Chapter 20
Fluids, Electrolytes, and Blood Component Therapy
Fluid Compartments
Total body water is partitioned into two principal compartments: the intracellular fluid (ICF) and the extracellular fluid (ECF). The extracellular compartment is further subdivided into intravascular fluid (IVF) and interstitial fluid (ISF) spaces. The fluid compartments are divided by water-permeable membranes1; the intracellular space is separated from the extracellular space by the cell membrane, and the extracellular space is divided into intravascular and interstitial spaces by the capillary membrane.
The ICF compartment contains approximately two thirds of the body’s total fluid volume2 and is characterized by high concentrations of potassium, phosphate, and magnesium. The adenosine triphosphatase (ATPase)–driven sodium-potassium pump (Na-K–ATPase pump) located in the cell membrane maintains the high concentration of potassium found in ICF3 (Figure 20-1 and Table 20-1). The Na-K–ATPase pump exchanges three sodium ions for two potassium ions and offsets the tendency for sodium to diffuse into the intracellular space.
TABLE 20-1
Osmolar Substances in Extracellular and Intracellular Fluids
From Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia: Saunders; 2011:288.
The ECF compartment contains approximately one third of the body’s fluid volume2 and contains high concentrations of sodium and chloride compared with the ICF compartment. The IVF (also known as plasma) space contains approximately one quarter of the ECF volume and has essentially the same composition and concentration of electrolytes as the ISF. The presence in the IVF of relatively high concentrations of osmotically active plasma proteins, of which albumin is most important, is a significant difference distinguishing ISF from IVF.4 The capillary membrane is relatively impermeable to the plasma proteins contained within the vascular space, unless a disease state such as trauma or sepsis alters the capillary permeability.
The properties of the membranes that separate the fluid compartments, as well as the relative concentration of osmotically active substances within each compartment, are the factors primarily responsible for the movement of fluid (water and electrolytes) among compartments in the body. Because the intravascular space is the fluid compartment accessible to the clinician and the chief focus of fluid therapy, it is useful to understand the motion of fluid from the IVF space to the ISF space across the capillary membrane. Four forces known commonly as Starling forces determine the motion of fluids across the capillary membrane. The four forces that govern fluid dynamics in the microcirculation are capillary pressure, ISF pressure, ISF colloid osmotic pressure, and plasma colloid osmotic pressure.2
Influences of Surgery and Anesthesia on Fluid Balance
Preoperatively, patients can become volume depleted and experience alterations of electrolyte balance due to several processes. Burns, vomiting, diarrhea, fever, and gastric suction can lead to hypovolemia before surgery.5 If a large volume of fluid is lost from the gastrointestinal (GI) tract, careful evaluation of electrolytes and appropriate replacement is indicated.4 Quite often, preoperative hypovolemia is at least in part an iatrogenic phenomenon secondary to bowel preparation and preoperative fasting. Unless surgery is of the greatest urgency, to reduce the risk of hypotension and complications resulting from electrolyte imbalances, preoperative fluid deficits and electrolyte abnormalities should be corrected before anesthetic induction.6
During the intraoperative period, the effects of surgery and anesthesia combine to challenge fluid and electrolyte homeostasis. Surgery can lead to hemorrhage and a need to replace fluids or blood. Surgery can also lead to evaporative loss; loss from exposed viscera is composed entirely of water (without electrolytes) and is most appropriately replaced with free water (water available for dissolving substances). Manipulation of tissues during surgery can lead to “third spacing,” which is the redistribution of fluid from the intravascular space to the interstitial space. Replacement of fluid lost from the intravascular space in the phenomenon of third spacing is best carried out by balanced salt solutions that have an electrolyte composition similar to ECF.1,6 Absorption of electrolyte-free irrigation solutions during transurethral prostate surgery or endometrial ablation can result in a life-threatening hypo-osmolar state that must be addressed appropriately by the clinician.7
Anesthesia in and of itself can lead to derangements of fluid balance in surgical patients. The vasodilatory effects of both regional and general anesthesia can result in a relative hypovolemia, which may lead to hypotension on induction. General anesthesia increases the release of antidiuretic hormone, causing increased retention of water,1,8 which can predispose the patient to hyponatremia.9 Mechanical ventilation can increase evaporative loss of water and decrease the release of atrial natriuretic peptide, leading to renal conservation of sodium.1
The effects of surgery on fluid balance can persist into the postoperative period. Third-spaced fluids are typically mobilized (returned to the intravascular space) on the third postoperative day. The increased circulating volume may be poorly tolerated by patients with marginal renal or cardiovascular performance and can result in congestive heart failure or pulmonary edema.4,10
Fluid Volume Disorders
Fluid volume disorders, particularly hypovolemia, are often encountered in patients undergoing surgery. Discussion of disorders of concentration and volume of body fluids is facilitated by careful consideration of the concepts of osmolarity, osmolality, and tonicity. Osmolarity is an expression of the number of osmoles of solute in a liter of solution, whereas osmolality expresses the number of osmoles of solute in a kilogram of solvent. Because of the dilute nature of body fluids, the difference between osmolarity and osmolality is minimal. Tonicity, a concept related to osmolarity and osmolality, describes how a solution affects cell volume. Isotonic solutions have an effective osmolality close to that of body fluids (approximately 285 mOsm/L)3; therefore cells placed in an isotonic solution are not expected to swell or shrink.
Volume depletion, or hypovolemia, refers to the loss of ECF and is not to be confused with dehydration, which refers to a concentration disorder in which insufficient water is present relative to sodium levels.3 Hypovolemia can result from an absolute loss of fluid from the body or a relative loss of bodily fluids in which water is redistributed within the body, leading to a reduced circulating volume. Causes of absolute fluid loss include loss of fluid from the GI tract, polyuria, and diaphoresis. Decreased intake of fluids is a common cause of absolute fluid deficit in surgical patients because of intolerance to oral fluids and prolonged preoperative fasting. Relative fluid losses can be caused by conditions such as burns and third-space losses resulting from surgery. It should be noted that patient weight does not decrease in cases of relative fluid loss.
Because most cases of hypovolemia are caused by the loss of ECF, replacement with isotonic crystalloids (which have a composition similar to ECF) is appropriate.3 Determining the appropriate volume of fluids to administer for maintenance and replacement needs is discussed later; however, in certain circumstances such as oliguria or hemodynamic instability, a fluid bolus (also known as fluid challenge) may be warranted. Four components of a fluid challenge are the type of fluid, rate of administration, critical end points, and safety factors. (Table 20-2). Estimated fluid and blood requirements based on the clinical presentation of a patient have been classified into four stages of shock (Table 20-3).
TABLE 20-2
Adapted from Vincent JL, Weil MH. Fluid challenge revisited. Crit Care Med. 2006;34(5):1333-1337.
TABLE 20-3
Four Classes of Hemorrhagic Shock
Modified from Rhee P. Shock fluids and electrolytes. In: Townsend CM, et al, eds. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. 19th ed. Philadelphia: Saunders; 2012:72.
Disorders of Sodium Balance
Disorders of sodium balance may be encountered in anesthetic care and are of great clinical significance. Sodium is the most abundant electrolyte in the ECF; along with its accompanying chloride anion (NaCl), it is responsible for most of the osmotic activity of the ECF. The physiologic significance of sodium can be appreciated when one considers that gain or loss of sodium is accompanied by a gain or loss of water, respectively.3 Because sodium concentration in the ECF is much higher than in the intracellular space (as a result of the action of the Na-K–ATPase pump in the cell membrane), alteration of sodium levels in the extracellular space greatly affects the osmotic relationship between intracellular and extracellular spaces, leading to movement of water across the cell membrane.
The clinical importance of sodium disorders is due largely to the influence of sodium on the water content in brain cells. The blood-brain barrier, unlike peripheral capillary beds, has only limited permeability to ionic solutes. The result of this limited permeability in the blood-brain barrier is the prevention of equilibration of osmotically active ionic solutes between intravascular and interstitial spaces. This lack of permeability to sodium (and consequent failure to equilibrate osmotically active solutes between the intravascular and interstitial spaces) changes the osmotic gradients between fluid compartments, leading to the precedence of sodium over plasma proteins as the most important osmotically active substance influencing the water content of the brain tissues.10,11
Hyponatremia may have multiple causes (Box 20-1). Of particular interest to anesthetists is hyponatremia resulting from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which is discussed in Chapter 33. Water intoxication resulting from the absorption of electrolyte-free irrigation solution during procedures such as transurethral resection of the prostate and endometrial ablation is discussed in Chapter 29. Water intoxication and SIADH lead to hyponatremia from an excess of water, not loss of sodium.1,12
Hyponatremia results in a condition in which the intracellular environment is hyperosmolar relative to the ECF, leading to an influx of water into the intracellular space. One of the most significant consequences of hyponatremia is cerebral edema. Because the brain is contained within the fixed confines of the skull, cerebral edema is poorly tolerated.13 Compensatory mechanisms can forestall the development of symptomatic cerebral edema for a period of time.14 Brain cells can maintain osmotic equilibrium by extruding intracellular solutes, thereby reducing intracellular osmolality.9,13 However, if the extrusion of solute by brain cells is inadequate to compensate for the hypo-osmolar influence of the ECF, an intracellular influx of water may lead to symptomatic cerebral edema.13
Clinical studies have demonstrated that compared with men or postmenopausal women, menstruating women are at increased risk of brain damage resulting from hyponatremia.3,13 It is believed that estrogen and progesterone inhibit the efficiency of the Na-K–ATPase pump, which is essential to the extrusion of intracellular solutes to maintain osmotic equilibrium in hyponatremia; female sex hormones may facilitate movement of water into the brain through the mediation of antidiuretic hormone (ADH).13
Hyponatremia is the most common electrolyte abnormality in hospitalized patients. The development of hypervolemic hyponatremia in patients with congestive heart failure (CHF) or cirrhosis is associated with an increased risk of death. Even mild stable euvolemic hyponatremia due to SIADH has been associated with cognitive defects and gait disturbances. Overly rapid correction of serum sodium, particularly in patients with chronic hyponatremia, can cause neurologic complications such as seizures, spastic quadriparesis, and coma due to osmotic demyelination.15 There are two drugs available for the treatment of hypervolemic or euvolemic hyponatremia due to CHF, cirrhosis, or SIADH. Tolvaptan (Samsca) and conivaptan (Vaprisol) are vasopressin receptor antagonists. Tolvaptan is an oral preparation and conivaptan is available for intravenous use. Treatment of hyponatremia usually includes fluid restriction and diuresis. IV conivaptan has been used for short-term treatment of euvolemic hyponatremia. Oral treatment with tolvaptan can increase serum sodium concentrations in patients with hypervolemic or euvolemic hyponatremia due to cirrhosis, heart failure, or SIADH, but has not been shown to reduce mortality. Overly rapid correction of serum sodium, which can cause osmotic demyelination, has not been reported to date with tolvaptan.15–17
Controversy exists as to how aggressively hyponatremia should be treated (Figure 20-2). In chronically hyponatremic patients, rapid correction of serum sodium can lead to the neurologic disorder known as myelinolysis. Myelinolysis, originally known as central pontine myelinolysis, can lead to disorders of the upper neurons, spastic quadriparesis, pseudobulbar palsy, mental disorders, and in some cases death.14 Patients at particular risk for myelinolysis are those who have been hyponatremic for more than 48 hours9,14 and individuals who have had orthotopic liver transplantation or a history of alcohol abuse.14 Optimal treatment of hyponatremia must balance the risks of cerebral edema against the risks of myelinolysis.12
The risk of myelinolysis can be reduced by correcting serum sodium levels in a deliberate manner. It has been suggested that serum sodium concentrations should be increased by no more than 1 to 2 mEq/L/hr. In symptomatic patients, this is accomplished by infusing 3% saline at a rate of 1 to 2 mL/kg/hr. Once the patient is clinically stable, sodium administration should be slowed to raise serum sodium not more than 10 to 15 mmol/L in 24 hours.9,12,14
Hypernatremia can result from several causes (Figure 20-3, Box 20-2, and Table 20-4) but is usually the result of impaired water intake.12 Inadequate administration of free water to hospitalized patients can lead to an iatrogenic hypernatremia. Debilitated, mentally impaired, and intubated individuals are at particular risk for developing hypernatremia.4,12 In cases of slow-onset hypernatremia, the brain can adapt by conserving intracellular solutes, which allows maintenance of normal intracellular volume. Rapidly occurring hypernatremia can be accompanied by rapid shrinking of the brain and concomitant traction on intracranial veins and venous sinuses, leading to intracranial hemorrhage.7
TABLE 20-4
Clinical Signs of Hypernatremia at Increasing Serum Osmolality
| Osmolality (mOsm/kg) | Neurologic Symptoms |
| 350-375 | Confusion, restlessness, agitation, headache |
| 375-400 | Ataxia, tremors, weakness |
| 400-430 | Cramps, hyperreflexia, twitches, spasms |
| > 430 | Coma, seizures, death |
As with hyponatremia, overly aggressive treatment of chronic hypernatremia can lead to unwanted effects. In the case of hypernatremia, rapid correction of serum sodium with solutions containing large amounts of free water may lead to cerebral edema.7
Correction of hypernatremia is carried out by replacement of the water deficit, which can be calculated by the formula shown in Box 20-3. If the hypernatremia is acute (i.e., less than 24 hours’ duration), water deficits can be replaced relatively rapidly with hypotonic solutions. If chronic hypernatremia accompanied by volume depletion is present, the volume disorder is corrected first with isotonic crystalloids. Once the circulating volume has been restored, hypotonic solutions are used to correct the water deficit. Correction of chronic hypernatremia, like treatment of chronic hyponatremia, calls for prudence. Plasma sodium should be decreased by 1 to 2 mEq/hr until the patient is clinically stable, and correction of serum sodium to normal levels should gradually progress over the subsequent 24 hours.12
Disorders of Potassium Balance
Potassium is the principal electrolyte of the ICF, where 98% of the body’s supply of potassium is located. The difference between intracellular and extracellular potassium concentration is in large part responsible for the resting membrane potential of the cell.18 Potassium exists in a dynamic balance between the intracellular and extracellular compartments. Abnormal serum potassium levels may be the result of disturbances in the balance between intracellular and extracellular distribution of potassium or an abnormality in the total body store of potassium. Evaluation and treatment of disorders of potassium homeostasis should address factors that can shift potassium into the cell and total body levels of potassium. The symptoms associated with disorders of potassium homeostasis are largely a reflection of disorders of resting membrane potential.
Hypokalemia, defined as plasma potassium of less than 3.5 mEq/L, can result from an absolute deficiency caused by GI loss, renal loss, or from a poor intake of potassium (Box 20-4). Redistribution of potassium from the extracellular to the intracellular compartment can also lead to hypokalemia. β-Adrenergic stimulation, insulin, and alkalosis all promote movement of potassium into the intracellular space.19
Treatment of hypokalemia depends on the severity of the symptoms accompanying the potassium deficit. In the face of malignant dysrhythmias, aggressive IV administration of potassium is warranted.18 IV replacement of potassium should be accomplished with the patient under continuous electrocardiographic (ECG) monitoring. Rates of IV administration as fast as 40 mEq/hr have been reported,19 although a maximum rate of 10 to 20 mEq/hr is usually recommended to avoid an iatrogenic hyperkalemia.4,7
Once serious symptoms of hypokalemia such as respiratory muscle weakness or dysrhythmias have ceased, IV replacement can be discontinued in favor of oral supplementation.19 It is recommended that IV potassium be replaced as a chloride, because the hypochloride state makes it difficult for the kidney to conserve potassium.4 Furthermore, potassium chloride should be mixed in a dextrose-free solution to prevent stimulation of insulin, leading to increased redistribution of potassium to the intracellular space.7,20
Some clinicians have questioned whether surgery should be canceled because of low serum potassium. In a study of 447 patients scheduled for cardiovascular surgery, Hirsch and co-workers used continuous ECG monitoring to evaluate the preoperative and intraoperative incidence of ectopy. They found no significant difference in frequent or complex ventricular ectopy among patients with normal serum potassium and those with mild to severe hypokalemia. The authors concluded that cancellation of surgery based on low serum potassium was not warranted.21
Hyperkalemia is less common than hypokalemia if renal causes are excluded.19 In addition to impaired renal excretion of potassium, causes of hyperkalemia include a high intake of potassium and a shift of potassium from the intracellular to the extracellular space. Movement of potassium from the intracellular to the extracellular compartment can result from lysis of cells, as well as from acidemia and the administration of β-adrenergic blockers, which inhibit the Na-K–ATPase pump and disrupt movement of potassium into the cell (Box 20-5). Electrocardiographic changes associated with increased levels of potassium are outlined in Table 20-5.
TABLE 20-5
| Potassium mEq/L | ECG Change |
| 6.0-7.5 | Prolonged PR interval, peaked tall T waves, shortened QT interval |
| 7.5-8 | P wave flat, wide QRS, nodal and escape ventricular arrhythmias |
| >8.5 | QRS complex degrades to sine wave pattern, ventricular fibrillation and cardiac arrest |
Treatment of hyperkalemia should be preceded by exclusion of pseudohyperkalemia, which is a laboratory artifact. Pseudohyperkalemia results from hemolysis of the blood sample, leukocytosis, thrombosis, or prolonged fist clenching during blood drawing. Treatment of hyperkalemia is based on the severity of the patient’s presenting signs and symptoms (Table 20-6).
Disorders of Calcium Balance
Calcium is a divalent cation, 99% of which is found in bones. Calcium has an important structural function, but perhaps most important to anesthetists is its role as a second messenger that couples cell membrane receptors to cellular responses. The action of calcium as a second messenger is critical to functions such as muscle contractions and release of hormones and neurotransmitters.2,22 In addition to the second messenger function, calcium plays an important role in coagulation of blood and in muscle function.
Although most of the body’s calcium is found in the bones, a small percentage is freely exchangeable with the ECF. Calcium in the ECF is found in three distinct fractions. Ionized calcium accounts for 50% of the calcium in the ECF and is the physiologically active portion of circulating calcium.1 The remainder of the circulating calcium is bound either to anions (10%) or plasma proteins, primarily albumin (40%).23 Changes in pH alter the extracellular distribution of calcium, with acidemia decreasing the protein-bound fraction and increasing the ionized fraction.4
Because the ionized fraction of calcium is the most clinically significant form, and total serum calcium levels are largely dependent on albumin levels, direct measurement of ionized calcium is the preferred method in critically ill patients.3 Mathematical formulas to “correct” total calcium measurement for albumin concentration are available but have been characterized as inaccurate.4,23
Hypocalcemia has numerous causes (Box 20-6). In the intraoperative period, the most likely causes of hypocalcemia are hyperventilation and massive transfusion of citrated blood. Hyperventilation leads to an increased pH and an increased protein-bound fraction of calcium. Massive transfusion of citrated blood is discussed later in this chapter.
