AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium. Clinically significant hyponatremia is relatively uncommon and is nonspecific in its presentation; therefore, the ED physician must consider the diagnosis in patients presenting with vague constitutional symptoms or with altered level of consciousness. Irreparable harm can befall the patient when abnormal serum sodium levels are corrected too quickly or too slowly. The ED physician must have a thorough understanding of the pathophysiology of hyponatremia to initiate safe and effective corrective therapy. The patient's fluid status must be accurately assessed upon presentation, as it guides the approach to correction.

Hypovolemic hyponatremia

Total body water (TBW) decreases; total body sodium (Na⁺) decreases to a greater extent. The extracellular fluid (ECF) volume is decreased.

Euvolemic hyponatremia

TBW increases while total sodium remains normal. The ECF volume is increased minimally to moderately but without the presence of edema.

Hypervolemic hyponatremia

Total body sodium increases, and TBW increases to a greater extent. The ECF is increased markedly, with the presence of edema.

Redistributive hyponatremia

Water shifts from the intracellular to the extracellular compartment, with a resultant dilution of sodium. The TBW and total body sodium are unchanged. This condition occurs with hyperglycemia.

Pseudohyponatremia

The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged. This condition is seen with hypertriglyceridemia and multiple myeloma.

Pathophysiology

Serum sodium concentration is regulated by stimulation of thirst, secretion of ADH, feedback mechanisms of the renin-angiotensin-aldosterone system, and variations in renal handling of filtered sodium. Increases in serum osmolarity above the normal range (280-300 mOsm/kg) stimulate hypothalamic osmoreceptors, which, in turn, cause an increase in thirst and in circulating levels of ADH. ADH increases free water reabsorption from the urine, yielding urine of low volume and relatively high osmolarity and, as a result, returning serum osmolarity to normal. ADH is also secreted in response to hypovolemia, pain, fear, nausea, and hypoxia.

Aldosterone, synthesized by the adrenal cortex, is regulated primarily by serum potassium but also is released in response to hypovolemia through the renin-angiotensin-aldosterone axis. Aldosterone causes absorption of sodium at the distal renal tubule. Sodium retention obligates free water retention, helping to correct the hypovolemic state. The healthy kidney regulates sodium balance independently of ADH or aldosterone by varying the degree of sodium absorption at the distal tubule. Hypovolemic states, such as hemorrhage or dehydration, prompt increases in sodium absorption in the proximal tubule. Increases in vascular volume suppress tubular sodium reabsorption, resulting in natriuresis and helping to restore normal vascular volume. Generally, disorders of sodium balance can be traced to a disturbance in thirst or water acquisition, ADH, aldosterone, or renal sodium transport.

Hyponatremia is physiologically significant when it indicates a state of extracellular hypoosmolarity and a tendency for free water to shift from the vascular space to the intracellular space. Although cellular edema is well tolerated by most tissues, it is not well tolerated within the rigid confines of the bony calvarium. Therefore, clinical manifestations of hyponatremia are related primarily to cerebral edema. The rate of development of hyponatremia plays a critical role in its pathophysiology and subsequent treatment. When serum sodium concentration falls slowly, over a period of several days or weeks, the brain is capable of compensating by extrusion of solutes and fluid to the extracellular space. Compensatory extrusion of solutes reduces the flow of free water into the intracellular space, and symptoms are much milder for a given degree of hyponatremia.

When serum sodium concentration falls rapidly, over a period of 24-48 hours, this compensatory mechanism is overwhelmed and severe cerebral edema may ensue, resulting in brainstem herniation and death.

Frequency

United States

Hyponatremia is the most common electrolyte disorder, with a marked increase among hospitalized and nursing home patients. A 1985 prospective study of inpatients in a US acute care hospital found an overall incidence of approximately 1% and a prevalence of approximately 2.5%. On the surgical ward, approximately 4.4% of postoperative patients developed hyponatremia within 1 week of surgery. Hyponatremia has also been observed in approximately 30% of patients treated in the intensive care unit.¹

International

Hyponatremia has been observed in 42.6% of patients in a large acute care hospital in Singapore and in 30% of patients hospitalized in an acute care setting in Rotterdam.^{2, 3}

Mortality/Morbidity

Pathophysiologic differences between patients with acute and chronic hyponatremia engender important differences in their morbidity and mortality.

• Patients with acute hyponatremia (developing over 48 h or less) are subject to more severe degrees of cerebral edema for a given serum sodium level. The primary cause of morbidity and death is brainstem herniation and mechanical compression of vital midbrain structures. Rapid identification and correction of serum sodium level is necessary in patients with severe acute hyponatremia to avert brainstem herniation and death.
• Patients with chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema for a given serum sodium level. Brainstem herniation has not been observed in patients with chronic hyponatremia. The principal causes of morbidity and death are status epilepticus (when chronic hyponatremia reaches levels of 110 mEq/L or less) and cerebral pontine myelinolysis (an unusual demyelination syndrome that occurs in association with chronic hyponatremia).
• The distinction between acute hyponatremia and chronic hyponatremia has critical implications in terms of morbidity and mortality and in terms of proper corrective therapy.

Sex

Incidence is approximately equal in males and females.

Age

Hyponatremia is most common in the very young and in the very old; these groups are less able to experience and express thirst and less able to regulate fluid intake autonomously. Specific high-risk groups include the following:

• Infants fed tap water in an effort to treat symptoms of gastroenteritis
• Infants fed dilute formula in attempt to ration
• Elderly patients with diminished sense of thirst, especially when physical infirmity limits independent access to food and drink

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The number and severity of symptoms increase with the degree of hyponatremia and the rapidity with which it develops. When the serum sodium level falls gradually, over a period of several days or weeks, sodium levels as low as 110 mEq/L may be reached with minimal symptomatology. In contrast, an equivalent fall in serum sodium level over 24-48 hours may overwhelm compensatory mechanisms, leading to severe cerebral edema, coma, or brainstem herniation.
• Symptoms range from mild anorexia, headache, and muscle cramps, to significant alteration in mental status including obtundation, coma, or status epilepticus.
• Hyponatremia is often seen in association with pulmonary/mediastinal disease or CNS disorders. The ED physician should have an increased index of suspicion of hyponatremia in patients with pneumonia, active tuberculosis, pulmonary abscess, neoplasm, or asthma as well as in patients with CNS infection, trauma, or neoplasm. Patients with carcinoma of the nasopharynx, duodenum, stomach, pancreas, ureter, prostate, or uterus also have an increased risk.
• Hyponatremia is associated with numerous medications. The patient's medication list should be examined for drugs known to cause hyponatremia.
• Hyponatremia has been noted in patients with poor dietary intake who consume large amounts of beer (called beer potomania) and after use of the recreational drug N-methyl-3,4-methylenedioxyamphetamine (ie, MDMA or ecstasy). MDMA-induced hyponatremia occurs via multiple mechanisms; these include the induction of syndrome of inappropriate antidiuretic hormone (SIADH), the encouragement to drink large amounts of water to prevent unpleasant side effects of the drug, and the tendency among those intoxicated to be involved in vigorous physical activity that results in heavy sweating.
• A history of hypothyroidism or adrenal insufficiency should be sought because each is associated with hypoosmolar hyponatremia.
• Patients with clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema. These symptoms, especially when coupled with a recent history of altered fluid balance, should suggest the possibility of hyponatremia.
• • Anorexia

  • Nausea and vomiting

  • Difficulty concentrating

  • Confusion

  • Lethargy

  • Agitation

  • Headache

  • Seizures

Physical

Physical findings are highly variable and dependent on the degree and the chronicity of hyponatremia. Patients with acutely developing hyponatremia are typically symptomatic at a level of approximately 120 mEq/L. Those patients with chronic hyponatremia tolerate much lower levels.

• Most abnormal findings on physical examination are characteristically neurologic in origin.
• • Level of alertness ranging from alert to comatose

  • Variable degrees of cognitive impairment (eg, difficulty with short-term recall; loss of orientation to person, place, or time; frank confusion or depression)

  • Focal or generalized seizure activity

  • In those patients with acute severe hyponatremia, signs of brainstem herniation, including coma; fixed, unilateral, dilated pupil; decorticate or decerebrate posturing; and respiratory arrest

• In addition to neurologic findings, patients may exhibit signs of hypovolemia or hypervolemia. Determining the hydration status of the patient may help establish the etiology of the hyponatremia and direct subsequent treatment.
• • Dry mucous membranes, tachycardia, diminished skin turgor, and orthostasis suggest hypovolemic hyponatremia due to excessive loss of body fluids and replacement with inappropriately dilute fluids.

  • Pulmonary rales, S₃ gallop, jugular venous distention, peripheral edema, or ascites suggest hypervolemic hyponatremia due to excess retention of sodium and free water (ie, cirrhosis, nephrotic syndrome, congestive heart failure).

  • Patients who lack findings of hypovolemia or hypervolemia are considered to have euvolemic hyponatremia, which is consistent with such etiologies as exogenous free water load, hypothyroidism, cortisol deficiency, or SIADH.

• Other nonspecific signs include muscle weakness and cramping. Rhabdomyolysis is an occasional consequence of hyponatremia and should be considered in patients with muscle pain or tenderness.

Causes

• Hypovolemic hyponatremia develops as sodium and free water are lost and replaced by inappropriately hypotonic fluids, such as tap water, half-normal saline, or dextrose in water. Sodium can be lost through renal or nonrenal routes. Nonrenal routes include GI losses, excessive sweating, third spacing of fluids (eg, ascites, peritonitis, pancreatitis, burns), and cerebral salt-wasting syndrome.
• • Excess fluid losses (eg, vomiting, diarrhea, excessive sweating, GI fistulas or drainage tubes, pancreatitis, burns) that have been replaced primarily by hypotonic fluids
  
  
  • Acute or chronic renal insufficiency, in which the patient may be unable to excrete adequate amounts of free water
  
  
  • Salt-wasting nephropathy
  
  
  • Cerebral salt-wasting syndrome seen in patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial surgery (Cerebral salt-wasting must be distinguished from SIADH because both conditions can cause hyponatremia in neurosurgical patients, and yet the pathophysiology and treatment are different.)⁴
  
  
  • Prolonged exercise in a hot environment, especially in patients who hydrate aggressively with hypoosmolar fluids during exertion (Severe symptomatic hyponatremia has been reported in marathon runners and in recreational hikers in the Grand Canyon.)


• Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. This occurs in patients who take in excess fluids.
• • Psychogenic polydipsia, often in psychiatric patients
  
  
  • Administration of hypotonic intravenous or irrigation fluids in the immediate postoperative period
  
  
  • In a recent meta-analysis, administration of hypotonic maintenance intravenous fluids to hospitalized children has been associated with an increased incidence of acute hyponatremia compared with administration of isotonic maintenance fluids.⁵
  
  
  • Infants who may have been given inappropriate amounts of free water
  
  
  • Ingestion of sodium phosphate or sodium picosulfates and magnesium citrate combination as a bowel preparation before colonoscopy or colorectal surgery⁶
  
  
  • SIADH


• Hypervolemic hyponatremia occurs when sodium stores increase inappropriately.
• • This may result from renal causes such as acute or chronic renal failure, when dysfunctional kidneys are unable to excrete the ingested sodium load. It also may occur in response to states of decreased effective intravascular volume.
  
  
  • History of hepatic cirrhosis, congestive heart failure, or nephrotic syndrome, in which patients are subject to insidious increases in total body sodium and free water stores


• Uncorrected hypothyroidism or cortisol deficiency (adrenal insufficiency, hypopituitarism)


• Consumption of large quantities of beer or use of the recreational drug MDMA (ecstasy)


• Hyponatremia can be caused by many medications. Known offenders include acetazolamide, amiloride, amphotericin, aripiprazole, atovaquone, thiazide diuretics, amiodarone, basiliximab, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, carbamazepine, carboplatin, carvedilol, celecoxib, cyclophosphamide, clofibrate, desmopressin, donepezil, duloxetine, eplerenone, gabapentin, haloperidol, heparin, hydroxyurea, indomethacin, ketorolac, levetiracetam, loop diuretics, mirtazapine, mitoxantrone, nimodipine, oxcarbazepine, opiates, oxytocin, pimozide, propafenone, proton pump inhibitors, quetiapine, sirolimus, ticlopidine, tolterodine, vincristine, selective serotonin reuptake inhibitors, sulfonylureas, trazodone, tolbutamide, venlafaxine, zalcitabine, and zonisamide.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Cirrhosis
Nephrotic syndrome
Psychogenic polydipsia
Pseudohyponatremia
Iatrogenic
Medication effects

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The diagnosis of hyponatremia depends entirely on the ability to properly obtain a sample of the patient's serum and to accurately measure its concentration of sodium.
• When interpreting serum sodium levels, always consider the possibility of sampling error, especially when the reported value does not seem consistent with the history or physical findings.
• • Was the patient's blood sample properly labeled?

  • Was it obtained from a venous site proximal to an infusion of hypotonic saline or dextrose in water?

  • Is laboratory measurement or reporting in error?

  • If an error is suspected, a second sample should be submitted for testing before therapeutic measures are initiated.

• In addition to sampling and analysis errors, several physiologic states exist in which correct laboratory analysis yields low serum sodium levels, but these levels do not reflect a true hypoosmolar state.
• • The most common example is serum hyperglycemia.
    • Accumulation of extracellular glucose induces a shift of free water from the intracellular space to the extracellular space.

    • Serum sodium concentration is diluted by a factor of 1.6 mEq/L for each 100 mg/dL increase above normal serum glucose concentration.

    • Systemic osmolarity is normal or even increased, not decreased, as in true (ie, hypoosmolar) hyponatremia.

    • This hypertonic hyponatremia has no physiologic significance, and serum sodium concentration corrects as normoglycemia is reestablished.

  • A similar phenomenon is observed in patients treated with glycerol or mannitol in an effort to control acute glaucoma or intracranial hypertension. This phenomenon is also seen in patients with advanced renal disease who receive radiocontrast agents for diagnostic testing.

  • Hyponatremia may be noted in patients whose serum contains unusually large quantities of protein or lipid.
    • In these patients, an expanded plasma protein or lipid fraction leads to a decrease in the plasma water fraction in which sodium is dissolved.

    • Laboratory techniques that measure absolute sodium content per unit of plasma water report low sodium levels despite the fact that the concentration of sodium in serum water remains within the normal range.

    • This phenomenon, known as pseudohyponatremia, occurs when flame emission spectrophotometry or indirect potentiometry is used to assay serum sodium levels rather than direct potentiometry techniques. This occurs in approximately 60% of US laboratories.

    • Serum osmolarity remains undisturbed, and attempts at correcting serum sodium level are not indicated.

    • Hyperlipidemia that is severe enough to produce pseudohyponatremia almost always is accompanied by a notably lipemic appearance of the serum sample.

    • Hyperproteinemia of sufficient magnitude to induce pseudohyponatremia commonly is due to coexisting multiple myeloma.

• Serum osmolarity is helpful in establishing the diagnosis of true hypoosmolar hyponatremia. Serum osmolarity is abnormally low in patients with hypoosmolar hyponatremia, but it is normal in patients with pseudohyponatremia due to hyperlipidemia or hyperproteinemia and normal or elevated in patients with hypertonic hyponatremia due to serum hyperglycemia.
• Urine sodium levels are helpful in distinguishing renal causes of hyponatremia from nonrenal causes.
• • Patients with hypovolemic hyponatremia due to nonrenal causes (eg, vomiting, diarrhea, fistulas, GI drainage, third spacing of fluids) have avid renal absorption of tubular sodium and urine sodium levels of less than 20 mEq/L, whereas those with hypovolemic hyponatremia due to renal causes (eg, diuretics, salt-losing nephropathy, aldosterone deficiency) have inappropriately elevated urine sodium levels in excess of 20 mEq/L.

  • Patients with hypervolemic hyponatremia due to decreases in effective circulating volume (eg, cirrhosis, nephrosis, congestive heart failure) have urine sodium levels of less than 20 mEq/L, whereas those with renal causes of hypervolemic hyponatremia or with SIADH have urine sodium levels in excess of 20 mEq/L.

• Urine osmolarity may be helpful in establishing the diagnosis of SIADH.
• • Typically, patients with SIADH have inappropriately concentrated urine, with urine osmolarities in excess of 100 mOsm/L.

  • Patients with other forms of hyponatremia and appropriately depressed levels of ADH have urine osmolarities below 100 mOsm/L.

• Serum thyroid-stimulating hormone (TSH) and free thyroxine levels should be checked if the clinical presentation is consistent with hypothyroidism.
• Adrenal function should be assessed, via random serum cortisol levels or adrenocorticotropic hormone (ACTH) stimulation test, in patients who have recently taken oral steroids or in any patient suspected of having cortisol deficiency.

Imaging Studies

• Imaging studies may be indicated depending on the underlying etiology of the hyponatremia (eg, chest radiograph in a patient with congestive heart failure).
• Usually, a head CT scan is indicated in the patient with altered mental status to ensure that no other underlying cause for the mental status is present.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Hyponatremia is necessarily a hospital-based diagnosis, but patients may exhibit signs of severe neurologic dysfunction during prehospital evaluation and transport.

• Address acute life-threatening conditions and initiate supportive care.
• Establish reliable intravenous access and give supplemental oxygen to patients with lethargy or obtundation. In these patients, evaluate the possibility of hypoglycemia with a rapid glucose check. Administer intravenous glucose to hypoglycemic patients.
• Administer standard prehospital anticonvulsant therapy to patients experiencing seizures. Seizures secondary to hyponatremia are unlikely to respond to this therapy, but it should be administered until a definitive diagnosis and therapy are available.
• Intubate and initiate hyperventilation to reduce intracranial pressure in patients exhibiting signs of brainstem herniation (eg, obtundation; fixed, unilateral, dilated pupil; decerebrate or decorticate posturing) until a more definitive therapy can be initiated.
• Avoid giving hypotonic intravenous fluids because they may exacerbate cerebral edema.

Emergency Department Care

The ED evaluation of patients with hyponatremia includes determining the cause and the chronicity of the hyponatremic state in order to direct appropriate therapy.

• Acute hyponatremia is less common than chronic hyponatremia and typically is seen in patients with a history of sudden free water loading (eg, patients with psychogenic polydipsia, infants fed tap water for 1-2 d, patients given hypotonic fluids in the postoperative period).
• • Acute evolution of hyponatremia leaves little opportunity for compensatory extrusion of CNS intracellular solutes.
  
  
  • The ultimate danger for these patients is brainstem herniation when sodium levels fall below 120 mEq/L.
  
  
  • The therapeutic goal is to increase the serum sodium level rapidly by 4-6 mEq/L over the first 1-2 hours.
  
  
  • The source of free water must be identified and eliminated.
  
  
  • In patients with healthy renal function and mild to moderately severe symptoms, the serum sodium level may correct spontaneously without further intervention.
  
  
  • Patients with seizures, severe confusion, coma, or signs of brainstem herniation should receive hypertonic (3%) saline to rapidly correct serum sodium level toward normal but only enough to arrest the progression of symptoms. An increase in serum sodium level of 4-6 mEq/L is generally sufficient.
  
  


• Chronic hyponatremia is more common than acute hyponatremia.
• • Patients with mild symptoms and a serum sodium level of 125 mEq/L or less often have chronic hyponatremia.
  
  
  • These patients lack any history of sudden free water loading.
  
  


• Chronic hyponatremia must be managed with extreme care.
• • Correction of chronic hyponatremia has been associated with the development of central pontine myelinolysis (CPM) characterized by focal demyelination in the pons and extrapontine areas associated with serious neurologic sequelae.
  
  
  • The pathophysiology of CPM is controversial. Initial data suggested that overly rapid correction of chronic hyponatremia might lead to the development of CPM. More recently, investigators note that CPM often develops when chronic hyponatremia is complicated by hypoxia. Thus, CPM may be a form of hypoxic encephalopathy associated with hyponatremia and not a complication of therapy.⁷ Until further data are available, management should include meticulous attention to adequate oxygenation and a gradual increase in serum sodium level to 120-125 mEq/L. Serum sodium level should not be allowed to reach normal levels or hypernatremic levels within the first 48 hours.
  
  
  • Symptoms of CPM (eg, dysarthria, dysphagia, seizures, altered mental status, quadriparesis, hypotension) typically begin 1-3 days after correction of serum sodium level.
  
  
  • The condition is often irreversible; slow, cautious correction of serum sodium level and maintenance of adequate oxygenation in these patients is important.
  
  
  • Patients with hypokalemia, female gender, or history of alcoholism or liver transplant seem to be particularly prone to develop CPM.⁸ Exercise extreme caution in treating hyponatremia in these subgroups.
  
  
  • The risk of CPM appears to be minimal in patients whose chronic hyponatremia is corrected at a rate of less than 0.5 mEq/L/h or 12 mEq/L/d.
  
  
  • Patients with chronic hyponatremia and severe symptoms (eg, severe confusion, coma, seizures) should receive hypertonic saline but only enough to raise the serum sodium level by 4-6 mEq/L and to arrest seizure activity.
    
    
    • Further correction should proceed at an overall rate that is no greater than 0.5 mEq/L/h or 12 mEq/L/d.
    
    
    • Anecdotal reports suggest that therapeutic relowering of the serum sodium level with hypotonic fluids and desmopressin (DDAVP) may help avert neurologic sequelae in patients whose chronic hyponatremia is inadvertently corrected too quickly.
  
  


• In treating patients with chronic hyponatremia and mild to moderately severe symptoms, consider the cause of the hyponatremic state. Patients are classified as having hypovolemic, euvolemic, or hypervolemic hyponatremia based on historical clues and physical examination.
• • Hypovolemic hyponatremia: Patients have decreased total body sodium stores. If symptoms are mild to moderately severe, treat with isotonic saline; monitor serum sodium levels frequently to ensure that serum sodium level increases no faster than 0.5 mEq/L/h or 12 mEq/L/d.
  
  
  • Hypervolemic hyponatremia: Patients have increased total body sodium stores. Treatment consists of sodium and water restriction and attention to the underlying cause.
  
  
  • Euvolemic hyponatremia: This implies normal sodium stores and a total body excess of free water. Treatment consists of free water restriction and correction of the underlying condition. Recently developed AVP (vasopressin) receptor antagonists show promise as effective and well-tolerated therapy for SIADH. Further studies are needed to better define their role in the treatment of hyponatremia associated with SIADH.⁹

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Appropriate treatment of hyponatremia depends on the correct classification of hyponatremia, the concomitant disease state, the severity of symptoms, and the severity of hyponatremia.

Drug Category: Electrolyte supplements

Hypertonic saline may be used to rapidly increase serum sodium level in patients with severe acute or chronic hyponatremia, as manifested by severe confusion, coma, seizures, or evidence of brainstem herniation.

Drug Category: Arginine vasopressin antagonists

These agents treat hyponatremia through V2 antagonism of AVP in the renal collecting ducts. This effect results in aquaresis (excretion of free water).

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients with severely symptomatic hyponatremia manifested by coma, recurrent seizures, or evidence of brainstem dysfunction to an ICU and monitor serum sodium levels closely.
• Admit patients with a propensity toward inappropriate free water ingestion to a unit where free water access is restricted. Clozapine appears to be effective in the long-term treatment of schizophrenic patients with compulsive water drinking.
• Discontinue medications known to be associated with hyponatremia. Thiazide diuretics are a well-known cause of profound hyponatremia, especially in elderly patients, and should be discontinued in all admitted patients.

Complications

• Complications related to hyponatremia include rhabdomyolysis, seizures, permanent neurologic sequelae related to ongoing seizures or cerebral edema, respiratory arrest, and death.
• Complications related to therapy of hyponatremia include fluid overload and CPM.

Prognosis

• Prognosis is dependent on the underlying condition and the severity of disease.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the possibility of sampling or analysis error, hyperglycemia, hyperproteinemia, or hyperlipidemia before making the diagnosis of hypovolemic hyponatremia
• Failure to recognize high-risk groups, including elderly patients, patients on diuretics, infants, postoperative patients, and patients with malignancy
• Failure to quickly recognize severe acute hyponatremia and to correct it promptly, allowing ongoing risk of brainstem herniation
• Correcting serum sodium level too rapidly in patients with chronic hyponatremia (in excess of 0.5 mEq/L/h or 12 mEq/L/d), thereby incurring the risk of CPM

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. Jul 2006;119(7 Suppl 1):S30-5. [Medline].
2. Hawkins RC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. Nov 2003;337(1-2):169-72. [Medline].
3. Hoorn E, Lindemans J, Zietse R. Hyponatremia in hospitalized patients epidemiology, etiology and symptomatology. J Am Soc Nephrol. 2004;15:561(A).
4. Cole CD, Gottfried ON, Liu JK, Couldwell WT. Hyponatremia in the neurosurgical patient: diagnosis and management. Neurosurg Focus. Apr 15 2004;16(4):E9. [Medline].
5. Choong K, Kho ME, Menon K, Bohn D. Hypotonic versus isotonic saline in hospitalised children: a systematic review. Arch Dis Child. Oct 2006;91(10):828-35. [Medline].
6. Frizelle FA, Colls BM. Hyponatremia and seizures after bowel preparation: report of three cases. Dis Colon Rectum. Feb 2005;48(2):393-6. [Medline].
7. Arieff AI. Influence of hypoxia and sex on hyponatremic encephalopathy. Am J Med. Jul 2006;119(7 Suppl 1):S59-64. [Medline].
8. Murase T, Sugimura Y, Takefuji S, et al. Mechanisms and therapy of osmotic demyelination. Am J Med. Jul 2006;119(7 Suppl 1):S69-73. [Medline].
9. Olson BR. Vasopressin-receptor antagonists: a new class of agents for the treatment of hyponatremia. Endocr Metab Immune Disord Drug Targets. Sep 2006;6(3):249-58. [Medline].
10. Arieff AI. Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med. Jun 12 1986;314(24):1529-35. [Medline].
11. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med. Dec 1 1992;117(11):891-7. [Medline].
12. Bachu K, Godkar D, Gasparyan A, et al. Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). Am J Ther. Jul-Aug 2006;13(4):370-2. [Medline].
13. Backer HD, Shopes E, Collins SL, Barkan H. Exertional heat illness and hyponatremia in hikers. Am J Emerg Med. Oct 1999;17(6):532-9. [Medline].
14. Berry PL, Belsha CW. Hyponatremia. Pediatr Clin North Am. Apr 1990;37(2):351-63. [Medline].
15. Brown RG. Disorders of water and sodium balance. Postgrad Med. Mar 1993;93(4):227-8, 231-4, 239-40 passim. [Medline].
16. Canuso CM, Goldman MB. Clozapine restores water balance in schizophrenic patients with polydipsia-hyponatremia syndrome. J Neuropsychiatry Clin Neurosci. 1999;11(1):86-90. [Medline].
17. Cluitmans FH, Meinders AE. Management of severe hyponatremia: rapid or slow correction?. Am J Med. Feb 1990;88(2):161-6. [Medline].
18. Dehoorne JL, Raes AM, van Laecke E, et al. Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal enuresis. J Urol. Aug 2006;176(2):754-7; discussion 757-8. [Medline].
19. Egger C, Muehlbacher M, Nickel M, et al. A case of recurrent hyponatremia induced by venlafaxine. J Clin Psychopharmacol. Aug 2006;26(4):439. [Medline].
20. Goldszmidt MA, Iliescu EA. DDAVP to prevent rapid correction in hyponatremia. Clin Nephrol. Mar 2000;53(3):226-9. [Medline].
21. Hettema ME, Halma C. Beer drinker's hyponatraemia: a case report. Neth J Med. Mar 1999;54(3):105-7. [Medline].
22. Holmes SB, Banerjee AK, Alexander WD. Hyponatraemia and seizures after ecstasy use. Postgrad Med J. Jan 1999;75(879):32-3. [Medline].
23. Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. Sep 2006;40(9):1618-22. [Medline].
24. Norman NE, Sneed AM, Brown C, et al. Heparin-induced hyponatremia. Ann Pharmacother. Mar 2004;38(3):404-7. [Medline].
25. O'Connor RE. Exercise-induced hyponatremia: causes, risks, prevention, and management. Cleve Clin J Med. Sep 2006;73 Suppl 3:S13-8. [Medline].
26. Odeh M, Schiff E, Oliven A. Hyponatremia during therapy with amiodarone. Arch Intern Med. Nov 22 1999;159(21):2599-600. [Medline].
27. Oh MS, Carroll HJ. Disorders of sodium metabolism: hypernatremia and hyponatremia. Crit Care Med. Jan 1992;20(1):94-103. [Medline].
28. Oster JR, Singer I. Hyponatremia, hyposmolality, and hypotonicity: tables and fables. Arch Intern Med. Feb 22 1999;159(4):333-6. [Medline].
29. Sirken G, Raja R, Garces J, et al. Contrast-induced translocational hyponatremia and hyperkalemia in advanced kidney disease. Am J Kidney Dis. Feb 2004;43(2):e31-5. [Medline].
30. Soupart A, Ngassa M, Decaux G. Therapeutic relowering of the serum sodium in a patient after excessive correction of hyponatremia. Clin Nephrol. Jun 1999;51(6):383-6. [Medline].
31. Sterns RH. The treatment of hyponatremia: first, do no harm. Am J Med. Jun 1990;88(6):557-60. [Medline].
32. Trimarchi H, Gonzalez J, Olivero J. Hyponatremia-associated rhabdomyolysis. Nephron. 1999;82(3):274-7. [Medline].
33. van den Heuvel OA, Bet PM, van Dam EW. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) during treatment with the antipsychotic agents haloperidol and quetiapine [in Dutch]. Ned Tijdschr Geneeskd. Sep 2 2006;150(35):1944-8. [Medline].
34. Watanabe N, Tani M, Tanaka Y, et al. Severe hyponatremia with consciousness disturbance caused by hydroxyurea in a patient with chronic myeloid leukemia [in Japanese]. Rinsho Ketsueki. Mar 2004;45(3):243-6. [Medline].
35. Weisberg LS. Pseudohyponatremia: a reappraisal. Am J Med. Mar 1989;86(3):315-8. [Medline].
36. Wong LL, Verbalis JG. Systemic diseases associated with disorders of water homeostasis. Endocrinol Metab Clin North Am. Mar 2002;31(1):121-40. [Medline].

Article Last Updated: Jan 18, 2007