Older adults who are immobile also may have a concomitant increase in total body water with lower serum sodium. Some of the many other causes include postoperative complications, acute illness, hypocortisolism, and hypothyroidism.2,15
Patients with hypervolemic hyponatremia may have a history of liver and kidney failure, and the physical examination may reveal jugular venous distension, peripheral edema, and pulmonary congestion.7,10,16 If the patient is not taking diuretics, the fractional excretion of sodium (FENa) can be calculated; the result should be less than 1% if the patient has cardiac failure or cirrhosis, and greater than 1% in patients with acute kidney injury or chronic kidney disease.7
Patients with euvolemic hyponatremia have total body sodium close to normal without extracellular fluid volume abnormalities such as edema, ascites, pulmonary congestion, or pleural effusion.7,10,16 With euvolemic hyponatremia, clinicians must rule out hypothyroidism, hypopituitarism, pharmacologic stimulation of ADH (Table 1), severe emotional and physical stress including psychosis, anesthesia, and surgery before considering a diagnosis of SIADH. Laboratory studies to evaluate SIADH include thyroid stimulating hormone (TSH) and cortisol response to adrenocorticotropic hormone (ACTH).7
Patients with SIADH generally have low urine output (for example, 500 mL/24 hours) with a concomitant increase in urine sodium concentration.7 For a diagnosis of SIADH, the patient must be euvolemic, with a urine osmolality greater than 100 mOsm/kg and low serum osmolality.17 The patient also should be evaluated for pulmonary, nervous system, vascular, and neoplastic conditions, which are responsible for more than 90% of cases of SIADH.7,10
Hyponatremia can present with varied tonicity:
- Hypertonic hyponatremia occurs when another osmole, such as glucose, draws water into the intravascular space, diluting the serum sodium content. This type of hyponatremia can occur in patients with hyperglycemia and after mannitol or contrast media administration.4,8,10,18
- Isotonic hyponatremia, also known as pseudohyponatremia, is a rare finding often resulting from hyperlipidemia or hyperproteinemia causing an artificially low serum sodium due to a dilutional effect.4,10,18 In such cases the plasma may be isotonic or hypertonic to the intracellular fluid, but neither results in intracellular fluid shifts and will not result in adverse reactions.4
- Hypotonic hyponatremia is the most common of the hyponatremias, occurring when the patient has excess free water relative to serum sodium levels.3,18 Common causes of hypotonic hyponatremia are listed in Table 2.
Hypotonic hyponatremia can be further subdivided based on the patient's volume level, and many causes of hyponatremia can be categorized by volume status.
Euvolemic hyponatremia is most common due to the abundance of disease states presenting with concomitant SIADH.3,5 This type of hypotonic hyponatremia is characterized by an increase in total body water with no concurrent change to serum sodium levels. SIADH, the most common cause of hyponatremia, is more common in older adults.17
Hypervolemic hyponatremia results when both total body water and sodium retention are increased with overall water retention exceeding sodium retention.
Hypovolemic hyponatremia is defined as sodium loss that far surpasses water loss in spite of both water and sodium levels decreasing.3,10,18–20
PATHOPHYSIOLOGY AND RISK FACTORS
The principal mechanisms of water and sodium homeostasis in the body are controlled by hypothalamic osmoreceptors, which regulate the secretion of ADH and perception of thirst.2,5,21 When osmoreceptors sense slight increases in plasma tonicity, ADH is released from the posterior pituitary, causing increased kidney tubule permeability, increased water reabsorption, and formation of more concentrated urine.2
In older adults, osmoreceptors are hypersensitive compared with younger adults, as shown by hypertonic fluid administration and water deprivation tests.5 The same phenomenon can be observed by administering metoclopramide to stimulate vasopressin, resulting in significantly higher ADH release in older adults.5 Hypersensitivity of these mechanisms along with increased time to excrete excess water predispose older adults to hyponatremia.5
Structural changes in the aging kidney also can contribute to the development of hyponatremia. These changes include glomerular sclerosis of the superficial cortex, tubular atrophy, interstitial fibrosis, and hyalinosis of the arterioles. This leads to functional declines including decreases in glomerular filtration rate (GFR), creatinine clearance, renal plasma flow, and the ability to dilute and concentrate filtrate.2,22 Normally, older adults are able to compensate for these changes and sustain a normal balance of electrolytes. However, illness or injury may potentiate loss of electrolyte homeostasis and lead to dysnatremias and volume dysregulation.2
Hormonal changes with aging result in decreased renin and renin activity, decreased aldosterone, and may contribute to heightened excretion of sodium into the urine, especially in patients with hypovolemia.2 Natural age-related changes also occur in atrial natriuretic hormone secretion and the renin-angiotensin-aldosterone system (RAAS). These changes alter homeostatic regulation of fluid balance and may lead to hyponatremia.5
Risk factors for hyponatremia in older adults include administration of hypotonic fluid, low dietary sodium intake, low-sodium enteral nutrition formulas for primary nutrition, previous brain injury, age, and idiopathic SIADH. Whites and Hispanics appear to be at higher risk than African Americans.5 Thiazide diuretics and selective serotonin reuptake inhibitors are more likely to cause hyponatremia in older adults than in younger adults.2 Clinicians must take steps to avoid promoting hyponatremia in older adults because of these structural and functional alterations, comorbid conditions, and medications that can lead to fluid and sodium dysregulation.
Patients may present with varying signs and symptoms, including headache, muscle weakness, nausea, vomiting, lethargy, disorientation, depressed reflexes, or seizures.1 The severity depends on many factors, including the duration of the condition, serum sodium levels, and the acute or chronic nature of onset.23,24
The symptoms of mild-to-moderate hyponatremia—lethargy, weakness, irritability, nausea, abdominal pain, confusion, and tachypnea—also may be characteristic of hypothyroidism, hypoglycemia, viral or psychiatric illness, and various other electrolyte imbalances. Patients with more severe hyponatremia may present with a head injury resulting from a fall or seizure. Head injury secondary to a fall also may be characteristic of nonhyponatremia-related seizures, stroke, polysubstance abuse, and cardiac emergencies.10
Acute hypotonic hyponatremia This electrolyte imbalance arises in less than 48 hours.24 Common symptoms include mental status changes (confusion, lethargy, and irritability), anorexia, and nausea.7 The rapid change in sodium levels may cause cerebral edema and intracranial hypertension (Figure 1), which can quickly progress to brainstem herniation, seizure, coma, and respiratory arrest.9,24 In very severe cases (serum sodium less than 125 mEq/L), patients may suffer permanent neurologic damage, coma, or death.1 Cerebral edema, if present, is visible on CT and MRI. Acute hyponatremia is a medical emergency and must be corrected promptly to avoid irreversible consequences.25 Within a few hours of onset, brain volume begins adaptation via excretion of intracellular and extracellular solutes to stimulate water loss and decrease brain swelling.24 Within 2 days, intracranial pressure can essentially stabilize. Although brain adaptation helps reduce symptoms of hyponatremia, it also greatly increases the patient's risk for osmotic demyelination.9 Prompt and appropriate treatment is essential to prevent further neurologic damage.
Chronic hyponatremia This type of hyponatremia has a gradual onset (over more than 48 hours), and occurs when the brain volume is able to adapt with concomitant fluid loss; brain volume is near-normal in spite of the significant decrease in serum sodium levels.23,24 Modest symptoms were thought to be the only manifestation of chronic hyponatremia.16 However, recent insight into older adults has revealed that manifestations of chronic hyponatremia may include gait instability leading to increased falls and fractures, as well as attention difficulties.15,16,23,24,26–28 Osteoporosis has also been linked to chronic hyponatremia because patients with chronic hyponatremia mobilize bone matrix sodium stores at an increased rate and also have heightened osteoclast activity.15,16,23,24 Chronic hyponatremia can lead to increased osteoporosis and fractures and increased patient morbidity and mortality.15,23,24
Hospitalized patients with hyponatremia have a 50% greater risk of death than normonatremic patients; older adults with hyponatremia have a doubled risk of death compared with normonatremic older adults.2,29–31 Studies evaluating mortality in patients with various severities of hyponatremia found an overall increase in mortality regardless of degree of severity, and increased mortality especially in patients with multiple underlying illnesses.2,29–31 Hyponatremia is also a marker in heart, liver, and kidney disease or injury, as well as brain tumors, brain hemorrhages, and malignancy.31 Waikar and Chawla found that underlying illness contributed more to mortality than the severity of hyponatremia; Whelan adjusted for such factors and still found hyponatremia independently and significantly associated with mortality.30–32
Obtain a thorough history and physical examination, assessing the patient's medications, neurologic state, and extracellular fluid volume status. These objective methods may add insight into volume status to help better classify the suspected hyponatremia. For example, patients with hypovolemic hyponatremia may present with vomiting, diarrhea, diuretic use, hyperglycemia with glucosuria, increased thirst, weight loss, orthostatic hypotension, tachycardia, dry mucous membranes, decreased skin turgor, and decreased capillary refill.10,16
To differentiate GI and renal losses, calculate the patient's FENa, the ratio between sodium excreted via urine and the amount of sodium filtered and reabsorbed by the kidney. The calculation is based on the concentrations of sodium and creatinine in the blood and urine.33 The values needed are serum sodium (PNa), urine sodium (UNa), serum creatinine (PCr), and urine creatinine (UCr), and the formula is FENa = ((UNa x PCr)/(PNa x UCr) x 100.34
In patients with GI losses from vomiting and diarrhea, the FENa should be within normal limits and less than 1%. In patients with renal losses, such as from diuretics, glucosuria, and bicarbonaturia, the FENa will be greater than 1%.7 Clinical presentation should always be taken into account when examining FENa.
Patients with hyponatremia should undergo a full laboratory workup to identify potential causes of the disorder, differentiate between types of hyponatremia, and investigate other comorbidities. Urine osmolality, serum osmolality, and urine sodium concentrations are the three cornerstone tests that help to differentiate between causes of the electrolyte disorder (Table 3).35,36
Confirmed normal or elevated serum osmolality suggests the presence of another osmole, aside from sodium, that draws water out of the cells and into the intravascular space. Most commonly, low serum osmolality is found on laboratory analysis, and in that case, the next step is urinalysis, to determine urine osmolality and whether the patient's renal function is intact. Maximally dilute urine (less than 100 mOsm/L) indicates normal kidney function and may suggest primary polydipsia or low solute intake; excessively concentrated urine (more than 200 mOsm/L) indicates some impairment of renal filtration or dilution as in SIADH or cerebral salt wasting (urinary sodium concentrations greater than 40 mEq/L).16,37 These diagnostic tests will guide later treatment because management is based on the apparent cause of hyponatremia.
Evidence of osmotic demyelination is not usually visible on CT or MRI until 6 to 10 days after clinical symptoms appear.7,25 Uric acid generally rises with volume depletion and is low in SIADH.3 Arterial sodium can be measured with a blood gas device to rule out suspected pseudohyponatremia.4 To aid in determining the cause of hyponatremia, assess serum osmolality as promptly as possible.
Management depends on the patient's clinical presentation (including volume status and severity of symptoms) and the cause of the electrolyte imbalance.4,10,19 Because hyponatremia is potentially fatal, prompt intervention is important. The appropriate rate of correction depends on whether the patient has acute or chronic hyponatremia.4,7,12 Next, assess the patient's volume status to determine the appropriate correction strategy (Table 4).4,7
Acute hyponatremia Acute onset of symptomatic hyponatremia can be a medical emergency leading to cerebral edema, brain herniation, and cardiopulmonary arrest, and requires rapid correction with 3% hypertonic saline.7 If the patient is hypervolemic because of heart failure or underlying cardiovascular disease, also administer a loop diuretic to avoid volume overload.4,7,10 Closely monitor patients receiving hypertonic saline for extracellular volume status, neurologic symptoms, and serum sodium trends to avoid rapid overcorrection.4,7
Once the patient's severe signs and symptoms have resolved, discontinue 3% hypertonic saline, reassess volume status, and tailor treatment based on the patient's volume status and cause of the hyponatremia (Table 4).4
Chronic hyponatremia Patients with chronic hyponatremia are unlikely to present with serious signs and symptoms. If they do, carefully tailor sodium correction to reverse serious signs and symptoms only and avoid overcorrection.4 Too-rapid correction of chronic hyponatremia with hypertonic saline can cause excessive loss of intracellular water, cell shrinkage, and osmotic demyelination syndrome (damage to the myelin sheaths covering axons of the brainstem, which can lead to permanent neurologic damage).1,4,7 Patients with osmotic demyelination syndrome may show improved mental status initially, accompanied by neurologic declines, paresis, flaccid paralysis, dysarthria, dysphagia, hypotension, and possible death.4 Patients who are malnourished; abuse alcohol; have hypokalemia, burns, or advanced liver disease; and older women on thiazide diuretics have much lower thresholds for osmotic demyelination and should be corrected much more slowly.3,4,7
Patients with chronic hyponatremia who do not display serious signs and symptoms do not need immediate treatment to correct serum sodium, but may be mildly symptomatic, putting them at increased risk for falls and development of osteoporosis.4,15,27 Fluid restriction is the treatment of choice; instruct patients not to take in more fluid than they excrete in urine and insensible losses.3,4,13,38 Water excretion can be calculated from solute intake and urine osmolarity.4
Other chronically hyponatremic patients have shown asymptomatic sodium levels as low as 115 to 120 mEq/L due to cerebral adaptation. In such cases, consider reversible causes of excess water (such as continuous maintenance fluid infusions or excess oral fluid intake) and eliminate them when possible.4
If the timing of hyponatremia development is unknown, clinicians should assume the hyponatremia is chronic and should apply conservative measures, avoiding too-rapid correction to prevent osmotic demyelination.4,9 Patients presenting with severe neurologic signs and symptoms require immediate increases in serum sodium, whether hyponatremia is acute or chronic.4,20 When the patient's neurologic symptoms improve, treatment can be adjusted depending on how long the hyponatremia is thought to have been present. In nonemergent cases, initial treatment should be based on volume status (Table 4).4,12
RATE OF CORRECTION
A patient's serum sodium level should be increased by no more than 10 to 12 mmol/L in the first 24 hours and then by no more than 18 mmol/L in the first 48 hours of therapy.3,4,7,12 Rates of correction should be even lower in patients with chronic hyponatremia and signs or symptoms of cerebral edema. Terminating fluids before the serum sodium has increased 10 to 12 mmol/L in the first 24 hours is also important because the sodium level can continue to rise after fluids have been discontinued.4
As emphasized previously, great care must be taken to avoid overcorrection. If overcorrection results, discontinue all sodium-containing therapies and immediately administer IV D5W.10 Although more research is needed about using desmopressin to manage sodium overcorrection, this drug may be given for prevention and reversal of serum sodium overcorrection.4,39 Desmopressin decreases sodium by 2 to 9 mmol/L without serious adverse reactions and can be given alone or with D5W.
EMERGING THERAPIES: VASOPRESSIN ANTAGONISTS
Vasopressin antagonists are fairly new drugs that inhibit the V1A, V1B, or V2 subtypes of vasopressin receptors and block ADH action.40 Vasopressin antagonists are indicated for use in patients with severe hyponatremia (serum sodium less than 125 mEq/L) or in those with less severe hyponatremia who are symptomatic and ineffectively treated with fluid restriction.41 Based on recent studies, therapy with vasopressin antagonists appears promising; however, further recommendations are necessary to ensure that they can be used safely to correct hyponatremia.3,4,7,38,40 Concerns about vasopressin antagonists include their high cost, the adverse reaction of increased thirst, and whether they can be used safely in patients with cirrhosis-related ascites.4,7,40
Because of the limited experience in using vasopressin antagonists to treat signs and symptoms of cerebral edema in patients with hyponatremia, 3% hypertonic saline remains the gold standard for treatment.
Hyponatremia is a complex condition that demands a systematic approach to diagnosis and management.23 In older adults, hyponatremia is one of the most common electrolyte imbalances and is associated with increased mortality.11 Careful attention to common causes, clinical presentation, laboratory diagnosis, and appropriate treatment will help practitioners safely reverse this potentially life-threatening condition. The primary treatment for hyponatremia is to identify and correct underlying causes and, if necessary, correct sodium imbalances slowly to lessen the chance of neurologic disease. Vasopressin antagonists have emerged as promising new treatments that may improve outcomes.29
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Keywords:© 2014 American Academy of Physician Assistants.
hyponatremia; older adults; acute; chronic; long-term care; syndrome of inappropriate antidiuretic hormone