Electrolyte Disorders

Chapter 39


Electrolyte Disorders image




Electrolyte disturbances are common among patients in intensive care units (ICUs). Anticipation and prompt recognition of these disorders are crucial skills for the physician providing care for critically ill patients. Appropriate treatment depends on an understanding of the underlying pathophysiologic processes, as well as an appreciation of the often complex and multisystem disorders affecting these patients. This chapter addresses electrolyte disorders of potassium, calcium, magnesium, and phosphorus. Separate chapters address acid-base disorders (Chapters 82 and 83) and disorders of water homeostasis and the serum sodium concentration (Chapter 84).



Potassium Disorders


Approximately 98% of total body potassium is intracellular, a balance that is maintained by the Na+-K+-ATPase and the influence of several hormones such as insulin and catecholamines. Most of the clinical effects of potassium disturbances are related to alterations of the cellular membrane potential that result from changes in the extracellular potassium concentration. The normal potassium concentration in extracellular serum ranges from 3.5 to 4.5 mmol/L. Because the cellular membrane potential is a function of the ratio of the intracellular to extracellular potassium concentration, and the intracellular potassium concentration is relatively constant in the range of 120 to 150 mmol/L, even relatively small changes in the extracellular potassium concentration can significantly alter the cellular membrane potential. Significant clinical consequences are rarely seen, however, unless the potassium concentration in the blood falls below 3 mmol/L (hypokalemia) or rises above 5.5 mmol/L (hyperkalemia).



Hyperkalemia


Box 39.1 lists common acute causes of hyperkalemia relevant to the ICU setting. Before pursuing a diagnosis of hyperkalemia, it is important to consider pseudohyperkalemia, when an elevation in measured serum potassium concentration is due to potassium movement out of cells into the serum during or after the blood specimen has been obtained. In pseudohyperkalemia, the true potassium concentration in blood and plasma is normal, but when measured in the serum by the clinical laboratory, an elevated value is reported. Major causes of pseudohyperkalemia include hemolysis resulting from mechanical trauma during venipuncture, severe thrombocytosis (> 400,000/mm3) or leukocytosis (> 100,000/mm3), repeated fist clenching during blood drawing (resulting from the release of potassium by exercising muscle), and, less commonly, hereditary spherocytosis and familial pseudohyperkalemia. Diagnosis of pseudohyperkalemia caused by the release of intracellular potassium from platelets or white blood cells within the specimen container can be made by obtaining a plasma (unclotted) potassium concentration, which is normally < 0.5 mmol/L lower than the serum potassium concentration.



BOX 39.1   Causes of Hyperkalemia





Multiple factors are necessary to overcome the several autoregulatory mechanisms protective of the extracellular potassium concentration, in order to produce acute or chronic hyperkalemia. Homeostatic mechanisms maintain balance between intracellular and extracellular potassium (internal balance) and control renal (and to a much lesser extent gastrointestinal [GI] tract) potassium excretion (external balance) to prevent development of significant hyperkalemia even despite large increases in potassium intake. Consequently, clinically significant sustained hyperkalemia generally requires both disturbed internal balance and impaired renal excretion. Impaired adrenal function or impaired responsiveness to the effect of adrenal hormones, particularly aldosterone, is also often present, as a consequence of intrinsic adrenal gland disease or medications that inhibit aldosterone synthesis or interfere with the renin-angiotensin-aldosterone system (see Box 39.1).



Clinical Manifestations


Because of its critical role in establishing transmembrane potential, elevations in serum potassium concentration affect cardiac membrane potential and neuromuscular transmission with related clinical effects predominantly involving the myocardium and skeletal muscles. The earliest manifestation, usually seen when potassium concentration is above 5.5 to 6 mmol/L, is peaking of the T waves on the electrocardiogram (ECG) with shortening of the QT interval (Figure 39.E1A) image. More severe hyperkalemia (i.e., > 6 mEq/L) is first associated with prolongation of the PR interval and QRS complex duration. As the potassium concentration rises further, the P wave may be lost entirely, the QRS complex widens further and merges with the T wave producing a “sine wave” pattern; ventricular fibrillation or ventricular standstill with cardiac arrest may occur (Figure 39.E1B image). However, serum potassium concentration poorly correlates with observed ECG changes in hyperkalemia, and the effect of hyperkalemia on myocardium is influenced by acidosis, hyponatremia, and hypocalcemia, all of which increase the neuromuscular effects of hyperkalemia. Careful monitoring and prompt treatment of patients with even minor ECG findings are essential.


The most prominent neuromuscular effects of hyperkalemia are muscle weakness and fatigue; eventually paralysis occurs, usually seen only with severe hyperkalemia (> 8 mmol/L). Impairment of respiratory muscle function may also occur with severe hyperkalemia.



Treatment


Prompt reversal of hyperkalemia and prevention of its cardiac effects are necessary to mitigate the life-threatening nature of hyperkalemia-induced cardiac arrhythmias. In all hyperkalemic patients, excessive potassium intake in the diet, medications, and enteral or parenteral nutrition should be eliminated. If possible, discontinue medications that impair urinary potassium excretion (see Box 39.1). In the setting of the previous ECG or other neuromuscular manifestations, treatment should proceed in three phases.



1 Stabilization of Cardiac Membrane Potential

Calcium salts antagonize the cardiac effects of high extracellular potassium concentration through unclear mechanisms. They do not lower the serum potassium concentration. Intravenous (IV) administration of one 10-mL ampule of 10% calcium gluconate (1000 mg in 10 mL, which contains 4.65 mEq Ca++) given over 2 to 3 minutes will typically reverse ECG manifestations of hyperkalemia within minutes. This dose can be repeated after 5 minutes if ECG abnormalities persist. Constant ECG monitoring is essential. Calcium chloride is sclerosing and should be avoided or given only via central venous access. Caution is necessary in patients taking digitalis, as hypercalcemia can provoke digitalis toxicity. If required, these patients should receive a slow IV infusion of calcium over 20 minutes.



2 Shift of Potassium into Cells

The movement of extracellular potassium into cells will lower the extracellular potassium concentration and allow time for initiating more definitive therapy aimed at reducing total body potassium. Insulin and beta-adrenergic agonists are the most potent and reliable agents used for this purpose; both work by stimulating the Na+-K+-ATPase.


Regular insulin (10 units as a rapid intravenous bolus) along with 50 mL of 50% dextrose in patients who are not hyperglycemic (to prevent insulin-induced hypoglycemia) lowers the serum potassium concentration by 0.5 to 1 mmol/L, an effect that peaks at about 60 minutes and lasts for several hours.


Beta-agonists also stimulate the Na+-K+-ATPase and cellular potassium uptake. Albuterol sulfate 10 to 20 mg via nebulizer over 10 minutes (a dose 5 times higher than that used for asthma treatment) lowers serum potassium concentration within about 90 minutes and can lower the serum potassium concentration to an extent similar to insulin (i.e., ~0.5 to 1 mmol/L), although a response is seen less consistently than with insulin. Subcutaneous terbutaline (7 mcg/kg) can also be used with similar effect. Because of their cardiac effects, beta-agonists should not be used in patients with active ischemic coronary artery disease.


By buffering extracellular H+ and raising blood pH, sodium bicarbonate given as 50 mL of 7.5% solution intravenously over several minutes can lead to an exchange of intracellular hydrogen for extracellular potassium. Intravenous sodium bicarbonate is not as effective as insulin or beta-agonists in lowering the serum potassium concentration, especially in the absence of severe acidosis, and risks volume overload and hypernatremia. In addition, the hypertonic nature of the solution will cause water movement from the intracellular to extracellular space, carrying via convection the intracellular potassium concentration of 120 meq/L, thus potentially increasing serum potassium concentration. As such, the use of IV sodium bicarbonate should be limited to patients with hyperkalemia and concomitant severe acidemia.





3 Reduction of Total Body Potassium

Although these therapies will stave off cardiac disaster associated with acute hyperkalemia, only a reduction of total body potassium will prevent persistent hyperkalemia. With adequate renal function, treatment with a thiazide or loop diuretic (with supplemental IV fluid if needed) increases urinary excretion of potassium, although the extent and rate of potassium excretion with diuretics are neither consistent nor significant enough to be relied on for treatment of other than very mild acute hyperkalemia. Loop diuretics in particular can be useful in the prevention of chronic hyperkalemia.


The cation exchange resin sodium polystyrene sulfonate (SPS; Kayexalate) binds potassium (and to a lesser extent calcium and magnesium) in exchange for sodium when present in the lumen of the GI tract; each gram of SPS binds approximately 1 mmol of potassium and releases up to 2 mmol of sodium. SPS can be given orally or by retention enema. Because oral SPS tends to be constipating, 15 to 30 grams is usually administered in a 20% sorbitol solution to prevent constipation. Sorbitol also causes an osmotic diarrhea, which, independent of the SPS, can help to lower the serum potassium concentration. A powdered form that can be mixed with sorbitol or other liquids is also available. The dose can be repeated every 4 to 6 hours as necessary. Higher oral doses (60 g) can be used, but the sodium load must be considered in patients with advanced renal failure and heart failure. An enema of 30 to 60 grams of SPS mixed with tap water (not sorbitol) should be retained in the colon for at least 30 to 60 minutes and preferably up to 4 hours; this can be repeated in 2 to 4 hours if needed. Colonic necrosis has been reported in patients receiving SPS orally in sorbitol or by enema; this risk appears to be greatest in patients who have recently had abdominal surgery, so avoid SPS administration in these patients.


Hemodialysis will rapidly and definitively reduce total body potassium and is indicated if the more conservative measures described earlier are not successful. Dialysis is particularly likely to be necessary in patients with severe hyperkalemia that is associated with tissue breakdown (such as rhabdomyolysis or tumor lysis syndrome), acute kidney injury (especially if oliguric), and in patients with chronic end-stage renal disease who are already on dialysis. Hemodialysis can remove as much as 50 mmol of potassium per hour and lower the serum potassium concentration by 2 to 3 mmol/L or more within a few hours of starting the hemodialysis treatment. Remember that a serum potassium concentration obtained shortly after the completion of a hemodialysis treatment will be lower, often substantially, than one obtained a few hours later, as potassium moves from cells to the extracellular fluid compartment. The initial low postdialysis potassium concentration should not prompt potassium supplementation in patients dialyzed to treat hyperkalemia. Peritoneal dialysis and continuous renal replacement therapy are both less efficient at removing potassium than hemodialysis, but can be used in mild hyperkalemia.



Hypokalemia


Hypokalemia can develop from an internal shift of potassium from the extracellular to intracellular spaces without a deficiency of total body potassium. More commonly, hypokalemia results from total body potassium deficits that can be in the range of several hundreds of mmol because of excessive losses via the GI tract, kidneys, or both, often exacerbated by inadequate oral intake. Box 39.2 lists important causes of hypokalemia (serum potassium concentration < 3.5 mmol/L) that are commonly seen in ICU patients. Hypokalemic patients with primarily extrarenal potassium losses and intact renal resorptive capacity should have daily urinary potassium excretion < 20 mmol and urinary potassium concentration < 10 mmol/L. Levels exceeding these values suggest at least some element of urinary potassium wasting.



BOX 39.2   Causes of Hypokalemia





Clinical Manifestations


Even though hyperkalemia has primarily neuromuscular and cardiac effects, hypokalemia has more varied effects impacting multiple organ systems, although patients with mild hypokalemia or hypokalemia that develops slowly may be asymptomatic.


Gastrointestinal symptoms include constipation that can progress to paralytic ileus, depending on the severity of the hypokalemia. Musculoskeletal effects range from mild generalized weakness, cramps, paresthesias, and myalgias with mild hypokalemia to loss of deep tendon reflexes, rhabdomyolysis, and skeletal and respiratory muscle paralysis at serum potassium concentration < 2 to 2.5 mmol/L. ECG changes include ST segment depression, reduced T-wave amplitude, and development of prominent U waves. Cardiac arrhythmias associated with hypokalemia include sinus bradycardia, paroxysmal tachycardia, atrioventricular blocks, premature atrial and ventricular beats, and ventricular tachycardia and fibrillation. Use of digitalis glycosides, concomitant cardiac ischemia, and hypomagnesemia potentiate the likelihood of hypokalemia-associated cardiac arrhythmias. Hypokalemia also impairs urinary concentrating ability with symptoms of nocturia and polyuria because of nephrogenic diabetes insipidus and increases renal ammoniagenesis, which can precipitate or worsen hepatic encephalopathy. It augments renal hydrogen ion (H+) excretion, promoting development of metabolic alkalosis (Chapter 83). If long-standing and severe, hypokalemia can cause renal interstitial fibrosis, tubular atrophy, and renal cyst formation associated with reduced glomerular filtration rate and chronic kidney disease (CKD).



Treatment


Potassium repletion along with reversal of underlying and ongoing potassium losses is the mainstay of therapy for hypokalemia. Anticipate total body potassium deficits of at least 200 to 400 mmol in most patients with clinically significant hypokalemia. At serum potassium concentration < 2 mmol/L the deficit may exceed 600 to 800 mmol.


Take care during repletion of critically ill patients with long-standing hypokalemia, as they may not be able to rapidly shift administered potassium loads intracellularly. Overly aggressive intravenous repletion can result in dangerous hyperkalemia. Therefore, oral or enteral repletion with 40 mmol of elemental potassium as potassium chloride capsules, tablets, or elixir (potassium citrate or potassium bicarbonate may be given in patients with metabolic acidosis) is safest for mild and moderate hypokalemia. Monitor the serum potassium concentration every 4 to 6 hours and administer repeat doses as needed until the potassium concentration normalizes and remains within the normal range. The serum potassium concentration can acutely rise by as much as 1.5 mmol/L after an oral dose of 60 meq but will typically subsequently decline because of cellular potassium uptake until the total body potassium deficit has been corrected.


When hypokalemia is severe or oral administration is contraindicated, IV potassium chloride can be given in concentrations of 20 to 60 mmol/L. Avoid higher concentrations, which can be painful and sclerosing to veins and be potentially dangerous if infused too rapidly. In patients who cannot tolerate large volumes of fluid, more concentrated solutions can be infused into a large central vein but not via catheters with their tips in the distal superior vena cava or right atrium, as direct delivery of high concentrations of potassium to the heart can cause serious arrhythmias. To prevent potentially fatal transient hyperkalemia, repletion should generally not exceed 10 to 20 mmol per hour although higher rates of infusion with continuous cardiac monitoring and frequent serum potassium concentration measurements may be necessary in patients with severe life-threatening hypokalemia. Clinicians should avoid the common tendency to underdose potassium repletion in patients with renal failure because of the concern of precipitating hyperkalemia. In these patients, frequent administration of small doses of potassium is advised with regular monitoring of the serum potassium concentration. Intravenous potassium should be given in saline rather than dextrose-containing fluids, as a glucose-induced increase in insulin release can shift potassium intracellularly, further decreasing its serum concentration. Supplemental potassium phosphate (15 to 30 mmol over 3 to 6 hours) can be used instead of KCl or other potassium salts in patients with hypokalemia and hypophosphatemia.


Hypokalemia can be accompanied by hypomagnesemia because of processes that cause both disorders as well as an effect of hypomagnesemia to induce urinary K+ wasting. Correction of the hypomagnesemia will be necessary to reverse the hypokalemia.



Calcium Disorders


Normal calcium balance is maintained through a variety of hormonal actions and physiologic feedback loops. Cholecalciferol (vitamin D3), synthesized in sun-exposed skin and provided in the diet, is hydroxylated in the liver to 25-OH vitamin D and then in the kidneys to the primary active form of 1,25-(OH)2 vitamin D; 1,25-(OH)2 vitamin D acts to increase intestinal absorption of calcium and phosphate and to increase bone mineralization. The serum calcium concentration is tightly regulated by combined actions of 1,25-(OH)2 vitamin D and parathyroid hormone (PTH) on the GI tract, bone, and kidneys.


Clinical laboratories report total serum calcium concentrations (normal range 9 to 10.5 mg/dL; 2.25 to 2.60 mmol/L). Approximately 45% of total serum calcium is protein bound, primarily to albumin, and about 10% is complexed with bicarbonate, phosphate, citrate, and other anions in the circulation. The remainder is the biologically active free, ionized serum calcium (normal range 4.5 to 5.3 mg/dL; 1.12 to 1.32 mmol/L). Although total serum calcium correlates well with ionized levels in healthy patients, several factors make this relationship less reliable in the ICU, particularly hypoalbuminemia and changes in blood pH. As a consequence, ionized calcium levels are best for diagnosing and managing calcium disorders in ICU settings.


Changes in the serum albumin concentration are associated with parallel changes in total serum calcium concentration. A commonly used approximation is that for each 1 g/dL decrease in albumin concentration below 4.5, the total serum calcium would be expected to fall by 0.8 mg/dL. This relationship allows clinicians to estimate the “corrected” total serum calcium accounting for the presence of hypoalbuminemia. Systemic pH and other factors (serum phosphate concentration, PTH level) can also influence the ionized calcium concentration. Acidemia decreases calcium binding to albumin and increases the fraction of total calcium that is in the ionized form. Conversely, alkalemia decreases the ionized calcium concentration by increasing the binding of calcium to albumin. For instance, acute respiratory alkalosis causes the ionized calcium concentration to decline by approximately 0.16 mg/dL (0.04 mmol/L) for each 0.1 unit increase in pH. Direct measurement of ionized calcium is possible in most clinical laboratories and should be employed in any patient with signs or symptoms concerning for hyper- or hypocalcemia with a normal total serum calcium concentration and in patients in whom serum total calcium measurements may be unreliable because of the presence of factors mentioned previously.



Hypercalcemia


Box 39.3 lists some of the more common causes of hypercalcemia relevant to the ICU setting. Asymptomatic or mildly symptomatic hypercalcemia, particularly if relatively chronic, is more likely to be due to hyperparathyroidism, whereas severe and acute hypercalcemia is more often a complication of underlying malignancy. Appropriate initial workup includes a careful review of the diet and medication list (prescription, over-the counter, vitamin and calcium supplements) as well as measurement of the intact PTH level. Further diagnosis should proceed according to the clinical presentation and may include measurement of serum phosphate, 25-(OH) vitamin D, 1,25-(OH)2 vitamin D level, PTH-related protein, serum and urine protein electrophoreses, and evaluation for malignancy.



BOX 39.3   Causes of Hypercalcemia


Excess parathyroid hormone (PTH) effect


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Jul 7, 2016 | Posted by in CRITICAL CARE | Comments Off on Electrolyte Disorders

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