Syndrome of Inappropriate Antidiuresis.

Syndrome of inappropriate antidiuresis (SIAD)-the most frequent cause of hypotonic hyponatremia-is mediated by nonosmotic release of arginine vasopressin, which promotes water retention by activating renal vasopressin type 2 (V2) receptors. There are numerous causes of SIAD, including malignancy, pulmonary and central nervous system diseases, and medications. Rare activating mutations of the V2 receptor can also cause SIAD.

Treatment Guidelines for Hyponatremia: Stay the Course.

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago.

Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day.

Background: Overly rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome. European guidelines recommend a correction to ≤10 mEq/L in 24 hours to prevent this complication. However, osmotic demyelination syndrome may occur despite adherence to these guidelines.

Estimating urine volume from the urine creatinine concentration.

Spot determinations of the urine creatinine concentration are widely used as a substitute for 24-h urine collections. Expressed as the amount excreted per gram of creatinine, urine concentrations in a single-voided sample are often used to estimate 24-h excretion rates of protein, sodium, potassium, calcium, magnesium, urea and uric acid. These estimates are predicated on the assumption that daily creatinine excretion equals 1 g (and that a urine creatinine concentration of 100 mg/dL reflects a 1 L 24-h urine volume).

Hypertonic Saline for Hyponatremia: Meeting Goals and Avoiding Harm.

Hypertonic saline has been used for the treatment of hyponatremia for nearly a century. There is now general consensus that hypertonic saline should be used in patients with hyponatremia associated with moderate or severe symptoms to prevent neurological complications. However, much less agreement exists among experts regarding other aspects of its use.

Fatal case of hospital-acquired hypernatraemia in a neonate: lessons learned from a tragic error.

A 3-week-old boy with viral gastroenteritis was by error given 200 mL 1 mmol/mL hypertonic saline intravenously instead of isotonic saline. His plasma sodium concentration (PNa) increased from 136 to 206 mmol/L. Extreme brain shrinkage and universal hypoperfusion despite arterial hypertension resulted.

Adverse Consequences of Overly-Rapid Correction of Hyponatremia.

A time-dependent loss of cell solute protects against lethal cerebral edema in hyponatremia. This adaptation, which makes survival possible when the serum sodium concentration is extremely low, also makes the brain vulnerable to injury if chronic (>48 hours) hyponatremia is corrected more rapidly than lost brain solutes can be recovered. Rapid correction of chronic hyponatremia results in programmed cell death of astrocytes and oligodendrocytes and presents clinically with a delayed onset of neurological findings, known as the osmotic demyelination syndrome.

Allostasis and the Clinical Manifestations of Mild to Moderate Chronic Hyponatremia: No Good Adaptation Goes Unpunished.

When homeostatic regulatory systems are unable to maintain a normal serum sodium concentration, the organism must adapt to demands of a disordered internal environment, a process known as "allostasis." Human cells respond to osmotic stress created by an abnormal serum sodium level with the same adaptations used by invertebrate organisms that do not regulate body fluid osmolality. To avoid intolerable changes in their volume, cells export organic osmolytes when exposed to a low serum sodium concentration and accumulate these intracellular solutes when serum sodium concentration increases.

Where Do the Salt and Water Go? A Case of Profound Hyponatremia.

Treatment of profound hyponatremia is challenging. Severe symptoms mandate correction by 4 to 6 mEq/L within hours, but with risk factors for osmotic demyelination, daily correction should be <8 mEq/L. With a therapeutic window this narrow, clinicians would like to know how serum sodium (SNa) concentration will respond to their therapy.

Treatment of Severe Hyponatremia.

Patients with severe (serum sodium ≤120 mEq/L), symptomatic hyponatremia can develop life-threatening or fatal complications from cerebral edema if treatment is inadequate and permanent neurologic disability from osmotic demyelination if treatment is excessive. Unfortunately, as is true of all electrolyte disturbances, there are no randomized trials to guide the treatment of this challenging disorder. Rather, therapeutic decisions rest on physiologic principles, animal models, observational studies, and single-patient reports.

Formulas for fixing serum sodium: curb your enthusiasm.

A variety of formulas have been proposed to predict changes in serum sodium concentration. All are based on an experiment done over 50 years ago by Edelman, who derived a formula relating the plasma sodium concentration to isotopically measured body sodium, potassium, and water. Some of these formulas fail because they do not include urinary losses of electrolytes and water.

Treatment of hyperkalemia: something old, something new.

Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin, sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals, Cary, NC), over 50 years ago. Although clinicians of that era did not have ready access to hemodialysis or loop diuretics, the other tools that we use today-calcium, insulin, and bicarbonate-were well known to them. Currently recommended insulin regimens provide too little insulin to achieve blood levels with a maximal kalemic effect and too little glucose to avoid hypoglycemia.

Complications and management of hyponatremia.

Purpose Of Review: Hyponatremia causes significant morbidity, mortality, and disability. This review considers the literature of the past 18 months to improve understanding of these complications and to identify therapeutic strategies to prevent them.

Recent Findings: Acute hyponatremia causes serious brain swelling that can lead to permanent disability or death.

Urea for hyponatremia?

Once the standard of care for cerebral edema, urea can also be used to treat hyponatremia. The 2014 European Clinical Practice Guidelines recommend urea for the treatment of the syndrome of inappropriate antidiuretic hormone, while discouraging use of vasopressin antagonists. Although there is evidence that urea can diminish hypertonic injury to brain cells caused by rapid correction of hyponatremia, clinical trials are needed that include patients at high risk to develop complications from overcorrection.