- 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
Table of Contents
- 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.
- The serum sodium concentration reflects the balance between total body water (TBW) and total body sodium. (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).
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 . 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
- See algorithm in Figure 1.
- 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) , 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) 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, 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
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- Diuretic therapy
- Cerebral salt wasting
- Mineralocorticoid deficiency
- GI losses
- Sweat losses, i.e., endurance exercise
- Third spacing
- SIADH resulting from tumors, CNS pathology, drugs, or miscellaneous (pain, nausea, postoperative state)
- Glucocorticoid deficiency
- Decreased urinary solute excretion: malnutrition, beer potomania
- Excessive water intake: psychogenic polydipsia, fresh water drowning
- Congestive heart failure
- Nephrotic syndrome
- Renal failure
- Serum osmolality = [2 × Na (mEq/L)] + [BUN (mg/dL)]/2.8 + [glucose (mg/dL)]/18 + [ethanol]/4.6
- 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.
- Total sodium deficit (mEq) = [total body water in L)] × [(desired Na+) - (actual Na+)] Na+ is in mEq/L
- 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
- Total liters IV fluids needed = total Na+ deficit (mEq)/Na+ concentration in IV fluid (mEq/L)
- Serum Na+ change with 1 L of IVF = Na+ in IVF (mEq/L) - serum Na+ (mEq/L)/Total body water (L) + 1
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