Other

Causes of Metabolic Alkalosis

Metabolic alkalosis is rarely encountered in patients given even large doses of
NaHCO3 unless renal excretion of HCO3– is impaired. The administration of
large amounts of blood products and some plasma protein–containing colloid
solutions frequently results in metabolic alkalosis because citrate, lactate, and
acetate contained in these fluids are converted by the liver into HCO3–. Patients
receiving high doses of sodium penicillin (particularly carbenicillin) can develop
metabolic alkalosis. Because penicillins act as nonabsorbable anions in the renal
tubules, increased H+ (or K+) secretion must accompany sodium absorption. For
reasons that are not clear, hypercalcemia that results from nonparathyroid causes
(milk-alkali syndrome and bone metastases) is also often associated with
metabolic alkalosis.

Treatment of Metabolic Alkalosis

As with other acid–base disorders, correction of metabolic alkalosis is never
complete until the underlying disorder is corrected. When ventilation is
controlled, any respiratory component contributing to alkalemia should be
corrected by decreasing minute ventilation to normalize PaCO2. The treatment of
choice for chloride-sensitive metabolic alkalosis is administration of intravenous
saline (NaCl) and potassium (KCl). H2-blocker therapy is useful when excessive
loss of gastric fluid is a factor. Acetazolamide may also be useful in edematous
patients. Alkalosis associated with primary increases in mineralocorticoid
activity readily responds to aldosterone antagonists (spironolactone). When
arterial blood pH is greater than 7.60, treatment with intravenous hydrochloric
acid (0.1 mol/L), ammonium chloride (0.1 mol/L), arginine hydrochloride, or
hemodialysis should be considered.

ANESTHETIC CONSIDERATIONS IN PATIENTS

WITH ALKALEMIA
Cerebral ischemia can occur from marked reduction in cerebral blood flow
during respiratory alkalosis, particularly during hypotension. The
combination of alkalemia and hypokalemia can precipitate severe atrial and
ventricular arrhythmias. Reports of effects of alkalemia on neuromuscular
blockers are inconsistent.
DIAGNOSIS OF ACID–BASE DISORDERS
Interpretation of acid–base status from analysis of blood gases requires a
systematic approach. A recommended approach follows (see Figure 50–3):
1. Examine arterial pH: Is acidemia or alkalemia present?
2. Examine PaCO2: Is the change in PaCO2 consistent with a respiratory
component?
3. If the change in PaCO2 does not explain the change in arterial pH, does the
change in [HCO3–] indicate a metabolic component?
4. Make a tentative diagnosis (see Table 50–1).
5. Compare the change in [HCO3–] with the change in PaCO2. Does a
compensatory response exist (Table 50–7)? Because arterial pH is related to
the ratio of PaCO2 to [HCO3–], both respiratory and renal compensatory
mechanisms are always such that PaCO2 and [HCO3–] change in the same
direction. A change in opposite directions implies a mixed acid–base
disorder.

TABLE 50–7 Normal compensatory responses in acid–base disturbances.

6. If the compensatory response is more or less than expected, by definition, a
mixed acid–base disorder exists.
7. Calculate the plasma anion gap in the case of metabolic acidosis.
8. Measure urinary chloride concentration in the case of metabolic alkalosis.

An alternative approach that is rapid, though less precise, is to correlate

changes in pH with changes in CO2 or HCO3. For a respiratory disturbance,
every 10 mm Hg change in CO2 should change arterial pH by approximately
0.08 U in the opposite direction. During metabolic disturbances, every 6 mEq
change in HCO3 also changes arterial pH by 0.1 in the same direction. If the
change in pH is greater or less than predicated, a mixed acid–base disorder is
likely to be present.

MEASUREMENT OF BLOOD GAS TENSIONS &

pH
Values obtained by routine blood gas measurement include oxygen and carbon
dioxide tensions (PO2 and PCO2), pH, [HCO3–], base excess, hemoglobin, and the
percentage oxygen saturation of hemoglobin. As a rule, only PO2, PCO2, and pH
are measured. Hemoglobin and percentage oxygen saturation are measured with
a cooximeter. [HCO3–] is derived using the Henderson–Hasselbalch equation
and base excess from the Siggaard–Andersen nomogram.

Sample Source & Collection

Arterial blood samples are most commonly utilized clinically, though capillary
or venous blood can be used if the limitations of such samples are recognized.
Oxygen tension in venous blood (normally 40 mm Hg) reflects tissue extraction,
not pulmonary function. Venous PCO2 is usually 4 to 6 mm Hg higher than
PaCO2. Consequently, venous blood pH is usually 0.05 U lower than arterial
blood pH. Despite these limitations, venous blood is often useful in determining
acid–base status. Capillary blood represents a mixture of arterial and venous
blood, and the values obtained reflect this fact. Samples are usually collected in
heparin-coated syringes and should be analyzed as soon as possible. Air bubbles
should be eliminated, and the sample should be capped and placed on ice to
prevent significant uptake of gas from blood cells or loss of gases to the
atmosphere. Although heparin is highly acidic, excessive heparin in the sample
syringe usually lowers pH only minimally, but decreases PCO2 in direct
proportion to percentage dilution and has a variable effect on PO2.

Temperature Correction
Changes in temperature affect PCO2, PO2, and pH. Decreases in temperature
lower the partial pressure of a gas in solution—even though the total gas content
does not change—because gas solubility is inversely proportionate to
temperature. Both PCO2 and PO2 therefore decrease during hypothermia, but pH
increases because temperature does not appreciably alter [HCO3–] and the
dissociation of water decreases (decreasing H+ and increasing pH). Because
blood gas tensions and pH are always measured at 37°C, controversy exists over
whether to correct the measured values to the patient’s actual temperature.
“Normal” values at temperatures other than 37°C are not known. Many
clinicians use the measurements at 37°C directly (α-stat), regardless of the
patient’s actual temperature (see Chapter 22).
CASE DISCUSSION

A Complex Acid–Base Disturbance

A 1-month-old male infant with an anorectal malformation undergoes
anoplasty. Postoperatively, he is found to be in congestive heart failure
resulting from coarctation of the aorta. He is noted to have tachypnea,
decreased urinary output, poor peripheral perfusion, hepatomegaly,
and cardiomegaly. Following tracheal intubation, the infant is placed
on a ventilator (pressure support ventilation, fraction of inspired
oxygen [Fio2] = 1.0). Initial arterial blood gas, hemoglobin, and
electrolyte measurements are as follows:
PaCO2 = 11 mm
pH = 7.47
PaO2 = 209 mm Hg
Calculated [HCO3–] = 7.7 mEq/L
Base deficit (BD) = –14.6 mEq/L
Hemoglobin (Hb) = 9.5 g/Dl
[Na+] = 135 mEq/L
[Cl–] = 95 mEq/L
[K+] = 5.5 mEq/L
[Total CO2] = 8 mEq/L
Note that the [total CO2] normally measured with electrolytes
includes both plasma [HCO3–] and dissolved CO2 in plasma.

What is the acid–base disturbance?

Using the approach described earlier, the patient clearly has an alkalosis
(pH >7.45), which is at least partly respiratory in origin (PaCO2 <40 mm
Hg). Because PaCO2 has decreased by nearly 30 mm Hg, we would expect
[HCO3–] to be 18 mEq/L:

In fact, the patient’s [HCO3–] is nearly 10 mEq/L less than that! The
patient therefore also has a mixed acid–base disturbance: primary
respiratory alkalosis and primary metabolic acidosis. Note that the
difference between the patient’s [HCO3–] and the [HCO3–] expected for a
pure respiratory alkalosis roughly corresponds to the base excess.
What are likely causes of these disturbances?
The respiratory alkalosis is probably the result of congestive heart
failure, whereas the metabolic acidosis results from lactic acidosis
secondary to poor perfusion. The latter is suggested by the calculated
plasma anion gap:

Anion gap = 135 – (95 + 8) = 32 mEq/L

The lactate level was in fact measured and found to be elevated at 14.4
mEq/L. It is probable that fluid overload precipitated the congestive heart
failure.
What treatment is indicated?
Treatment should be directed at the primary process (ie, the congestive
heart failure). The patient was treated with diuresis and inotropes.
Following diuresis, the patient’s tachypnea has improved, but perfusion
still seems to be poor. Repeat laboratory measurements are as follows (FiO2
= 0.5):
PaCO2 = 23 mm Hg
pH = 7.52
PaO2 = 136 mm Hg
Calculated [HCO3–] = 18 mEq/L
BD = –3.0 mEq/L
Hb = 10.3 g/dL
[Na+] = 137 mEq/L
[Cl–] = 92 mEq/L
[K+] = 3.9 mEq/L
[Total CO2] = 18.5 mEq/L

What is the acid–base disturbance?

Respiratory alkalosis is still present, whereas the BD has improved. Note
that the hemoglobin concentration has increased slightly, but [K+] has
decreased as a result of the diuresis. With the new PaCO2, the expected
[HCO3–] should be 20.6 mEq/L:

Therefore, the patient still has metabolic acidosis because the [HCO3–] is
2 mEq/L less. Note again that this difference is close to the given BD and
that the anion gap is still high:

Anion gap = 137 – (92 + 18) = 27

The repeat lactate measurement is now 13.2 mEq/L.

The high anion gap and lactate level explain why the patient is still not
doing well and indicate that a new process is masking the severity of the
metabolic acidosis (which is essentially unchanged).
Given the clinical course, it is likely that the patient now has a triple
acid–base disorder: respiratory alkalosis, metabolic acidosis, and now
metabolic alkalosis. The latter probably resulted from hypovolemia
secondary to excessive diuresis (chloride-sensitive metabolic alkalosis).
Note also that the metabolic alkalosis is nearly equal in magnitude to the
metabolic acidosis.
The patient was subsequently given packed red blood cells in saline, and
within 24 h all three disorders began to improve:
PaCO2 = 35 mm Hg
pH = 7.51
PaO2 = 124 mm Hg
Calculated [HCO3–] = 26.8 mEq/L
Base excess = +5.0 mEq/L
Hb = 15 g/dL
[Na+] = 136 mEq/L
[Cl–] = 91 mEq/L
[K+] = 3.2 mEq/L
[Total CO2] = 27 mEq/L
Lactate = 2.7 mEq/L
 Outcome
The respiratory alkalosis and the metabolic acidosis have now resolved,
and the metabolic alkalosis is now most prominent.
Intravenous KCl replacement and a small amount of saline were
judiciously given, followed by complete resolution of metabolic alkalosis.
The patient subsequently underwent surgical correction of the coarctation.

SUGGESTED READINGS
Ayers P, Dixon C, Mays A. Acid-base disorders: Learning the basics. Nutr Clin
Pract. 2015;30:14.
Corey HE. Bench-to-bedside review: Fundamental principles of acid-base
physiology. Crit Care. 2005;9:184.
Dhondup T, Qian Q. Electrolyte and acid-base disorders in chronic kidney
disease and end-stage kidney failure. Blood Purif. 2017;43:179.
Dzierba AL, Abraham P. A practical approach to understanding acid-base
abnormalities in critical illness. J Pharm Pract. 2011;24:17.
Gunnerson KJ. Clinical review: The meaning of acid-base abnormalities in the
intensive care unit—epidemiology. Crit Care. 2005;9:508.
Handy JM, Soni N. Physiological effects of hyperchloraemia and acidosis. Br J
Anaesth. 2008;101:141.
Kaplan LJ, Frangos S. Clinical review: Acid-base abnormalities in the intensive
care unit. Crit Care. 2005;9:198.
Kellum JA. Acid-base disorders and strong ion gap. Contrib Nephrol Basel.
2007;156:158.
Kraut JA, Madias NE. Metabolic acidosis: Pathophysiology, diagnosis and
management. Nature Rev Nephrol. 2010;6:274.
Morgan TJ. Clinical review: The meaning of acid-base abnormalities in the
intensive care unit—effects of fluid administration. Crit Care. 2005;9:204.
Morris CG, Low J. Metabolic acidosis in the critically ill: Part 1. Classification
and pathophysiology. Anaesthesia. 2008;63:294.
Morris CG, Low J. Metabolic acidosis in the critically ill: Part 2. Causes and
treatment. Anaesthesia. 2008;63:396.
Seifter JL, Chang H-Y. Disorders of acid-base balance: New perspectives.
Kidney Dis. 2016;2:170.
Yessayan L, Yee J, Finak S, et al. Continuous renal replacement therapy for the
management of acid-base and electrolyte imbalances in acute kidney injury.
Adv Chron Kidney Dis. 2016;23:203.
 CHAPTER

51
Fluid Management & Blood
Component Therapy

KEY CONCEPTS

Although the intravascular half-life of a crystalloid solution is 20 to 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% to 20% of their blood volume. The timing
of transfusion initiation is based on the patient’s surgical procedure,
comorbid conditions, and rate of blood loss.
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, diffuse oozing in the surgical field, or a combination
of these findings.
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 normal tissue perfusion is restored, any metabolic acidosis
typically resolves, and metabolic alkalosis commonly occurs as citrate
and lactate contained in transfusions and resuscitation fluids are
converted to bicarbonate by the liver.

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.

Evaluation of Intravascular Volume

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 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 may reveal 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, frequently alter these
signs and render them unreliable in the immediate postoperative period.
Intraoperatively, in addition to heart rate and blood pressure, the fullness of a
peripheral pulse, urinary flow rate, and indirect signs, such as the blood pressure
response to positive-pressure ventilation and to vasodilating or negative
inotropic effects of anesthetics, are often used for guidance.

TABLE 51–1 Signs of fluid loss (hypovolemia).

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, tachypnea, elevated jugular pulse pressure, pulmonary
crackles, 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, because these measurements are only indirect indices
of intravascular volume, they are affected by many perioperative factors, and
because laboratory results are often delayed, they often cannot be relied upon
intraoperatively. 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. Ultrasound can reveal a nearly collapsed vena cava or
incompletely filled cardiac chambers. Radiographic indicators of volume
overload include increased pulmonary vascular and interstitial markings (Kerley
“B” lines), diffuse alveolar infiltrates, or both.

HEMODYNAMIC MEASUREMENTS
Hemodynamic monitoring is discussed in Chapter 5. Central venous pressure
(CVP) monitoring has been used 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 accurate or reliable indication of volume status.
Pulmonary artery pressure monitoring has been used in settings where CVP
readings 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 may indicate hypovolemia in
patients with normal left ventricular compliance; 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 may 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, 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 noninvasive fluid
therapy guidance utilizing arterial pulse contour analysis and estimation of
stroke volume variation (eg, LIDCOunity, Vigileo FloTrak), esophageal Doppler,
transesophageal echocardiography, or transthoracic 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% to 15% for patients on controlled
ventilation. Patients with greater degrees of SVV are likely to be responsive to
fluid therapy. In addition to providing more accurate assessment of volume and
hemodynamic status than that obtained with CVP monitoring, these noninvasive
modalities avoid multiple risks associated with central venous and pulmonary
artery catheters. Consequently, we infrequently employ pulmonary artery
catheters to guide hemodynamic therapy.

Intravenous Fluids
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 remains 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 are 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 often
associated with tissue edema.

Tissue edema secondary to excessive fluid administration can impair oxygen

transport, tissue healing, and return of bowel function following surgery and may
increase the risk of surgical site infection.

CRYSTALLOID SOLUTIONS
Crystalloids are often 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, and choice is according to the type of
fluid loss being replaced. For losses primarily involving water, replacement is
with hypotonic solutions, and if losses involve both water and electrolytes,
replacement is with isotonic electrolyte 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, isotonic crystalloid
solutions such as normal saline or balanced electrolyte solutions (low-[Cl–]
crystalloids, which have preserved ionic “balance” by replacing Cl– with lactate,
gluconate, or acetate) such as lactated Ringer’s solution or PlasmaLyte are most
commonly used for replacement (Table 51–2). Normal saline, when given in
large volumes, produces hyperchloremic metabolic acidosis because of its
high chloride content and lack of bicarbonate (see Chapter 50). In addition,
chloride-rich crystalloids such as normal saline may contribute to
perioperative acute kidney injury. Therefore, we prefer balanced salt
solutions for most intraoperative uses. 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.

TABLE 51–2 Composition of plasma, 0.9% saline, and commonly used

balanced crystalloids.1

COLLOID SOLUTIONS
The osmotic activity of high-molecular-weight substances in colloids tends to
maintain these solutions intravascularly. Although the intravascular half-life of
a crystalloid solution is 20 to 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, 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 to 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 earlier
discussion). 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 allergic reactions. Synthetic colloids include gelatins and
dextrose starches. Gelatins (eg, Gelofusine) are associated with histamine-
mediated allergic reactions and are not available in the United States. Dextran is
a complex polysaccharide available as dextran 70 (Macrodex) and dextran 40
(Rheomacrodex), which have average molecular weights of 70,000 and 40,000,
respectively. Dextran is used as a volume expander but also reduces blood
viscosity, von Willebrand factor antigen, platelet adhesion, and red blood cell
aggregation. Because of these latter properties, it is used by microsurgeons to
improve microcirculatory flow and decrease risk of microthrombus formation.
Infusions exceeding 20 mL/kg per day can interfere with blood typing, may
prolong bleeding time, and have been associated with bleeding complications.
Dextran has been associated with acute kidney injury and failure and should not
be administered to patients with a history of kidney disease or to those at risk for
acute kidney injury (eg, elderly or critically ill). Anaphylactoid and anaphylactic
reactions have been reported. 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 that 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. 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. Allergic reactions are rare, but anaphylactoid and
anaphylactic reactions have been reported. Hetastarch can decrease von
Willebrand factor antigen levels, may prolong the prothrombin time, and has
been associated with hemorrhagic complications. It is potentially nephrotoxic
and should not be administered to patients at risk for acute kidney injury,
including those who are elderly, critically ill, or have a history of kidney disease.
However, its perioperative use in patients who are not critically ill or are not at
increased risk of acute kidney injury remains controversial and is subject to a
great deal of current debate.

Perioperative Fluid Therapy

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.

TABLE 51–3 Estimating maintenance fluid requirements.1

PREEXISTING DEFICITS
Patients presenting for surgery after a traditional 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 1 L of fluid upon awakening after 8 h of sleep? However, current
anesthesia practice often allows oral fluids up to 2 h prior to an elective
procedure, and the preoperative regimen may include preoperative carbohydrate
fluid loading (see Chapters 18 and 48). Such patients will present for surgical or
procedural care with essentially no fluid deficit, as will the hospitalized patient
who has received intravenous maintenance fluids preoperatively.
Abnormal fluid losses frequently contribute to preoperative deficits.
Preoperative bleeding, vomiting, nasogastric suction, diuresis, and diarrhea are
often contributory. Losses (actually, redistribution; see next section) due to fluid
sequestration by traumatized or infected tissues, coagulopathy-related occult
hematoma formation, or 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, and the
fluids administered should be similar in composition to the fluids lost (Table 51–
4).

TABLE 51–4 Electrolyte content of body fluids.

SURGICAL FLUID LOSSES

Blood Loss
One of the most important, yet difficult, tasks in anesthesia practice 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” is generally considered to hold 10 mL of blood, whereas a soaked
“lap” may hold 100 to 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 volume should be noted and an attempt made to compensate. Serial
hematocrits or hemoglobin concentrations reflect the ratio of RBCs to plasma,
not necessarily blood loss, and rapid fluid shifts and intravenous replacement
affect such 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,
especially burns, 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 in patients 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 (edema) is especially important; protein-free fluid shift across an intact
vascular barrier into the interstitial space is exacerbated by hypervolemia (water
and sodium excess), 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 or no blood loss, minimal or no
fluid is often administered other than for drug delivery and for maintenance of
intravenous line patency. For all other procedures, a balanced crystalloid such as
lactated Ringer’s solution or Plasmalyte is generally used for maintenance
requirements.

Goal-Directed Fluid Therapy

The concept of goal-directed fluid therapy (GDFT) arose from a 1983 study by
Shoemaker and colleagues that demonstrated lower mortality in critically ill
patients in whom tissue oxygen delivery was optimized through “physiological
goals” related to cardiac output and fluid administration. The current concept of
GDFT has many variations but in general assumes no need for maintenance fluid
administration, instead using hemodynamic variables such as stroke volume,
cardiac output, cardiac index, and mean arterial blood pressure to determine
volume responsiveness and to guide fluid administration by bolus. Some
anesthesiologists also incorporate the use of inotropes and vasopressors in their
GDFT regimens. GDFT has been widely incorporated into enhanced recovery
protocols, but studies of GDFT have been inconsistent to date, with some
investigators reporting fewer postoperative complications and shorter hospital
lengths of stay. Inconsistent reports of GDFT results may be due to inconsistent
GDFT regimens, or to the possibility that not all operations (eg, those with less
physiological trespass, such as laparoscopic or robotic procedures) require
GDFT. The precise role of GDFT in perioperative care related to various surgical
procedures is currently the subject of intense scrutiny.

Replacing Blood Loss

Ideally, blood loss should be replaced with sufficient crystalloid or colloid
solutions to maintain normovolemia until the danger of anemia outweighs the
risks of transfusion. At that point, further blood loss is replaced with transfusion
of red blood cells to maintain hemoglobin concentration (or hematocrit) at an
acceptable 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 beneficial.
In settings other than massive trauma, most clinicians administer lactated
Ringer’s solution or Plasmalyte in approximately three to four times the volume
of the blood lost, or colloid in a 1:1 ratio, until the transfusion trigger point is
reached. At that time, blood is replaced unit-for-unit as it is lost, with
reconstituted packed red blood cells (see Chapter 39).
The transfusion point can be determined preoperatively from the hematocrit
and by estimating blood volume (Table 51–5). Patients with a normal
hematocrit should generally be transfused only after losses greater than 10% to
20% of their blood volume. The timing of transfusion initiation is based on the
patient’s surgical procedure, comorbid conditions, and rate of blood loss. The
amount of blood loss necessary for the hematocrit to fall to 30% can be
calculated as follows:

TABLE 51–5 Average blood volumes.

1. Estimate blood volume from Table 51–5.

2. Estimate the red blood cell volume (RBCV) at the preoperative hematocrit
(RBCVpreop).
3. Estimate RBCV at a hematocrit of 30% (RBCV30%), assuming normal blood
volume is maintained.
4. Calculate the RBCV lost when the hematocrit is 30%; RBCVlost =
RBCVpreop – RBCV30%.
5. Allowable blood loss = RBCVlost × 3.
Example: An 85-kg woman has a preoperative hematocrit of 35%. How much
blood loss will decrease her hematocrit to 30%?

Therefore, transfusion should be considered only when this patient’s blood

loss exceeds 800 mL. Increasingly, transfusions are not recommended until
the hematocrit decreases to 24% or lower (hemoglobin <8.0 g/dL), but it is
necessary to take into account the potential for further blood loss, rate of
blood loss, and comorbid conditions (eg, cardiac disease).
Clinical guidelines for transfusion commonly used include the following: (1)
transfusing 1 unit of red blood cells will increase hemoglobin 1 g/dL and the
hematocrit 2% to 3% in adults; and (2) a 10-mL/kg transfusion of red blood cells
will increase hemoglobin concentration by 3 g/dL and the hematocrit by 10%.

Replacing Redistributive & Evaporative Losses

Because redistributive and evaporative losses are primarily related to wound size
and the extent of surgical dissections and manipulations, procedures can be
classified according to the degree of tissue trauma. These additional fluid losses
can be replaced according to Table 51–6, based on whether tissue trauma is
minimal, moderate, or severe. These values are only guidelines, and actual needs
vary considerably from patient to patient. Fluid replacement can also be guided
by a GDFT regimen.

TABLE 51–6 Redistribution and evaporative surgical fluid losses.

Transfusion

BLOOD GROUPS
Human red cell membranes are estimated to contain at least 300 different
antigenic determinants, and at least 20 separate blood group antigen systems are
known. Fortunately, only the ABO and the Rh systems are important in the
majority of blood transfusions. Individuals often produce antibodies
(alloantibodies) to the alleles they lack within each system. Such antibodies are
responsible for the most serious reactions to transfusions. Antibodies may occur
spontaneously or in response to sensitization from a previous transfusion or
pregnancy.

The ABO System

ABO blood group typing is determined by the presence or absence of A or B red
blood cell (RBC) surface antigens: Type A blood has A RBC antigen, type B
blood has B RBC antigen, type AB blood has both A and B RBC antigens, and
type O blood has neither A nor B RBC antigen present. Almost all individuals
not having A or B antigen “naturally” produce antibodies, mainly
immunoglobulin (Ig) M, against those missing antigens within the first year of
life.

The Rh System
There are approximately 46 Rhesus group red cell surface antigens, and patients
with the D Rhesus antigen are considered Rh-positive. Approximately 85% of
the white population and 92% of the black population has the D antigen, and
individuals lacking this antigen are called Rh-negative. In contrast to the ABO
groups, Rh-negative patients usually develop antibodies against the D antigen
only after an Rh-positive transfusion or with pregnancy, in the situation of an
Rh-negative mother delivering an Rh-positive baby.

Other Red Blood Cell Antigen Systems

Other red cell antigen systems include Lewis, P, Ii, MNS, Kidd, Kell, Duffy,
Lutheran, Xg, Sid, Cartright, YK, Ss, and Chido Rodgers. Fortunately, with
some exceptions (Kell, Kidd, Duffy, and Ss), alloantibodies against these
antigens rarely cause serious hemolytic reactions.

COMPATIBILITY TESTING
The purpose of compatibility testing is to predict and to prevent antigen–
antibody reactions resulting from red cell transfusions.

ABO–Rh Testing
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. The patient’s red
cells are tested with serum known to have antibodies against A and against B to
determine blood type. Because of the almost universal prevalence of natural
ABO antibodies, confirmation of blood type is then made by testing the patient’s
serum against red cells with a known antigen type.
The patient’s red cells are also tested with anti-D antibodies to determine Rh
status. If the subject is Rh-negative, the presence of anti-D antibody is checked
by mixing the patient’s serum against Rh-positive red cells. The probability of
developing anti-D antibodies after a single exposure to the Rh antigen is 50% to
70%.

Antibody Screen
The purpose of this test is to detect in the serum the presence of the antibodies
that are most commonly associated with non-ABO hemolytic reactions. The test
(also known as the indirect Coombs test) requires 45 min and involves mixing
the patient’s serum with red cells of known antigenic composition; if specific
antibodies are present, they will coat the red cell membrane, and subsequent
addition of an antiglobulin antibody will result in red cell agglutination.
Antibody screens are routinely done on all donor blood and are frequently done
for a potential recipient instead of a crossmatch (described next).

Crossmatch
A crossmatch mimics the transfusion: Donor red cells are mixed with recipient
serum. Crossmatching serves three functions: (1) it confirms ABO and Rh
typing, (2) it detects antibodies to the other blood group systems, and (3) it
detects antibodies in low titers or those that do not agglutinate easily.

Type & Crossmatch versus Type & Screen

In the situation of negative antibody screen without crossmatch, the incidence of
serious hemolytic reaction with ABO- and Rh-compatible transfusion is less than
1:10,000. Crossmatching, however, assures optimal safety and detects the
presence of less common antibodies not usually tested for in a screen. Because
of the expense and time involved (45 min), crossmatches are often now
performed before the need to transfuse only when the patient’s antibody screen is
positive, when the probability of transfusion is high, or when the patient is
considered at risk for alloimmunization.

EMERGENCY TRANSFUSIONS
When a patient is exsanguinating, the urgent need to transfuse may arise prior to
completion of a crossmatch, screen, or even blood typing. If the patient’s blood
type is known, an abbreviated crossmatch, requiring less than 5 min, will
confirm ABO compatibility. If the recipient’s blood type and Rh status are
not known with certainty and transfusion must be started before
determination, type O Rh-negative (universal donor) red cells may be used.
Red blood cells, fresh frozen plasma, and platelets are often transfused in a
balanced ratio (1:1:1) in massive transfusion protocols and in trauma damage
control resuscitation (see later discussion and Chapter 39).

BLOOD BANK PRACTICES

Blood donors are screened to exclude medical conditions that might adversely
affect the donor or the recipient. Once the blood is collected, it is typed, screened
for antibodies, and tested for hepatitis B, hepatitis C, syphilis, and human
immunodeficiency virus. A preservative–anticoagulant solution is added. The
most commonly used solution is CPDA-1, which contains citrate as an
anticoagulant (by binding calcium), phosphate as a buffer, dextrose as a red cell
energy source, and adenosine as a precursor for adenosine triphosphate (ATP)
synthesis. CPDA-1-preserved blood can be stored for 35 days, after which the
viability of the red cells rapidly decreases. Alternatively, use of either AS-1
(Adsol) or AS-3 (Nutrice) extends the shelf-life to 6 weeks.
Nearly all units collected are separated into their component parts (ie, red
cells, platelets, and plasma), and whole blood units are rarely available for
transfusion in civilian practice. When centrifuged, 1 unit of whole blood yields
approximately 250 mL of packed red blood cells (PRBCs) with a hematocrit of
70%; following the addition of saline preservative, the volume of a unit of
PRBCs often reaches 350 mL. Red cells are normally stored at 1°C to 6°C but
may be frozen in a hypertonic glycerol solution for up to 10 years. The latter
technique is usually reserved for storage of blood with rare phenotypes.
The supernatant is centrifuged to yield platelets and plasma. The unit of
platelets obtained generally contains 50 to 70 mL of plasma and can be stored at
20°C to 24°C for 5 days. The remaining plasma supernatant is further processed
and frozen to yield fresh frozen plasma; rapid freezing helps prevent inactivation
of the labile coagulation factors V and VIII. Slow thawing of fresh frozen
plasma yields a gelatinous precipitate (cryoprecipitate) that contains high
concentrations of factor VIII and fibrinogen. Once separated, cryoprecipitate can
be refrozen for storage. One unit of blood yields about 200 mL of plasma, which
is frozen for storage; once thawed, it must be transfused within 24 h. Most
platelets are now obtained from donors by apheresis, and a single platelet
apheresis unit is equivalent to the amount of platelets derived from 6 to 8 units
of whole blood.
The use of leukocyte-reduced (leukoreduction) blood products has been
rapidly adopted by many countries, including the United States, in order to
decrease the risk of transfusion-related febrile reactions, infections, and
immunosuppression.

INTRAOPERATIVE TRANSFUSION PRACTICES

Packed Red Blood Cells
Blood transfusions should usually be given as PRBCs, which allows optimal
utilization of blood bank resources. Surgical patients require volume as well as
red cells, and crystalloid or colloid can be infused simultaneously through a
second intravenous line for volume replacement.
Prior to transfusion, each unit should be carefully checked against the blood
bank slip and the recipient’s identity bracelet. The transfusion tubing should
contain a 170-μm filter to trap any clots or debris. Blood for intraoperative
transfusion should be warmed to 37°C during infusion, particularly when more
than 2 to 3 units will be transfused; failure to do so can result in profound
hypothermia. The additive effects of hypothermia and the typically low levels of
2,3-diphosphoglycerate (2,3-DPG) in stored blood can cause a marked leftward
shift of the hemoglobin–oxygen dissociation curve (see Chapter 23) and, at least
theoretically, promote tissue hypoxia.

Fresh Frozen Plasma

Fresh frozen plasma (FFP) contains all plasma proteins, including most clotting
factors. Transfusions of FFP are indicated in the treatment of isolated factor
deficiencies, the reversal of warfarin therapy, and the correction of
coagulopathy associated with liver disease. Each unit of FFP generally
increases the level of each clotting factor by 2% to 3% in adults. The initial
therapeutic dose is usually 10 to 15 mL/kg. The goal is to achieve 30% of the
normal coagulation factor concentration. Administration of FFP and platelets in
treatment of coagulopathy is optimally guided by point-of-care coagulation
analysis, such as thromboelastography (TEG) or rotational thromboelastometry
(ROTEM).
FFP may also be used in patients who have received massive blood
transfusions (see later discussion and Chapter 39) and continue to bleed
following platelet transfusions. Patients with antithrombin III deficiency or
thrombotic thrombocytopenic purpura also benefit from FFP transfusions.
Each unit of FFP carries the same infectious risk as a unit of whole blood. In
addition, occasional patients may become sensitized to plasma proteins. ABO-
compatible units are usually given but are not mandatory. As with red cells, FFP
should generally be warmed to 37°C prior to transfusion.

Platelets
Platelet transfusions should be given to patients with thrombocytopenia or
dysfunctional platelets in the presence of bleeding. Prophylactic platelet
transfusions are also indicated in patients with platelet counts below 10,000 to
20,000 × 109/L because of an increased risk of spontaneous hemorrhage.
Platelet counts less than 50,000 × 109/L are associated with increased blood
loss during surgery, and such thrombocytopenic patients often receive
prophylactic platelet transfusions prior to surgery or invasive procedures.
Vaginal delivery and minor surgical procedures may be performed in patients
with normal platelet function and counts greater than 50,000 × 109/L.
Administration of a single unit of platelets may be expected to increase the
platelet count by 5000 to 10,000 × 109/L, and with administration of a platelet
apheresis unit, by 30,000 to 60,000 × 109/L.
ABO-compatible platelet transfusions are desirable but not necessary.
Transfused platelets generally survive only 1 to 7 days following transfusion.
ABO compatibility may increase platelet survival. Rh sensitization can occur in
Rh-negative recipients due to the presence of a few red cells in Rh-positive
platelet units. Moreover, anti-A or anti-B antibodies in the 70 mL of plasma in
each platelet unit can cause a hemolytic reaction against the recipient’s red cells
when a large number of ABO-incompatible platelet units is given.
Administration of Rh immunoglobulin to Rh-negative individuals can protect
against Rh sensitization following Rh-positive platelet transfusions.

Granulocyte Transfusions
Granulocyte transfusions, prepared by leukapheresis, may be indicated in
neutropenic patients with bacterial infections not responding to antibiotics.
Transfused granulocytes have a very short circulatory life span, so that daily
transfusions of 1010 granulocytes are usually required. Irradiation of these units
decreases the incidence of graft-versus-host reactions, pulmonary endothelial
damage, and other problems associated with transfusion of leukocytes (see next
section), but may adversely affect granulocyte function. The availability of
granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage
colony-stimulating factor (GM-CSF) has greatly reduced the need for
granulocyte transfusions.

Indications for Procoagulant Transfusions

Blood products can be misused in surgical settings. Use of a transfusion
algorithm, particularly for components such as plasma, platelets, and
cryoprecipitate, and particularly when the algorithm is guided by appropriate
laboratory testing, will reduce unnecessary transfusion of these precious and
costly (but dangerous) resources (see Chapter 22). Following military
experience, major civilian trauma care units commonly transfuse blood products
in equal ratios early in severe trauma resuscitation efforts in order to preempt or
correct trauma-induced coagulopathy. This balanced approach to transfusion of
blood products, 1:1:1 (one unit of FFP and one unit of platelets with each unit of
PRBCs), is termed damage control resuscitation (see Chapter 39).

Complications of Blood Transfusion

IMMUNE COMPLICATIONS
Immune complications following blood transfusions are primarily due to
sensitization of the recipient to donor red cells, white cells, platelets, or plasma
proteins. Less commonly, the transfused cells or serum may mount an immune
response against the recipient.

1. Hemolytic Reactions
Hemolytic reactions usually involve specific destruction of the transfused red
cells by the recipient’s antibodies. Less commonly, hemolysis of a recipient’s red
cells occurs as a result of transfusion of red cell antibodies. Incompatible units of
platelet concentrates, FFP, clotting factor concentrates, or cryoprecipitate may
contain small amounts of plasma with anti-A or anti-B (or both) alloantibodies.
Transfusions of large volumes of such units can lead to intravascular hemolysis.
Hemolytic reactions are commonly classified as either acute (intravascular) or
delayed (extravascular).

Acute Hemolytic Reactions

Acute intravascular hemolysis is usually due to ABO blood incompatibility, and
the reported frequency is approximately 1:38,000 transfusions. The most
common cause is misidentification of a patient, blood specimen, or
transfusion unit, a risk that is not abolished with autologous blood
transfusion. These reactions are often severe, and may occur after infusion of as
little as 10 to 15 mL of ABO-incompatible blood. The risk of a fatal hemolytic
reaction is about 1 in 100,000 transfusions. In awake patients, symptoms include
chills, fever, nausea, and chest and flank pain. In anesthetized patients, an
acute hemolytic reaction may be manifested by a rise in temperature,
unexplained tachycardia, hypotension, hemoglobinuria, diffuse oozing in
the surgical field, or a combination of these findings. Disseminated
intravascular coagulation, shock, and kidney acute failure can develop rapidly.
The severity of a reaction often depends upon the volume of incompatible blood
that has been administered.
Management of hemolytic reactions can be summarized as follows:

1. If a hemolytic reaction is suspected, the transfusion should be stopped

immediately and the blood bank should be notified.
2. The unit should be rechecked against the blood slip and the patient’s identity
bracelet.
3. Blood should be drawn to identify hemoglobin in plasma, to repeat
compatibility testing, and to obtain coagulation studies and a platelet count.
4. A urinary bladder catheter should be inserted, and the urine should be
checked for hemoglobin.
5. Forced diuresis should be initiated with mannitol and intravenous fluids, and
with a loop diuretic if necessary.

Delayed Hemolytic Reactions

A delayed hemolytic reaction—also called extravascular hemolysis—is
generally mild and is caused by antibodies to non-D antigens of the Rh system or
to foreign alleles in other systems such as the Kell, Duffy, or Kidd antigens.
Following an ABO and Rh D-compatible transfusion, patients have a 1% to
1.6% chance of forming antibodies directed against foreign antigens in these
other systems. By the time significant amounts of these antibodies have formed
(weeks to months), the transfused red cells have been cleared from the
circulation. Moreover, the titer of these antibodies subsequently decreases and
may become undetectable. Reexposure to the same foreign antigen during a
subsequent red cell transfusion, however, triggers an anamnestic antibody
response against the foreign antigen. The hemolytic reaction is therefore
typically delayed 2 to 21 days after transfusion, and symptoms are generally
mild, consisting of malaise, jaundice, and fever. The patient’s hematocrit
typically fails to rise, or rises only transiently, in spite of the transfusion and the
absence of bleeding. The serum unconjugated bilirubin increases as a result of
hemoglobin breakdown.
Diagnosis of delayed antibody-mediated hemolytic reactions may be
facilitated by the antiglobulin (Coombs) test. The direct Coombs test detects the
presence of antibodies on the membrane of red cells. In this setting, however,
this test cannot distinguish between recipient antibodies coated on donor red
cells and donor antibodies coated on recipient red cells. The latter requires a
more detailed reexamination of pretransfusion specimens from both the patient
and the donor.
The treatment of delayed hemolytic reactions is primarily supportive. The
frequency of delayed hemolytic transfusion reactions is estimated to be
approximately 1:12,000 transfusions. Pregnancy (exposure to fetal red cells) can
also be responsible for the formation of alloantibodies to red cells.

2. Nonhemolytic Immune Reactions

Nonhemolytic immune reactions are due to sensitization of the recipient to the
donor’s white cells, platelets, or plasma proteins; the risk of these reactions may
be minimized by the use of leukoreduced blood products.

Febrile Reactions
White cell or platelet sensitization is typically manifested as a febrile reaction.
Such reactions are relatively common (1–3% of transfusion episodes) and are
characterized by an increase in temperature without evidence of hemolysis.
Patients with a history of repeated febrile reactions should receive leukoreduced
transfusions only.

Urticarial Reactions
Urticarial reactions are usually characterized by erythema, hives, and itching
without fever. They are relatively common (1% of transfusions) and are thought
to be due to sensitization of the patient to transfused plasma proteins. Urticarial
reactions can be treated with antihistaminic drugs (H1 and perhaps H2 blockers)
and steroids.

Anaphylactic Reactions
Anaphylactic reactions are rare (approximately 1:150,000 transfusions). These
severe reactions may occur after only a few milliliters of blood has been given,
typically in IgA-deficient patients with anti-IgA antibodies who receive IgA-
containing blood transfusions. The prevalence of IgA deficiency is estimated to
be 1:600 to 1:800 in the general population. Such reactions require treatment
with epinephrine, fluids, corticosteroids, and H1 and H2 blockers. Patients with
IgA deficiency should receive thoroughly washed packed red cells,
deglycerolized frozen red cells, or IgA-free blood units.

Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) presents as acute hypoxia and
noncardiac pulmonary edema occurring within 6 h of blood product transfusion.
It may occur as frequently as 1:5000 transfused units, and with transfusion of
any blood component, but especially platelets and FFP. Treatment is similar to
that for acute respiratory distress syndrome (see Chapter 58), with the important
difference that TRALI may resolve within a few days with supportive therapy.
The incidence of TRALI, until recently the leading cause of transfusion-related
death, has markedly declined with the recognition that the presence of HLA
antibodies in donor plasma is the principal TRALI risk factor (see Chapter 39).

Transfusion-Associated Circulatory Overload

Transfusion-associated circulatory overload (TACO) occurs when blood
products are administered at a rate greater than the patient’s cardiac output,
usually in a massive hemorrhage resuscitation scenario. This is most likely to
occur when the provider administering blood products has not recognized that
the source of bleeding has been successfully controlled. Communication in this
situation is critical between the team members resuscitating the patient with
blood products and those attempting to control the hemorrhage (see Chapter 39).
TACO has replaced TRALI as the leading transfusion-related risk for
trauma patients.

Graft-Versus-Host Disease
This type of reaction may be seen in immunocompromised patients. Cellular
blood products contain lymphocytes capable of mounting an immune response
against the compromised recipient. Use of special leukocyte filters alone does
not reliably prevent graft-versus-host disease; irradiation of red cell, granulocyte,
and platelet transfusions effectively eliminates lymphocytes without altering the
efficacy of such transfusions.

Post-Transfusion Purpura
Post-transfusion purpura is a potentially fatal thrombocytopenic disorder that
occurs, rarely, following blood or platelet transfusion. It results from
development of platelet alloantibodies that destroy the patient’s own platelets.
The platelet count typically drops precipitously 5 to 10 days following
transfusion. Treatment may include intravenous IgG and plasmapheresis.

Transfusion-Related Immunomodulation
Allogeneic transfusion of blood products may diminish
immunoresponsiveness and promote inflammation. Post-transfusion
immunosuppression is clearly evident in kidney transplant recipients, in whom
preoperative blood transfusion improves graft survival. Recent studies suggest
that perioperative transfusion may increase the risk of postoperative
bacterial infection, cancer recurrence, and mortality, all of which emphasize
the need to avoid unnecessary blood product administration.

INFECTIOUS COMPLICATIONS
Viral Infections
A. Hepatitis
The incidence of post-transfusion viral hepatitis varies greatly, from
approximately 1:200,000 transfusions (for hepatitis B) to approximately
1:1,900,000 (for hepatitis C). Most acute cases are anicteric. Hepatitis C is the
more serious infection; most cases progress to chronic hepatitis, with cirrhosis
developing in 20% of chronic carriers and hepatocellular carcinoma developing
in up to 5% of chronic carriers.

B. Acquired Immunodeficiency Syndrome (AIDS)

All blood is tested for the presence of anti-HIV-1 and anti-HIV-2 antibodies. The
requirement for donor blood testing by the U.S. Food and Drug Administration
(FDA) has decreased the risk of transfusion-transmitted HIV to approximately
1:1,900,000 transfusions.

C. Other Viral Infections

Cytomegalovirus (CMV) and Epstein–Barr virus usually cause asymptomatic or
mild systemic illness. Some individuals infected with these viruses become
asymptomatic infectious carriers; the white cells in blood units from such donors
are capable of transmitting either virus. Immunocompromised and
immunosuppressed patients (eg, premature infants, organ transplant recipients,
and cancer patients) are particularly susceptible to severe transfusion-related
CMV infections. Ideally, such patients should receive only CMV-negative units.
However, recent studies indicate that the risk of CMV transmission from
transfusion of leukoreduced blood products is equivalent to CMV test-negative
units. Human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) are
leukemia and lymphoma viruses, respectively, that have been reported to be
transmitted by blood transfusion; the former has also been associated with
myelopathy. Parvovirus transmission has been reported following transfusion of
coagulation factor concentrates and can result in transient aplastic crises in
immunocompromised hosts. West Nile virus infection may result in encephalitis
with a fatality rate of up to 10%, and transmission of this virus by transfusion
has been reported.

Parasitic Infections
Parasitic diseases that can be transmitted by transfusion include malaria,
toxoplasmosis, and Chagas disease. Such cases are very rare in developed
countries.

Bacterial Infections
Bacterial contamination of blood products is the second leading cause of
transfusion-associated mortality. The prevalence of positive bacterial cultures
in blood products ranges from 1:2000 for platelets to 1:7000 for PRBCs and may
be due to transient donor bacteremia or to inadequate antisepsis during
phlebotomy. The prevalence of sepsis due to blood transfusion ranges from
1:25,000 for platelets to 1:250,000 for PRBCs. Both gram-positive
(Staphylococcus) and gram-negative (Yersinia and Citrobacter) bacteria can
contaminate blood transfusions and transmit disease. To avoid the possibility of
significant bacterial contamination, blood products should be administered over
a period shorter than 4 h. Specific bacterial diseases rarely transmitted by blood
transfusions from donors include syphilis, brucellosis, salmonellosis, yersiniosis,
and various rickettsioses.

MASSIVE BLOOD TRANSFUSION

Massive transfusion is most often defined as the need to transfuse the patient’s
total estimated blood volume in less than 24 h, or one-half the patient’s total
estimated blood volume in 1 h. For most adult patients, the total estimated blood
volume is the equivalent of 10 to 20 units. The approach to massive transfusion
(and to lesser degrees of transfusion) after trauma injury has been greatly
influenced by recent military experience in which outcomes have improved with
concurrent transfusion of packed red cells, FFP, and platelets to avoid dilutional
coagulopathy (see Chapter 39).

Coagulopathy
The most common cause of nonsurgical bleeding following massive blood
transfusion is dilutional thrombocytopenia, although clinically significant
dilution of coagulation factors may also occur. Point-of-care coagulation studies
and platelet counts should guide platelet and FFP transfusion. Although most
clinicians will be familiar with “routine” coagulation tests (eg, prothrombin time
[PT], activated partial thromboplastin time [aPTT], international normalized
ratio [INR], platelet count, fibrinogen), multiple studies show that viscoelastic
analysis of whole blood clotting (thromboelastography, rotation
thromboelastometry, or Sonoclot analysis) is more useful in resuscitation, liver
transplantation, and cardiac surgical settings.

Citrate Toxicity
Calcium binding by the citrate preservative can rise in importance following
transfusion of large volumes of blood or blood products. 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.
Because citrate metabolism is primarily hepatic, patients with hepatic disease or
dysfunction (and possibly hypothermic patients) may demonstrate hypocalcemia
and require calcium infusion during massive transfusion, as may small children
and others with relatively impaired parathyroid–vitamin D function.

Hypothermia
Massive blood transfusion is an absolute indication for warming all blood
products and intravenous fluids to normal body temperature. Ventricular
arrhythmias progressing to fibrillation often occur at temperatures close to 30°C,
and hypothermia will hamper cardiac resuscitation. The customary use of rapid
infusion devices with efficient heat transfer capability has decreased the
incidence of transfusion-related hypothermia.

Acid–Base Balance
Although stored blood is acidic due to the citric acid anticoagulant and
accumulation of red cell metabolites (carbon dioxide and lactic acid), metabolic
acidosis due to transfusion is uncommon because citric acid and lactic acid are
rapidly metabolized to bicarbonate by the normal liver. However, in the situation
of massive blood transfusion, acid–base status is largely dependent upon tissue
perfusion, rate of blood transfusion, and citrate metabolism. Once normal
tissue perfusion is restored, any metabolic acidosis typically resolves, and
metabolic alkalosis commonly occurs as citrate and lactate contained in
transfusions and resuscitation fluids are converted to bicarbonate by the liver.

Serum Potassium Concentration

The extracellular concentration of potassium in stored blood steadily
increases with time. The amount of extracellular potassium transfused with
each unit is typically less than 4 mEq per unit. Hyperkalemia can develop
regardless of the age of the blood when transfusion rates exceed 100 mL/min.
The treatment of hyperkalemia is discussed in Chapter 49. In contrast,
hypokalemia is commonly encountered postoperatively, particularly in
association with metabolic alkalosis (see Chapters 49 and 50).

Alternative Strategies for Management of Blood Loss

During Surgery

AUTOLOGOUS TRANSFUSION
Patients undergoing some elective surgical procedures with a high probability
for transfusion can donate their own blood for use during that surgery. Collection
is usually started 4 to 5 weeks prior to the procedure. The patient is usually
allowed to donate a unit as long as the hematocrit is at least 34% or hemoglobin
at least 11 g/dL. A minimum of 72 h is required between donations to ensure
plasma volume has returned to normal. With iron supplementation and
erythropoietin therapy, at least 3 or 4 units can usually be collected prior to
operation. Autologous blood transfusions probably do not adversely affect
survival in patients undergoing operations for cancer. Although autologous
transfusions likely reduce the risk of infection and transfusion reactions, they are
not risk-free. Risks include those of immunological reactions due to clerical
errors in collection, labeling, and administration; bacterial contamination; and
improper storage. Allergic reactions can occur due to allergens (eg, ethylene
oxide) that dissolve into the blood from collection and storage equipment.

BLOOD SALVAGE & REINFUSION

This technique is used widely during cardiac, major vascular, and orthopedic
surgery (see Chapter 22). The shed blood is aspirated intraoperatively into a
reservoir and mixed with heparin. After a sufficient amount of blood is collected,
the red cells are concentrated and washed to remove debris and anticoagulant
and then reinfused into the patient. The concentrates obtained usually have
hematocrits of 50% to 60%. To be used effectively, this technique requires blood
losses greater than 1000 to 1500 mL. Contraindications to blood salvage and
reinfusion include septic contamination of the wound and perhaps malignancy.
Newer, simpler systems allow reinfusion of shed blood without centrifugation.

NORMOVOLEMIC HEMODILUTION
Acute normovolemic hemodilution relies on the premise that if the concentration
of red cells is decreased, total red cell loss is reduced when large amounts of
blood are shed; moreover, cardiac output remains normal because intravascular
volume is maintained. One or 2 units of blood are typically removed just prior to
surgery from a large-bore intravenous catheter and replaced with crystalloid and
colloids so that the patient remains normovolemic but has a hematocrit of 21%
to 25%. The blood that is removed is stored in a CPD bag at room temperature
(up to 6 h) to preserve platelet function; the blood is given back to the patient
after the blood loss, or sooner if necessary. The use of normovolemic
hemodilution is now rare because of progressive improvements in transfusion
safety.

DONOR-DIRECTED TRANSFUSIONS
Patients can request donated blood from family members or friends known to be
ABO compatible. Most blood banks discourage this practice and generally
require donation at least 7 days prior to surgery in order to process the donated
blood and confirm compatibility. Studies comparing the safety of donor-directed
units to that of random donor units have found either no difference or that
random units from blood banks are safer than directed units.

CASE DISCUSSION

A Patient with Sickle Cell Disease

A 24-year-old woman with a history of sickle cell anemia presents with
abdominal pain and is scheduled for cholecystectomy.
What is sickle cell anemia?
Sickle cell anemia is a hereditary hemolytic anemia resulting from the
formation of an abnormal hemoglobin (HbS). HbS differs structurally from
the normal adult hemoglobin (HbA) only in the substitution of valine for
glutamic acid at the sixth position of the β chain. Functionally, sickle
hemoglobin has less affinity for oxygen (P50 = 31 mm Hg) as well as less
solubility. Upon deoxygenation, HbS readily polymerizes and precipitates
inside RBCs, causing them to sickle. Sickle cell patients produce variable
amounts (2–20%) of fetal hemoglobin (HbF), and it is likely that cells with
large amounts of HbF are somewhat protected from sickling. The
continuous destruction of irreversibly sickled cells leads to anemia, and
hematocrits are typically 18% to 30% due to the extravascular hemolysis.
RBC survival is reduced to 10 to 15 days, compared with up to 120 days in
normal individuals.
What is the difference between sickle cell anemia and sickle cell
trait?
When the genetic defect for adult hemoglobin is present on both the
maternally and paternally derived chromosomes (No. 11), the patient is
homozygous for HbS and has sickle cell anemia (HbSS). When only one
chromosome has the sickle gene, the patient is heterozygous and has sickle
cell trait (HbAS). Patients with the sickle trait produce variable amounts of
HbA (55–60%) and HbS (35–40%). Unlike those with HbSS, they are
generally not anemic, are asymptomatic, and have a normal life span.
Sickling occurs only under extreme hypoxemia or in low-flow states.
Sickling is particularly apt to occur in the renal medulla; indeed, many
patients with the sickle trait have impaired renal concentrating ability.
Patients with HbAS may have renal medullary, splenic, and pulmonary
infarcts.
Sickle cell anemia is primarily a disease of individuals of Central
African ancestry. Approximately 0.2% to 0.5% of African Americans are
homozygous for the sickle gene and approximately 8% to 10% are
heterozygous. Sickle cell anemia is found less commonly in patients of
Mediterranean ancestry.
What is the pathophysiology?
Conditions favoring the formation of deoxyhemoglobin (eg, hypoxemia,
acidosis, intracellular hypertonicity or dehydration, increased 2,3-DPG
levels, or increased temperature) can precipitate sickling in patients with
HbSS. Hypothermia may also be detrimental because of associated
vasoconstriction (see below). Intracellular polymerization of HbS distorts
red cells, makes them less pliable and more “sticky,” increasing blood
viscosity. Sickling may initially be reversible but eventually becomes
irreversible in some RBCs. Formation of red cell aggregates in capillaries
can obstruct tissue microcirculation, and a vicious cycle is established in
which circulatory stasis leads to localized hypoxia, which, in turn, causes
more sickling.
With what symptoms do patients with sickle cell anemia usually
present?
Patients with HbSS generally first develop symptoms in infancy, when
levels of HbF decline. The disease is characterized by both acute episodic
crises and chronic and progressive features (Table 51–7). Children display
retarded growth and have recurrent infections. Recurrent splenic infarction
leads to splenic atrophy and functional asplenism by adolescence. Patients
usually die from recurrent infections or kidney failure. Chronic abdominal,
bone, and joint pain is typical, often complicated by repeated, acutely
painful sickling crises, and patients frequently require chronic opioid
therapy. Because of issues related to analgesic tolerance and addiction,
these patients often benefit from management by pain specialists. Crises are
often precipitated by infection, cold weather, dehydration, or other forms of
stress. Crises may be divided into three types:

TABLE 51–7 Manifestations of sickle cell anemia.

1. Vasoocclusive crises: Depending on the vessels involved, these acute
episodes can result in micro- or macroinfarctions. Most painful crises
are thought to be due to microinfarcts in various tissues. Clinically, they
present as acute abdominal, chest, back, or joint pain. Differentiation
between surgical and nonsurgical causes of abdominal pain is difficult.
Most patients form pigmented gallstones by adulthood, and many
present with acute cholecystitis. Vasoocclusive phenomena in larger
vessels can produce thromboses resulting in splenic, cerebral,
pulmonary, hepatic, renal, and, less commonly, myocardial infarctions.
2. Aplastic crisis: Profound anemia (Hb 2–3 g/dL) can rapidly occur
when red cell production in the bone marrow is exhausted or
suppressed. Infections and folate deficiency may play a major role.
Some patients also develop leukopenia.
3. Splenic sequestration crisis: Sudden pooling of blood in the spleen can
occur in infants and young children and can cause life-threatening
hypotension. The mechanism is thought to be partial or complete
occlusion of venous drainage from the spleen.
How is sickle cell anemia diagnosed?
RBCs from patients with sickle cell anemia readily sickle following
addition of an oxygen-consuming reagent (metabisulfite) or a hypertonic
ionic solution (solubility test). Confirmation requires hemoglobin
electrophoresis.
What would be the best way to prepare patients with sickle cell
anemia for surgery?
Optimal preoperative preparation includes the following: patients should
be well hydrated, infections should be controlled, and the hemoglobin
concentration should be at an acceptable level. Preoperative transfusion
must be individualized for the patient and to the surgical procedure. Partial
exchange transfusions before major surgical procedures are usually
advocated, which decrease blood viscosity, increase blood oxygen-carrying
capacity, and decrease likelihood of sickling. The goal of such transfusions
is generally to achieve a hematocrit of 35% to 40% with 40% to 50%
normal hemoglobin (HbA). Chronic management of sickle cell disease has
been revolutionized by the introduction of hydroxyurea.
Are there any special intraoperative considerations?
Conditions that might promote hemoglobin desaturation or low-flow
states should be avoided. Every effort must be made to avoid hypothermia,
hyperthermia, acidosis, and even mild degrees of hypoxemia, hypotension,
or hypovolemia, and generous hydration and a relatively high (>50%)
inspired oxygen tension are important. The principal compensatory
mechanism for impaired tissue oxygen delivery in these patients is
increased cardiac output, which should be maintained intraoperatively.
GDFT may be useful. Mild alkalosis may help avoid sickling, but even
moderate degrees of respiratory alkalosis may have an adverse effect on
cerebral blood flow. Tourniquet use, other than brief, should be avoided.
Are there any special postoperative considerations?
Most perioperative deaths occur in the postoperative period, and the
same management principles applied intraoperatively should be utilized
following surgery. Hypoxemia and pulmonary complications (particularly
acute chest syndrome) are major risk factors. Supplemental oxygen; optimal
hemodynamic, fluid, and pain and symptom management; and pulmonary
physiotherapy with early mobilization all help minimize the risk of these
complications.
What is the pathophysiology of thalassemia?
Thalassemia is a hereditary defect in the production of one or more of
the normal subunits of hemoglobin. Patients with thalassemia may be able
to produce normal HbA but have reduced amounts of α- or β-chain
production; the severity of this defect depends on the subunit affected and
the degree to which hemoglobin production is affected. Symptoms range
from absent to severe. Patients with α-thalassemia produce reduced
amounts of the α subunit, whereas patients with β-thalassemia produce
reduced amounts of the β subunit. The formation of hemoglobins with
abnormal subunit composition can alter the red cell membrane and lead to
variable degrees of hemolysis as well as ineffective hematopoiesis. The
latter can result in hypertrophy of the bone marrow and often an abnormal
skeleton. Maxillary hypertrophy may make tracheal intubation difficult.
Thalassemias are most common in patients of Southeast Asian, African,
Mediterranean, and Indian ancestry.
What is the significance of sickle cell anemia and thalassemia
in the same patient?
The combination of HbS and thalassemia, most commonly sickle β-
thalassemia, has a variable and unpredictable effect on disease severity.
What is hemoglobin C disease?
Substitution of lysine for glutamic acid at position 6 on the β subunit
results in hemoglobin C (HbC). Approximately 0.05% of African
Americans carry the gene for HbC. Patients homozygous for HbC generally
have only a mild hemolytic anemia and splenomegaly and rarely develop
significant complications. The tendency for HbC to crystallize in hypertonic
environments is probably responsible for the hemolysis and
characteristically produces target cells on the peripheral blood smear.
What is the significance of the genotype HbSC?
Nearly 0.1% of African Americans are simultaneously heterozygous for
both HbS and HbC (HbSC). These patients generally have a mild to
moderate hemolytic anemia. Some patients occasionally have painful crises,
splenic infarcts, and hepatic dysfunction. Eye manifestations similar to
those associated with HbSS disease are particularly prominent. Women
with HbSC have a high rate of complications during the third trimester of
pregnancy and delivery.
What is hemoglobin E?
Hemoglobin E is the result of a single substitution on the β chain and is
the second most common hemoglobin variant worldwide. It is most often
encountered in patients from Southeast Asia. Although oxygen-binding
affinity is normal, the substitution impairs production of β chains (similar to
β-thalassemia). Homozygous patients have marked microcytosis and
prominent target cells, but are not usually anemic and lack any other
manifestations.
What is the hematologic significance of glucose-6-phosphate
dehydrogenase (G6PD) deficiency?
RBCs are normally well-protected against oxidizing agents. The
sulfhydryl groups on hemoglobin are protected by reduced glutathione. The
latter is regenerated by NADPH (reduced nicotinamide adenine
dinucleotide phosphate), which itself is regenerated by glucose metabolism
in the hexose monophosphate shunt. G6PD is a critical enzyme in this
pathway. A defect in this pathway results in an inadequate amount of
reduced glutathione, which can potentially result in the oxidation and
precipitation of hemoglobin in red cells (seen as Heinz bodies) and
hemolysis.
Abnormalities in G6PD are relatively common, with over 400 variants
described. Clinical manifestations are variable, depending on the functional
significance of the enzyme abnormality. Up to 15% of African American
males have the common, clinically significant, A– variant. A second variant
is common in individuals of eastern Mediterranean ancestry, and a third in
individuals of Chinese ancestry. Because the locus for the enzyme is on the
X chromosome, abnormalities are X-linked traits, with males being
primarily affected. G6PD activity decreases as RBCs age; therefore, aging
red cells are most susceptible to oxidation. This decay is markedly
accelerated in patients with the Mediterranean variant, but only moderately
so in patients with the A– variant.
Most patients with G6PD deficiency are not anemic but can develop
hemolysis following stresses such as viral and bacterial infections, or after
administration of certain drugs (Table 51–8). Hemolytic episodes can be
precipitated by metabolic acidosis (eg, diabetic ketoacidosis) and may
present with hemoglobinuria and hypotension. Such episodes are generally
self-limited because only the older population of RBCs is destroyed.
Mediterranean variants may be associated with chronic hemolytic anemia
of varying severity and may include the classic feature of marked
sensitivity to fava beans.

TABLE 51–8 Drugs to avoid in patients with G6PD1 deficiency.

 Management of G6PD deficiency is primarily preventive, avoiding
factors known to promote or exacerbate hemolysis. Measures aimed at
preserving kidney function (see above) are indicated in patients who
develop hemoglobinuria.

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 CHAPTER

52
Thermoregulation, Hypothermia, &
Malignant Hyperthermia

KEY CONCEPTS

When there is no attempt to actively warm an anesthetized patient, core

temperature usually decreases 1°C to 2°C during the first hour of
general anesthesia (phase one), followed by a more gradual decline
during the ensuing 3 to 4 h (phase two), eventually reaching a point of
steady state.
In the normal, unanesthetized patient the hypothalamus maintains core
body temperature within very narrow tolerances, termed the
interthreshold range, with the threshold for sweating and vasodilation at
one extreme and the threshold for vasoconstriction and shivering at the
other.
Anesthetics inhibit central thermoregulation by interfering with these
hypothalamic reflex responses.
Postoperative hypothermia should be treated with a forced-air warming
device, if available; alternately (but less satisfactorily) warming lights
or heating blankets can be used to restore body temperature to normal.
Nearly 50% of patients who experience an episode of malignant
hyperthermia (MH) have had at least one previous uneventful exposure
to anesthesia during which they received a recognized triggering agent.
Why MH fails to occur after every exposure to a triggering agent is
unclear.
The earliest signs of MH during anesthesia include muscle rigidity,
tachycardia, unexplained hypercarbia, and increased temperature.
Susceptibility to MH may be increased in several musculoskeletal
diseases. These include central-core disease, multi-minicore myopathy,
and King–Denborough syndrome.
 Treatment of an MH episode is directed at terminating the episode and
treating complications such as hyperthermia and acidosis. The mortality
rate for MH, even with prompt treatment, ranges from 5% to 30%. First
and most importantly, the triggering agent must be stopped; second,
dantrolene must be given immediately.
Dantrolene, a hydantoin derivative, directly interferes with muscle
contraction by inhibiting calcium ion release from the sarcoplasmic
reticulum. The dose is 2.5 mg/kg intravenously every 5 min until the
episode is terminated (upper limit, 10 mg/kg). Dantrolene should be
continued for 24 h after initial treatment.
Propofol, etomidate, benzodiazepines, ketamine, thiopental,
methohexital, opiates, droperidol, nitrous oxide, nondepolarizing
muscle relaxants, and all local anesthetics are safe for use in MH-
susceptible patients.

THERMOREGULATION & HYPOTHERMIA

Anesthesia and surgery predispose patients to hypothermia, usually defined as a
body temperature less than 36°C. Unintentional perioperative hypothermia is
more common in patients at the extremes of age, and in those undergoing
abdominal surgery or procedures of long duration, especially with cold ambient
operating room temperatures; it will occur in nearly every such patient unless
steps are taken to prevent this complication.
Hypothermia (in the absence of shivering) reduces metabolic oxygen
requirements and can be protective during cerebral or cardiac ischemia.
Nevertheless, hypothermia has multiple deleterious physiological effects
(Table 52–1). In fact, unintended perioperative hypothermia has been associated
with an increased mortality rate.

TABLE 52–1 Deleterious effects of hypothermia.

 Core temperature is normally the same as the central venous blood
temperature (except during periods of relatively rapid temperature change as can
occur during and after extracorporeal perfusion). When there is no attempt to
actively warm an anesthetized patient, core temperature usually decreases 1°C to
2°C during the first hour of general anesthesia (phase one), followed by a more
gradual decline during the ensuing 3 to 4 h (phase two), eventually reaching a
point of steady state (phase three). With general, epidural, or spinal anesthesia
most of the initial decrease in temperature during phase one is explained by
redistribution of heat from warm “central” compartments (eg, abdomen, thorax)
to cooler peripheral tissues (eg, arms, legs) from anesthetic-induced vasodilation.
Actual heat loss from the patient to the environment is a minor contributor.
Continuous heat loss to the environment is the primary driver for the slower
decline during phase two. At steady state, heat loss equals metabolic heat
production (Figure 52–1).
FIGURE 52–1 Unintentional hypothermia during general anesthesia follows a
typical pattern: a steep drop in core temperature during the first hour (phase one,
redistribution), followed by a gradual decline during the next 3 to 4 h (phase
two, heat loss), eventually reaching a steady state (phase three).

In the normal unanesthetized patient the hypothalamus maintains core body

temperature within very narrow tolerances, termed the interthreshold range, with
the threshold for sweating and vasodilation at one extreme and the threshold for
vasoconstriction and shivering at the other. Increasing core temperature a
fraction of a degree induces sweating and vasodilation, whereas a minimally
reduced core temperature triggers vasoconstriction and shivering. Anesthetic
agents inhibit central thermoregulation by interfering with these hypothalamic
reflex responses. For example, isoflurane produces a dose-dependent decrease in
the threshold temperature that triggers vasoconstriction (3°C decrease for each
percent of inhaled isoflurane). Both general and neuraxial anesthetics increase
the interthreshold range, albeit by different mechanisms. Spinal and epidural
anesthetics, like general anesthetics, lead to hypothermia by causing vasodilation
and internal redistribution of heat. The thermoregulatory impairment from
conduction anesthesia that allows continued heat loss is likely also due to altered
perception by the hypothalamus of temperature in the anesthetized dermatomes.

Intraoperative Considerations
A cold ambient temperature in the operating room, prolonged exposure of a large
wound, and the use of large amounts of room-temperature intravenous fluids or
high flows of unhumidified gases can contribute to hypothermia. Prewarming
the patient for half an hour with convective forced-air warming blankets
prevents phase one hypothermia by eliminating the central–peripheral
temperature gradient. Methods to minimize phase two hypothermia from heat
loss during anesthesia include use of forced-air warming blankets and warm-
water blankets, heated humidification of inspired gases, warming of intravenous
fluids, and increasing ambient operating room temperature. Passive insulators
such as heated cotton blankets or so-called space blankets have limited utility
unless virtually the entire body is covered.

Postoperative Considerations
Shivering can occur in postanesthesia care units (PACUs) or critical care units as
a result of actual hypothermia or neurological aftereffects of general anesthetic
agents. Shivering is also common immediately postpartum. Shivering in such
instances represents the body’s effort to increase heat production and raise body
temperature and may be associated with intense vasoconstriction. Emergence
from even brief general anesthesia is sometimes also associated with shivering.
Although shivering can be part of nonspecific neurological signs (posturing,
clonus, or the Babinski sign) sometimes observed during emergence, shivering is
typically associated with hypothermia and volatile anesthetics. Shivering appears
to be more common after longer durations of surgery and the use of greater
concentrations of a volatile agent. Occasionally, shivering is intense enough to
cause hyperthermia (38–39°C) and metabolic acidosis, both of which promptly
resolve when the shivering stops. Both spinal and epidural anesthesia lower the
shivering threshold and vasoconstrictive response to hypothermia; shivering may
also be encountered in the PACU following regional anesthesia. Other causes of
shivering should be excluded, such as sepsis, drug allergy, or a transfusion
reaction. Intense shivering may increase oxygen consumption, CO2 production,
and cardiac output. These physiological effects are often poorly tolerated by
patients with preexisting cardiac or pulmonary impairment.
Postoperative shivering may increase oxygen consumption as much as
fivefold, may decrease arterial oxygen saturation, and may be associated with an
increased risk of myocardial ischemia. Although postoperative shivering can be
effectively treated with small intravenous doses of meperidine (12.5–25 mg) in
adults, the better option is to reduce the likelihood of shivering by maintaining
normothermia. Shivering in intubated and mechanically ventilated patients can
also be controlled with sedation and a muscle relaxant pending normothermia
and dissipation of all effects of anesthesia.
Postoperative hypothermia should be treated with a forced-air warming
device, if available; alternately (but less satisfactorily) warming lights or heating
blankets can be used. In addition to an increased incidence of myocardial
ischemia, hypothermia has been associated with arrhythmias, increased
transfusion requirements, and increased duration of muscle relaxant effects, the
latter of which can be especially harmful in the recently extubated patient.

MALIGNANT HYPERTHERMIA
Malignant hyperthermia (MH) is a rare (1:15,000 in pediatric patients and
1:40,000 in adult patients) genetic hypermetabolic muscle disease, the
characteristic phenotypical signs and symptoms of which most commonly
appear with exposure to inhaled general anesthetics or succinylcholine
(triggering agents). MH may occasionally present more than an hour after
emergence from an anesthetic, and rarely may occur without exposure to known
triggering agents. Most cases have been reported in young males; almost none
have been reported in infants, and few have been reported in the elderly.
Nevertheless, all ages and both sexes may be affected. The incidence of MH
varies greatly from country to country and even among different geographic
localities within the same country, reflecting varying gene pools. The upper
Midwest appears to have the greatest incidence of MH in the United States.

Pathophysiology
A halogenated anesthetic agent alone may trigger an episode of MH (Table 52–
2). In many of the early reported cases, both succinylcholine and a halogenated
anesthetic agent were used and so-called masseter muscle rigidity was observed.
However, succinylcholine is less frequently used in modern practice, and about
half of the cases in the past decade were associated with a volatile anesthetic as
the only triggering agent. Whether succinylcholine is a trigger in the absence of
a volatile agent is now controversial. Nearly 50% of patients who experience an
episode of MH have had at least one previous uneventful exposure to anesthesia
during which they received a recognized triggering agent. Why MH fails to
occur after every exposure to a triggering agent is unclear. Investigations into the
biochemical causes of MH reveal an uncontrolled increase in intracellular
calcium in skeletal muscle. The sudden release of calcium from sarcoplasmic
reticulum removes the inhibition of troponin, resulting in sustained muscle
contraction. Markedly increased adenosine triphosphatase activity results in an
uncontrolled hypermetabolic state with significantly increased oxygen
consumption and CO2 production, producing severe lactic acidosis and
hyperthermia.

TABLE 52–2 Drugs known to trigger malignant hyperthermia.

Most patients with an episode of MH have relatives who have had a similar
episode or who have an abnormal halothane–caffeine contracture test (see later
discussion). The complexity of genetic inheritance patterns in families reflects
the fact that MH can be associated with a variety of different mutations. The
major focus of investigations into the genetic mechanisms of MH has been on
the gene for the ryanodine (Ryr1) receptor, located on chromosome 19. Ryr1 is a
calcium channel responsible for calcium release from the sarcoplasmic reticulum
and it plays an important role in muscle depolarization. Most investigators
believe that MH results from abnormalities in this channel. The great majority of
families in which there is susceptibility to MH harbor one of the known
mutations of Ryr1.

Clinical Manifestations
The earliest signs of MH during anesthesia include muscle rigidity,
tachycardia, unexplained hypercarbia, and increased temperature (Table 52–3).
Two or more of these signs greatly increase the likelihood that the clinical signs
are the result of MH. The hypercarbia (due to increased CO2 production) results
in tachypnea when muscle relaxants are not used. Overactivity of the
sympathetic nervous system produces tachyarrhythmias, hypertension, and
mottled cyanosis. Hyperthermia may be an early sign, and when it occurs, core
temperature can rise as much as 1°C every 5 min. Generalized muscle rigidity is
not always present. Hypertension may be rapidly followed by hypotension if
cardiac depression occurs. Dark-colored urine reflects myoglobinemia and
myoglobinuria.

TABLE 52–3 Signs of malignant hyperthermia.

Laboratory testing typically reveals mixed metabolic and respiratory acidosis

with a marked base deficit, hyperkalemia, hypermagnesemia, and reduced
mixed-venous oxygen saturation. Some case reports describe isolated respiratory
acidosis early in the course of an episode of MH. Serum ionized calcium
concentration is variable: It may initially increase before a later decrease.
Patients typically have increased serum myoglobin, creatine kinase (CK), lactic
dehydrogenase, and aldolase levels. When peak serum CK levels (the maximum
is usually measured 12–18 h after anesthesia) exceed 20,000 IU/L the diagnosis
is strongly suspected. It should be noted that succinylcholine administration to
some normal patients without MH may cause serum myoglobin and CK levels to
increase markedly.
Much of the problem in diagnosing MH arises from its variable presentation.
An unanticipated doubling or tripling of end-tidal CO2 (in the absence of a
ventilatory change) is an early and sensitive indicator of MH. If the patient
survives the initial presentation, acute kidney failure and disseminated
intravascular coagulation (DIC) can rapidly ensue. Other complications of MH
include cerebral edema with seizures and hepatic failure. Most MH deaths are
due to DIC and organ failure due to delayed or no treatment with dantrolene.
Susceptibility to MH may be increased in several musculoskeletal diseases.
These include central-core disease, multi-minicore myopathy, and King–
Denborough syndrome. Duchenne and other muscular dystrophies, nonspecific
myopathies, heat stroke, and osteogenesis imperfecta have been associated with
MH-like symptoms in some reports; however, their association with MH is
controversial. Other possible clues to susceptibility include a family history of
anesthetic complications, or a history of unexplained fevers or muscular cramps.
There are several reports of MH episodes occurring in patients with a history of
exercise-induced rhabdomyolysis. Prior uneventful anesthetics and absence of a
positive family history are notoriously unreliable predictors of lack of
susceptibility to MH. Any patient who develops masseter muscle rigidity during
induction of anesthesia should be considered potentially susceptible to MH.

Intraoperative Considerations
Treatment of an MH episode is directed at terminating the episode and treating
complications such as hyperthermia and acidosis. The mortality rate for MH,
even with prompt treatment, ranges from 5% to 30%. Table 52-4 illustrates a
standard protocol for management of MH.

TABLE 52–4 Protocol for immediate treatment of malignant

hyperthermia.1
A. Acute Treatment Measures
First and most importantly, volatile agents and succinylcholine must be
discontinued immediately. Even trace amounts of anesthetics released from soda
lime, breathing tubes, and breathing bags may be detrimental. The patient should
be hyperventilated with 100% oxygen to counteract the effects of uncontrolled
CO2 production and increased oxygen consumption.

B. Dantrolene Therapy
The mainstay of therapy for MH is immediate administration of intravenous
dantrolene. Its safety and efficacy mandate its immediate use in this potentially
life-threatening situation. Dantrolene, a hydantoin derivative, directly
interferes with muscle contraction by binding the Ryr1 receptor channel and
inhibiting calcium ion release from the sarcoplasmic reticulum. The dose is 2.5
mg/kg intravenously every 5 min until the episode is terminated (upper limit, 10
mg/kg). “Conventional” dantrolene is packaged as 20 mg of lyophilized powder
to be dissolved in 60 mL of sterile water, thus, reconstitution of the initial dose
can be unavoidably time consuming. A new, more costly formulation is available
in which 250 mg can be reconstituted in 5 mL, making it an attractive option for
the “initial” dose of dantrolene given as an emergency treatment when MH is
first diagnosed (Table 52–5). The effective half-life of dantrolene is about 6 h.

TABLE 52–5 Dantrolene formulations.

After initial control of symptoms, 1 mg/kg of dantrolene intravenously is

recommended every 6 h for 24 to 48 h to prevent relapse (MH can recur within
24 h of an initial episode). Dantrolene is a relatively safe drug that is also used to
decrease temperature in patients with thyroid “storm” and neuroleptic malignant
syndrome. Although its use in chronic therapy for spastic disorders has been
associated with hepatic dysfunction, the most serious complication following
acute administration is generalized muscle weakness that may result in
respiratory insufficiency or aspiration pneumonia. Dantrolene can cause phlebitis
in small peripheral veins and should be given through a central venous line if
one is available. Following administration of dantrolene, most patients revert to
normal acid–base status promptly and no further pharmacological treatment is
necessary.

C. Correction of Acid–Base/Electrolyte Imbalances

Persisting metabolic acidosis should be treated with intravenous sodium
bicarbonate, recognizing that this treatment will worsen the hypercarbia.
Hyperkalemia should be treated with glucose, insulin, and diuresis. There is no
useful role for intravenous calcium salts in treatment of MH. Antiarrhythmic
agents, vasopressors, and inotropes should be administered if indicated. Calcium
channel blockers should not be given to patients receiving dantrolene because
this combination appears to promote hyperkalemia. Furosemide may be used to
establish diuresis and prevent acute kidney failure, which may develop as a
consequence of myoglobinuria. Dantrolene contains a considerable amount of
mannitol (3 g per 20-mg bottle); thus furosemide or bumetanide should be used
in preference to mannitol for diuresis.

D. Cooling the Patient

If fever is present, cooling measures should be instituted immediately. Surface
cooling with ice packs over major arteries, cold air convection, and cooling
blankets are used. Iced saline lavage of the stomach and any open body cavities
(eg, in patients undergoing abdominal surgery) should also be instituted. Use of
hypothermic cardiopulmonary bypass may be appropriate if other measures fail.

E. Management of the Patient with Isolated Masseter Muscle

Rigidity
Masseter muscle rigidity, or trismus, is a forceful contraction of the jaw
musculature that prevents full mouth opening. This must be distinguished from
incomplete jaw relaxation due to inadequate dosing or inadequate delay after
dosing of muscle relaxants. Both myotonia and MH can cause masseter spasm.
The two disorders can be differentiated by the medical history, neurological
examination, and electromyography. The historical incidence of masseter muscle
rigidity following administration of succinylcholine with halothane to pediatric
patients was 1% or more; fortunately, only a small fraction of these patients
actually developed MH. Isolated masseter muscle rigidity is now of mostly
historical interest given the rare combination of halothane and succinylcholine in
current pediatric practice. When this occurs and there is no other sign of MH,
most anesthesiologists would allow surgery to continue using nontriggering
anesthetic agents. Elevated serum CK levels after an episode of masseter muscle
rigidity may indicate an underlying myopathy.

Postoperative Considerations
A. Confirmation of the Diagnosis
Patients who have survived an unequivocal episode of MH are considered
susceptible. If the diagnosis remains in doubt postoperatively, testing is
indicated. Baseline CK may be elevated chronically in 50% to 70% of people at
risk for MH but is not diagnostic. A halothane-caffeine contracture test will
require that a fresh biopsy specimen of living skeletal muscle be exposed to a
caffeine, halothane, or combination caffeine–halothane bath. The halothane–
caffeine contracture test may have a 10% to 20% false-positive rate, but the
false-negative rate is close to zero. Very few centers worldwide perform this test,
and there are only two such sites remaining in the United States. More
commonly (and much more conveniently) genetic testing of patients and first-
degree relatives is performed.
Both European and North American MH registries have been established to
help physicians identify and treat patients with suspected MH, as well as provide
standardization for diagnosis and testing. The Malignant Hyperthermia
Association of the United States (MHAUS, telephone 1-800-986-4287) operates
a 24-hour hotline (1-800-644-9737) and a web site (http://www.mhaus.org). This
web site has a useful and frequently updated section on the genetic testing and
diagnosis of patients suspected of having MH.

1. Differential diagnosis—Several disorders may superficially resemble MH

(Table 52–6). However, MH is associated with greater degrees of metabolic
acidosis and venous desaturation than any of these other conditions. In current
practice, the most common condition confused with MH is hypercarbia from
CO2 insufflation for laparoscopy. This condition can result in an unexpected
increase in end-tidal CO2 with accompanying tachycardia. Surgery and
anesthesia can precipitate thyroid storm in undiagnosed or poorly controlled
hyperthyroid patients. The signs of thyroid storm include tachycardia,
tachyarrhythmias (particularly atrial fibrillation), hyperthermia (often ≥40°C),
hypotension, and in some cases congestive heart failure. In contrast to MH,
hypokalemia is very common. Also unlike the typical intraoperative presentation
of MH, thyroid storm generally develops postoperatively (see Chapter 35).
Pheochromocytoma is associated with dramatic increases in heart rate and blood
pressure but not with an increase in CO2 production, end-tidal CO2, or
temperature (see Chapter 35). Cardiac arrhythmias or ischemia may also be
prominent. Rarely such patients may have hyperthermia (>38°C), which is
generally thought to be due to increased heat production from catecholamine-
mediated increases in metabolic rate together with decreased heat elimination
from intense vasoconstriction. Sepsis shares several characteristics with MH,
including fever, tachypnea, tachycardia, and metabolic acidosis (see Chapter 57).
Sepsis can be difficult to diagnose if there is no obvious primary site of
infection.

TABLE 52–6 Differential diagnosis of hyperthermia in the intraoperative

and immediate postoperative periods.

Less commonly, drug-induced hyperthermia may be encountered in the

perioperative period. In these cases, the drugs appear to markedly increase
serotonin activity in the brain, causing hyperthermia, confusion, shivering,
diaphoresis, hyperreflexia, and myoclonus. Drug combinations associated with
this serotonin syndrome include monoamine oxidase inhibitors (MAOIs) and
meperidine, and MAOIs and selective serotonin reuptake inhibitors (SSRIs).
Hyperthermia can also be caused by some illicit drugs, including 3,4-
methylenedioxymethamphetamine (MDMA or “ecstasy’), “crack” cocaine,
amphetamines, phencyclidine (PCP), and lysergic acid diethylamine (LSD).
Iatrogenic hyperthermia is also a possibility, particularly in pediatric patients.
Common sources of excessive heat in the operating room include humidifiers on
ventilators, warming blankets, heat lamps, and increased ambient temperature.
Injuries to the brainstem, hypothalamus, or nearby regions can be associated
with marked hyperthermia.

2. Neuroleptic malignant syndrome (NMS)—NMS is characterized by

hyperthermia, muscle rigidity with extrapyramidal signs (dyskinesia), altered
consciousness, and autonomic lability in patients receiving antidopaminergic
agents. The syndrome is caused by an imbalance of neurotransmitters in the
central nervous system. It can occur either during drug therapy with
antidopaminergic agents (eg, phenothiazines, butyrophenones, thioxanthenes, or
metoclopramide) or less commonly following the withdrawal of dopaminergic
agonists (levodopa or amantadine) in patients with Parkinson disease. Thus, it
appears to involve abnormal central dopaminergic activity, as opposed to the
altered peripheral calcium release seen in MH. These differing mechanisms
probably explain why nondepolarizing relaxants reverse the rigidity of NMS, but
not the rigidity associated with MH.
NMS does not appear to be inherited and typically takes hours to weeks to
develop; the majority of episodes develop within 2 weeks of a dose adjustment.
Hyperthermia generally tends to be mild, and appears to be proportional to the
amount of rigidity. Autonomic dysfunction results in tachycardia, labile blood
pressure, diaphoresis, increased secretions, and urinary incontinence. Muscle
rigidity can produce dyspnea and respiratory distress and, together with the
increased secretions, can promote aspiration pneumonia. CK levels are typically
elevated; some patients may develop rhabdomyolysis resulting in
myoglobinemia, myoglobinuria, and kidney failure.
Mild forms of NMS promptly resolve after withdrawal of the causative drug
(or reinstitution of antiparkinsonian therapy). Initial treatment of more severe
forms of NMS should include oxygen therapy and endotracheal intubation for
respiratory distress or altered consciousness. Marked muscle rigidity can be
controlled with muscle paralysis, dantrolene, or a dopaminergic agonist
(amantadine, bromocriptine, or levodopa), depending on the severity and acuity
of the syndrome. Resolution of the muscle rigidity usually decreases body
temperature.
This syndrome is considered a separate entity from MH; nevertheless, some
clinicians believe that NMS may predispose patients to MH and recommend that
patients with NMS should not receive succinylcholine or a volatile anesthetic. In
contrast to patients with NMS, patients susceptible to MH can safely receive
phenothiazines.

B. Prophylaxis, Postanesthesia Care, and Discharge

Propofol, etomidate, benzodiazepines, ketamine, thiopental, methohexital,
opiates, droperidol, nitrous oxide, nondepolarizing muscle relaxants, and all
local anesthetics are safe for use in MH-susceptible patients. An adequate supply
of dantrolene should always be available wherever general anesthesia is
provided. Prophylactic administration of intravenous dantrolene to susceptible
patients is not appropriate if a nontriggering anesthetic is administered.
For MH-susceptible patients, the consensus is that the vaporizers should be
removed from the anesthesia workstation (or fixed in an “off” position) and the
machine should be flushed with 10 L/min of fresh gas (air or oxygen) for at least
5 min. This step should reduce concentrations of volatile anesthetics to less than
1 part per million. Additionally, the CO2 absorbent and circle system (or other
anesthetic circuit) hoses should be changed. Manufacturers of modern
anesthesia machines make differing recommendation (based on the design
of their machine) for how to prepare their machines to manage MH-
susceptible patients. We strongly recommend that the reader review the
specific recommendations for the anesthesia machine(s) at their hospital.
MH-susceptible patients who have undergone an uneventful procedure with a
nontriggering anesthetic can be discharged from the PACU or ambulatory
surgery unit when they meet standard criteria. There are no reported cases of
MH-susceptible patients experiencing MH after receiving a nontriggering
anesthetic during uneventful surgery.

SUGGESTED READINGS
Arrich J, Holzer M, Havel C, Müllner M, Herkner H. Hypothermia for
neuroprotection in adults after cardiopulmonary resuscitation. Cochrane
Database Syst Rev. 2016;(2):CD004128.
Campbell G, Alderson P, Smith AF, Warttig S. Warming of intravenous and
irrigation fluids for preventing inadvertent perioperative hypothermia.
Cochrane Database Syst Rev. 2015;(4):CD009891.
Dietrich WD, Bramlett HM. Therapeutic hypothermia and targeted temperature
management in traumatic brain injury: Clinical challenges for successful
translation. Brain Res. 2016;1640(Pt A):94.
Galvin IM, Levy R, Boyd JG, Day AG, Wallace MC. Cooling for cerebral
protection during brain surgery. Cochrane Database Syst Rev. 2015;
(1):CD006638.
Kim TW, Nemergut ME. Preparation of modern anesthesia workstations for
malignant hyperthermia-susceptible patients: A review of past and present
practice. Anesthesiology. 2011;114:205.
Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant
hyperthermia: A review. Orphanet J Rare Dis. 2015;10:93.
Sessler DI. Temperature monitoring and perioperative thermoregulation.
Anesthesiology. 2008;109:318.

WEB SITES
Association of Anaesthetists of Great Britain & Ireland. http://www.aagbi.org/
Malignant Hyperthermia Association of the United States.
http://www.mhaus.org/
 CHAPTER

53
Nutrition in Perioperative & Critical
Care

KEY CONCEPTS

The fit, previously well-nourished patient undergoing elective surgery

could be fasted for up to a week postoperatively without apparent
adverse effect on outcomes, provided that fluid and electrolyte needs
are met. On the other hand, it is well established in multiple studies that
malnourished patients benefit from nutritional repletion via either
enteral or parenteral routes prior to surgery.
The indications for total parenteral nutrition (TPN) are narrow,
including those patients who cannot absorb enteral solutions (small
bowel obstruction, short gut syndrome, etc); partial parenteral nutrition
may be indicated to supplement enteral nutrition (EN) when EN cannot
fully provide for nutritional needs.
TPN will generally require a venous access line with its catheter tip in
the superior vena cava. The line or port through which the TPN
solution will be infused should be dedicated to this purpose, if at all
possible, and strict aseptic techniques should be employed for insertion
and care of the catheter.
In the patient with critical illness, discontinuing an EN infusion may
require multiple potentially dangerous adjustments in insulin infusions
and maintenance of intravenous fluid rates. Meanwhile, the evidence is
sparse that EN infusions delivered through an appropriately sited
gastrointestinal feeding tube increases the risk of aspiration
pneumonitis.
Regardless of whether the TPN infusion is continued, reduced, replaced
with 10% dextrose, or stopped, blood glucose monitoring will be
needed during all but short, minor surgical procedures.
Issues related to nutrition tend to be far removed from the usual concerns of the
surgical anesthesiologist, other than those related to whether patient listed for
elective surgery has fasted for whatever interval one’s institution or colleagues
insist upon (this highly controversial issue is also considered in Chapter 19). On
the other hand, appropriate nutritional support has been recognized to be of key
importance for favorable outcomes in patients with critical illness, a large
fraction of whom will require procedural services. Severe malnutrition causes
widespread organ dysfunction and increases the risk of perioperative morbidity
and mortality. Nutritional repletion may improve wound healing, restore immune
competence, and reduce morbidity and mortality rates in critically ill patients.
Nutritional support is a key element of an enhanced recovery program (these
issues are dealt with in Chapter 48).
This chapter does not provide a complete review of nutrition in the patient
undergoing surgery or with critical illness, but rather offers the framework for
providing basic nutritional support in such patients. We consider, for example,
whether enteral nutrition (EN) or parenteral nutrition (PN) will best meet the
needs of an individual patient. This chapter also briefly reviews the conditions
under which the ongoing nutritional needs of patients may come into conflict
with anesthetic preferences and dogmas, such as the duration that patients must
not receive EN before undergoing general anesthesia.

BASIC NUTRITIONAL NEEDS

Maintenance of normal body mass, composition, structure, and function requires
intake of water, energy substrates, and specific nutrients. Ions and compounds
that cannot be synthesized from other nutrients are characterized as “essential.”
Relatively few essential nutrients are required to form the thousands of
compounds that make up the body. Known essential nutrients include 8 to 10
amino acids, 2 fatty acids, 13 vitamins, and approximately 16 minerals.
Energy is normally derived from dietary or endogenous carbohydrates, fats,
and protein. Metabolic breakdown of these substrates yields the adenosine
triphosphate required for normal cellular function. Dietary fats and
carbohydrates normally supply most of the body’s energy requirements. Dietary
proteins provide amino acids for protein synthesis; however, when their supply
exceeds requirements, amino acids also function as energy substrates. The
metabolic pathways of carbohydrate, fat, and amino acid substrates overlap, such
that some interconversions can occur (see Figure 33–4). Excess amino acids can
be converted to carbohydrate or fatty acid precursors. Excess carbohydrates are
stored as glycogen in the liver and skeletal muscle. When glycogen stores are
saturated (200–400 g in adults), excess carbohydrate is converted to fatty acids
and stored as triglycerides, primarily in fat cells.
During starvation, the protein content of essential tissues is spared. As blood
glucose concentration begins to fall during fasting, insulin secretion decreases
and counterregulatory hormones (eg, glucagon) increase. Hepatic and, to a lesser
extent, renal glycogenolysis and gluconeogenesis are enhanced. As glycogen
supplies are depleted (within 24 h), gluconeogenesis from amino acids becomes
increasingly important. Only neural tissue, renal medullary cells, and
erythrocytes continue to utilize glucose—in effect, sparing tissue proteins.
Lipolysis is enhanced, and fats become the principal energy source. Glycerol
from triglycerides enters the glycolytic pathway, and fatty acids are broken down
to acetylcoenzyme A (acetyl-CoA). Excess acetyl-CoA results in the formation
of ketone bodies (ketosis). Some fatty acids can contribute to gluconeogenesis. If
starvation is prolonged, the brain, kidneys, and muscle also begin to utilize
ketone bodies efficiently.
The previously well-nourished patient undergoing elective surgery could be
fasted for up to a week postoperatively, provided fluid and electrolyte needs are
met. Whether early postoperative nutritional support influences outcomes likely
relates to the degree of preoperative malnutrition, number of nutrient
deficiencies, and severity of the illness, injury, or surgical procedure. The
optimal timing and amount of nutrition support following acute illness remain
unknown. On the other hand, malnourished patients likely benefit from
nutritional repletion prior to and after surgery.
Modern surgical practice has evolved to an expectation of an accelerated
(“enhanced”) recovery. Enhanced recovery programs generally include early
enteral feeding, even in patients undergoing surgery on the gastrointestinal tract,
so prolonged periods of postoperative starvation are no longer common practice.
Such protocols often specify a carbohydrate drink the night before surgery and
again shortly before operation. Previously well-nourished patients should receive
nutritional support after no more than 5 days of postsurgical starvation, and those
with ongoing critical illness or severe malnutrition should be given nutritional
support immediately. The healing of wounds requires energy, protein, lipids,
electrolytes, trace elements, and vitamins. Depletion of any of these substrates
may delay wound healing and predispose to complications, such as infection.
Nutrient depletion may also delay optimal muscle function, which is important
for supporting increased respiratory demands and early mobilization of the
patient.
The resting metabolic rate can be measured (but often inaccurately) using
indirect calorimetry (known as a metabolic cart) or by estimating energy
expenditure using standard nomograms (such as the Harris–Benedict equation)
to approximate the daily energy requirements. Alternatively, a simple and
practical approach assumes that patients require 25 to 30 kcal/kg daily. The
weight is usually taken as the ideal body weight or adjusted body weight. One
determines the daily requirements to ensure that patients are not unnecessarily
overfed, recognizing that nutritional requirements can increase greatly above
basal levels with certain conditions (eg, burns). Thus, obese patients require an
estimation of ideal body weight to prevent overfeeding.

HOW TO FEED THE PATIENT

After total parenteral nutrition (TPN) was established as a feasible approach for
feeding patients lacking a functional gut, physicians extended the practice of
TPN to many circumstances where “logic” or “clinical experience” suggested
that it would be better than EN. In the past, one such indication was acute
pancreatitis: In the 1970s, many clinicians thought that a period of TPN would
put the gut and pancreas at “rest,” allowing for weight gain and resolution of
pain. Unfortunately, both “logic” and “clinical experience” were incorrect. Now,
the worldwide consensus expressed in clinical practice guidelines is that patients
with acute pancreatitis (and indeed all others with functioning guts) will have
worse outcomes if TPN is provided, rather than EN. Today, the indications for
TPN are narrow and include patients who cannot absorb enteral solutions (small
bowel obstruction, short gut syndrome, etc); partial PN may be indicated to
supplement EN when EN cannot fully provide for nutritional needs. In the latter
circumstance, recent evidence supports delaying supplemental PN in previously
well-nourished patients. Earlier initiation of supplemental PN in previously well-
nourished patients, as had been supported by 2009 European guidelines, resulted
in worse outcomes in a large randomized clinical trial; however, smaller
randomized clinical trials have suggested findings to the contrary. The divergent
results from these recent trials may be associated with the type of parenteral
formulations being used, types of patients being studied, timing of PN
administration, and treatment in the control groups. Thus, further studies are
needed to better define patients who may benefit from PN, as well as the optimal
timing of nutritional support and formulations for feeding. In short, EN should
be the primary mode of nutritional support, and PN should be used when EN is
not indicated, not tolerated, or not sufficient.
 There was a time when nearly every physician who took care of critically ill
patients was in the position of frequently ordering TPN for patients. This is no
longer the case, given that EN is now so much more widely employed. As a
consequence, many hospitals and health systems insist that a nutrition support
team take responsibility for those rarer patients who require TPN.
In general, patients with critical illness should undergo whatever initial
hemodynamic resuscitation they require before initiation of nutritional support
(either EN or PN). Absorption, distribution, and metabolism of nutrients require
tissue blood flow, oxygen, and carbon dioxide removal. Adequate tissue blood
flow requires an adequately resuscitated patient. Patients with critical illness
who require EN will usually require placement of a feeding tube. Feeding tubes
may be placed into the stomach in patients with adequate gastric emptying and
low risk of aspiration. In patients with delayed gastric emptying or those at high
risk of aspiration, feeding tubes are best placed into the small intestine. Ideally,
the tip of such tubes will be sited within the small intestine, either by
transpyloric placement of a nasoenteral tube or directly into the jejunum (via a
percutaneous route) during abdominal surgery, reducing the likelihood of gastric
distention and regurgitation. Patients who are unable to eat, but require EN over
long periods of time, will often undergo percutaneous endoscopic placement of
gastrostomy (PEG) tubes (the tips of such tubes can be sited distal to the
pylorus). One should confirm that the tips of all feeding tubes are appropriately
located before initiating feeds to reduce the likelihood that EN solutions will be
accidentally infused, say, into the tracheobronchial tree or abdominal cavity.
TPN will generally require that a venous access line be placed with the
catheter tip in the superior vena cava. PN can be given through a peripheral
intravenous catheter but will require larger volumes of fluid (to accommodate
the requirement for reduced osmolarity) and will carry an increased risk of
phlebitis. The catheter or port through which the TPN solution will be infused
should be dedicated to this purpose, if at all possible, and strict aseptic
techniques should be employed for insertion and care of the catheter.

COMPLICATIONS OF NUTRITIONAL SUPPORT

Diarrhea is a common problem with EN and may be related to either
hyperosmolarity of the solution or lactose intolerance. Gastric distention is
another complication that increases the risk of regurgitation and pulmonary
aspiration; the use of duodenal or jejunostomy tubes should decrease the
likelihood of gastric distention. Complications of TPN are either metabolic or
related to central venous access (Table 53–1). Bloodstream infections associated
with central and peripheral venous lines remain a major concern, particularly in
patients with critical illness and immunocompromised states.

TABLE 53–1 Complications of total parenteral nutrition.

Overfeeding with excess amounts of glucose can increase energy

requirements and production of carbon dioxide; the respiratory quotient can be
greater than 1 because of lipogenesis. Overfeeding can lead to reversible
cholestatic jaundice. Mild elevations of serum transaminases and alkaline
phosphatase may reflect fatty infiltration of the liver as a result of overfeeding.

SPECIFIC NUTRIENTS
Certain nutrients have been associated with improved outcomes. Surgery and
anesthesia are well-recognized inducers of inflammation, producing changes in
local (near the wound) and plasma concentrations of neurohormones, cytokines,
and other mediators. Many investigators have hypothesized that adverse
neurohormonal and inflammatory responses to surgery and anesthesia can be
ameliorated through specific diets. Several clinical trials (and a recent meta-
analysis) suggest that the addition of “immunomodulating” nutrients
(specifically arginine and “fish” oil) to EN may reduce the risk of infection and
reduce the length of hospital stay in high-risk surgical patients. Similarly, current
guidelines for perioperative PN also advocate the inclusion of n-3 fatty acids.
There is some evidence that inclusion of long-chain n-3 polyunsaturated fatty
acids (n-3 PUFAs), long-chain monounsaturated fatty acids (found in olive oil),
or medium-chain fatty acids may be preferable to the use of solutions (such as
soybean-derived lipids) that are rich in longer chain n-6 PUFA. However, such
solutions (although widely available outside of the United States) are not
approved for use in the United States.
In the past, it was customary to individualize TPN solutions for each patient.
Currently, there is little evidence that this is necessary, except in patients who
cannot handle a sodium load (eg, those with severe heart failure). Adjustments
may also be made in patients requiring renal replacement therapy; however, in
most cases this is not necessary. Similarly, except in patients who are already
suffering from hepatic encephalopathy, most patients with liver disease can
safely receive standard amino acid solutions. Thus, most patients receiving EN
and PN can be safely managed with standardized, “off-the-shelf” nutritional
formulations. Both EN and PN standardized formulations are available in ready-
to-use formats that decrease preparation times, reduce contamination risks
during formulation, and are associated with lower costs and similar outcomes to
compounded solutions.

ENTERAL NUTRITION & NIL PER OS RULES

PRIOR TO ELECTIVE SURGERY
Long before the recognition by Mendelsohn of the problem posed by aspiration
pneumonitis, anesthesiologists were reluctant to anesthetize patients scheduled
for elective surgery if they had not been fasted overnight. Over time, the duration
of obligatory time of no solid food per os has steadily declined, particularly in
infants and young children. In the patient with critical illness, discontinuing an
EN infusion may require multiple potentially dangerous adjustments in insulin
infusions and maintenance of intravenous fluid rates. Meanwhile, the evidence is
sparse that EN infusions delivered through an appropriately sited gastrointestinal
feeding tube increases the risk of aspiration pneumonitis. It is also relatively
easy to empty the stomach immediately prior to anesthesia and surgery using 5
to 10 minutes of intermittent suction through a nasogastric tube. Therefore,
current guidelines and current published evidence support continuing EN
infusions (particularly when they are delivered distal to the pylorus)
perioperatively and intraoperatively. Similarly, allowing preoperative patients to
consume clear liquids, as desired, up to the time of surgery seems to have no
influence on the risk of adverse outcomes from aspiration pneumonitis.
Moreover, there is abundant evidence that administering a preoperative
carbohydrate “load” to nondiabetic patients shortly before surgery will have the
salutary metabolic effect of increasing plasma insulin concentrations, decreasing
postoperative insulin resistance, reducing the likelihood of hemodynamic
instability, and reducing the likelihood of postoperative nausea or vomiting.
Such preoperative carbohydrate loading is not nearly as commonplace as we
believe it should be.

TPN & SURGERY

Patients who receive TPN often require surgical procedures. Metabolic
abnormalities are relatively common and, ideally, should be corrected
preoperatively. For example, hypophosphatemia is a serious and often
unrecognized complication that can contribute to postoperative muscle weakness
and respiratory failure.
When TPN infusions are suddenly stopped or decreased perioperatively,
hypoglycemia may develop. Frequent measurements of blood glucose
concentration are therefore required in such instances during general anesthesia.
Conversely, if the TPN solution is continued unchanged, excessive
hyperglycemia resulting in hyperosmolar nonketotic coma or ketoacidosis (in
patients with diabetes) is also possible. The neuroendocrine stress response to
surgery frequently aggravates glucose intolerance. Regardless of whether the
TPN infusion is continued, reduced, replaced with 10% dextrose, or stopped,
blood glucose monitoring will be needed during all but short, minor surgical
procedures.

GUIDELINES
American Dietetic Association. Critical illness evidence-based nutrition practice
guideline. http://www.guidelines.gov/content.aspx?
id=12818&search=ada+critical+illness+nutrition
American Society for Parenteral and Enteral Nutrition.
http://www.nutritioncare.org/Guidelines_and_Clinical_Resources/Clinical_Guidelines/
Braga M, Ljungqvist O, Soeters P, et al. ESPEN guidelines on parenteral
nutrition: Surgery. Clin Nutr. 2009;28:378.
European Society for Clinical Nutrition and Metabolism.
http://www.espen.org/education/espen-guidelines
Mechanick Ji, Youdim A, Jones DB, et al. Clinical practice guidelines for the
perioperative nutritional, metabolic, and nonsurgical support of the bariatric
surgery patient—2013 update: Cosponsored by American Association of
Clinical Endocrinologists, The Obesity Society, and American Society for
Metabolic & Bariatric Surgery. Endocr Pract. 2013;19:337.

SUGGESTED READINGS
Awad S, Lobo DN. Metabolic conditioning to attenuate the adverse effects of
perioperative fasting and improve patient outcomes. Curr Opin Clin Nutr
Metab Care. 2012;15:194.
Escuro AA, Hummell AC. Enteral formulas in nutrition support practice: Is there
a better choice for your patient? Nutr Clin Pract. 2016;31:709.
Magee G, Zaloga GP, Turpin RS, Sanon M. A retrospective, observational study
of patient outcomes for critically ill patients receiving parenteral nutrition.
Value Health. 2014;17:328.
Marcotte E, Chand B. Management and prevention of surgical and nutritional
complications after bariatric surgery. Surg Clin North Am. 2016;96:843.
Marik PE, Zaloga GP. Immunonutrition in high-risk surgical patients: A
systematic review and analysis of the literature. J Parenter Enteral Nutr.
2010;34:378.
Patkova A, Joskova V, Havel E, et al. Energy, protein, carbohydrate, and lipid
intakes and their effects on morbidity and mortality in critically ill adult
patients: A systematic review. Adv Nutr. 2017;8:624.
Reintam Blaser A, Starkopf J, Alhazzani W, et al; ESICM Working Group on
Gastrointestinal Function. Early enteral nutrition in critically ill patients:
ESICM clinical practice guidelines. Intensive Care Med. 2017;43:380.
Tilg H. Diet and intestinal immunity. N Engl J Med. 2012;366:181.
Yao H, He C, Deng L, Liao G. Enteral versus parenteral nutrition in critically ill
patients with severe pancreatitis: A meta-analysis. Eur J Clin Nutr.
2018;72:66.
Yeung SE, Hilkewich L, Gillis C, Heine JA, Fenton TR. Protein intakes are
associated with reduced length of stay: A comparison between Enhanced
Recovery After Surgery (ERAS) and conventional care after elective
colorectal surgery. Am J Clin Nutr. 2017;106:44.
Zaloga GP. Parenteral nutrition in adult inpatients with functioning
gastrointestinal tracts: Assessment of outcomes. Lancet. 2006;367:1101.
 CHAPTER

54
Anesthetic Complications

KEY CONCEPTS

The likelihood of anesthetic complications will never be zero. All

anesthesia practitioners, irrespective of their experience, abilities,
diligence, and best intentions, will participate in anesthetics that are
associated with patient injury.
Malpractice occurs when four requirements have been met: (1) the
practitioner must have a duty to the patient; (2) there must have been a
breach of duty (deviation from the standard of care); (3) the patient
(plaintiff) must have suffered an injury; and (4) the proximate cause of
the injury must have been the practitioner’s deviation from the standard
of care.
Anesthetic mishaps can be categorized as preventable or unpreventable.
Of the preventable incidents, most involve human error, as opposed to
equipment malfunctions.
The relative decrease in death attributed to respiratory rather than
cardiovascular damaging events has been attributed to the increased use
of pulse oximetry and capnometry.
Many anesthetic fatalities occur only after a series of coincidental
circumstances, misjudgments, and technical errors combine (mishap
chain).
Despite differing mechanisms, anaphylactic and anaphylactoid reactions
are typically clinically indistinguishable and equally life threatening.
True anaphylaxis due to anesthetic agents is rare; anaphylactoid
reactions are much more common.
Patients with spina bifida, spinal cord injury, and congenital
abnormalities of the genitourinary tract have a markedly increased
incidence of latex allergy. The incidence of latex anaphylaxis in
children is estimated to be 1 in 10,000.
 There is no clear evidence that exposure to trace amounts of anesthetic
agents presents a health hazard to operating room personnel; however,
the U.S. Occupational Health and Safety Administration continues to
set maximum acceptable trace concentrations of less than 25 ppm for
nitrous oxide and 0.5 ppm for halogenated anesthetics (2 ppm if the
halogenated agent is used alone).
Hollow (hypodermic) needles pose a greater risk than do solid (surgical)
needles because of the potentially larger inoculum. The use of gloves,
needleless systems, or protected needle devices may decrease the
incidence of some (but not all) types of injury.
Anesthesiology is a high-risk medical specialty for substance abuse.
The three most important methods of minimizing radiation doses are
limiting total exposure time during procedures, using proper barriers,
and maximizing one’s distance from the source of radiation.

The likelihood of anesthetic complications will never be zero. All anesthesia

practitioners, irrespective of their experience, abilities, diligence, and best
intentions, will participate in anesthetics that are associated with patient injury.
Moreover, unexpected adverse perioperative outcomes can lead to litigation,
even if those outcomes did not directly arise from anesthetic mismanagement.
This chapter reviews management approaches to complications secondary to
anesthesia and discusses medical malpractice and legal issues from an American
(U.S.) perspective. Readers based in other countries may not find this section to
be as relevant to their practices.

LITIGATION & ANESTHETIC COMPLICATIONS

All anesthesia practitioners will have patients with adverse outcomes, and in the
United States most anesthesiologists will at some point in their career be
involved to one degree or another in malpractice litigation. Consequently,
anesthesia staff should expect litigation to be a part of their professional lives
and maintain adequate medical malpractice liability insurance with coverage
appropriate for the community in which they practice.
When unexpected events occur, anesthesia staff must generate an appropriate
differential diagnosis, seek any necessary consultation, and execute a treatment
plan to mitigate (to the greatest degree possible) any patient injury. Appropriate
documentation in the patient record is helpful, as adverse outcomes may be
reviewed by quality assurance and performance improvement authorities.
Deviations from acceptable practice will likely be noted in the practitioner’s
quality assurance file. Should an adverse outcome lead to litigation, the medical
record documents the practitioner’s actions at the time of the incident. Years may
pass before litigation proceeds to the point where the anesthesia provider is
asked about the case in question. Although memories fade, a clear and complete
anesthesia record can provide evidence that a complication was recognized and
appropriately treated.
It is often difficult to predict which cases will be pursued by plaintiffs!
Litigation may ensue when it is clear (at least to the defense team) that the
anesthesia care conformed to standards, and, conversely, a suit may not be filed
when there is obvious anesthesia culpability. That said, anesthetics that are
followed by unexpected death, paralysis, or brain injury of young, economically
productive individuals are particularly attractive to plaintiff’s lawyers. When a
patient has an unexpectedly poor outcome, one should expect litigation
irrespective of one’s “positive” relationship with the patient or the injured
patient’s family or guardians.
Malpractice occurs when four requirements are met: (1) the practitioner must
have a duty to the patient; (2) there must have been a breach of duty (deviation
from the standard of care); (3) the patient (plaintiff) must have suffered an
injury; and (4) the proximate cause of the injury must have been the
practitioner’s deviation from the standard of care. A duty is established when the
practitioner has an obligation to provide care (physician–patient relationship).
The practitioner’s failure to execute that duty constitutes a breach of duty.
Injuries can be physical, emotional, or financial. Causation is established if but
for the breach of duty, the patient would not have experienced the injury. When a
claim is meritorious, the tort system attempts to compensate the injured patient
or family members, or both, by awarding them monetary damages.
Being sued is stressful, regardless of the perceived “merits” of the claim.
Preparation for defense begins before an injury has occurred. The patient grants
informed consent following a discussion of the risks and benefits of the
anesthesia options that are available and reasonable. Informed consent does not
consist of handing the patient a form to sign. Informed consent requires that the
patient understand the choices being presented. As previously noted, appropriate
documentation of patient care activities, differential diagnoses, and therapeutic
interventions helps to provide a defensible record of the care that was provided,
resistant to the passage of time and the stress of the litigation experience.
When an adverse outcome occurs, the hospital or practice risk management
group, or both, should be immediately notified. Likewise, one’s liability
insurance carrier should be notified of the possibility of a claim for damages.
Some policies have a clause that disallows the practitioner from admitting errors
to patients and families. Consequently, it is important to know and obey the
institution’s and insurer’s approach to adverse outcomes. Nevertheless, most risk
managers advocate a frank and honest disclosure of adverse events to patients or
approved family members. It is possible to express sorrow about an adverse
outcome without admitting “guilt.” It may be helpful to have such discussions
while accompanied by risk management personnel or a departmental leader.
It must never be forgotten that the tort system is designed to be adversarial.
Unfortunately, this makes every patient a potential courtroom adversary.
Malpractice insurers will hire a defense firm to represent the anesthesia staff
involved. Typically, multiple practitioners and the hospitals in which they work
will be named to involve the maximal number of insurance policies that might
pay in the event of a plaintiff’s victory, and to ensure that the defendants cannot
choose to attribute “blame” for the adverse event to whichever person or entity
was not named in the suit. In some systems (usually when everyone in a health
system is insured by the same carrier), all of the named entities are represented
by one defense team. More commonly, various insurers and attorneys represent
specific practitioners and institutional providers. In this instance, those involved
may deflect and diffuse blame from themselves and focus blame on others also
named in the action. Discovery is the process by which the plaintiff’s attorneys
access the medical records and depose witnesses under oath to establish the
elements of the case: duty, breach, injury, and causation. False testimony can
lead to criminal charges of perjury. One should not discuss elements of any case
with anyone other than a risk manager, insurer, or attorney, as other
conversations are not protected from discovery.
Oftentimes, expediency and financial risk exposure will argue for settlement
of the case. The practitioner may or may not be able to participate in this
decision depending upon the insurance policy. Settled cases are reported to the
National Practitioner Data Bank and become a part of the physician’s record.
Moreover, malpractice suits, settlements, and judgments must be reported to
hospital authorities as part of the credentialing process. When applying for
licensure or hospital appointment, all such actions must be reported. Failure to
do so can lead to adverse consequences.
For a medical defendant, the litigation process begins with the delivery of a
summons indicating that an action is pending. Once delivered, the anesthesia
defendant must contact his or her malpractice insurer/risk management
department, who will appoint legal counsel. Counsel for both the plaintiff and
defense will identify “independent experts” to review the cases. These “experts”
are paid for their time and expenses and can arrive at dramatically different
assessments of the case materials. Following review by expert consultants, the
plaintiff’s counsel may depose the principal actors involved in the case.
Providing testimony can be stressful. Generally, one should follow the advice of
one’s attorney. Oftentimes, plaintiff’s attorneys will attempt to anger or confuse
the deponent, hoping to provoke a response favorable to the claim. Most defense
attorneys will advise their clients to answer questions as literally and simply as
possible, without offering extraneous commentary. Should the plaintiff’s
attorney become abusive, the defense attorney will object for the record.
However, depositions, also known as “examinations before trial,” are not held in
front of a judge (only the attorneys, the deponent, the court reporter[s], and
[sometimes] the videographer are present).
Following discovery, the insurers, plaintiffs, and defense attorneys will
“value” the case and attempt to monetize the damages. Items, such as pain and
suffering, loss of consortium with spouses, lost wages, and many other factors,
are included in determining what the injury is worth. Also during this period, the
defense attorney may petition the court to grant defendants a “summary
judgment,” dismissing the defendant from the case if there is no evidence of
malpractice elicited during the discovery process. At times, the plaintiff’s
attorneys will dismiss the suit against certain named individuals after they have
testified, particularly when their testimony implicates other named defendants.
Settlement negotiations will occur in nearly every action. Juries are
unpredictable, and both parties are often hesitant to take a case to trial. There are
expenses associated with litigation, and both plaintiff and defense attorneys will
try to avoid uncertainties. Many anesthesia providers will not want to settle a
case because the settlement must be reported. Nonetheless, an award in excess of
the insurance policy maximum may (depending on the jurisdiction) place the
personal assets of the defendant providers at risk. One should remember that an
adverse judgment may arise from a case in which most anesthesiologists would
find the care to meet acceptable standards!
When a case proceeds to trial, the first step is jury selection in the process of
voir dire—from the French—“to see, to say.” In this process, attorneys for the
plaintiff and defendant will use various profiling techniques to attempt to
identify (and remove) jurors who are less likely to be sympathetic to their case,
while keeping the jurors deemed most likely to favor their side. Each attorney is
able to strike a certain number of jurors from the pool because they perceive an
inherent bias. The jurors will be questioned about such matters as their
educational level, history of litigation themselves, professions, and so forth.
Following empanelment, the case is presented to the jury. Each attorney
attempts to educate the jurors—who usually have limited knowledge of
healthcare (physicians and nurses will usually be struck from the jury)—as to the
standard of care for this or that procedure and how the defendants did or did not
breach their duty to the patient to uphold those standards. Expert witnesses will
attempt to define what the standard of care is for the community, and the plaintiff
and defendant will present experts with views that are favorable to their
respective cause. The attorneys will attempt to discredit the opponent’s experts
and challenge their opinions. Exhibits are often used to explain to the jury what
should or should not have happened and why the injuries for which damages are
being sought were caused by the practitioner’s negligence.
After the attorneys conclude their closing remarks, the judge will “charge” the
jurors with their duty and will delineate what they can consider in making their
judgment. Once a case is in the hands of a jury, anything can happen. Many
cases will settle during the course of the trial, as neither party wishes to be
subject to the arbitrary decisions of an unpredictable jury. Should the case not
settle, the jurors will reach a verdict. When a jury determines that the defendants
were negligent and negligence was the cause of the plaintiff’s injuries, the jury
will determine an appropriate award. If the award is so egregiously large that it is
inconsistent with awards for similar injuries, the judge may reduce its amount.
Of course, following any verdict, there are numerous appeals that may be filed.
It is important to note that appeals typically do not relate to the medical aspects
of the case, but are filed because the trial process itself was somehow flawed.
Unfortunately, a malpractice action can take years to reach a conclusion.
Consultation with a mental health professional may be appropriate for the
defendant when the litigation process results in unmanageable stress and
depression.
Determining what constitutes the “standard of care” is increasingly
complicated. In the United Sates, the definition of “standard of care” is made
separately by each state. The standard of care is not necessarily “best practices”
or even the care that another physician would prefer. Generally, the standard of
care is met when a patient receives care that other reasonable physicians in
similar circumstances would regard as adequate. The American Society of
Anesthesiologists (ASA) has published standards, and these provide a basic
framework for routine anesthetic practice (eg, monitoring). Increasingly, a
number of “guidelines” have been developed by the multiple specialty societies
to identify best practices in accordance with assessments of the evidence in the
literature. The increasing number of guidelines proffered by the numerous
anesthesia and other societies and their frequent updating can make it difficult
for clinicians to stay abreast of the changing nature of practice. This is a
particular problem when two societies produce conflicting guidelines on the
same topic using the same data. Likewise, the information upon which
guidelines are based can range from randomized clinical trials to the opinion of
“experts” in the field. Consequently, guidelines do not hold the same weight as
standards. Guidelines produced by reputable societies will generally include an
appropriate disclaimer based on the level of evidence used to generate the
guideline. Nonetheless, plaintiff’s attorneys will attempt to use guidelines to
establish a “standard of care,” when, in fact, clinical guidelines are prepared to
assist in guiding the delivery of therapy. However, if deviation from guidelines is
required for good patient care, the rationale for such actions should be
documented on the anesthesia record, as plaintiff’s attorneys may attempt to use
the guideline as a de facto standard of care.

ADVERSE ANESTHETIC OUTCOMES

Incidence
There are several reasons why it is difficult to accurately measure the incidence
of adverse anesthesia-related outcomes. First, it is often difficult to determine
whether a poor outcome arises from the patient’s underlying disease, the surgical
procedure, or the anesthetic management. In some cases, all three factors
contribute to a poor outcome. Clinically important measurable outcomes are
relatively rare after elective anesthetics. For example, death is a clear endpoint,
and perioperative deaths do occur with some regularity. But, because deaths
attributable to anesthesia are much rarer, a very large series of patients must be
studied to assemble conclusions that have statistical significance. Nonetheless,
many studies have attempted to determine the incidence of complications due to
anesthesia. Unfortunately, studies vary in criteria for defining an anesthesia-
related adverse outcome and are limited by retrospective analysis.
Perioperative mortality is usually defined as death within 48 h of surgery. It is
clear that most perioperative fatalities are due to the patient’s preoperative
disease or the surgical procedure. In a study conducted between 1948 and 1952,
anesthesia mortality in the United States was approximately 5100 deaths per
year or 3.3 deaths per 100,000 population. A review of cause of death files in the
United States showed that the rate of anesthesia-related deaths was
1.1/1,000,000 population or 1 anesthetic death per 100,000 procedures between
1999 and 2005 (Figure 54–1). These results suggest a 97% decrease in
anesthesia mortality since the 1940s. However, a 2002 study reported an
estimated rate of 1 death per 13,000 anesthetics. Due to differences in
methodology, there are discrepancies in the literature as to how well
anesthesiology is doing in achieving safe practice. In a 2008 study of 815,077
patients (ASA class 1, 2, or 3) who underwent elective surgery at U.S.
Department of Veterans Affairs hospitals, the mortality rate was 0.08% on the
day of surgery. The strongest association with perioperative death was the type
of surgery (Figure 54–2). Other factors associated with increased risk of death
included dyspnea, reduced albumin concentrations, increased bilirubin, and
increased creatinine concentrations. A subsequent review of the 88 deaths that
occurred on the surgical day noted that 13 of the patients might have benefitted
from better anesthesia care, and estimates suggest that death might have been
prevented by better anesthesia practice in 1 of 13,900 cases. Additionally, this
study reported that the immediate postsurgical period tended to be the time of
unexpected mortality. Indeed, often missed opportunities for improved anesthetic
care occur following complications when “failure to rescue” contributes to
patient demise.

FIGURE 54–1 Annual in-hospital anesthesia-related deaths rates per million

hospital surgical discharges and 95% confidence intervals by age, United States,
1999-2005. (Reproduced with permission from Li G, Warner M, Lang B, et al. Epidemiology of
anesthesia-related mortality in the United States 1999–2005. Anesthesiology. 2009 Apr;110(4):759-765.)
FIGURE 54–2 Total number of deaths by type of surgery in Veterans Affairs
hospitals. (Reproduced with permission from Bishop M, Souders J, Peterson C, et al. Factors associated
with unanticipated day of surgery deaths in Department of Veterans Affairs hospitals. Anesth Analg. 2008
Dec;107(6):1924-1935.)

American Society of Anesthesiologists Closed Claims

Project
The goal of the ASA Closed Claims Project is to identify common events
leading to claims in anesthesia, patterns of injury, and strategies for injury
prevention. It is a collection of closed malpractice claims that provides a
“snapshot” of anesthesia liability rather than a study of the incidence of
anesthetic complications, as only events that lead to the filing of a malpractice
claim are considered. The Closed Claims Project consists of trained physicians
who review claims against physician anesthesiologists represented by some U.S.
malpractice insurers. The number of claims in the database continues to rise each
year as new claims are closed and reported. The claims are grouped according to
specific damaging events and complication type. Closed Claims Project analyses
have been reported for airway injury, nerve injury, awareness, and so forth.
These analyses provide insights into the circumstances that result in claims;
however, the incidence of a complication cannot be determined from closed
claim data, because we know neither the actual incidence of the complication
(some with the complication may not file suit), nor how many anesthetics were
performed for which the particular complication might possibly develop. Other
similar analyses have been performed in the United Kingdom, where National
Health Service (NHS) Litigation Authority claims are reviewed.
Causes
Anesthetic mishaps can be categorized as preventable or unpreventable.
Examples of the latter include fatal idiosyncratic drug reactions or any poor
outcome that occurs despite proper management. However, studies of anesthetic-
related deaths or near misses suggest that many accidents are preventable. Of
these preventable incidents, most involve human error (Table 54–1), as opposed
to equipment malfunctions (Table 54–2). Unfortunately, some rate of human
error is inevitable,. During the 1990s, the top three causes for claims in the ASA
Closed Claims Project were death (22%), nerve injury (18%), and brain damage
(9%). In a 2009 report based on an analysis of NHS litigation records,
anesthesia-related claims accounted for 2.5% of total claims filed and 2.4% of
the value of all NHS claims. Moreover, regional and obstetrical anesthesia were
responsible for 44% and 29%, respectively, of anesthesia-related claims filed.
The authors of the latter study noted that there are two ways to examine data
related to patient harm: critical incident and closed claim analyses. Clinical (or
critical) incident data consider events that either cause harm or result in a “near-
miss.” Comparison between clinical incident datasets and closed claims analyses
demonstrates that not all critical events generate claims and that claims may be
filed in the absence of negligent care. Consequently, closed claims reports must
always be considered in this context.

TABLE 54–1 Human errors that may lead to preventable anesthetic

accidents.

TABLE 54–2 Equipment malfunctions that may lead to preventable

anesthetic accidents.
MORTALITY & BRAIN INJURY
Trends in anesthesia-related death and brain damage have been tracked for many
years. In a Closed Claims Project report examining claims in the period between
1975 and 2000, there were 6750 claims (Figure 54–3A and B), 2613 of which
were for brain injury or death. The proportion of claims for brain injury or death
was 56% in 1975, but had decreased to 27% by 2000. The primary pathological
mechanisms by which these outcomes occurred were related to cardiovascular or
respiratory problems. Early in the study period, respiratory-related damaging
events were responsible for more than 50% of brain injury/death claims, whereas
cardiovascular-related damaging events were responsible for 27% of such
claims; however, by the late 1980s, the percentage of damaging events related to
respiratory issues had decreased, with both respiratory and cardiovascular events
being equally likely to contribute to severe brain injury or death. Respiratory
damaging events included difficult airway, esophageal intubation, and
unexpected extubation. Cardiovascular damaging events were usually
multifactorial. Closed claims reviewers found that anesthesia care was
substandard in 64% of claims in which respiratory complications contributed to
brain injury or death, but in only 28% of cases in which the primary mechanism
of patient injury was cardiovascular in nature. Esophageal intubation, premature
extubation, and inadequate ventilation were the primary mechanisms by which
less than optimal anesthetic care was thought to have contributed to patient
injury related to respiratory events. The relative decrease in causes of death
being attributed to respiratory rather cardiovascular damaging events during the
review period was attributed to the increased use of pulse oximetry and
capnometry.
FIGURE 54–3 A: The total number of claims by the year of injury.
Retrospective data collection began in 1985. Data in this analysis include data
collected through December 2003. B: Claims for death or permanent brain
damage as percentage of total claims per year by year of injury. (Reproduced with
permission from Cheney FW, Domino KB, Caplan RA, Posner KL. Nerve injury associated with anesthesia:
A closed claims analysis. Anesthesiology. 1999 Apr; 90(4):1062-1069.)

A 2010 study examining the NHS Litigation Authority dataset noted that
airway-related claims led to higher awards and poorer outcomes than did non–
airway-related claims. Indeed, airway manipulation and central venous
catheterization claims in this database were most associated with patient death.
Trauma to the airway also generates significant claims if esophageal or tracheal
rupture occur. Postintubation mediastinitis should always be considered
whenever there are repeated unsuccessful airway manipulations, as early
intervention presents the best opportunity to mitigate any injuries incurred.

VASCULAR CANNULATION
Claims related to central venous access in the ASA database were associated
with patient death 47% of the time and represented 1.7% of the 6449 claims
reviewed. Complications secondary to guidewire or catheter embolism,
tamponade, bloodstream infections, carotid artery puncture, hemothorax, and
pneumothorax all contributed to patient injury. Although guidewire and catheter
embolisms were associated with generally lower level patient injuries, these
complications were generally attributed to substandard care. Tamponade
following line placement often led to a claim for patient death. The authors of a
2004 closed claims analysis recommended reviewing the chest radiograph
following line placement and repositioning lines found in the heart or at an acute
angle to reduce the likelihood of vascular perforation and tamponade. Brain
damage and stroke are associated with claims secondary to carotid cannulation.
Multiple confirmatory methods including ultrasound should be used to ensure
that the internal jugular and not the carotid artery is cannulated.
Claims related to peripheral vascular cannulation in the ASA database
accounted for 2% of 6849 claims, 91% of which were for complications
secondary to the extravasation of fluids or drugs from peripheral intravenous
catheters that resulted in extremity injury (Figure 54–4). Air embolisms,
infections, and vascular insufficiency secondary to arterial spasm or thrombosis
also resulted in claims. Of interest, intravenous catheter claims in patients who
had undergone cardiac surgery formed the largest cohort of claims related to
peripheral intravenous catheters, most likely due to the usual practice of tucking
the arms alongside the patient during the procedure, placing them out of view of
the anesthesia providers. Radial artery catheters seem to generate few closed
claims; however, femoral artery catheters can lead to greater complications and
potentially increased liability exposure.

FIGURE 54–4 Injuries related to IV catheters (n = 127). (Reproduced with permission

from Bhananker S, Liau D, Kooner P, et al. Liability related to peripheral venous and arterial
catheterization: A closed claims analysis. Anesth Analg. 2009 July;109(1):124-129.)
OBSTETRIC ANESTHESIA
Both critical incident and closed claims analyses have been reported regarding
complications and mortality related to obstetrical anesthesia.
In a study reviewing anesthesia-related maternal mortality in the United
States using the Pregnancy Mortality Surveillance System, which collects data
on all reported deaths causally related to pregnancy, 86 of the 5946 pregnancy-
related deaths reported to the Centers for Disease Control and Prevention were
thought to be anesthesia related or approximately 1.6% of total pregnancy
related-deaths in the period 1991 to 2002. The anesthesia mortality rate in this
period was 1.2 per million live births, compared with 2.9 per million live births
in the period 1979 to 1990. The decline in anesthesia-related maternal mortality
may be secondary to the decreased use of general anesthesia in parturients,
reduced doses of bupivacaine in epidurals, improved airway management
protocols and devices, and greater use of incremental (rather than bolus) dosing
of epidural catheters.
In a 2009 study examining the epidemiology of anesthesia-related
complications in labor and delivery in New York State during 2002 to 2005, an
anesthesia-related complication was reported in 4438 of 957,471 deliveries
(0.46%). The incidence of complications was increased in patients undergoing
cesarean section, those living in rural areas, and those with other medical
conditions. Complications of neuraxial anesthesia (eg, postdural puncture
headache) were most common, followed by systemic complications, including
aspiration or cardiac events. Other reported problems were related to anesthetic
dose administration and unintended overdosages.
ASA Closed Claims Project analyses were reported in 2009 for the period
1990 to 2003. Four hundred twenty-six claims from this period were compared
with 190 claims in the database prior to 1990. After 1990, the proportion of
claims for maternal or fetal demise was lower than that recorded prior to 1990.
After 1990, the number of claims for maternal nerve injury increased. In the
review of claims in which anesthesia was thought to have contributed to the
adverse outcome, anesthesia delay, poor communication, and substandard care
were thought to have resulted in poor newborn outcomes. Prolonged attempts to
secure neuraxial blockade in the setting of emergent cesarean section can
contribute to adverse fetal outcome. Additionally, the closed claims review
indicated that poor communication between the obstetrician and the
anesthesiologist regarding the urgency of newborn delivery was likewise thought
to have contributed to newborn demise and neonatal brain injury.
Maternal death claims were secondary to airway difficulty, maternal
hemorrhage, and high neuraxial blockade. The most common claim associated
with obstetrical anesthesia was related to nerve injury following regional
anesthesia. Nerve injury can be secondary to neuraxial anesthesia and analgesia,
but also due to obstetrical causes. Early neurological consultation to identify the
source of nerve injury is suggested to discern if injury could be secondary to
obstetrical rather than anesthesia interventions.

REGIONAL ANESTHESIA
In a closed claims analysis, peripheral nerve blocks were involved in 159 of the
6894 claims analyzed. Peripheral nerve block claims were for death (8%),
permanent injuries (36%), and temporary injuries (56%). The brachial plexus
was the most common location for nerve injury. In addition to ocular injury,
cardiac arrest following retrobulbar block contributed to anesthesiology claims.
Cardiac arrest and epidural hematomas are two of the more common damaging
events leading to severe injuries related to regional anesthesia. Neuraxial
hematomas in both obstetrical and nonobstetrical patients were associated with
coagulopathy (either intrinsic to the patient or secondary to medical
interventions). In one study, cardiac arrest related to neuraxial anesthesia
contributed to roughly one-third of the death or brain damage claims in both
obstetrical and nonobstetrical patients. Accidental intravenous injection and
local anesthesia toxicity also contributed to claims for brain injury or death.
Nerve injuries constitute the third most common source of anesthesia
litigation. A retrospective review of patient records and a claims database
showed that 112 of 380,680 patients (0.03%) experienced perioperative nerve
injury. Patients with hypertension and diabetes and those who were smokers
were at increased risk of developing perioperative nerve injury. Perioperative
nerve injuries may result from compression, stretch, ischemia, other traumatic
events, and unknown causes. Improper positioning can lead to nerve
compression, ischemia, and injury; however, not every nerve injury is the result
of improper positioning. The care received by patients with ulnar nerve injury
was rarely judged to be inadequate in the ASA Closed Claims database. Even
awake patients undergoing spinal anesthesia have been reported to experience
upper extremity injury. Moreover, many peripheral nerve injuries do not become
manifest until more than 48 h after anesthesia and surgery, suggesting that some
nerve damage that occurs in surgical patients may arise from events taking place
after the patient leaves the operating room setting.
PEDIATRIC ANESTHESIA
In a 2007 study reviewing 532 claims in pediatric patients younger than 16 years
of age in the ASA Closed Claims database from 1973 to 2000 (Figure 54–5), a
decrease in the proportion of claims for death and brain damage was noted over
the three decades. Likewise, the percentage of claims related to respiratory
events also was reduced. Compared with before 1990, the percentage of claims
secondary to respiratory events decreased during the years 1990 to 2000,
accounting for only 23% of claims in the latter study years compared with 51%
of claims in the 1970s. Moreover, the percentage of claims that could be avoided
by better monitoring decreased from 63% in the 1970s to 16% in the 1990s.
Death and brain damage constitute the major complications for which claims are
filed. In the 1990s, cardiovascular events joined respiratory complications in
sharing the primary causes of pediatric anesthesia litigation. In the previously
mentioned study, better monitoring and newer airway management techniques
may have reduced the incidence of respiratory events leading to litigation-
generating complications in the latter years of the review period. Additionally,
the possibility of a claim being filed secondary to death or brain injury is greater
in children who are in ASA classes 3, 4, or 5.

FIGURE 54–5 Trends over time. Outcome, type of event, and prevention by
better monitoring. Years are grouped for illustration. (Reproduced with permission from
Jimenez N, Posner K, Cheney F, et al. An update on pediatric anesthesia liability: A closed claims analysis.
Anesth Analg. 2007 Jan;104(1):147-129.)

In a review of the Pediatric Perioperative Cardiac Arrest Registry, which

collects information from about 80 North American institutions that provide
pediatric anesthesia, 193 arrests were reported in children between 1998 and
2004. During the study period, 18% of the arrests were “drug related,” compared
with 37% of all arrests during the years 1994 to 1997. Cardiovascular arrests
occurred most often (41%), with hypovolemia and hyperkalemia being the most
common causes. Respiratory arrests (27%) were most commonly associated with
laryngospasm. Central venous catheter placement with resultant vascular injury
also contributed to some perioperative arrests. Arrests from cardiovascular
causes occurred most frequently during surgery, whereas arrests from respiratory
causes tended to occur after surgery.
A review of data from the Pediatric Perioperative Cardiac Arrest Registry
with a focus on children with congenital heart disease found that such children
were more likely to arrest perioperatively secondary to a cardiovascular cause. In
particular, children with a single ventricle were at increased risk of perioperative
arrest. Children with aortic stenosis and cardiomyopathy were similarly found to
be at increased risk of cardiac arrest perioperatively.
Increasingly, obese children present for anesthesia and surgery. These
children are at particular risk for obstructive sleep apnea, increased sensitivity to
opioids, and respiratory arrest. In particular, death and neurological injury have
been reported following tonsillectomy in children at risk for sleep apnea. At-risk
children require an extended period of postoperative monitoring to prevent death
from perioperative apnea.

OUT OF THE OPERATING ROOM ANESTHESIA

& MONITORED ANESTHESIA CARE
Review of the ASA Closed Claims Project database indicates that anesthesia at
remote (non–operating room) locations poses a risk to patients secondary to
hypoventilation and excessive sedation. Remote location anesthesia care was
more likely than operating room anesthesia care to involve a claim for death
(54% vs 29%, respectively). The endoscopy suite and cardiac catheterization
laboratory were the most frequent locations from which claims were generated.
Monitored anesthesia care (MAC) was the most common technique employed in
these claims. Overwhelmingly, adverse respiratory events were most frequently
responsible for the injury.
An analysis of the ASA Closed Claims Project database focusing on MAC
likewise revealed that oversedation and respiratory arrest frequently led to
claims. Claims for burn injuries suffered in operating room fires were also found
in the database. Supplemental oxygen, draping, pooling of flammable antiseptic
preparatory solutions, and surgical cautery combine to produce the potential for
operating room fires (see Chapter 2).

EQUIPMENT PROBLEMS
“Equipment problems” is probably a misnomer; the ASA Closed Claims Project
review of 72 claims involving gas delivery systems found that equipment misuse
was three times more common than equipment malfunction. Anesthesia gas
delivery claims have decreased in recent years, accounting for just 1% of claims
in the new millennium. Provider equipment misuse was associated with severe
patient injuries.
Errors in drug administration also typically involve human error. It has been
suggested that as many as 20% of the drug doses given to hospitalized patients
are incorrect. Errors in drug administration account for 4% of cases in the ASA
Closed Claims Project. Errors resulting in claims were most frequently due to
either incorrect dosage or unintentional administration of the wrong drug
(syringe swap). In the latter category, accidental administration of epinephrine
proved particularly dangerous.
Another type of human error occurs when the most critical problem is ignored
because the anesthesia provider’s attention is inappropriately focused on a less
important problem or an incorrect solution (fixation error). Serious anesthetic
mishaps are often associated with distractions and other factors (Table 54–3).
The harmful impact of most equipment failures can be decreased or avoided
when the problem is identified during the mandatory preoperative anesthesia
workstation inspection and checkout. Many anesthetic fatalities occur only
after a series of coincidental circumstances, misjudgments, and technical errors
combine (mishap chain).

TABLE 54–3 Factors associated with human errors and equipment misuse.