Barash Clinical Anesthesia PDFDrive .pdf - Acid-Base PDF

4 Metabolic acidosis occurs as a consequence of the use of bicarbonate to buffer endogenous organic acids or as a consequence of external bicarbonate loss. The former causes an increase in the anion gap, calculated as [Na+] − ([Cl−] + [HCO3−]). 5 When substituting mechanical ventilation for spontan...

4 Metabolic acidosis occurs as a consequence of the use of bicarbonate to buffer endogenous organic acids or as a consequence of external bicarbonate loss. The former causes an increase in the anion gap, calculated as [Na+] − ([Cl−] + [HCO3−]). 5 When substituting mechanical ventilation for spontaneous ventilation in a patient with severe metabolic acidosis, appropriate ventilatory compensation should be maintained, pending effective treatment of the primary cause for the metabolic acidosis. 6 Sodium bicarbonate, never proved to alter outcome in acidemic patients, should be reserved for those patients with severe acidemia. 7 Control of blood glucose in critically ill surgical patients has been associated with improvements in clinical outcomes. However, a blood glucose target of 180 mg/dL or less is associated with a lower mortality than a target of 81 to 108 mg/dL. 8 In patients undergoing moderate surgical procedures, generous administration of fluids is associated with fewer minor complications, such as nausea, vomiting, and drowsiness. 9 In patients undergoing colon surgery, careful perioperative fluid restriction has been associated with lower mortality and better wound healing. 10 Homeostatic mechanisms are usually adequate for the maintenance of electrolyte balance. However, critical illnesses and their treatment strategies can cause significant perturbations in electrolyte status, possibly leading to worsened patient outcome. 11 Disorders of the concentration of sodium, the principal extracellular cation, depend on the total body water (TBW) concentration and can lead to neurologic dysfunction. Disorders of potassium, the principal intracellular cation, are influenced primarily by insults that result in increased total body losses of potassium or changes in the distribution between extracellular and intracellular compartments. 12 Calcium, phosphorus, and magnesium are all essential for maintenance and function of the cardiovascular system. In addition, they also provide the milieu that ensures neuromuscular transmission. Disorders affecting any one of these electrolytes may lead to significant dysfunction and possibly result in cardiopulmonary arrest. As a consequence of underlying diseases and of therapeutic manipulations, surgical patients develop potentially harmful disorders of acid–base equilibrium, intravascular and extravascular volume, and serum electrolytes. Precise perioperative management of acid–base status, fluids, and electrolytes may limit perioperative morbidity and mortality. 998 Acid–Base Interpretation and Treatment Management of perioperative acid–base disturbances requires an understanding of the four simple acid–base disorders—metabolic alkalosis, metabolic acidosis, respiratory alkalosis, and respiratory acidosis—as well as more complex combinations of disturbances. This section will review the pathogenesis, major complications, physiologic compensatory mechanisms, and treatment of common perioperative acid–base abnormalities. Overview of Acid–Base Equilibrium Conventionally, acid–base equilibrium is described using the Henderson– Hasselbalch equation: where 6.1 = the pKa of carbonic acid and 0.03 is the solubility coefficient in blood of carbon dioxide (CO2).1 Within this context, pH is the dependent variable, while the bicarbonate concentration ([HCO3−]) and PaCO2 are independent variables; therefore, metabolic alkalosis and acidosis are defined as disturbances in which [HCO3−] is primarily increased or decreased, and respiratory alkalosis and acidosis are defined as disturbances in which PaCO2 is primarily decreased or increased. pH, the negative logarithm of the hydrogen ion concentration ([H+]), defines the acidity or alkalinity of solutions or blood. The simpler Henderson equation, after calculation of [H+] from pH, also describes the relationship between the three major variables measured or calculated in blood gas samples: To approximate the logarithmic relationship of pH to [H+], assume that [H+] is 40 mmol/L at a pH of 7.4; that an increase in pH of 0.10 pH units reduces [H+] to 0.8 × the starting [H+] concentration; that a decrease in pH of 0.10 pH units increases the [H+] by a factor of 1.25; and that small changes (i.e., <0.05 pH units) produce reciprocal increases or decreases of 1 mmol/L in [H+] for each 0.01 decrease or increase in pH units. The alternative “Stewart” approach to acid–base interpretation distinguishes between the independent variables and dependent variables that determine pH.2,3 The independent variables are PaCO2, the strong (i.e., highly dissociated) ion difference, and the concentration of proteins, which usually are not strong ions. The strong ions include sodium (Na+), potassium (K+), 999 chloride (Cl−), and lactate. The strong ion difference, calculated as (Na+ + K+ − Cl−), is approximately 42 mEq/L. Although the Stewart approach provides more insight into the mechanisms underlying acid–base disturbances than does the more descriptive Henderson–Hasselbalch approach, the clinical interpretation or treatment of common acid–base disturbances is rarely handicapped by the simpler constructs of the conventional Henderson– Hasselbalch or Henderson equations.4 Metabolic Alkalosis Metabolic alkalosis, characterized by hyperbicarbonatemia (>27 mEq/L) and usually by an alkalemic pH (>7.45), occurs frequently in postoperative and critically ill patients. Factors that generate metabolic alkalosis include vomiting and diuretic administration (Table 16-1).5 Maintenance of metabolic alkalosis depends on a continued stimulus, such as renal hypoperfusion, hypokalemia, hypochloremia, or hypovolemia, for distal tubular reabsorption of [HCO3−] (Table 16-2).5 Metabolic alkalosis is associated with hypokalemia, ionized hypocalcemia, secondary ventricular arrhythmias, increased digoxin toxicity, and compensatory hypoventilation (hypercarbia), although compensation rarely results in PaCO2 above 55 mmHg (Table 16-3). Alkalemia may reduce tissue oxygen availability by shifting the oxyhemoglobin dissociation curve to the left and by decreasing cardiac output.5 During anesthetic management, inadvertent addition of iatrogenic respiratory alkalosis to preexisting metabolic alkalosis may produce severe alkalemia and precipitate cardiovascular depression, dysrhythmias, and hypokalemia. In patients in whom arterial blood gases have not yet been obtained, serum electrolytes and a history of major risk factors, such as vomiting, nasogastric suction, or chronic diuretic use, can suggest metabolic alkalosis. Estimates of [HCO3−] on serum electrolyte results (often abbreviated as total CO2) should be about 1 mEq/L greater than [HCO3−] on simultaneously obtained arterial blood gases. If either calculated [HCO3−] on the arterial blood gases or “CO2” on the serum electrolytes exceeds normal (24 and 25 mEq/L, respectively) by more than 4 mEq/L, the patient either has a primary metabolic alkalosis or has conserved bicarbonate in response to chronic hypercarbia. Recognition of hyperbicarbonatemia on the preoperative serum electrolytes justifies arterial blood gas analysis and should alert the anesthesiologist to the likelihood of factors that generate or maintain metabolic alkalosis (Tables 16-1 and 16-2). 1000 Table 16-1 Generation of Metabolic Alkalosis Table 16-2 Factors That Maintain Metabolic Alkalosis Treatment of metabolic alkalosis consists of etiologic and nonetiologic therapies. Etiologic therapy consists of measures such as expansion of intravascular volume or the administration of potassium. Infusion of 0.9% saline will dose-dependently increase serum [Cl−] and decrease serum [HCO3−].6 Nonetiologic therapy includes administration of acetazolamide (a carbonic anhydrase inhibitor that causes renal bicarbonate wasting), dialysis against a high-chloride/low bicarbonate dialysate or infusion of [H+] in the form of ammonium chloride, arginine hydrochloride, or 0.1 N hydrochloric acid (100 mmol/L).5 Of the previously mentioned factors, 0.1 N hydrochloric 1001 acid most rapidly corrects life-threatening metabolic alkalosis but must be infused into a central vein; peripheral infusion will cause severe tissue damage. Table 16-3 Respiratory Compensation in Response to Metabolic Alkalosis and Metabolic Acidosis Metabolic Acidosis Metabolic acidosis, characterized by hypobicarbonatemia (<21 mEq/L) and usually by an acidemic pH (<7.35), can be innocuous or reflect a lifethreatening emergency. Metabolic acidosis occurs as a consequence of buffering by bicarbonate of endogenous or exogenous acid loads or as a consequence of abnormal external loss of bicarbonate.7–9 Approximately 70 mmol of acid metabolites are produced, buffered, and excreted daily; these include about 25 mmol of sulfuric acid from amino acid metabolism, 40 mmol of organic acids, and phosphoric and other acids. Extracellular volume (ECV) in a 70-kg adult contains 336 mmol of bicarbonate buffer (24 mEq/L × 14 L of ECV). Glomerular filtration of plasma volume (PV) necessitates reabsorption of 4,500 mmol of bicarbonate daily, of which 85% is reabsorbed in the proximal tubule and 10% in the thick ascending limb, and the remainder is titrated by proton secretion in the collecting duct. Calculation of the anion gap [AG; [Na+] − ([Cl−] + [HCO3−])] distinguishes between two types of metabolic acidosis (Table 16-4).10 The AG is normal (<13 mEq/L) in situations such as diarrhea, biliary drainage, and renal tubular acidosis, in which bicarbonate is lost externally, and is also normal or reduced in hyperchloremic acidosis associated with perioperative infusion of substantial quantities of 0.9% saline.6,11 Metabolic acidosis associated with a high AG (>13 mEq/L) occurs because of excess production or decreased excretion of organic acids or ingestion of one of several toxic compounds (Table 16-4). In metabolic acidosis associated with a high AG, bicarbonate ions are consumed in buffering hydrogen ions, while the associated anion replaces bicarbonate in serum. Three quarters of the normal 1002 AG consists of albumin; to correct the calculated AG for hypoalbuminemia, add to the calculated AG the difference between measured serum albumin and normal albumin concentration (4 g/dL) multiplied by 2 to 2.5.12 The albumincorrected AG should exceed the normal anion gap by an amount (ΔAG) approximately equal to the decrease below normal of serum [HCO3−] (ΔHCO3−).13 A ratio of ΔAG:ΔHCO3− that is below 0.8 or above 1.2 should prompt consideration of a mixed acid–base disturbance. Table 16-4 Differential Diagnosis of Metabolic Acidosis Table 16-5 Failure to Maintain Appropriate Ventilatory Compensation for Metabolic Acidosisa Sufficient reductions in pH may reduce myocardial contractility, increase pulmonary vascular resistance, and decrease systemic vascular resistance. It is particularly important to note that failure of a patient to appropriately hyperventilate in response to metabolic acidosis is physiologically equivalent to respiratory acidosis7 and suggests clinical deterioration. If a patient with metabolic acidosis requires mechanical ventilation, for example, during general anesthesia, every attempt should be made to maintain an 1003 appropriate level of ventilatory compensation (Table 16-3) until the primary process can be corrected. Table 16-5 illustrates failure to maintain compensatory hyperventilation. The anesthetic risk associated with metabolic acidosis is proportional to the severity of the underlying process that produces the metabolic acidosis. Although a patient with hyperchloremic metabolic acidosis may be relatively healthy, those with lactic acidosis, ketoacidosis, uremia, or toxic ingestions will be chronically or acutely ill. Preoperative assessment should emphasize volume status and renal function. If shock has caused metabolic acidosis, direct arterial pressure monitoring may be necessary, and preload may require assessment via echocardiography or pulmonary arterial catheterization. Intraoperatively, one should be concerned about the possibility of exaggerated hypotensive responses to drugs and positive pressure ventilation. In planning intravenous fluid therapy, consider that balanced salt solutions tend to increase pH and [HCO3−] (i.e., by metabolism of lactate to bicarbonate) and 0.9% saline tends to decrease pH and [HCO3−]. The treatment of metabolic acidosis consists of treatment of the primary pathophysiologic process, for example, hypoperfusion or hypoxia, and if pH is severely decreased, administration of NaHCO3−. Hyperventilation, although an important compensatory response to metabolic acidosis, is not a definitive therapy for metabolic acidosis. The initial dose of NaHCO3 can be calculated as: where 0.3 = the assumed distribution space for bicarbonate and 24 mEq/L is the normal value for [HCO3−] on arterial blood gas determination. The calculation markedly underestimates dosage in severe metabolic acidosis. In infants and children, a customary initial dose is 1 to 2 mEq/kg of body weight. Both evidence and opinion suggest that NaHCO3 should rarely be used to treat acidemia induced by metabolic acidosis.7,8,14 In critically ill patients with lactic acidosis, there were no important differences between the physiologic effects (other than changes in pH) of 0.9 M NaHCO3 and 0.9 M sodium chloride.15 Importantly, NaHCO3 did not improve the cardiovascular response to catecholamines and actually reduced plasma ionized calcium.15 Although many clinicians choose to administer NaHCO3 to patients with persistent lactic acidosis and ongoing deterioration, there are no clinical trials that demonstrate improved outcome. In contrast to NaHCO3, the buffer tris-hydroxymethyl aminomethane (THAM) effectively reduces [H+], does not increase plasma [Na+], does not generate CO2 as a byproduct of buffering, 1004 and does not decrease plasma [K+]16; however, there is no generally accepted indication for THAM. Respiratory Alkalosis Respiratory alkalosis, always characterized by hypocarbia (PaCO2 ≤35 mmHg) and usually characterized by an alkalemic pH (>7.45), results from an increase in minute alveolar ventilation (VA) that is greater than that required to excrete metabolic CO2 production. Because respiratory alkalosis may be a sign of pain, anxiety, hypoxemia, central nervous system disease, or systemic sepsis, the development of spontaneous respiratory alkalosis in a previously normocarbic patient requires prompt evaluation. The hyperventilation syndrome, a diagnosis of exclusion, is most often encountered in the emergency department.17 Respiratory alkalosis may produce hypokalemia, hypocalcemia, cardiac dysrhythmias, bronchoconstriction, and hypotension, and may potentiate the toxicity of digoxin. In addition, both brain pH and cerebral blood flow are tightly regulated and respond rapidly to changes in PaCO2.18 Doubling VA reduces PaCO2 to 20 mmHg and halves cerebral blood flow; conversely, halving minute ventilation doubles PaCO2 and doubles cerebral blood flow. Therefore, acute hyperventilation may be useful in neurosurgical procedures to reduce brain bulk and to control intracranial pressure (ICP) during emergent surgery for noncranial injuries associated with acute closed head trauma. In those situations, intraoperative monitoring of arterial blood gases, correlated with capnography, will document adequate reduction of PaCO2. Acute profound hypocapnia (<20 mmHg) may produce electroencephalographic evidence of cerebral ischemia. If PaCO2 is maintained at abnormally high or low levels for 8 to 24 hours, cerebral blood flow will return toward previous levels, associated with a return of cerebrospinal fluid [HCO3−] toward normal. Treatment of respiratory alkalosis per se is often not required. The most important steps are recognition and treatment of the underlying cause.17 For instance, correction of hypoxemia or effective management of sepsis should result in resolution of the associated increases in respiratory drive. Preoperative recognition of chronic hyperventilation necessitates intraoperative maintenance of a similar PaCO2. Respiratory Acidosis Respiratory acidosis, always characterized by hypercarbia (PaCO2 >45 mmHg) and usually characterized by a low pH (<7.35), occurs because of a decrease in VA, an increase in production of carbon dioxide (VCO2) or both, 1005 from the equation: where K = constant (rebreathing of exhaled, carbon dioxide–containing gas may also increase PaCO2). Respiratory acidosis may be either acute, without compensation by renal [HCO3−] retention, or chronic, with [HCO3−] retention, offsetting the decrease in pH (Table 16-6). A reduction in VA may be due to an overall decrease in total minute ventilation (VE) or to an increase in the amount of wasted ventilation (VD), according to the equation: Decreases in VE may occur because of central ventilatory depression by drugs or central nervous system injury, because of increased work of breathing, or because of airway obstruction or neuromuscular dysfunction. Increases in VD occur with chronic obstructive pulmonary disease, pulmonary embolism, decreased cardiac output, and most forms of respiratory failure. VCO2 may be increased by sepsis, high-glucose parenteral feeding, or fever. Patients with chronic hypercarbia due to intrinsic pulmonary disease require careful preoperative evaluation. The ventilatory restriction imposed by upper abdominal or thoracic surgery may aggravate ventilatory insufficiency after surgery. Administration of narcotics and sedatives, even in small doses, may cause hazardous ventilatory depression. Preoperative evaluation should consider direct arterial pressure monitoring and frequent intraoperative blood gas determinations, as well as strategies to manage postoperative pain with minimal doses of systemic opioids. Intraoperatively, a patient with chronically compensated hypercarbia should be ventilated to maintain a normal pH. Inadvertent restoration of normal VA may result in profound alkalemia. Postoperatively, prophylactic ventilatory support may be required for selected patients with chronic hypercarbia. The treatment of respiratory acidosis depends on whether the process is acute or chronic. Acute respiratory acidosis may require mechanical ventilation unless a simple etiologic factor (i.e., narcotic overdosage or residual muscular blockade) can be treated quickly. Bicarbonate administration is never indicated unless severe metabolic acidosis is also present or unless mechanical ventilation is ineffective in reducing acute hypercarbia. In contrast, chronic respiratory acidosis is rarely managed with ventilation but rather with efforts to improve pulmonary function. In patients requiring mechanical ventilation for acute respiratory failure, ventilation with a lung-protective strategy may result in hypercapnia, which occasionally may require administration of buffers to avoid excessive acidemia.19 1006 Table 16-6 Changes of [HCO3−] and pH in Response to Acute and Chronic Changes in PaCO2 Practical Approach to Acid–Base Interpretation Rapid interpretation of a patient’s acid–base status involves the integration of three sets of data: arterial blood gases, electrolytes, and history. A systematic approach facilitates interpretation (Table 16-7). Acid–base assessment usually can be completed before initiating therapy; however, the first step should be to determine whether there are life-threatening pH disturbances (e.g., respiratory acidosis or metabolic acidosis with pH < 7.1) that require immediate attention. The second step is to determine whether a patient is acidemic (pH < 7.35) or alkalemic (pH > 7.45). The pH status will usually indicate the predominant primary process, that is, acidosis produces acidemia and alkalosis produces alkalemia. Note that the suffix “-osis” indicates a primary process that, if unopposed, will produce the corresponding pH change. The suffix “-emia” refers to the pH. A compensatory process is not considered an “-osis.” Of course, a patient may have mixed “-oses,” that is, more than one primary process. The third step is to determine whether the entire arterial blood gas picture is consistent with a simple acute respiratory alkalosis or acidosis (Table 16-6). For example, a patient with acute hypocarbia (PaCO2 30 mmHg) would have a pH increase of 0.10 units to a pH of 7.50 and a decrease of calculated [HCO3−] to 22 mEq/L. As the fourth step, recognition that changes in PaCO2, pH, and [HCO3] which are not consistent with a simple acute respiratory disturbance should prompt consideration of chronic respiratory acidosis (≥24 hours) or metabolic acidosis or alkalosis. In chronic respiratory acidosis, pH returns to nearly normal as bicarbonate is retained by the kidneys (Table 16-6), usually 1007 at a ratio of 4 to 5 mEq/L per 10 mmHg chronic increase in PaCO2.20 For example, chronic hypoventilation at a PaCO2 of 60 mmHg would be associated with an increase in [HCO3−] of 8 to 10 mEq/L so that [HCO3−] would be expected to range from 32 to 34 mEq/L and pH would be expected to be within the low normal range (7.35 to 7.38). If neither an acute nor chronic respiratory change appears to explain the arterial blood gas data, then a metabolic disturbance must also be present. Table 16-7 Sequential Approach to Acid–Base Interpretation The fifth question addresses respiratory compensation for metabolic disturbances, which occurs more rapidly than renal compensation for respiratory disturbances (Table 16-3). Several general rules describe compensation. First, overcompensation is rare. Second, inadequate or excessive compensation suggests an additional primary disturbance. Third, hypobicarbonatemia associated with an increased anion gap is never compensatory. The sixth question, whether an anion gap is present, should be assessed even if the arterial blood gases appear straightforward. The simultaneous occurrence of metabolic alkalosis and metabolic acidosis may result in an unremarkable pH and [HCO3−]; therefore, the combined abnormality may only be appreciated by examining the anion gap (if the cause of the metabolic acidosis is associated with a high anion gap). As noted previously, correct assessment of the anion gap requires correction for hypoalbuminemia.12 Metabolic acidoses associated with increased anion gaps require specific treatments, thus necessitating a correct diagnosis and differentiation from hyperchloremic metabolic acidosis. For instance, if metabolic acidosis results from administration of large volumes of 0.9% saline, no specific treatment of metabolic acidosis would usually be necessary. The seventh and final question is whether the clinical data are consistent with the proposed acid–base interpretation. Failure to integrate clinical findings with arterial blood gas and plasma electrolyte data may lead to serious errors in interpretation and management. 1008 Examples The following two hypothetical cases illustrate the use of the algorithm and rules of thumb previously discussed. Example 1 A 65-year-old woman has undergone 12 hours of an expected 16-hour radical neck dissection and flap construction. Estimated blood loss is 1,000 mL. She has received three units of packed red blood cells and 6 L of 0.9% saline. Her blood pressure and heart rate have remained stable while anesthetized with 0.5% to 1% isoflurane in 70:30 nitrous oxide and oxygen. Urinary output is adequate. Arterial blood gas levels are shown in Table 16-8. The step-by-step interpretation is as follows: 1. The pH requires no immediate treatment. 2. The pH is normal. 3. The arterial blood gases cannot be adequately explained by acute hypocarbia. The predicted pH would be 7.48 and the predicted [HCO3−] would be 22 mEq/L (Table 16-6). 4. A metabolic acidosis appears to be present. 5. Patients under general anesthesia with controlled mechanical ventilation cannot compensate for metabolic acidosis. However, spontaneous hypocarbia of this magnitude would represent slight overcompensation for metabolic acidosis (Table 16-3) and would suggest the presence of a primary respiratory alkalosis. 6. Metabolic acidosis occurring during prolonged anesthesia and surgery could suggest lactic acidosis and prompt additional fluid therapy or other attempts to improve perfusion. However, serum electrolytes reveal an AG that is slightly less than normal (Table 16-8), suggesting that the metabolic acidosis is probably the result of dilution of the ECV with a high-chloride fluid. Correction of the AG for the serum albumin of 3 g/dL only increases the anion gap to 10 to 11 mEq/L, again consistent with hyperchloremic metabolic acidosis. After differentiation from high-AG metabolic acidoses, hyperchloremic acidosis secondary to infusion of high-chloride fluid usually requires no treatment. The arterial blood gases and serum electrolytes are compatible with the clinical picture. 1009 Table 16-8 Hyperchloremic Metabolic Acidosis during Prolonged Surgery Example 2 A 35-year-old man, 3 days after appendectomy, develops nausea with recurrent emesis persisting for 48 hours. An arterial blood gas reveals the results shown in the third column of Table 16-9. 1. The pH of 7.50 requires no immediate intervention. 2. The pH is alkalemic, suggesting a primary alkalosis. 3. An acute PaCO2 of 46 mmHg would yield a pH of approximately 7.37; therefore, this is not simply an acute ventilatory disturbance. 4. The patient has a primary metabolic alkalosis as suggested by the [HCO3−] of 35 mEq/L. 5. The limits of respiratory compensation for metabolic alkalosis are wide and difficult to predict for individual patients. The rules of thumb, summarized in Table 16-3, suggest that [HCO3−] + 15 should equal the last two digits of the pH and that the PaCO2 should increase 5 to 6 mmHg for every 10 mEq/L change in serum [HCO3−]; that is, a pH of 7.50 and a PaCO2 of 46 mmHg are within the expected range. Table 16-9 Metabolic Alkalosis Secondary to Nausea and Vomiting with Subsequent Lactic Acidosis Secondary to Hypovolemia 6. The anion gap is 10 mEq/L. 1010 7. The diagnosis of a primary metabolic alkalosis with compensatory hypoventilation is consistent with the history of recurrent vomiting. Consider how the arterial blood gases could change if vomiting were sufficiently severe to produce hypovolemic shock and lactic acidosis (fourth column of Table 16-9). This sequence illustrates the important concept that the final pH, PaCO2, and [HCO3−] represent the result of all of the vectors operating on acid–base status. Complex or “triple disturbances” can only be interpreted using a thorough, stepwise approach. Fluid Management Physiology Body Fluid Compartments Accurate replacement of fluid deficits necessitates an understanding of the expected volumes of distribution spaces for water, sodium, and colloid. The sum of intracellular volume (ICV; 40% of total body weight), ECV (20% of body weight), equals total body water (TBW), which therefore approximates 60% of total body weight. Plasma volume equals about 3 L, one-fifth of ECV, the remainder of which is interstitial fluid volume (IFV). Red cell volume, approximately 2 L, is part of ICV. The volume of distribution of sodium-free water is TBW while the distribution volume of infused sodium is ECV. The sodium concentrations ([Na+]) in PV and IFV, the two components of the ECV, are approximately 140 mEq/L. The predominant intracellular cation, potassium, has an intracellular concentration ([K+]) approximating 150 mEq/L. The volume of distribution for colloid solutions is the ECV. Albumin, the most important oncotically active colloid in the ECV, is unequally distributed in PV (∼4 g/dL) and IFV (∼1 g/dL). However, the IFV concentration of albumin varies greatly among tissues. Distribution of Infused Fluids Conventionally, clinical prediction of PV expansion after fluid infusion assumes that body fluid spaces are static. Kinetic analysis of PV expansion replaces the static assumption with a dynamic description. As an example of the static approach, assume that a 70-kg patient has suffered an acute blood loss of 2,000 mL, approximately 40% of the predicted 5 L blood volume. The formula describing the effects of replacement with 5% dextrose in water (D5W), lactated Ringer solution, or 5% or 25% human serum albumin is as follows: 1011 Calculating the volume of a given fluid required to produce a certain PV increment requires the following rearrangement of the equation: To restore blood volume using D5W, assuming a distribution volume for sodium-free water of TBW, requires 28 L: where 2 L is the desired PV increment, 42 L = TBW in a 70-kg person, and 3 L is the normal estimated PV. To restore blood volume using lactated Ringer solution requires 9.1 L: where 14 L = ECV in a 70-kg person. If 5% albumin, which exerts colloid osmotic pressure similar to plasma, were infused, the infused volume initially would remain in the PV, perhaps attracting additional interstitial fluid intravascularly. Twenty-five percent human serum albumin, a concentrated colloid, expands PV by approximately 400 mL for each 100 mL infused. However, these static analyses are simplistic. Infused fluid does not simply equilibrate throughout an assumed distribution volume but is added to a complex system that regulates intravascular, interstitial, and ICV. A more comprehensive kinetic model was proposed by Svensén and Hahn.21 Kinetic models of intravenous fluid therapy allow clinicians to predict more accurately the time course of volume changes produced by infusions of fluids of various compositions. Kinetic analysis permits estimation of peak volume expansion and rates of clearance of infused fluid and complements analysis of “pharmacodynamic” effects, such as changes in cardiac output or cardiac filling pressures.22 Using a kinetic approach to fluid therapy permits analysis of the effects of common physiologic and pharmacologic influences on fluid distribution in experimental animals or humans. For example, in chronically instrumented sheep, fluid infusion during isoflurane anesthesia was associated with greater expansion of extravascular volume than in the conscious state.23 The kinetics of PV expansion after fluid infusion were similar in conscious and anesthetized sheep, but reduced urinary output under anesthesia was associated with greater expansion of extravascular volume; this effect was attributable to isoflurane and not to mechanical ventilation.23 Similar studies 1012 in volunteers suggested that the influence of anesthesia on fluid kinetics could be related to lower mean arterial pressures and activation of the renin/angiotensin/aldosterone system.24 In subsequent studies in sheep, administration of catecholamine infusions before and during fluid infusions profoundly altered intravascular fluid retention, with phenylephrine diminishing and isoproterenol enhancing intravascular fluid retention (Fig. 16-1).25 The influence of rapid fluid infusion on the integrity of the endothelial glycocalyx potentially confounds volume kinetic assessment of PV. Rapid infusion of crystalloid fluids can potentially release noncirculating fluid volume that is trapped within the endothelial glycocalyx,26 resulting in apparent rather than actual plasma dilution. Regulation of Osmolarity and Effective Circulating Volume TBW content is the net result of intake and output of water. Water intake includes ingested liquids plus an average of 750 mL ingested in solid food and 350 mL that is generated metabolically. Water output consists of insensible losses (∼1,000 mL/day), gastrointestinal losses (100 to 150 mL/day), and urinary output, the volume of which is regulated to maintain TBW. Thirst, the primary mechanism of controlling water intake, is triggered by an increase in body fluid tonicity or by a decrease in effective circulating volume. 1013 Figure 16-1 A: Blood hemoglobin (mean ± SEM) sampled at three baseline periods during a 30-minute catecholamine infusion and for 3 hours after starting a 20-minute 0.9% NaCl bolus of 24 mL/kg. Catecholamine protocols are dopamine (Dopa, open diamonds), isoproterenol (Iso, closed circles), phenylephrine (Phen, open triangles), and no-drug control (Control, closed squares). The 0.9% NaCl bolus decreased hemoglobin in all protocols at the end of the 20-minute 0.9% NaCl infusion and in all protocols except the Phen protocol thereafter. Postinfusion protocol differences were Phen > Dopa = Control > Iso. B: Calculated blood volume (mean ± SEM) at three baseline periods during a catecholamine infusion and for 3 hours after starting a 20minute 0.9% NaCl bolus of 24 mL/kg. The 0.9% NaCl bolus increased blood volume in all protocols at T 20 and in all protocols except the Phen protocol thereafter. Postinfusion protocol differences were Iso > Dopa = Control > Phen. NS, normal saline bolus. (Adapted with permission from Vane LA, Prough DS, Kinsky MA, et al. Effects of different catecholamines on the dynamics of volume expansion of crystalloid infusion. Anesthesiology. 2004;101:1136–1144.) Renal reabsorption of filtered water and sodium is regulated by the renin/angiotensin/aldosterone system, antidiuretic hormone (ADH), and natriuretic peptides.27 Renal water handling has three important components: (1) delivery of tubular fluid to the diluting segments of the nephron, (2) 1014 separation of solute and water in the diluting segment, and (3) variable reabsorption of water in the collecting ducts. In the descending loop of Henle, water is reabsorbed while solute is retained to achieve a final osmolality of tubular fluid of approximately 1,200 mOsm/kg (Fig. 16-2). This concentrated fluid is then diluted by the active reabsorption of sodium via the NaKCl2 transporter in the ascending limb of the loop of Henle28 and via the Na/Cl transporter in the distal tubule, both of which are relatively impermeable to water. Within the collecting duct, water reabsorption is modulated by ADH (also called vasopressin).29 Vasopressin binds to V2 receptors (G-protein coupled receptors) along the basolateral membrane of the collecting duct cells; the resulting increased cAMP levels then stimulate the synthesis and insertion of the aquaporin-2 water channel into the apical membrane of collecting duct cells.30,31 Plasma hypotonicity suppresses ADH release, resulting in excretion of dilute urine. Hypertonicity stimulates ADH secretion, which increases the permeability of the collecting duct to water and enhances water reabsorption. In response to changing plasma [Na+], changing secretion of ADH can vary urinary osmolality from 50 to 1,200 mOsm/kg and urinary volume from 0.4 to 20 L/day (Fig. 16-3).32 Nonosmotic modulators of ADH secretion include hemodynamic (hypotension, hypovolemia, congestive heart failure, cirrhosis, nephrotic syndrome, and adrenal insufficiency) and nonhemodynamic stimuli (nausea, pain, and medications, including opiates).33 Two powerful hormonal systems regulate total body sodium. The natriuretic peptides, ANP, brain natriuretic peptide, and C-type natriuretic peptide, defend against sodium overload34,35 and the renin–angiotensin– aldosterone axis defends against sodium depletion and hypovolemia. ANP, released from the cardiac atria in response to increased atrial stretch, exerts vasodilatory effects and increases the renal excretion of sodium and water. ANP secretion is decreased during hypovolemia. Even in patients with chronic (nonoliguric) renal insufficiency, infusion of ANP in low, nonhypotensive doses increased sodium excretion and augmented urinary losses of retained solutes.34 Aldosterone is the final common pathway in a complex response to decreased effective arterial volume, whether decreased effective arterial volume is absolute or relative, as in edematous states or hypoalbuminemia. In this pathway, decreased stretch in the baroreceptors of the aortic arch and carotid body and stretch receptors in the great veins, pulmonary vasculature, and atria result in increased sympathetic tone. Increased sympathetic tone, in combination with decreased renal perfusion, leads to renin release and formation of angiotensin I from angiotensinogen. Subsequently, in the lungs, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, which stimulates the adrenal cortex to synthesize and release aldosterone.36 1015 Acting primarily in the distal tubules, high concentrations of aldosterone cause sodium reabsorption and may reduce urinary excretion of sodium nearly to zero. Intrarenal physical factors are also important in regulating sodium balance. Sodium loading decreases colloid osmotic pressure, thereby increasing the glomerular filtration rate (GFR), decreasing net sodium reabsorption, and increasing distal sodium delivery, which, in turn, suppresses renin secretion. Fluid Replacement Therapy Maintenance Requirements for Water, Sodium, and Potassium Calculation of maintenance fluid requirements is of limited value in determining intraoperative fluid requirements. However, calculation of maintenance fluid requirements (Table 16-10) is useful for estimating water and electrolyte deficits that result from preoperative restriction of oral food and fluids and for estimating the ongoing requirements for patients with prolonged postoperative bowel dysfunction. In healthy adults, sufficient water is required to balance gastrointestinal losses (100 to 200 mL/day), insensible losses (500 to 1,000 mL/day), and urinary losses of 1,000 mL/day. Urinary losses exceeding 1,000 mL/day may represent an appropriate physiologic response to ECV expansion or pathophysiologic inability to conserve salt or water. Figure 16-2 Renal filtration, reabsorption, and excretion of water. Open arrows represent water and solid arrows represent electrolytes. Water and electrolytes are filtered by the glomerulus. In the proximal tubule (1), water and electrolytes are absorbed isotonically. In the descending loop of Henle (2), water is absorbed to achieve osmotic equilibrium with the interstitium while electrolytes are retained. The numbers (300, 600, 900, and 1,200) between the descending and ascending limbs represent the osmolality of the interstitium in milliosmoles per kilogram. The delivery of solute and fluid to the distal nephron is a function of proximal tubular reabsorption; as proximal tubular 1016 reabsorption increases, delivery of solute to the medullary (3a) and cortical (3b) diluting sites decreases. In the diluting sites, electrolyte-free water is generated through selective reabsorption of electrolytes while water is retained in the tubular lumen, generating a dilute tubular fluid. In the absence of vasopressin, the collecting duct (4a) remains relatively impermeable to water and diluted urine is excreted. When vasopressin acts on the collecting ducts (4b), water is reabsorbed from these vasopressin-responsive nephron segments, allowing the excretion of concentrated urine. (Adapted with permission from Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin North Am. 1997:585–609.) Daily adult requirements for sodium and potassium are approximately 75 and 40 mEq respectively, although wider ranges of sodium intake than potassium intake are physiologically tolerated because renal sodium conservation and excretion are more efficient than potassium conservation and excretion. Therefore, healthy, 70-kg adults require 2,500 mL/day of water containing [Na+] of 30 mEq/L and [K+] of 15 to 20 mEq/L. Intraoperatively, fluids containing sodium-free water (i.e., [Na+] < 130 mEq/L) are rarely used in adults because of the necessity for replacing isotonic losses and the risk of postoperative hyponatremia.37–40 Figure 16-3 Left: The sigmoid relationship between plasma vasopressin (VP) and urinary osmolality. Data were obtained during water loading and fluid restriction in a group of healthy adults. Maximum urinary concentration is achieved by plasma VP values of 3 to 4 pmol/L. Right: The linear relationship between plasma osmolality and plasma VP. Increases in VP in response to hypertonicity induced by infusion of 855 mmol/L saline in a group of healthy adults. The shaded area represents the reference range response. LD represents the limit of detection of the VP assay, 0.3 pmol/L. (Adapted with permission from Ball SG. Vasopressin and disorders of water balance: the physiology and pathophysiology of vasopressin. Ann Clin Biochem. 2007;44:417–431.) 1017 Dextrose Traditionally, glucose-containing intravenous fluids have been given in an effort to prevent hypoglycemia and limit protein catabolism. However, because of the hyperglycemic response associated with surgical stress, only infants and patients receiving insulin or drugs that interfere with glucose synthesis are at risk for hypoglycemia. Iatrogenic hyperglycemia can limit the effectiveness of fluid resuscitation by inducing an osmotic diuresis and, in animals, may aggravate ischemic neurologic injury.41 Although associated with worsened clinical outcome after subarachnoid hemorrhage42 and traumatic brain injury,43 hyperglycemia may also constitute a hormonally mediated response to more severe injury. In a meta-analysis of studies performed in critically ill patients, targeted blood glucose management, at a target of 180 mg/dL or less, was associated with reduced mortality and morbidity in comparison with a tighter control target of 81 to 108 mg/dL.44 Table 16-10 Hourly and Daily Maintenance Water Requirements Surgical Fluid Requirements Water and Electrolyte Composition of Fluid Losses Surgical patients require replacement of PV and ECV losses secondary to wound or burn edema, ascites, and gastrointestinal secretions. The fluid composition of wound and burn edema and ascitic fluid is protein-rich, with electrolyte concentrations similar to those of plasma. Although gastrointestinal secretions vary greatly in composition, the composition of replacement fluid need not be closely matched if ECV is adequate and renal and cardiovascular functions are normal. Substantial loss of gastrointestinal fluids requires more accurate replacement of electrolytes (i.e., potassium, magnesium, phosphate). Chronic gastric losses may produce hypochloremic metabolic alkalosis that can be corrected with 0.9% saline; chronic diarrhea may produce hyperchloremic metabolic acidosis that may be prevented or corrected by infusion of fluid containing bicarbonate or bicarbonate substrate (e.g., lactate). If cardiovascular or renal function is impaired, more precise replacement may require frequent assessment of serum electrolytes. Influence of Perioperative Fluid Infusion Rates on Clinical Outcomes 1018 Conventionally, intraoperative fluid management included replacement of fluid (“third space fluid”) that was assumed to accumulate extravascularly in surgically manipulated tissue.45 Until recently, perioperative clinical practice included, in addition to replacement of estimated blood loss, 4 to 6 mL/kg/hr for procedures involving minimal tissue trauma, 6 to 8 mL/kg/hr for those involving moderate trauma, and 8 to 12 mL/kg/hr for those involving severe trauma. However, clinical trials strongly link perioperative fluid management to both minor and major morbidities. Moreover, the influence of fluid volume and composition appear to be specific to the type of surgery used . Maharaj et al.46 randomized 80 ASA I–II patients scheduled for gynecologic laparoscopy to either large volume, defined as 2 mL/kg/hr of fasting over 20 minutes preoperatively (e.g., 1,440 mL/60 kg in a patient who had been fasting for 12 hours) or small volume, defined as total fluid of 3 mL/kg over 20 minutes preoperatively. In patients receiving the higher dose, postoperative nausea and vomiting and pain were significantly reduced (Fig. 16-4).46 Holte et al.47 randomized 48 ASA I–II patients undergoing laparoscopic cholecystectomy to receive either 15 or 40 mL/kg of lactated Ringer solution intraoperatively; the higher dose of fluid was associated with improved postoperative pulmonary function and exercise capacity, reduced neurohumoral stress response, and improvements in nausea, general sense of well-being, thirst, dizziness, drowsiness, fatigue, and balance function. Holte et al.48 randomized 48 ASA I–III patients undergoing fast-track elective knee arthroplasty under intraoperative epidural/spinal anesthesia and postoperative epidural analgesia to either liberal or restricted fluids. Median intravenous fluid administered intraoperatively and in the postanesthesia care unit in the restrictive group was 1,740 mL (range, 1,100–2,165 mL) of lactated Ringer solution and in the liberal group was 3,275 mL (range, 2,400– 4,000 mL). Restrictive fluid administration was associated with a higher incidence of vomiting but less hypercoagulability and no difference in shortterm postoperative mobility or ileus. Therefore, in patients undergoing surgery of limited scope, fluid restriction appears to be less well tolerated than more liberal fluid therapy, but perhaps at the expense of hypercoagulability. 1019 Figure 16-4 Top: Mean postoperative verbal analogue scale (VAS) nausea scores in each group over the first 72 postoperative hours. Mean VAS nausea scores were significantly lower in the group that received the large-volume intravenous fluid infusion compared with the control group at 1, 4, 24, and 72 hours postoperatively. Bottom: Mean postoperative VAS pain scores in each group over the first 72 postoperative hours. Mean VAS pain scores were significantly lower in the group that received the large-volume intravenous fluid infusion compared with the control group at 0, 1, 24, and 72 hours postoperatively. *Significantly higher (p < 0.05, t-test postanalysis of variance) VAS score compared with the large volume group. PACU, postanesthesia care unit. (Adapted with permission from Maharaj CH, Kallam SR, Malik A, et al. Preoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth Analg. 2005;100:675–682.) In patients undergoing major intra-abdominal surgery, recent randomized controlled trials also suggest that restrictive fluid administration is associated with a combination of positive and negative effects. Brandstrup et al.49 randomized 172 elective colon surgery patients to either restrictive perioperative fluid management or standard perioperative fluid management, with the primary goal of maintaining preoperative body weight in the fluidrestricted group. By design, the fluid-restricted group received less 1020 perioperative fluid and gained less than 1 kg (the weight of 1 L of fluid), in contrast to more than 3 kg in the standard therapy group. More importantly, cardiopulmonary complications, tissue-healing complications, and total postoperative complications were significantly fewer in the fluid-restricted group. In 152 patients undergoing intra-abdominal surgery, including colon surgery, Nisanevich et al.50 reported less prompt return of gastrointestinal function and longer hospital stays in patients receiving conventional fluid therapy (10 mL/kg/hr of lactated Ringer solution) than in patients receiving restricted fluid therapy (4 mL/kg/hr). In a small clinical trial comparing gastric emptying in patients randomized to receive postoperative fluids at a restricted (≤2 L/day of water; ≤77 mEq/day of Na+) or liberal regimen (≥3 L/day; ≥154 mEq/day), gastric emptying time for both liquids and solids was significantly reduced in patients receiving restricted fluids (Fig. 165).51 Khoo et al.52 randomized 70 ASA I–III patients undergoing elective colorectal surgery to conventional perioperative management, including intraoperative fluid management at the discretion of the anesthesiologist, or to multimodal perioperative management, including intraoperative fluid restriction, unrestricted postoperative oral intake, prokinetic agents, early ambulation, and postoperative epidural analgesia. Multimodal perioperative management was associated with a reduced median stay (5 vs. 7 days) and fewer cardiorespiratory and anastomotic complications, but more hospital readmissions. Holte et al.53 randomized 32 ASA I–III patients undergoing “fast-track” colon resection under combined epidural/general anesthesia to intraoperative fluid administration using either a restrictive (median: 1,640 mL; range: 935 to 2,250 mL) or liberal (median: 5,050 mL; range: 3,563 to 8,050 mL) regimen. Fluid-restricted patients had significantly improved postoperative forced vital capacity and fewer, less severe episodes of oxygen desaturation, but at the expense of increased stress responses (aldosterone, ADH, and angiotensin II measurements), and a statistically insignificantly increased number of complications. In a recent meta-analysis, Corcoran et al.54 reviewed 23 randomized trials involving 3,861 patients assigned to liberal or goal-directed therapy during major surgery. Patients in both the liberal and goal-directed therapy groups received more fluid during surgery than their respective comparative groups (restrictive fluid administration). However, the patients in the liberal groups had a higher risk of pneumonia (risk ratio 2.2), pulmonary edema (risk ratio 3.8), and longer hospital stay (mean difference 2 days) than their comparative groups. The patients in the goal-directed therapy groups had a lower risk of pneumonia and renal complications (risk ratio 0.7), and shorter hospital stay (mean difference 2 days) compared to the patients in the non–goal-directed therapy group. These authors concluded that goal-directed fluid therapy was associated with fewer adverse outcomes than non–goal-directed, liberal fluid administration. 1021 However, they also concluded that the data do not establish whether goaldirected fluid therapy is superior to non–goal-directed restrictive fluid therapy. Figure 16-5 Solid and liquid phase gastric emptying times (T 50) after 4 days of standard or restricted intravenous postoperative fluid therapy. Solid lines are medians, shaded areas interquartile ranges, and whiskers represent extreme values. Differences between medians for solid and liquid phase T 50 were 56 minutes (95% confidence interval: 12 to 132 minutes) and 52 minutes (9 to 95 minutes), respectively. (Adapted with permission from Lobo DN, Bostock KA, Neal KR, et al. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet. 2002;359:1812.) Critically ill patients with acute lung injury represent an important group that may benefit from careful regulation of fluid intake. The ARDS Clinical Trials Network55 randomized 1,000 patients with acute lung injury to a 7-day 1022 trial comparing a conservative fluid strategy with a liberal fluid strategy. Over the course of the trial the conservative strategy group had a cumulative net fluid balance that was slightly negative in comparison to a mean net cumulative fluid balance in the liberal group of nearly 7 L. Although overall mortality was no different in the two groups, the conservative fluid group had improved oxygenation and required fewer days of mechanical ventilation and intensive care. Despite achieving a negative fluid balance, the conservative strategy group had no greater incidence of acute renal failure. Colloids, Crystalloids, and Hypertonic Solutions Physiology and Pharmacology Osmotically active particles attract water across semipermeable membranes until equilibrium is attained. Osmolarity is defined as the number of osmotically active particles per liter of solvent; osmolality, defined as the number of osmotically active particles per kilogram, can be estimated as follows: where osmolality is expressed in mmol/kg, [Na+] is expressed in mEq/L, serum glucose is expressed in mg/dL, and BUN is blood urea nitrogen expressed in mg/dL. Sugars, alcohols, and radiographic dyes increase measured osmolality, generating an increased “osmolal gap” between the measured and calculated values. High concentrations of osmotically active particles lead to hyperosmolar states. Both uremia (increased BUN) and hypernatremia (increased serum sodium) increase serum osmolality. However, because urea distributes throughout TBW, an increase in BUN does not cause hypertonicity. Sodium, largely restricted to the ECV, causes hypertonicity, that is, osmotically mediated redistribution of water from ICV to ECV. The term tonicity is also used colloquially to compare the osmotic pressure of a parenteral solution to that of plasma. Although only a small proportion of the osmotically active particles in blood consist of plasma proteins, those particles are essential in determining the equilibrium of fluid between the interstitial and plasma compartments of ECV. The reflection coefficient (σ) describes the permeability of capillary membranes to individual solutes, with 0 representing free permeability and 1 representing complete impermeability. The reflection coefficient for albumin ranges from 0.6 to 0.9 in various capillary beds. Because capillary protein concentrations exceed interstitial concentrations, the osmotic pressure exerted by plasma proteins (termed colloid osmotic pressure or oncotic pressure) is 1023 higher than interstitial oncotic pressure and tends to preserve PV. The filtration rate of fluid from the capillaries into the interstitial space is the net result of a combination of forces, including the gradient from intravascular to interstitial colloid osmotic pressures and the hydrostatic gradient between intravascular and interstitial pressures. The net fluid filtration at any point within a systemic or pulmonary capillary is approximated by Starling law of capillary filtration, as expressed in the equation: where Q = fluid filtration, k = capillary filtration coefficient (conductivity of water), A = area of the capillary membrane, Pc = capillary hydrostatic pressure, Pi = interstitial hydrostatic pressure, σ = the reflection coefficient for albumin, πi = interstitial colloid osmotic pressure, and πc = capillary colloid osmotic pressure. However, it is important to note that the Starling law does not account for the influence on fluid filtration of the capillary glycocalyx, which is strongly influenced by disease processes and fluid administration.56 Attachment of albumin to the endothelial glycocalyx results in the colloid osmotic pressure gradient actually being the difference between πc and the colloid osmotic pressure in the space between the endothelial glycocalyx and the capillary wall.57 The IFV is determined by the relative rates of capillary filtration and lymphatic drainage. Pc, the most powerful factor promoting fluid filtration, is determined by capillary flow, arterial resistance, venous resistance, and venous pressure. If capillary filtration increases, the rates of water and sodium filtration usually exceed protein filtration, resulting in preservation of πc, dilution of πi, and preservation of the oncotic pressure gradient, the most powerful factor opposing fluid filtration. When coupled with increased lymphatic drainage, preservation of the oncotic pressure gradient limits the accumulation of IF. If Pc increases at a time when lymphatic drainage is maximal, then IFV accumulates, forming edema. However, because of the influence of the glycocalyx, theoretical rates of fluid filtration usually substantially exceed actual filtration rates, a phenomenon termed the “low lymph flow paradox.”57 Clinical Implications of Choices between Alternative Fluids If membrane permeability is intact, colloids such as albumin or hydroxyethyl starch (HES) preferentially expand PV rather than IFV. Concentrated colloidcontaining solutions (e.g., 25% albumin) exert sufficient oncotic pressure to translocate substantial volumes of IFV into the PV, thereby increasing PV by a volume that exceeds the original infused volume. PV expansion unaccompanied by IFV expansion offers apparent advantages: Lower fluid 1024 requirements, less peripheral and pulmonary edema accumulation, and reduced concern about the cardiopulmonary consequences of later fluid mobilization (Table 16-11). However, exhaustive research has failed to establish the superiority of either colloid-containing or crystalloid-containing fluids for either intraoperative or postoperative use. Despite the lack of conclusive evidence of efficacy, albumin has been used in critically ill patients for decades.58 In patients with sepsis or septic shock, the Early Albumin Resuscitation during Septic Shock (EARSS) study59 and the Albumin Italian Outcome Sepsis (ALBIOS) trial60 failed to find any overall difference in mortality. However, in the ALBIOS trial, time to discontinue vasoactive agents was shorter in the albumin group and, in a post hoc analysis, the subgroup of patients presenting with septic shock had a significantly reduced 90-day mortality if they received albumin. This benefit remained after adjustment of confounding variables.61 Meta-analyses have generated conflicting information regarding the influence of albumin administration on outcome. In burn patients who received albumin, mortality and the incidence of abdominal compartment syndrome were reduced.62 In hypoalbuminemic patients who were resistant to diuretics, coadministration of albumin and furosemide transiently improved urinary output and sodium excretion.63 In a meta-analysis of clinical trials in patients with acute respiratory distress syndrome (ARDS), albumin administration was associated with improved oxygenation but no increase in survival.64 Overall, the findings of these reviews are confounded by heterogeneity and by the paucity of available clinical data, thus making it more difficult to elucidate the benefit of albumin resuscitation in critically ill patients. HES, once a commonly used synthetic colloid, has been linked in critically ill patients to increased mortality and morbidity such as coagulopathy, pruritus, nephrotoxicity, and acute renal failure.65 In the “6S Trial,” HES was associated with an increased risk of death and end-stage renal failure in comparison to Ringer acetate.66 As a consequence, the Surviving Sepsis Campaign recommended that HES be eliminated from treatment of septic patients.67 Subsequently, the US Food and Drug Administration banned all marketing of HES due to lack of evidence of clinical benefit in any patient population, with abundant evidence of harm, especially kidney failure. Eventually, HES was recalled from the US market. 1025 Table 16-11 Claimed Advantages and Disadvantages of Colloid Versus Crystalloid Intravenous Fluids Colloids and Traumatic Brain Injury Two-year follow-up of a subset of 460 patients with traumatic brain injury (Glasgow Coma Scale score ≤ 13) demonstrated a nearly twofold increased risk of death in patients receiving colloid fluid management.68 A subsequent secondary analysis suggested that patients receiving 4% albumin had a higher incidence of refractory intracranial hypertension.69 Van Aken et al.70 offered a plausible explanation, in that the 4% albumin solution used in the SAFE trial was suspended in a hypo-osmolar carrier solution, so that the adverse effects of the infusion could have been due to reduced osmolality, independent of the colloid content. Cirrhotic patients may represent a specific subset of patients in whom albumin infusion could be beneficial. In patients with decompensated cirrhosis, infusion of albumin reduced prostaglandin E2 and improved macrophage function.71 In rodents with cirrhosis and ascites, albumin improved cardiac function, apparently by