritis, in particular, result in
disproportional water loss.
• Insensible losses of water may increase in the
setting of fever, exercise, heat exposure,
severe burns, or mechanical ventilation.
9. • Renal water loss results from either osmotic
diuresis or diabetes insipidus (DI).
• Osmotic diuresis is frequently associated with
glycosuria and high osmolar feeds.
In addition, increased urea generation from
accelerated catabolism, high protein feeds,
and stress-dose steroids can also result in an
osmotic diuresis.
10. • Hypernatremia secondary to nonosmotic urinary
water loss is usually caused by
(a) impaired vasopressin secretion (central
diabetes insipidus [CDI]) or
(b) resistance to the actions of vasopressin
(nephrogenic diabetes insipidus [NDI]).
Partial defects occur more commonly than
complete defects in both types.
Patients with DI generally do not develop
hypernatremia if they are able to maintain fluid
intake adequate to compensate for the water
loss.
11. • The most common cause of CDI is destruction
of the neurohypophysis from trauma,
neurosurgery, granulomatous disease,
neoplasms, vascular accidents, or infection.
In many cases, CDI is idiopathic.
12. • NDI may either be inherited or acquired.
The latter often results from a disruption to
the renal concentrating mechanism due to
drugs (lithium, demeclocycline, amphotericin),
electrolyte disorders (hypercalcemia,
hypokalemia), medullary washout (loop
diuretics), and intrinsic renal diseases.
13.
14. • Gestational diabetes insipidus is a rare
complication of late-term pregnancy in which
increased activity of a circulating placental
protease with vasopressinase activity leads to
reduced circulating AVP and polyuria, often
accompanied by hypernatremia.
DDAVP is an effective therapy for this
syndrome because of its resistance to the
vasopressinase enzyme.
15. • Hypernatremia due to primary Na gain occurs
infrequently due to the kidney's capacity to
excrete the retained Na.
However, it can rarely occur after repetitive
hypertonic saline administration or chronic
mineralocorticoid excess.
• Transcellular water shift from ECF to ICF can
occur in circumstances of transient
intracellular hyperosmolality, as in seizures or
rhabdomyolysis.
18. Clinical Presentation
• Hypernatremia results in contraction of brain cells as
water shifts to attenuate the rising ECF osmolality.
• Thus, the most severe symptoms of hypernatremia are
neurologic, including altered mental status, weakness,
neuromuscular irritability, focal neurologic deficits,
and, occasionally, coma or seizures. The presence of
encephalopathy is a poor prognostic sign in
hypernatremia, and carries a mortality rate as high as
50%.
• As with hyponatremia, the severity of the clinical
manifestations is related to the acuity and magnitude
of the rise in plasma [Na].
19.
20. • The sudden shrinkage of brain cells in acute
hypernatremia may lead to parenchymal or
subarachnoid hemorrhages and/or subdural
hematomas; however, these vascular
complications are encountered primarily in
pediatric and neonatal patients.
• Osmotic damage to muscle membranes also
can lead to hypernatremic rhabdomyolysis.
23. • Brain cells accommodate to a chronic increase
in ECF osmolality (>48 h) by activating
membrane transporters that mediate influx
and intracellular accumulation of organic
osmolytes (creatine, betaine, glutamate, myo-
inositol, and taurine); this results in an
increase in ICF water and normalization of
brain parenchymal volume.
24. • Chronic hypernatremia is generally less
symptomatic as a result of adaptive
mechanisms designed to defend cell volume.
• However, the cellular response to chronic
hypernatremia predisposes these patients to
the development of cerebral edema and
seizures during overly rapid hydration
(overcorrection of plasma Na + concentration
by >10 mM /d).
25. • CDI and NDI generally present with complaints
of polyuria and thirst.
Signs of volume depletion or neurologic
dysfunction are generally absent unless the
patient has an associated thirst abnormality.
26. Diagnostic Approach
• The history should focus on the presence or absence of
thirst, polyuria, and/or an extrarenal source for water
loss, such as diarrhea.
• The physical examination should include a detailed
neurologic exam and an assessment of the ECFV;
patients with a particularly large water deficit and/or a
combined deficit in electrolytes and water may be
hypovolemic, with reduced JVP and orthostasis.
• Accurate documentation of daily fluid intake and daily
urine output is also critical for the diagnosis and
management of hypernatremia.
30. • Adequate differentiation between
nephrogenic and central causes of DI requires
the measurement of the response in urinary
osmolality to DDAVP, combined with
measurement of circulating AVP in the setting
of hypertonicity.
31. • By definition, patients with baseline
hypernatremia are hypertonic, with an adequate
stimulus for AVP by the posterior pituitary.
• Therefore, in contrast to polyuric patients with a
normal or reduced baseline plasma Na +
concentration and osmolality, a water deprivation
test is unnecessary in hypernatremia; indeed,
water deprivation is absolutely contraindicated in
this setting because of the risk for worsening the
hypernatremia.
35. • Patients with NDI will fail to respond to DDAVP,
with a urine osmolality that increases by <50% or
<150 mosmol/kg from baseline, in combination
with a normal or high circulating AVP level.
• Patients with central DI will respond to DDAVP,
with a reduced circulating AVP. Patients may
exhibit a partial response to DDAVP, with a >50%
rise in urine osmolality that nonetheless fails to
reach 800 mosmol/kg; the level of circulating AVP
will help differentiate the underlying cause, i.e.,
nephrogenic versus central DI.
36. • In pregnant patients, AVP assays should be
drawn in tubes containing the protease
inhibitor 1,10-phenanthroline to prevent in
vitro degradation of AVP by placental
vasopressinase.
37. Treatment
• Management requires one to determine
i. the rate of correction,
ii. the appropriate intervention, and
iii. the presence of other underlying disorders.
• The goal of correction should be to bring Na+
to 145 meq/L.
38. • Symptomatic hypernatremia
As in hyponatremia, aggressive correction of
hypernatremia is potentially dangerous.
The rapid shift of water into brain cells
increases the risk of seizures or permanent
neurologic damage.
Therefore, the water deficit should be
reduced gradually by roughly 10 to 12
mEq/L/d.
39. • Chronic asymptomatic hypernatremia
The risk of treatment-related complication is
increased due to the cerebral adaptation to
the chronic hyperosmolar state, and the
plasma [Na] should be lowered at a more
moderate rate (between 5 and 8 mEq/L/d).
40. • Intervention
The mainstay of management is the
administration of water, preferably by mouth
or nasogastric tube.
Alternatively, 5% dextrose in water (D5W) or
quarter NS can be given intravenously.
41. Traditionally, correction of hypernatremia has
been accomplished by calculating free water
deficit by the equation:
Free water deficit = {([Na] - 140)/140} X (TBW)
42. • Alternatively,
• The change in [Na] from the administration of
1000 ml fluid can be estimated as follows:
• Because hypernatremia suggests a contraction
in water content, TBW is estimated by
multiplying lean weight (in kilograms) by 0.5 in
men (rather than 0.6) and 0.4 in women.
45. • Hypovolemic hypernatremia
In patients with mild volume depletion, Na-containing
solutions, such as 0.45% NS, can be used to replenish
the ECF as well as the water deficit.
If patients have severe or symptomatic volume
depletion, correction of volume status with isotonic
fluid should take precedence over correction of the
hyperosmolar state. Once the patient is
hemodynamically stable, administration of hypotonic
fluid can be given to replace the free water deficit.
• Hypernatremia from primary Na gain is unusual.
Cessation of iatrogenic Na is typically sufficient.
46. • DI without hypernatremia
DI is best treated by removing the underlying
cause.
Despite the renal water loss, DI should not
result in hypernatremia if the thirst
mechanism remains intact.
Therefore, therapy, if required at all, is
directed toward symptomatic polyuria.
47. • CDI
Because the polyuria is the result of impaired
secretion of vasopressin, treatment is best
accomplished with the administration of
DDAVP, a vasopressin analog.
48. • NDI
A low-Na diet combined with thiazide
diuretics will decrease polyuria through
inducing mild volume depletion. This
enhances proximal reabsorption of salt and
water, thus decreasing urinary free water loss.
Decreasing protein intake will further
decrease urine output by minimizing the
solute load that must be excreted.
49. • Patients with NDI due to lithium may reduce
their polyuria with amiloride (2.5–10 mg/d));
in practice, however, most patients with
lithium-associated DI are able to compensate
for their polyuria simply by increasing their
daily water intake.
• Occasionally, nonsteroidal anti-inflammatory
drugs (NSAIDs) have been used to treat
polyuria associated with NDI; however, this
creates the risk of NSAID-associated gastric
and/or renal toxicity.
50. • It must be emphasized that thiazides,
amiloride, and NSAIDs are appropriate only
for chronic management of polyuria from NDI
and have no role in the acute management of
associated hypernatremia, in which the focus
is on replacing free-water deficits and ongoing
free-water loss.
52. • A 76-year-old man presents with a severe
obtundation, dry mucous membranes,
decreased skin turgor, fever, tachypnea, and a
blood pressure of 142/82 mm Hg without
orthostatic changes. The serum sodium
concentration is 168 mmol per liter, and the
body weight is 68 kg.
• Hypernatremia caused by pure water
depletion due to insensible losses is diagnosed
and an infusion of 5 percent dextrose is
planned.
53. • The estimated volume of total body water is 34 liters
(0.5X68). According to formula, the retention of 1 liter
of 5 percent dextrose will reduce the serum sodium
concentration by 4.8 mmol per liter ([0-168]÷[34+1]=-
4.8).
• The goal of treatment is to reduce the serum sodium
concentration by approximately 10 mmol per liter over
a period of 24 hours. Therefore, 2.1 liters of the
solution (10÷4.8) is required. With 1.5 liters added to
compensate for average obligatory water losses over
the 24-hour period, a total of 3.6 liters will be
administered for the next 24 hours, or 150 ml per hour.
• The serum glucose concentration will be monitored,
with insulin therapy started at the first indication of
hyperglycemia, a complication that would aggravate
the hypertonicity.
54. • A 58-year-old woman with postoperative ileus is
undergoing nasogastric suction. She is obtunded
and has diminished skin turgor and mild
orthostatic hypotension. The serum sodium
concentration is 158 mmol per liter, the
potassium concentration is 4.0 mmol per liter, and
the body weight is 63 kg.
• Hypernatremia caused by hypotonic fluid loss is
diagnosed and an infusion of 0.45 percent
sodium chloride is planned, with the goal of
decreasing the serum sodium concentration by 5
mmol per liter over the next 12 hours. Although
there is evidence of a depletion in the volume of
extracellular fluid, the patient’s hemodynamic
status is not sufficiently compromised to warrant
the initial use of 0.9 percent sodium chloride.
55. • The estimated volume of total body water is 31.5
liters (0.5X63). It is estimated that the retention
of 1 liter of 0.45 percent sodium chloride will
reduce the serum sodium concentration by 2.5
mmol per liter ([77-158]÷[31.5+1]=-2.5). Since
the goal is to reduce the serum sodium
concentration by 5 mmol per liter over the next
12 hours, 2 liters of the solution is required
(5÷2.5).
• With 1 liter added to compensate for ongoing
losses of gastric and other fluids, a total of 3 liters
will be administered for the next 12 hours, or 250
ml per hour.
56. • A 62-year-old man with advanced alcoholic cirrhosis is
receiving lactulose for the management of hepatic
encephalopathy. On examination, confusion, ascites,
and asterixis are present. The blood pressure is 105/58
mm Hg while the patient is in the supine position, and
the pulse is 110 beats per minute. The serum sodium
concentration is 160 mmol per liter, the potassium
concentration is 2.6 mmol per liter, and the body
weight is 64 kg.
• The hypernatremia reflects hypotonic sodium and
potassium losses induced by lactulose therapy .Thus, in
addition to the withdrawal of lactulose, 0.2 percent
sodium chloride containing 20 mmol of potassium
chloride per liter will be administered.
57. • With the presence of ascites, the estimated
volume of total body water is about 38 liters
(0.6 X 64).
• According to the formula, the retention of 1 liter
of 0.2 percent sodium chloride containing 20
mmol of potassium chloride will reduce the
serum sodium concentration by 2.7 mmol per
liter ([(34+20)-160]÷[38+1]=-2.7). To reduce the
serum sodium concentration by 10 mmol per liter
over the next 24 hours, 3.7 liters of solution
(10÷2.7) is required.
• With 1.5 liters added to compensate for ongoing
obligatory fluid and electrolyte losses, a total of
5.2 liters will be administered
58. • A 60-year-old man has received 10 ampules of sodium
bicarbonate over a period of six hours during
resuscitation after recurrent cardiac arrest. He is
stuporous and is undergoing mechanical ventilation.
His blood pressure is 138/86 mm Hg, and peripheral
edema (+++) is present. The serum sodium
concentration is 156 mmol per liter, the body weight is
85 kg, and the urinary output is 30 ml per hour.
• The hypernatremia is caused by hypertonic sodium
gain, and its correction requires that the excess sodium
and water be excreted. The administration of
furosemide alone will not suffice, because furosemide-
induced diuresis is equivalent to one-half isotonic
saline solution; thus, the hypernatremia will be
aggravated.
59. • The administration of both furosemide and
electrolyte-free water will meet the
therapeutic goal. The estimated volume of
total body water is 51 liters (0.6X85).
• The retention of 1 liter of 5 percent dextrose is
estimated to decrease the serum sodium
concentration by 3.0 mmol per liter ([0-156]÷
[51+1]=-3.0). To reduce the serum sodium
concentration by 6.0 mmol per liter over a
period of eight hours, 2.0 liters of 5 percent
dextrose will be infused at a rate of 250 ml per
hour.
60.
61. References
• Hypernatremia, NEJM 2000; 342:1493-1499
• Hyponatremia and Hypernatremia : Disorders
of Water Balance, JAPI Vol 56, Dec 2008
• Washington Manual of Medical Therapeutics
• Harrison Principles of Internal Medicine
• A Clinical Approach to the Treatment of
Chronic Hypernatremia, Am J Kidney Dis.
2012;60(6):1032-1038
Hypernatremia is a “water problem,” not a problem of sodium homeostasis.
Secretory diarrhea patients e.g., VIPoma, carcinoid syndrome, and cholera, generally do not present with hypernatremia due to loss of both electrolytes andwater
Adipsic hypernatremia (sometimes called essential hypernatremia) results from congenital or acquired defect in hypothalamic osmoreceptors. It is associated with partial or complete loss of osmoregulation of vasopressin, lack of thirst,hypernatremia and evidence of hypovolemia.Patients with this condition may have associated elevated renin and aldosterone, hypokalemia and alkalosis.
Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.
As for hyponatremia, the initial evaluation of the patient with hypernatremia involves assessment of volume status. Patients with hypovolemic hypernatremia lose both sodium and water, but relatively more water. On physical examination, they exhibit signs of hypovolemia. The causes listed reflect principally hypotonic water losses from the kidneys or the gastrointestinal tract. Euvolemic hyponatremia reflects water losses accompanied by inadequate water intake. Since such hypodipsia is uncommon, hypernatremia usually supervenes in persons who have no access to water or who have a neurologic deficit that impairs thirst perception—the very young and the very old. Extrarenal water loss occurs from the skin and respiratory tract, in febrile or other hypermetabolic states. Very high urine osmolality reflects an intact osmoreceptor–antidiuretic hormone–renal response. Thus, the defense against the development of hyperosmolality requires appropriate stimulation of thirst and the ability to respond by drinking water. The urine sodium (UNa) value varies with the sodium intake. The renal water losses that lead to euvolemic hypernatremia are a consequence of either a defect in vasopressin production or release (central diabetes insipidus) or failure of the collecting duct to respond to the hormone (nephrogenic diabetes insipidus)
Pure water loss is associated with a lesser degree of ECF volume contraction than hypotonic fluid loss as most of the lost water comes from ICF compartment. As a result hypovolemia may not be evident clinically in patients who have lost pure water e.g., DI, and insensible losses. Serum glucose should be checked in all patientsto rule out osmotic diuresis. Measurement of urine output and urine osmolality helps in the determination of etiology. Measurement of urine Na+ can help in the assessment of the volume status of the patient. Diuretic use can confuse the picture by altering urine sodium
As this formula can underestimate the amount of water
deficit in patients with hypotonic fluid loss rather than
pure water loss, Adrogué et al have suggested an alternate
formula predicting the effect of 1000ml of an infusate as
follows:
