Hyponatremia in Emergency Medicine: Practice Essentials, Pathophysiology, Epidemiology (original) (raw)

Overview

Practice Essentials

Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium. Clinically significant hyponatremia is relatively uncommon and is nonspecific in its presentation; therefore, the physician must consider the diagnosis in patients presenting with vague constitutional symptoms or with altered level of consciousness. Irreparable harm can befall the patient when abnormal serum sodium levels are corrected too quickly or too slowly. The physician must have a thorough understanding of the pathophysiology of hyponatremia to initiate safe and effective corrective therapy. The patient's fluid status must be accurately assessed upon presentation, as it guides the approach to correction. [1, 2]

Hypovolemic hyponatremia

Total body water (TBW) decreases; total body sodium (Na+) decreases to a greater extent. The extracellular fluid (ECF) volume is decreased.

Euvolemic hyponatremia

TBW increases while total sodium remains normal. The ECF volume is increased minimally to moderately but without the presence of edema.

Hypervolemic hyponatremia

Total body sodium increases, and TBW increases to a greater extent. The ECF is increased markedly, with the presence of edema.

Redistributive hyponatremia

Water shifts from the intracellular to the extracellular compartment, with a resultant dilution of sodium. The TBW and total body sodium are unchanged. This condition occurs with hyperglycemia or administration of mannitol.

Pseudohyponatremia

The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged. This condition is seen with hypertriglyceridemia and multiple myeloma.

Signs and symptoms of hyponatremia

Patients with clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema. These symptoms, especially when coupled with a recent history of altered fluid balance, should suggest the possibility of hyponatremia:

• Anorexia
• Nausea and vomiting
• Difficulty concentrating
• Confusion
• Lethargy
• Agitation
• Headache
• Seizures

Workup in hyponatremia

The diagnosis of hyponatremia depends entirely on the ability to properly obtain a sample of the patient's serum and to accurately measure its concentration of sodium.

Serum osmolarity is helpful in establishing the diagnosis of true hyposmolar hyponatremia. Urine sodium levels are helpful in distinguishing renal causes of hyponatremia from nonrenal causes.

Patients with hypovolemic hyponatremia due to nonrenal causes (eg, vomiting, diarrhea, fistulas, GI drainage, third spacing of fluids) have avid renal absorption of tubular sodium and urine sodium levels of less than 20 mEq/L, whereas those with hypovolemic hyponatremia due to renal causes (eg, diuretics, salt-losing nephropathy, aldosterone deficiency) have inappropriately elevated urine sodium levels in excess of 20 mEq/L.

Patients with hypervolemic hyponatremia due to decreases in effective circulating volume (eg, cirrhosis, nephrosis, congestive heart failure) have urine sodium levels of less than 20 mEq/L, whereas those with renal causes of hypervolemic hyponatremia or with syndrome of inappropriate antidiuretic hormone secretion (SIADH) have urine sodium levels in excess of 20 mEq/L.

Management of hyponatremia

The therapeutic goal in acute hyponatremia is to increase the serum sodium level rapidly by 4-6 mEq/L over the first 1-2 hours.

The source of free water must be identified and eliminated.

In patients with healthy renal function and mild to moderately severe symptoms, the serum sodium level may correct spontaneously without further intervention.

Patients with seizures, severe confusion, coma, or signs of brainstem herniation should receive hypertonic (3%) saline to rapidly correct the serum sodium level toward normal, but only enough to arrest the progression of symptoms.

Patients with chronic hyponatremia and severe symptoms (eg, severe confusion, coma, seizures) should receive hypertonic saline, but only enough to raise the serum sodium level by 4-6 mEq/L and to arrest seizure activity. After this, we recommend no further correction of the sodium for the first 24 hours.

Pathophysiology

Serum sodium concentration is regulated by stimulation of thirst, secretion of ADH, feedback mechanisms of the renin-angiotensin-aldosterone system, and variations in renal handling of filtered sodium. Increases in serum osmolarity above the normal range (280-300 mOsm/kg) stimulate hypothalamic osmoreceptors, which, in turn, cause a rise in thirst and in circulating levels of ADH. ADH increases free water reabsorption from the urine, yielding urine of low volume and relatively high osmolarity and, as a result, returning serum osmolarity to normal. ADH is also secreted in response to hypovolemia, pain, fear, nausea, and hypoxia.

Aldosterone, synthesized by the adrenal cortex, is regulated primarily by serum potassium but also is released in response to hypovolemia through the renin-angiotensin-aldosterone axis. Aldosterone causes absorption of sodium at the distal renal tubule. Sodium retention obligates free water retention, helping to correct the hypovolemic state. The healthy kidney regulates sodium balance independently of ADH or aldosterone by varying the degree of sodium absorption at the distal tubule. Hypovolemic states, such as hemorrhage or dehydration, prompt increases in sodium absorption in the proximal tubule. Increases in vascular volume suppress tubular sodium reabsorption, resulting in natriuresis and helping to restore normal vascular volume. Generally, disorders of sodium balance can be traced to a disturbance in thirst or water acquisition, ADH, aldosterone, or renal sodium transport.

Hyponatremia is physiologically significant when it indicates a state of extracellular hyposmolarity and a tendency for free water to shift from the vascular space to the intracellular space. Although cellular edema is well tolerated by most tissues, it is not well tolerated within the rigid confines of the bony calvarium. Therefore, clinical manifestations of hyponatremia are related primarily to cerebral edema. The rate of development of hyponatremia plays a critical role in its pathophysiology and subsequent treatment. When serum sodium concentration falls slowly, over a period of several days or weeks, the brain is capable of compensating by extrusion of solutes and fluid to the extracellular space. Compensatory extrusion of solutes reduces the flow of free water into the intracellular space, and symptoms are much milder for a given degree of hyponatremia.

When serum sodium concentration falls rapidly, over a period of 24-48 hours, this compensatory mechanism is overwhelmed and severe cerebral edema may ensue, resulting in brainstem herniation and death.

Epidemiology

Frequency

United States

Hyponatremia is the most common electrolyte disorder, with a marked increase among hospitalized and nursing home patients. In 2022, according to an estimate by Woolley and Singh, almost 6 million adults in the United States had hyponatremia. [3] A retrospective, single-center study by Otterness et al of 57,427 adults who came to an academic suburban emergency department (ED) in 2019 found the rate of mild, moderate, and severe hyponatremia among these patients to be 8%, 2%, and 0.1%, respectively. [4]

International

A cross-sectional study by researchers in Switzerland and Austria indicated that among emergency patients with acute kidney injury (AKI), dysnatremias are common, with 23.16% of the report’s patients having hyponatremia, and 1.4% having hypernatremia. [5]

Though clearly not indicative of the overall prevalence internationally, hyponatremia has been observed in up to 42.6% of patients in a large acute care hospital in Singapore and in 30% of patients hospitalized in an acute care setting in Rotterdam. [6, 7]

Mortality/Morbidity

Pathophysiologic differences between patients with acute and chronic hyponatremia engender important differences in their morbidity and mortality.

Patients with acute hyponatremia (developing over 48 h or less) are subject to more severe degrees of cerebral edema for a given serum sodium level. The primary cause of morbidity and death is brainstem herniation and mechanical compression of vital midbrain structures. Rapid identification and correction of serum sodium level is necessary in patients with severe acute hyponatremia to avert brainstem herniation and death.

Patients with chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema for a given serum sodium level. Brainstem herniation has not been observed in patients with chronic hyponatremia. The principal direct causes of morbidity and death are status epilepticus (when chronic hyponatremia reaches levels of 110 mEq/L or less) and cerebral pontine myelinolysis (an unusual demyelination syndrome that occurs in association with chronic hyponatremia and its rapid correction).

The distinction between acute hyponatremia and chronic hyponatremia has critical implications in terms of morbidity and mortality and in terms of proper corrective therapy.

A study of 98,411 hospitalized patients found that even mild degrees of hyponatremia were associated with increased inhospital, 1-year, and 5-year mortality rates. Mortality was particularly increased in those with cardiovascular disease or metastatic cancer or those undergoing orthopedic procedures. [8]

Similarly, a study by Ryoo et al indicated that among pediatric patients in the ED, even mild hyponatremia can have a deleterious impact. The report found that patients with mild hyponatremia had, in comparison with normonatremic patients, a significantly longer median length of stay in the pediatric ED (5.8 h vs 4.4 h, respectively), as well as a significantly increased ward admission rate (51.1% vs 35.6%, respectively), vasopressor administration rate (1.1% vs 0.6%, respectively), pediatric intensive care unit (ICU) admission rate (2.4% vs 0.9%, respectively), and mortality rate (1.5% vs. 0.3%, respectively). The investigators also noted that increased severity of hyponatremia was characterized by an increase in adverse outcomes, including in vasopressor administration, pediatric ICU admission, and mortality. [9]

Also similarly, a study by McCarthy et al found that patients with lower sodium levels at emergency admission tended to have a longer hospital stay than did those with normal sodium concentrations (6.8 vs 4.9 days, respectively), with the hyponatremic patients also having a higher 30-day inhospital mortality rate (6.4% vs 4.4%, respectively). [10]

A study in Copenhagen concluded that hyponatremia in the range of 130-137 mEq/L is associated with increased mortality rates in the general population. [11]

In the aforementioned Swiss-Austrian study, hyponatremia and severe hypernatremia were independently associated with increased mortality in emergency patients with AKI. [5]

Sex

The overall incidence of hyponatremia is thought to be approximately equal in males and females, though postoperative hyponatremia appears to be more common in menstruant females.

In contrast to the above, however, the aforementioned study by Woolley and Singh of the general rate of hyponatremia in US adults found a greater prevalence in women. [3]

Age

Hyponatremia is most common in the extremes of age; these groups are less able to experience and express thirst and less able to regulate fluid intake autonomously. Specific settings that have been known to pose particular risk include the following:

• Infants fed tap water in an effort to treat symptoms of gastroenteritis
• Infants fed dilute formula in attempt to ration
• Elderly patients with diminished sense of thirst, especially when physical infirmity limits independent access to food and drink [12, 13]

Prognosis

Prognosis is dependent on the underlying condition and the severity of disease.

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Author

Coauthor(s)

Sandy Craig, MD Residency Program Director, Carolinas Medical Center; Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill School of Medicine

Sandy Craig, MD is a member of the following medical societies: Alpha Omega Alpha, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinology, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.