• DOI:10.7326/AITC201508040
• Corpus ID: 12434550

Hyponatremia

@article{Henry2015Hyponatremia,
  title={Hyponatremia},
  author={Daniel A. Henry},
  journal={Annals of Internal Medicine},
  year={2015},
  volume={163},
  pages={ITC1}
}

• D. Henry
• Published 2015
• Medicine
• Annals of Internal Medicine

Hyponatremia is the most common electrolyte disorder in hospitalized patients. Hospital-associated hyponatremia includes admission hyponatremia (community-acquired hyponatremia) and hospital-acquired hyponatremia. The reported incidence of hospital-associated hyponatremia ranges between 10% and 30%, depending on the definition, patient population, and case mix. It is associated with increased mortality, hospital length of stay, hospital costs, intensive care unit (ICU) days, and chance of readmission (1). Acute onset or rapid correction of severe chronic cases can cause extensive or fatal brain damage, but even mild chronic cases can have adverse outcomes, such as decreased cognition, osteoporosis, increased risk for falls, and fractures (2). Patients with no underlying disease can maintain normal plasma sodium levels. Levels are determined by the total exchangeable extracellular sodium and intracellular potassium divided by total body water. Hyponatremia is a disorder of water balance. The ability to excrete dilute urine allows people without any underlying disease to drink large amounts of water (nearly a liter an hour) without becoming hyponatremic. Maintenance of water balance requires normally functioning kidneys; sufficient urine urea (the end-product of protein metabolism); and suppressed secretion of the antidiuretic hormone, arginine vasopressin (AVP), when plasma sodium levels fall below 135 mEq/L. Hyponatremia develops if more water is ingested than can be excreted by the kidneys or if the ability to excrete a large volume of dilute urine is compromised because of kidney disease, diuretics, low protein intake, or the presence of AVP. The amount of free water excreted is determined by urine volume, sodium, and potassium. If the sum of urinary sodium and potassium is less that of plasma sodium, free water is excreted (3). A complete overview of sodium and water balance can be found elsewhere (4). Prevention Who is at risk for hyponatremia? Up to 13% of individuals participating in endurance exercise (marathons and triathlons) develop hyponatremia, which can be severe (<120 mEq/L) when water intake exceeds water loss (5). Institutionalized patients with schizophrenia can become hyponatremic, despite an intact ability to excrete maximally dilute urine, after rapidly ingesting large quantities of water. People who consume large quantities of fluid but little protein (beer potomania, or tea and toast diet) may also become hyponatremic, because decreased excretion of urea results in limited water excretion even when urine osmolality is < 100 mOsm/kg. Patients with severe kidney disease are unable to increase urine water loss and are susceptible to hyponatremia. In a study of patients with chronic kidney disease and a mean estimated glomerular filtration rate (GFR) of 50.2 ± 14.1 mL/min/1.73 m2, prevalence of hyponatremia was 13.6% at baseline and 26% of patients had >1 episode of hyponatremia during a follow-up period of 5.5 years (6). Diuretics impair the kidney's ability to excrete dilute urine. Thiazides are a particularly common cause of hyponatremia—30% of thiazide-treated patients develop hyponatremia over 10 years (7). In 1 study of patients who became hyponatremic after receiving thiazides, the electrolyte disturbance developed within 2 weeks in approximately two thirds of cases and within 5 days in half (8). In another study, patients developed hyponatremia after a median of 116 days (9). Elderly patients as well as those with low body weight and hypokalemia have an increased risk for thiazide-associated hyponatremia (9). Other drugs can interfere with the ability to dilute the urine, most commonly selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), carbamazepine, and oxcarbazepine. Hyponatremia develops in 0.5%–30% of patients receiving SSRIs and SNRIs, usually within 2 weeks. Elderly patients, those who had previous episodes of hyponatremia, and patients receiving concurrent thiazide treatment are at increased risk (10). The ability to excrete water is also limited when the posterior pituitary continues to secrete AVP despite a low plasma sodium concentration. AVP is secreted without an osmotic stimulus if circulation is inadequate, as in patients with hypovolemia or heart or liver disease. "Inappropriate secretion" of AVP occurs in the absence of both osmotic and hemodynamic stimulus. Affected patients have the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH is common in hospitalized patients because AVP is released in response to hypoxia, pain, or stress. Patients at particularly high risk include postsurgery patients, elderly persons, persons admitted to the intensive care unit, and patients with central nervous system disorders. Finally, hyponatremia is especially common among hospitalized children receiving hypotonic fluids, and fewer patients develop hyponatremia if isotonic saline rather than hypotonic saline is used to treat gastroenteritis (11). What potential measures can prevent or limit the severity of hyponatremia? Clinicians should encourage runners to drink fluids only when they have increased thirst and to monitor their body weight to avoid weight gain during exercise. Plasma sodium levels should be checked 1–2 weeks after initiation of thiazide, SNRI, and SSRI therapy, especially in patients at high risk for hyponatremia. Thiazides should be avoided in persons with high fluid or low protein intake and during acute illness. Plasma sodium levels should be measured in all hospitalized patients on admission; low sodium levels should be treated based on the underlying cause. Hypotonic fluids and thiazide diuretics should be avoided, especially in patients at increased risk for hyponatremia. Clinicians should monitor daily plasma sodium levels in patients with hyponatremia or in those at increased risk. Clinical Bottom Line: Prevention Hyponatremia is common in patients participating in endurance exercise and those receiving thiazides, SSRIs, or SNRIs. Elderly patients; those with congestive heart failure, cirrhosis, or pneumonia; and persons admitted to the ICU are at increased risk for hospital-acquired hyponatremia. Hypotonic fluids should be avoided in hospitalized patients at increased risk. Diagnosis What characteristic symptoms or physical findings should alert clinicians to the diagnosis of hyponatremia? Hyponatremic patients can be asymptomatic or have symptoms that are moderate (nausea, confusion, headache, vomiting) or severe (delirium; impaired consciousness; seizures; and, rarely, cardiorespiratory arrest). Notably, mild chronic hyponatremia (plasma sodium 125–135 mEq/L) may cause subtle neurocognitive deficits that can only be detected by careful testing; these deficits improve when the plasma sodium is normalized (12). Because hyponatremic patients are at risk for osteoporosis, falls, and hip fractures, it should be considered in the differential diagnosis of these conditions (2). What conditions should clinicians consider when evaluating patients with hyponatremia? Hyponatremia can occur when release of AVP is physiologically appropriate, due to decreased effective circulating volume, or inappropriate (that is, no physiologic reason). Urine volume decreases in response to the release of AVP, and hyponatremia will develop if water intake exceeds urinary and insensible losses of water. Patients are typically classified based on their total body sodium as hypovolemic, euvolemic, and hypervolemic (Table 1 ). Table 1. Major Causes of Hyponatremia Based on Volume Status Hypovolemic hyponatremia Patients with hypovolemic hyponatremia have a loss (renal or extrarenal) of sodium and/or potassium and water. Extrarenal sodium losses can occur with excessive sweating, pancreatitis, small bowel obstruction, vomiting, and diarrhea. If these losses are not replaced, they lead to decreased effective circulating volume and nonosmotic release of AVP. Hypovolemic hyponatremia caused by diarrhea or third-space loss results in low urine sodium levels due to increased renal sodium reabsorption. Hypovolemia caused by gastric losses of hydrochloric acid results in low urine chloride due to increased renal chloride reabsorption, but urine sodium may not be low because of metabolic alkalosis and resulting bicarbonaturia. Renal sodium losses occur with glycosuria, cerebral salt wasting (CSW), primary adrenal insufficiency, and diuretics. Loop diuretics can cause hypovolemic hyponatremia, but patients with thiazide-associated hyponatremia are usually clinically euvo-lemic (see next section). CSW is uncommon and can be difficult to differentiate from SIADH. Conditions associated with CSW include head injury, subarachnoid hemorrhage, meningitis, encephalitis, and central nervous system tumors or surgery. Patients with CSW have urinary loss of sodium and water due to a proximal sodium reabsorption deficit (also decreased reabsorption of urea and uric acid). Because it is often difficult to assess volume status in postneurosurgery patients in the ICU, finding a significant negative fluid balance on reviews of the chart—Intake/Output—may indicate CSW. In these patients, volume depletion leads to non-osmotic release of AVP and subsequent water retention. Similar to patients with SIADH, patients with CSW have decreased serum levels of sodium and increased urinary sodium and osmolality. A rare but important cause of hypovolemic hyponatremia is primary adrenal insufficiency (loss of mineralocorticoids and glucocorticoids, also known as Addison disease). Primary adrenal insufficiency leads to renal sodium wasting with subsequent volume depletion, causing non-osmotic release of AVP. Lack of cortisol also increases AVP release (see isolated glucocorticoid deficiency in euvolemic hyponatremia). Patients with Addison disease typically present with hypovolemia; hyponatremia; hyperkalemia; decreased bicarbonate; and i