Hyponatremia (defined as a serum sodium concentration < 135 mEq/L) is one of the most common disorders of electrolytes in clinical practice, occurring in up to 30% of both acutely and chronically hospitalized patients.49 The majority of patients who present to the ED with hyponatremia do not require emergent management; however, patients who present with severe hyponatremia need immediate attention and an appropriate rate of correction to prevent devastating neurologic deficits or even death. Recognizing and appropriately instituting treatment is critical for this life-threatening electrolyte emergency.
Brain Adaptation And Osmotic Demyelination Syndrome
To understand the reasoning behind the recommended guidelines for treating severe hyponatremia (including the pitfalls of overly rapid correction), it is necessary to review how the brain adapts to hyponatremia and the time course over which this occurs. Brain adaptation to hyponatremia begins fairly quickly after an acute fall in serum sodium and is complete within 2 days.50 Initially, water moves from the hyposomolar extracellular compartment to the relatively hyperosmolar cells. There is a loss of interstitial sodium and water in the cerebrospinal fluid due to increased hydraulic pressure. Within hours, intracellular potassium, sodium, and organic solutes are pumped out of the cell. This adaptation helps reduce the severity of neurologic symptoms and the risk of cerebral edema. Once adaptation is complete, however, the neurons are hyposmolar and, if exposed to excess sodium (as may occur during overcorrection of the hyponatremia), are prone to suffering cellular injury; this is termed osmotic demyelination syndrome (ODS). (See Figure 1.)
ODS is an irreversible or only partially reversible neurologic injury that may include dysarthria, dysphagia, paraparesis or quadriparesis, behavioral disturbances, lethargy, confusion, obtundation, or coma. The most important risk factors for the development of ODS include the serum sodium concentration at presentation, the duration of hyponatremia, and the rate of correction. While no rate of correction is totally protective, ODS can usually be avoided by limiting correction of chronic hyponatremia (ie, hyponatremia lasting > 48 h) to no more than 10 to 12 mEq/L in 24 hours.51 Certain patients may be at a particularly high risk of ODS secondary to underlying abnormalities in cerebral osmotic regulation. These include patients with alcoholism, malnutrition, hypokalemia, and burns as well as elderly women on diuretics.52
Considerations For The Treatment Of Severe Hyponatremia
When considering whether or not to treat hyponatremia with HTS, 3 questions must first be answered:
The corrected serum sodium should correlate with the patient’s neurologic symptoms. Most patients with severe neurologic symptoms from hyponatremia have serum sodium levels < 115 mEq/L. If a patient’s serum sodium level does not correlate with his neurologic symptoms, consider an alternative etiology for their presentation (such as toxicological, infectious, or metabolic).
Patients who present with acute severe hyponatremia (ie, hyponatremia for < 48 h) have had little time for their brain to adapt and are more prone to cerebral edema, but they are less likely to develop ODS with rapid correction. These patients usually present with seizures, encephalopathy, or focal neurologic signs. The most common clinical scenario an emergency physician might encounter is water intoxication that is secondary to psychosis, ecstasy use, or endurance sports (such as marathon running).
Patients with chronic hyponatremia (ie, hyponatremia lasting > 48 h) have had time for their brain to adapt, are less prone to cerebral edema, and are more likely to develop ODS with rapid correction. These patients generally present with only mild neurologic symptoms (such as gait disturbances, confusion, lethargy, and nausea). Sometimes, the duration of hyponatremia is not known. In this setting, it is safest to assume that the patient has chronic hyponatremia and to treat accordingly.
Patients who have only mild symptoms of hyponatremia (eg, confusion) are unlikely to have severe neurologic sequelae from their hyponatremia, if treated conservatively. Only patients with severe neurologic symptoms such as coma, seizure, or focal neurologic signs warrant treatment with HTS.
Treatment Of Severe Hyponatremia
Optimal treatment strategies with HTS for severe hyponatremia are based on expert consensus and are not well defined. (See Table 2.) There is no study that compares the efficacy and safety of different treatment regimens. Therefore, patients treated with HTS should have frequent neurologic checks and measurement of serum sodium levels every 1 to 2 hours.
The initial goal of treating hyponatremic patients with severe neurological symptoms is to reverse the cerebral edema with 3% HTS. Perhaps the easiest method of administration was developed by the Second International Exercise-Associated Consensus Development conference.53 They recommend that any athlete with severe hyponatremia and encephalopathy be treated immediately with a bolus infusion of 100 mL of 3% NaCl to acutely reduce brain edema. Two additional 100-mL boluses of 3% NaCl should be repeated at 10-minute intervals if there is no clinical improvement. This would translate to 6 mL/kg of 3% NaCl for a 50-kg woman, which is enough to raise the serum sodium concentration by 5 to 6 mEq/L. While this guideline was developed to treat those with exercise-associated hyponatremia, it is probably a reasonable regimen to extrapolate to all patients with severe hyponatremia, regardless of etiology or duration.
After the initial treatment with HTS to address the serious signs and symptoms of hyponatremia, the subsequent rate of correction should be closely monitored. The goal is not to correct the patient’s serum sodium to “normal” values. For patients with either chronic hyponatremia or hyponatremia of an unknown duration, an expert panel suggested a correction of no more than 10 to 12 mEq/L during the first 24 hours of treatment.51 They also suggested that, due to a sometimes unexpected “autocorrection” during the course of treatment, it may be best to aim for undercorrection (more near the rate of 8 mEq/L/d). It is important to emphasize that these recommendations were derived from relatively small numbers of patients and that they only give an estimate of reasonable correction rates.
Jeffrey A. Holmes, MD
February 4, 2013