Sodium

The body's normal daily sodium requirement is 1.0 to 1.5 mEq/kg (80-130 mEq, which is 80-130 mmol) to maintain a normal serum sodium concentration of 136 to 145 mEq/L (136-145 mmol/L).15 Sodium is the predominant cation of the ECF and largely determines ECF volume. Sodium is also the primary factor in establishing the osmotic pressure relationship between the ICF and ECF. All body fluids are in osmotic equilibrium and changes in serum sodium concentration are associated with shifts of water into and out of body fluid compartments. When sodium is added to the in-travascular fluid compartment, fluid is pulled intravascularly from the interstitial fluid and the ICF until osmotic balance is restored. As such, a patient's measured sodium concentration should not be viewed as an index of sodium need because this parameter reflects the balance between total body sodium content and TBW. Disturbances in the sodium concentration most often represent disturbances of TBW. Sodium imbalances cannot be properly assessed without first assessing the body fluid status.

Hyponatremia is very common in hospitalized patients and is defined as a serum sodium concentration below 136mEq/L (136 mmol/L). Clinical signs and symptoms appear at concentrations below 120 mEq/L (120 mmol/L) and typically consist of agitation, fatigue, headache, muscle cramps, and nausea. With profound hyponatremia (less than 110 mEq/L [110 mmol/L]), confusion, seizures, and coma may be seen. Because therapy is also influenced by volume status, hypo-natremia is further defined as: (a) hypertonic hyponatremia; (b) hypotonic hyponatremia with an increased ECF volume; (c) hypotonic hyponatremia with a normal ECF volume; and (d) hypotonic hyponatremia with a decreased ECF volume.16

Hypertonic hyponatremia is usually associated with significant hyperglycemia. Glucose is an osmotically active agent that leads to an increase in TBW with little change in total body sodium. For every 60 mg/dL (3.33 mmol/L) increase in serum glucose above 200 mg/dL (11.1 mmol/L), the sodium concentration is expected to decrease by approximately 1 mEq/L (1 mmol/L). Appropriate treatment of the hyper-glycemia will return the serum sodium concentration to normal.15

Hypotonic hyponatremia with an increase in ECF (hypervolemic hyponatremia) is also known as dilutional hyponatremia. In this scenario, patients have an excess of total body sodium and TBW; however, the excess in TBW is greater than the excess in total body sodium. Common causes include CHF, hepatic cirrhosis, and nephrotic syndrome. Treatment includes sodium and fluid restriction in conjunction with treatment of the underlying disorder—for example, salt and water restrictions are used in the setting of CHF along with loop diuretics, angiotensin-converting enzyme inhibitors, and spironolactone. 5

In hypotonic hyponatremia with a normal ECF volume (euvolemic hyponatremia), patients have an excess of TBW with relatively normal sodium content. In essence, there is a presence of excess free water. This is most frequently seen in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Common causes of SIADH include carcinomas (e.g., lung or pancreas), pulmonary disorders (e.g., pneumonias or tuberculosis), CNS disorders (e.g., meningitis, stroke, tumor, or trauma), and medications (e.g., sulfonylureas, antineoplastic agents, barbiturates, morphine, antipsychotics, tricyclics, nonsteroidal anti-inflammatory agents, selective serotonin reuptake inhibitors, dopamine agonists, and general anesthetics). These medications stimulate the release of antidiuretic hormone (ADH) from the pituitary gland resulting in water retention and dilution of the body's sodium stores. Treatment generally consists of fluid restriction alone. Hypertonic saline is used only when the sodium concentration is less than 110 mEq/L (110 mmol/L) and/or severe symptoms (e.g., seizures) are present. Refractory SIADH may respond to demeclocycline (Declomycin, ESP Pharma) dosed at 900 to 1,200 mg/day, lithium (various generics), furosemide (various generics), or urea. Given the limitations associated with these treatment strategies (unpredictable therapeutic effects and side effects), the arginine vasopressin antagonist conivaptan (Vaprisol, Astellas) was developed for short-term treatment of euvolemic hyponatremia. While conivaptan can also be used to manage hypervolemic hyponatremia in hospitalized patients, it should not be used for hypo-volemic hyponatremia. Conivaptan is dosed 20 mg IV over 30 minutes, followed by a 20 mg continuous infusion over 24 hours for up to 4 days.

In hypotonic hyponatremia with a decreased ECF volume (hypovolemic hyponatremia), patients usually have a deficit of both total body sodium and TBW, but the sodium deficit exceeds the TBW deficit. Common causes include diuretic use, profuse sweating, wound drainage, burns, GI losses (vomiting or diarrhea), hypoad-renalism (low cortisol and low aldosterone), and renal tubular acidosis. Treatment includes the administration of sodium to correct the sodium deficit and water to correct the TBW deficit. The sodium deficit can be calculated with the following equation :

Sodium deficit (mEq) = (TBW [in liters]) (desired Na+ concentration [mEq/L or mmol/L] - current Na+ concentration).

Although both water and sodium are required in this instance, sodium needs to be provided in excess of water to fully correct this abnormality. As such, hypertonic saline (3% NaCl) is often used. One can estimate the change in serum sodium concentration after 1 L of 3% NaCl infusion using the following equation16:

Change in serum

Na+ (mEq/L or mmol/L) = (infusate Na+ - serum Na+)/(TBW + 1).

In this formula, TBW is increased by 1 to account for the addition of the liter of 3% NaCl. Patient Encounters 4 and 5 illustrate the concepts of calculating and correcting the sodium deficit.

Depending on the severity of the hyponatremia and acuity of onset, 0.9%, 3%, or 5% NaCl can be utilized. Most patients can be adequately managed with normal saline rehydration, which is generally the safest agent. Hypertonic saline (3% or 5% NaCl) is generally reserved for patients with severe hyponatremia (less than 120 mEq/L [120 mmol/L]) accompanied by coma, seizures, or high urinary sodium losses. Roughly one-third of the sodium deficit can be replaced over the first 12 hours as long as the replacement rate is less than 0.5 mEq/h (0.5 mmol/L). The remaining two-

thirds of the deficit can be administered over the ensuing days. Overly aggressive correction of symptomatic hyponatremia (greater than 12 mEq/L [12 mmol/L] per day)

can result in central pontine myelinolysis. Given the potential for irreversible neurologic damage if untreated or if improperly treated, acute hyponatremia is an urgent condition that should be promptly treated with careful attention to monitoring serial sodium values and adjusting therapeutic infusions accordingly.18

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