• Although the intravascular half-life of a crystalloid solution is 20-30 min, most colloid solutions have intravascular half-lives between 3 and 6 h.
  
• Patients with a normal hematocrit should generally be transfused only after losses greater than 10-20% of their blood volume. The exact point is based on the patient’s medical condition and the surgical procedure.
  
• The most severe transfusion reactions are due to ABO incompatibility; naturally acquired antibodies can react against the transfused (foreign) antigens, activate complement, and result in intravascular hemolysis.
  
• In anesthetized patients, an acute hemolytic reaction is manifested by a rise in temperature, unexplained tachycardia, hypotension, hemoglobinuria, and diffuse oozing in the surgical field.
  
• Allogeneic transfusion of blood products may diminish immunoresponsiveness and promote inflammation.
  
• Immunocompromised and immunosuppressed patients (eg, premature infants, organ transplant recipients, and cancer patients) are particularly susceptible to severe transfusion-related cytomegalovirus (CMV) infections. Ideally, such patients should receive only CMV-negative units.
  
• The most common cause of nonsurgical bleeding following massive blood transfusion is dilutional thrombocytopenia.
  
• Clinically important hypocalcemia, causing cardiac depression, will not occur in most normal patients unless the transfusion rate exceeds 1 unit every 5 min, and intravenous calcium salts should rarely be required in the absence of measured hypocalcemia.
  
• Once adequate tissue perfusion is restored, the most consistent acid-base abnormality following massive blood transfusion is metabolic alkalosis, caused by the rapid hepatic metabolism of citric acid and lactic acid to bicarbonate.

Almost all patients undergoing surgical procedures require venous access for administration of intravenous fluids and medication, and some patients will require transfusion of blood components. The anesthesia provider should be able to assess intravascular volume with sufficient accuracy to correct existing fluid or electrolyte deficits and replace ongoing losses. Errors in fluid and electrolyte replacement or transfusion may result in morbidity or death.

Clinical estimation of intravascular volume must be relied upon because objective measurements of fluid compartment volumes are not practical in the clinical environment. Intravascular volume can be estimated using patient history, physical examination, and laboratory analysis, often with the aid of sophisticated hemodynamic monitoring techniques. Regardless of the method employed, serial evaluations are necessary to confirm initial impressions and to guide fluid, electrolyte, and blood component therapy. Multiple modalities should complement one another, because all parameters are indirect, nonspecific measures of volume; reliance upon any one parameter may lead to erroneous conclusions.

Patient History

The patient history is an important tool in preoperative volume status assessment. Important factors include recent oral intake, persistent vomiting or diarrhea, gastric suction, significant blood loss or wound drainage, intravenous fluid and blood administration, and recent hemodialysis if the patient has kidney failure.

Physical Examination

Indications of hypovolemia include abnormal skin turgor, dehydration of mucous membranes, thready peripheral pulses, increased resting heart rate and decreased blood pressure, orthostatic heart rate and blood pressure changes from the supine to sitting or standing positions, and decreased urinary flow rate (Table 51-1). Unfortunately, many medications administered during anesthesia, as well as the neuroendocrine stress response to operative procedures, alter these signs and render them unreliable in the immediate postoperative period. Intraoperatively, the fullness of a peripheral pulse, urinary flow rate, and indirect signs such as the response of blood pressure to positive-pressure ventilation and to the vasodilating or negative inotropic effects of anesthetics, are most often used.

Pitting edema—presacral in the bedridden patient or pretibial in the ambulatory patient—and increased urinary flow are signs of excess extracellular water and likely hypervolemia in patients with normal cardiac, hepatic, and renal function. Late signs of hypervolemia in settings such as congestive heart failure may include tachycardia, elevated jugular pulse pressure, pulmonary crackles and rales, wheezing, cyanosis, and pink, frothy pulmonary secretions.

Laboratory Evaluation

Several laboratory measurements may be used as surrogates of intravascular volume and adequacy of tissue perfusion, including serial hematocrits, arterial blood pH, urinary specific gravity or osmolality, urinary sodium or chloride concentration, serum sodium, and the blood urea nitrogen (BUN) to serum creatinine ratio. However, these measurements are only indirect indices of intravascular volume, and they often cannot be relied upon intraoperatively because they are affected by many perioperative factors and because laboratory results are often delayed. Laboratory signs of dehydration may include rising hematocrit and hemoglobin, progressive metabolic acidosis (including lactic acidosis), urinary specific gravity greater than 1.010, urinary sodium less than 10 mEq/L, urinary osmolality greater than 450 mOsm/L, hypernatremia, and BUN-to-creatinine ratio greater than 10:1. The hemoglobin and hematocrit are usually unchanged in patients with acute hypovolemia secondary to acute blood loss because there is insufficient time for extravascular fluid to shift into the intravascular space. Radiographic indicators of volume overload include increased pulmonary vascular and interstitial markings (Kerley “B” lines) or diffuse alveolar infiltrates.

Hemodynamic Measurements

Hemodynamic monitoring is discussed in Chapter 5. Central venous pressure (CVP) monitoring has been used in patients with normal cardiac and pulmonary function when volume status is difficult to assess by other means or when rapid or major alterations are expected. However, static CVP readings do not provide an accurate or reliable indication of volume status.

Pulmonary artery pressure monitoring has been used in settings where central venous pressures do not correlate with the clinical assessment or when the patient has primary or secondary right ventricular dysfunction; the latter is usually due to pulmonary or left ventricular disease, respectively. Pulmonary artery occlusion pressure (PAOP) readings of less than 8 mm Hg indicate hypovolemia in the presence of confirmatory clinical signs; however, values less than 15 mm Hg may be associated with relative hypovolemia in patients with poor ventricular compliance. PAOP measurements greater than 18 mm Hg are elevated and generally imply left ventricular volume overload. The normal relationship between PAOP and left ventricular end-diastolic volume is altered by the presence of mitral valve disease (particularly stenosis), severe aortic stenosis, or a left atrial myxoma or thrombus, as well as by increased thoracic and pulmonary airway pressures (see Chapters 5, 20, 21, and 22). All PAOP measurements should be obtained at end expiration and interpreted in the context of the clinical setting. Finally, one should recognize that multiple studies have failed to show that pulmonary artery pressure monitoring leads to improved outcomes in critically ill patients, and that echocardiography provides a much more accurate and less invasive estimate of cardiac filling and function.

Intravascular volume status is often difficult to assess, and goal-directed hemodynamic and fluid therapy utilizing arterial pulse contour analysis and estimation of stroke volume variation (eg, LIDCOrapid, Vigileo FloTrak), esophageal Doppler, or transesophageal echocardiography should be considered when accurate determination of hemodynamic and fluid status is important. Stroke volume variation (SVV) is calculated as follows:

SVV = SVmax – SVmin /SVmean

The maximum, minimum and mean SV are calculated for a set period of time by the various measuring devices. During spontaneous ventilation the blood pressure decreases on inspiration. During positive pressure ventilation the opposite occurs. Normal SVV is less than 10-15% for patients on controlled ventilation. Patients with greater degrees of SVV are likely to be responsive to fluid therapy. In addition to providing a better assessment of the patient’s volume and hemodynamic status than that obtained with CVP monitoring, these modalities avoid the multiple risks associated with central venous and pulmonary artery catheters.

Intravenous fluid therapy may consist of infusions of crystalloids, colloids, or a combination of both. Crystalloid solutions are aqueous solutions of ions (salts) with or without glucose, whereas colloid solutions also contain high-molecular-weight substances such as proteins or large glucose polymers. Colloid solutions help maintain plasma colloid oncotic pressure (see Chapter 49) and for the most part remain intravascular, whereas crystalloid solutions rapidly equilibrate with and distribute throughout the entire extracellular fluid space.

Controversy exists regarding the use of colloid versus crystalloid fluids for surgical patients. Proponents of colloids justifiably argue that by maintaining plasma oncotic pressure, colloids are more efficient (ie, a smaller volume of colloids than crystalloids is required to produce the same effect) in restoring normal intravascular volume and cardiac output. Crystalloid proponents, on the other hand, maintain that the crystalloid solutions are equally effective when given in appropriate amounts. Concerns that colloids may enhance the formation of pulmonary edema fluid in patients with increased pulmonary capillary permeability appear to be unfounded (see Chapter 23). Several generalizations can be made:

1. 
   

   Crystalloids, when given in sufficient amounts, are just as effective as colloids in restoring intravascular volume.

   
   
2. 
   

   Replacing an intravascular volume deficit with crystalloids generally requires three to four times the volume needed when using colloids.

   
   
3. 
   

   Surgical patients may have an extracellular fluid deficit that exceeds the intravascular deficit.

   
   
4. 
   

   Severe intravascular fluid deficits can be more rapidly corrected using colloid solutions.

   
   
5. 
   

   The rapid administration of large amounts of crystalloids (>4-5 L) is more frequently associated with tissue edema.

Some evidence suggests that marked tissue edema can impair oxygen transport, tissue healing, and return of bowel function following major surgery.

Crystalloid Solutions

Crystalloids are usually considered as the initial resuscitation fluid in patients with hemorrhagic and septic shock, in burn patients, in patients with head injury (to maintain cerebral perfusion pressure), and in patients undergoing plasmapheresis and hepatic resection. Colloids may be included in resuscitation efforts following initial administration of crystalloid solutions depending upon anesthesia provider preferences and institutional protocols.

A wide variety of solutions is available (Table 51-2), and choice is according to the type of fluid loss being replaced. For losses primarily involving water, replacement is with hypotonic solutions, also called maintenance-type solutions. If losses involve both water and electrolytes, replacement is with isotonic electrolyte solutions, also called replacement-type solutions. Glucose is provided in some solutions to maintain tonicity, or prevent ketosis and hypoglycemia due to fasting, or based on tradition. Children are prone to developing hypoglycemia (<50 mg/dL) following 4- to 8-h fasts.

Because most intraoperative fluid losses are isotonic, replacement-type solutions are generally used. The most commonly used fluid is lactated Ringer’s solution. Although it is slightly hypotonic, providing approximately 100 mL of free water per liter and tending to lower serum sodium, lactated Ringer’s generally has the least effect on extracellular fluid composition and appears to be the most physiological solution when large volumes are necessary. The lactate in this solution is converted by the liver into bicarbonate. When given in large volumes, normal saline produces a dilutional hyperchloremic acidosis because of its high sodium and chloride content (154 mEq/L): plasma bicarbonate concentration decreases as chloride concentration increases. Normal saline is the preferred solution for hypochloremic metabolic alkalosis and for diluting packed red blood cells prior to transfusion. Five percent dextrose in water (D5W) is used for replacement of pure water deficits and as a maintenance fluid for patients on sodium restriction. Hypertonic 3% saline is employed in therapy of severe symptomatic hyponatremia (see Chapter 49). Hypotonic solutions must be administered slowly to avoid inducing hemolysis.

Colloid Solutions

The osmotic activity of the high-molecular-weight substances in colloids tends to maintain these solutions intravascularly. Although the intravascular half-life of a crystalloid solution is 20-30 min, most colloid solutions have intravascular half-lives between 3 and 6 h. The relatively greater cost and occasional complications associated with colloids may limit their use. Generally accepted indications for colloids include (1) fluid resuscitation in patients with severe intravascular fluid deficits (eg, hemorrhagic shock) prior to the arrival of blood for transfusion, and (2) fluid resuscitation in the presence of severe hypoalbuminemia or conditions associated with large protein losses such as burns. For burn patients, colloids are not included in most initial resuscitation protocols (and we strongly recommend that burn surgeons and anesthesia personnel develop a resuscitation protocol and follow it), but may be considered following initial resuscitation with more extensive burn injuries during subsequent operative procedures.

Many clinicians also use colloid solutions in conjunction with crystalloids when fluid replacement needs exceed 3-4 L prior to transfusion. It should be noted that colloid solutions are prepared in normal saline (Cl− 145-154 mEq/L) and thus can also cause hyperchloremic metabolic acidosis (see above). Some clinicians suggest that during anesthesia, maintenance (and other) fluid requirements be provided with crystalloid solutions and blood loss be replaced on a milliliter-per-milliliter basis with colloid solutions (including blood products).

Several colloid solutions are generally available. All are derived from either plasma proteins or synthetic glucose polymers and are supplied in isotonic electrolyte solutions.

Blood-derived colloids include albumin (5% and 25% solutions) and plasma protein fraction (5%). Both are heated to 60°C for at least 10 h to minimize the risk of transmitting hepatitis and other viral diseases. Plasma protein fraction contains α- and β-globulins in addition to albumin and has occasionally resulted in hypotensive reactions. These reactions are allergic in nature and may involve activators of prekallikrein.

Synthetic colloids include dextrose starches and gelatins. Gelatins are associated with histamine-mediated allergic reactions and are not available in the United States. Dextran is available as dextran 70 (Macrodex) and dextran 40 (Rheomacrodex), which have average molecular weights of 70,000 and 40,000, respectively. Although dextran 70 is a better volume expander than dextran 40, the latter also improves blood flow through the microcirculation, presumably by decreasing blood viscosity, and is often administered to take advantage of these rheological properties rather than to meet “fluid requirements.” Antiplatelet effects are also described for dextrans. Infusions exceeding 20 mL/kg per day can interfere with blood typing, may prolong bleeding time, and have been associated with kidney failure. Dextrans can also be antigenic, and both mild and severe anaphylactoid and anaphylactic reactions are described. Dextran 1 (Promit) may be administered prior to dextran 40 or dextran 70 to prevent severe anaphylactic reactions; it acts as a hapten and binds any circulating dextran antibodies.

Hetastarch (hydroxyethyl starch) is available in multiple formulations, which are designated by concentration, molecular weight, degree of starch substitution (on a molar basis), and ratio of hydroxylation between the C2 and the C6 positions. Thus in some countries a wide variety of formulations are available with concentrations between 6% and 10%, molecular weights between 200 and 670, and degree of molar substitution between 0.4 and 0.7. A greater ratio of C2 versus C6 substitution leads to longer persistence in plasma. The starch molecules are derived from plants. Smaller starch molecules are eliminated by the kidneys, whereas large molecules must first be broken down by amylase. Hetastarch is highly effective as a plasma expander and is less expensive than albumin. Moreover, hetastarch is nonantigenic, and anaphylactoid reactions are rare. Coagulation studies and bleeding times are generally not significantly affected following infusions of older, higher molecular weight formulations up to 1.0 L in adults. Newer, lower molecular weight formulations can safely be given in larger volumes.

Perioperative fluid therapy includes replacement of normal losses (maintenance requirements), of preexisting fluid deficits, and of surgical wound losses including blood loss.

Normal Maintenance Requirements

In the absence of oral intake, fluid and electrolyte deficits can rapidly develop as a result of continued urine formation, gastrointestinal secretions, sweating, and insensible losses from the skin and lungs. Normal maintenance requirements can be estimated from Table 51-3.

Preexisting Deficits

Patients presenting for surgery after an overnight fast without any fluid intake will have a preexisting deficit proportionate to the duration of the fast. The deficit can be estimated by multiplying the normal maintenance rate by the length of the fast. For the average 70-kg person fasting for 8 h, this amounts to (40 + 20 + 50) mL/h × 8 h, or 880 mL. In fact, the real deficit is less as a result of renal conservation. (After all, how many of us would feel the need to consume nearly 1L of fluid upon awakening after 8 hours of sleep?)

Abnormal fluid losses frequently contribute to preoperative deficits. Preoperative bleeding, vomiting, diuresis, and diarrhea are often contributory. Occult losses (really redistribution; see below) due to fluid sequestration by traumatized or infected tissues or by ascites can also be substantial. Increased insensible losses due to hyperventilation, fever, and sweating are often overlooked.

Ideally, deficits should be replaced preoperatively in surgical patients. The fluids used should be similar in composition to the fluids lost (Table 51-4).

Surgical Fluid Losses

Blood Loss

One of the most important, yet difficult, tasks of anesthesia personnel is to monitor and estimate blood loss. Although estimates are complicated by occult bleeding into the wound or under the surgical drapes, accuracy is important to guide fluid therapy and transfusion.

The most commonly used method for estimating blood loss is measurement of blood in the surgical suction container and visual estimation of the blood on surgical sponges (“4 by 4’s”) and laparotomy pads (“lap sponges”). A fully soaked 4 × 4 sponge is said to hold 10 mL of blood, whereas a soaked “lap” holds 100-150 mL. More accurate estimates are obtained if sponges and “laps” are weighed before and after use, which is especially important during pediatric procedures. Use of irrigating solutions complicates estimates, but their use should be noted and an attempt made to compensate. Serial hematocrits or hemoglobin concentrations reflect the ratio of blood cells to plasma, not necessarily blood loss, and rapid fluid shifts and intravenous replacement affect measurements.

Other Fluid Losses

Many surgical procedures are associated with obligatory losses of fluids other than blood. Such losses are due mainly to evaporation and internal redistribution of body fluids. Evaporative losses are most significant with large wounds and are proportional to the surface area exposed and to the duration of the surgical procedure.

Internal redistribution of fluids—often called third-spacing—can cause massive fluid shifts and severe intravascular depletion. Everything related to “third-space” fluid loss is controversial, including whether it actually exists in patients other than those with peritonitis, burns, and similar situations characterized by inflamed or infected tissue. Traumatized, inflamed, or infected tissue can sequester large amounts of fluid in the interstitial space and can translocate fluid across serosal surfaces (ascites) or into bowel lumen. Shifting of intravascular fluid into the interstitial space is especially important; protein-free fluid shift across an intact vascular barrier into the interstitial space is exacerbated by hypervolemia, and pathological alteration of the vascular barrier allows protein-rich fluid shift.

Intraoperative Fluid Replacement

Intraoperative fluid therapy should include supplying basic fluid requirements and replacing residual preoperative deficits as well as intraoperative losses (blood loss, fluid redistribution, and evaporation). Selection of the type of intravenous solution depends on the surgical procedure and the expected blood loss. For minor procedures involving minimal blood loss, dilute maintenance solutions can be used. For all other procedures, lactated Ringer’s solution or Plasmalyte is generally used even for maintenance requirements.

Replacing Blood Loss

Ideally, blood loss should be replaced with crystalloid or colloid solutions to maintain intravascular volume (normovolemia) until the danger of anemia outweighs the risks of transfusion. At that point, further blood loss is replaced with transfusions of red blood cells to maintain hemoglobin concentration (or hematocrit) at that level. There are no mandatory transfusion triggers. The point where the benefits of transfusion outweigh its risks must be considered on an individual basis.

Below a hemoglobin concentration of 7 g/dL, the resting cardiac output increases to maintain a normal oxygen delivery. An increased hemoglobin concentration may be appropriate for older and sicker patients with cardiac or pulmonary disease, particularly when there is clinical evidence (eg, a reduced mixed venous oxygen saturation and a persisting tachycardia) that transfusion would be useful.