Infectious Diseases and Biologic Weapons

C H A P T E R
12
Infectious Diseases and Biologic Weapons
PATRICK NELIGAN, MA, MD, FCAI n
n Patients with multiorgan dysfunction syndrome (MODS)

Sepsis and Systemic Inflammatory Response Syndrome become confused, delirious, and ultimately stuporous and
Pathophysiology of Sepsis
comatose.
Multiorgan Dysfunction Syndrome
n The four main pillars in the management of the patient with
Treating the Patient with Septic Shock
severe sepsis are immediate resuscitation, empiric therapy,
Transmissible Infections source control, and prevention of further complications.
Hepatitis B
n Infection with HIV is the most feared of all occupation-
Hepatitis C
ally acquired diseases. Management of HIV-seropositive
Human Immunodeficiency Virus
pregnant women includes minimizing the infant's risk of
Tuberculosis
acquired infection. Patients with HIV are at particular risk
Prions
for biliary tract disease.
Intra-Abdominal Infections and Anesthesia n A patient with active tuberculosis represents major infec-
Pyogenic Liver Abscess
tion risk for other patients and health care workers.
Amebic Liver Abscess
n Intra-abdominal abscesses are walled-off collections of
Hydatid Disease
pus or parasites surrounded by fibrotic tissue, induced by
Splenic Abscess
inflammation.
Appendiceal Abscess
n Anesthesiologists are involved with necrotizing fasciitis
Diverticular Abscess
patients at initial presentation (fulminant sepsis) or during
Necrotizing Soft Tissue Infections subsequent OR visits (tissue debridement).
Necrotizing Fasciitis
n Soft tissue infections of the neck are of particular impor-
Clostridial Myonecrosis (Gas Gangrene)
tance to anesthesiologists because of possibly significant
Soft Tissue Infections of Head and Neck
airway obstruction.
Epiglottitis
n In epiglottitis patients, intubation should be performed
Infectious Agents as Biologic Weapons by the most skilled anesthesiologist, with a full airway
Anthrax
team, including otolaryngologist, and open tracheostomy
Smallpox
pack.
Tularemia
n In a terrorist biologic attack, the anesthesiologist is involved
Plague
with triage and resuscitation of injured patients and should
Biologic Toxins be familiar with potential bioweapons.
Sarin
n Anesthesiologists may be involved with the critical care
Ricin
management of the patient with inhalational anthrax, for
Botulinum
intubation and supportive care. There is no risk of person-
to-person transmission.
n With plague patients, the anesthesiologist should wear a
gown, mask, and eye protection because of the potential for
KEY POINTS contagion.
n Patients with severe sepsis are at particular risk for hepatic n In emergency care of patients with organophosphate poi-
and renal injuries. soning, the anesthesiologist usually secures the airway, ini-
n The major cardiovascular events in sepsis are vasoplegia, tiates mechanical ventilation, and transfers the patient to
reduced stroke volume, and microcirculatory failure. the ICU.
369
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370 ANESTHESIA AND UNCOMMON DISEASES
n Infection has killed more soldiers in war than gunfire.

Although the age of infectious diseases has all but passed in BOX 12-1 n SEPSIS AND ORGAN FAILURE: DEFINITIONS
AND THERAPEUTIC GUIDELINES
the Western world, infection, and the means by which the
body deals with it, remains a major problem in critical care Infection
and perioperative medicine. A host response to the presence of microorganisms or tissue
invasion by microorganisms.
A clear distinction must be made between infections, sep-
sis, infectiousness, and carrier states. Infection refers to the Bacteremia
host response to the presence of microorganisms or tis- The presence of viable bacteria in circulating blood.
sue invasion by microorganisms. The microorganisms Systemic Inflammatory Response Syndrome (SIRS)
may be bacteria, viruses, fungi, parasites, or prions. Sepsis The systemic inflammatory response to a wide variety of severe
clinical insults, manifested by two or more of the following conditions:
is a syndrome—the systemic inflammatory response to the
microorganism and associated toxins. Infectiousness or con- Temperature >38° C or <36° C
tagiousness refers to the transmissibility of pathogens from Heart rate >90 beats/min
Respiratory rate >20 breaths/min or Paco2 <32 mm Hg
one host to another. A carrier state refers to the persistence
WBC count >12,000/mm,3 <4000/mm,3 or >10% immature (band)
of a contagious organism within a host who may not demon- forms
strate signs of infection.
Sepsis
Each of these situations is of importance to anesthesiolo- The systemic inflammatory response to infection. In association with
gists. For example, patients with fulminant surgical sepsis infection, manifestations of sepsis are the same as those previously
(e.g., necrotizing pancreatitis or gas gangrene) may come to defined for SIRS. It should be determined whether they are a direct
the operating room (OR) for debridement and source con- systemic response to the presence of an infectious process and
represent an acute alteration from baseline in the absence of other
trol. Anesthesia management is significantly influenced by the
known causes for such abnormalities. The clinical manifestations
immunologic and hemodynamic impact of sepsis. Likewise, would include two or more of the following conditions as a result of a
patients with transmissible diseases (e.g., tuberculosis, HCV, documented infection:
HIV) represent a significant risk to health care personnel,
Temperature >38° C or <36° C
who may contract the disease.1 The anthrax fatalities after Heart rate >90 beats/min
September 2001 refocused attention of previously eradicated Respiratory rate >20 breaths/min or Paco2 <32 mm Hg
infectious organisms as potential weapons of terrorism.2 WBC count >12,000/mm,3 <4000/mm,3 or > 10% immature
(band) forms
Severe Sepsis/SIRS
SEPSIS AND SYSTEMIC INFLAMMATORY Sepsis (SIRS) associated with organ dysfunction, hypoperfusion, or
RESPONSE SYNDROME hypotension. Hypoperfusion and perfusion abnormalities may include,
but are not limited to, lactic acidosis, oliguria, or an acute alteration
Physicians managing intensive care units (ICUs) have long in mental status.
used a variety of terms to describe illnesses associated with
Refractory (Septic) Shock/SIRS Shock
infection or with infectious-appearing illnesses. These terms
A subset of severe sepsis (SIRS) and defined as sepsis (SIRS)–
included sepsis, septicemia, bacteremia, infection, septic induced hypotension despite adequate fluid resuscitation, along with
shock, and toxic shock. Unfortunately, there were no strict def- the presence of perfusion abnormalities that may include, but are not
initions for the terms used, which were often used incorrectly, limited to, lactic acidosis, oliguria, or an acute alteration in mental
and emerging evidence indicated that systemic inflammation, status. Patients receiving inotropic or vasopressor agents may no
longer be hypotensive by the time they manifest hypoperfusion
rather than infection, was responsible for multiple-organ fail-
abnormalities or organ dysfunction, yet they would still be considered
ure. In the 1990s the American College of Chest Physicians to have septic (SIRS) shock.
(ACCP) and Society for Critical Care Medicine (SCCM) rede-
Multiple Organ (Multiorgan) Dysfunction Syndrome (MODS)
fined inflammation and sepsis (Box 12-1).3 Presence of altered organ function in an acutely ill patient such that
The host response to both infectious and noninfectious homeostasis cannot be maintained without intervention.
injuries is similar4; the clinical signs are essentially the same.
This inflammatory response is determined, qualitatively and From Bone RC, et al: Crit Care Med 20:864-874, 1992.
Paco2, Partial pressure (tension) of carbon dioxide in arterial blood; WBC,
quantitatively, by genetic and environmental factors.5 Thus,
white blood cell.
the term “sepsis” had come to be used, incorrectly, to describe
the host response to a variety of infectious and noninfectious
injuries (Fig. 12-1). The term systemic inflammatory response
syndrome (SIRS) was introduced to describe the process of response to infection. A second consensus conference in 20015
inflammation without infection.3 This terminology is now addressed the ongoing problem with the vagueness of the defi-
accepted, with some reservations.6,7 nition of SIRS.8 The strengths and weaknesses of the current
Infection is a microbial phenomenon characterized by sepsis definitions were reviewed. The definitions were left
an inflammatory response to the presence of microorgan- unchanged with the exception of an expansion in the list of
isms or the invasion of normally sterile host tissue by those signs and symptoms of sepsis to reflect the spectrum of man-
organisms.3 Sepsis is the presence of a systemic inflammatory ifestations at the bedside. These definitions have significant
Chapter 12 Infectious Diseases and Biologic Weapons 371
Microbes possess specific virulence factors to overcome

host defenses. The cell wall of gram-negative bacteria consists
Bacteremia of an inner phospholipid bilayer and an outer layer that con-
Other
tains lipopolysaccharide (LPS). This consists of polysaccharide
SIRS O, which protrudes from the exterior cell surface, a core poly-
Fungemia saccharide, and a lipid component (lipid A) that faces the cell
INFECTION
SEPSIS Trauma interior. Lipid A, or endotoxin, is responsible for the toxicity of
this molecule. It is released with cell lysis. In meningococce-
Parasitemia mia, plasma levels of endotoxin correlate well with the devel-
opment of multiorgan dysfunction syndrome (MODS).
Viremia Burns Gram-positive organisms, such as Staphylococcus, Strept
ococcus, and Enterococcus species, actively secrete an exotoxin,
Other which consists of two polypeptide components: the first binds
Pancreatitis
the protein to the host cell, and the second has toxic effects.
Staphylococcus aureus produces four cytolytic exotoxins, the
FIGURE 12-1 Infection and sepsis. SIRS, Systemic inflammatory most important of which—α toxin—punctures holes in the
response syndrome. (From Bone RC, et al: Crit Care Med 20:864- membranes of cells, leading to osmotic lysis. In addition,
874, 1992.) S. aureus produces a number of superantigens that have an
affinity for T-cell receptor major histocompatibility complex
epidemiologic value: there is a clear increase in mortality as (MHC) class II antigen complexes. They activate a large num-
patients pass from SIRS, with progressive organ failure, to sep- ber of T cells, leading to massive release of cytokines and toxic
sis, to septic shock (Box 12-2).9,10 shock. Clostridium difficile produces two exotoxins: toxin A
and toxin B.
In addition to toxins, bacteria possess a variety of viru-
Pathophysiology of Sepsis lence factors that contribute to the establishment of infection.
The presence of pathogens in the bloodstream or tissues elic- For example, group A streptococci produce hyaluronidase
its an inflammatory response. There are five stages4: (1) estab- and various proteases and collagenases, which facilitate the
lishment of infection, (2) preliminary systemic inflammatory spread of the bacteria along tissue planes. Staphylococcus
response, (3) overwhelming systemic inflammatory response, epidermidis produces a biofilm that coats intravascu-
(4) compensatory anti-inflammatory response, and (5) immu- lar devices and endotracheal tubes, making elimination
nomodulatory failure. by antibiotics almost impossible. Coliform bacteria and
BOX 12-2 n DIAGNOSTIC CRITERIA FOR SEPSIS*
General Coagulation abnormalities (INR >1.5 or aPTT >60 seconds)

Fever (core temperature >38.3°C) Ileus (absent bowel sounds)
Hypothermia (core temperature <36°C) Thrombocytopenia (platelet count <100,000/μL)
Heart rate >90 beats/min or >2 SD above normal value for age Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L)
Tachypnea
Tissue Perfusion
Altered mental status
Hyperlactatemia (>1 mmol/L)
Significant edema or positive fluid balance (>20 mL/kg over 24 hours)
Decreased capillary refill or mottling
Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in absence
of diabetes
From Levy MM, et al: Crit Care Med 31:1250-1256, 2003.
Inflammatory
Leukocytosis (WBC count >12,000/μL) Note: Diagnostic criteria for sepsis in the pediatric population are signs and
Leukopenia (WBC count <4000/μL) symptoms of inflammation plus infection with hyperthermia or hypothermia
Normal WBC count with >10% immature forms (rectal temperature >38.5° C or <35° C), tachycardia (may be absent in
Plasma C reactive protein >2 SD above the normal value hypothermic patients), and at least one of the following indications of altered
organ function: altered mental status, hypoxemia, increased serum lactate
Plasma procalcitonin >2 SD above the normal value
level, or bounding pulses.
Hemodynamic variables *Infection, documented or suspected, and defined as a pathologic process
Arterial hypotension† (SBP <90 mm Hg, MAP <70 mm Hg, or SBP induced by a microorganism, and some of the criteria listed.
decrease >40 mm Hg in adults or <2 SD below normal for age) †Sv o >70% is normal in children (normal, 75%-80%), and cardiac index of
2
Svo2 >70%† 3.5 to 5.5 L/min/m2 is normal in children; therefore, neither should be used
Cardiac index >3.5 L/min/m2 as a sign of sepsis in newborns or children.
SD, Standard deviation; WBC, white blood cell; SBP, systolic blood pressure;
Organ Dysfunction MAP, mean arterial pressure; Sv o2, mixed venous oxygen saturation;
Arterial hypoxemia (Pao2/Fio2 <300) Pao2, arterial oxygen partial pressure; Fio2, fraction of inspired oxygen
Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hr) concentration; INR, international normalized ratio; aPTT, activated partial
Creatinine increase >0.5 mg/dL thromboplastin time.
Predisposition Response ultimately broken down by plasmin, which is activated by tis-

Genetics Physiologic sue plasminogen activator (t-PA) from plasminogen; PAI-1
Chronic illness Specific mediators inhibits t-PA.
Cultural attitudes Generic markers
Thrombin itself is an activator of inflammation and
inhibitor of fibrinolysis. The latter is achieved by the activa-
PIRO tion of thrombin-activatable fibrinolysis inhibitor (TAFI).
Thrombomodulin, another modulator of fibrinolysis, is
impaired by inflammation and endothelial injury. The func-
Insult Organ dysfunction
Shock, ARDS, renal
tion of this compound is to activate protein C. Activated pro-
Infection
Endotoxin failure, etc. tein C modifies the inflammatory and coagulant response at
Injury, ischemia several different levels; a deficiency results from inhibition of
FIGURE 12-2 The PIRO model of sepsis and SIRS. ARDS,
thrombomodulin in sepsis.
Acute respiratory distress syndrome. (Modified from Levy MM
et al: Crit Care Med 31:1250-1256, 2003.) HEMODYNAMIC DERANGEMENT IN SEPSIS
Three major cardiovascular events occur in sepsis, as follows:
Pseudomonas species have pili that allow the organism to
1. Vasoplegia. Pathologic vasodilation results from loss of
bind and anchor to the epithelium, potentially a mechanism
normal sympathetic tone, caused by the combination of
of bacterial translocation.
local vasodilator metabolites. There is activation of ade-
Fungal infections are common in the hospitalized popula-
nosine triphosphate–sensitive potassium channels, lead-
tion. Commensal organisms, such as Candida spp., become
ing to hyperpolarization of smooth muscle cells.13,14 There
pathogenic as a result of host factors (e.g., immunosuppres-
is increased production of inducible nitric oxide synthetase
sion, concomitant infection, diabetes) and iatrogenic factors
(iNOS), which manufactures massive amounts of nitric
(e.g., multiple antibiotics, critical illness, parenteral nutrition,
oxide. In addition, there is acute depletion of vasopressin.15
abdominal surgery). The gastrointestinal (GI) tract appears to
Vasoplegia leads to relative hypovolemia. Vascular tone is
be an important source of Candida; the mechanism of candi-
characteristically resistant to catecholamine therapy but
demia is unclear (Fig. 12-2).
very sensitive to vasopressin.
2. Reduced stroke volume. This results from the presence of a
THE INFLAMMATORY CASCADES
circulating myocardial depressant factor, probably TNF-α.
Tissue injury or pathogens (bacteria, viruses, fungi, or para-
There is reversible biventricular failure, a decreased ejec-
sites) cause monocyte activation, which produces interleukin
tion fraction, myocardial edema, and ischemia. Cardiac
(IL-1, IL-6), tumor necrosis factor alpha (TNF-α), plasmino-
output is maintained by a dramatic increase in heart rate.16
gen activator inhibitor 1 (PAI-1), and interferon-γ (IFN-γ).11,12
3. Microcirculatory failure.17 The small blood vessels vasodi-
These cytokines subsequently modulate the release and activa-
late, and there is widespread capillary leak, maldistribution
tion of a medley of different agents: interleukin-8 (IL-8), com-
of flow, arteriovenous shunting, and oxygen (O2) utilization
plement, histamine, kinins, serotonin, selectins, eicosanoids,
defects.18 These abnormalities are incompletely understood.
and neutrophils. This leads to local vasodilation, release of
In addition, there is initial activation of the coagulation sys-
various cytotoxic chemicals, and destruction of the invading
tem and deposition of intravascular clot, causing ischemia.
pathogen. The release of cytotoxic material and proinflamma-
tory cytokines results in the systemic inflammatory response: The relative hypovolemia of early sepsis is virtually indis-
fever or hypothermia, tachypnea, tachycardia, and leukocyto- tinguishable from hypovolemic or hemorrhagic shock. In
sis or neutropenia. response to intravascular volume depletion (distributive or
A subgroup of patients has an abnormal (“malignant”) hypovolemic shock), the precapillary arterioles and postcap-
inflammatory response: tissue destruction by neutrophils, illary venules vasoconstrict, increasing blood flow velocity,
endothelial cell destruction, and massive systemic release of which draws fluid in from the interstitium (a net influx of fluid
mediators. The result is vasoplegia, capillary leak, and activa- into the circulation). This is known as transcapillary refill.
tion of clotting cascades. Fluid effectively shifts from the extravascular to the intravas-
Damage to the endothelium exposes a procoagulant fac- cular space. An O2 debt is incurred, and there may be lactic
tor known as tissue factor. Tissue factor exists in the suben- acidosis. At this stage, patients are highly sensitive to volume
dothelial space and has a reparative role after tissue damage. resuscitation.
In sepsis, there is massive exposure. Tissue factor binds to Eventually, persistent release of cytokines leads to deple-
activated factor VII. The resulting complex activates in turn tion of reserve: there is hyperpolarization of vascular smooth
factors IX and X. Factor X converts prothrombin into throm- muscles, massive release of iNOS, vasopressin depletion,
bin, which cleaves fibrinogen into fibrin—a blood clot. At and widespread increase in vascular permeability. The
the same time, the fibrinolytic system is inhibited. Cytokines result is vasoplegia and sequestration of intravascular fluid
and thrombin stimulate the release of PAI-1 from platelets into extracellular space. The patient has interstitial edema,
and the endothelium. In the human body, when a clot forms, it is hemoconcentration, and increased blood viscosity. There is
50 In the lungs, ventilation/perfusion mismatches occur, ini-

tially from increased dead space (caused by hypotension and
45
fluid shifts) and subsequently from shunt.20 There is increased
40 extravascular lung water and widespread disruption of the
alveolar-capillary basement membrane, leading to acute
35
lung injury. Up to 70% of patients develop nosocomial pneu-
30 monia. Cytokines released as a result of ventilator-induced
Percent
lung injury may have adverse effects at distant organs.21 This

25
hypothesis was confirmed from data in the Acute Respiratory
20 Distress Syndrome (ARDS) Network trial supported by the
National Institutes of Health.22 Blood samples were obtained
15
from 204 of the first 234 patients for measurement of plasma
10 IL-6 concentration. Levels of this cytokine were significantly
higher in the “high stretch” (tidal volume, 10- 12 mL/kg) com-
5
pared with the “low stretch” (tidal volume, 5-6 mL/kg) group.
0 In addition to lower mortality, this group had a significantly
No SIRS2 SIRS3 SIRS4 Sepsis Severe Septic
SIRS sepsis shock lower incidence of nonpulmonary organ injury (the lung ori-
gin theory of sepsis).
FIGURE 12-3 Mortality in SIRS/sepsis/septic shock. SIRS,
Systemic inflammatory response syndrome. (From Rangel-Frausto M,
There is significant hepatic dysfunction in sepsis. Uncon
et al: JAMA 273:117-125, 1995.) trolled production of inflammatory cytokines by the Kupffer
cells (of the liver), primed by ischemia and stimulated by
endotoxin (derived from the gut), leads to cholestasis and
parallel activation of clotting cascades, intravascular throm- hyperbilirubinemia. There is decreased synthesis of albumin,
bosis, and bleeding. The capacity of mitochondria to extract clotting factors, cytochrome P450, and biliary transporters.
O2 is impaired, and multiorgan dysfunction results (Fig. 12-3). Impaired ketogenesis, ureagenesis, and gluconeogenesis are
caused by decreased expression of genes encoding gluconeo-
genic, β-oxidative, and ureagenic enzymes.23 Gut mucosa is
Multiorgan Dysfunction Syndrome
usually protected from injury by autoregulation. Hypotension
The brain and kidneys are normally protected from swings and hypovolemia lead to superficial mucosal injury. This
in blood pressure (BP) by autoregulation. In early sepsis the results in atrophy and possible translocation of bacteria into
autoregulation curve shifts rightward (because of an increase the portal circulation, stimulating liver macrophages, causing
in sympathetic tone). In late sepsis, vasoplegia occurs and cytokine release, and amplifying SIRS (the gut origin theory
autoregulation fails, making these organs susceptible to the of sepsis).24,25
swings that occur in systemic BP. In addition, “steal” phe- Metabolic abnormalities in sepsis include hyperglyce-
nomena may occur (areas of ischemia may have their blood mia caused by glycogenolysis, insulin resistance, and massive
“stolen” by areas with good perfusion). This is known as release of catecholamines and lactic acidosis. A generalized
vasomotor neuropathy. Acute tubular necrosis results from catabolic state leads to muscle breakdown, not unlike maras-
cellular apoptosis, toxic injury (mechanism unclear, pos- mus. The patient has relative hypothyroidism, hypopituita-
sibly cellular lysosomes and debris), hypotension, and rism, and adrenal insufficiency.26,27
hypovolemia.19
Patients with multiorgan dysfunction syndrome (MODS) ACTIVATED PROTEIN C
become confused, delirious, and ultimately stuporous and Protein C is an important anticoagulant and anti-
comatose as a result of a variety of insults: hypoperfusion inflammatory protein. The main effect of activated protein
injury, septic encephalopathy, metabolic encephalopathy, and, C (APC) is to reduce the production of thrombin, by inac-
of course, drugs used for sedation. tivating factors Va and VIII. Thrombin is proinflammatory,
Myocardial O2 supply is dependent on diastolic BP, procoagulant, and antifibrinolytic.28 In addition, protein C
which falls following vasoplegia, and on intravascular vol- inhibits the influence of tissue factor on the clotting system,
ume depletion. This may lead to ischemia. There is revers- reduces the production of IL-1, IL-6, and TNF-α by mono-
ible biventricular dilation, decreased ejection fraction, and cytes, and has profibrinolytic properties through the inacti-
decreased response to fluid resuscitation and catecholamine vation of PAI-1.24 The Prowess trial suggested that exogenous
stimulation. A circulating myocardial depressant substance administration of APC to patients, in severe sepsis, may
is responsible for this phenomenon. This substance has been improve outcome.29 However, the results of the single trial
shown to represent low concentrations of TNF-α and IL-1β have been controversial, and there is no survival benefit in
acting in synergy on the myocardium through mechanisms patients with severe sepsis and Apache II scores less than 25.
that include nitric oxide and cyclic guanosine monophos- The major clinical drawback of treatment with APC is bleed-
phate generation. ing, particularly in perioperative patients.
Treating the Patient with Septic Shock Early Phase

Behaves like hypovolemic shock
Patients with acute severe sepsis (e.g., necrotizing fasciitis or Absolute and relative hypovolemia
gas gangrene) are infrequently brought to the OR for emer- Increased oxygen extraction
gent source control. In this circumstance, the anesthesiolo- Lactic acidosis
gist will be required to both administer anesthesia, ensuring
amnesia, analgesia, and hypnosis, and resuscitate the patient.
Later Phase
A familiarity with modern resuscitation practices is thus Vasoplegia
important. The four main pillars in the management of Continued fluid sequestration
the patient with severe sepsis are immediate resuscitation, Mitochondrial dysfunction ( O2 extraction)
Multiorgan dysfunction
empiric therapy, source control, and prevention of further Neuroendocrine failure
complications (Fig. 12-4).
FIGURE 12-5 Two phases of sepsis resuscitation.
STAGE 1: IMMEDIATE RESUSCITATION
Immediate Stabilization (Airway and Breathing). crystalloid, to replete interstitial fluid debt. Subsequent efforts
The initial treatment priority in patients with severe sepsis is to are directed at maintenance of intravascular volume. If crys-
reverse life-threatening physiologic abnormalities. The airway talloid resuscitation is continued, there is significant extrava-
must be controlled and the patient oxygenated and ventilated. sation of fluid, and the patient becomes edematous.31,32 Many
This usually requires endotracheal intubation and initiation favor high-molecular-weight (“colloid”) compounds as a
of mechanical ventilation. Care must be taken when admin- means of minimizing resuscitation volume and for potential
istering anesthetic agents for gaining airway control. Propofol positive oncotic effects.31 Although the use of colloid is con-
usually causes dramatic hypotension, from peripheral vasodi- troversial,33,34 evidence supports its use in perioperative medi-
lation and vagotonia, and should be avoided. Etomidate and cine and critical illness as part of a goal-directed paradigm.35–39
ketamine are reasonable choices. Although frequently used The main limiting factors for colloids are availability (gelatins
in cardiac anesthesia for hemodynamic stability, opioids have and pentastarches are not available in the United States) and
significant antiadrenergic effects in sepsis and may cause dra- cost. Available colloids include blood products, hydroxyethyl
matic hypotension. Therapies directed at slowing heart rate starches, and albumin. Previous concerns regarding albumin
should be avoided, because tachycardia is the main compensa- safety are unfounded.40
tory mechanism in maintenance of cardiac output. The goal-directed approach to resuscitation involves the
After intubation, extreme care must be taken with institu- use of specific monitors to measure input (fluid loading), tis-
tion of positive-pressure ventilation. The increase in intratho- sue blood flow, and response (Fig. 12-6). Arterial and central
racic pressure will reduce venous return: aggressive “bagging” lines are placed, and goals for resuscitation are set: these
invariably leads to severe hypotension. include a central venous pressure (CVP) of 8 to 12 cm H2O; a
Re-establishing the Circulation mean arterial pressure (MAP) of more than 65 mm Hg; and, if
Volume Resuscitation. In early sepsis, hypotension is the appropriate device is placed, a mixed venous oxygen satu-
caused by relative hypovolemia, secondary to peripheral vaso- ration (S o2) of more than 70%; and stroke volume (SV)
dilation. Later, hypotension is caused by myocardial depres- between 0.7 and 1 mL/kg.
sion, vasoplegia, and absolute hypovolemia secondary to
capillary leak (Fig. 12-5). Regardless, the initial resuscitative
effort is to attempt to correct the absolute and relative hypo- Response
volemia by refilling the vascular tree. Volume resuscitation
should be early (in OR or emergency department), aggressive,
and goal directed.30 Input Flow
The choice of fluids early in resuscitation remains con-
troversial. Initial resuscitation should include isotonic CVP Objective: Laboratory:
PAOP MAP Base deficit
PADP UO Lactate
Mentation
Maintain oxygenation SV
Empiric therapy
Restore the circulation FVT
CO/Ci
SvO2
Source control
FIGURE 12-6 Goal-directed resuscitation. CVP, Central venous
pressure; PAOP, pulmonary artery opening “wedge” pressure;
PADP, pulmonary artery diastolic pressure; MAP, mean arterial
Prevent further complications
pressure; UO, urine output; SV, stroke volume; FVT, flow velocity
time; CO, cardiac output; Ci, cardiac index; Sv o2, mixed venous
FIGURE 12-4 Treating sepsis: the four pillars of therapy. oxygen saturation.
Supplemental oxygen/
Endotracheal intubation/IPPV
Central venous and arterial

catheter placement
Fluid load to
8 cm H2O 12 cm H2O
CVP Crystalloid of colloid
65 mm Hg Norepinephrine targeted

to65 mm Hg
MAP Vasoactive agents
65 mm Hg
70% Transfuse to
hemoglobin10 g/L
SvO2 RBC transfusion
70% Hb10 g/L
70% Dobutamine
No
Goals achieved
FIGURE 12-7 Goal-directed resuscitation using oximetric central venous pressure (CVP) catheter based on the Surviving
Sepsis Campaign. IPPV, Intermittent positive-pressure ventilation; MAP, mean arterial pressure; Sv o2, mixed venous oxygen saturation;
RBC, red blood cell.
Central Venous and Pulmonary Artery Catheters. The A more elegant approach involves insertion of an oximetric
Surviving Sepsis Campaign41 promotes the use of oximetric pulmonary artery catheter rather than a CVP line. In this par-
CVP catheters to monitor input and flow (Fig. 12-7) based on adigm, SV is used as the main end point of resuscitation, and
the work of Rivers et al.42 Fluid is administered until the CVP CVP or pulmonary artery pressure is used to determine the
reaches and stays in the target range: 8 to 12 cm H2O for the presence of heart failure (Fig. 12-9); a Starling curve is con-
majority of patients (Fig. 12-8). Once fluid loading has been structed (Fig. 12-10). Fluid is administered to the patient until
achieved, hypotension is managed with vasopressors (norepi- SV is a sustained 0.7 to 1 mL/kg (Fig. 12-11).
nephrine or dopamine; see later) to a target MAP of 65 mm Hg. If
S o2 is less than 70%, with CVP and MAP in the target range,
blood is transfused until the hematocrit exceeds 30% (hemoglo- Overfilled
bin [Hb] 10 g/L). If this fails to restore the S o2, an inotrope is
added, such as dobutamine or a phosphodiesterase inhibitor.
Target range
Stroke volume
Target range
Central venous pressure (cm H2O)
Fa
ed
ilin
fill I
g
r
de D
Un E
8 A
L
Pulmonary
edema
Filling pressure
(CVP, PCWP, LVEDP, PADP)
2 FIGURE 12-9 Using stroke volume to construct Starling
Bolus 1 Bolus 2 Bolus 3 curves. CVP, Central venous pressure; PCWP, pulmonary capillary
FIGURE 12-8 Goal-directed approach using central venous wedge pressure; LVEDP, left ventricular end-diastolic pressure;
pressure. PADP, pulmonary artery diastolic pressure.
Supplemental oxygen/
Endotracheal intubation/IPPV
Oximetric PAC and arterial

catheter placement
Fluid load to SV
0.7–1 mL/kg
Crystalloid of colloid
SV 0.7 mL/kg
0.7–1.5 mL/kg:
CVP SV hold fluids
Fluid load to CVP 16 cm H2O 1.5 mL/kg: hold

fluids and diurese
0.7 mL/kg
CVP16 SV0.7 mL/kg
65 mm Hg Norepinephrine targeted
to MAP65 mm Hg
MAP Vasoactive agents
Inotrope required
65 mm Hg
70%
Transfuse to hemoglobin10 g/L
Dobutamine SvO2 RBC transfusion
70% Hb10 g/L 70%

No
Goals achieved
FIGURE 12-10 Algorithm for goal-directed resuscitation. Using stroke volume as a measure of flow. IPPV, Intermittent positive-
pressure ventilation; PAC, pulmonary artery catheter; CVP, central venous pressure; SV, stroke volume; MAP, mean arterial pressure; Svo2,
mixed venous oxygen saturation; RBC, red blood cell.
Stroke Clinical
the body (brain, heart, splanchnic organs, kidneys). Currently,
CVP SVO2 norepinephrine is the agent of choice in the fluid-resuscitated
Volume Impression
patient.
Underfilled
8 cm H2O 55% 45 mL Underresuscitated Norepinephrine. Norepinephrine has pharmacologic
effects on both α1 and β1 adrenoceptors. In low-dosage
Filled
ranges, the beta effect is noticeable, with a mild increase in
12 cm H2O 70% 79 mL Resuscitated cardiac output. In most dosage ranges, vasoconstriction and
increased MAP are evident. Norepinephrine does not increase
heart rate. The main beneficial effect of norepinephrine is to
Overfilled
18 cm H2O 80% 110 mL Overresuscitated
increase organ perfusion by increasing vascular tone. Studies
comparing norepinephrine to dopamine favored the former
FIGURE 12-11 Goal-directed approach to determine
in terms of overall improvements in O2 delivery, organ per-
effectiveness of fluid resuscitation. In this situation, the goal fusion, and O2 consumption. Norepinephrine is more effec-
for stroke volume was 65 to 80 mL and for Svo2 it was 70. CVP, tive at fulfilling targeted end points than dopamine,43 is less
central venous pressure; Svo2, mixed venous oxygen saturation. metabolically active than epinephrine, and reduces serum lac-
tate levels. Norepinephrine significantly improves renal perfu-
Overresuscitation. An SV in excess of 1 mL/kg is indica- sion and splanchnic blood flow in sepsis,44,45 particularly when
tive of overresuscitation, and fluids are withheld until the SV combined with dobutamine.45
drifts back into normal range. If the SV exceeds 1.5 mL/kg,
Dopamine. Dopamine has predominantly β-adrenergic
serious consideration should be given to the administration
effects in low to moderate dose ranges (up to 10 MIC/kg/ min),
of diuretics.
although there is much interpatient variability. This effect
Vasopressor Therapy may result from its conversion to norepinephrine in the
Hypotension, unresponsive to fluid therapy, in patients with myocardium and its activation of adrenergic receptors. In
sepsis is an indication for vasopressor use (Table 12-1). The higher dose ranges, α-adrenoceptor activation increases
ideal pressor agent would restore BP while maintaining car- and causes vasoconstriction. Dopamine is thus a mixed ino-
diac output and preferentially perfuse the midline structures of trope and vasoconstrictor. At all dose ranges, it is a potent
TABLE 12-1 n Pharmacologic Support of the Circulation in Sepsis
Agent a1 b1 b2 Heart Rate Organs Perfused
Epinepthrine ++++ ++++ ++++ ↑↑↑↑ Skin, muscle
Norepinephrine ++++ ++++ ++ ↑↑ Central organs
Dopamine ++ ++ ++++ ↑↑↑↑ Skin, muscle
Phenylephrine ++ — — — No real change
chronotrope. Much controversy has surrounded other meta- STAGE 2: EMPIRIC THERAPY—ANTIBIOTICS
bolic functions of this agent. Dopamine is a potent diuretic; The selection of specific antibiotics depends on the following:
it neither saves nor damages the kidneys.46 Dopamine has
1. The presumed site of infection (see Box 12-1)
complex neuroendocrine effects; it may interfere with thy-
2. Gram's stain results
roid47 and pituitary47 function and may have an immuno-
3. Suspected or known organisms
suppressive effect.48 Overall, there is no benefit to dopamine
4. Resistance patterns of the common hospital microbial
administration over norepinephrine.
flora
Dobutamine. Dobutamine is a potent β1 agonist, with pre- 5. Patient's immune status (especially neutropenia and immu-
dominant effects in the heart, where it increases myocardial nosuppressive drugs), allergies, renal dysfunction, and
contractility and thus SV and cardiac output. Dobutamine is hepatic dysfunction
associated with much less increase in heart rate than dopa- 6. Antibiotic availability, hospital resistance patterns, and
mine. In sepsis, dobutamine, although a vasodilator, increases clinical patient variables to be treated
O2 delivery and consumption. Dobutamine appears partic-
ularly effective at splanchnic resuscitation, increasing pHi Suggested Antimicrobial Regimens
(gastric mucosal pH) and improving mucosal perfusion in Sepsis Source Unknown. Combining either an antipseu-
comparison with dopamine.49 domonal cephalosporin (ceftazidime) or an antipseudomonal
penicillin (piperacillin + tazobactam) (particularly if anaer-
Epinephrine. Epinephrine has potent β1-, β2-, and α1-
obes are suspected) with either an aminoglycoside (gentami-
adrenergic activity, although the increase in MAP in sepsis is
cin or amikacin) or a fluoroquinolone (ciprofloxacin) can be
mainly from an increase in cardiac output (SV). Epinephrine
done. If an antipseudomonal cephalosporin is used and anaer-
has three major drawbacks: (1) it increases myocardial oxy-
obes are a possible cause, the addition of metronidazole or
gen demand; (2) it increases serum glucose lactate, which may
clindamycin should be considered.
be caused by a worsening of perfusion to certain tissues or by
a calorigenic effect (increased release and anaerobic break- n Piperacillin + tazobactam/imipenem + gentamicin/
down of glucose); and (3) it appears to have adverse effects on ciprofloxacin
splanchnic blood flow,50 redirecting blood peripherally as part
Catheter-Related Bloodstream Infection. There is a strong
of the “fight or flight” response. The metabolic and hemody-
possibility of infection with staphylococci, coagulase positive
namic effects make epinephrine an unsuitable first-line agent
or negative.
in sepsis.
n Vancomycin should be added to, for example, piperacillin +
Phenylephrine. Phenylephrine is an almost pure α1 agonist
tazobactam.
with moderate potency. Although widely used in anesthesia to
treat iatrogenic hypotension, it is an ineffective agent in sep- Once the infecting organisms have been isolated, the
sis. Phenylephrine is a less effective vasoconstrictor than nor- spectrum of antimicrobials should be narrowed; if methicillin-
epinephrine or epinephrine. Compared with norepinephrine, resistant S. aureus (MRSA) is isolated, the piperacillin +
phenylephrine reduces splanchnic blood flow, O2 delivery, and tazobactam should be discontinued.
lactate uptake.51
n Vancomycin + piperacillin + tazobactam or ciprofloxacin
Vasopressin. Vasopressin has emerged as an additive vaso-
Community-Acquired Pneumonia. The most likely organ-
constrictor in septic patients who have become resistant to cat-
isms are pneumococci, Mycoplasma, and Legionella. The
echolamines.52 There appears to be a quantitative deficiency of
patient requires coverage for both gram-positive and atypical
this hormone in sepsis,15,53–55 and administration in addition to
organisms (IV, intravenously; PO, orally).
norepinephrine surprisingly increases splanchnic blood flow
and urine output. The most efficacious dose appears to be n Cephalosporin IV + macrolide PO or fluoroquinolone
0.04 unit/min,56 and this is not titrated. This relatively low n Cefuroxime/ceftriaxone IV + azithromycin PO or
dose has little or no effect on normotensive patients. levofloxacin
Intra-Abdominal Sepsis. The most likely infecting organ- Source Control–4 Ds

isms are Enterobacteriaceae, enterococci, S. pneumoniae, and Intra-abdominal abscess
anaerobes. Broad-spectrum treatment is required, without Drainage Thoracic empyema
cover for Pseudomonas. Septic arthritis
Pyelonephritis, cholangitis
n Penicillin + β-lactam inhibitor or ampicillin + aminoglyco-
Necrotizing soft tissue
side + antianaerobic agent Debridement infections
n Ampicillin + sulbactam or piperacillin + tazobactam or Pancreatic necrosectomy
ampicillin + gentamicin/aztreonam + metronidazole or Mediastinitis
imipenem Infected intravascular device
Device removal Urinary catheter
Urosepsis. The most common organisms causing urinary Colonized endotracheal tube
tract infections are Enterobacteriaceae and enterococci, and Infected IUCD
the treatment is ciprofloxacin or ampicillin and gentamicin. In
this case, however, the patient has been admitted from a nurs- Bowel resection
Definitive control
ing home, and Pseudomonas is a strong possibility. Twin ther- Cholecystectomy
apy is often required, not mixing β-lactam antibiotics: FIGURE 12-12 The “four Ds” of source control.
IUCD, Intrauterine contraceptive device.
n Antipseudomonal quinolone or aminoglycoside + antipseu-
domonal penicillin or cephalosporin
n Ciprofloxacin/gentamicin/amikacin + piperacillin or ceftazidime STAGE 4: PREVENTION OF FURTHER COMPLICATIONS
A significant aspect of the critical care management of sep-
Cellulitis. The most likely organisms are streptococci and
tic patients is prevention of complications. This applies also
staphylococci. If the infection is community acquired, cloxa-
to their perioperative care. Many patients with acute severe
cillin is adequate. Again, this patient was institutionalized, and
sepsis have a concomitant hypoxic lung injury (e.g., ARDS)
the infection must be treated as hospital acquired:
requiring intensive mechanical ventilatory support. This usu-
n Vancomycin + gentamicin ally involves the application of high mean airway pressures to
prevent derecruitment of involved lung tissue. It is imperative
Necrotizing Fasciitis. Type 1 (see later) is caused by group
that lung volume be maintained perioperatively. If the patient
A streptococci, and type 2 is polymicrobial and caused by
is requiring more than 10 cm H2O of positive end-expiratory
streptococci, staphylococci, Bacteroides, and Clostridium.57
pressure (PEEP) or is on inverse-ratio pressure-controlled or
n Penicillin (high dose) or ciprofloxacin (if penicillin allergic) + airway pressure–release ventilation, the following guidelines
clindamycin should be followed58:
n Add ampicillin + sulbactam or piperacillin + tazobactam
1. The OR mechanical ventilator must be of sufficient capac-
Meningococcemia. Bacterial meningitis is meningococcal ity to maintain high mean airway pressure. Although some
septicemia until proved otherwise. The most likely alterna- modern ventilators have this capacity, the majority of “bag
tive organisms are pneumococci, Haemophilus influenzae, and in bottle” bellows are insufficient. When there is doubt,
rarely, Enterobacteriaceae and Listeria. the patient should be transferred to the OR with their ICU
ventilator.
n Third-generation cephalosporin + vancomycin (if penicillin-
2. Extreme care must be taken to avoid disconnection from
resistant S. pneumoniae suspected) + ampicillin (if Listeria
the ventilator; even short periods of disconnection (i.e., for
suspected)
changing from ventilator to anesthesia machine) may result
n Cefotaxime + vancomycin
in significant derecruitment of the lung and life-threatening
hypoxemia.
STAGE 3: SOURCE CONTROL 3. The endotracheal tube should be clamped before discon-
Source control is the essential curative measure in the man- nections to maintain lung recruitment.
agement of sepsis and the associated inflammatory response. 4. If accidental disconnection should occur, sustained infla-
Although there is a myriad of potential causes of sepsis, tion maneuvers should be performed to re-recruit the lung.
beyond medical causes, such as pneumonia or meningitis, 5. Critically ill patients are usually nursed in the semirecum-
source control can be neatly summarized by applying the bent position. Patients lie supine in the OR. This often
“four Ds” rule (Fig. 12-12)41: abscesses should be drained, results in an increase in chest wall elastance, requiring
necrotic tissue should be debrided, infected devices removed, higher levels of PEEP to maintain lung volumes.
and recurrent sources of infection/inflammation (e.g., cho- 6. The standard of care in the management of patients with
lecystitis or diverticulitis) definitively controlled. This repre- ARDS is to limit end inspiratory lung volumes to a plateau
sents the major involvement of anesthesiologists within the pressure of 30 cm H2O or less and tidal volume of 6 mL/kg
sepsis paradigm: patients travel to the OR for source control or less.31 This is to avoid “volutrauma,” a ventilator-associated
under anesthesia. lung injury.
Care must be taken to maintain circulating volume and

blood flow to tissues. During surgical debridement of, for BOX 12-3 n PERIOPERATIVE CARE OF THE PATIENT
WITH ESTABLISHED SEVERE SEPSIS
example, necrotizing pancreatitis or fasciitis, handling of
inflamed or infected tissues usually leads to significant sys- Monitoring: Continuation of all monitoring procedures in ICU
temic release of cytokines, worsening vasoplegia and increas- Fluid administration: Goal directed, based on predetermined end points
Anesthesia agents: Determined by hemodynamic stability, whether
ing myocardial depression. The anesthesiologist must be
the patient will tolerate volatile agents, pre-existing infusions (e.g.,
careful to titrate vasopressors and bolus fluids in response to lorazepam, morphine), and pharmacokinetics
rapidly changing hemodynamics. Mechanical ventilation: Transport with ICU ventilator if PEEP >10 cm
Patients with severe sepsis are at significant risk of sec- H2O, inverse-ratio pressure-controlled or airway pressure–release
ondary organ injuries, particularly to the liver and kid- ventilation in use
Avoid ventilator disconnection (use clamp)
neys. Medications that are renally metabolized or excreted
Accidental disconnection should be followed by recruitment maneuvers
(e.g., pancuronium, morphine) should be used with cau- Inhaled nitric oxide or prostacyclin should be continued
tion. Aminoglycosides and glycopeptides (e.g., vancomycin) Vasopressors: Therapy should be continued; additional bags of
must be administered with reference to pharmacokinetics. medication should be available to avoid catastrophic cessation
Nonsteroidal anti-inflammatory drugs should be avoided Corticosteroids (for adrenal insufficiency) should be continued
Nutrition: Gastric feeding should be discontinued 6 hours before
because NSAIDs may precipitate acute renal failure, worsen
surgery; postpyloric feeding may be continued (at anesthesiologist's
coagulopathy, and induce upper GI bleeding in a vulnerable discretion)
population. Although hepatic metabolism is well preserved in Total parenteral nutrition should be continued
patients with liver dysfunction in sepsis, consideration should Coagulation: All anticoagulants should be stopped before surgery
be given to the use of agents metabolized independently of Activated protein C should be stopped 2 hours before surgery
Renal replacement therapy: Continuous therapy should be stopped
the liver (e.g., cisatracurium rather than vecuronium or pan-
6 hours before surgery to allow autoreversal of heparin
curonium; remifentanil rather than fentanyl or morphine). Antimicrobials: Dosage based on predicted microbes, resistance
The choice of anesthesia agents depends on several fac- patterns of patient and hospital, renal function, and
tors. Many patients are transported to the OR in an induced pharmacokinetics
coma (e.g., lorazepam or midazolam plus morphine or hydro-
ICU, Intensive care unit; PEEP, positive end-expiratory pressure.
morphone infusions), and minimal additional anesthesia is
required. In the awake patient being induced, care should be
taken as described previously. For maintenance of anesthesia,
sufficient agents must be administered to maintain hypno-
sis and amnesia. Frequently, this is not possible with volatile core. The presence of this antigen in the serum is indicative
agents because of peripheral vasodilation and hypotension. of active viral replication. The presence of the antibody to
Ketamine is a good alternative, particularly if accompanied by this particle (anti-HBe) is indicative of the end of active viral
an infusion of fentanyl or remifentanil, or hydromorphone. replication.
Patients with acute severe sepsis are at high risk for peri- One to 6 weeks after exposure, HBsAg appears in the
operative bleeding as a result of sepsis-induced coagulopathy serum; its disappearance after 6 months indicates recovery
and thrombocytopenia. Aggressive volume repletion with red (Fig. 12-13). The presence of HBsAg for greater than 6 months
blood cells, thawed plasma, and platelets is recommended. indicates chronic disease/carrier status (5%-10% of infec-
APC (drotrecogin alfa activated) significantly increases the tions). Past exposure of immunization can be detected by
risk of bleeding and must be discontinued at least 2 hours anti-HBs. In the majority of patients, anti-HBs does not rise to
before surgical procedures and not restarted until at least detectable levels until several weeks after the disappearance of
2 hours after surgery (Box 12-3). the surface antigen and remains detectable for life. There may
be a window in which neither antibody nor antigen is detect-
able. Consequently, another test is required to ensure diagno-
TRANSMISSIBLE INFECTIONS sis. This is to detect the presence of immunoglobulin M (IgM)
antibody directed against the core antigen (IgM anti-HBc),
Hepatitis B
which is the earliest discernible anti–hepatitis B antibody. The
Hepatitis B virus (HBV) is a small, double-stranded (ds) DNA presence of HBeAg implies high infectivity; it is usually pres-
hepadnavirus. HBV is spread by sexual intercourse, with a ent from 11⁄2 to 3 months after acute infection. The presence of
high degree of infectivity, via secretions and blood products. anti-HBc indicates past exposure (see Fig. 12-13).
Health care workers are at particularly high risk of exposure After exposure, the incubation period is approximately
through handling of blood/tissue or needlestick injuries. The 12 weeks, with resolution of symptoms after 30 to 60 days.
outer core of the virus contains a surface antigen (HBsAg) that Symptoms include a prodrome of pyrexia, anorexia, myalgia,
elicits production of a neutralizing antibody (anti-HBs). In urticaria, and nausea, followed by jaundice, hepatosplenomeg-
addition, the body generates a separate antibody (anti-HBc) aly, and lymphadenopathy. There is an increase in serum bili-
against the viral core antigen (HBcAg). A third viral antigen— rubin and hepatic transaminases. From 5% to 10% of patients
the hepatitis B e antigen (HBeAg)—is also released from the go on to develop chronic active hepatitis.
Acute Hepatitis B is positive for both HBsAg and HBeAg, is approximately 25%
Anti-HBc Anti-HBs and 50%, respectively. If the blood is HBsAg positive and HBeAg
Jaundice IgM anti-HBc negative, however, the respective risks are only 3% and 30%.
Symptoms
Health care workers who have antibodies to HBV either
from pre-exposure vaccination or prior infection are not at
risk. In addition, if a susceptible worker is exposed to HBV,
postexposure prophylaxis with hepatitis B immune globulin
and initiation of hepatitis B vaccine is more than 90% effective
HBeAg in preventing HBV infection (Table 12-2).
HBV DNA (PCR)
Hepatitis C
HBsAg
Hepatitis C is the most common chronic blood-borne viral
infection in the United States. It affects 300 million people
0 1 2 3 4 5 6 12 worldwide, including 4 million Americans. Hepatitis C virus
Months after exposure (HCV), a single-strand (ss) RNA, was first identified in 1989.
FIGURE 12-13 Serologic course of acute hepatitis B HCV infection is primarily spread by parenteral adminis-
virus (HBV) infection. PCR, Polymerase chain reaction. (From tration of blood, blood products, and needle sharing among
Goldman L, Bennett JC, editors: Cecil textbook of medicine, ed 21, intravenous (IV) drug users. The incubation period for HCV
Philadelphia, 2002, Saunders.) is 6 to 10 weeks. The majority of patients remain asymptom-
atic. From 50% to 70% of HCV-infected patients develop
ANESTHETIC CONSIDERATIONS chronic hepatitis C, of which 50% will develop cirrhosis over
Patients with acute HBV infection who present for surgery 20 to 30 years. Hepatitis C is a leading cause of hepatic fail-
represent a unique risk for health care personnel, particularly ure in the United States. About 40% of patients who undergo
anesthesiologists. Universal precautions should be taken when hepatic transplantation have hepatitis C.
dealing with tissues or body fluids (Box 12-4). Following needle- The nosocomial risk of hepatitis C seroconversion after a
stick injury, the risk of developing clinical hepatitis B or sero- single incident of a needlestick in the health care setting is esti-
logic conversion, in a worker who is not immune, if the blood mated to be in the 2% to 8% range. Needlestick injury with hol-
low needles is associated with a 6- to 10-fold greater likelihood
of transmission than when it occurs from contaminated solid-
BOX 12-4 n UNIVERSAL PRECAUTIONS bore needles. There is no vaccine or effective immunoglobulin
for these patients. Seroconversion is confirmed by the detection
1. Use barrier protection at all times to prevent skin and mucous
membrane contamination with blood, body fluids containing visible
of HCV RNA in the serum. Treatment is targeted at a sustained
blood, or other body fluids (cerebrospinal, synovial, pleural, peritoneal, virologic response using interferon alfa and ribavirin. This results
pericardial, and amniotic fluids, semen and vaginal secretions). in normalization of serum transaminase levels in 50% of patients.
a. Barrier protection should be used with all tissues.
b. The type of barrier protection used should be appropriate for
ANESTHETIC CONSIDERATIONS
the type of procedures being performed and the type of expo-
sure anticipated. Examples of barrier protection include dispos-
The anesthesiologist and OR staff are particularly vulnerable
able laboratory coats, gloves, and eye/face protection. to acquiring hepatitis C by way of needlestick injury or from
2. Wear gloves when the potential exists for hand or skin contact contaminated blood or tissues. Patients with a known history
with blood, other potentially infectious material, or items and of hepatitis B or C or high-risk patients (e.g., IV drug abusers)
surfaces contaminated with these materials.
should be managed with strict barrier precautions (see Box 12-4).
3. Wear face protection (face shield) during procedures that are
likely to generate droplets of blood or body fluid to prevent
High-quality gloves (or two pairs of gloves) should be worn.
exposure to mucous membranes of the mouth, nose, and eyes. Hands must be rigorously washed after gloves are removed,
4. Wear protective body clothing (disposable laboratory coats) when and contaminated gloves should be disposed of rapidly. Barrier
there is a potential for splashing of blood or body fluids. protection of the eyes and mouth is imperative. Contaminated
5. Wash hands or other skin surfaces thoroughly and immediately if
needles should not be recapped, manipulated with both hands,
contaminated with blood, body fluids containing visible blood, or
other body fluids to which universal precautions apply.
or manually removed from a syringe. They should be dis-
6. Wash hands immediately after gloves are removed. posed of, alongside contaminated sutures and other sharps, in
7. Avoid accidental injuries caused by needles, scalpel blades, and a solid, carefully marked container adjacent to the operative site.
laboratory instruments when performing procedures, cleaning
instruments, handling sharp instruments, and disposing of used
equipment (e.g., needles, pipettes). Human Immunodeficiency Virus
8. Used needles, disposable syringes, scalpel blades, pipettes, and
other “sharps” are placed in puncture-resistant containers marked About 40 million people (range, 34-46 million) were living
with a biohazard symbol for disposal. with human immunodeficiency virus (HIV) infection and
acquired immunodeficiency syndrome (AIDS) at the end of
TABLE 12-2 n Recommended Postexposure Prophylaxis for HBV Infection
TREATMENT
Vaccination and Antibody

Response Status of Exposed Source HBsAg Source Unknown or Not Available
Workers* Source HBsAg† Positive Negative for Testing
Unvaccinated HBIG‡ × 1 and initiate HB vaccine Initiate HB Initiate HB vaccine series

series§ vaccine series
Previously vaccinated known No treatment No treatment No treatment

responder||
Known nonresponder¶ HBIG × 1 and initiate revaccination or No treatment If known high risk source, treat as if
HBIG × 2** source were HBsAg positive
Antibody response unknown Test exposed person for anti-HBs†† No treatment Test exposed person for anti-HBs
1. If adequate,|| no treatment is 1. If adequate,|| no treatment is
necessary. necessary.
2. If inadequate,¶ administer HBIG × 1 2. If inadequate,¶ administer
and vaccine booster. vaccine booster and recheck titer
in 1-2 months.
Data from Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for
postexposure prophylaxis, MMWR 50(RR-11):22, 2001.
*Persons who have previously been infected with hepatitis B virus (HBV) are immune to reinfection and do not require postexposure prophylaxis.
†Hepatitis B surface antigen.
‡Hepatitis B immune globulin; dose is 0.06 mL/kg intramuscularly.
§Hepatitis B vaccine.
||A responder is a person with adequate levels of serum antibody to HBsAg (i.e., anti-HBs ≥10 mIU/mL).
¶A nonresponder is a person with inadequate response to vaccination (i.e., serum anti-HBs <10 mIU/mL).
**The option of giving one dose of HBIG and reinitiating the vaccine series is preferred for nonresponders who have not completed a second three-dose vaccine
series. For persons who previously completed a second vaccine series but failed to respond, two doses of HBIG is preferred.
††Antibody to HBsAg.
2003, with 5 million new cases that year. An estimated 20% each day. The T lymphocytes are replenished, and immune
to 25% of HIV-positive patients will require surgery during status remains functional.
their illness.59 Before the development of “full-blown AIDS,” the patient
After entering the cell, HIV type 1, an ssRNA retrovirus, is enters a stage of persistent generalized lymphadenopathy. In
copied by a reverse transcriptase (RT), enabling the virus to this stage, nodes greater than 1 cm in more than two nonin-
produce dsDNA, which then integrates into the host's cells. guinal sites are present for more than 3 months. The patient
The most common mode of infection is sexual transmis- may lose weight and develop seborrheic dermatitis. AIDS is
sion through the genital mucosa. HIV may also be spread by diagnosed by a CD4+ count of less than 200 cells/μL or the
transfusion of contaminated blood or by needle sharing or presence of one or more defining illnesses (Box 12-5). The
needlestick injury. Within 2 days the virus can be detected patient is at significant risk for opportunistic infections and
in the internal iliac lymph nodes, and within 5 days (range, malignancies, including toxoplasmosis, cryptococcal menin-
4-11 days) the virus can be cultured from the plasma. There gitis, progressive multifocal leukoencephalopathy, cytomega-
is rapid dissemination to lymphoid tissue and the brain. The lovirus (CMV) infection, herpes simplex virus infection, brain
CD4+ T lymphocytes (T-helper cells) are the primary target of lymphomas, and tuberculosis. HIV is thus a multisystem dis-
infection. Progression of HIV illness is defined by the decline ease (Box 12-6).
in CD4+ cell count leading to immune deficiency and mani- With the development of constitutional symptoms (physi-
fest by opportunistic infections and unusual neoplasia. Thus, ologic reserve is depleted), viral load again increases, and the
progression is followed by monitoring the cell count per cubic patient becomes extremely infectious. This has significant
millimeter. implications for health care providers.
Plasma viral load (which can be quantified) is initially
extremely high and then declines in the clinical latency period. ANESTHETIC CONSIDERATIONS
This early acute infection, the seroconversion illness, is tran- Perioperative risk correlates well with immune function. A
sient; symptoms include fever, fatigue, rash, headache, lymph- CD4+ cell count of less than 200 cells/μL puts the patient at
adenopathy, pharyngitis, myalgia or arthralgia, and nausea, significant risk for opportunistic infections and increased
vomiting, and diarrhea. This may be confused with a flulike infectious risk associated with surgery.60 The presence of
illness. The clinical latency period may last 7 to 12 years, dur- pulmonary, cardiac, or renal disease may also lead to periop-
ing which billions of virions and CD4+ cells are destroyed erative complications. Consequently, the patient with AIDS
BOX 12-5 n AIDS-DEFINING ILLNESSES BOX 12-6 n COMPLICATIONS OF HIV MULTIORGAN

DISEASE
Candidiasis of bronchi, trachea, lungs, or esophagus
Invasive cervical cancer Respiratory
Coccidioidomycosis, disseminated or extrapulmonary Pneumocystis jiroveci (formerly P. carinii)
Cryptococcosis, extrapulmonary Bacterial pneumonia
Cryptosporidiosis, chronic intestinal (>1 month) Tuberculosis
Cytomegalovirus disease (other than liver, spleen, or nodes) Aspergillosis
Cytomegalovirus retinitis (with loss of vision) Cytomegalovirus
Encephalopathy, HIV related Oropharyngeal candidiasis, herpetic infections
Herpes simplex: chronic ulcer(s) (>1 month); or bronchitis, pneumonitis,
Hematologic
or esophagitis
Leukopenia, lymphopenia
Histoplasmosis, disseminated or extrapulmonary
Thrombocytopenia
Isosporiasis, chronic intestinal (>1 month)
Anemia
Kaposi's sarcoma
Drug toxicity, bone marrow suppression
Lymphoma, Burkitt's (or equivalent term)
Lymphoma, immunoblastic (or equivalent term) Cardiac
Lymphoma, primary, of brain Pericarditis effusion
Mycobacterium avium-intracellulare complex or Mycobacterium Pericarditis
kansasii, disseminated or extrapulmonary Myocarditis (late stages of infection)
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Dilated cardiomyopathy
Mycobacterium, other species or unidentified species, disseminated Endocarditis (intravenous drug use)
or extrapulmonary Pulmonary hypertension
Pneumocystis jiroveci (P. carinii) pneumonia Drug-related cardiotoxicity
Pneumonia, recurrent Thromboembolitic events
Progressive multifocal leukoencephalopathy Myocardial infarction
Salmonella septicemia, recurrent
Gastrointestinal
Toxoplasmosis of brain
Infectious diarrhea, proctitis
Gastrointestinal bleeding
Acalculous cholecystitis
requires significant preoperative workup. This should include Vomiting, loss of appetite, cachexia
complete blood cell count, a coagulation panel, and liver and Dysphagia (Candida albicans, cytomegalovirus), esophagitis
Liver disease, hepatitis B and C, other infections
renal function tests. The patient should have an electrocar-
diogram and chest radiograph, regardless of age and gender. Neurologic Problems in AIDS Patients
Distal, symmetric sensory neuropathy: numbness, tingling, painful
If there is a history of pulmonary disease, and the patient is
dysesthesias and paresthesias
undergoing major surgery, pulmonary function testing is Chronic, inflammatory demyelinating polyneuropathy
necessary. AIDS encephalopathy or AIDS dementia complex: cognitive, motor,
There are numerous airway complications of HIV/AIDS: and behavioral changes
oral candidiasis, herpes simplex ulcers (risk of transmission Vacuolar myelopathy: sensory disturbance, spasticity and
hyperreflexia (acute or chronic progression)
to the laryngoscopist), and hemorrhagic Kaposi's sarcoma
Segmental (focal) myelopathy, acute or subacute (less common)
lesions. Lung parenchyma may be damaged by Pneumocystis,
histoplasmosis, CMV, or tuberculosis, with significant impact Data from Hughes SC: Anesthesiol Clin North Am 22:379-404, 2004.
on gas exchange. This may lead to a higher Fio2 requirement
intraoperatively, and prolonged postoperative mechanical
ventilation.
The cardiovascular system may be affected by autonomic A variety of opportunistic infections of the GI tract mani-
neuropathy (inadequate heart rate response to vasodilatory fest in HIV/AIDS. Chronic diarrhea is common and associated
effects of anesthetic agents), cardiomyopathy, and myocardial with hypokalemia and volume depletion. Colonic perforation
lymphoma. If cardiac involvement is suspected, the patient has been associated with cytomegalic colitis. Lymphoma has
should have preoperative echocardiography to determine been associated with bowel obstruction, increasing the risk
both systolic and diastolic function. The presence of signif- of aspiration pneumonitis. Patients with HIV/AIDS have a
icant cardiac dysfunction is an indication for invasive peri- predisposition for anemia, as a consequence of bone marrow
operative monitoring. Neurologic problems associated with suppression, associated with chronic disease, malnutrition
HIV/AIDS include delirium, headache, localized or general- (GI involvement impairs iron, vitamin B12, and folate absorp-
ized seizures, limb weakness, and visual loss. It is important tion), and drug therapy (zidovudine).
to document, preoperatively, the presence or absence of focal Past medical/social history is of particular importance in
neurologic deficit to avoid confusion with complications of this patient population. Substance abuse, and IV drug abuse
anesthesia and surgery. The presence of AIDS-related demen- in particular, remains the most significant risk factor. The
tia may preclude the patient consenting to both surgery and concurrent presence of sexually transmitted diseases such
anesthesia.61 as hepatitis B, hepatitis C (severe hepatic involvement), and
Abdominal Surgery. Patients with HIV may develop

TABLE 12-3 n Antiretroviral Drug Therapy: Side Effects
with Anesthetic Significance
abdominal pain for a variety of reasons, rarely requiring
laparotomy. Surgery may be required for resection of neo-
Side Effects Responsible Antiretroviral Drug plasm, particularly if there is bowel obstruction, drainage of
intra-abdominal abscess, and appendectomy. The presence of
Neutropenia Ganciclovir immunodeficiency may mask the signs (leukocytosis) of infection,
Trimethoprim/sulfamethoxazole
leading to delayed diagnosis.65 Moreover, these patients may
Thrombocytopenia Isoniazid mount a less dramatic SIRS response than expected, leading to
Phenytoin dramatic development of severe sepsis without warning. Low
Rifampin
CD4+ count independently predicts an increased incidence of
Zidovudine
postoperative sepsis.60
Electrolyte disturbances Protease inhibitors Patients with HIV are at particular risk for biliary tract dis-
Pentamidine ease: cholecystitis, cholangitis, and infections with opportunis-
Hepatic dysfunction Ethambutol tic organisms such as Salmonella, CMV, and Cryptosporidium.
Phenytoin Risk of extrahepatic biliary obstruction is increased by exter-
Peripheral neuropathy Didanosine
nal compression of the common bile duct by enlarged portal
Lamivudine lymph nodes (or lymphoma).66 Laparoscopic cholecystectomy
Stavudine or choledochojejunostomy may be required.
Zalcitabine Patients infected with HIV, or with AIDS, frequently
Bronchospasm Pentamidine require anorectal surgery for excision of extensive condy-
lomata, anal fistulas, or perirectal abscesses. The patient is
Cardiac dysrhythmias Pentamidine positioned in the prone-jackknife position. General or spinal
Data from Kuczkowski KM: J Clin Anesth 15:224-233, 2003. anesthesia (assuming the patient does not have a coagulopa-
thy) can be safely administered, as with patients who are not
infected. Postoperative wound healing in patients with HIV,
syphilis (neurologic deficits in late stage) may alter anesthetic
but not AIDS, is not impaired.67
management.62
The current standard therapy for HIV/AIDS is highly active Neurosurgery. Intracranial pyogenic abscess, toxoplasmo-
antiretroviral therapy (HAART), which involves combination sis, or lymphoma may cause neurologic symptoms in HIV-
chemotherapy. These drugs fall into four categories: nucleo- infected patients. Infrequently, stereotactic needle biopsy is
side analog reverse transcriptase inhibitors, nonnucleoside required for diagnosis. The procedure is usually carried out
analog reverse transcriptase inhibitors, protease inhibitors, under monitored anesthesia care, for example with a remifen-
and the new category of fusion inhibitors (Table 12-3). From tanil-propofol infusion and spontaneous ventilation.
the anesthesiologist's perspective, protease inhibitors are the
Thoracic Surgery. The HIV-infected patient will occa-
most important agents. These potent CYP450 inhibitors pro-
sionally require open-lung biopsy to clarify the diagnosis in
long duration of action of hepatically metabolized drugs, such
the event of respiratory failure. Opportunistic infections can
as fentanyl, midazolam, and morphine. Judicious dosing and
usually be diagnosed by sputum examination or bronchoal-
careful titration are recommended.
veolar lavage. However, the identification, classification, and
The anesthesia care plan should take into account immu-
staging of lymphoma may require surgery. Additional risk of
nosuppression, systemic disease, and the risk of HIV transmis-
recurrent pneumothorax and empyema can be managed by
sion to health care providers. There is no evidence of increased
video-assisted thoracoscopic surgery (VATS). It is important
anesthesia risk in this patient population or of increased com-
to assess and clarify the extent of the respiratory insult and the
plications associated with regional anesthesia.63,64
degree of hypoxemia in these patients before surgery. Careful
Surgery attention must be placed in the ventilation strategy in the pres-
Splenectomy. Patients with HIV may develop a variant of ence of hypoxemic respiratory failure. The patient with signif-
thrombocytopenia purpura (ITP) known as HIV-associated icant parenchymal lung disease may be intolerant of one-lung
immune ITP. This characteristically does not respond to corti- anesthesia.
costeroid therapy and may occur with HIV infection or AIDS.
The treatment of choice is combination retroviral therapy; in Pregnancy
refractory cases, however, splenectomy is required.64 The anes- Management of HIV-seropositive pregnant women includes
thesiologist must be aware that the patient is at significantly attempts to minimize the infant's risk of acquired infection.
increased risk of bleeding, and that the platelet count cannot Perinatal HIV transmission occurs antepartum, intrapartum,
be raised by administration of corticosteroids or platelet trans- or postpartum. High maternal viral load increases the likeli-
fusion. Consequently, epidural anesthesia should be avoided, hood of perinatal transmission of HIV. Most perinatal HIV
as should the placement of large-bore IV catheters in noncom- transmissions occur during labor and vaginal delivery. Thus,
pressible vessels. obstetric care is targeted at minimizing exposure to maternal
Tuberculosis
TABLE 12-4 n Elective Cesarean Delivery to Reduce
HIV Transmission: Rates of Vertical Tuberculosis (TB) remains a major worldwide scourge.
Transmission Approximately one third of the world's population has been
Elective Cesarean Other Mode exposed, and there are about 8 million new cases per year and
Delivery of Delivery 4 million deaths. Nevertheless, until the AIDS epidemic, the
prevalence of TB declined dramatically from the 1950s to the
No antiretroviral 10.4% 19.0% 1980s. There was a 20% increase in the incidence of TB in
therapy
the United States between 1985 and 1992, principally caused
Antiretroviral 2.0% 7.3% by AIDS but also associated with immigration from coun-
therapy tries with endemic TB, poverty, and limited health services in
Data from International Perinatal HIV Group: N Engl J Med 340:977-987, 1999.
impoverished areas. After peaking at 25,287 cases in 1993, the
number of reported cases began to fall again. In 2001, 15,989
cases of TB were reported to the U.S. Centers for Disease
blood and genital secretions. This involves avoiding percuta- Control and Prevention (CDC). Three fourths of cases among
neous umbilical cord sampling, fetal scalp clips (when pos- foreign immigrants came from seven countries: Vietnam, the
sible), fetal scalp sampling, delivery techniques that could Philippines, India, China, South Korea, Mexico, and Haiti.
produce abrasions in the infant's skin (e.g., vacuum or for- Mycobacterium tuberculosis is an aerobic rod that thrives in
ceps), and immediate removal of maternal blood and fluids an aerobic environment, at a Po2 of 140 mm Hg. Consequently,
from the infant.59 There is a relationship between the mode it preferentially infects the anterior apical segments of the lung.
of delivery and risk of transmission: the risk is significantly The bacilli are transmitted via droplet infection as a result of
reduced by elective cesarean section68,69 (Table 12-4). This coughing or sneezing. TB may also be transmitted from one
benefit may be lost if spontaneous rupture of the membranes patient to another through anesthesia breathing systems or
has occurred. HIV may be transmitted through breast milk so mechanical ventilators.
breast feeding is discouraged. The principal site of infection of tuberculosis is the lung,
Elective cesarean section should be performed under spinal but the bacterium may infect other organs, including the kid-
anesthesia, as in noninfected parturients.61,63 neys, brain, bones, joints, spine, and genitourinary tract.
Pulmonary TB typically presents as general malaise,
RISK TO ANESTHESIOLOGIST anorexia, weight loss, fever, night sweats, productive cough,
Infection with HIV is the most feared of all occupa- and hemoptysis. Diagnosis is made by serial sputum s ampling
tionally acquired diseases. It is important to note that for detection of acid-fast bacilli. In active primary TB, chest
patients with HIV/AIDS represent a reservoir of poten- radiography reveals lobar pneumonia, with subsegmental
tial infectious exposures, in addition to the virus itself. atelectasis and ipsilateral hilar adenopathy. The more classic
The most important of these is tuberculosis. The patient “reactivation” form of TB manifests with cavitating lesions
may also be simultaneously infected with hepatitis B or in the posterior segment of the right upper lobe and apical
C, or both. segments of the lower lobes. A normal radiograph does not
Universal precautions should be employed when handling exclude TB, and in the presence of HIV the lesions are often
body fluids, tissue, blood, and blood products (see Box 12-4). atypical. If TB is suspected, respiratory isolation precautions
The anesthesiologist must wear gloves at all times when in should be instituted immediately, until the patient is deemed
contact with the patient, the patient's blood, or tissues.70 not to be infectious (acid-fast bacillus negative on three suc-
Where there is significant risk of exposure to the patient's cessive sputum samples, improving symptoms, and improving
body fluids—inserting arterial or central lines, performing chest radiograph).
bronchoscopy or fiberoptic intubation, or using epidural, spi- Current therapeutic regimens for TB involve four-drug
nal or regional anesthetic—a gown and face mask with eye therapy, over 6 months, as follows:
protection is recommended. Contaminated needles should
n Initial 2 months (all oral doses): isoniazid (INH), 300 mg/
not be recapped by hand.
day; rifampin (RIF), 600 mg/day; pyrazinamide (PZA), 2 g/
The risk of HIV transmission from a needlestick injury
day); and ethambutol (ETB), 2 g/day.
with HIV-infected blood is approximately 0.32%, a much
n Final 4 months (if initial 2 months are successful by smear
lower risk than with hepatitis C.70 Immediately after
conversion and resolving symptoms): INH, 300 mg/day,
needlestick injury, the health care worker should be treated
and RIF, 600 mg/day, or alternatively, INH, 900 mg, and RIF,
with antiretroviral drugs (within 1 hour); this can reduce
600 mg, twice weekly.
the rate of seroconversion by 80%.1 Factors determining
the risk to the exposed health care provider include type of Patients suspected of having active TB are nursed in respi-
procedure using needle, depth of needlestick injury, quan- ratory isolation, in special negative-pressure isolation rooms.
tity of blood involved, and viral titers in the HIV-infected Precautions can be supplemented with high-efficiency par-
patient.61 ticulate air (HEPA) filters and ultraviolet irradiation devices
installed near the ceiling. Clear infection control guidelines Prions

must be in place and followed rigorously. The patient should
Prions (proteinaceous infective particles) are infectious
wear a surgical mask when outside an isolation room.
proteins without (known) nucleic acid genomes. A num-
ber of these agents infect mammals, preferentially target-
ANESTHETIC CONSIDERATIONS ing neurologic tissue, causing spongiform encephalopathies.
A patient with active TB represents major infection risk These include Creutzfeldt-Jakob disease (CJD), Gerstmann-
for other patients and health care workers. Elective surgery Straussler-Scheinker syndrome, and kuru in humans; scrapie
should be avoided and postponed until the patient is no lon- in sheep; and bovine spongiform encephalopathy (BSE) in cat-
ger infectious. For emergent or semi-emergent surgery, spe- tle (“mad cow disease”). These neurodegenerative diseases are
cial precautions should be taken. Contact with health care universally lethal.
workers should be minimized; the number of staff in the OR Renewed interest in these agents followed the 1996 descrip-
should be kept to a minimum. The OR doors should be kept tion of a new form of CJD, known as variant CJD (vCJD),
closed and infectious risk signs placed prominently as alerts which appears to have crossed over from BSE.71,72 After a clus-
to unwitting staff. The anesthesia breathing system should ter of reported cases in the United Kingdom, the specter of
be separated from the mechanical ventilator by a HEPA fil- perioperative transmission of CJD and vCJD has emerged.
ter. The breathing system should be disposed of at the end Moreover, emerging data suggest that these diseases may be
of the case. spread by blood transfusion.73 Variant CJD affects mainly
Standard surgical face masks provide insufficient pro- young people (average age 29), and the median duration of ill-
tection from droplet infection; the anesthesiologist should ness is 14 months. Since first reported in the United Kingdom
wear a National Institute for Occupational Safety and Health in 1996, by 2005 there were 151 cases of definite or probable
(NIOSH) N95 standard face mask and eye protection. The vCJD and 146 deaths, with 1010 reported cases of CJD of all
mask should fit snugly over the face such that all inspired air causes in the UK alone.
passes through it. Extreme care should attend the disposal of Creutzfeldt-Jakob disease causes progressive neuropsy-
soiled endotracheal tubes, suction tubing, and so on. If laryn- chiatric degeneration, associated with gradual reduction in
geal mask anesthesia is performed, the mask should not be consciousness, myoclonus, ataxia, chorea, or dystonia. In the
recycled. The patient should undergo recovery in isolation. If late stages the patient progresses to a near catatonic state. The
no isolation room is available, recovery is in the OR or an ICU prions causing vCJD are found in high concentration in the
isolation room (Box 12-7). brain, spinal cord, and eye. They are also found in lymphore-
ticular tissue, a potential source of infectiousness.
Diagnosis of vCJD is difficult with no reliable investiga-
BOX 12-7 n ASA GUIDELINES FOR OPERATIVE CARE tion available. Diagnosis is made by a combination of clinical
OF TUBERCULOSIS PATIENT symptoms and signs and a positive tonsillar biopsy or by the
1. Elective surgical procedures on a patient who has tuberculosis presence of bilateral high pulvinar signal on magnetic reso-
should be delayed until the patient is no longer infectious. nance imaging (MRI).
2. Patients should be transported to the OR wearing surgical masks
to prevent respiratory secretions from entering the air. ANESTHETIC CONSIDERATIONS
3. The doors of the OR should be closed, and traffic into and out of
Anesthesia may be required for patients with vCJD for tonsillar
OR should be minimized.
4. Perform the procedure at a time when other patients are not or brain biopsy, tracheostomy, or placement of a percutaneous
present in the OR suite and when minimal personnel are present endoscopic gastrostomy (PEG) feeding tube. This has signifi-
(e.g., end of workday). cant implications for the performance of anesthesia and for the
a. Ideally, the OR should have an anteroom that is negative pres- OR staff. Most important is the potential for transmission of
sure to the corridor and the OR.
disease between patients through contaminated instruments.
b. The anesthesiologist and other health care workers should
wear a NIOSH N95–compatible face mask. Prions are small enough to reside in the microscopic crypts on
5. Exhausted air should be diverted away from hospital. stainless steel instruments and are not removed easily by stan-
6. A bacterial filter between the anesthesia circuit and the patient's dard washing techniques; furthermore, they are resistant to
airway will prevent contamination of anesthesia equipment or deactivation by traditional methods of decontamination. Novel
discharge of tubercle bacilli into the ambient air.
approaches have been suggested but not widely adopted.74
7. These filters can be placed between the Y-connector and the
mask, laryngeal mask, or endotracheal tube. All unnecessary equipment and staff should be removed or
8. During recovery from anesthesia, the patient should be monitored excluded from the OR, and warning signs placed outside. Staff
and placed in an isolation room. must take extraordinary barrier measures such as double glov-
9. Alternatively, the patient should undergo recovery in the OR or in ing, eye protection, aprons, and disposable liquid-repellent
own room.
gowns. Where possible, disposable equipment should be used
ASA, American Society of Anesthesiologists; OR, operating room; NIOSH, (e.g., laryngoscopes, face masks, orolaryngeal mask airways)
National Institute for Occupational Safety and Health. and incinerated. If the diagnosis of CJD or vCJD is confirmed,
all instruments should be disposed of immediately.75
In the anesthetic setup, it is preferable to use an ICU-style

ventilator, which can be stripped afterward, with disposables BOX 12-8 n ORIGINS AND CAUSES OF PYOGENIC
incinerated. If the patient is already intubated, the ventilator LIVER ABSCESS
from the ICU should travel with the patient. Total intrave- Liver and Biliary Tract
nous anesthesia can be administered. Although there are no Gallstones
specific contraindications to anesthesia agents, succinylcho- Biliary strictures
line should be avoided when degenerative myopathy exists. Cholangiocarcinoma
Pipeline vacuum systems should not be used, and a portable Blocked biliary stent
Liver biopsy
machine should accompany the patient in the OR, recovery, Gallbladder empyema
and ward.76 During surgery, all needles, clamps, sutures, and Secondary infection of hepatic cyst
sharps should be directly disposed of into a suitable receptacle.
Extrahepatic Causes
Tissue matter should be carefully disposed of in clearly labeled Appendicitis
bags. The patient proceeds to the recovery room or is returned Diverticulitis
directly to the ICU. Crohn's disease
Trauma
Abscess Extension
INTRA-ABDOMINAL INFECTIONS AND Perforated peptic ulcer
ANESTHESIA Subphrenic abscess
Disseminated sepsis
Intra-abdominal abscesses are walled-off collections of pus Catheter-related bloodstream infection
or parasites surrounded by fibrotic tissue, induced by inflam- Infective endocarditis
mation, occurring within the abdomen. They may be located Dental infection
within viscera, in the peritoneum, between loops of bowel, or
in the retroperitoneal space. Intraperitoneal infections result Data from Krige JEJ, Beckingham IJ: BMJ 322:537-540, 2001.
from postsurgical anastomotic leakage, viscus perforation

(e.g., a ruptured diverticulum), resolution of diffuse peritoni-
tis into multiple small abscesses, or infection with parasites. presence of biliary tree compression caused by mass effect,
increased serum transaminase and alkaline phosphatase (ALP)
levels. Ultrasonography is the preferred imaging technique,
Pyogenic Liver Abscess
because internal septations or daughter cysts (hydatid disease)
Liver abscesses are divided into pyogenic and parasitic (ame- are more clearly visualized.
bic and hydatid). The incidence of hepatic abscess is estimated Treatment is determined by the size, number, and nature
as 13 to 20 cases per 100,000.77 Most pyogenic liver abscesses of the lesions within the liver. Multiple small abscesses are
are secondary to infection originating in the abdomen treated by antimicrobial therapy alone, which must include
(Box 12-8). Cholangitis resulting from stones or strictures is a penicillinase-resistant penicillin, an anti–gram-negative
the most common cause, followed by abdominal infection agent, and metronidazole. In the absence of an intra-abdominal
from diverticulitis or appendicitis. In 15% of cases, no cause source, aspiration of the abscess under ultrasound or com-
can be found. puted tomography (CT) can be performed. Usually a con-
In the United States 80% of cases of liver abscess are pyo- tinuous-drainage catheter is left in place. If an abdominal
genic. The majority of pyogenic liver abscesses are polymi- source is present, if there is a very large abscess or multilocular
crobial infections, usually with gram-negative aerobic and abscesses, or if antibiotics fail, surgical drainage is necessary.
anaerobic organisms. Most organisms are of bowel origin, with
Escherichia coli, Klebsiella pneumoniae, Bacteroides, entero-
Amebic Liver Abscess
cocci, anaerobic streptococci, and microaerophilic streptococci
being most common. In approximately 50% of cases there is About 10% of the world's population is chronically infected
infection with anaerobic organisms. In patients with pre-exist- with Entamoeba histolytica.78 Amebiasis is the third most com-
ing infections such as dental abscess or endocarditis, infection mon parasitic cause of death, surpassed only by malaria and
with hemolytic streptococci, staphylococci, or Streptococcus schistosomiasis. The prevalence of infection varies widely,
milleri may occur. In the immunosuppressed population, such occurring most often in tropical and subtropical climates.
as patients undergoing chemotherapy, with AIDS, or after Overcrowding and poor sanitation are the main predisposing
transplantation, opportunistic organisms or fungi may infect factors.
the liver.78 The classic presentation of pyogenic liver abscess The parasite is transmitted through the fecal-oral route
is with abdominal pain, swinging fever, night sweats, nausea, with the ingestion of viable protozoal cysts. The cyst wall dis-
vomiting, anorexia, anergia, and malaise. There is usually hep- integrates in the small intestine, releasing motile trophozoites.
atomegaly, tenderness in the right upper quadrant, and raised These migrate to the large bowel, where pathogenic strains
right hemidiaphragm (with sympathetic pleural effusion) on may cause invasive disease. Mucosal invasion results in the
chest radiography. There is leukocytosis, anemia, and in the formation of flask-shaped ulcers through which amebae gain
access to the portal venous system. The abscess is usually soli- the guidelines established for the management of the septic
tary and affects the right lobe in 80% of cases. The abscess con- patients, described earlier in the chapter, should be followed. If
tains sterile pus and reddish brown (“anchovy paste”) liquefied the patient is bacteremic, epidural analgesia and placement of
necrotic liver tissue. Amebae are occasionally present at the CVP catheters should be avoided, to prevent the development
periphery of the abscess. of catheter-related infection.
Patients may have had symptoms from a few days to several
weeks before presentation. Pain is a prominent feature, and the
patient appears toxic, febrile, and chronically ill. Hydatid Disease
The diagnosis is based on clinical, serologic, and radiologic
Hydatid disease in humans is caused by the dog tapeworm
features. The patient is usually resident in an endemic area
Echinococcus granulosus. Dogs are the definitive host. Ova
or has visited one recently, although there may be no history
are shed in the feces and then infect the natural intermedi-
of diarrhea. Patients typically have leukocytosis, with 70% to
ate hosts such as sheep or cattle. Hydatid disease is endemic
80% polymorphs (eosinophilia is not a feature), a raised eryth-
in many sheep-raising countries. Increasing migration and
rocyte sedimentation rate, and moderate anemia. In patients
world travel have made hydatidosis a global problem of
with severe disease and multiple abscesses, ALP activity and
increasing importance. Human infection follows accidental
bilirubin concentration are raised. Stools may contain cysts, or
ingestion of ova passed in dog feces. The ova penetrate the
in the case of dysentery, hematophagous trophozoites.
intestinal wall and pass through the portal vein to the liver,
Chest radiography usually shows a raised right hemidia-
lung, and other tissues. Hydatid cysts can develop anywhere
phragm with atelectasis or pleural effusion. Ultrasonography
in the body, but two thirds of cysts occur in the liver and one
shows the size and position of the abscess and is useful when
fourth in the lungs.
aspiration is necessary and to assess response to treatment.
Patients with a liver hydatid may present either with liver
Serologic tests provide a rapid means of confirming the diag-
enlargement and right upper quadrant pain caused by pressure
nosis, but the results may be misleading in endemic areas
from the cyst or acutely with a complication. Complications
because of previous infection. Indirect hemagglutination
include rupture of the cyst into the peritoneal cavity, which
titers for Entamoeba are raised in more than 90% of patients.
results in urticaria, anaphylactic shock, eosinophilia, and
In areas where amebiasis is uncommon, failure to consider the
implantation into the omentum and other viscera. Cysts may
infection may delay diagnosis.
compress or erode into a bile duct, causing pain, jaundice, or
Serious complications occur as a result of secondary infec-
cholangitis, or the cyst may become infected secondary to a
tion or rupture into adjacent structures such as pleural, peri-
bile leak.
cardial, or peritoneal spaces. Two thirds of ruptures occur
Ultrasonography and CT will show the size, position, and
intraperitoneally and one third are intrathoracic.
number of liver cysts and any extrahepatic cysts. Classically,
About 95% of uncomplicated amebic abscesses resolve
“daughter cysts” are visualized within the main collection.
with metronidazole alone (800 mg three times daily for
About 10% of patients with a liver cyst will also have a lung
5 days). Supportive measures such as adequate nutrition and
hydatid on chest radiography. The diagnosis is confirmed by
pain relief are important. Clinical symptoms usually improve
hemagglutination and complement fixation tests. Aspiration
greatly within 24 hours. Lower doses of metronidazole are
of the cyst for diagnostic purposes is avoided until the diagno-
often effective in invasive disease but may fail to eliminate
sis is confirmed. Biliary tree compression may increase serum
the intraluminal infection, allowing clinical relapses to occur.
bilirubin and transaminase levels. Eosinophilia is present in
After the amebic abscess has been treated, patients are pre-
40% of patients.
scribed diloxanide furoate, 500 mg every 8 hours for 7 days, to
eliminate intestinal amebae. Surgery. All symptomatic cysts require surgical removal
Patients should have ultrasonographically guided nee- to prevent complications. Radiologic cyst drainage has been
dle aspiration if serology gives negative results or the abscess described but is not widely practiced.79 Consequently, the
is large (>10 cm), if they do not respond to treatment, or if majority of these patients require general anesthesia. The
there is impending peritoneal, pleural, or pericardial rupture. primary goal of surgery is careful dissection and removal of
Surgical drainage is required only if the abscess has ruptured the intact cyst, avoiding spillage of its contents, which would
causing amebic peritonitis or if the patient has not responded result in the development of secondary cysts in the perito-
to drugs despite aspiration or catheter drainage. neum. The patient is treated with albendazole for 4 weeks pre-
operatively, to shrink the cyst. The surgical field is carefully
ANESTHESIA CONSIDERATIONS isolated by abdominal swabs soaked in scolicidal fluid. The
Abnormal liver function is unusual except in the event of bil- cyst fluid is aspirated and replaced by a scolicidal agent such as
iary obstruction or parenchymal compression. The presence 0.5% sodium hypochlorite, 0.5% cetrimide, 0.5% silver nitrate,
of jaundice or increased serum transaminase levels likely has 30% hypertonic saline, or sodium hydroxide. This sterilizes
minimal effect on the conduct of anesthesia, because inher- the cyst cavity. After decompression, the cyst and contents are
ent liver metabolic function is usually intact. The patient may carefully shelled and the cavity filled with isotonic saline or
have evidence of low-grade or frank sepsis, in which case omentum and closed.
ANESTHETIC CONSIDERATIONS There are two surgical approaches to appendiceal abscess:

Liver dysfunction caused by an enlarging cyst rarely interferes (1) immediate appendectomy with abscess drainage, the
with metabolic function. There may be compressive atelecta- major risk of which is pus dissemination through the perito-
sis in the lower segments of the right lung, leading to hypox- neum caused by the friability of tissues, and (2) delayed sur-
emia, which worsens after induction of anesthesia. PEEP is gery, awaiting abscess organization. If the second approach is
recommended. There is no contraindication to epidural cath- planned, spontaneous resolution of the abscess is anticipated
eter placement, although epidural infusion should be delayed and appendectomy planned at 6 to 8 weeks. If the abscess per-
until the cyst has been successfully excised. An arterial line sists, however, it should be drained percutaneously.
should be placed to monitor beat-to-beat BP variation. Two
major intraoperative complications are cyst rupture, leading to
anaphylactic shock,80 and hyperosmolar coma, following the
Diverticular Abscess
administration of hypertonic saline.81,82 Anaphylaxis is treated Diverticular abscesses form after perforation of a diverticu-
with IV fluid, epinephrine, antihistamines, and corticoste- lum. Perforation into the peritoneum leads to diffuse peritoni-
roids, all of which should be at hand in the OR. Pretreatment tis, requiring immediate surgery. Often, however, the abscess
with H1 and H2 antagonists may be beneficial.83 may be contained by mesentery or local structures. The patient
thus presents with malaise, pyrexia, leukocytosis, and general-
ized abdominal pain. The diagnosis is confirmed by CT. The
Splenic Abscess
most common site of diverticular disease is the sigmoid colon.
Splenic abscesses are rare. There are five major causes: (1) The patient usually develops a colonic ileus.
metastatic spread from septic foci—including IV drug use, In the early stages, after perforation, when there is fecal
endocarditis, salmonella (in AIDS), osteomyelitis, TB, den- soiling of the peritoneum, the patient may remain surpris-
tal extractions, infected intravascular devices; (2) spread from ingly well, leading to a false sense of security. This “honey-
adjacent organs—pancreatic and subphrenic abscesses, gas- moon” period lasts 24 to 48 hours, followed by a dramatic
tric and colonic perforations; (3) infection of splenic infarct— SIRS response, fluid sequestration, and hypoxemia. This is
seen in hemoglobinopathies, including sickle cell disease the clinical manifestation of the proliferation of bowel bacte-
and splenic artery embolization; (4) splenic trauma, and (5) ria in the peritoneum. Early laparotomy allows for peritoneal
immunocompromise. Patients present with fever, leukocyto- irrigation and colonic resection. At this stage, mild to moder-
sis, and right upper quadrant pain. It may be associated with ate vasodilation may be present, but patients rarely have overt
raised left hemidiaphragm, pleural effusion, and pain referred signs of sepsis.
to the left shoulder. Splenic abscess is most effectively diag- Diverticular abscesses are usually drained radiologically,
nosed by CT or MRI. In approximately 50% of patients, blood using CT guidance. This may require sequential proce-
cultures are positive. In the majority of abscesses, strepto- dures. Once the initial inflammatory response has resolved
cocci or staphylococci are present; gram-negative rods are and the source is controlled, laparotomy and bowel resec-
present in 30%, anaerobes in 12%, and mixed organisms in tion are performed. Antimicrobial coverage should include
25%. Antimicrobial treatment includes penicillinase-resistant therapy for gram-positive organisms and anaerobes and
β-lactam, aminoglycoside, or aztreonam and metronidazole. includes ampicillin/sulbactam or ampicillin, gentamicin, and
metronidazole.
Appendiceal Abscess
Appendiceal abscesses result from acute rupture of an acutely
NECROTIZING SOFT TISSUE INFECTIONS
inflamed appendix. Appendicitis is the consequence of Necrotizing soft tissue infections (NSTIs) represent a group
obstruction of the appendiceal lumen by a fecalith. There is of diseases characterized by rapidly spreading necrotizing
increased intraluminal pressure associated with bacterial pro- infection of subcutaneous tissue, fascial planes, and muscle.
liferation. There is venous congestion, distention of the organ, NSTIs are classified anatomically, determined by the depth
and eventually arterial compromise. Ischemia and gangrene of infection and the tissues involved84 (Box 12-9). The his-
result. In the majority of cases this results in abscess forma- tory is usually minor trauma or surgery in a vulnerable
tion. However, rupture may also result in diffuse peritonitis, patient.85 Often-unexplained pain that increases rapidly over
which represents a surgical emergency. time is the first manifestation. The patient may develop early
Patients present with lower abdominal pain, guarding, leu- dramatic symptoms and signs of sepsis (confusion, delirium,
kocytosis, and low-grade fever. The diagnosis is confirmed by tachycardia, tachypnea, hypotension, oliguria). The source
CT. If a contrast agent is given, abscesses are well defined with may not be readily apparent. Clinical findings include ery-
rim enhancement; a phlegmon does not enhance. This will also thema, edema, and induration of the tissues, occasionally
provide information regarding the feasibility of percutaneous with bullae formation. NSTIs share the features of extensive
drainage. Antimicrobial therapy is targeted at the polymicrobial tissue destruction, thrombosis of blood vessels, abundant
nature of the abscess—a combination of gentamicin or amika- bacteria spreading along fascial planes, and relatively few
cin plus either metronidazole or clindamycin is recommended. acute inflammatory cells.
response. There may be a history of surgery, trauma, or minor

BOX 12-9 n NECROTIZING SOFT TISSUE INFECTIONS injury, for example, in a diabetic patient. Infection rapidly
Classification
spreads throughout the subcutaneous tissues and along fas-
Infections of Skin and Subcutaneous Tissue cial planes. Localized thrombosis of blood vessels may lead to
Progressive synergistic bacterial gangrene loss of perfusion and necrosis/gangrene. Crepitus may result
Chronic undermining burrowing ulcer (Meleney's ulcer) from gas production in the tissues. The natural progression of
Idiopathic scrotal gangrene (Fournier's gangrene) necrotizing fasciitis is severe sepsis, septic shock, multiorgan
Infections Involving Subcutaneous Tissue and Fascia failure, and death. Early aggressive skin debridement is imper-
Hemolytic streptococcal gangrene ative, often with the patient in extremis. In addition to source
Necrotizing fasciitis
control, empiric antibiotics must be administered, principally
Gram-negative synergistic necrotizing cellulitis
Clostridial cellulitis
clindamycin, aminoglycosides, or third-generation cephalo-
sporins and metronidazole. Supportive care usually involves
Infections Involving Muscle
Clostridial myonecrosis
aggressive volume resuscitation and vasopressors, which can
Streptococcal myositis usually be weaned with removal of necrotic tissue. Surgical
debridement of necrotic tissue is often extensive and usually
Risk Factors
Diabetes
involves multiple OR trips. Amputation of limbs may be nec-
Peripheral vascular disease essary. In addition, when anaerobic, gas-producing bacteria
Chronic liver disease are involved, hyperbaric O2 therapy may be indicated.
Cancer
AIDS
Collagen vascular diseases
Chronic renal failure
Anesthesiologists may be involved with patients with necro-
Recent surgery tizing fasciitis either during the initial presentation, where
Penetrating trauma fulminant sepsis is the major manifestation, or during subse-
Systemic sepsis (the “second hit”) quent visits to the OR for tissue debridement. Surgery should
Corticosteroids
not be delayed by the anesthesiologist, because resuscitation
Advanced age
Malnutrition
and hemodynamic stabilization is usually impossible without
Alcoholism surgical debridement. The incision is made directly over the
Intravenous drug use area of skin involved or the most indurated region. The skin
Postoperative infection incision parallels the neurovascular bundles and carries down
Morbid obesity
to the fascia. The underlying muscle and fascia is inspected
Data from Kuncir EJ, Tillou A, St. Hill CR, et al: Emerg Med Clin North Am
and all necrotic tissue excised in all directions until healthy
21:1075-1087, 2003. tissue is reached. Debridement is adequate when a finger can
no longer easily separate the subcutaneous fat from the fascia.
The wound is left exposed, without skin flaps, for subsequent
assessment.
Necrotizing Fasciitis
The patient may be intolerant of the vasodilatory effects of
Necrotizing fasciitis is a deep-seated infection of the subcu- volatile agents and may require massive volume resuscitation
taneous tissue that results in progressive destruction of fascia plus vasopressor therapy, as described earlier. Importantly, as
and fat, although it may spare the skin. It usually involves the debridement progresses, cytokine release is reduced, and the
extremities, abdominal wall, or perineum. Much confusion patient usually becomes hemodynamically more stable. In the
surrounds nomenclature; for example, necrotizing infection absence of a volatile agent, ketamine is a suitable alternative
of the perineum is often called Fournier's gangrene. Other to maintain hypnosis during surgery, along with fentanyl or
names used include progressive bacterial synergistic gangrene hydromorphone for analgesia.
(PBSG) and Meleney's ulcer. It is simpler to classify necrotiz-
ing fasciitis according to the type of microbes involved. There
are two types of necrotizing fasciitis, as follows:
Clostridial Myonecrosis (Gas Gangrene)
Type 1: Polymicrobial form is an infection with mixed Clostridial species are obligate anaerobes that infect devital-
bowel organisms. Microbes may be aerobic (e.g., staphylo- ized tissue. Three types of clostridial infections have been
cocci, group A streptococci, Escherichia coli) or anaerobic identified: simple wound contamination or colonization,
(e.g., Clostridium, Bacteroides, Peptostreptococcus). anaerobic cellulitis, and clostridial gas gangrene. Myonecrosis
Type 2: Monomicrobial form is caused by group A strepto- is caused by Clostridium perfringens, an exotoxin-secreting
cocci, which produces a number of cellular components and and spore-forming bacterium found in the soil. This infection
exotoxins that lead to the destruction of tissue and spread of is often called “gas gangrene” because of the palpable crepitus
infection. caused by liberation of gas. Muscle is remarkably resistant to
The patient usually presents with pain out of proportion to infection. Infection follows significant loss of barrier function,
the apparent tissue injury and malaise with significant SIRS as occurs with contamination of deep-seated wounds, as in
trauma, knife wounds, septic abortions, immunocompromise, ANESTHETIC CONSIDERATIONS

and surgery. The introduction of the organism is comple- Urgent airway control is usually advised in the Ludwig's angina
mented by the presence of an anaerobic environment with a patient. Traditionally, tracheostomy has been performed
low oxidation-reduction potential and acid pH, which is ideal under local anesthesia but this may be technically difficult
for the growth of clostridial organisms. Another form of myo- because of extensive edema and inflammation, as well as inev-
necrosis, spontaneous gangrenous myositis, is caused by group itable infection and inflammation of the stoma site. Incision
A streptococci. and drainage is indicated if suppurative infection develops,
The toxic effects of clostridial organisms result from the or if fluctuance, crepitus, and soft tissue gas mandate surgical
release of toxins (12 in number). Alpha toxin is lecithinase intervention. CT can be used to help identify these suppura-
(phospholipase C), which degrades lecithin in cell membranes tive complications. Surgical drainage has been required in 50%
causing lysis. In addition, C. perfringens produces a variety of of patients, performed under local anesthesia or cervical block.86
hydrolytic enzymes (proteases, DNases, hyaluronidase, colla- Any suggestion of airway compromise demands the airway be
genases) that liquefy tissue, thus promoting spread of infec- secured. From 40% to 60% of patients with Ludwig's angina
tion. The patient presents with sudden onset of malaise and require tracheostomy or endotracheal intubation.87
painful swelling of the affected area. There may be a smelly Conventional IV induction and neuromuscular blockade is
purulent discharge and discoloration of skin. Gram stain of unacceptable; spontaneous ventilation should be maintained.
infected material reveals gram-positive rods. Exotoxins and An awake fiberoptic “look see” approach appears optimal. The
proteolytics released by the organism cause fermentation of airway is visualized after appropriate topical preparation. If
tissue carbohydrates and accumulation of gas bubbles in the the glottis and supraglottic area are patent, the anesthesiolo-
subcutaneous space, resulting in crepitus. gist proceeds to intubation. If not, awake tracheostomy is per-
Treatment of patients with clostridial myonecrosis is extensive formed. An alternative approach is inhalational induction of
surgical debridement of all infected tissue and IV antibiotics: anesthesia with sevoflurane; the major drawback is difficulty
benzylpenicillin, 2.4 g every 4 hours, plus clindamycin, 500 mg in maintaining airway patency (from edematous neck tissue),
every 6 hours. Again, hyperbaric O2 may have a role, but this obstruction, and hypoxemia. Cricothyroidotomy is extremely
has not been proved by prospective clinical trials. Anesthesia difficult in this situation. Penicillin with a β-lactamase inhibi-
care of the patient with myonecrosis is similar to that of the tor is the agent of choice for patients with Ludwig's angina:
patient with necrotizing fasciitis. ampicillin/sulbactam or piperacillin-tazobactam, with
clindamycin or metronidazole.
Soft Tissue Infections of Head and Neck
Epiglottitis
Soft tissue infections of the neck are of particular importance
to anesthesiologists because of the potential for significant airway Acute epiglottitis is inflammation of the epiglottis secondary
obstruction. The most common sources of life-threatening to bacterial infection, usually Haemophilus influenzae type B.
infections of the head and neck are the teeth and tonsils. The Infection results in significant edema and airway compromise,
majority are polymicrobial, usually oral flora (Bacteroides, which may be life threatening. Inflammation can also occur in
Peptostreptococcus, Actinomyces, Fusobacterium, and micro- the arytenoid cartilage, false vocal cords, or pharyngeal wall,
aerophilic streptococci) that become virulent. Infection resulting in acute supraglottitis. The mean age at presentation
spreads along facial planes to distant sites. ranges from 42 to 50 years, with male predominance and an
The most well-known neck space infection was described association with cigarette smoking.
by Wilhelm von Ludwig in 1836 and is known as Ludwig's Patients typically present after approximately 2 days of
angina. This severe cellulitis of the mouth floor tissue, with symptoms and sore throat and pain in swallowing (Table 12-5).
involvement of the submandibular and sublingual spaces, is Thickening of the epiglottis is the classic radiographic finding
marked by edema of the neck and tongue, cellulitis, and grad- and is present on 73% to 86% of lateral neck radiographs.88
ual airway compromise. The source of infection is almost Other radiographic findings strongly suggestive of acute epi-
always the second and third mandibular molars. If the infec- glottitis and supraglottitis include enlargement of aryepiglottic
tion is allowed to continue, there may be local lymphadenitis, folds, arytenoid enlargement, prevertebral soft tissue swelling,
systemic sepsis, and extension of the disease to involve deep and an emphysematous epiglottitis.
cervical fascia with a cellulitis that extends from the clavicle to
the superficial tissues of the face. The disease is almost always ANESTHETIC CONSIDERATIONS
polymicrobial, including α-hemolytic streptococci and anaer- Although generally avoided in children, laryngoscopy appears
obes such as Peptostreptococcus, Prevotella melaninogenica, to be safe in adults and can be used to evaluate patients with
and Fusobacterium nucleatum. Most patients with Ludwig's a clinical suspicion of acute epiglottitis but with a negative
angina are young, healthy adults. Patients usually present with neck radiograph. A “cherry red” epiglottitis is the classic find-
mouth pain, dysphagia, drooling, and stiff neck. The patient ing, and most patients have supraglottic inflammation and
often maintains the neck in an extended position and may edema. The need to sit upright, bacteremia, and a rapid onset
have a muffled or “hot potato” voice. of serious symptoms have been associated with the need for
during the battle of Stalingrad. From 1975 to 1983, Soviet-

TABLE 12-5 n Acute Epiglottitis: Signs, Symptoms, and
Frequency (Adults)
backed forces in Laos, Cambodia, and Afghanistan allegedly
used trichothecene mycotoxins (T-2 toxins), called “yellow
Sign/Symptom % Frequency rain.” In 1979 an outbreak of pulmonary anthrax occurred in
Yekaterinburg in the Soviet Union as a result of an accidental
Muffled voice 54-79 release of anthrax in aerosol form from a bioweapons facil-
Pharyngitis 57-73 ity. Iraq is suspected to have used bombs and scud warheads
filled with Botulinum toxin, anthrax, and aflatoxin against
Fever 54-70
Kurds in 1991.
Tenderness of anterior neck 79 In the 21st century, interest in biologic weapons has
Dyspnea 29-37
increased with the rise of terror networks and the produc-
tion of such weapons by “rogue states.” Successful attacks have
Drooling 22-39 included sarin in Japan (1994-1995) and salmonella (1984)
Stridor 12-27 and anthrax (2001) in the United States. In 2004, Viktor
Yushchenko, the opposition candidate of the presidency of
Data from Bansal A, Miskoff J, Lis RJ: Crit Care Clin 19:55-72, 2003.
Ukraine, was poisoned with dioxin, leading to severe facial
disfiguration, abdominal pain, and extensive GI ulceration.
In the event of a terrorist biologic attack, the anesthesiolo-
airway intervention: intubation or tracheostomy (5%-20% of gist will be intensely involved with triage and resuscitation of
patients). The patient should continue to breathe spontane- the injured patient. A familiarity with potential bioweapons
ously while the airway is secured. Therefore, awake fiberoptic is necessary (Table 12-6). An ideal biologic weapon is robust,
intubation or inhalational induction with sevoflurane should highly infectious, and highly potent and can be delivered as an
be performed. Care should be taken with topicalization to aerosol. A vaccine should be available. In addition, the weapon
prevent precipitation of acute airway obstruction. Intubation is one that should be able to be manufactured quickly and eas-
should be performed by the most skilled anesthesiologist and ily. In general, the primary difficulty is not the production of
a full airway team, including an otolaryngologist, with an open the biologic agent but rather the development of an effective
tracheostomy pack, should be present. delivery system to infect the intended target (Table 12-7).
The antimicrobial of choice is a second- or third-generation
cephalosporin with activity against H. influenzae. Additional Anthrax
therapy, such as racemic epinephrine or dexamethasone, is of
undetermined utility.89 Bacillus anthracis is a gram-positive rod that primarily infects
animals, particularly herbivores. Humans can contract the
disease from infected animals or animal products. In most
countries, however, domestic animal vaccinations have all
INFECTIOUS AGENTS AS BIOLOGIC
but eliminated the disease. In an unfavorable environment,
WEAPONS
anthrax endospores are formed that are highly resistant to dis-
Biologic agents have been weaponized to wage war and pro- infectants, temperature, and alkali. These spores have been
mote terror throughout history. In the 6th century bc the manufactured by a number of countries as biologic weapons.
Assyrians poisoned enemy wells with rye ergot. In 1347 ad the In fall 2001, letters with spores were sent from Trenton, NJ, to
Tartar army catapulted the bodies of bubonic plague victims five media offices and two U.S. senators; 22 individuals devel-
over the walls of the city of Kaffa in the Crimea, leading to oped anthrax infections, mainly cutaneous, and five died of
a plague epidemic. In 1495 the Spanish infected French wine inhalation anthrax from cross-contamination of the mail.
with blood from leprosy patients. In the mid-1600s a Polish Infection occurs with the introduction of the spore through
military general reportedly put saliva from rabid dogs into a break in the skin, causing cutaneous anthrax, or through
hollow artillery spheres for use against his enemies. Smallpox the mucosa of the GI tract. To cause pulmonary infection,
was used as a biologic weapon in South America in the 15th weapons-grade anthrax spores must be used. The reason for
century and during the French-Indian and Civil wars in the this is that anthrax must be delivered as single spores, which
United States. In each case, clothes from smallpox victims can work their way down into small airways, where they are
were given to natives or prisoners. phagocytosed and transported to the hilar lymph nodes, where
In World War I, horses, mules, and cattle were deliberately bacteria proliferate. To deliver single spores, anthrax must be
infected with anthrax and glanders to infect Allied military treated, to “unclump” the spores by making them electrostati-
personnel in 1915. In World War II the Japanese military exten- cally neutral. Proliferating bacteria produce three exotoxins;
sively used aerosolized anthrax and air-dropped 150 million protective antigen binds to cell surface receptors, facilitating
plague-infected fleas over villages in China and Manchuria in entry of other the two exotoxins into the cell through a chan-
1941, resulting in several plague outbreaks. In 1942 the Soviet nel; edema factor causes cell swelling; and lethal factor has
military used weaponized tularemia on German soldiers protease activity, which causes cell lysis.
Expiratory stridor, from tracheal compression by enlarged

TABLE 12-6 n Agents of Concern for Use as Biologic
Weapons
paratracheal nodes, may accompany other respiratory symp-
toms. The diagnosis of inhalational anthrax is suspected by
Microbe or Toxin Disease circumstances (e.g., mail worker with acute respiratory fail-
ure), sepsis, and respiratory failure in a patient with a widened
HIGHEST PRIORITY (CATEGORY A) mediastinum (i.e., adenopathy) on chest radiography.90
Bacillus anthracis Anthrax Cutaneous anthrax presents as a painless, pruritic papule
on the skin up to 1 week after infection. Progression of the dis-
Variola virus Smallpox
eased lesion involves the development of one or more vesicles
Yersinia pestis Plague and edema surrounding the primary lesion, fever, and mal-
Clostridium botulinum Botulism
aise. The vesicles subsequently rupture, revealing a necrotic
ulcer and a characteristic black eschar. This dries and falls off
Francisella tularensis Tularemia after 1 week to 10 days. The most important clinical approach
Filoviruses Ebola hemorrhagic fevers, to cutaneous anthrax is to avoid surgical debridement, which
Marburg disease may be associated with bacteremia and systemic infection.91
Gastrointestinal anthrax is contracted by ingesting food
Arenaviruses Lassa fever, South American
hemorrhagic fevers contaminated with anthrax spores; 3 to 5 days after infec-
tion the patient develops fever, malaise, nausea, vomiting, and
Bunyaviruses Rift Valley fever, Congo-Crimean diarrhea, associated with abdominal pain. Ulcers may develop
hemorrhagic fevers
in the intestinal mucosa, leading to profuse bleeding, mesen-
MODERATELY HIGH PRIORITY (CATEGORY B) teric lymphadenitis, and ascites.
Coxiella burnetti Q fever
Definitive diagnosis is the identification of encapsulated
broad gram-positive bacilli on examination of skin smears,
Brucella spp. Brucellosis blood, or cerebrospinal fluid.
Burkholderia mallei Glanders Treatment of inhalational anthrax is ciprofloxacin plus
clindamycin, rifampicin, or vancomycin.92 For postexposure
Alphaviruses Viral encephalitides
chemoprophylaxis, ciprofloxacin, doxycycline, and penicil-
Ricin Ricin intoxication lin G have been recommended. Amoxicillin is recommended
for cutaneous anthrax. Information is negligible regarding
Staphylococcus aureus Staphylococcal toxin illness
enterotoxin B hospital infection control and anthrax. There is no risk of
person-to-person transmission with inhalational anthrax. If
Salmonella spp., Shigella Food-borne and water-borne discharging skin lesions are present, contact precautions are
dysenteriae; E. coli O gastroenteritis
157:H7; Vibrio cholerae,
necessary. Contaminated surfaces should be treated with spo-
Cryptosporidium parvum ricidal solutions.
CATEGORY C
Hantaviruses Viral hemorrhagic fevers The anesthesiologist may be involved with the critical care
management of the patient with inhalational anthrax—for
Flaviviruses Yellow fever
intubation and supportive care. There is no risk of person-to-
Mycobacterium tuberculosis Multidrug-resistant tuberculosis person transmission (Table 12-8).
MISCELLANEOUS
Genetically engineered vaccine-resistant and/or antimicrobial- Smallpox

resistant category
A or B agents
Smallpox is caused by the variola virus. The disease was eradi-
Human immunodeficiency virus type 1 (HIV-1) cated worldwide in 1977 but exists in two known repositories,
Adenoviruses at the CDC in Atlanta and at the Institute of Viral Preparations
Influenza in Moscow. It is feared that stockpiles of this virus are in the
Rotaviruses hands of others and may be used as a biological weapon.
Hybrid pathogens (e.g., smallpox-plague, smallpox-Ebola)
Smallpox is spread from person to person without animal
vector. The virus is inhaled into the respiratory tract and makes
its way into the blood, to all body organs, through pulmonary
Anthrax is a biphasic disease. Inhalational anthrax manifests, lymph nodes. During the incubation period of 1 to 2 weeks,
following an incubation period of 3 to 6 days, as nonspecific the virus replicates in the reticuloendothelial system, followed
symptoms of pyrexia, malaise, myalgia, and dry cough. The by a prodromal syndrome (i.e., fever, backache, headaches,
second stage begins 2 days thereafter, with fulminant sepsis malaise, rigors, delirium, nausea and vomiting), after which a
associated with pyrexia, dyspnea, and vasoplegic shock. rash appears. At this point and for several weeks, the disease is
TABLE 12-7 n Differential Diagnosis for Inhalational Anthrax
Diagnosis Distinguishing Features
Pneumonic plague (Yersinia pestis) Hemoptysis relatively common with pneumonic plague but rare with
inhalational anthrax
Tularemia (Francisella tularensis) Clinical course usually indolent, lasting weeks; less likely to be fulminant
Community-acquired bacterial pneumonia Rarely as fulminant as inhalational anthrax

Mycoplasmal pneumonia (Mycoplasma pneumoniae) Legionellosis and many other bacterial agents (S. aureus, S. pneumoniae,
Pneumonia caused by Chlamydia pneumoniae H. influenzae, K. pneumoniae, M. catarrhalis) usually occur in persons with
Legionnaires’ disease (Legionella pneumophila or other underlying pulmonary or with other disease or in elderly patients.
Legionella spp.) Bird exposure occurs with psittacosis.
Psittacosis (Chlamydia psittaci) Gram stain of sputum may be useful.
Other bacterial agents (e.g., Staphylococcus aureus, Community outbreaks caused by other etiologic agents not likely to be as
Streptococcus pneumoniae, Haemophilus influenzae, explosive as pneumonic plague outbreak.
Klebsiella pneumoniae, Moraxella catarrhalis) Outbreaks of S. pneumoniae usually institutional.
Community outbreaks of legionnaires’ disease often involve exposure to
cooling towers.
Viral pneumonia Influenza generally seasonal (October-March in United States) or involves

Influenza history of recent cruise ship travel or travel to tropics
Hantavirus Exposure to mice droppings, feces with hantavirus
Respiratory syncytial virus (RSV) RSV usually occurs in children (although may be cause of pneumonia in
Cytomegalovirus (CMV) elderly); tends to be seasonal (winter/spring)
CMV usually occurs in immunocompromised patients
Q fever (Coxiella burnetii) Exposure to infected parturient cats, cattle, sheep, goats
Severe pneumonia not prominent feature
communicable. The most prominent manifestation of small-

TABLE 12-8 n Infection Control Issues for Select
Bioweapons
pox is its characteristic centrifugal rash, which appears on the
extremities first and then the trunk. This initially appears as a
Incubation Person to Infection widespread macular eruption, with associated skin edema. An
Disease Period Person Precautions extensive pustular eruption follows; after 14 days these lesions
rupture, necrose, and leave prominent pockmark scars.
Inhalational 2-43 days No Standard
anthrax
Death from smallpox results from septic shock and multi-
organ dysfunction syndrome.
Botulism 12-72 No Standard The rash of smallpox must be differentiated from that of
hours
chickenpox (varicella zoster). In varicella infection there is a
Primary 1-6 days Yes Droplet shorter prodrome, lesions appear predominantly on the trunk
pneumonic with facial sparing, and the rash is different. The lesions in
plague chickenpox are soft and do not scar and are at different stages
Smallpox 7-17 days Yes Contact and of development; in smallpox the lesions progress in synchrony.
airborne There is no known treatment for smallpox. Patients should
Tularemia 1-14 days No Standard
be managed supportively, with full isolation and barrier pre-
cautions, in a negative-pressure room. Meticulous contact
Viral 2-21 days Yes Contact and tracing is imperative. A vaccine is available, based on live vac-
hemorrhagic airborne
cinia virus. Routine vaccination of children was abandoned
fevers
in the 1960s because of the high incidence of vaccine-related
Viral 2-14 days No Standard complications. If the affected patient is in the early phase of
encephalitides the disease, he or she should be vaccinated.93
Q fever 2-14 days No Standard
Brucellosis 5-60 days No Standard Tularemia

Glanders 10-14 days No Standard Tularemia is an acute, febrile, granulomatous, infectious zoo-
Data from Cohen J, Powderly W: Infectious diseases, ed 2, St Louis, 2004, nosis caused by the aerobic gram-negative pleomorphic bacil-
Mosby, p 101. lus Francisella tularensis. Its name relates to the description
Plague
in 1911 of a plaguelike illness in ground squirrels in Tulare
County, California. The disease commonly infects rab- Yersinia pestis is a gram-negative bacillus that causes plague.
bits and rodents, including mice, groundhogs, squirrels, and As with B. anthracis, Y. pestis primarily infects animals, par-
sheep. There are 150 to 300 tularemia cases reported in the ticularly rodents. Plague is spread to humans through the
United States annually, with a majority of those from Alaska, bite of infected rodent fleas. In this form, known as bubonic
Arkansas, Illinois, Oklahoma, Missouri, Tennessee, Texas, plague, approximately 10 cases per year are reported in the
Utah, and Virginia. United States (Table 12-9). Numerous epidemics of bubonic
Francisella tularensis was weaponized by the United States plague have swept the world in the last 1000 years. One third
(until the 1960s) and the former Soviet Union (until the of the European population succumbed in the 14th century
1990s). Other countries have been or are suspected to have to plague, commonly known as the Black Death. Plague was
weaponized this bacterium. This organism can be produced used as a biologic weapon during World War II when infected
in wet or dry form and is introduced by aerosolization or con- fleas were released. The United States and the Soviet Union
tamination of food and water sources. developed an aerosolized version during the Cold War and
Many routes of human exposure to the tularemia organism still maintain stockpiles.
are known to exist. The common routes include direct contact The bubonic plague typically presents 2 to 8 days after
with blood or tissue while handling infected animals, the bite exposure, with sudden onset of fever, chills, weakness, and
of arthropods (e.g., ticks, mosquitoes), and handling or eating acutely swollen lymph nodes, termed buboes, usually in the
undercooked small game animals (e.g., rabbit). Less common groin, axillae, or cervical regions. Buboes are egg shaped,
means of transmission are drinking or swimming in contami- 1 to 10 cm in length, and often exquisitely tender. The patient
nated water, from animal scratches or bites of animals contam- develops acute severe sepsis, progressing over 2 days to mul-
inated from eating infected animals, and inhaling dust from tiorgan failure, characterized by microvascular thrombosis.
contaminated soil or handling contaminated pelts or paws of Peripheral tissue necrosis is seen, similar to that in meningo-
animals. Tularemia is not directly transmitted from person coccemia (i.e., necrotitis fulminans). Person-to-person spread
to person. Laboratory workers exposed to the bacteria are at of bubonic plague does not occur.
higher risk. The clinical form of tularemia reflects the mode When Yersinia is spread by aerosolized droplets, the sub-
of transmission. Some classify the disease as typhoidal (pre- sequent disease is known as pneumonic plague. It is highly
dominance of systemic symptoms), pneumonic (pulmonary contagious. This would be the route of attack by a terrorist or
f indings), or ulceroglandular (regional symptoms). military group.
Weaponized tularemia is most likely acquired by inhala- After exposure there is an incubation period of 2 to 4
tion or consumption of contaminated food. The most com- days, with sudden onset of fever, rigors, and muscular pain.
mon form of tularemia is usually acquired through the bite of Within 24 hours the patient develops hemoptysis, resulting
blood-sucking arthropods or from contact with infected ani- from the production of coagulase and fibrolysin by the bac-
mals. Inhalation of the organism will result in sudden chills, terium, leading to tissue necrosis. The patient may complain
fever, weight loss, abdominal pain, fatigue, and headaches. of abdominal pain, chest pain, nausea, and vomiting. The dis-
Inhalation of F. tularensis may result in tularemic pneumonia. ease progresses to ARDS, with severe hypoxemia, and to sep-
Patchy, poorly defined infiltrates appear in one or more lobes tic shock. Without appropriate antibiotics within 18 hours,
on chest radiography. Bilateral hilar adenopathy may be pres- the patient will die.
ent. Bloody pleural effusions are characteristic and demon- The diagnosis of plague may be difficult in isolated
strate a mononuclear cellular response. This may progress to cases; the symptoms and signs may be indistinguishable
acute respiratory distress syndrome (ARDS). Ingestion of the from other forms of acute severe sepsis (e.g., meningococ-
organism in contaminated food or water may result in pain- cemia, pneumococcal pneumonia). A history of hemoptysis
ful pharyngitis, abdominal pain, diarrhea, and vomiting. As on presentation should alert the clinician to the possibility
many as 20% of patients have a rash that may begin as blotchy, of plague. Moreover, if a biologic attack is carried out with
macular, or maculopapular and progress to pustular lesions. Yersinia, multiple patients will begin presenting to the emer-
Erythema nodosum and erythema multiforme rarely occur. gency department with symptoms of rapidly progressing
Involvement of other systems may lead to meningitis, pericar- pneumonia and hemoptysis. Sputum Gram stain reveals
ditis, peritonitis, and osteomyelitis. gram-negative rods. Blood cultures are usually positive, but
Symptoms generally appear between 1 and 14 days, but the diagnosis is usually retrospective because, by the time the
usually within 3 to 5 days. Diagnosis is exceedingly difficult cultures emerge, without treatment the patient will be dead.
to make. It is usually based on serology (the tularemia tube The treatment of choice for plague is streptomycin, gen-
agglutination test). However, there is a 12- to 14-day delay in tamicin, doxycycline, or ciprofloxacin. These agents are not
receiving the result of this test. Treatment is with gentamicin routinely used or recommended for community-acquired
or streptomycin. Otherwise, therapy is supportive. Mortality pneumonia. If the patient has symptoms or signs of menin-
in untreated patients is 5% to 15% and in treated patients, gitis, chloramphenicol should be used. Strict isolation with
1% to 3%. droplet precautions should be enforced for 48 hours.
TABLE 12-9 n Select Bioweaponized Diseases: Clinical Presentation and Differential Diagnosis
Clinical Presentation Disease Differential Diagnosis
Nonspecific “flulike” symptoms with nausea, Inhalation anthrax Bacterial mediastinitis, tularemia, Q fever,
emesis, cough with or without chest discomfort, psittacosis, legionnaires’ disease, influenza,
without coryza or rhinorrhea, leading to abrupt Pneumocystis jiroveci pneumonia, viral
onset of respiratory distress with or without pneumonia, ruptured aortic aneurysm,
shock, mental status changes, with chest superior vena cava syndrome, histoplasmosis,
radiographic abnormalities (wide mediastinum, coccidioidomycosis, sarcoidosis
infiltrates, pleural effusions)
Pruritic, painless papule, leading to vesicle(s), leading Cutaneous anthrax Recluse spider bite, plague, staphylococcal
to ulcer, leading to edematous black eschar with lesion, atypical Lyme disease, orf, glanders,
or without massive local edema and regional tularemia, rat-bite fever, ecthyma gangrenosum,
adenopathy and fever, evolving over 3 to 7 days rickettsialpox, atypical mycobacteria, diphtheria
Rapidly progressive respiratory illness with cough, Primary pneumonic plague Severe community-acquired bacterial or viral
fever, rigors, dyspnea, chest pain, hemoptysis, pneumonia, inhalational anthrax, inhalational
possible GI symptoms, lung consolidation with or tularemia, pulmonary infarct, pulmonary
without shock hemorrhage
Sepsis, disseminated intravascular coagulation Septicemic plague Meningococcemia; gram-negative streptococcal,

(DIC), purpura, acral gangrene pneumococcal, or staphylococcal bacteremia
with shock; overwhelming postsplenectomy
sepsis; acute leukemia; Rocky Mountain spotted
fever; hemorrhagic smallpox; hemorrhagic
varicella (in immunocompromised patients)
Fever, malaise, prostration, headache; myalgias Smallpox Varicella, drug eruption, Stevens-Johnson syndrome,
followed by development of synchronous, measles, secondary syphilis, erythema
progressive papular leading to vesicular and multiforme, severe acne, meningococcemia,
then pustular rash on face, mucous membranes monkeypox (with African travel history),
(extremities more than trunk); rash may become generalized vaccinia, insect bites, coxsackievirus
generalized, with hemorrhagic component and infection, vaccine reaction
systemic toxicity
Nonspecific flulike, febrile illness with Inhalational tularemia Inhalational anthrax, pneumonic plague, influenza,
pleuropneumonitis, bronchiolitis with or without mycoplasmal pneumonia, legionnaires’ disease,
hilar lymphadenopathy; variable progression to Q fever, bacterial pneumonia
respiratory failure
Acute onset of afebrile, symmetric, descending Botulism Myasthenia gravis, brainstem cerebrovascular
flaccid paralysis that begins in bulbar muscles; accident, polio, Guillain-Barré syndrome variant,
dilated pupils, diplopia or blurred vision; tick paralysis, chemical intoxication
dysphagia, dysarthria, ptosis; dry mucous
membranes, leading to airway obstruction with
respiratory muscle paralysis; clear sensorium
and absence of sensory changes
Acute-onset fevers, malaise, prostration, myalgias, Viral hemorrhagic fever Malaria, meningococcemia, leptospirosis, rickettsial
headache, GI symptoms, mucosal hemorrhage, infection, typhoid fever, borreliosis, fulminant
altered vascular permeability, DIC; hypotension hepatitis, hemorrhagic smallpox, acute leukemia,
leading to shock, with or without hepatitis and TTP, hemolytic uremic syndrome, systemic lupus
neurologic findings erythematosus
GI, Gastrointestinal; TTP, thrombotic thrombocytopenic purpura.
ANESTHESTIC CONSIDERATIONS given chemoprophylaxis with doxycycline for at least 7 days.

The anesthesiologist may be involved with airway manage- Patients are managed supportively in the ICU. There are
ment and initiation of mechanical ventilation. Extreme pre- no indications for surgery in the early stages. In particular,
cautions should be taken to avoid contact with patients’ buboes should not be incised or debrided because of the risk
secretions. The anesthesiologist should wear a gown, mask, of spreading the infection. Peripheral necrosis requires surgi-
and eye protection because of the potential for contagion. All cal debridement or amputation, but this is delayed until the
health care workers involved in face-to-face contact must be patient is in the recovery stage of the disease.
BIOLOGIC TOXINS Inhalation of large quantities of nerve agent leads to acute

respiratory distress, loss of consciousness, flaccid paralysis,
Sarin convulsions, and coma. Physical signs include dyspnea, tachy-
Sarin (GB) is an organophosphate nerve agent first devel- pnea, and wheezing. There may be tachycardia or bradycardia,
oped by Nazi German scientists in 1938. A number of simi- reduced levels of consciousness, weakness, muscle fascicula-
lar agents exist, such as tabun (GA), soman (GD), cyclosarin tion, flaccid paresis. Examination of the eyes reveals miosis
(GF), and VX toxin. VX is the most potent known biotoxin. and lacrimation.
Sarin is one of the few biologic weapons known to have been If a sarin gas attack is suspected, it is imperative that
used in military and terrorist attacks. Sarin was probably used health care providers take extraordinary measures. Personal
by the Iraqi military against Kurdish villagers in 1988 as well protective equipment (PPE) includes protective suits, heavy
as during the Iraq-Iran War.94 A Japanese terrorist cult known butyl rubber gloves, and self-contained breathing apparatus.
as Aum Shinrikyo used sarin against civilians in Japan, first Aggressive decontamination of victims is required to prevent
in Matsumoto in 1994, killing eight people, then in the Tokyo further exposure to them and others. Goals of decontami-
subway system in 1995, killing 13 and injuring hundreds.95 nation are to prevent further absorption of nerve agents by
At room temperature, sarin is a volatile liquid that can be victims and to prevent the spread of nerve agents to others.
aerosolized by explosive devices. Exposure to sarin occurs by Decontamination is necessary only with topical exposure. The
one of two routes: topically/transdermally or inhaled into the skin should be washed with an alkaline solution of soap and
lungs.96 Once acquired, organophosphate nerve agents bind to water or 0.5% hypochlorite solution (made by diluting house-
and inactivate acetylcholinesterase (AChE). This leads to toxic hold bleach 1:10). This chemically neutralizes the nerve agent.
accumulation of acetylcholine at nicotinic, muscarinic, and
CNS synapses. Thus, sarin is a noncompetitive agonist at neu- ANESTHETIC CONSIDERATIONS
romuscular junctions, parasympathetic nerve terminals, and The anesthesiologist's involvement in the emergency care of
nicotinic adrenergic receptors. The result is a medley of symp- patients poisoned with organophosphates usually involves
toms97 (Table 12-10). securing the airway, commencing mechanical ventilation,
Initial symptoms and signs depend on the route of expo- and transferring the patient to the ICU. The patient should
sure and quantity of agent involved.96 Transdermal poisoning be treated with supplemental oxygen before intubation.
causes insidious symptoms—initially vasodilation, sweating, A hypnotic agent is administered to facilitate intubation.
localized muscle fasciculations, and paralysis and then gener- Succinylcholine should be avoided because it is metabolized
alized muscle weakness, paralysis, and respiratory depression. by cholinesterase and will have a prolonged duration of action.
Neuromuscular blockade is usually unnecessary. Intubation
may be made more difficult because of excessive salivation
TABLE 12-10 n Sarin or Organophosphate Poisoning and airway secretions.
Symptoms Two essential antidotes are required to treat organophos-
System Symptom(s)
phate poisoning.96 Atropine reverses the muscarinic effects
of the poison, which include bronchoconstriction, abdomi-
Respiratory Dyspnea, cough, chest tightness, nal pain, nausea, vomiting, and bradycardia. Pralidoxime acts
wheezing (bronchospasm) by disrupting covalent bonds between nerve agent and AChE
Cardiovascular* Tachycardia, hypertension before they become permanent; thus, AChE is reactivated and
skeletal muscle weakness is reversed. Convulsions are treated
Neurologic Headache, weakness, fasciculations, with benzodiazepines.97
extremity numbness, decreased level
of consciousness, vertigo, dizziness,
convulsions Ricin
Ophthalmic Eye pain, blurred vision, dim vision,
Ricin is a plant carbohydrate-binding protein (lectin) found
conjunctival injection, tearing
in high concentration in castor beans. Ricin is active orally or
Ear, nose, throat Rhinorrhea on inhalation and thus could be aerosolized or used to poi-
Gastrointestinal Nausea, vomiting, diarrhea, tenesmus, son food. Ricin has relatively low potency, although it has been
fecal incontinence used as a bioweapon, most famously in the assassination of
Georgi Markov in 1978 after skin perforation with the tip of an
Genitourinary Urinary incontinence
umbrella. Ricin and castor bean extraction equipment found
Dermal Sweating during a police raid of a UK apartment and in a U.S. postal
Psychological Agitation
facility suggests interest by terrorist organizations.
Ricin is composed of two hemagglutinins and two tox-
General Fatigue ins. The toxins, RCL III and RCL IV, are dimers of approxi-
Data from Lee EC: JAMA 290:659-662, 2003. mately 66,000 daltons. The toxins have an A and a B chain,
*Adrenal medullary stimulation. which are polypeptides and joined by a disulfide bond. The
B chain binds to cell surface glycoproteins and affects entry Following infection, the neurotoxin is absorbed through
into the cell by an unknown mechanism. The A chain acts the intestinal mucosa and is widely distributed throughout the
on the 60 S ribosomal subunit and prevents the binding of body. Initial presentation includes GI problems that rapidly
elongation factor-2. This inhibits protein synthesis and leads progress to cranial nerve abnormalities (e.g., diplopia, dys-
to cell death. phagia, dysarthria), particularly bulbar deficits. A progressive,
After inhalation exposure there is an incubation period of bilateral, descending motor neuron flaccid paralysis ensues,
4 to 8 hours, followed by fever, cough, dyspnea, nausea, and followed by respiratory failure and death. The toxin combines
the development of ARDS. By the oral route there is necrosis irreversibly with peripheral cholinergic synapses, preventing
of the GI tract and significant bleeding. In parenteral expo- acetylcholine release98 and leading to flaccid paralysis resem-
sure there is induration, erythema, and gradual development bling that seen with neuromuscular blockers. There are no
of systemic symptoms. antiadrenergic effects. Blockade of neurotransmitter release
Mortality and morbidity depend on the delivery route and at the terminal is permanent, and recovery only occurs when
amount of ricin exposure. Therapy is supportive. The airway is the axon sprouts a new terminal to replace the toxin-damaged
secured, and ventilation is ensured. Decontamination for ricin one. Mortality is less than 5% if the infection is treated but
exposure is similar to that for sarin infection. approaches 60% if untreated (Table 12-11).
Botulinum
Treatment of botulism involves immediate administration of
Botulism is caused by the toxin of Clostridium botulinum, an antitoxin, respiratory monitoring, and mechanical ventilation.
aerobic, spore-forming bacterium. The bacterium occurs nat- Once forced vital capacity falls below 30% of predicted value,
urally in soil. Botulism is a neuroparalytic disease. Although intubation is necessary. No specific interventions are required
manufactured as a bioweapon, botulinum toxin has never for intubation. The administration of neuromuscular blockers
been used as such. The most likely bioterrorism dissemination is unnecessary. Patients with botulism may require mechani-
scenarios include contamination of food and aerosolization. cal ventilation for up to 6 weeks. Full recovery may take 1 year.
TABLE 12-11 n Differential Diagnosis of Botulism
Condition Features that Distinguish Each Condition from Botulism
Guillain-Barré syndrome (GBS) Usually an ascending paralysis, although Miller-Fisher variant may be descending with pronounced
(particularly Miller-Fisher cranial nerve involvement
variant) Abnormal CSF protein 1 to 6 weeks after illness onset, although may be normal early in clinical course
Paresthesias typically occur (often stocking/glove pattern)
EMG shows abnormal nerve conduction velocity; facilitation with repetitive nerve stimulation does not
occur (as with botulism)
History of antecedent diarrheal illness (suggestive of Campylobacter infection)
Myasthenia gravis Dramatic improvement with edrophonium chloride (although some botulism patients may exhibit
partial improvement following administration of edrophonium chloride)
EMG shows decrease in muscle action potentials with repetitive nerve stimulation
Tick paralysis Ascending paralysis; paresthesias common

Careful examination reveals presence of tick attached to skin
Recovery occurs within 24 hours after tick removal
EMG shows abnormal nerve conduction velocity and unresponsiveness to repetitive stimulation
Usually does not involve cranial nerves
Lambert-Eaton syndrome Typically associated with carcinoma (often oat cell carcinoma of lung)
Although EMG findings are similar to those in botulism, repetitive nerve stimulation shows much
greater augmentation of muscle action potentials, particularly at 20 to 50 Hz
Stroke or CNS mass lesion Paralysis usually asymmetric

Brain imaging (CT or MRI) usually abnormal
Sensory deficits common
Altered mental status may be present
Poliomyelitis Febrile illness present

CSF shows pleocytosis and increased protein
Altered mental state may be present
Paralysis often asymmetric
(Continued)
TABLE 12-11 n Differential Diagnosis of Botulism—Cont'd
Condition Features that Distinguish Each Condition from Botulism
Paralytic shellfish poisoning or History of shellfish (i.e., clams, mussels) or puffer fish ingestion within several hours before symptom
ingestion of puffer fish onset
Paresthesias of mouth, face, lips, and extremities occur
Belladonna toxicity History of recent exposure to belladonna-like alkaloids

Fever: tachycardia
Altered mental status
Aminoglycoside toxicity History of recent exposure to aminoglycoside antibiotics

More likely to occur in patient with renal insufficiency
Most often seen with neomycin administration
Most frequently associated with other neuromuscular blockers (e.g., succinylcholine, paralytic agents)
Other toxicities History of exposure to toxic agents

(hypermagnesemia, Carbon monoxide toxicity: Altered mental status may occur; cherry-colored skin
organophosphates, nerve gas, Hypermagnesemia: History of cathartic or antacid use may be present, elevated serum magnesium
carbon monoxide) level
Organophosphate toxicity: Fever, excessive salivation, altered mental status, paresthesias, miosis
Other conditions CNS infections (particularly brainstem infections)

Inflammatory myopathy
Hypothyroidism
Diabetic neuropathy
Viral infections
Streptococcal pharyngitis (pharyngeal erythema and sore throat can occur in botulism as a result of
dryness caused by parasympathetic cholinergic blockade)
Data from Infections Disease Society of North America. www.cidrap.umn.edu/cidrap/content/bt/botulism/biofacts/botulismfactsheet.html.

CSF, Cerebrospinal fluid; EMG, electromyogram; CT, computed tomography; MRI, magnetic resonance imaging; CNS, central nervous system.
REFERENCES 14. Quayle JM, Nelson MT, Standen NB: ATP-sensitive and inwardly recti-
1. Gerberding JL: Management of occupational exposures to blood-borne fying potassium channels in smooth muscle, Physiol Rev 77:1165–1232,
viruses, N Engl J Med 332:444–451, 1995. 1997.
2. Braun BI, Darcy L, Divi C, et al: Hospital bioterrorism preparedness link- 15. Landry DW, Levin HR, Gallant EM, et al: Vasopressin deficiency contrib-
ages with the community: improvements over time, Am J Infect Control utes to the vasodilation of septic shock, Circulation 95:1122–1125, 1997.
32:317–326, 2004. 16. Kumar A, Haery C, Parrillo JE: Myocardial dysfunction in septic shock,
3. Bone RC, Balk RA, Cerra FB, et al: Definitions for sepsis and organ failure Crit Care Clin 16:251–287, 2000.
and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM 17. Ince C, Sinaasappel M: Microcirculatory oxygenation and shunting in
Consensus Conference Committee, American College of Chest Physicians sepsis and shock, Crit Care Med 27:1369–1377, 1999.
and Society of Critical Care Medicine, Chest 101:1644–1655, 1992. 18. Hinds C, Watson D: Distributive shock, microcirculatory changes. In
4. Bone RC: Sir Isaac Newton, sepsis, SIRS, and CARS, Crit Care Med Intensive care, ed 2, Philadelphia, 1996, Saunders, pp 73–74.
24:1125–1128, 1996. 19. Schrier RW, Wang W: Acute renal failure and sepsis, N Engl J Med
5. Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ 351:159–169, 2004.
ATS/SIS International Sepsis Definitions Conference, Crit Care Med 20. Fein AM, Calalang-Colucci MG: Acute lung injury and acute respiratory
31:1250–1256, 2003. distress syndrome in sepsis and septic shock, Crit Care Clin 16:289–317,
6. Dellinger RP, Bone RC: To SIRS with love, Crit Care Med 26:178–179, 2000.
1998. 21. Dreyfuss D, Saumon G: From ventilator-induced lung injury to multiple
7. Vincent JL: Dear SIRS, I'm sorry to say that I don't like you, Crit Care Med organ dysfunction? Intensive Care Med 24:102–104, 1998.
25:372–374, 1997. 22. Ventilation with lower tidal volumes as compared with traditional tidal
8. Marshall JC: SIRS and MODS: what is their relevance to the science and volumes for acute lung injury and the acute respiratory distress syn-
practice of intensive care? Shock 14:586–589, 2000. drome. The Acute Respiratory Distress Syndrome Network, N Engl J Med
9. Rangel-Frausto MS, Pittet D, Costigan M, et al: The natural history of the 342:1301–1308, 2000.
systemic inflammatory response syndrome (SIRS): a prospective study, 23. Kim PK, Chen J, Andrejko KM, et al: Intraabdominal sepsis down-regulates
JAMA 273:117–123, 1995. transcription of sodium taurocholate cotransporter and multidrug resis-
10. Alberti C, Brun-Buisson C, Goodman SV, et al: Influence of systemic tance-associated protein in rats, Shock 14:176–181, 2000.
inflammatory response syndrome and sepsis on outcome of critically ill 24. Grinnell BW, Joyce D: Recombinant human activated protein C: a system
infected patients, Am J Respir Crit Care Med 168:77–84, 2003. modulator of vascular function for treatment of severe sepsis, Crit Care
11. Kim PK, Deutschman CS: Inflammatory responses and mediators, Surg Med 29:S53–S61, 2001.
Clin North Am 80:885–894, 2000. 25. Marshall JC, Christou NV, Meakins JL: The gastrointestinal tract: the
12. Casey LC: Immunologic response to infection and its role in septic shock, “undrained abscess” of multiple organ failure, Ann Surg 218:111–119, 1993.
Crit Care Clin 16:193–213, 2000. 26. Annane D, Bellissant E, Bollaert PE, et al: Corticosteroids for severe sep-
13. Jackson WF: Ion channels and vascular tone, Hypertension 35:
sis and septic shock: a systematic review and meta-analysis, BMJ 329:
173–178, 2000. 480, 2004.
27. Van den BG, de Zegher F, Baxter RC, et al: Neuroendocrinology of pro- 50. Meier-Hellmann A, Reinhart K, Bredle DL, et al: Epinephrine impairs
longed critical illness: effects of exogenous thyrotropin-releasing hor- splanchnic perfusion in septic shock, Crit Care Med 25:399–404, 1997.
mone and its combination with growth hormone secretagogues, J Clin 51. Reinelt H, Radermacher P, Kiefer P, et al: Impact of exogenous beta-
Endocrinol Metab 83:309–319, 1998. adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and
28. Faust SN, Heyderman RS, Levin M: Coagulation in severe sepsis: a cen- metabolic activity in septic shock, Crit Care Med 27:325–331, 1999.
tral role for thrombomodulin and activated protein C, Crit Care Med 29: 52. Malay MB, Ashton RC Jr, Landry DW, et al: Low-dose vasopressin in the
S62–S68, 2001. treatment of vasodilatory septic shock, J Trauma 47:699–703, 1999.
29. Bernard GR, Vincent JL, Laterre PF, et al: Efficacy and safety of recom- 53. Buijk SE, Bruining HA: Vasopressin deficiency contributes to the vasodi-
binant human activated protein C for severe sepsis, N Engl J Med 344: lation of septic shock, Circulation 98:187, 1998.
699–709, 2001. 54. Goldsmith SR: Vasopressin deficiency and vasodilation of septic shock,
30. Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the Circulation 97:292–293, 1998.
treatment of severe sepsis and septic shock, N Engl J Med 345:1368–1377, 55. Reid IA: Role of vasopressin deficiency in the vasodilation of septic shock,
2001. Circulation 95:1108–1110, 1997.
31. Ernest D, Belzberg AS, Dodek PM: Distribution albumin infusions in sep- 56. Tsuneyoshi I, Yamada H, Kakihana Y, et al: Hemodynamic and metabolic
tic patients of normal saline and 5, Crit Care Med 27:46–50, 1999. effects of low-dose vasopressin infusions in vasodilatory septic shock, Crit
32. Ernest D, Belzberg AS, Dodek PM: Distribution of normal saline and Care Med 29:487–493, 2001.
5% albumin infusions in cardiac surgical patients, Crit Care Med 29: 57. Hill MK, Sanders CV: Skin and soft tissue infections in critical care, Crit
2299–2302, 2001. Care Clin 14:251–262, 1998.
33. Schierhout G, Roberts I: Fluid resuscitation with colloid or crystalloid 58. Dreyfuss D, Saumon G: Ventilator-induced lung injury: lessons from
solutions in critically ill patients: a systematic review of randomised trials, experimental studies, Am J Respir Crit Care Med 157:294–323, 1998.
BMJ 316:961–964, 1998. 59. Hughes SC: HIV and anesthesia, Anesthesiol Clin North America 22:
34. Choi PT, Yip G, Quinonez LG: Crystalloids vs. colloids in fluid resuscita- 379–404, v, 2004.
tion: a systematic review, Crit Care Med 27:200–210, 1999. 60. Emparan C, Iturburu IM, Ortiz J, et al: Infective complications after
35. Moretti EW, Robertson KM, El Moalem H, et al: Intraoperative colloid abdominal surgery in patients infected with human immunodeficiency
administration reduces postoperative nausea and vomiting and improves virus: role of CD4+ lymphocytes in prognosis, World J Surg 22:778–782,
postoperative outcomes compared with crystalloid administration, 1998.
Anesth Analg 96:611–617, 2003. 6 1. Kuczkowski KM: Human immunodeficiency virus in the parturient,
36. Gan TJ, Soppitt A, Maroof M, et al: Goal-directed intraoperative fluid J Clin Anesth 15:224–233, 2003.
administration reduces length of hospital stay after major surgery, 62. Birnbach DJ, Bourlier RA, Choi R, et al: Anaesthetic management of cae-
Anesthesiology 97:820–826, 2002. sarean section in a patient with active recurrent genital herpes and AIDS-
37. Lang K, Boldt J, Suttner S, et al: Colloids versus crystalloids and tissue related dementia, Br J Anaesth 75:639–641, 1995.
oxygen tension in patients undergoing major abdominal surgery, Anesth 63. Avidan MS, Groves P, Blott M, et al: Low complication rate associated
Analg 93:405–409, 2001. with cesarean section under spinal anesthesia for HIV-1–infected women
38. Mythen MG, Webb AR: Perioperative plasma volume expansion reduces on antiretroviral therapy, Anesthesiology 97:320–324, 2002.
the incidence of gut mucosal hypoperfusion during cardiac surgery, Arch 64. Tyler DS, Shaunak S, Bartlett JA, et al: HIV-1–associated thrombocytope-
Surg 130:423–429, 1995. nia: The role of splenectomy, Ann Surg 211:211–217, 1990.
39. Sinclair S, James S, Singer M: Intraoperative intravascular volume optimi- 65. Bova R, Meagher A: Appendicitis in HIV-positive patients, Aust N Z J
sation and length of hospital stay after repair of proximal femoral fracture: Surg 68:337–339, 1998.
randomised controlled trial, BMJ 315:909–912, 1997. 66. Bonacini M: Hepatobiliary complications in patients with human immu-
40. Finfer S, Bellomo R, Boyce N, et al: A comparison of albumin and saline nodeficiency virus infection, Am J Med 92:404–411, 1992.
for fluid resuscitation in the intensive care unit, N Engl J Med 350:2247–2256, 67. Buehrer JL, Weber DJ, Meyer AA, et al: Wound infection rates after inva-
2004. sive procedures in HIV-1 seropositive versus HIV-1 seronegative hemo-
41. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign philiacs, Ann Surg 211:492–498, 1990.
guidelines for management of severe sepsis and septic shock, Crit Care 68. International Perinatal HIV Group: The mode of delivery and the risk of
Med 32:858–873, 2004. vertical transmission of human immunodeficiency virus type 1: a meta-
42. Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treat- analysis of 15 prospective cohort studies, N Engl J Med 340:977–987, 1999.
ment of severe sepsis and septic shock, N Engl J Med 345:1368–1377, 2001. 69. European Mode of Delivery Collaboration: Elective caesarean-section
43. Marik PE, Mohedin M: The contrasting effects of dopamine and norepi- versus vaginal delivery in prevention of vertical HIV-1 transmission: a
nephrine on systemic and splanchnic oxygen utilization in hyperdynamic randomised clinical trial, Lancet 353:1035–1039, 1999.
sepsis, JAMA 272:1354–1357, 1994. 70. Kristensen MS, Sloth E, Jensen TK: Relationship between anesthetic
44. Martin C, Saux P, Eon B, et al: Septic shock: A goal-directed therapy using procedure and contact of anesthesia personnel with patient body fluids,
volume loading, dobutamine and/or norepinephrine, Acta Anaesthesiol Anesthesiology 73:619–624, 1990.
Scand 34:413–417, 1990. 71. Will RG, Ironside JW, Zeidler M, et al: A new variant of Creutzfeldt-Jakob
45. Hannemann L, Reinhart K, Grenzer O, et al: Comparison of dopamine to disease in the UK, Lancet 347:921–925, 1996.
dobutamine and norepinephrine for oxygen delivery and uptake in septic 72. Beghi E, Gandolfo C, Ferrarese C, et al: Bovine spongiform encephalopathy
shock, Crit Care Med 23:1962–1970, 1995. and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal
46. Bellomo R, Chapman M, Finfer S, et al: Low-dose dopamine in patients link between animal and human diseases, Neurol Sci 25:122–129, 2004.
with early renal dysfunction: a placebo-controlled randomised trial. 73. Wilson K, Ricketts MN: Transfusion transmission of vCJD: a crisis

Australian and New Zealand Intensive Care Society (ANZICS) Clinical avoided? Lancet 364:477–479, 2004.
Trials Group, Lancet 356:2139–2143, 2000. 74. Fichet G, Comoy E, Duval C, et al: Novel methods for disinfection of
47. Van den BG, de Zegher F, Lauwers P: Dopamine and the sick euthyroid prion-contaminated medical devices, Lancet 364:521–526, 2004.
syndrome in critical illness, Clin Endocrinol (Oxf) 41:731–737, 1994. 75. Estebe JP: Prion disease and anaesthesia, Ann Fr Anesth Reanim 16:955–963,
48. Denton R, Slater R: Just how benign is renal dopamine? Eur J Anaesthesiol 1997.
14:347–349, 1997. 76. Farling P, Smith G: Anaesthesia for patients with Creutzfeldt-Jakob dis-
49. Neviere R, Mathieu D, Chagnon JL, et al: The contrasting effects of dobu- ease: a practical guide, Anaesthesia 58:627–629, 2003.
tamine and dopamine on gastric mucosal perfusion in septic patients, Am 77. Huang CJ, Pitt HA, Lipsett PA, et al: Pyogenic hepatic abscess: changing
J Respir Crit Care Med 154:1684–1688, 1996. trends over 42 years, Ann Surg 223:600–607, 1996.
78. Krige JEJ, Beckingham IJ: ABC of diseases of liver, pancreas, and bili- 88. Neff SP, Merry AF, Anderson B: Airway management in Ludwig's angina,
ary system: liver abscesses and hydatid disease, BMJ 322:537–540, Anaesth Intensive Care 27:659–661, 1999.
2001. 89. Bansal A, Miskoff J, Lis RJ: Otolaryngologic critical care, Crit Care Clin
79. Men S, Hekimoglu B, Yucesoy C, et al: Percutaneous treatment of hepatic 19:55–72, 2003.
hydatid cysts: an alternative to surgery, AJR Am J Roentgenol 172:83–89, 90. Dixon TC, Meselson M, Guillemin J, et al: Anthrax, N Engl J Med 341:815–826,
1999. 1999.
80. Wellhoener P, Weitz G, Bechstein W, et al: Severe anaphylactic shock in a 91. Swartz MN: Recognition and management of anthrax: an update, N Engl
patient with a cystic liver lesion, Intensive Care Med 26:1578, 2000. J Med 345:1621–1626, 2001.
81. Albi A, Baudin F, Matmar M, et al: Severe hypernatremia after hypertonic 92. Centers for Disease Control, Prevention: Update: investigation of

saline irrigation of hydatid cysts, Anesth Analg 95:1806–1808, 2002. bioterrorism-related anthrax and interim guidelines for exposure man-
82. Rakic M, Vegan B, Sprung J, et al: Acute hyperosmolar coma complicat- agement and antimicrobial therapy, JAMA 286:2226–2232, 2001.
ing anesthesia for hydatid disease surgery, Anesthesiology 80:1175–1178, 93. Breman JG, Henderson DA: Diagnosis and management of smallpox,
1994. N Engl J Med 346:1300–1308, 2002.
83. Kambam JR, Dymond R, Krestow M, et al: Efficacy of histamine H1 and 94. Newmark J: The birth of nerve agent warfare: lessons from Syed Abbas
H2 receptor blockers in the anesthetic management during operation for Foroutan, Neurology 62:1590–1596, 2004.
hydatid cysts of liver and lungs, South Med J 81:1013–1015, 1988. 95. Yokoyama K, Yamada A, Mimura N: Clinical profiles of patients with
84. Kuncir EJ, Tillou A, St Hill CR, et al: Necrotizing soft-tissue infections, sarin poisoning after the Tokyo subway attack, Am J Med 100:586, 1996.
Emerg Med Clin North Am 21:1075–1087, 2003. 96. Newmark J: Therapy for nerve agent poisoning, Arch Neurol 61:649–652,
85. Headley AJ: Necrotizing soft tissue infections: A primary care review, Am 2004.
Fam Physician 68:323–328, 2003. 97. Lee EC: Clinical manifestations of sarin nerve gas exposure, JAMA

86. Mehrotra M, Mehrotra S: Decompression of Ludwig angina under cervi- 290:659–662, 2003.
cal block, Anesthesiology 97:1625–1626, 2002. 98. Arnon SS, Schechter R, Inglesby TV, et al: Botulinum toxin as a biological
87. Moreland LW, Corey J, McKenzie R: Ludwig's angina: report of a case and weapon: medical and public health management, JAMA 285:1059–1070,
review of the literature, Arch Intern Med 148:461–466, 1988. 2001.

Infectious Diseases and Biologic Weapons

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Infectious Diseases and Biologic Weapons

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C H A P T E R

n Patients with multiorgan dysfunction syndrome (MODS)

n Infection has killed more soldiers in war than gunfire.

Microbes possess specific virulence factors to overcome

BOX 12-2 n DIAGNOSTIC CRITERIA FOR SEPSIS*

General Coagulation abnormalities (INR >1.5 or aPTT >60 seconds)

Predisposition Response ultimately broken down by plasmin, which is activated by tis-

50 In the lungs, ventilation/perfusion mismatches occur, ini-

lung injury may have adverse effects at distant organs.21 This

Treating the Patient with Septic Shock Early Phase

Central venous and arterial

65 mm Hg Norepinephrine targeted

Oximetric PAC and arterial

Fluid load to CVP 16 cm H2O 1.5 mL/kg: hold

70% Hb10 g/L 70%

TABLE 12-1 n Pharmacologic Support of the Circulation in Sepsis

Agent a1 b1 b2 Heart Rate Organs Perfused

Epinepthrine ++++ ++++ ++++ ↑↑↑↑ Skin, muscle

Norepinephrine ++++ ++++ ++ ↑↑ Central organs

Dopamine ++ ++ ++++ ↑↑↑↑ Skin, muscle

Phenylephrine ++ — — — No real change

Intra-Abdominal Sepsis. The most likely infecting organ- Source Control–4 Ds

Care must be taken to maintain circulating volume and

TABLE 12-2 n Recommended Postexposure Prophylaxis for HBV Infection

Vaccination and Antibody

Unvaccinated HBIG‡ × 1 and initiate HB vaccine Initiate HB Initiate HB vaccine series

Previously vaccinated known No treatment No treatment No treatment

BOX 12-5 n AIDS-DEFINING ILLNESSES BOX 12-6 n COMPLICATIONS OF HIV MULTIORGAN

Abdominal Surgery. Patients with HIV may develop

installed near the ceiling. Clear infection control guidelines Prions

In the anesthetic setup, it is preferable to use an ICU-style

from postsurgical anastomotic leakage, viscus perforation

ANESTHETIC CONSIDERATIONS There are two surgical approaches to appendiceal abscess:

response. There may be a history of surgery, trauma, or minor

trauma, knife wounds, septic abortions, immunocompromise, ANESTHETIC CONSIDERATIONS

during the battle of Stalingrad. From 1975 to 1983, Soviet-

Expiratory stridor, from tracheal compression by enlarged

Genetically engineered vaccine-resistant and/or antimicrobial- Smallpox

TABLE 12-7 n Differential Diagnosis for Inhalational Anthrax

Diagnosis Distinguishing Features

Community-acquired bacterial pneumonia Rarely as fulminant as inhalational anthrax

Viral pneumonia Influenza generally seasonal (October-March in United States) or involves

communicable. The most prominent manifestation of small-

Brucellosis 5-60 days No Standard Tularemia

TABLE 12-9 n Select Bioweaponized Diseases: Clinical Presentation and Differential Diagnosis

Clinical Presentation Disease Differential Diagnosis

Sepsis, disseminated intravascular coagulation Septicemic plague Meningococcemia; gram-negative streptococcal,

GI, Gastrointestinal; TTP, thrombotic thrombocytopenic purpura.

ANESTHESTIC CONSIDERATIONS given chemoprophylaxis with doxycycline for at least 7 days.

BIOLOGIC TOXINS Inhalation of large quantities of nerve agent leads to acute

TABLE 12-11 n Differential Diagnosis of Botulism

Condition Features that Distinguish Each Condition from Botulism

Tick paralysis Ascending paralysis; paresthesias common

Stroke or CNS mass lesion Paralysis usually asymmetric

Poliomyelitis Febrile illness present

TABLE 12-11 n Differential Diagnosis of Botulism—Cont'd

Condition Features that Distinguish Each Condition from Botulism

Belladonna toxicity History of recent exposure to belladonna-like alkaloids

Aminoglycoside toxicity History of recent exposure to aminoglycoside antibiotics

Other toxicities History of exposure to toxic agents

Other conditions CNS infections (particularly brainstem infections)

Data from Infections Disease Society of North America. www.cidrap.umn.edu/cidrap/content/bt/botulism/biofacts/botulismfactsheet.html.

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65 mm Hg Norepinephrine targeted

Fluid load to CVP 16 cm H2O 1.5 mL/kg: hold

70% Hb10 g/L 70%

BOX 12-5 n AIDS-DEFINING ILLNESSES BOX 12-6 n COMPLICATIONS OF HIV MULTIORGAN