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Hyponatremia

Essential Evidence


Authors:
Kiran V. Sarikonda, MD, Assistant Professor, Michigan State University
Ralph E. Watson, MD, Associate Professor, Michigan State University

Editors:
Gary Ferenchick, MD, Chief, Division of General Medicine, Michigan State University
Mark H. Ebell, MD, Associate Professor, University of Georgia

Last updated: 2009-10-11 © 2009 John Wiley & Sons, Inc.

Overall Bottom Line

  • Hyponatremia represents a relative excess of water compared with sodium in the extracellular fluid; SORT C the most common cause is syndrome of inappropriate antidiuretic hormone (SIADH). SORT C
  • Among patients with severe hyponatremia (Na+ <115 mEq/L), 51.7% had altered sensorium, 12 and 22.5% had seizures. SORT C1
  • Serum osmolality, urine osmolality, and urine sodium are helpful to establish the diagnosis. SORT C
  • Treatment is based on the rapidity of onset of hyponatremia and presence or absence of symptoms. SORT C
  • Carefully monitor during treatment to avoid osmotic demyelination syndrome; rate of correction should not be more than 0.5 mEq/L per hour or 10-12 mEq/L in 24 hours. SORT B

Hyponatremia

Background

Hyponatremia is defined as a serum sodium concentration <136 mEq/L.

Prevalence

  • Most common electrolyte disorder encountered in hospitalized patients.
  • Prevalence at initial presentation to acute care setting reported as high as 28%. 14
  • Prevalence of hyponatremia in hospitalized patients has been reported as 15-18%.
  • Common in nursing home residents (18% prevalence).

Causes of the Condition

  • See Table 1 for a list of causes of hyponatremia.
  • At-risk populations include nursing home patients, hospitalized patients, postoperative patients, marathon runners, and patients with AIDS or ARC.

Pathophysiology

  • The serum sodium concentration reflects the balance between total body water (TBW) and total body sodium. Arginine vasopressin (AVP), the antidiuretic hormone (ADH), is released from the hypothalamus and promotes water reabsorption in response to increased osmolality or decreases in blood pressure.
  • Hyponatremia usually is a state of low osmolality with relative excess of water compared with sodium in the extracellular fluid.
  • Inappropriately high ADH levels (inappropriate for the low serum osmolality) are the most common cause for hyponatremia (SIADH).

Hyponatremia

Screening and Prevention

Bottom Line

  • Runners should drink primarily when thirsty, with input no greater than 400-800 mL/h. SORT C
  • Athletes should monitor weight, before and after exertion, as a guide to fluid consumption, with the goal to avoid weight gain. SORT C

Hyponatremia

Diagnosis

Bottom Line

  • Among patients with severe hyponatremia (Na+ <115 mEq/L), 51.7% had altered sensorium, 12 and 22.5% had seizures. SORT C1
  • Physical examination should focus on assessment of volume status (orthostatic blood pressures, skin turgor, edema) and neurological status. SORT C
  • Serum osmolality, urine osmolality, urine sodium provide important information in the differential diagnosis of hyponatremia (Figure 1). SORT C13

Differential Diagnosis

Diagnosis

Using the History and Physical

  • Most patients with mild hyponatremia are asymptomatic. Symptoms are more prominent when the decrease in serum sodium is large or occurs rapidly and usually reflect CNS dysfunction. Among patients with severe hyponatremia (Na+ <115 mEq/L), 51.7% had altered sensorium, 12 and 22.5% had seizures. 1
  • Obtaining a detailed medication history is important, because many medications can cause hyponatremia.
  • Physical examination should focus on evaluation of volume status (skin turgor, jugular venous pressure, heart rate, and orthostatic blood pressures) and neurological status.

Selecting Diagnostic Tests

  • The initial step in assessment of hyponatremia is to check serum osmolality; in normal subjects; sodium, glucose and urea are the primary circulating solutes. The normal range is from 275 to 290 mOsm/kg. Serum osmolality is expected to be low in hyponatremia, because sodium is the primary contributor to the osmolality. See Figure 1 for a suggested approach to hyponatremia.
  • Hyponatremia with normal osmolality can be seen in hyperproteinemia and hyperlipidemia. This represents a lab artifact, which is therefore known as "pseudohyponatremia," and is less of a problem with newer ion-selective electrodes.
  • Hyponatremia with elevated osmolality can be seen in hyperglycemia or with administration of hypertonic mannitol. Both contribute to hyponatremia by inducing water movement out of the cells into the extracelluar fluid compartment.
  • If a hypoosmolar state is confirmed, the next step is to determine whether the ability of kidneys to dilute the urine is intact by measuring urine osmolality. The normal response of the kidney to a hypoosmolar state is to excrete maximally dilute urine, and urine osmolality is usually less than 100 mOsm/kg. If the urine is maximally dilute, it indicates that ADH secretion is appropriately suppressed and hyponatremia is unlikely to develop in this setting of an intact urine-diluting mechanism. However, it may develop in the rare instance of patients ingesting large amounts of water.
  • In patients with hypoosmolar hyponatremia and inappropriately concentrated urine (urine osmolality >100 mOsm/kg), urine sodium concentration along with clinical volume assessment is useful to differentiate between hypovolemic and euvolemic hyponatremia. Typically, urine sodium concentration is less than 20 mEq/L in hypovolemia and is >40 mEq/L in SIADH (euvolemic hyponatremia).
  • Other tests: in patients in whom the diagnosis is not apparent after the initial evaluation, measurement of plasma uric acid, thyroid-stimulating hormone (TSH), and cortisol may be useful to establish the diagnosis.

Clinical Decision Rules

  • Serum osmolality calculator

Approach to the Patient

Hyponatremia

Treatment

Bottom Line

  • The need for treatment is guided by the rapidity of development of hyponatremia, its severity, and the presence or absence of symptoms. SORT C13
  • Prompt, controlled correction of sodium is indicated for acute symptomatic hyponatremia. The goal of treatment is to prevent seizures. Hypertonic saline may be continued until the patient is asymptomatic or until the sodium concentration reaches 118-120 mEq/L. Do not correct more than 10-12 mEq/L in 24 hours. SORT C111
  • Risk of osmotic demyelination syndrome is higher during correction of chronic hyponatremia but can be avoided by limiting the correction to <10-12 mEq/L in 24 hours. SORT B10
  • Vasopressin receptor antagonists have shown improvement in the serum sodium concentration in the short term in placebo-controlled trials. SORT C89

Drug Therapy

  • Treatment of hyponatremia should consider the rapidity of development of hyponatremia, its severity, and the presence or absence of symptoms.
  • Acute (<48 hours) symptomatic (typically CNS dysfunction) hyponatremia: initial goal is to increase serum sodium and to avoid seizures with hypertonic saline (3% sodium chloride) until the patient is asymptomatic or until sodium reaches 118-120 mEq/L. Total increase in 24 hours should not be more than 10-12 mEq/L. 111 Several formulae (Table 2) are available to estimate the sodium deficit in hypovolemic hyponatremia and to estimate the effect of 1 L IV fluids. However, the formulae rely on total body water (TBW), and the clinical estimates of TBW are not completely accurate, so frequent measurements of serum Na MUST be performed in concert with the calculation used. 7
  • Chronic (>48 hours) symptomatic hyponatremia: risk of complications from rapid correction is higher than in acute hyponatremia. Treatment is similar to acute symptomatic hyponatremia with frequent monitoring; do not correct more than 10-12 mEq/L in the first 24 hours. Deterioration of mental status or progressive neurological deficits such as pseudobulbar palsies or spastic quadriparesis, after initial improvement during correction of hyponatremia should raise suspicion of osmotic demyelination syndrome (also known as "central pontine myelinolysis").
  • Chronic (>48 hours) asymptomatic hyponatremia: treatment is based on the etiology (hypovolemic hyponatremia, SIADH, or hypervolemic hyponatremia). Rate of correction should be less than 0.5 mEq/L per hour and less than 12 mEq/L in 24 hours. 10
  • Hypovolemic hyponatremia: fluid replacement with isotonic saline until clinical euvolemia is achieved
  • SIADH: fluid, not sodium, restriction is the least toxic therapy. Drug choices are: 1) demeclocycline, which interferes with ADH action at the collecting tubule; hypersensitivity and nephrotoxicity are the limitations; 2) urea, which acts as an osmotic diuretic; palatability and azotemia limit the use; and 3) vasopressin receptor antagonists, which interfere with ADH action. Conivaptan is approved for short-term parenteral use in euvolemic and hypervolemic hyponatremia. Incomplete data on chronic use and interactions with cytochrome P450-metabolized drugs limit use.
  • Hypervolemic hyponatremia: treat with fluid restriction, vasopressin receptor antagonists.

When to Refer or Hospitalize

  • Hospitalize patients with hyponatremia who present with CNS symptoms, including mild cognitive dysfunction, representing a change from the patient's baseline. 6

Hyponatremia

Prognosis

Bottom Line

  • Mortality rates as high as 18-30% are reported for hyponatremic patients. High mortality rates reflect the severity of underlying conditions and are not influenced by treatment of hyponatremia. 5
  • Hyponatremia prior to initiation of treatment is shown to be a predictor of cardiovascular mortality in severe CHF patients. Hyponatremic patients have a substantially shortened median survival compared with nonhyponatremic patients (164 vs. 373 days). 4

Hyponatremia

Management of Special Populations

The Elderly

  • Water excretory capacity is impaired with aging, making the elderly population more vulnerable to hyponatremia. 3
  • Prevalence of hyponatremia is 15-20% in nursing home residents.
  • Mild asymptomatic hyponatremia may influence gait and attention in elderly, resulting in a higher incidence of falls. 2

Hyponatremia

References and Additional Resources

References

  1. Nzerue CM, Baffoe-Bonnie H, You W, Falana B, Dai S. Predictors of outcome in hospitalized patients with severe hyponatremia. J Natl Med Assoc. 2003;95:335-43. PubMed
  2. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119:71.e1-8. PubMed
  3. Miller M, Morley JE, Rubenstein LZ. Hyponatremia in a nursing home population. J Am Geriatr Soc. 1995;43:1410-3. PubMed
  4. Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986;73:257-67. PubMed
  5. Hochman I, Cabili S, Peer G. Hyponatremia in internal medicine ward patients: causes, treatment and prognosis. Isr J Med Sci. 1989;25:73-6. PubMed
  6. Fraser CL, Arieff AI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997;102:67-77. PubMed
  7. Nguyen MK, Kurtz I. Analysis of current formulas used for treatment of the dysnatremias. Clin Exp Nephrol. 2004;8:12-6. PubMed
  8. Konstam MA, Gheorghiade M, Burnett JC Jr, et al., Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297:1319-31. PubMed
  9. Schrier RW, Gross P, Gheorghiade M, et al., SALT, Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099-112. PubMed
  10. Sterns RH, Cappuccio JD, Silver SM, Cohen EP. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4:1522-30. PubMed
  11. Hew-Butler T, Almond C, Ayus JC, et al., Exercise-Associated Hyponatremia (EAH) Consensus Panel. Consensus statement of the 1st International Exercise-Associated Hyponatremia Consensus Development Conference, Cape Town, South Africa 2005. Clin J Sport Med. 2005;15:208-13. PubMed
  12. Han DS, Cho BS. Therapeutic approach to hyponatremia. Nephron. 2002;92(suppl 1):9-13. PubMed
  13. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120:S1-21. PubMed
  14. Hawkins RC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. 2003;337:169-72. PubMed

Hyponatremia

Tools, Tables, and Images

Tools

Tables

Table 1: Causes of Hyponatremia

Pseudohyponatremia
  • Hyperlipidemia
  • Hyperproteinemia
Isotonic or hypertonic hyponatremia
  • Hyperglycemia
  • Mannitol
Hypotonic hyponatremiaHypovolemic hyponatremia (renal sodium loss with water retention)
  • Diuretic therapy
  • Cerebral salt wasting
  • Mineralocorticoid deficiency
Hypovolemic hyponatremia (extrarenal sodium loss with water retention)
  • GI losses
  • Sweat losses, i.e., endurance exercise
  • Third spacing
Euvolemic hyponatremia
  • SIADH resulting from tumors, CNS pathology, drugs, or miscellaneous (pain, nausea, postoperative state)
  • Glucocorticoid deficiency
  • Hypothyroidism
  • Decreased urinary solute excretion: malnutrition, beer potomania
  • Excessive water intake: psychogenic polydipsia, fresh water drowning
Hypervolemic hyponatremia
  • Congestive heart failure
  • Cirrhosis
  • Nephrotic syndrome
  • Renal failure

Table 2: Formulas Used in Management of Hyponatremia

  1. Serum osmolality = [2 × Na (mEq/L)] + [BUN (mg/dL)]/2.8 + [glucose (mg/dL)]/18 + [ethanol]/4.6
  2. Total body water (L) = (body weight in kg) × (correction factor) Correction factor is 0.6 for children and nonelderly men, 0.5 for elderly men and nonelderly women, and 0.45 for elderly women.
  3. Total sodium deficit (mEq) = [total body water in L)] × [(desired Na+) - (actual Na+)] Na+ is in mEq/L
  4. Sodium concentration in IV fluids is 0 mEq/L in 5% dextrose in water, 34 mEq/L in 0.2% saline, 77 mEq/L in 0.45% saline, 154 mEq/L in 0.9% saline, and 513 mEq/L in 3% saline
  5. Total liters IV fluids needed = total Na+ deficit (mEq)/Na+ concentration in IV fluid (mEq/L)
  6. Serum Na+ change with 1 L of IVF = Na+ in IVF (mEq/L) - serum Na+ (mEq/L)/Total body water (L) + 1
Example: A 60-kg young male presents with serum sodium of 116 mEq/L. Assuming a desired sodium level of 140 mEq/L, the sodium deficit = (60 × 0.6) × (140 - 116), which is a total sodium deficit of 864 mEq. Because 1 L of 0.9% saline has approximately 154 mEq of sodium, it would take 864/154 = 5.6 L of normal saline to increase the sodium to 140 mEq/L. However, the rate of correction should not exceed 0.5 mEq/L per hour or 12 mEq/L per 24 hours, so the 24 mEq/L rise in sodium should be achieved in no less than 48 hours. Thus, the rate of IV fluids is 5.6 L divided by 48 hours which is 116 mL/h of normal saline.

ICD9 Codes

DiagnosisICD9 code
Hyponatremia276.1