Water and Electrolyte Disturbances

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Chapter 32 Water and Electrolyte Disturbances

Disturbances in water and electrolytes are common in the intensive care unit (ICU). In the first section of this chapter the physiology of water balance, including the distribution of intravenous fluids and the effects of cardiopulmonary bypass (CPB), are briefly reviewed. In the second section, clinical abnormalities of water and electrolytes are discussed. Common terms are explained in Table 32-1. Relevant physiology discussed in Chapter 1 is referred to throughout.

Table 32-1 Definitions of Terms

Osmosis	The movement of water caused by a concentration difference in the water on each side of a semipermeable membrane
Osmotic pressure	The hydrostatic pressure that must be applied to stop osmosis
Osmole	The number of molecules present in 1 g of a substance, multiplied by its molecular weight (of undissociated solute)
	Performing this calculation allows the concentration of a solute to be expressed in terms of the number of molecules. For example, if 60 g urea ([NH₂]₂CO, molecular weight = 60 g) is dissolved in 1 kg of water, the osmolality of the solution is 1 osmole per kg. For a substance that fully dissociates (e.g., NaCl), if the molecular weight (in grams) is dissolved in 1 kg of solute, the concentration is 2 osmoles per kg.
Osmolality	The number of osmoles per kilogram of water
Osmolarity	The number of osmoles per (total) liter of solution
	When solute is dissolved in solvent, the volume is greater than the volume of the solvent alone.
	In dilute solutions with small solute molecules, osmolarity is (approximately) equal to osmolality.
	In concentrated solutions of large solvent molecules, osmolality is greater than osmolarity.
Tonicity	The “effective” osmolality
	Solutes that are distributed evenly across semipermeable membranes do not exert osmotic pressure.
	Solutes that are restricted in their movement across compartments are “effective osmoles,” and tonicity describes their concentration.

PHYSIOLOGY

Body Water: Distribution, Constituents, and Movement

Depending on age and gender, between 45% and 60% of body weight is water. The percentage of water is higher in men and older people because they have a lower percentage of body fat than women and younger people. Body water is divided between intracellular (60%) and extracellular (40%) compartments. The extracellular compartment is composed of the interstitial, plasma, and transcellular (e.g., synovial fluid, cerebrospinal fluid, etc.) spaces, which constitute about 70%, 20%, and 10% of the extracellular fluid, respectively. Thus, a 70-kg male has about 10 liters of interstitial fluid, 3 liters of plasma, and 1 liter of transcellular fluid. The interstitium occupies the space between cells. It is a gel-like substance that contains extracellular fluid and two solid substances: collagen fibers, which provide tensile strength, and proteoglycan filaments, which trap water forming a “tissue gel.”

The intracellular and interstitial (extracellular) compartments are separated by cellular membranes. Water distributes freely between these two compartments according to the osmotic pressure difference across cellular membranes. At equilibrium, the number of osmotically active particles inside and outside cells is equal (about 285 mOsm/l). However, the constituents of the intracellular and extracellular fluids are quite different (Table 32-2). Some substances diffuse freely across cell membranes (e.g., oxygen, carbon dioxide, urea) and are therefore at the same concentration inside and outside cells. The movement of other substances (notably ions and glucose) across cell membranes is tightly controlled by selective permeability and active transport, which results in different concentrations inside and outside cells (see Table 32-2). The major cation in the extracellular fluid is sodium, and under normal circumstances it is the primary determinant of plasma osmolarity. The major anions in the extracellular fluid are chloride and bicarbonate. Because ions carry positive and negative charges, the active transport and selective permeability of ions allows variable charge separation to occur across the cell membrane, leading to the formation of resting and active membrane potentials (see Chapter 1).

Table 32-2 Composition of Intracellular and Extracellular Fluid

Electrolyte	Intracellular Fluid (mmol/l)	Extracellular Fluid^* (mmol/l)
Sodium	10	140
Potassium	155	3.8
Chloride	3	108
Bicarbonate	10	26
Calcium (ionized)	<0.01	1.2
Magnesium	10	0.8
Phosphate	105	1.0

* Because the plasma contains highly negatively charged protein molecules, minor differences exist between the electrolyte content of the interstitial fluid and the plasma.

The plasma and interstitial compartments are separated by the capillary endothelium. Spaces, known as gap junctions, exist between the endothelial cells that allow the free diffusion of all small particles between the interstitial and plasma spaces. Thus, the electrolyte, hydrogen ion, and glucose concentrations of the interstitium and plasma are identical. (However, the plasma concentration—but not the serum concentration—differs from the interstitial concentration because of the mass effect of the plasma proteins.) Under normal circumstances the capillary endothelium is impermeable to proteins larger than about 30 kiloDaltons (kD).

In addition to diffusion and osmosis, there is mass movement (filtration) of fluid between the capillary and the interstitium based on the balance of Starling forces across the capillary wall. The Starling forces are composed of the hydrostatic and the oncotic pressure gradients between the capillary lumen and the interstitial space (see Equation 1-12). The balance of the Starling forces varies among capillary beds, but overall there is a net loss of fluid from plasma to the interstitium. Filtered fluid is returned to the plasma through the lymphatic system.

Blood contains both extracellular and intracellular fluid. Approximately 35% to 45% of the blood water is intracellular, located almost exclusively within red blood cells. The circulating volume (cellular and extracellular fluid) in adults is about 70 ml/kg.

Intravenous Fluids

Intravenous fluids may be crystalloids (Table 32-3) or colloids. They are used mainly for treating hypovolemia (resuscitation fluid) and for replacement of obligatory daily losses (maintenance fluid). They are administered intravenously (i.e., into the plasma space) and, depending on their constituents and tonicity, the water is distributed to a variable extent throughout the extracellular and intracellular compartments.

Table 32-3 Composition of Crystalloids

Crystalloids

Crystalloid solutions generally contain sodium (plus an anion) or glucose as their major osmotically active molecules, and they may be hypotonic (e.g., 0.45% sodium chloride), isotonic (e.g., 0.9% sodium chloride, 5% dextrose), or hypertonic in comparison to plasma. Because sodium is retained primarily within the extracellular fluid, the water in isotonic sodium solutions (e.g., 0.9% sodium chloride, Hartmann, Plasma-Lyte) is distributed to the extracellular compartment. Theoretically, assuming an extracellular volume of 14 liters and a plasma volume of 3 liters in a 70-kg patient, 1 liter of 0.9% sodium chloride increases the plasma volume (3/14 × 1) by about 200 ml. Isotonic, sodium-containing crystalloids are used to treat hypovolemia.

The anion in sodium-based crystalloids is predominantly chloride. Chloride is the only anion in 0.9% sodium chloride and Ringer solution and is therefore present in supraphysiologic concentrations. Large volumes of these solutions can cause a hyperchloremic metabolic acidosis (see Chapter 31). More physiologic concentrations of chloride are present in buffered, balanced electrolyte solutions such as Hartmann (lactated Ringer) and Plasma-Lyte. Because bicarbonate is not stable in solution for long periods, these solutions contain lactate (Hartmann) or acetate and gluconate (Plasma-Lyte) as the nonchloride anion.

Dextrose is rapidly taken up by cells and metabolized, so solutions in which dextrose is the osmotically active substance are equivalent to administering water (“free water”). Thus, the water in 5% dextrose is distributed evenly throughout the intracellular and extracellular spaces. Theoretically, assuming a total body water of 45 liters and a plasma volume of 3 liters in a 70-kg patient, 1 liter of 5% dextrose will increase plasma volume by (3/45), about 65 ml. Solutions that are entirely (i.e., 5% dextrose) or predominantly (0.18% sodium chloride + 4% dextrose) dextrose are used as maintenance fluids. Dextrose solutions should never be used to treat hypovolemia because not only do they result in minimal expansion of the plasma volume, they also can cause hyperglycemia, increased carbon dioxide production, and lactic acidosis (due to increased glycolysis).

Hypotonic sodium solutions reduce the tonicity of the extracellular fluid and therefore, by osmosis, some water will be distributed to the intracellular space. For instance, with 0.45% sodium chloride, which has an osmolarity of 150 mOsm/l, about half of the water will be distributed to the intracellular compartment. In contrast, hypertonic sodium solutions increase the tonicity of the extracellular fluid, and “drag” water from the intracellular compartment by osmosis. Thus, the extracellular compartment will expand by a volume greater than the volume administered. Hypotonic and hypertonic solutions are used in special circumstances. For instance, 0.45% sodium chloride is used to replace hypotonic renal losses during the polyuric phase of acute renal failure, whereas hypertonic sodium chloride is used to reduce intracranial pressure in patients with cerebral edema. Rapid administration of large volumes of hypotonic solutions (e.g., pure water) into a peripheral vein (where flow may be sluggish) may cause osmotically mediated swelling—and potential lysis—of red blood cells. Ideally these solutions should be administered slowly via a central line.

Colloids

Colloid solutions contain large, oncotically active molecules in a base solution of either 0.9% sodium chloride or a buffered, balanced electrolyte solution. Colloid molecules are too big to traverse gap junctions, so more of the water in these solutions tends to be retained within the plasma space. Theoretically, assuming a plasma volume of 3 liters in a 70-kg patient, 1 liter of an isooncotic colloid solution increases plasma volume by 1 liter, which is 4 to 5 times the plasma volume expansion achieved by the same volume of an isotonic sodium-based crystalloid. However, with critical illness, the vascular endothelium “leaks,” allowing colloid molecules to pass into the interstitium, where they exert an osmotic pressure effect. This probably explains the observation that when resuscitating critically ill patients with 0.9% sodium chloride only 1.3 times the volume is required (not four times as predicted) compared with 4% albumin to achieve the same hemodynamic end points.¹

Commonly used natural colloids include albumin and fresh-frozen plasma. Albumin is available as 4%, 5%, and 20% preparations. Both 4% and 5% solutions are approximately isooncotic with plasma; 20% albumin is hyperoncotic and therefore expands the plasma volume by about four times its volume. Commonly used artificial colloids include modified gelatins (e.g., Gelofusine) and hydroxyethyl starch compounds. Hydroxyethyl starch comprises a family of colloids that are categorized on the basis of their average size into high (>400 kD), medium (200 kD), and low (70 kD) molecular weight preparations.² Two commonly used hydroxyethyl starches are hetastarch (average molecular weight 480 kD) and pentastarch (average molecular weight 200 kD). By comparison, Gelofusine has an average molecular weight of about 35 kD. Most artificial colloids are isooncotic or slightly hyperoncotic. The plasma half-time of artificial colloids varies among preparations but is typically on the order of 4 to 6 hours. Thus, the colloid effect has largely dissipated by 24 hours. Large volumes of hydroxyethyl starch can cause impaired hemostasis, mainly because of reduced effectiveness of the factor VIII/von Willebrand factor complex (i.e., acquired von Willebrand disease).² High molecular weight compounds such as hetastarch appear to cause greater impairment of hemostasis than do medium-sized compounds such as pentastarch.^3,⁴ Impaired hemostasis may also occur with gelatin-based colloids.⁵ To avoid hemostatic problems, the dosages of these artificial colloids should be kept below 20 ml/kg. All artificial colloids can cause allergic (including anaphylactic) reactions.

Crystalloids Versus Colloids for Fluid Resuscitation

There has been a great deal of debate over many decades on the pros and cons of crystalloids versus colloids for fluid resuscitation. Some ICUs use predominantly colloids, others predominantly crystalloids. Colloids are popular in Europe, whereas crystalloids are popular in North America. However, as long as fluids are administered to appropriate physiologic end points the choice between a colloid and a crystalloid is not important.^1,⁶ In view of the additional cost and potential for adverse events with artificial colloids, a primarily crystalloid-based fluid regime seems preferable.

In 1998, a metaanalysis found an apparent excess mortality rate associated with the use of albumin in critically ill patients.⁷ This and a subsequent analysis by the same group⁸ created a storm of controversy and led to the publication of other metaanalyses that did not support the original finding.^9,¹⁰ The issue of the safety of albumin was resolved in 2004 with the publication of a prospective, randomized trial involving nearly 7000 patients that found no difference in mortality rates between patients resuscitated with 4% albumin and those given 0.9% sodium chloride.¹

Regulation of the Osmolarity and Volume of the Extracellular Compartment

The osmolarity (i.e., sodium concentration) and volume of the extracellular spaces are tightly controlled and intimately connected. Plasma osmolarity is regulated by controlling the intake and loss of water, whereas extracellular volume is regulated by controlling the excretion of sodium.

Regulation of Water Balance

A change in the osmolarity of the extracellular fluid is sensed by osmoreceptors in the anterior hypothalamus. An increase in plasma osmolarity of only 1 to 2 mOsm/l provokes thirst and causes the secretion of antidiuretic hormone (vasopressin), which leads to increased reabsorption of water in the distal nephron and collecting ducts of the kidney. Antidiuretic hormone secretion increases in proportion to the increase in plasma osmolarity, reaching a maximum at 295 mOsm/l. Under full antidiuretic hormone stimulation, urine concentration may reach up to 1200 mOsm/l, maximizing body water conservation. A fall in plasma osmolarity to less than 280 mOsm/l completely suppresses antidiuretic hormone secretion, resulting in a urine osmolarity as low as 50 mOsm/l.

In addition to increased osmolarity, antidiuretic hormone secretion is also stimulated by hypotension and hypovolemia. In the presence of two competing pathophysiologic states—hypovolemia and low tonicity— circulating volume is defended over tonicity.

Regulation of Sodium Balance

Reduced circulating volume (e.g., due to hemorrhage) leads to the renal retention of sodium via the renin-angiotensin-aldosterone system (see Chapter 1). A change in the volume of the plasma is also sensed by arterial baroreceptors and atrial stretch receptors. This leads to a reduction in the release of the natriuretic peptides, which also promotes a reduction in renal sodium loss. Both of these mechanisms cause an increase in plasma osmolarity which, under the influence of antidiuretic hormone, promotes water retention. Thus, sodium and water are retained together and the volume of the extracellular fluid is determined by sodium balance.

Effects of Cardiopulmonary Bypass and Cardiac Surgery

Patients undergoing CPB have an obligatory fluid load related to the bypass circuit prime volume—typically a total of 4 ml/kg of crystalloid, colloid, or both. In addition, several liters of colloid or crystalloid fluids may be given during the intraoperative and the early postoperative periods. This occurs for a number of reasons. First, fluid is needed to replace urinary and blood losses. Second, in patients with impaired cardiac function, fluid may be given to optimize cardiac performance. Third, third-space fluid loss occurs. Third-space loss is abnormal filtrative loss from the plasma to the interstitium. It occurs due to the perturbations in the Starling forces that accompany cardiac surgery. In particular, the systemic inflammatory response to CPB can result in arteriolar vasodilatation and leakiness of the capillary endothelium, which increases fluid filtration from plasma to the interstitium (see Chapters 1 and Chapter 2).

A further consequence of surgery is abnormal fluid retention by the kidneys. During the early postoperative period patients are often polyuric due to the effects of hypothermic CPB and the use of diuretics such as mannitol in the bypass prime. Subsequently, the effects of surgical stress, systemic inflammation, mechanical ventilation, and certain drugs lead to the activation of the renin-aldosterone-angiotensin system and increased secretion of antidiuretic hormone. Fluid retention is typically over and above that required to defend circulating volume.

These effects—increased fluid administration, third-space losses, and excessive salt and water retention—cause a significant increase in total extracellular fluid volume during the early postoperative period. Weight gains of 7.4% on postoperative day 1 and of 6.6% on day 2 have been described following routine cardiac surgery.¹¹ Third-space losses are far greater in critically ill patients with endothelial dysfunction.

Maintenance Fluids

In patients who are not drinking or eating, maintenance fluids and electrolytes must be given to replace obligatory losses. In health, on a normal diet, 500 to 1000 ml/day of water are required to excrete renally the solute load generated by metabolism. A further 500 to 1000 ml is needed to replace obligatory losses through the skin (evaporation, sweat), respiratory tract, and gastrointestinal tract. Respiratory tract losses during mechanical ventilation, assuming adequate humidification, are low. Thus, maintenance water requirements in “normal” ventilated ICU patients are only approximately 20 ml/kg/day. Obligatory sodium and potassium losses are in the range of 1 to 2 mmol/kg/day and 0.5 to 1.5 mmol/kg/day, respectively. These basal maintenance requirements for sodium and water are provided by 1 ml/kg/hr of 4% dextrose with 0.18% sodium chloride (dextrose-sodium chloride). In theory, in volume-expanded cardiac surgery patients (see earlier material) essentially no maintenance fluid is required during the first few postoperative days. In this circumstance, a low fixed rate of 5% dextrose (e.g., 40 ml/hr) may be used as a carrier fluid for the administration of medications. However, many patients have a degree of endothelial dysfunction, resulting in continued redistribution of fluid away from the plasma, which necessitates continued infusion of resuscitation fluids. Similarly, highly febrile patients may have insensible water (and sodium) losses that total several liters per day and also require replacement.

CLINICAL ABNORMALITIES OF WATER AND ELECTROLYTES

Disorders of Sodium and Water Balance

Abnormal Extracellular Volume

Abnormalities of extracellular volume include abnormalities of plasma volume and total extracellular volume. Often the two compartments change together; thus, increased plasma volume usually coexists with expansion of the entire extracellular compartment. This is the case with heart failure. However, it is possible to have low plasma volume (i.e., hypovolemia) despite an expanded extracellular space. Hypovolemia is discussed in Chapter 20.

Expansion of the extracellular volume occurs because of abnormal sodium retention or excessive sodium administration. It causes systemic edema but not necessarily pulmonary edema. In cardiac surgery patients, systemic edema typically occurs in two situations: (1) with severe cardiac dysfunction, in which case plasma (circulating) volume is high; and (2) with marked systemic inflammation, in which case plasma volume may be low or normal.

There is no simple tool for measuring extracellular volume. Patients may appear swollen, particularly in areas where skin is normally lax (e.g., around the eyes and eyelids). Pitting edema may be present in dependent regions such as the sacrum and the scrotum (in bed-bound patients) or ankles (in ambulant patients). However, expansion of the extracellular volume by several liters may not produce any clinical signs. The 24-hour ICU chart may show a persistently positive fluid balance, but fluid balance calculations must be interpreted with caution because they do not track respiratory and skin losses. In febrile patients, insensible losses may total several liters per day. Fluid losses due to diarrhea or wound ooze are also difficult to track accurately. Weighing the patient every second or third day may be helpful but is often impractical.

Systemic edema resolves with resolution of the underlying condition. Treatment should therefore be directed at the underlying condition, not at the edema. In the absence of pulmonary congestion, there is no absolute indication for diuretics, although in practice they are commonly administered. Diuretics must be administered cautiously because they can lead to intravascular volume depletion despite persisting systemic edema.

Disorders of Sodium Concentration: Hyponatremia and Hypernatremia

The normal plasma sodium concentration is 135 to 145 mmol/l. Disorders of sodium concentration reflect abnormal water homeostasis. They are linked to abnormalities of osmolarity and extracellular volume, so the evaluation of hyponatremia or hypernatremia should include measurement of plasma osmolarity and clinical assessment of extracellular volume status. When hyperglycemia is present, the corrected sodium concentration should be calculated. Hyperglycemia increases the osmolarity of the extracellular space, which (by osmosis) causes water movement from cells into the extracellular space; this “dilutes” sodium, causing hyponatremia. For every 100 mg/dl (5.5 mmol/l) rise in glucose concentration, sodium concentration decreases by 1.4 mmol/l; or sodium concentration falls 1 mmol/l for each 4 mmol/l rise in glucose concentration.

In the cardiothoracic ICU, hyponatremia usually occurs in association with a low plasma osmolarity and represents a relative excess of water, whereas hypernatremia occurs in association with a high plasma osmolarity and represents a relative lack of water. The common causes of hyponatremia and hypernatremia are listed in Table 32-4 and Table 32-5, respectively.

Table 32-4 Causes of Hyponatremia

Water excess with normal or increased extracellular fluid volume

Excess administration of free water (e.g., intravenous

5% dextrose) (SIADH)

• Surgery

• Nausea

• Acute respiratory failure

• Neoplasm

• Drugs (corticosteroids, opioids, major tranquillizers)

Renal failure

Heart failure

Hepatic failure

Hypothyroidism

Water excess with reduced extracellular fluid volume

Diuretics

Adrenal insufficiency

Hyperglycemia

SIADH, syndrome of inappropriate antidiuretic hormone secretion. Note: All causes of hyponatremia are associated with reduced plasma osmolarity except hyperglycemia; see text for details.

Table 32-5 Causes of Hypernatremia

Sodium excess (high extracellular fluid volume)

Administration of isotonic or hypertonic sodium chloride

Administration of sodium bicarbonate

Water loss (low extracellular fluid volume)

Polyuric phase of acute renal failure

High gastric or large bowel fluid losses

Sweating

Diuretics (loop, osmotic)

Diabetes insipidus: nephrogenic or central (see text for details)

Note: All causes are associated with increased plasma osmolarity.

Hyponatremia.

Mild hyponatremia does not produce symptoms, but an acute fall in plasma sodium below 125 mmol/l can cause cerebral edema, which manifests as lethargy, headache, nausea, confusion, and eventually obtundation and seizures. The most common cause of hyponatremia in postoperative patients is excessive administration of low-sodium crystalloid solutions (i.e., 5% dextrose, dextrose-sodium chloride) in combination with the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Some degree of SIADH occurs in all postoperative patients due to the effects of surgical stress, pain, nausea, and drugs (morphine, corticosteroids). Postoperative SIADH is usually mild, but severe hyponatremia can develop due to SIADH resulting from other causes (e.g., certain infections and tumors). Urinary sodium tends to be higher with pure SIADH (>20 to 40 mmol/l) than with pure water intoxication (<10 mmol/l). Chronic treatment with diuretics can also cause hyponatremia if diuretic-induced sodium and water losses are replaced with sodium-poor fluid. This is often the situation in chronic diuretic use. Severe hypovolemia also induces antidiuretic hormone secretion because the body attempts to defend volume over tonicity, which further exacerbates hyponatremia.

Heart failure is commonly associated with hyponatremia as a consequence of increased secretion of antidiuretic hormone and chronic diuretic use. Severe chronic renal failure leads to hyponatremia due to an inability of the kidneys to achieve a low urine osmolarity in response to high water intake. Hyponatremia is common with adrenal insufficiency because of reduced aldosterone secretion. All of the causes of hyponatremia described are associated with reduced plasma osmolarity; by contrast, hyponatremia secondary to hyperglycemia is associated with increased osmolarity.

When hyponatremia occurs in association with hypovolemia (diuretic excess, adrenal insufficiency), initial resuscitation should be performed using an isotonic salt solution (e.g., 0.9% sodium chloride). When hyponatremia occurs in association with euvolemia or hypervolemia (heart failure, excess free water, SIADH), treatment involves water restriction to 1 to 1.5 l/day (or less) and by eliminating any aggravating factors such as the administration of 5% dextrose. Water restriction may be combined with furosemide in patients with marked systemic edema.

For severe acute hyponatremia, hypertonic sodium chloride may be administered. However, rapid correction of hyponatremia can lead to acute pontine demyelination, which manifests as paraparesis, dysarthria, seizures, coma, and death. This risk is greatest with the rapid correction of severe, chronic hyponatremia. In patients with mild or no symptoms and severe hyponatremia, the plasma sodium concentration should be increased by no more than 8 mmol/l/day (0.3 mmol/l/hr).¹² In patients with severe symptoms of hyponatremia (confusion, obtundation, and seizures), a maximum rate of correction of 1.5 to 2 mmol/l/hr for 3 to 4 hours is acceptable until symptoms abate; this is followed by minimal further increase in the ensuing 20 hours to ensure that acute pontine demyelination is not precipitated. However, should severe symptoms persist (e.g., coma, seizures) a rise of more than 8 mmol/l/day may be justified.^12,¹³

The approximate amount of sodium required to raise the plasma sodium concentration by 8 mmol/l is given by the equation:

(32-1)

Thus, in a 70-kg patient with confusion and a plasma sodium concentration of 110 mmol/l, this amounts to 280 mmol of sodium. This may be administered at 35 to 70 mmol/hr until the confusion resolves or the limit of 280 mmol is reached. If the confusion improves before this total dose is administered, the rate of administration should be reduced so as to deliver the remainder over approximately 16 to 20 hours.

Hypernatremia.

Hypernatremia is associated with increased plasma osmolarity and is usually associated with a relative water deficit. Hypernatremia can produce symptoms of weakness, drowsiness, obtundation, and seizures. The plasma sodium concentration at which symptoms occur depends on the rapidity with which hypernatremia has developed, but symptoms are unlikely with a plasma sodium concentration of less than 155 mmol/l.

Hypernatremia may occur as the result of vigorous administration of sodium-rich solutions (0.9% sodium chloride and 8.4% sodium bicarbonate) or due to the loss of sodium-poor, hypotonic fluids. Patients are typically hypervolemic with the former and hypovolemic with the latter. Diarrhea, gastric secretions, and sweat all have sodium concentrations of less than 100 mmol/l. (In contrast, small bowel and pancreatic secretions have a sodium concentration similar to that of extracellular fluid.) During the polyuric recovery phase of acute renal failure, the ability of the renal tubules to concentrate urine is impaired, and the sodium concentration of urine is typically less than 100 mmol/l. The urinary sodium concentration in patients receiving furosemide is also less than 100 mmol/l. Untreated, the loss of water in excess of sodium leads to hypernatremia and hypovolemia.

An important cause of hypernatremia is diabetes insipidus. Diabetes insipidus involves either a failure of production of antidiuretic hormone (central diabetes insipidus) or lack of renal responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus). Central diabetes insipidus may occur in patients with neurologic injury or brain death (see Chapter 38). Nephrogenic diabetes insipidus may occur due to loss of the hypertonic medullary interstitium (see Chapter 1). This is the cause of the polyuria that accompanies renal failure and diuretic administration. Nephrogenic diabetes insipidus may also occur because of reduced responsiveness of the distal nephron to antidiuretic hormone; causes of this state include drugs (e.g., amphotericin B, aminoglycosides, and lithium), hypokalemia, and hypercalcemia. Patients with diabetes insipidus produce large volumes of very dilute urine (urinary osmolality <200 mosmol/l) which, if not replaced, causes hypovolemia.

The treatment of hypernatremia depends on the cause and on the patient’s intravascular volume status. With hypovolemia, initial resuscitation should include a balanced crystalloid solution such as Plasma-Lyte. Subsequent treatment should be directed at the relative water deficit. For ongoing losses of sodium-poor fluid, administration of half-normal sodium chloride (0.45% sodium chloride) or free water is appropriate. Half-normal sodium chloride is particularly useful in the management of the polyuric phase of acute renal failure. Because 0.45% sodium chloride is hypotonic, it should be given slowly or administered into a central vein to avoid hemolysis. Free water may be given enterally (as tap water added to enteral feeds) or intravenously as 5% dextrose. A dosage of between 50 and 150 ml/hr is appropriate in most circumstances. Treatment of central diabetes insipidus is described in Chapter 38.

Abnormalities of Potassium, Magnesium, Calcium, and Phosphate

Potassium

The normal plasma potassium concentration is 3.5 to 5 mmol/l. Potassium homeostasis is markedly abnormal in patients undergoing cardiac surgery. Large quantities of potassium, often in excess of 50 mmol, may be given in cardioplegia solutions. Renal losses may be substantial as a result of diuretics, such as furosemide and mannitol, and the effects of hypothermic CPB. Hyperglycemia is common during surgery and, if severe, has an osmotic diuretic effect, enhancing renal potassium losses. The use of insulin to treat hyperglycemia promotes cellular uptake of potassium. Potassium uptake by cells is also promoted by β₂-adrenoreceptor agonists (e.g., epinephrine, albuterol, and isoproterenol) and alkalosis. Acidosis, particularly that due to renal failure, causes the release of potassium from cells.

Virtually all of the potassium filtered at the glomerulus is reabsorbed, and renal control of potassium balance is determined by secretion in the distal nephron. The main determinants of potassium secretion are the plasma potassium concentration and aldosterone activity. Aldosterone causes the renal reabsorption of sodium in exchange for either potassium or hydrogen ions (see Chapter 31). Thus, mineralocorticoid excess (e.g., treatment with corticosteroids) can cause hypervolemia, hypokalemia, and metabolic alkalosis. The causes of hypokalemia and hyperkalemia in the cardiothoracic ICU are listed in Table 32-6 and Table 32-7, respectively.

Table 32-6 Causes of Hypokalemia

Increased urinary loss

Diuretics (loop, thiazide, osmotic)

Polyuria secondary to hypothermic CPB

Mineralocorticoid excess (e.g., Cushing syndrome, Conn syndrome, treatment with corticosteroids, renal artery stenosis)

Hypomagnesemia

Other drugs (e.g., amphotericin B)

Renal tubular acidosis (types 1 and 2)

Increased gastrointestinal loss

High nasogastric aspirates

Vomiting

Diarrhea or fistula loss

Potassium movement into cells

Alkalemia

Insulin

β₂-adrenoceptor agonists (epinephrine, albuterol, isoproterenol)

Methylxanthines (aminophylline)

Periodic paralysis (hypokalemic form)

Other losses

Renal replacement therapy

Sweating

CPB, cardiopulmonary bypass.

Table 32-7 Causes of Hyperkalemia

Artefact (blood trauma during sampling)

Decreased potassium excretion

Chronic renal failure

Acute renal failure

Potassium-sparing diuretics

ACE inhibitors and angiotensin receptor blockers

Nonsteroidal antiinflammatory drugs

Cyclosporin (aldosterone resistance)

Adrenal dysfunction (Addison disease)

Renal tubular acidosis (type 4)

Periodic paralysis (hyperkalemic form)

Potassium movement out of cells

Cessation of insulin treatment

β blockers

Suxamethonium

Acidemia

Tissue necrosis or reperfusion

Digoxin toxicity

Rhabdomyolysis

Increased intake

Overcorrection of hypokalemia

ACE, angiotensin-converting enzyme.

Hypokalemia.

Hypokalemia is very common during the early postoperative period and is associated with a range of cardiac arrhythmias, including atrial and ventricular premature beats, atrial fibrillation, and torsades de pointes ventricular tachycardia. On the resting electrocardiogram (ECG), hypokalemia produces characteristic changes related to delayed ventricular repolarization. Initially there is reduced amplitude of the T wave and an increase in the U wave; later there may be ST segment depression or T wave inversion with a marked increase in the U wave and prolongation of the QU interval.

The likelihood of developing arrhythmias is dependent on the rapidity with which hypokalemia has developed and the irritability of the myocardium. In the early period following cardiac surgery, hypokalemia can develop very quickly at a time when the heart is particularly vulnerable to arrhythmias. Thus, aggressive potassium supplementation is commonly needed. Plasma potassium should be kept above 4 mmol/l or above 4.5 mmol/l when there are arrhythmias. Potassium should be administered as 10 to 20 mmol of potassium chloride or, if phosphate is low, potassium dihydrogen phosphate. This should be given intravenously over 30 minutes and then the potassium level rechecked. Bolus or very rapid intravenous injection of potassium can cause life-threatening arrhythmias or cardiac arrest.

Once patients have been extubated and are eating, oral potassium supplements may be given if required. In addition to hypokalemia, potassium supplementation may also be indicated for the treatment of metabolic alkalosis (see Chapter 31).

Hyperkalemia.

Unless caused by excessive potassium supplementation, hyperkalemia is uncommon in the first few hours following cardiac surgery. It usually develops in the context of acute renal dysfunction or abrupt cessation of insulin therapy. Even moderate (acute) renal dysfunction can precipitate life-threatening hyperkalemia when patients are treated with angiotensin-converting enzyme inhibitors, potassium-sparing diuretics, or β blockers or when insulin is stopped. In certain situations, massive hyperkalemia can occur with the administration of suxamethonium (see Table 4-6). Artefactual hyperkalemia may occur due to mechanical trauma to red blood cells during blood sampling. This cause should always be considered when the blood sample is difficult to obtain or no other cause is likely.

The main adverse effect of hyperkalemia is cardiac arrhythmias, particularly bradycardia, atrioventricular block, an inability to pace, and asystole; ventricular fibrillation can also occur. Characteristic changes on the resting ECG are seen with progressive hyperkalemia. Tall, narrow T waves and a short QT interval appear first, usually when the plasma potassium concentration is in the range of 6 to 7 mmol/l. Subsequently, the QRS becomes widened and the P wave disappears. Finally, the QRS and T waves merge, forming a sinusoidal complex, and cardiac arrest occurs. As with hypokalemia, the likelihood of developing arrhythmias depends on cardiac function and the acuity of the hyperkalemia. In acute hyperkalemia, significant arrhythmias are rare when the plasma potassium level is less than 6 mmol/l and common when it is above 7 mmol/l. With chronic hyperkalemia, a plasma potassium concentration as high as 8 mmol/l may be well tolerated.

Treatment options for hyperkalemia and their mechanisms of action are listed in Table 32-8. For life-threatening hyperkalemia (i.e., an acute rise in potassium above 7 mmol/l), the following interventions are appropriate: (1) intravenous calcium chloride 5 mg/kg (0.035 mmol/kg); (2) intravenous sodium bicarbonate (50 mmol, given separately from calcium); (3) intravenous glucose (50 ml 50% dextrose) and insulin (15 units of a rapidly acting formulation); (4) modest hyperventilation (in intubated patients). For less severe forms of hyperkalemia (i.e., potassium >6.0 to 6.5 mmol/l), continuous nebulized albuterol (5 mg administered until the potassium falls below 6 mmol/l) combined with intravenous furosemide (40 mg) is safe and effective. If there are ECG changes indicative of hyperkalemia, calcium chloride should be given. Most treatments listed in Table 32-8 increase cellular uptake of potassium and therefore are only temporizing measures. Increased potassium removal is facilitated by diuretics, cation-exchange resins, and renal replacement therapy (see Chapter 33); if hyperkalemia is rapidly progressive and occurs in the context of acute renal failure, early institution of renal replacement therapy is indicated.

Table 32-8 Treatment of Hyperkalemia

Stabilization of the myocardium

Calcium

Increased potassium entry into cells

β₂-adrenoceptor agonists (e.g., albuterol)

Insulin (with glucose)

Sodium bicarbonate

Modest hyperventilation/avoidance of hypercarbia

Removal of potassium

Loop diuretics

Cation-exchange resins (calcium resonium)

Renal replacement therapy

Magnesium

The normal plasma magnesium concentration is 0.75 to 1.0 mmol/l (1.8 to 2.4 mg/dl). The majority of the magnesium present in the body is in cells and bone, with only 1% in the extracellular fluid. Magnesium balance is regulated primarily by renal excretion under the influence of parathyroid hormone and vitamin D. Diuretics, metabolic acidosis, volume expansion, and catecholamines all enhance renal magnesium loss. Thus, hypomagnesemia is common during the postoperative period. Hypomagnesemia can also occur with high gastrointestinal fluid losses, pancreatitis, and parenteral nutrition. Hypomagnesemia predisposes to cardiac arrhythmias both directly and by potentiating renal potassium loss. The ECG findings in hypomagnesemia are similar to those in hypokalemia. The use of magnesium as an antiarrhythmic drug is described in Chapters 3 and Chapter 21. Occasionally, very high plasma magnesium levels (2 to 3 mmol/l) are required for arrhythmia suppression. Hypermagnesemia typically occurs secondary to renal failure or drug administration. Side effects of hypermagnesemia include vasodilation, bradycardia, atrioventricular block, weakness, and marked augmentation of the effect of neuromuscular blocking drugs.

Calcium

The normal plasma calcium concentration is 2.1 to 2.6 mmol/l (8.4 to 10.2 mg/dl), of which about 40% is bound to plasma proteins (mainly albumin) and a further 10% is bound to plasma anions such as sulfates and phosphates. The normal ionized plasma calcium concentration is 1.1 to 1.3 mmol/l (4.6 to 5.2 mg/dl). An important cause of (total) hypocalcemia is low albumin concentration. When plasma albumin concentration is low, only the ionized calcium concentration should be considered. The vast majority of calcium in the body is in bone, with only 0.1% in the extracellular fluid and virtually none present intracellularly. Plasma calcium levels are tightly regulated (by parathyroid hormone and vitamin D) because calcium plays a key role in many physiologic processes, including muscle excitation and coagulation. Moderate ionized hypocalcemia (<1 mmol/l) can contribute to myocardial dysfunction and arrhythmias; profound ionized hypocalcemia (<0.5 mmol/l) impairs coagulation. Severe hypocalcemia can also cause hyperreflexia, tetany, and seizures.

Ionized hypocalcemia is common in the cardiothoracic ICU, and the causes are listed in Table 32-9. CPB is associated with heparin and protamine use and with major fluid shifts, all of which can cause hypocalcemia. Large-volume blood transfusion can cause hypocalcemia due to the binding of calcium by citrate. Alkalosis increases the binding of calcium to albumin, which results in a normal total calcium and ionized hypocalcemia. Alkalosis is an important cause of severe symptomatic ionized hypocalcemia. Sodium bicarbonate, used to treat non-anion-gap metabolic acidosis (see Chapter 31), can bind with calcium to cause ionized hypocalcemia. The reduced elimination of phosphate in chronic renal failure leads to hyperphosphatemia. This causes the formation of insoluble calcium phosphate salts, resulting in hypocalcemia (see Chapter 33). Hypomagnesemia inhibits secretion of parathyroid hormone, which causes secondary hypocalcemia. In this situation, the treatment is magnesium, not calcium.

Table 32-9 Causes of Ionized Hypocalcemia

Binding with other substances

Alkalosis

Massive transfusion

Pancreatitis

Hyperphosphatemia

Drugs

Protamine

Heparin

Aminoglycosides

Phenytoin

Other

Sepsis

Hypomagnesemia (inhibition of parathyroid hormone secretion)

Cardiopulmonary bypass

Renal failure (due to hyperphosphatemia and low vitamin D)

Chronic liver disease

Hypercalcemia is very uncommon in cardiac surgery patients and usually results from overtreatment of hypocalcemia. The most common cause of hypercalcemia is malignancy, particularly involving bone; occasionally, hypercalcemia occurs in patients with non-small cell lung cancer; it is caused by the ectopic secretion of parathyroid hormone (see Table 12-1).

For symptomatic hypocalcemia (or hyperkalemia; see earlier material), intravenous calcium chloride (5 mg/kg or 0.035 mmol/kg) may be given. Moderate ionized hypocalcemia, such as commonly occurs in the first few hours following cardiac surgery, does not require treatment; over a period of hours, mobilization of calcium from bone stores restores plasma levels to normal.

Phosphorus

Inorganic phosphorus (PO₄ ²) is found predominantly inside cells, where it plays an important role in intermediary metabolism. The normal plasma concentration is 0.70 to 1.50 mmol/l (2.2 to 4.6 mg/dl). Hyperphosphatemia is usually due to renal failure or tissue necrosis. It may be an early marker of mesenteric ischemia (see Chapter 34). The main consequence of hyperphosphatemia is ionized hypocalcemia. Hypophosphatemia may arise because of high phosphate loss (due mainly to renal replacement therapy) or increased cellular uptake. Increased cellular uptake of phosphate occurs with (1) glucose loading (e.g., in parenteral nutrition)—particularly after a period of starvation (See Chapter 34); (2) treatment with β₂-adrenoreceptor agonists; (3) respiratory alkalosis; (4) sepsis. Aluminum-containing antacids (e.g., sucralfate) inhibit the gastrointestinal absorption of phosphate and can cause hypophosphatemia. (Hyperphosphatemia due to renal failure may be treated with aluminum hydroxide gels so as to prevent bone disease.) The consequences of hypophosphatemia are unclear. It is usually clinically silent but, if severe, may contribute to muscle weakness and cardiac dysfunction. Treatment is with intravenous supplementation, either as sodium or potassium phosphate.

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