37: Fluid & Electrolyte Abnormalities

Fluid and electrolyte abnormalities are common among older adults as a consequence of age-related functional changes in the kidney, multiple comorbidities, and polypharmacy. This chapter discusses concepts of sodium disorders, potassium disorders, and nocturnal polyuria as they relate to older adults.

General Principles in Older Adults

Older adults are more vulnerable to developing sodium disorders as a result of age-related changes in water and sodium metabolism. Older adults may have an impaired ability to excrete water and to dilute urine because of reductions in the number of functioning nephrons and decreased renal blood flow with age, predisposing them to water overload and possible hyponatremia. Geriatric patients also tend to be on multiple medications that are associated with sodium disorders, such as diuretics and psychotropic medications (Table 37–1). Reviewing all medications is an integral part of evaluating patients with sodium disorders.

Hyponatremia is commonly defined as a serum sodium concentration less than 135 mEq/L (or 135 mmol/L). This occurs in 7% to 11% of older patients and up to 50% of older hospitalized patients.

Pathogenesis

Hypervolemic Hyponatremia

In older adults, the most common etiology of hyponatremia is increased intake and subsequent retention of water. This type of hyponatremia is commonly described as dilutional or hypervolemic hyponatremia. These patients typically will exhibit edematous states, resulting from conditions such as congestive heart failure, cirrhosis, or the nephrotic syndrome. These conditions decrease effective circulating blood volume, leading to increased antidiuretic hormone (ADH) secretion, which results in water retention. Dilutional hyponatremia can also be iatrogenic, as a result of administration of excess IV fluids, especially in hospitalized patients.

Hypovolemic Hyponatremia

Although less common, salt depletion with or without loss of extracellular fluid, can cause depletional or hypovolemic hyponatremia. Hypovolemic hyponatremia can be caused by renal losses (eg, diuretic use) or from extrarenal losses, such as vomiting, diarrhea, laxative abuse, ostomies, or the presence of large burns. A particular etiology to consider in geriatric patients is restricted sodium intake, especially in the setting of tube feeding.

Euvolemic Hyponatremia

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder in which water excretion is partially impaired because of the inability to suppress secretion of ADH. Patients with SIADH will generally appear euvolemic. Many diseases that are common in older adults are associated with SIADH such as central nervous system disorders and malignancies (Table 37–2). In addition, although rare, older age itself may be a risk factor for SIADH. Medications (Table 37–1) are also an important cause of SIADH. As a result of multimorbidity, older adults are at higher risk for polypharmacy, typically defined as the use of 5 or more medications. In older patients, careful medication review is imperative. Other causes of euvolemic hyponatremia include hypothyroidism and adrenal insufficiency. An elevated serum potassium level in conjunction with hyponatremia should increase suspicion for adrenal insufficiency. Lastly, it is important to include pseudohyponatremia in the differential, which can occur in the setting of hyperlipidemia or hyperproteinemia.

Clinical Findings

Symptoms & Signs

The primary symptoms for sodium disorders (hyper- or hyponatremia) are neurologic. Slow changes in serum sodium concentration (chronic hyponatremia) are more likely to be asymptomatic as the brain has had time to adapt to osmotic changes. Symptoms associated with hyponatremia include anorexia, nausea, vomiting, headache, weakness, loss of coordination, muscle cramps, agitation, tremors, disorientation, psychosis, delirium, seizures, and coma. Patients with chronic hyponatremia are more prone to have marked gait and attention impairments leading to increased risk of falls.

Evaluation of Volume Status

After obtaining the history, the next step in the work-up of a patient with hyponatremia is to evaluate the volume status. Patients who are hypovolemic may have dry mucous membranes, tachycardia, and/or relative or orthostatic hypotension. On the other hand, hypervolemic patients may have increased jugular vein pressures, crackles at lung bases, ascites, and/or peripheral edema.

Laboratory Findings

On laboratory exam, serum osmolality, urine osmolality, and urine sodium should be obtained. Hyponatremia secondary to pseudohyponatremia or hyperglycemia will have a normal serum osmolality while all other etiologies will demonstrate a low serum osmolality. Urine osmolality of more than 100 mOsm/kg is consistent with an inability to normally excrete water, which is generally caused by SIADH or low effective circulating volume depletion, such as true hypovolemia, heart failure, and cirrhosis. Urine sodium is useful in differentiating between the two. A urine sodium of less than 25 mEq/L suggests hypovolemia and more than 40 mEq/L suggests SIADH.

Treatment

Treatment of hyponatremia is based on the presence of symptoms, the severity of symptoms when present, and the acuity of the condition.

Acute Hyponatremia

Asymptomatic patients with acute hyponatremia may be treated like those with chronic hyponatremia (see below). Otherwise, therapy is aimed at correcting the major symptomatic consequences of hyponatremia while avoiding induction of central pontine myelinolysis (CPM). In patients with severe hyponatremia (serum sodium below 120 mEq/L) with severe neurologic symptoms such as seizures, the use of 3% hypertonic IV saline is recommended. In the first 2–3 hours, the saline should be infused to increase the serum sodium by 1–2 mEq/L per hour. Then the infusion should be slowed to increase the serum sodium an additional 8–12 mEq/L over the next 24 hours. The rate of infusion for each patient based on the desired change in the serum sodium can be calculated using the following formula:

Change in serum sodium in older men = (infusate Na – serum Na)/[(0.50 × body weight) + 1]

Change in serum sodium in older women = (infusate Na – serum Na)/[(0.45 × body weight) + 1]

These equations have limitations and thus the actual change in serum sodium may differ. The equations should be used to guide the initial infusion rate, which should then be adjusted by obtaining frequent serum sodium levels to avoid rapid overcorrection, which can cause CPM. Symptoms of CPM include behavioral disturbances, movement disorders, and seizures, usually occurring several days after treatment. Furosemide can be used in conjunction with IV hypertonic saline to limit treatment-induced expansion of extracellular fluid volume.

Chronic Hyponatremia

The goal is to identify underlying causes and intervene appropriately. For example, patients who are hyponatremic because of volume depletion secondary to diuretic use should hold their diuretics and receive volume repletion, such as IV isotonic saline. In contrast, patients with SIADH will not benefit from IV isotonic saline as the infused salt will be excreted in the concentrated urine, resulting in net retention of water and worsening of their hyponatremia. In these patients, long-term water restriction may be needed. Use of demeclocycline in patients who do not respond to water restriction is also an option.

General Principles in Older Adults

Older adults have a decreased ability to concentrate urine and a reduced sensation of thirst, which, if combined with limited access to fluids, may predispose older adults to water depletion and hypernatremia. Hypernatremia is commonly defined as a serum sodium greater than 148 mEq/L (or 148 mmol/L). Hypernatremia is associated with high mortality. In hospitalized patients 65 years and older, the prevalence is approximately 1%, and the mortality rate is 7 times that of age-matched hospitalized patients. In a study of patients with hypernatremia in short-term and long-term geriatric care units, the mortality was roughly 40%.

Pathogenesis

There are 4 clinical conditions that can lead to hypernatremia in older patients. In many patients, there will be overlap of these conditions. Hypernatremia usually results from excessive loss of body water relative to the loss of sodium, and in older patients hypernatremia is most often associated with inadequate fluid intake. Hypernatremia secondary to excess salt intake is rare.

Insufficient Intake

There are multiple reasons why older adults may have inadequate fluid intake. Many older adults, have impaired thirst or hypodipsia. Cognitive impairment such as underlying dementia and decreased level of consciousness such as delirium especially in the hospital setting present barriers to adequate hydration. Another common cause of insufficient fluid intake in older adults is impaired mobility or dependence on caregivers for access to water. Older adults with dysphagia may also have inadequate fluid intake.

Loss of Water

This is seen with increased insensible losses (eg, from fever) and in diabetes insipidus. Diabetes insipidus (DI) is a syndrome characterized by hypotonic polyuria from either inadequate ADH secretion (central DI) or inadequate renal response to ADH (nephrogenic DI). Nephrogenic DI can be induced by drugs such as lithium and cisplatin. Patients with DI usually compensate by increasing their fluid intake; thus, when they have adequate access to water, most patients maintain normal sodium concentrations. It is when they have limited access to water or have inadequate intake, that they usually develop hypernatremia.

Water Deficiency in Excess of Salt Deficiency

This can be caused by gastrointestinal losses, such as vomiting and diarrhea; or renal losses, such as osmotic diuresis secondary to hyperglycemia, solute load with parenteral nutrition, tube feeding, or IV contrast. Diuretics can lead to excess renal loss as well. Skin losses can occur from burns and severe dermatitis.

Salt Excess

This is usually iatrogenic, for example, from the administration of excess saline or sodium bicarbonate.

Clinical Findings

Symptoms of hypernatremia include confusion, restlessness, hyperreflexia, progressive obtundation, coma, and, in severe cases, death.

Treatment

The main goal of treatment is to administer dilute fluids to replace the water deficit and to limit further water loss. The first step is calculation of the total body water deficit.

Water deficit in older men = body weight × 0.50(Pna–140)/Pna

Water deficit in older women = body weight × 0.45(Pna–140)/Pna

where Pna = sodium concentration in mEq/L, weight in kg.

The next step is to determine the rate at which to correct the hypernatremia. In general, efforts should be made to replace the total water deficit over a 48-hour period, with a decrease in serum sodium of no more than 0.5 mEq/L per hour. The serum sodium level should be monitored frequently. Replacement fluid should be similar in osmolality as that of the bodily fluid lost. In general, hypotonic fluids, usually 0.5% normal saline (NS), should be used for replacement. In the setting of asymptomatic or chronic hypernatremia, oral fluid replacement is preferred. However, because hypernatremia is usually a result of insufficient intake from impaired thirst or inability to respond to thirst, older patients more commonly require hospitalization and correction with IV fluids.

Treatment of DI differs in that (in addition to the correction of water deficit as above) efforts must be made to reduce the excessive urinary water loss. In central DI, intranasal or oral desmopressin is used. In nephrogenic DI, treatment includes sodium restriction and administration of a thiazide diuretic plus a prostaglandin synthesis inhibitor such as indomethacin or ibuprofen.

General Principles in Older Adults

Although less common than disorders of sodium balance, disorders of potassium balance can have serious consequences for older adults. Older adults are susceptible to disorders of potassium balance for several reasons—underlying changes in the structure and function of the kidney that occur with aging, common chronic medical conditions that disrupt potassium homeostasis, and polypharmacy that affects potassium regulation.

Hypokalemia is typically defined as a serum potassium concentration of <3.5 mEq/L.

Pathogenesis

Hypokalemia is usually a result of depletion of serum potassium from extrarenal losses, intrarenal losses, or iatrogenic causes. Rarely, hypokalemia can result from an acute shift of potassium from the extracellular compartment into cells.

Extrarenal Losses

Extrarenal losses of potassium occur in the GI tract. Chronic diarrhea can cause a loss of serum potassium because of an increase in stool volume. Among older adults, diarrhea is associated with many commonly prescribed medications, including antibiotics, proton pump inhibitors, allopurinol, neuroleptics, serotonin reuptake inhibitors, and angiotensin II receptor blockers. More rarely, diarrhea may occur because of malabsorptive disorders or GI infections. Habitual laxative use can also result in loss of potassium. As many as one-third of older adults suffer from chronic constipation and resort to chronic use of laxatives.

Though not a cause of potassium depletion, decreased nutritional intake of potassium can potentiate the hypokalemia caused by extrarenal losses. Older adults may have limited nutrition because of impaired access as a result of financial constraints or institutionalization, or because of poor dentition or swallowing disorders.

Intrarenal Losses

Intrarenal losses of potassium occur as a result of conditions that directly affect the kidney. These include renal tubular acidosis (types I and II), vitamin D deficiency, malignancy, medications, acute kidney injury, postobstructive and osmotic diuresis (Table 37–3). Other conditions that may result in intrarenal losses of potassium, although less commonly in older adults, include diabetic ketoacidosis and ureterosigmoidectomy.

Iatrogenic Causes

The most common cause of hypokalemia among older adults is medications. Thiazide and loop diuretics are commonly prescribed to older adults for management of blood pressure, congestive heart failure, and edema. Mineralocorticoids and glucocorticoids may also affect potassium levels, although they do not exert direct effects on the kidney. Medications that cause transcellular shifts in potassium are generally transient with reversibility within several hours of administration. Selective β₂-sympathomimetic agonists such as pseudoepinephrine and albuterol, xanthines including theophylline, and high doses of calcium channel blockers such as verapamil can cause transient shifts of potassium into cells (Table 37–4).

Clinical Findings

Although mild hypokalemia is generally asymptomatic, more severe hypokalemia (less than 3 mEq/L) can result in neuromuscular weakness, including paralysis and respiratory muscle dysfunction, rhabdomyolysis, GI disruption including constipation and ileus, and cardiac dysregulation evidenced by electrocardiogram (ECG) changes and cardiac arrhythmias.

Treatment

Because only a small portion of total-body potassium is present in the extracellular space, estimation of potassium deficiency from serum potassium levels is crude. In general, each 1 mEq/L decrease is equivalent to between 150 and 400 mEq/L in total-body potassium. For older adults with decreased muscle mass, the lower estimates are most appropriate.

Treatment of hypokalemia involves replacement of potassium. However, supplemental administration of potassium can be dangerous because of the high risk of severe hyperkalemia, particularly in hospitalized patients and those with underlying chronic kidney disease. Intravenous potassium is associated with the highest risk of hyperkalemia and should be avoided if possible. Oral potassium supplementation is preferable. Generally potassium chloride is the preferred choice for potassium repletion because it effectively treats most causes of hypokalemia. Potassium phosphate may be used in situations where phosphate replacement is also required. Potassium bicarbonate may be used in the setting of metabolic acidosis. For older patients on diuretics, instruction in adequate potassium intake through the diet is important. Also combining a potassium-sparing diuretic (amiloride, triamterene, or spironolactone) may offset potassium loses from thiazide or loop diuretics. However, caution must be taken to avoid overcorrection that results in hyperkalemia.

Hyperkalemia is typically defined as a serum potassium concentration >5 mEq/L.

Pathogenesis

Hyperkalemia is the result of underlying physiologic and pathophysiologic changes that commonly occur in older adults which predispose to elevated potassium levels and is augmented by iatrogenic factors. Age-related changes in the kidney include the development of glomerulosclerosis and arteriosclerosis which lead to a gradual decline in glomerular filtration rate over time. Although these structural and functional changes do not cause hyperkalemia, they do predispose older adults to experience hyperkalemia if also affected by medical conditions or medications that disrupt potassium balance.

Older adults are more likely to experience pathologic changes to the kidney as a result of common comorbidities such as diabetes, hypertension, and urinary obstruction. These comorbidities can lead to disruptions in renin and aldosterone activity which impair renal tubular potassium secretion into the urine resulting in increased serum potassium levels. The degree of hyperkalemia can be affected by the intravascular volume status, the amount of dietary potassium intake, medications, and presence of kidney failure.

Intravascular Volume Status

Older adults are at risk for decreased intravascular volume for several reasons. First, older adults commonly experience dehydration secondary to hypodipsia. Decreased fluid intake leads to increased sodium and water reabsorption (hypernatremia) and decreased potassium secretion with subsequent hyperkalemia. Older adults are also subject to intravascular volume depletion as a result of volume overload states, such as congestive heart failure or other edematous states where there is third spacing of fluid. Persons with hypoaldosteronism (primary adrenal failure caused by autoimmune disease, hemorrhage, or tumor infiltration), hyporeninemic hypoaldosteronism (commonly caused by diabetes), or tubular unresponsiveness to aldosterone (interstitial renal disease) are most vulnerable to the effects of decreased intravascular volume.

Potassium Intake

Increased potassium consumption is also a cause of hyperkalemia. This may result from increased dietary potassium or potassium supplements. Older adults have higher rates of potassium supplement use as these are commonly prescribed concurrently with loop or thiazide diuretics to prevent hypokalemia. In addition, older adults may use nonprescription supplements that contain potassium either out of concern about potassium deficiency or inadvertently, not realizing that such supplements contain potassium as one of the ingredients. Similarly, older adults may be using salt substitutes in their diets to control hypertension or edema. Many of these salt substitutes use potassium rather than sodium and can result in a potentially dangerous potassium load to predisposed individuals.

Medication-Induced Hyperkalemia

The primary etiology of hyperkalemia in older adults is drug-induced. The incidence of hyperkalemia among those patients taking offending medications approaches 10% with older adults at increased risk. Several commonly prescribed classes of medications can cause hyperkalemia (Table 37–5).

Kidney Failure

Hyperkalemia occurs in kidney failure because potassium excretion is proportional to glomerular filtration rate (GFR). As GFR declines, the ability of the kidney to effectively excrete potassium also declines. The degree of hyperkalemia is dependent on potassium intake and is affected by compensatory kidney potassium secretion mechanisms and losses of potassium in the stool. When hyperkalemia occurs in the setting of mild or moderate decreases in GFR (>10% normal), another etiology should be identified.

Clinical Findings

The clinical consequences of hyperkalemia generally occur at severe elevations of serum potassium (>6.5 mEq/L). The clinical manifestations involve neuromuscular signs including weakness, ascending paralysis, and respiratory failure, muscle cramping and cardiac abnormalities including chest pain and progressive ECG changes (peaked T waves → flattened p waves → prolonged PR interval → idioventricular rhythm → widened QRS with deep S waves → ventricular fibrillation → cardiac arrest).

Treatment

Diagnosis of hyperkalemia is made by laboratory evaluation. Elevated potassium levels should be confirmed with a repeated plasma sample as problems with drawing or processing blood samples may result in hemolysis, which releases intracellular potassium, leading to inaccurate serum potassium levels. Once hyperkalemia is confirmed, any exogenous potassium should be discontinued. An ECG should be obtained to determine if there are any changes related to hyperkalemia. The presence of ECG changes determines the urgency of treatment.

Acute Hyperkalemia

Emergency treatment of severe hyperkalemia with associated ECG changes may be accomplished using several rapidly acting agents.

Calcium infusion—

Calcium temporarily antagonizes the cardiac effects of hyperkalemia and allows for the institution of more definitive treatment. The effects of calcium on hyperkalemia are immediate but short-lived, lasting only 30–60 minutes. Calcium may be administered as calcium gluconate or calcium carbonate. Calcium gluconate 1000 mg (10 mL of 10% solution) infused over 3–5 minutes may be administered peripherally. Calcium chloride 500–100 mg (5–10 mL of 10% solution) also can be infused over 3–5 minutes. However, calcium chloride should be delivered via central or deep vein as it can cause vein irritation and extravasation can lead to tissue necrosis.

Insulin with glucose—

Insulin temporarily translocates potassium into cells by enhancing the activity of the Na-K-ATPase pump in skeletal muscle. Glucose should be administered simultaneously with insulin to avoid hypoglycemia. Several regimens are generally used. Ten units of regular insulin in 10% dextrose solution can be infused over 60 minutes. Alternatively, a bolus of 10 units regular insulin is given followed by 50 mL of 50% dextrose solution (25 g glucose). Serum glucose should be monitored closely because of the risks of hypoglycemia.

β2-Adrenergic agonists—

β₂-Adrenergic agonists also enhance the activity of the Na-K-ATPase pump in skeletal muscle and activate the Na-K-2Cl cotransporter to translocate potassium into cells. Albuterol can be administered as a nebulized solution (10–20 mg in 4 mL of saline) over 10 minutes with peak effect at 90 minutes or as an IV infusion (0.5 mg) with peak effect at 30 minutes.

Sodium bicarbonate—

Sodium bicarbonate raises the systemic pH resulting in release of hydrogen ions with movement of potassium into cells to maintain electroneutrality. Bicarbonate is used to treat hyperkalemia in setting of acidosis and is not recommended as single-agent therapy. In the acute setting, one 50 mL ampule of sodium bicarbonate (50 mEq) IV over 5–10 minutes can be administered.

Potassium Removal

The acute treatment of hyperkalemia described above is useful in lowering dangerously high serum potassium levels temporarily but additional therapy is required to remove potassium. There are several modalities available to remove potassium from the body.

Loop or thiazide diuretics—

Loop and thiazide diuretics increase potassium loss in the urine. These diuretics are particularly effective for patients with normal to moderately impaired kidney function.

Sodium polystyrene sulfonate—

Sodium polystyrene sulfonate or Kayexalate is a cation exchange resin that binds potassium in the gut and causes an osmotic diuresis when combined with sorbitol. Sodium polystyrene sulfonate is effective at lowering serum potassium levels when given in multiple doses over several days. Sodium polystyrene sulfonate can be used to control hyperkalemia in patients with chronic kidney disease who are not yet on dialysis. This can be delivered orally 15–30 g every 4–6 hours or as a retention enema with 50 g in 150 mL tap water (without sorbitol) for severe hyperkalemia. Lower doses can be used for chronic hyperkalemia. The main concern with use of sodium polystyrene in sorbitol suspension is the potential for intestinal necrosis. Intestinal necrosis is a particular concern for older adults with postoperative ileus, those receiving opiates, and kidney transplant recipients.

Dialysis—

Dialysis is indicated for the treatment of severe hyperkalemia, hyperkalemia that does not respond to other measures, or conditions where cellular breakdown can release large amounts of potassium such as crush injuries or tumor lysis syndrome. Hemodialysis is the preferred modality because of the faster rate of potassium removal.

General Principles in Older Adults

Nocturnal polyuria is a syndrome in which excessive urine is produced at night. Nocturnal polyuria is highly prevalent in older adults, with estimates suggesting that nearly 90% of adults older than age 80 years are affected. Nocturnal polyuria causes disruptions in sleep, which can lead to daytime somnolence, cognitive impairment, and poorer quality of life.

Nocturnal polyuria is considered to be present when 1 of the following criteria are met: (a) urine production during 8 hours of sleep is >33% of 24-hour urine production; (b) nighttime urine production rate is >0.9 mL/min; and (c) 7 PM to 7 AM urine volume is >50% of total 24-hour volume.

Pathogenesis

The cause of nocturnal polyuria is usually multifactorial. First, there are aging-related changes in the diurnal pattern of ADH secretion that lead to increased urine flow at night, sometimes exceeding that during the day. There are also structural and functional changes in the urinary tract that commonly occur with age, such as decreased functional bladder capacity, bladder outlet obstruction caused by benign prostatic hypertrophy, and detrusor overactivity. These structural and functional changes in the urinary tract can predispose older adults to infections which can cause nocturnal polyuria. Also, many medical conditions that affect older adults, such as diabetes mellitus, DI, congestive heart failure, chronic kidney disease, hypokalemia, and hypercalcemia, may also cause nocturnal polyuria. Finally, many common drugs, such as diuretics, calcium channel blockers, lithium, selective serotonin reuptake inhibitors, caffeine, and alcohol may also contribute to nocturnal polyuria.

Treatment

A careful history and review of medical conditions and medications is important in identifying the etiology and recommending treatment. If urinary tract infection is present, then treatment with antibiotics is indicated and reevaluation is necessary to determine if nocturnal polyuria has resolved. If there is no evidence of infection, then nonpharmacologic treatments, such as reduction of fluid intake and avoidance of diuretics and caffeine before bedtime, should be attempted. In patients with edema, use of compression stockings and elevation of the legs during the day is recommended. In women with urge incontinence, Kegel exercises and scheduled voiding during the day may be helpful. In patients with chronic illnesses contributing to nocturia, treating the underlying disease is the primary treatment.

There are several pharmacologic treatments. Diuretics taken 6–8 hours prior to bedtime may decrease a patient’s overall volume status, thus decreasing nocturnal urine production. If benign prostatic hypertrophy is present, α blockers and 5α-reductase inhibitors can be used. In women with detrusor overactivity and urge incontinence, medications such as oxybutynin, propantheline, and solifenacin may be useful. However, caution should be exercised when prescribing anticholinergic medications to older adults because of increased risk of falls. Starting with low doses and slowly escalating to the lowest effective dose is recommended.