Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 12 – Infectious Diseases and Bioterrorism

Patrick J. Neligan, MD



Sepsis, Systemic Inflammatory Response Syndrome, and Multiorgan Dysfunction Syndrome






Pathophysiology of Sepsis



Multiorgan Dysfunction Syndrome



Treating the Patient with Septic Shock



Transmissible Infections and Anesthesia



Hepatitis B and C












Intra-abdominal Infections and Anesthesia



Pyogenic Liver Abscess



Amebic Liver Abscess



Hydatid Disease



Splenic Abscess



Appendiceal Abscess



Diverticular Abscess



Necrotizing Soft Tissue Infections



Necrotizing Fasciitis



Clostridial Myonecrosis (Gas Gangrene)



Soft Tissue Infections of the Head and Neck






Infectious Agents of Bioterrorism















Biological Toxins










Infection has killed more soldiers in war than gunfire. Although the age of infectious diseases has all but passed in the western world, infection, and the means by which the body deals with it, remains a major problem in critical care and perioperative medicine.

A clear distinction must be made between infections, sepsis, infectiousness, and carrier states. Infection refers to the host response to the presence of microorganisms or tissue invasion by microorganisms. The microorganisms may be bacteria, viruses, fungi, parasites, or prions. Sepsis is a syndrome the systemic inflammatory response to the microorganism and associated toxins. Infectiousness or contagiousness refers to the transmissibility of pathogens from one host to another. A carrier state refers to the persistence of a contagious organism within a host who may not demonstrate signs of infection. Each of these situations is of importance to anesthesiologists. For example, patients with fulminant surgical sepsis (e.g., necrotizing pancreatitis or gas gangrene) may come to the operating room for débridement and source control. Anesthesia management is significantly influenced by the immunologic and hemodynamic impact of sepsis. Likewise, patients with transmissible diseases (e.g., tuberculosis, hepatitis C, or HIV) represent a significant risk to health care personnel, who may contract the diseases.[1] Finally, the dramatic events of September 2001, the subsequent anthrax scare, and the war in Iraq have refocused attention of previously eradicated infectious organisms as potential weapons of terrorism.[2]



For many years doctors attending intensive care units (ICUs) used a variety of terms to describe illnesses associated with infection or with illness that looked like infection. These terms included sepsis, septicemia, bacteremia, infection, septic shock, toxic shock, and so on. Unfortunately, there were two problems with these terms: (1) there were no strict definitions for the terms used, and often these words or phrases were used incorrectly; and (2) an emerging body of evidence arose that led us to believe that systemic inflammation, rather than infection, was responsible for multiorgan failure. In the early 1990s a consensus conference between the American College of Chest Physicians (ACCP) and the Society for Critical Care Medicine (SCCM) laid out a new series of definitions for what is inflammation and what is sepsis ( Table 12-1 ).[3] The reason for this is that the host response to both infectious and noninfectious injuries is similar[4]; the clinical signs are essentially the same. This inflammatory response is determined, qualitatively and quantitatively, by genetic and environmental factors.[5] Hence 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 ). A new term SIRS (systemic inflammatory response syndrome) was introduced to describe the process of inflammation without infection.[3] This terminology has come into common usage, albeit with some reservations. [6] [7]

TABLE 12-1   -- Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis






A host response to the presence of microorganisms or tissue invasion by microorganisms.






The presence of viable bacteria in circulating blood



Systemic Inflammatory Response Syndrome (SIRS)



The systemic inflammatory response to a wide variety of severe clinical insults, manifested by two or more of the following conditions:



Temperature > 38°C or < 36°C



Heart rate > 90 beats per minute



Respiratory rate > 20 breaths per minute or PaCO2 < 32 mm Hg



WBC count > 12,000/mm3, < 4,000/mm3, or > 10% immature (band) forms






The systemic inflammatory response to infection. In association with infection, manifestations of sepsis are the same as those



previously defined for SIRS. It should be determined whether they are a direct systemic response to the presence of an infectious



process and represent an acute alteration from baseline in the absence of other known causes for such abnormalities. The clinical



manifestations would include two or more of the following conditions as a result of a documented infection:



Temperature > 38°C or < 36°C



Heart rate > 90 beats per minute



Respiratory rate > 20 breaths per minute or PaCO2 < 32 mm Hg



WBC count > 12,000/mm3, < 4,000/mm3, or > 10% immature (band) forms



Severe Sepsis/SIRS



Sepsis (SIRS) associated with organ dysfunction, hypoperfusion, or hypotension. Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status.



Refractory (Septic) Shock/SIRS Shock



A subset of severe sepsis (SIRS) and defined as sepsis (SIRS)-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status. Patients receiving inotropic or vasopressor agents may no longer be hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunction, yet they would still be considered to have septic (SIRS) shock.



Multiple Organ Dysfunction Syndrome (MODS)



Presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

From Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Consensus document ACCP/SCCM. Crit Care Med 1992;20:864-874.





FIGURE 12-1  Infection, sepsis and SIRS.  (From Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Consensus document ACCP/SCCM. Crit Care Med 1992;20:864-874.)




Infection, according to the 1992 definitions,[3] is a microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms. Sepsis is the presence of a systemic inflammatory response to infection. A second consensus conference was held in 2001[5] to deal with the ongoing problem with the vagueness of the definition of SIRS.[8] The strengths and weaknesses of the current sepsis definitions were reviewed. The definitions were left unchanged with the exception of an expansion in the list of signs and symptoms of sepsis to reflect the spectrum of manifestations at the bedside. These definitions have significant epidemiologic value: there is a clear increase in mortality as patients pass from SIRS, with progressive organ failure, to sepsis, to septic shock ( Table 12-2 ). [9] [10]

TABLE 12-2   -- Diagnostic Criteria for Sepsis



Infection,[*] documented or suspected, and some of the following: 



General variables



Fever (core temperature > 38.3°C)



Hypothermia (core temperature < 36°C)



Heart rate > 90 beats per minute or > 2 SD above the normal value for age






Altered mental status



Significant edema or positive fluid balance (> 20 mL/kg over 24 hr)



Hyperglycemia (plasma glucose > 120 mg/dL or 7.7 mmol/L) in the absence of diabetes



Inflammatory variables



Leukocytosis (WBC count > 12,000/μL)



Leukopenia (WBC count, 4,000/μL)



Normal WBC count with > 10% immature forms



Plasma C-reactive protein > 2 SD above the normal value



Plasma procalcitonin > 2 SD above the normal value



Hemodynamic variables



Arterial hypotension† (SBP < 90 mm Hg, MAP < 70, or an SBP decrease > 40 mm Hg in adults or < 2 SD below normal for age) Sv–O2 > 70%†



Cardiac index > 3.5 L/min/m2



Organ dysfunction variables



Arterial hypoxemia (PaO2/FIO2 < 300)



Acute oliguria (urine output, 0.5 mL/kg/hr for at least 2 hr)



Creatinine increase > 0.5 mg/dL



Coagulation abnormalities (INR > 1.5 or aPTT > 60 seconds) Ileus (absent bowel sounds)



Thrombocytopenia (platelet count < 100,000/μL)



Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 mmol/L)



Tissue perfusion variables



Hyperlactatemia (> 1 mmol/L)



Decreased capillary refill or mottling

From 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250-1256.

WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial pressure; Sv–O2, mixed venous oxygen saturation; INR, international normalized ratio; aPTT, activated partial thromboplastin time.

Note: Diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus infection with hyperthermia or hypothermia (rectal temperature > 38.5° or < 35°C), tachycardia (may be absent in hypothermic patients), and at least one of the following indications of altered organ function: altered mental status, hypoxemia, increased serum lactate level, or bounding pulses.



Infection defined as a pathologic process induced by a microorganism.

Sv–O2 sat > 70% is normal in children (normally, 75%-80%), and CI 3.5–5.5 is normal in children; therefore, NEITHER should be used as signs of sepsis in newborns or children.



Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Pathophysiology of Sepsis

The presence of pathogens in the bloodstream or tissues elicits an inflammatory response. There are five stages[4]: (1) establishment of infection, (2) preliminary systemic inflammatory response, (3) overwhelming systemic inflammatory response, (4) compensatory anti-inflammatory response, and (5) immunomodulatory failure.

Microbes possess specific virulence factors to overcome host defenses. The cell wall of gram-negative bacteria consists of an inner phospholipid bilayer and an outer layer that contains lipopolysaccharide (LPS). This consists of polysaccharide O, which protrudes from the exterior cell surface, a core polysaccharide, and a lipid component (lipid A) that faces the cell interior. Lipid A, or endotoxin, is responsible for the toxicity of this molecule. It is released with cell lysis. In meningococcemia, plasma levels of endotoxin correlate well with the development of multiorgan dysfunction syndrome (MODS).

Gram-positive organisms, such as Staphylococcus, Streptococcus, and Enterococcus actively secrete an exotoxin, which consists of two polypeptide components: the first binds the protein to the host cell, and the second has toxic effects. Staphylococcus aureus produces four cytolytic exotoxins, the most important of which— α toxin—punctures holes in the membranes of cells leading to osmotic lysis. In addition, S. aureus produces a number of superantigens that have an affinity for T-cell receptor major histocompatibility complex (MHC) class II antigen complexes. They activate a large number of T cells, leading to massive release of cytokines and toxic shock. Clostridium difficile produces two exotoxins: toxin A and toxin B.

In addition to toxins, bacteria possess a variety of virulence factors that contribute to the establishment of infection. For example, group A streptococci produce hyaluronidase and various proteases and collagenases, which facilitate the spread of the bacteria along tissue plains. Staphylococcus epidermidis produces a biofilm that coats intravascular devices and endotracheal tubes, making elimination by antibiotics almost impossible. Coliforms and Pseudomonas species have pili that allow the organism to bind and anchor to the epithelium, potentially a mechanism of bacterial translocation.

Fungal infections are common in the hospitalized population. Commensal organisms, such as Candida species, become pathogenic as a result of host factors (e.g., immunosuppression, concomitant infection, diabetes) and iatrogenic factors (e.g., multiple antibiotics, critical illness, parenteral nutrition, abdominal surgery). The gastrointestinal tract appears to be an important source of Candida; the mechanism of candidemia is unclear ( Fig. 12-2 ).


FIGURE 12-2  The PIRO model of sepsis and SIRS.  (Adapted from SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-1256.)




The Inflammatory Cascades

Tissue injury or pathogens (bacteria, viruses, fungi, or parasites) cause monocyte activation, which produces interleukin (IL-1, IL-6), tumor necrosis factor-alpha (TNF-α), plasminogen inactivator inhibitor-1 (PAI-1), and interferon gamma. [11] [12] These cytokines subsequently modulate the release and activation of a medley of different agents: IL-8, complement, histamine, kinins, serotonin, selectins, eicosanoids, and neutrophils. This leads to local vasodilatation, release of various cytotoxic chemicals, and destruction of the invading pathogen. The release of cytotoxic material and proinflammatory cytokines results in the systemic inflammatory response: fever or hypothermia, tachypnea, tachycardia, and leukocytosis or neutropenia.

In a subgroup of patients there is an abnormal (“malignant”) inflammatory response: tissue destruction by neutrophils, endothelial cell destruction, and massive systemic release of mediators. The result is vasoplegia, capillary leak, and activation of clotting cascades.

Damage to the endothelium exposes a procoagulant factor known as tissue factor. This exists in the subendothelial space and has a role in reparation after tissue damage. In sepsis, there is massive exposure. Tissue factor binds to activated factor VII. The resulting complex activates, in turn, factors IX and X. Factor X converts prothrombin into thrombin, which cleaves fibrinogen into fibrin—a blood clot. At the same time, the fibrinolytic system is inhibited. Cytokines and thrombin stimulate the release of PAI-1 from platelets and the endothelium. In the human body, when a clot forms, it is ultimately broken down by plasmin, which is activated by tissue plasminogen activator (TPA) from plasminogen. PAI-1 inhibits TPA.

Thrombin itself is an activator of inflammation and inhibitor of fibrinolysis. The latter is achieved by the activation of thrombin-activatable fibrinolysis inhibitor (TAFI). Thrombomodulin, another modulator of fibrinolysis, is impaired by inflammation and endothelial injury. The function of this compound is to activate protein C. Activated protein C modifies the inflammatory and coagulant response at several different levels; a deficiency occurs owing to inhibition of thrombomodulin in sepsis.

Hemodynamic Derangement in Sepsis

There are three major cardiovascular upsets in sepsis:



Vasoplegia: pathologic vasodilatation is due to loss of normal sympathetic tone, caused by the combination of local vasodilator metabolites. There is activation of adenosine triphosphate-sensitive potassium channels, leading to hyperpolarization of smooth muscle cells. [13] [14] There is increased production of inducible nitric oxide synthetase (iNOS), which manufactures massive amounts of nitric oxide. In addition there is acute depletion of vasopressin.[15] Vasoplegia leads to relative hypovolemia. Vascular tone is characteristically resistant to catecholamine therapy but very sensitive to vasopressin.



Reduced stroke volume (SV): this results from the presence of a circulating myocardial depressant factor, probably TNF-α. There is reversible biventricular failure, a decreased ejection fraction, myocardial edema, and ischemia. Cardiac output is maintained by a dramatic increase in heart rate.[16]



Microcirculatory failure[17]: the small blood vessels vasodilate, and there is widespread capillary leak, maldistribution of flow, arteriovenous shunting, and oxygen utilization defects.[18] These abnormalities are incompletely understood. In addition, there is initial activation of the coagulation system and deposition of intravascular clot, causing ischemia.

The relative hypovolemia of early sepsis is virtually indistinguishable from hypovolemic or hemorrhagic shock. In response to intravascular volume depletion (distributive or hypovolemic shock), the precapillary arterioles and postcapillary venules vasoconstrict, increasing blood flow velocity, which draws fluid in from the interstitium (a net influx of fluid into the circulation). This is known astranscapillary refill. Fluid effectively shifts from the extravascular to the intravascular space. An oxygen debt is incurred, and there may be lactic acidosis. At this stage, patients are highly sensitive to volume resuscitation.

Eventually, persistent release of cytokines leads to depletion of reserve: there is hyperpolarization of vascular smooth muscles, massive release of iNOS, vasopressin depletion, and widespread increase in vascular permeability. The result is vasoplegia and sequestration of intravascular fluid into extracellular space. There is interstitial edema, hemoconcentration, and increased blood viscosity. There is parallel activation of clotting cascades, intravascular thrombosis, and bleeding. Finally, the capacity of mitochondria to extract oxygen is impaired and multiorgan dysfunction results ( Fig. 12-3 ).


FIGURE 12-3  Mortality in SIRS/sepsis/septic shock.  (From Rangel-Frausto M, Pittet D, Costigan M, et al: The natural history of the systemic inflammatory response syndrome [SIRS]: A prospective study. JAMA 1995; 273:117-125.)




Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Multiorgan Dysfunction Syndrome

The brain and kidneys are normally protected from swings in blood pressure by autoregulation. In early sepsis the autoregulation curve shifts rightward (owing to an increase in sympathetic tone). In late sepsis vasoplegia occurs and autoregulation fails, making these organs susceptible to the swings that occur in systemic blood pressure. In addition, “steal” phenomena may occur (areas of ischemia may have their blood “stolen” by areas with good perfusion). This is known as vasomotor neuropathy. Acute tubular necrosis results from cellular apoptosis, toxic injury (mechanism unclear—possibly cellular lysosomes and debris), hypotension, and hypovolemia.[19]

Patients become confused, delirious, and ultimately stuporous and comatose owing to a variety of insults: hypoperfusion injury, septic encephalopathy, metabolic encephalopathy, and, of course, drugs used for sedation.

Myocardial oxygen supply is dependent on diastolic blood pressure, which falls following vasoplegia, and on intravascular volume depletion. This may lead to ischemia. There is reversible biventricular dilatation, decreased ejection fraction, and decreased response to fluid resuscitation and catecholamine stimulation. A circulating myocardial depressant substance is responsible for this phenomenon. This substance has been shown to represent low concentrations of TNF-α and IL-1β acting in synergy on the myocardium through mechanisms that include nitric oxide and cyclic guanosine monophosphate generation.

In the lungs ventilation-perfusion mismatches occur, initially owing to increased dead space (due to hypotension and fluid shifts) and subsequently due to shunt.[20] There is increased extravascular lung water and widespread disruption of the alveolar-capillary basement membrane, leading to acute lung injury. Up to 70% of patients develop nosocomial pneumonia. It has been suggested that cytokines released as a consequence of ventilator-induced lung injury may have adverse effects at distant organs.[21] This hypothesis was confirmed from data in the Acute Respiratory Distress Syndrome (ARDS) Network trial supported by the National Institutes of Health.[22] Blood samples were obtained from 204 of the first 234 patients for measurement of plasma IL-6 concentration. Levels of this cytokine were significantly higher in the high stretch (tidal volume, 10 to 12 mL/kg) compared with the low stretch (tidal volume, 5 to 6 mL/kg) group. In addition to lower mortality, this group had a significantly lower incidence of nonpulmonary organ injury (the lung origin theory of sepsis).

There is significant hepatic dysfunction in sepsis. Uncontrolled 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 hyperbilirubinemia. There is decreased synthesis of albumin, clotting factors, cytochrome P450, and biliary transporters. There is impaired ketogenesis, ureagenesis, and gluconeogenesis: this is due to decreased expression of genes encoding gluconeogenic, β-oxidative, and ureagenic enzymes.[23]

Gut mucosa is usually protected from injury by autoregulation. Hypotension and hypovolemia lead to superficial mucosal injury. This results in atrophy and possible translocation of bacteria into the portal circulation and stimulates liver macrophages, causing cytokine release and amplification of SIRS (the gut origin theory of sepsis). [24] [25]

Metabolic abnormalities in sepsis include hyperglycemia due to glycogenolysis, insulin resistance, and massive release of catecholamines and lactic acidosis. There is a generalized catabolic state that leads to muscle breakdown, not unlike marasmus. There is relative hypothyroidism, hypopituitarism, and adrenal insufficiency. [26] [27]

Activated Protein C

Protein C is an important anticoagulant and anti-inflammatory protein. The main effect of protein C is to reduce the production of thrombin, by inactivating factors Va and VIII. Thrombin is proinflammatory, procoagulant, and antifibrinolytic.[28] In addition, protein C inhibits the influence of tissue factor on the clotting system, reduces the production of IL-1, IL-6, and TNF-α by monocytes, and has profibrinolytic properties through the inactivation of PAI-1 (it inactivates the inhibitor of the activator of the agent that converts plasminogen into plasmin).[24]

The Prowess trial has suggested that the exogenous administration of activated protein C to patients, in severe sepsis, may improve outcome.[29] However, the results of the single trial have been controversial, and there is no survival benefit in patients with severe sepsis and Apache II scores less than 25. The major clinical drawback of treatment with activated protein C is bleeding, particularly in perioperative patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Treating the Patient with Septic Shock

Patients with acute severe sepsis (e.g., necrotizing fasciitis or gas gangrene) are infrequently brought to the operating room for emergent source control. In this circumstance, the anesthesiologist will be required to both administer anesthesia, ensuring amnesia, analgesia, and hypnosis, and resuscitate the patient. A familiarity with modern resuscitation practices is thus important.

There are four main pillars to the management of the patient with severe sepsis: (1) immediate resuscitation, (2) empirical therapy, (3) source control, and (4) preventing further complications ( Fig. 12-4 ).


FIGURE 12-4  Treating sepsis—the four pillars of therapy.



Stage 1: Immediate Resuscitation

Immediate Stabilization (Airway and Breathing).

The initial treatment priority in patients with severe sepsis is to reverse life-threatening physiologic abnormalities. The airway must be controlled and the patient oxygenated and ventilated. This usually requires endotracheal intubation and commencement of mechanical ventilation. Care must be taken when administering anesthetic agents for gaining airway control. Propofol usually causes dramatic hypotension, owing to peripheral vasodilatation and vagotonia, and should be avoided. Etomidate and ketamine are reasonable choices. Although opioids are frequently used in cardiac anesthesia for hemodynamic stability, they have significant antiadrenergic effects in sepsis and may cause dramatic hypotension. Therapies directed at slowing heart rate should be avoided, as tachycardia is the main compensatory mechanism in maintenance of cardiac output.

After intubation, extreme care must be taken with institution of positive-pressure ventilation. The increase in intrathoracic pressure will reduce venous return: aggressive “bagging” invariably leads to severe hypotension.

Reestablishing the Circulation.

Volume Resuscitation ( Fig. 12-5 ).

In early sepsis hypotension is caused by relative hypovolemia, secondary to peripheral vasodilation. Later, hypotension is caused by myocardial depression, vasoplegia, and absolute hypovolemia secondary to capillary leak. Regardless, the initial resuscitative effort is to attempt to correct the absolute and relative hypovolemia by refilling the vascular tree. Volume resuscitation should be early (in the operating room or emergency department), aggressive, and goal directed.[30]


FIGURE 12-5  Two phases of sepsis resuscitation.



The choice of fluids early in resuscitation remains controversial. Initial resuscitation should include isotonic crystalloid, to replete interstitial fluid debt. Subsequent efforts are directed at maintenance of intravascular volume. If crystalloid resuscitation is continued there is significant extravasation of fluid and the patient becomes edematous. [31] [32] The use of high-molecular-weight (“colloid”) compounds is favored by many as a means of minimizing resuscitation volume and for potential positive oncotic effects.[31] Although the use of colloid is controversial [33] [34] there is emerging evidence in support of its use in perioperative medicine and critical illness as part of a goal-directed paradigm. [35] [36] [37] [38] [39] The main limiting factors for colloids are availability (gelatins and pentastarches are not available in the United States) and cost. Available colloids include blood products, hydroxyethyl starches, and albumin. Previous concerns regarding albumin safety are unfounded.[40]

The goal-directed approach to resuscitation involves the use of specific monitors to measure input (fluid loading), tissue blood flow, and response ( Fig. 12-6 ). Arterial and central lines are placed, and goals for resuscitation are set: these include a central venous pressure (CVP) of 8 to 12 cm H2O, a mean arterial pressure (MAP) of more than 65 mm Hg, and, if the appropriate device is placed, a mixed venous oxygen saturation (Svo2) of more than 70% and an SV of between 0.7 and 1.0 mL/kg.


FIGURE 12-6  Goal-directed resuscitation. CVP, central venous pressure; PAOP, pulmonary artery opening “wedge” pressure; PADP, pulmonary artery diastolic pressure; MAP, mean arterial pressure; UO, urinary output; SV, stroke volume; FVT, flow velocity time; CO, cardiac output, Ci, cardiac index, Svo2, mixed venous oxygen saturation.



The Surviving Sepsis Campaign[41] promotes the use of oximetric CVP catheters to monitor input and flow ( Fig. 12-7 ) based on the work of Rivers and colleagues.[42] Fluid is administered until the CVP reaches and stays in the target range: 8 to 12 cm H2O for the majority of patients ( Fig. 12-8 ). Once fluid loading has been achieved, hypotension is managed with vasopressors (norepinephrine or dopamine—see later) to a target MAP of 65 mm Hg. If the Svo2 is less than 70%, with CVP and MAP in the target range, blood is transfused until the hematocrit exceeds 30% (hemoglobin 10 g/L). If this fails to restore the Svo2, an inotrope is added, such as dobutamine or a phosphodiesterase inhibitor.


FIGURE 12-7  Goal-directed resuscitation using Oximetric CVP catheter based on the Surviving Sepsis Campaign. IPPV, intermittent positive-pressure ventilation; CVP, central venous pressure; MAP, mean arterial pressure; Svo2, mixed venous oxygen saturation; RBC, red blood cell.




FIGURE 12-8  Goal-directed approach using central venous pressure.



A more elegant approach involves insertion of an oximetric pulmonary artery catheter rather than a CVP line. In this paradigm, SV is used as the main end point of resuscitation and CVP or pulmonary arterial pressure is used to determine the presence of heart failure ( Fig. 12-9 ): a Starling curve is constructed ( Fig. 12-10 ). Fluid is administered to the patient until the SV is in the range of 0.7 to 1 mL/kg for a sustained period ( Fig. 12-11 ).


FIGURE 12-9  Using stroke volume to construct Starling curves. CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; LVEDP, left ventricular end-diastolic pressure; PADP, pulmonary artery diastolic pressure.




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.




FIGURE 12-11  Using the goal-directed approach to determine the effectiveness of fluid resuscitation. In this situation, the goal for stroke volume was 65 to 80 mL and for Svo2 it was 70%. CVP, central venous pressure; Svo2, mixed venous oxygen saturation.



An SV in excess of 1.0 mL/kg is indicative of overresuscitation, and fluids are withheld until the SV drifts back into normal range. If the SV exceeds 1.5 mL/kg, serious consideration should be given to the administration of diuretics.

Vasopressor Therapy.

Hypotension, unresponsive to fluid therapy, in sepsis is an indication for vasopressor use ( Table 12-3 ). The ideal pressor agent would restore blood pressure while maintaining cardiac output and preferentially perfuse the midline structures of the body (brain, heart, splanchnic organs, and kidneys). Currently, norepinephrine is the agent of choice in the fluid-resuscitated patient.

TABLE 12-3   -- Pharmacologic Support of the Circulation in Sepsis





Heart Rate

Organs Perfused





↑ ↑ ↑ ↑

Skin, muscle





↑ ↑

Central organs





↑ ↑ ↑ ↑

Skin, muscle






No real change




Norepinephrine has pharmacologic effects on both α1 and β1 adrenoceptors. In low dosage ranges, the beta effect is noticeable and there is a mild increase in cardiac output. In most dosage ranges, vasoconstriction and increased mean arterial pressure are evident. Norepinephrine does not increase heart rate. The main beneficial effect of norepinephrine is to increase organ perfusion by increasing vascular tone. Studies that have compared norepinephrine to dopamine head to head have favored the former in terms of overall improvements in oxygen delivery, organ perfusion, and oxygen consumption. Norepinephrine is more effective at fulfilling targeted end points than dopamine,[43] is less metabolically active than epinephrine, and reduces serum lactate levels. Norepinephrine significantly improves renal perfusion and splanchnic blood flow in sepsis, [44] [45] particularly when combined with dobutamine.[45]


Dopamine has predominantly β-adrenergic effects in low to moderate dose ranges (up to 10 MIC/kg/ min), although there is much interpatient variability. This effect may be due to its conversion to norepinephrine in the myocardium and its activation of adrenergic receptors. In higher dose ranges, α-adrenoceptor activation increases and causes vasoconstriction. The agent is thus a mixed inotrope and vasoconstrictor. At all dose ranges it is a potent chronotrope. There has been much controversy about the other metabolic functions of this agent. Dopamine is a potent diuretic (it neither saves nor damages the kidneys).[46] Dopamine has complex neuroendocrine effects: it may interfere with thyroid[47] and pituitary[47] function and have an immunosuppressive effect.[48] Overall, there is no benefit to dopamine administration over norepinephrine.


Dobutamine is a potent β1 agonist, with predominant effects in the heart where it increases myocardial contractility and thus SV and cardiac output. Dobutamine is associated with much less increase in heart rate than dopamine. In sepsis, dobutamine, although a vasodilator, increases oxygen delivery and consumption. Dobutamine appears particularly effective at splanchnic resuscitation, increasing pHi (gastric mucosal pH) and improving mucosal perfusion in comparison with dopamine.[49]


Epinephrine has potent β1, β2, and α1-adrenergic activity, although the increase in MAP in sepsis is mainly from an increase in cardiac output (SV). There are three major drawbacks from using this drug: (1) epinephrine increases myocardial oxygen demand; (2) it increases serum glucose lactate, which may be due to either worsening of perfusion to certain tissues or to a calorigenic effect (increased release and anaerobic breakdown of glucose); and (3) epinephrine appears to have adverse effects on splanchnic blood flow,[50] redirecting blood peripherally as part of the fight or flight response.

The metabolic and hemodynamic effects makes epinephrine an unsuitable first-line agent in sepsis.


Phenylephrine is an almost pure α1 agonist with moderate potency. Although widely used in anesthesia to treat iatrogenic hypotension, it is an ineffective agent in sepsis. Phenylephrine is a less effective vasoconstrictor than norepinephrine or epinephrine. Compared with norepinephrine, phenylephrine reduces splanchnic blood flow, oxygen delivery, and lactate uptake.[51]


Vasopressin has emerged as an additive vasoconstrictor in septic patients who have become resistant to catecholamines.[52] There appears to be a quantitative deficiency of this hormone in sepsis, [15] [53] [54] [55] and administration in addition to norepinephrine surprisingly increases splanchnic blood flow and urinary output. The most efficacious dose appears to be 0.04 unit/min,[56] and this is not titrated. This relatively low dose has little or no effect on normotensive patients.

Stage 2: Empirical Therapy—Antibiotics

The selection of specific antibiotics depends on:



The presumed site of infection (see Table 12-1 ).



Gram's stain results



Suspected or known organisms



Resistance patterns of the common hospital microbial flora



Patient's immune status (especially neutropenia and immunosuppressive drugs), allergies, renal dysfunction, and hepatic dysfunction.



Antibiotic availability, hospital resistance patterns, and clinical variables of the patient to be treated

Suggested Antimicrobial Regimens.

Sepsis Source Unknown.

Combining either antipseudomonal cephalosporin (ceftazidine) or antipseudomonal penicillin (piperacillin + azobactam) (particularly if anaerobes are suspected) with either an aminoglycoside (gentamycin or amikacin) or a fluoroquinolone (ciprofloxacin) can be done. If an antipseudomonal cephalosporin is used and anaerobes are a possible cause, the addition of metronidazole or clindamycin should be considered.



Piperacillin + tazobactam/imipenem + gentamycin/ ciprofloxacin

Catheter-Related Bloodstream Infection.

There is a strong possibility of infection with staphylococci, coagulase positive or negative.



Vancomycin should be added to, for example, piperacillin + tazobactam. Once the infecting organisms have been isolated, the spectrum of antimicrobials should be narrowed (if methicillin-resistant S. aureus (MRSA) is isolated, the piperacillin + tazobactam should be discontinued).



Vancomycin + piperacillin + tazobactam or ciprofloxacin

Community-Acquired Pneumonia.

The most likely organisms are pneumococci, Mycoplasma, and Legionella. The patient requires coverage for both gram-positive and atypical organisms.



Cephalosporin IV + macrolide PO or fluoroquinolone



Cefuroxime/ceftriaxone IV + azithromycin PO or levofloxacin

Intra-abdominal Sepsis.

The most likely infecting organisms are Enterobacteriaceae, enterococci, S. pneumoniae, and anaerobes. Broad-spectrum treatment is required, without cover for Pseudomonas.



Penicillin + β-lactam inhibitor or ampicillin + aminoglycoside + antianaerobic agent



Ampicillin + sulbactam or piperacillin + tazobactam or ampicillin + gentamicin/aztreonam + metronidazole or imipenem


The most common organisms causing urinary tract infections are Enterobacteriaceae and enterococci, and the treatment is ciprofloxacin or ampicillin and gentamicin. In this case, however, the patient has been admitted from a nursing home and Pseudomonas is a strong possibility. Twin therapy is often required, not mixing β-lactam antibiotics:



Antipseudomonal quinolone or aminoglycoside plus antipseudomonal penicillin or cephalosporin.



Ciprofloxacin/gentamicin/amikacin plus piperacillin or ceftazidime


The most likely organisms are streptococci and staphylococci. If the infection is community acquired, then cloxacillin is adequate. Again, this patient was institutionalized and the infection must be treated as hospital acquired:



Vancomycin + gentamycin

Necrotizing Fasciitis.

Type 1 (see later) is due to group A streptococci, and type 2 is polymicrobial and due to streptococci, staphylococci, Bacteroides, and Clostridium.[57]



Penicillin (high dose) or ciprofloxacin (if penicillin allergic) + clindamycin



Add ampicillin + sulbactam or piperacillin + tazobactam


Bacterial meningitis is meningococcal septicemia until otherwise proven. The most likely alternative organisms are pneumococci, Hemophilus influenzae, and, rarely, Enterobacteriaceae and Listeria.



Third-generation cephalosporin + vancomycin (if penicillin-resistant S. pneumoniae suspected) + ampicillin (if Listeria suspected) Cefotaxime + vancomycin

Stage 3: Source Control

Source control is the essential curative measure in the management of sepsis and the associated inflammatory response. Although there is a myriad of potential causes of sepsis, beyond medical causes, such as pneumonia or meningitis, source control can be neatly summarized by applying the four Ds rule ( Fig. 12-12 )[41]: abscesses should be drained, necrotic tissue should be débrided, infected devices removed and recurrent sources of infection/inflammation (e.g., cholecystitis or diverticulitis) definitively controlled. This represents the major involvement of anesthesiologists within the sepsis paradigm: patients travel to the operating room for source control under anesthesia.


FIGURE 12-12  The 4 Ds of source control. IUCD, intrauterine contraceptive device.



Stage 4: Prevention of Further Complications

A significant aspect of the critical care management of septic patients is prevention of complications. This applies also to their perioperative care. Many patients with acute severe sepsis have a concomitant hypoxic lung injury (e.g., ARDS) requiring intensive mechanical ventilatory support. This usually involves the application of high mean airway pressures to prevent de-recruitment of involved lung tissue. It is imperative that lung volume be maintained perioperatively. If the patient is requiring more than 10 cm H2O of positive end-expiratory pressure (PEEP) or is on inverse-ratio pressure-controlled or airway pressure-release ventilation then the following guidelines should be followed:



The operating room mechanical ventilator must be of sufficient capacity to maintain high mean airway pressure. Although some modern ventilators have this capacity, the majority of “bag in bottle” bellows are insufficient. When there is doubt, the patient should be transferred to the operating room with their ICU ventilator.



Extreme care must be taken to avoid disconnection from the ventilator: even short periods of disconnection (i.e., for changing from ventilator to anesthesia machine) may result is significant de-recruitment of the lung and life-threatening hypoxemia.



The endotracheal tube should be clamped before disconnections to maintain lung recruitment.



If accidental disconnection should occur, sustained inflation maneuvers should be performed to re-recruit the lung.



Critically ill patients are usually nursed in the semi-recumbent position. Patients lie supine in the operating room. This often results in an increase in chest wall elastance, requiring higher levels of PEEP to maintain lung volumes.



The standard of care in the management of patients with ARDS is to limit end inspiratory lung volumes to a plateau pressure of 30 cm H2O or less and a tidal volume of 6 mL/kg or less.[31]This is to avoid “volutrama,” a ventilator-associated lung injury.[58]

Care must be taken to maintain circulating volume and blood flow to tissues. During surgical débridement of, for example, necrotizing pancreatitis or fasciitis, handling of inflamed or infected tissues usually leads to significant systemic release of cytokines, worsening vasoplegia and increasing myocardial depression. The anesthesiologist must be careful to titrate vasopressors and bolus fluids in response to rapidly changing hemodynamics.

Patients with severe sepsis are at significant risk of secondary organ injuries, particularly to the liver and kidneys. Medications that are renally metabolized or excreted (e.g., pancuronium, morphine) should be used with caution. Aminoglycosides and glycopeptides (e.g., vancomycin) must be administered with reference to pharmacokinetics. Nonsteroidal anti-inflammatory agents should be avoided, because they may precipitate acute renal failure, worsen coagulopathy, and induce upper gastrointestinal bleeding in a vulnerable population. Although hepatic metabolism is well preserved in patients with liver dysfunction in sepsis, consideration should be given to the use of agents metabolized independently of the liver (e.g., cisatracurium rather than vecuronium or pancuronium; remifentanil rather than fentanyl or morphine).

The choice of anesthesia agents is dependent on a number of factors. Many patients are transported to the operating room in an induced coma (e.g., lorazepam or midazolam plus morphine or hydromorphone infusions), and little additional anesthesia is required. In the awake patient, in whom anesthesia is being induced, care should be taken as described previously. For maintenance of anesthesia, sufficient agents must be administered to maintain hypnosis and amnesia. Frequently this is not possible with volatile agents, owing to peripheral vasodilatation and hypotension. Ketamine is a good alternative, particularly if accompanied by an infusion of fentanyl or remifentanil or hydromorphone.

Patients with acute severe sepsis are at high risk for perioperative bleeding, owing to sepsis-induced coagulopathy and thrombocytopenia. Aggressive volume repletion with red cells, thawed plasma, and platelets is recommended. Activated protein C (drotrecogin alfa activated) significantly increases the risk of bleeding and must be discontinued at least 2 hours before surgical procedures and not restarted until at least 2 hours after surgery ( Table 12-4 ).

TABLE 12-4   -- Perioperative Care of the Patient with Established Severe Sepsis


Continuation of all monitoring procedures in the ICU

Fluid Administration

Fluid administration should be goal directed based on predetermined end points.

Anesthesia Agents

Determined by hemodynamic stability, whether the patient will tolerate volatile agents, preexisting infusions (e.g., lorazepam and morphine), pharmacokinetics, etc.

Mechanical Ventilation

Transport with ICU ventilator if PEEP >10 cm H2O, inverse ratio pressure controlled or airway pressure release ventilation in use.


Avoid ventilator disconnection (use clamp).


Accidental disconnection should be followed by recruitment maneuvers.


Inhaled nitric oxide or prostacyclin should be continued.


Vasopressors should be continued; additional bags of medication should be available to avoid catastrophic cessation.


Corticosteroids (for adrenal insufficiency) should be continued.


Gastric feeds should be discontinued 6 hours before surgery; postpyloric feeds may be continued (at the discretion of the anesthesiologist).


Total parenteral nutrition should be continued.


All anticoagulants should be stopped before surgery.


Activated protein C should be stopped 2 hours before surgery.

Renal Replacement Therapy

Continuous renal replacement therapy should be stopped 6 hours before surgery to allow autoreversal of heparin.


Dosage based on predicted microbes, resistance patterns of patient and hospital, renal function, and pharmacokinetics.



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Hepatitis B and C

Hepatitis B

Hepatitis B is a small, double-stranded DNA hepadnavirus. It is spread by sexual intercourse, with a high degree of infectivity, via secretions and blood products. Health care workers are at particularly high risk of exposure through handling of blood/tissue or needle-stick injuries.

The outer core of the virus contains a surface antigen (HBsAg) that elicits production of a neutralizing antibody (anti-HBs). In addition, the body generates a separate antibody (anti-HBc) against the viral core antigen (HBcAg). A third viral antigen—the hepatitis B e antigen (HBeAg)—is also released from the core. The presence of this antigen in the serum is indicative of active viral replication. The presence of the antibody to this particle (anti-HBe) is indicative of the end of active viral replication.

Clinical and Pathologic Features.

One to 6 weeks after exposure, HBsAg appears in the serum; its disappearance after 6 months indicates recovery ( Fig. 12-13 ). The presence of HBsAg for greater than 6 months indicates chronic disease/ carrier status (5% to 10% of infections). Past exposure of immunization can be detected by anti-HBs. In the majority of patients, anti-HBs does not rise to detectable levels until several weeks after the disappearance of the surface antigen and remains detectable for life. There may be a window in which neither antibody nor antigen are detectable. Consequently, another test is required to ensure diagnosis. This is to detect the presence of IgM antibody directed against the core antigen (IgM-anti-HBc), which is the earliest discernible antihepatitis B antibody. The presence of HBeAg implies high infectivity—it is usually present from 1.5 to 3 months after acute infection. The presence of anti-HBc indicates past exposure (see Fig. 12-13 ).


FIGURE 12-13  The serologic course of acute hepatitis B.  (From Goldman L, Bennett JC [eds]: Cecil Textbook of Medicine, 21st ed. Philadelphia, WB Saunders, 2002.)


After exposure, the incubation period is approximately 12 weeks, with resolution of symptoms after 30 to 60 days. Symptoms include a prodrome of pyrexia, anorexia, myalgia, urticaria, and nausea, followed by jaundice, hepatosplenomegaly, and lymphadenopathy. There is an increase in serum bilirubin and hepatic transaminases. Five to 10 percent of patients go on to develop chronic active hepatitis.

Anesthesia Implications.

Patients who are acutely infected with hepatitis B who present for surgery represent a unique risk for health care personnel, particularly anesthesiologists. Universal precautions should be taken when dealing with tissues or body fluids ( Table 12-5 ). Following needle-stick injury, the risk of developing clinical hepatitis B or serologic conversion, in a worker who is not immune, if the blood is positive for both HBsAg and HBeAg is approximately 25% and 50%, respectively. If the blood is HBsAg positive and HBeAg negative, however, the respective risks are only 3% and 30%.

TABLE 12-5   -- Universal Precautions



Barrier protection should be used at all times to prevent skin and mucous membrane contamination with blood, body fluids containing visible blood, or other body fluids (cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids, semen and vaginal secretions). Barrier protection should be used with ALL tissues. The type of barrier protection used should be appropriate for the type of procedures being performed and the type of exposure anticipated. Examples of barrier protection include disposable laboratory coats, gloves, and eye and face protection.



Gloves are to be worn when there is potential for hand or skin contact with blood, other potentially infectious material, or items and surfaces contaminated with these materials.



Wear face protection (face shield) during procedures that are likely to generate droplets of blood or body fluid to prevent exposure to mucous membranes of the mouth, nose, and eyes.



Wear protective body clothing (disposable laboratory coats) when there is a potential for splashing of blood or body fluids.



Wash hands or other skin surfaces thoroughly and immediately if contaminated with blood, body fluids containing visible blood, or other body fluids to which universal precautions apply.



Wash hands immediately after gloves are removed.



Avoid accidental injuries that can be caused by needles, scalpel blades, laboratory instruments, etc., when performing procedures, cleaning instruments, handling sharp instruments, and disposing of used needles, pipettes, etc.



Used needles, disposable syringes, scalpel blades, pipettes, and other sharp items are to be placed in punctureresistant containers marked with a biohazard symbol for disposal.



Health care workers who have antibodies to hepatitis B virus either from pre-exposure vaccination or prior infection are not at risk. In addition, if a susceptible worker is exposed to hepatitis B virus, postexposure prophylaxis with hepatitis B immune globulin and initiation of hepatitis B vaccine is more than 90% effective in preventing hepatitis B infection (see Table 12-6 for recommendations).

TABLE 12-6   -- Recommended Postexposure Prophylaxis for Exposure to Hepatitis B Virus



Vaccination and Antibody Response Status of Exposed Workers[*]

Source HBsAg[†] Positive

Source HBsAg Negative

Source Unknown or Not Available for Testing


HBIG[‡] × 1 and initiate HB vaccine series[§]

Initiate HB vaccine series

Initiate HB vaccine series

Previously vaccinated known responder[‖]

No treatment

No treatment

No treatment

Known nonresponder[¶]

HBIG × 1 and initiate revaccination or HBIG. 2[**]

No treatment

If known high risk source, treat as if 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 necessary.


1. If adequate,[‖] no treatment is necessary.


2. If inadequate,[¶]administer HBIG × 1 and vaccine booster.


2. If inadequate, administer vaccine booster and recheck titer in 1-2 months.

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 Morbid Mortal Weekly Rep 2001;50(RR-11):22.


Persons who have previously been infected with 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 are preferred.


Antibody to HBsAg.



Hepatitis C

Hepatitis C is the most common chronic bloodborne viral infection in the United States. It affects 300 million people worldwide, including 4 million Americans. The virus involved, a single strand of RNA, was first identified in 1989. The infection is primarily spread by parenteral administration of blood, blood products, and needle sharing among intravenous drug abusers.

Clinical and Pathologic Features.

The incubation period is 6 to 10 weeks. The majority of patients remain asymptomatic. Fifty to 70 percent of infected patients develop chronic hepatitis C, of which 50% will develop cirrhosis over a period of 20 to 30 years. Hepatitis C is a leading cause of hepatic failure in the United States. Forty percent of patients who undergo hepatic transplantation have this disease.

The nosocomial risk of hepatitis C seroconversion after a single incident of a needle stick in the health care setting is estimated to be in the 2% to 8% range. Needle-stick injury with hollow needles is associated with a 6- to 10-fold greater likelihood of transmission than when it occurs from contaminated solid-bore needles. There is no vaccine or effective immunoglobulin for these patients. Seroconversion is confirmed by the detection of hepatitis C virus RNA in the serum. Treatment is targeted at a sustained virologic response using interferon alfa and ribavirin. This results in normalization of serum transaminase levels in 50% of patients.

Anesthesia Implications.

The anesthesiologist and operating room staff are particularly vulnerable to acquiring hepatitis C by way of needle-stick injury or from contaminated blood or tissues. Patients with a known history of hepatitis B or C or high-risk patients (e.g., intravenous drug abusers) should be managed with strict barrier precautions (see Table 12-5 ). High-quality gloves (or two pairs of gloves) should be worn. Hands must be rigorously washed after gloves are removed, and contaminated gloves should be disposed of rapidly. Barrier protection of the eyes and mouth is imperative. Contaminated needles should not be recapped, manipulated with both hands, or manually removed from a syringe. They should be disposed of, alongside contaminated sutures and other sharp objects, in a solid, carefully marked container adjacent to the operative site.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Forty million people (range, 34 to 46 million) were living with HIV/AIDS by the end of 2003 with 5 million new cases that year. It has been estimated that 20% to 25% of HIV-positive patients will require surgery during their illness.[59]

Clinical and Pathologic Features.

HIV-1 is a single-strand RNA retrovirus. After entering the cell, the virus is copied by a reverse transcriptase; this enables the virus to produce double-stranded DNA, which then integrates into the host's cells. The most common mode of infection is sexual transmission through the genital mucosa. HIV may also be spread by transfusion of contaminated blood or by needle sharing or needle-stick injury.

Within 2 days the virus can be detected in the internal iliac lymph nodes, and within 5 days (range, 4 to 11 days) the virus can be cultured from the plasma. There is rapid dissemination to lymphoid tissue and the brain. The CD4+ T lymphocytes (T-helper cells) are the primary target of infection. Progression of HIV illness is defined by the decline in CD4 + cell count leading to immune deficiency and manifest by opportunistic infections and unusual neoplasia. Thus progression is followed by monitoring the cell count per cubic millimeter.

Plasma viral load (which can be quantified) is initially extremely high and then declines in the clinical latency period. This early acute infection, the seroconversion illness, is transient; symptoms include fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, myalgia or arthralgia, and nausea, vomiting, and diarrhea. This may be confused with a flu-like illness.

The clinical latency period may last 7 to 12 years during which time billions of virions and CD4+ cells are destroyed each day. The T lymphocytes are replenished and immune status remains functional.

Prior to the development of “full blown AIDS” the patient enters a stage of persistent generalized lymphadenopathy. In this stage nodes of greater than 1 cm in more than two noninguinal sites are present for more than 3 months. The patient may lose weight and develop seborrheic dermatitis.

AIDS is diagnosed by a CD4+ count of less than 200 cells/μL or the presence of one or more defining illnesses ( Table 12-7 ). The patient is at significant risk for opportunistic infections and malignancies, including toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy, cytomegalovirus infection, herpes symplex virus infection, brain lymphomas, and tuberculosis. HIV is thus a multisystem disease ( Table 12-8 ).

TABLE 12-7   -- AIDS-Defining Illnesses



Candidiasis of bronchi, trachea, lungs, or esophagus Invasive cervical cancer



Coccidioidomycosis, disseminated or extrapulmonary



Cryptococcosis, extrapulmonary



Cryptosporidiosis, chronic intestinal (greater than 1 month's duration)



Cytomegalovirus disease (other than liver, spleen, or nodes)



Cytomegalovirus retinitis (with loss of vision)



Encephalopathy, HIV-related



Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis



Histoplasmosis, disseminated or extrapulmonary



Isosporiasis, chronic intestinal (greater than 1 month's duration)



Kaposi's sarcoma



Lymphoma, Burkitt's (or equivalent term)



Lymphoma, immunoblastic (or equivalent term)



Lymphoma, primary, of brain



Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary



Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)



Mycobacterium, other species or unidentified species, disseminated or extrapulmonary



Pneumocystis carinii pneumonia



Pneumonia, recurrent



Progressive multifocal leukoencephalopathy



Salmonella septicemia, recurrent



Toxoplasmosis of brain



TABLE 12-8   -- Complications of HIV Multiorgan Disease






Pneumocystis carinii



Bacterial pneumonia












Oral/pharyngeal candidiasis, herpetic infections






Leukopenia, lymphopenia









Drug toxicity, bone marrow suppression






Pericarditis effusion






Myocarditis (late stages of infection)



Dilated cardiomyopathy



Endocarditis (intravenous drug abuse)



Pulmonary hypertension



Drug-related cardiotoxicity



Thromboembolitic events



Myocardial infarction






Infectious diarrhea, proctitis



Gastrointestinal bleeding



Acalculous cholecystitis



Vomiting, loss of appetite, cachexia



Dysphagia (Candida albicans, cytomegalovirus), esophagitis



Liver disease, hepatitis B and C, other infections



Neurologic Problems in AIDS Patients



Distal, symmetrical sensory neuropathy: numbness, tingling, painful dysesthesias and paresthesias



Chronic, inflammatory demyelinating polyneuropathy



AIDS encephalopathy or AIDS dementia complex: cognitive, motor, and behavioral changes



Vacuolar myelopathy: sensory disturbance, spasticity and hyperreflexia (acute or chronic progression)



Segmental (focal) myelopathy, acute or subacute (less common)

Data from Hughes SC: HIV and Anesthesia. Anesthesiol Clin North Am 2004;22:379-404.




With the development of constitutional symptoms (physiologic reserve is depleted), viral load again increases and the patient becomes extremely infectious. This has significant implications for health care providers.

Anesthesia and HIV.

Perioperative risk correlates well with immune function. A CD4+ cell count of less than 200 cells/μL puts the patient at significant risk for opportunistic infections and increased infectious risk associated with surgery.[60] The presence of pulmonary, cardiac, or renal disease may also lead to perioperative complications. Consequently, the patient with AIDS requires significant preoperative workup. This should include complete blood cell count, a coagulation panel, and liver and renal function tests. The patient should have an electrocardiogram and chest radiograph, regardless of age and gender. If there is a history of pulmonary disease, and the patient is undergoing major surgery, pulmonary function testing is necessary.

There are numerous airway complications of HIV/AIDS: oral candidiasis, herpes simplex ulcers (risk of transmission to the laryngoscopist), and hemorrhagic Kaposi's sarcoma lesions. Lung parenchyma may be damaged by Pneumocystis, histoplasmosis, cytomegalovirus, or tuberculosis, with significant impact 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 neuropathy (inadequate heart rate response to vasodilatory effects of anesthetic agents), cardiomyopathy, and myocardial lymphoma. If cardiac involvement is suspected, the patient should have preoperative echocardiography to determine both systolic and diastolic function. The presence of significant cardiac dysfunction is an indication for invasive perioperative monitoring.

Many neurologic problems are associated with HIV/AIDS. These include delirium, headache, localized or generalized seizures, limb weakness, and visual loss. It is important to document, preoperatively, the presence or absence of focal neurologic deficit to avoid confusion with complications of anesthesia and surgery. The presence of AIDS-related dementia may preclude the patient consenting to both surgery and anesthesia.[61]

A variety of opportunistic infections of the gastrointestinal tract manifest in HIV/AIDS. Chronic diarrhea is common and associated with hypokalemia and volume depletion. Colonic perforation has been associated with cytomegalic colitis. Lymphoma has been associated with bowel obstruction, increasing the risk of aspiration pneumonitis.

Patients with HIV/AIDS have a predisposition for anemia, as a consequence of bone marrow suppression, associated with chronic disease, malnutrition (gastrointestinal involvement impairs iron, vitamin B12, and folate absorption), and drug therapy (zidovudine).

Past medical/social history is of particular importance in this patient population. Substance abuse, and intravenous drug abuse in particular, remains the most significant risk factor. The concurrent presence of sexually transmitted diseases such as hepatitis B, hepatitis C (severe hepatic involvement), and syphilis (neurologic deficits in late stage) may alter anesthetic management.[62]

The current standard therapy for HIV/AIDS is highly active antiretroviral therapy (HAART), which involves combination chemotherapy. These drugs fall into four categories: nucleoside analog reverse transcriptase inhibitors, non-nucleoside analog reverse transcriptase inhibitors, protease inhibitors, and the new category of fusion inhibitors ( Table 12-9 ).

TABLE 12-9   -- Antiretroviral Drug Therapy: Side Effects with Anesthetic Significance

Side Effect

Responsible Antiretroviral Drug













Electrolyte disturbances

Protease inhibitors



Hepatic dysfunction




Peripheral neuropathy










Cardiac dysrhythmias


From Kuczkowski KM: Human immunodeficiency virus in the parturient. J Clin Anesth 2003;15:224-233.




From the anesthesiologist's perspective, protease inhibitors are the most important agents. They are potent cytochrome P450 inhibitors, thus prolonging the duration of action of hepatically metabolized drugs, such as fentanyl, midazolam, and morphine. Judicious dosing and careful titration are recommended.

The anesthesia care plan should take into account immunosuppression, systemic disease, and the risk of transmission of the virus to health care providers. There is no evidence of increased anesthesia risk in this patient population, nor is there evidence of increased complications associated with regional anesthesia. [63] [64]

Specific surgical procedures associated with HIV/AIDS and anesthesia implications are described next.

Surgery and HIV.


Patients with HIV may develop a variant of thrombocytopenia purpura known as HIV-associated immune thrombocytopenia purpura (HIV-ITP). This characteristically does not respond to corticosteroid therapy and may occur with HIV infection or AIDS. The treatment of choice is combination retroviral therapy; however, in refractory cases splenectomy is required.[64]

The anesthesiologist must be aware that the patient is at significantly increased risk of bleeding and that the platelet count cannot be raised by administration of corticosteroids or platelet transfusion. Consequently, epidural anesthesia should be avoided, as should the placement of large-bore intravenous catheters in noncompressible vessels.

Abdominal Surgery.

Patients with HIV may develop abdominal pain for a variety of reasons, rarely requiring laparotomy. Surgery may be required for resection of neoplasm, particularly if there is bowel obstruction, drainage of intra-abdominal abscess, and appendectomy.

The presence of immunodeficiency may mask the signs (leukocytosis) of infection, leading to delayed diagnosis.[65] Moreover, these patients may mount a less dramatic SIRS response than expected, leading to dramatic development of severe sepsis without warning. Low CD4 + count independently predicts an increased incidence of postoperative sepsis.[60]

Patients with HIV are at particular risk for biliary tract disease—cholecystitis, cholangitis, and infections with opportunistic organisms such as Salmonella, cytomegalovirus, and Cryptosporidium. There is an increase risk of extrahepatic biliary obstruction caused by external compression of the common bile duct by enlarged portal lymph nodes (or lymphoma).[66] Laparoscopic cholecystectomy or choledochojejunostomy may be required.

Patients infected with HIV, or with AIDS, frequently require anorectal surgery for excision of extensive condylomata, anal fistulas, or perirectal abscesses. The patient is positioned in the prone-jackknife position. General or spinal anesthesia (assuming the patient does not have a coagulopathy) can be safely administered, as with patients who are not infected. Postoperative wound healing in patients with HIV, but not AIDS, is not impaired.[67]


Intracranial pyogenic abscess, toxoplasmosis, or lymphoma may cause neurologic symptoms in HIV-infected patients. Infrequently, stereotactic needle biopsy is required for diagnosis. The procedure is usually carried out under monitored anesthesia care, for example with a remifentanil-propofol infusion and spontaneous ventilation.

Thoracic Surgery.

The HIV-infected patient will occasionally require open lung biopsy to clarify the diagnosis in the event of respiratory failure. Opportunistic infections can usually be diagnosed by sputum examination or bronchoalveolar lavage. However, the identification, classification, and staging of lymphoma may require surgery. There is additional risk of recurrent pneumothorax and empyema, which can be managed by VATS.

It is important to assess and clarify the extent of the respiratory insult and the degree of hypoxemia in these patients before surgery. Careful attention must be placed in the ventilation strategy in the presence of hypoxemic respiratory failure. In the presence of significant parenchymal lung disease, the patient may be intolerant of one-lung anesthesia.


Management of HIV-seropositive pregnant women includes attempts to minimize the infant's risk of acquired infection. Perinatal HIV transmission occurs antepartum, intrapartum, or postpartum. High maternal viral load increases the likelihood of perinatal transmission of HIV. Most perinatal HIV transmissions occur during labor and vaginal delivery. Hence obstetric care is targeted at minimizing exposure to maternal blood and genital secretions. This involves avoiding the following: percutaneous umbilical cord sampling, fetal scalp clips (when possible), fetal scalp sampling, delivery techniques that could produce abrasions in the infant's skin (e.g., vacuum or forceps), and immediate removal of maternal blood and fluids from the infant.[59] There is a relationship between the mode of delivery and risk of transmission: the risk is significantly reduced by elective cesarean section ( Table 12-10 ). [68] [69] This benefit may be lost if spontaneous rupture of the membranes has occurred. HIV may be transmitted through breast milk so breast feeding is discouraged.

TABLE 12-10   -- Elective Cesarean Delivery to Reduce the Transmission of HIV: Rates of Vertical Transmission


Elective Cesarean Delivery

Other Mode of Delivery

No antiretroviral therapy



Antiretroviral therapy



From The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1—a meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group. N Engl J Med 1999;340:977-987.




Elective cesarean section should be performed under spinal anesthesia, as in noninfected parturients. [61] [63]

HIV and the Risk to the Anesthesiologist/Health Care Worker.

HIV is the most feared of all occupationally acquired diseases. It is important to note that patients with HIV/AIDS represent a reservoir of potential infectious exposures, in addition to the virus itself. The most important of these is tuberculosis. Additionally, the patient may be simultaneously infected with hepatitis B or C or both.

Universal precautions (see Table 12-5 ). should be employed when handling body fluids, tissue, blood, and blood products. The anesthesiologist must wear gloves at all times when in contact with the patient, the patient's blood, or tissues.[70] Where there is significant risk of exposure to the patient's body fluids—inserting arterial or central lines, performing bronchoscopy or fiberoptic intubation, or using epidural, spinal or regional anesthetic—a gown and face mask with eye protection is recommended. Contaminated needles should not be recapped by hand.

The risk of HIV transmission from a needle-stick injury with HIV-infected blood is approximately 0.32% (a far lower risk than with hepatitis C).[70] Immediately after needle-stick injury the health care worker should be treated with antiretroviral drugs (within 1 hour); this can reduce the rate of seroconversion by 80%.[1] Factors determining the risk to the exposed health care provider include type of the procedure for which needle was used, depth of needle-stick injury, the quantity of blood involved, and viral titers in the HIV-infected patient.[61]

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Tuberculosis (TB) remains a major worldwide scourge. Approximately one third of the world's population has been exposed, and there are about 8 million new cases per year and 4 million deaths. Nevertheless, until the AIDS epidemic, the prevalence of TB declined dramatically from the 1950s to the 1980s. There was a 20% increase in the incidence of TB in the United States between 1985 and 1992, due principally to AIDS but also associated with immigration form countries with endemic TB, poverty, and limited health services in 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 Control and Prevention (CDC). Three fourths of cases among foreign immigrants came from seven countries: Vietnam, the Philippines, India, China, South Korea, Mexico, and Haiti.

Mycobacterium tuberculosis is an aerobic rod that thrives in an aerobic environment, at a Po2 of 140 mm Hg. Consequently, it preferentially infects the anterior apical segments of the lung. The bacilli are transmitted via droplet infection as a result of coughing or sneezing. TB may also be transmitted from one patient to another through anesthesia breathing systems or mechanical ventilators.

The principal site of infection of tuberculosis is the lung, but the bacterium may infect other organs, including the kidneys, brain, bones, joints, spine, and genitourinary

TB typically presents as general malaise, anorexia, weight loss, fever, night sweats, productive cough, and hemoptysis. Diagnosis is made by serial sputum sampling for detection of acid-fast bacilli. In active primary TB, chest radiography reveals lobar pneumonia, with subsegmental atelectasis and ipsilateral hilar adenopathy. The more classic “reactivation” form of TB manifests with cavitating lesions in the posterior segment of the right upper lobe and apical segments of the lower lobes. A normal radiograph does not exclude TB, and in the presence of HIV the lesions are often atypical. If TB is suspected, respiratory isolation precautions should be instituted immediately, until the patient is deemed not to be infectious (acid-fast bacillus negative on three successive sputum samples, improving symptoms and improving chest radiograph).

Current therapeutic regimens for TB involve four-drug therapy, over 6 months:



Initial 2 months (all oral doses)—Isoniazid (INH), 300 mg/day; rifampin (RIF), 600 mg/day; pyrazinamide (PZA), 2 g/day); and ethambutol (ETB), 2 g/day



Final 4 months (if initial 2 months are successful by smear conversion and resolving symptoms)—INH, 300 mg/day, and RIF, 600 mg/day, or, alternatively, INH, 900 mg, and RIF, 600 mg, twice weekly.

Patients suspected of having active TB are nursed in respiratory isolation, in specially engineered negative pressure isolation rooms. Precautions can be supplemented with high-efficiency particulate air (HEPA) filters and ultraviolet irradiation devices installed near the ceiling of the room. Clear infection control guidelines must be in place and followed rigorously. The patient should wear a surgical mask when outside an isolation room.

Anesthesia Implications.

A patient with active TB represents major infection risk for other patients and health care workers. Elective surgery should be avoided and postponed until the patient is no longer infections. For emergent or semi-emergent surgery, special precautions should be taken.

Contact with health care workers should be minimized; the number of staff in the operating room should be kept to a minimum. The operating room doors should be kept closed and infectious risk signs placed prominently as alerts to unwitting staff. The anesthesia breathing system should be separated from the mechanical ventilator by a HEPA filter. The breathing system should be disposed of at the end of the case.

Standard surgical face masks provide insufficient protection from droplet infection: the anesthesiologist should wear a National Institute for Occupational Safety and Health (NIOSH) N95 standard face mask and eye protection. The mask should fit snugly over the face such that all inspired air passes through it.

Extreme care should be placed in the disposal of soiled endotracheal tubes, suction tubing, and so on. If laryngeal mask anesthesia is performed, the mask should not be recycled. The patient should undergo recovery in isolation. If no isolation room is available, recovery is in the operating room or in an ICU isolation room ( Table 12-11 ).

TABLE 12-11   -- American Society of Anesthesiologist's Guidelines for Operative Care of the Patient with Tuberculosis

1. Elective operative procedures on a patient who has tuberculosis should be delayed until the patient is no longer infectious.

2. Patients should be transported to the operating room wearing surgical masks to prevent respiratory secretions from entering the air.

3. The doors of the operating room should be closed, and traffic into and out of the room should be minimized.

4. Perform the procedure at a time when other patients are not present in the operating room suite and when a minimal number of personnel are present (e.g., at the end of the day). Ideally the operating room should have an anteroom that is negative pressure to the corridor and the operating room. The anesthesiologist and other health care workers should wear a NIOSH N95 compatible face mask.

5. Exhausted air should be diverted away from hospital.

6. A bacterial filter between the anesthesia circuit and the patient's airway will prevent contamination of anesthesia equipment or discharge of tubercle bacilli into the ambient air.

7. These filters can be placed between the Y-connector and the mask, laryngeal mask, or endotracheal tube.

8. During recovery from anesthesia, the patient should be monitored and should be placed in an isolation room.

9. Alternatively, the patient should undergo recovery in the operating room or the patient's own room.



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Prions (proteinaceous infective particles) are infectious proteins without (known) nucleic acid genomes. A number of these agents infect mammals, preferentially targeting neurologic tissue, causing spongiform encephalopathies. They include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and kuru, among others in humans; scrapie in sheep; and spongiform encephalopathy in cattle (bovine spongiform encephalopathy: BSE— “mad cow disease”). These neurodegenerative diseases are universally lethal.

Recent interest in these agents followed the description, in 1996, of a new variant of CJD (known as variant CJD [vCJD]), which appears to have crossed over from BSE. [71] [72] Following a cluster of reported cases in the United Kingdom, the specter of perioperative transmission of CJD and nvCJD has emerged. Moreover, emerging data suggest that these diseases may be spread by blood transfusion.[73]

Clinical and Pathologic Features.

Variant CJD affects mainly young people. The average age of patients is 29 years, and the median duration of illness is 14 months. Since vCJD was first reported in the UK in 1996, there have been 151 cases of definite or probable vCJD; and 146 deaths (http://www.cjd.ed.ac.uk/figures.htm). There have been 1010 reported cases of CJD of all causes in the United Kingdom alone.

CJD causes progressive neuropsychiatric degeneration, associated with gradual reduction in consciousness, myoclonus, ataxia, chorea, or dystonia. In the late stages the patient progresses to a near catatonic state.

The prions causing vCJD are found in high concentration in the brain, spinal cord, and eye. They are also found in lymphoreticular tissue, a potential source of infectiousness.

Diagnosis of vCJD is difficult with no reliable investigation available. Diagnosis is made by a combination of clinical symptoms and signs and a positive tonsillar biopsy or by the presence of bilateral high pulvinar signal on magnetic resonance imaging (MRI).

Anesthesia Implications.

Anesthesia may be required for patients with vCJD for tonsillar or brain biopsy, tracheostomy, or placement of a percutaneous endoscopic gastrostomy (PEG) feeding tube. This has significant implications for the performance of anesthesia and for the operating suite staff. Most important is the potential for transmission of disease between patients via contaminated instruments. Prions are small enough to reside in the microscopic crypts on stainless steel instruments and are not removed easily by standard washing techniques; furthermore, they are resistant to deactivation by traditional methods of decontamination. Although some novel approaches have been suggested, they have not been widely adopted.[74]

All unnecessary equipment and staff should be removed or excluded from the operating room, and warning signs placed outside. Staff must take extraordinary barrier measures such as double gloving, eye protection, aprons, and disposable liquid-repellant gowns.

Where possible, disposable equipment should be used—including laryngoscopes, face masks, and oral and laryngeal mask airways—these items should be incinerated. If the diagnosis of CJD or vCJD is confirmed, all instruments should be disposed of.[75]

In setting up the anesthetic it is preferable to use an ICU style ventilator, which can be stripped afterward and disposables incinerated. If the patient is already intubated, the ventilator from the ICU should travel with the patient. Total intravenous anesthesia can be administered. Although there are no specific contraindications to anesthesia agents, succinylcholine should be avoided when degenerative myopathy exists. Pipeline vacuum systems should not be used, and a portable machine should accompany the patient in the operating room, recovery, and ward.[76] During surgery all needles, clamps, sutures, or sharps should be directly disposed of into a suitable receptacle. Tissue matter should be carefully disposed of in clearly labeled bags.

The patient should either undergo recovery in the recovery room or be returned directly to the ICU.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

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Intra-abdominal abscesses are walled-off collections of pus or parasites surrounded by fibrotic tissue, induced by inflammation, occurring within the abdomen. They may be located within viscera, in the peritoneum, between loops of bowel, or in the retroperitoneal space.

Intraperitoneal infections result from postsurgical anastomotic leakage, viscus perforation (e.g., a ruptured diverticulum), resolution of diffuse peritonitis into multiple small abscesses, or infection with parasites.

Pyogenic Liver Abscess

Liver abscesses are divided into pyogenic and parasitic (amebic and hydatid). The incidence of hepatic abscess is estimated as 13 to 20 cases per 100,000.[77] Most pyogenic liver abscesses are secondary to infection originating in the abdomen ( Table 12-12 ). Cholangitis due to stones or strictures is the most common cause, followed by abdominal infection due to diverticulitis or appendicitis. In 15% of cases no cause can be found.

TABLE 12-12   -- Origins and Causes of Pyogenic Liver Abscess



Liver and Biliary Tract






Biliary strictures






Blocked biliary stent



Liver biopsy



Gallbladder empyema



Secondary infection of hepatic cyst












Crohn's disease






Abscess Extension



Perforated peptic ulcer



Subphrenic abscess



Disseminated Sepsis



Catheter-related bloodstream infection



Infective endocarditis



Dental infection

Data from Krige JEJ, Beckingham IJ: ABC of diseases of liver, pancreas, and biliary system: Liver abscesses and hydatid disease. BMJ 2001:322:537-540.




In the United States 80% of cases of liver abscess are pyogenic. The majority of pyogenic liver abscesses are polymicrobial infections, usually with gram-negative aerobic and anaerobic organisms. Most organisms are of bowel origin, with Escherichia coli, Klebsiella pneumoniae, Bacteroides, enterococci, anaerobic streptococci, and microaerophilic streptococci being most common. In approximately 50% of cases there is infection with anaerobic organisms. In patients with preexisting infections such as dental abscess or endocarditis, infection with hemolytic streptococci, staphylococci, or Streptococcus milleri may occur. In the immunosuppressed population, such as patients undergoing chemotherapy, with AIDS, or following transplantation, opportunistic organisms or fungi may infect the liver.[78] The classic presentation of pyogenic liver abscess is with abdominal pain, swinging fever, night sweats, nausea, vomiting, anorexia, anergia, and malaise. There is usually hepatomegaly, tenderness in the right upper quadrant, and raised right hemidiaphragm (with sympathetic pleural effusion) on chest radiography. There is leukocytosis, anemia, and, in the presence of biliary tree compression due to mass effect, increased serum transaminase and alkaline phosphatase levels. Ultrasonography is the preferred imaging technique, because internal septations or daughter cysts (hydatid disease) are more clearly visualized.

Treatment is determined by the size, number, and nature of the lesions within the liver. Multiple small abscesses are treated by antimicrobial therapy alone, which must include a penicillinase-resistant penicillin, an antigram-negative agent, and metronidazole. In the absence of an intra-abdominal source, aspiration of the abscess under ultrasound or computed tomography (CT) can be performed. Usually a continuous drainage catheter is left in place. If an abdominal source is present, if there is a very large abscess or multilocular abscesses, or if antibiotics fail, then surgical drainage is necessary.

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Amebic Liver Abscess

About 10% of the world's population is chronically infected with Entamoeba histolytica.[78] Amebiasis is the third most common parasitic cause of death, surpassed only by malaria and schistosomiasis. The prevalence of infection varies widely, and it occurs most commonly in tropical and subtropical climates. Overcrowding and poor sanitation are the main predisposing factors.

The parasite is transmitted through the fecal-oral route with the ingestion of viable protozoal cysts. The cyst wall disintegrates in the small intestine, releasing motile trophozoites. These migrate to the large bowel, where pathogenic strains may cause invasive disease. Mucosal invasion results in the formation of flask-shaped ulcers through which amebae gain access to the portal venous system. The abscess is usually solitary and affects the right lobe in 80% of cases. The abscess contains sterile pus and reddish brown (“anchovy paste”) liquefied necrotic liver tissue. Amebae are occasionally present at the periphery of the abscess.

Clinical and Pathologic Features.

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.

The diagnosis is based on clinical, serologic, and radiologic features. The patient is usually resident in an endemic area or has visited one recently, although there may be no history of diarrhea. Patients commonly have leukocytosis, with 70% to 80% polymorphs (eosinophilia is not a feature), a raised erythrocyte sedimentation rate, and moderate anemia. In patients with severe disease and multiple abscesses, alkaline phosphatase activity and bilirubin concentration are raised. Stools may contain cysts, or, in the case of dysentery, hematophagous trophozoites.

Chest radiography usually shows a raised right hemidiaphragm with atelectasis or pleural effusion. Ultrasonography shows the size and position of the abscess and is useful when aspiration is necessary and to assess response to treatment. Serologic tests provide a rapid means of confirming the diagnosis, but the results may be misleading in endemic areas because of previous infection. Indirect hemagglutination titers for Entamoeba are raised in over 90% of patients. In areas where amebiasis is uncommon, failure to consider the infection may delay diagnosis.

Serious complications occur as a result of secondary infection or rupture into adjacent structures such as pleural, pericardial, or peritoneal spaces. Two thirds of ruptures occur intraperitoneally and one third are intrathoracic.


Ninety-five percent of uncomplicated amoebic abscesses resolve with metronidazole alone (800 mg, three times a day for 5 days). Supportive measures such as adequate nutrition and pain relief are important. Clinical symptoms usually improve greatly within 24 hours. Lower doses of metronidazole are often effective in invasive disease but may fail to eliminate the intraluminal infection, allowing clinical relapses to occur. After the amebic abscess has been treated, patients are prescribed diloxanide furoate, 500 mg, every 8 hours for 7 days, to eliminate intestinal amebae.

Patients should have ultrasonographically guided needle aspiration if serology gives negative results or the abscess is large (<10 cm), if they do not respond to treatment, or if there is impending peritoneal, pleural, or pericardial rupture. Surgical drainage is required only if the abscess has ruptured causing amebic peritonitis or if the patient has not responded to drugs despite aspiration or catheter drainage.

Anesthesia Implications of Pyogenic and Amebic Abscesses.

Abnormal liver function is unusual except in the event of biliary obstruction or parenchymal compression. The presence of jaundice or raised serum transaminases likely has little effect on the conduct of anesthesia, because inherent liver metabolic function is usually intact. The patient may have evidence of low-grade or frank sepsis, in which case the guidelines established for the management of the septic patients, described earlier in the chapter, should be followed. If the patient is bacteremic, then epidural analgesia and placement of central venous catheters should be avoided, to prevent the development of catheter-related infection.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Hydatid Disease

Hydatid disease in humans is caused by the dog tapeworm Echinococcus granulosus. Dogs are the definitive host. Ova are shed in the feces and then infect the natural intermediate hosts such as sheep or cattle. Hydatid disease is endemic in many sheep-raising countries. Increasing migration and world travel have made hydatidosis a global problem of increasing importance. Human infection follows accidental ingestion of ova passed in dog feces. The ova penetrate the intestinal wall and pass through the portal vein to the liver, lung, and other tissues. Hydatid cysts can develop anywhere in the body, but two thirds occur in the liver and one fourth in the lungs.

Clinical and Pathologic Features.

Patients with a liver hydatid may present either with liver enlargement and right upper quadrant pain due to pressure from the cyst or acutely with a complication. Complications include rupture of the cyst into the peritoneal cavity, which results in urticaria, anaphylactic shock, eosinophilia, and implantation into the omentum and other viscera. Cysts may compress or erode into a bile duct causing pain, jaundice, or cholangitis, or the cyst may become infected secondary to a bile leak.

Ultrasonography and CT will show the size, position, and number of liver cysts and any extrahepatic cysts. Classically “daughter cysts” are visualized within the main collection. Around 10% of patients with a liver cyst will also have a lung hydatid on chest radiography. The diagnosis is confirmed by hemagglutination and complement fixation tests. Aspiration of the cyst for diagnostic purposes is avoided until the diagnosis is confirmed. Biliary tree compression may increase serum bilirubin and transaminase levels. Eosinophilia is present in 40% of patients.

Surgery and Hydatid Disease.

All symptomatic cysts require surgical removal to prevent complications. Radiologic cyst drainage has been described but is not widely practiced.[79] Consequently, the majority of these patients require general anesthesia.

The primary goal of surgery is careful dissection and removal of the intact cyst, avoiding spillage of its contents, which would result in the development of secondary cysts in the peritoneum. The patient is treated with albendazole for 4 weeks preoperatively, to shrink the cyst. The surgical field is carefully isolated by abdominal swabs soaked in scolicidal fluid. The cyst fluid is aspirated and replaced by a scolicidal agent such as 0.5% sodium hypochlorite, 0.5% cetrimide, 0.5% silver nitrate, 30% hypertonic saline, or sodium hydroxide. This sterilizes the cyst cavity. After decompression, the cyst and contents are carefully shelled and the cavity filled with isotonic saline or omentum and closed.

Anesthesia Implications.

Liver dysfunction caused by an enlarging cyst rarely interferes with metabolic function. There may be compressive atelectasis in the lower segments of the right lung, leading to hypoxemia, that worsens after induction of anesthesia. PEEP is recommended. There is no contraindication to epidural catheter placement, although epidural infusion should be delayed until the cyst has been successfully excised. An arterial line should be placed to monitor beat-to-beat variation in blood pressure.

Two major intraoperative complications have been described: cyst rupture, leading to anaphylactic shock,[80] and hyperosmolar coma, following the administration of hypertonic saline. [81] [82] Anaphylaxis is treated with intravenous fluid, epinephrine, antihistamines, and corticosteroids—all of which should be at hand in the operating room. Pretreatment with H1 and H2 antagonists may be beneficial.[83]

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Splenic Abscess

Splenic abscesses are rare. There are five major causes: (1) metastatic spread from septic foci—including intravenous drug abuse, endocarditis, salmonella (in AIDS), osteomyelitis, tuberculosis, dental extractions, infected intravascular devices; (2) spread from adjacent organs—pancreatic and subphrenic abscesses, gastric and colonic perforations; (3) infection of splenic infarct—seen in hemoglobinopathies, including sickle cell disease and splenic artery embolization; (4) splenic trauma, and (5) immunocompromise.

Clinical and Pathologic Features.

Patients present with fever, leukocytosis, and right upper quadrant pain. It may be associated with raised left hemidiaphragm, pleural effusion, and pain referred to the left shoulder.

Splenic abscess is most effectively diagnosed by CT or MRI. In approximately 50% of patients, blood cultures are positive. In the majority of abscesses streptococci or staphylococci are present, gram-negative rods are present in 30%, anaerobes in 12%, and mixed organisms in 25%. Antimicrobial treatment includes penicillinase-resistant β-lactam, aminoglycoside, or aztreonam and metronidazole.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

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Appendiceal Abscess

Appendiceal abscesses result from acute rupture of an acutely inflamed appendix. Appendicitis is the consequence of obstruction of the appendiceal lumen by a fecalith. There is increased intraluminal pressure associated with bacterial proliferation. There is venous congestion, distention of the organ, and eventually arterial compromise. Ischemia and gangrene result. In the majority of cases this results in abscess formation. However, rupture may also result in diffuse peritonitis, which represents a surgical emergency.

Clinical and Pathologic Features.

Patients present with lower abdominal pain, guarding, leukocytosis, and low-grade fever.

The diagnosis is confirmed by CT. If a contrast agent is given, abscesses are well defined with rim enhancement; a phlegmon does not enhance. This will also provide information regarding the feasibility of percutaneous drainage.

Antimicrobial therapy is targeted at the polymicrobial nature of the abscess—a combination of gentamicin or amikacin plus either metronidazole or clindamycin is recommended.

There are two surgical approaches to appendix abscess: (1) immediate appendectomy with abscess drainage, the major risk of which is pus dissemination through the peritoneum due to the friability of tissues, and (2) delayed surgery—awaiting abscess organization. If the latter approach is planned, spontaneous resolution of the abscess is anticipated and appendectomy is planned at 6 to 8 weeks. However, if the abscess persists it should be drained percutaneously.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

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Diverticular Abscess

Diverticular abscesses form after perforation of a diverticulum. Perforation into the peritoneum leads to diffuse peritonitis, requiring immediate surgery. Often, however, the abscess may be contained by mesentery and/or local structures. The patient thus presents with malaise, pyrexia, leukocytosis, and generalized abdominal pain. The diagnosis is confirmed by CT. The most common site of diverticular disease is the sigmoid colon. The patient usually develops a colonic ileus.

Clinical and Pathologic Features.

In the early stages, following perforation, when there is fecal soiling of the peritoneum, the patient may remain surprisingly well, leading to a false sense of security. This “honeymoon” period lasts 24 to 48 hours, followed by a dramatic SIRS response, fluid sequestration, and hypoxemia. This is the clinical manifestation of the proliferation of bowel bacteria in the peritoneum. Early laparotomy allows for peritoneal irrigation and colonic resection. At this stage mild to moderate vasodilatation may be present but patients rarely have overt signs of sepsis.

Diverticular abscesses are usually drained radiologically—using CT guidance. This may require sequential procedures. Once the initial inflammatory response has resolved and the source is controlled, laparotomy and bowel resection is performed.

Antimicrobial coverage should include therapy for gram-positive organisms and anaerobes and includes ampicillin/sulbactam or ampicillin, gentamicin, and metronidazole.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

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Necrotizing soft tissue infections (NSTIs) represent a group of diseases characterized by rapidly spreading necrotizing infection of subcutaneous tissue, fascial planes, and muscle. NSTIs are classified anatomically, determined by the depth of infection and the tissues involved ( Table 12-13 ).[84]

TABLE 12-13   -- Classification and Risk Factors of Necrotizing Soft Tissue Infections






Infections of skin and subcutaneous tissue



Progressive synergistic bacterial gangrene



Chronic undermining burrowing ulcer (Meleney's ulcer)



Idiopathic scrotal gangrene (Fournier's gangrene)



Infections involving subcutaneous tissue and fascia



Hemolytic streptococcal gangrene



Necrotizing fasciitis



Gram-negative synergistic necrotizing cellulitis



Clostridial cellulitis



Infections involving muscle



Clostridial myonecrosis



Streptococcal myositis



Risk Factors






Peripheral vascular disease



Chronic liver disease









Collagen vascular diseases



Chronic renal failure



Recent surgery



Penetrating trauma



Systemic sepsis (the “second hit”)






Advanced age









Intravenous drug abuse



Postoperative infection



Morbid obesity

Data from Kuncir EJ, Tillou A, St. Hill CR, et al: Necrotizing soft tissue infections. Emerg Med Clin North Am 2003:21:1075-1087.




The history is usually minor trauma or surgery in a vulnerable patient.[85] Often unexplained pain that increases rapidly over time is the first manifestation. The patient may develop early dramatic symptoms and signs of sepsis—confusion, delirium, tachycardia, tachypnea, hypotension, oliguria. The source may not be readily apparent. Clinical findings include erythema, edema, and induration of the tissues, occasionally with bullae formation.

Necrotizing infections have the following features in common:



Extensive tissue destruction



Thrombosis of blood vessels



Abundant bacteria spreading along fascial planes



Relatively few acute inflammatory cells

Necrotizing Fasciitis

Necrotizing fasciitis is a deep-seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat, although it may spare the skin. It usually involves the extremities, the abdominal wall, or the perineum. There is much confusion about the nomenclature of this disease. For example, necrotizing infection of the perineum is often called Fournier's gangrene. Other names used include progressive bacterial synergistic gangrene (PBSG) and Meleney's ulcer. It is simpler to classify necrotizing fasciitis according to the type of microbes involved. There are two types of necrotizing fasciitis:



Type 1 Polymicrobial form: This is an infection with mixed bowel organisms. Microbes may be aerobic (e.g., staphylococci, group A streptococci, Escherichia coli) or anaerobic (e.g.,Clostridium, Bacteroides, Peptostreptococcus).



Type 2 Monomicrobial form: This is caused by group A streptococci, which produces a number of cellular components and exotoxins that lead to the destruction of tissue and spread of infection.

Clinical and Pathologic Features.

The patient usually presents with pain, out of proportion to apparent tissue injury, and malaise, with significant SIRS response. There may be a history of surgery, trauma, or minor injury, for example, in a diabetic patient.

Infection rapidly spreads throughout the subcutaneous tissues and along fascial planes. There may be localized thrombosis of blood vessels, which leads to loss of perfusion and necrosis/gangrene. Crepitus may be present, owing to gas production in the tissues.

The natural progression of the disease is severe sepsis, septic shock, multiorgan failure, and death. Early aggressive skin débridement is imperative, often with the patient in extremis. In addition to source control, empirical antibiotics must be administered, principally clindamycin, aminoglycosides, or third-generation cephalosporins and metronidazole. Supportive care usually involves aggressive volume resuscitation and vasopressors, which can usually be weaned with removal of necrotic tissue.

Surgical débridement of necrotic tissue is often extensive and usually involves multiple trips to the operating room. Amputation of limbs may be necessary. In addition, where anaerobic, gas-producing bacteria are involved, hyperbaric oxygen therapy may be indicated.

Anesthesia Implications.

Anesthesiologists may be involved with patients with necrotizing fasciitis either during the initial presentation, where fulminant sepsis is the major manifestation, or during subsequent visits to the operating room for tissue débridement. Surgery should not be delayed by the anesthesiologist, because resuscitation and hemodynamic stabilization is usually impossible without surgical débridement. The incision is made directly over the area of skin involved or the most indurated region. The skin incision parallels the neurovascular bundles and carries down to the fascia. The underlying muscle and fascia is inspected and all necrotic tissue excised in all directions until healthy tissue is reached. Débridement 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.

The patient may be intolerant of the vasodilatory effects of volatile agents and may require massive volume resuscitation plus vasopressor therapy as is described earlier in this chapter. Importantly, as débridement progresses, cytokine release reduces and the patient usually becomes hemodynamically more stable. In the absence of a volatile agent, ketamine is a suitable alternative to maintain hypnosis during surgery, along with fentanyl or hydromorphone for analgesia.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

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Clostridial Myonecrosis (Gas Gangrene)

Clostridial species are obligate anaerobes that infect devitalized tissue. Three types of clostridial infections have been identified: (1) simple wound contamination or colonization, (2) anaerobic cellulitis, and (3) clostridial gas gangrene.

Myonecrosis is caused by Clostridium perfringens, an exotonin-secreting and spore-forming bacterium found in the soil. This infection is often called gas gangrene, owing to the palpable crepitus caused by liberation of gas. Muscle is remarkably resistant to infection. Infection follows significant loss of barrier function, as occurs with contamination of deep-seated wounds, as occurs in trauma, knife wounds, septic abortions, immunocompromise, and surgery. The introduction of the organism is complemented by the presence of an anaerobic environment with a low oxidation-reduction potential and acid pH, which is ideal for the growth of clostridial organisms. Another form of myonecrosis, spontaneous gangrenous myositis, is caused by group A streptococci.

The toxic effects of clostridial organisms result from the release of toxins (there are 12). Alpha toxin is lecithinase (phospholipase C), which degrades lecithin in cell membranes causing lysis. In addition, C. perfringens produces a variety of hydrolytic enzymes—proteases, DNases, hyaluronidase and collagenases—that liquefy tissue, thus promoting spread of infection.

Clinical and Pathologic Features.

The patient presents with sudden onset of malaise and painful swelling of the affected area. There may be a smelly purulent discharge and discoloration of skin. Gram stain of infected material reveals gram-positive rods. Exotoxins and proteolytics released by the organism cause fermentation of tissue carbohydrates and accumulation of gas bubbles in the subcutaneous space, resulting in crepitus.

Treatment is extensive surgical débridement of all infected tissue and intravenous antibiotics: benzylpenicillin, 2.4 g every 4 hours, plus clindamycin, 500 mg every 6 hours. Again, hyperbaric oxygen may have a role but has not been proven by prospective clinical trials.

Anesthesia Implications.

Anesthesia care of the patient with myonecrosis is similar to that of the patient with necrotizing fasciitis.

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Soft Tissue Infections of the Head and Neck

Soft tissue infections of the neck are of particular importance to anesthesiologists owing to the possibility of significant airway obstruction. The most common sources of life-threatening infections of the head and neck are the teeth and tonsils. The majority are polymicrobial in nature—usually oral flora (Bacteroides, Peptostreptococcus, Actinomyces, Fusobacterium, and microaerophilic streptococci) that become virulent. Infection spreads along facial planes to distant sites.

Clinical and Pathologic Features.

The most well-known neck space infection was described by Wilhelm von Ludwig in 1836 and is known as Ludwig's angina. This is a severe cellulitis of the tissue of the floor of the mouth with involvement of the submandibular and sublingual spaces. There is edema of the neck and tongue, cellulitis, and gradual airway compromise. The source of infection is almost always the second and third mandibular molars. If the infection is allowed to continue there may be local lymphadenitis, systemic sepsis, and extension of the disease to involve deep cervical fascia with a cellulitis that extends from the clavicle to the superficial tissues of the face. The disease is almost always polymicrobial, including α-hemolytic streptococci and anaerobes such as Peptostreptococcus, Prevotella melaninogenica, andFusobacterium nucleatum. Most patients with Ludwig's angina are young, healthy adults.

Patients usually present with mouth pain, dysphagia, drooling, and stiff neck. The patient often maintains the neck in an extended position and may have a muffled or “hot potato” voice.

Anesthesia Implications.

Urgent airway control is usually advised. Traditionally, tracheostomy has been performed under local anesthesia. This, however, may be technically difficult owing to extensive edema and inflammation, and inevitable infection and inflammation of the stoma site. Incision and drainage is indicated if suppurative infection develops and if the presence of fluctuance, crepitus, and soft tissue gas mandate the need for surgical intervention. CT can be used to help identify these suppurative complications. Surgical drainage has been required in 50% of patients. This may be performed under local anesthesia or cervical block.[86] If any question of airway compromise arises, then the airway must be secured. Forty to 60 percent of patients with Ludwig's angina require tracheostomy or endotracheal intubation.[87]Conventional intravenous induction and neuromuscular blockade is unacceptable; spontaneous ventilation should be maintained. An awake fiberoptic “look see” approach appears optimal. The airway is visualized after appropriate topical preparation. If the glottis and supraglottic area are patient, the anesthesiologist proceeds to intubation. If not, awake tracheostomy is performed. An alternative approach is inhalational induction of anesthesia with sevoflurane: the major drawback of this approach is difficulty in maintaining airway patency (owing to the edematous tissues of the neck), obstruction, and hypoxemia. Cricothyroidotomy is extremely difficult in this situation. Penicillin with a β-lactamase inhibitor is the agent of choice for Ludwig's angina: ampicillin/sulbactam or piperacillin-tazobactam, with either clindamycin or metronidazole.

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Acute epiglottitis is inflammation of the epiglottis secondary to bacterial infection, usually Hemophilus influenzae, type B. Infection results in significant edema and airway compromise, which may be life threatening. Inflammation can also occur in the arytenoid cartilage, false vocal cords, or pharyngeal wall, resulting in acute supraglottitis. The mean age at presentation ranges from 42 to 50 years, with male predominance and an association with cigarette smoking.

Clinical and Pathologic Features.

Patients typically present after approximately 2 days of symptoms and sore throat and pain in swallowing ( Table 12-14 ). Thickening of the epiglottis is the classic radiographic finding and is present on 73% to 86% of lateral neck radiographs.[88] Other radiographic findings strongly suggestive of acute epiglottitis and supraglottitis include enlargement of aryepiglottic folds, arytenoid enlargement, prevertebral soft tissue swelling, and an emphysematous epiglottitis.

TABLE 12-14   -- Signs and Symptoms of Acute Epiglottitis and Corresponding Frequency in Adults


Frequency (%)

Muffled voice








Tenderness of anterior neck








From Bansal A, Miskoff J, Lis RJ: Otolaryngologic critical care. Crit Care Clin 2003;19:55-72.




Anesthesia Implications.

Although generally avoided in children, laryngoscopy appears to be safe in adults and can be used to evaluate patients with a clinical suspicion of acute epiglottitis but with a negative neck radiograph. A “cherry red” epiglottitis is the classic finding, and most patients have supraglottic inflammation and edema. The need to sit upright, bacteremia, and a rapid onset of serious symptoms have been associated with the need for airway intervention: intubation or tracheostomy (5% to 20% of patients). The patient should continue to breath spontaneously while the airway is secured. Hence, awake fiberoptic intubation, or inhalational induction of anesthesia with sevoflurane, should be performed. Care should be taken with topicalization to prevent precipitation of acute airway obstruction. Intubation should be performed by the most skilled anesthesiologist, and a full airway team including an otolaryngologist, with an open tracheostomy pack, should be present.

The antimicrobial of choice is a second- or third-generation cephalosporin with activity against H. influenzae. Additional therapies such as the administration of racemic epinephrine or dexamethasone are of undetermined utility.[89]

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Biological weapons have been used to wage war and promote terror throughout history. One of the earliest uses of biological weapons occurred in the 6th century BC when the Assyrians poisoned enemy wells with rye ergot. In 1347, the Tartar army catapulted the bodies of bubonic plague victims over the walls of the city of Kaffa in the Crimea, leading to a plague epidemic. The Spanish, in 1495, infected French wine with blood from leprosy patients. In the mid 1600s, a Polish military general reportedly put saliva from rabid dogs into hollow artillery spheres for use against his enemies. On several occasions, smallpox was used as a biological weapon. This occurred in South America in the 15th century, during the French-Indian war, and during the Civil War. In each case, clothes from smallpox victims were given to natives or prisoners.

Horses, mules, and cattle were deliberately infected with anthrax and glanders in 1915 to infect Allied military personnel.

The Japanese extensively used aerosolized anthrax during the World War II. In 1941, the Japanese military released an estimated 150 million plague-infected fleas from airplanes over villages in China and Manchuria, resulting in several plague outbreaks. In 1942 the Soviet military used weaponized tularemia on German soldiers during the battle of Stalingrad.

From 1975 to 1983, Soviet-backed forces in Laos, Cambodia, and Afghanistan allegedly used tricothecene mycotoxins (T-2 toxins) in what was called “yellow rain.” In 1979, an outbreak of pulmonary anthrax occurred in Yekaterinburg in the Russia as a result of an accidental release of anthrax in aerosol form from a Soviet bioweapons facility.

Iraq is suspected to have used bombs and scud warheads filled with Botulinum toxin, anthrax, and aflatoxin against Kurds in 1991. At the dawn of the 21st interest in biological weapons has increased owing to the rise of terror networks and the production of such weapons by “rogue states.” There have been many foiled attempts by terrorists to produce bioweapons and several successful attacks; in Japan, in 1994-1995, in the United States in 1984 (salmonella), and in 2001 (anthrax).

In the fall of 2004, Viktor Yushchenko, the opposition candidate of the presidency of Ukraine, was poisoned with dioxin, leading to severe facial disfiguration, abdominal pain, and extensive ulceration of the gastrointestinal tract. It is presumed that he consumed food poisoned by supporters of his political opponent.

In the event of a terrorist biological attack, the anesthesiologist will be intensely involved with triage and resuscitation of the injured patient. A familiarity with potential bioweapons ( Table 12-15 ) is necessary.

TABLE 12-15   -- Agents of Concern for Use in Bioterrorism

Highest Priority (Category A)

Microbe or

Toxin Disease

Bacillus anthracis


Variola virus


Yersinia pestis


Clostridium botulinum


Francisella tularensis



Ebola hemorrhagic fevers, Marburg disease


Lassa fever, South American hemorrhagic fevers


Rift Valley fever, Congo-Crimean hemorrhagic fevers

Moderately High Priority (Category B)

Microbe or Toxin


Coxiella burnetti

Q fever

Brucella spp.


Burkholderia mallei



Viral encephalitides


Ricin intoxication

Staphylococcus aureus enterotoxin B

Staphylococcal toxin illness

Salmonellaspp., Shigella dysenteriae, Escherichia coli O 157:H7, Vibrio cholerae, Cryptosporidium parvum

Food- and water-borne gastroenteritis

Category C

Microbe or toxin



Viral hemorrhagic fevers


Yellow fever

Mycobacterium tuberculosis

Multidrug resistant tuberculosis


Genetically engineered vaccine- and/or antimicrobial-resistant category


A or B agents










Hybrid pathogens (e.g., smallpox-plague, smallpox-Ebola)




An ideal biological weapon is robust, is highly infectious, is highly potent, and can be delivered as an aerosol. A vaccine should be available. In addition, the weapons should be manufactured quickly and easily. In general, the primary difficulty is not the production of the biological agent but the development of an effective method of delivering the weapon to its intended target ( Table 12-16 ).

TABLE 12-16   -- Differential Diagnosis for Inhalational Anthrax


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, H. influenzae, K. pneumoniae, M. catarrhalis) usually occur in persons with underlying pulmonary or other disease or in elderly.

Pneumonia caused by Chlamydia pneumoniae

Legionnaires' disease (Legionella pneumophila or other Legionella species)

Psittacosis (Chlamydia psittaci)

Bird exposure occurs with psittacosis.

Other bacterial agents (e.g., Staphylococcus aureusStreptococcus pneumoniae,Haemophilus influenzaeKlebsiella pneumoniaeMoraxella catarrhalis)

Gram stain of sputum may be useful.

Community outbreaks caused by other etiologic agents not likely to be as explosive as pneumonic plague outbreak.

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 history of recent cruise ship travel or travel to tropics.



Exposure to mice droppings, feces with Hantavirus.

Respiratory syncytial virus

RSV usually occurs in children (although may be cause of pneumonia in 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




Bacillus anthracis is a gram-positive rod that primarily infects animals, particularly herbivores. Humans can contract the disease from infected animals or animal products. However, in most countries, domestic animal vaccinations have all but eliminated the disease. In an unfavorable environment anthrax endospores are formed that are highly resistant to disinfectants, temperature, and alkali. These spores have been manufactured by a number of countries as biological weapons. In the fall of 2001, letters with spores were sent from Trenton, New Jersey, to five media offices and two U.S. senators. Twenty-two individuals developed anthrax infections, mostly of the cutaneous variety. Five died of inhalation anthrax from cross contamination of the mail.

Clinical and Pathologic Features.

Infection occurs with the introduction of the spore through a break in the skin, causing cutaneous anthrax, or through the mucosa of the gastrointestinal tract.

To cause pulmonary infection, weapons-grade anthrax spores must be used. The reason for this is that anthrax must be delivered as single spores, which can work their way down into to small airways, where they are phagocytosed and transported to the hilar lymph nodes where bacteria proliferate. To deliver single spores, anthrax must be treated, to “unclump” the spores by being rendered electrostatically neutral.

Proliferating bacteria produce three exotoxins: edema factor, protective antigen, and lethal factor. Protective antigen binds to cell surface receptors, facilitating entry of the two other exotoxins into the cell by the creation of a channel. Edema factor causes cell swelling. Lethal factor has protease activity, which causes cell lysis.

Anthrax is a biphasic disease. Inhalational anthrax manifests, following a 3- to 6-day incubation period, as nonspecific symptoms of pyrexia, malaise, myalgia, and dry cough. The second stage begins 2 days hence, with fulminant sepsis associated with pyrexia, dyspnea, and vasoplegic shock. Expiratory stridor, owing to tracheal compression by enlarged paratracheal nodes, may accompany other respiratory symptoms.

The diagnosis of inhalational anthrax is suspected by circumstances (e.g., a mail worker with acute respiratory failure), sepsis, and respiratory failure in a patient with a widened mediastinum (i.e., adenopathy) on chest radiography.[90]

Cutaneous anthrax presents as a painless, pruritic papule on the skin up to 1 week after infection. Progression of the diseased lesion involves the development of one or more vesicles and edema surrounding the primary lesion, fever, and malaise. The vesicles subsequently rupture, revealing a necrotic ulcer and a characteristic black eschar. This dries and falls off after a week or 10 days.

The most important clinical approach to cutaneous anthrax is to avoid surgical débridement, which may be associated with bacteremia and systemic infection.[91]

Gastrointestinal anthrax is contracted by ingesting food contaminated with anthrax spores. Three to 5 days after infection the patient develops fever, malaise, nausea, vomiting, and diarrhea, associated with abdominal pain. Ulcers may develop in the intestinal mucosa, leading to profuse bleeding, mesenteric lymphadenitis, and ascites.

Definitive diagnosis is the identification of encapsulated broad gram-positive bacilli on examination of skin smears, blood, or cerebrospinal fluid.

Treatment of inhalational anthrax is ciprofloxacin plus clindamycin, rifampicin, or vancomycin.[92] For postexposure chemoprophylaxis, ciprofloxacin, doxycycline, and penicillin G have been recommended. Amoxicillin has been recommended for the treatment of cutaneous anthrax.

There is very little information available regarding hospital infection control and anthrax. There is no risk of person-to-person transmission with inhalational anthrax. If discharging skin lesions are present, contact precautions are necessary. Contaminated surfaces should be treated with sporicidal solutions.

Anesthesia Implications.

The anesthesiologist may be involved with the critical care management of the patient with inhalational anthrax—for intubation and supportive care. There is no risk of person-to-person transmission ( Table 12-17 ).

TABLE 12-17   -- Infection Control Issues for Selected Agents of Bioterrorism


Incubation Period (days)

Incubation Period (days)

Infection Control Precautions

Inhalational anthrax





12-72 hours



Primary pneumonic plague







Contact and airborne





Viral hemorrhagic fevers



Contact and airborne

Viral encephalitides




Q fever












From Cohen J, Powderly W: Infectious Diseases, 2nd ed. Philadelphia, Mosby, 2004, p 101.



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Smallpox is caused by the variola virus. The disease was eradicated worldwide in 1977 but exists in two known repositories, at the CDC in Atlanta and at the Institute of Viral Preparations in Moscow. It is feared that stockpiles of this virus are in the hands of others and may be used as a biological weapon.

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, and thence all body organs, via pulmonary lymph nodes. The incubation period is 1 to 2 weeks, during which the virus replicates in the reticuloendothelial system, followed by a prodromal syndrome (i.e., fever, backache, headaches, malaise, rigors, delirium, nausea and vomiting) after which a rash appears. At this point, and for a period of several weeks, the disease is communicable. The most prominent manifestation of smallpox is its characteristic centrifugal rash, which appears on the extremities first and then the trunk. This initially appears as a widespread macular eruption, with associated skin edema. An extensive pustular eruption follow; after 14 days these lesions rupture, necrose, and leave prominent pockmark scars.

Death from smallpox results from septic shock and MODS.

The rash of smallpox must be differentiated from that of chickenpox (varicella zoster). In varicella infection there is a shorter prodrome, lesions appear predominantly on the trunk with facial sparing, and the rash is different: the lesions in chickenpox are soft and do not scar and are at different stages of development; in smallpox the lesions progress in synchrony.

There is no known treatment for smallpox. Patients should be managed supportively, with full isolation and barrier precautions, in a negative-pressure room. Meticulous contact tracing is imperative. A vaccine is available, based on live vaccinia virus. Routine vaccination of children was abandoned in the 1960s because of the high incidence of vaccine-related complications. If the affected patient is in the early phase of the disease, he or she should be vaccinated.[93]

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Tularemia is an acute, febrile, granulomatous, infectious zoonosis caused by the aerobic gram-negative pleomorphic bacillus Francisella tularensis. Its name relates to the description in 1911 of a plague-like illness in ground squirrels in Tulare County, California. The disease commonly infects rabbits and rodents, including mice, groundhogs, squirrels, and sheep.

There are 150 to 300 tularemia cases reported in the United States annually, with a majority of those from Alaska, Arkansas, Illinois, Oklahoma, Missouri, Tennessee, Texas, Utah, and Virginia.

  1. tularensiswas weaponized by the United States (until the 1960s) and the former Soviet Union (until the 1990s). Other countries have been or are suspected to have weaponized this bacteria. This organism can potentially be produced in either a wet or dry form and introduced by aerosolization or contamination of food and water sources.

Many routes of human exposure to the tularemia organism are known to exist. The common routes include direct contact with blood or tissue while handling infected animals, through the bite of arthropods (e.g., ticks, mosquitoes) or from handling or eating undercooked small game animals (e.g., rabbit). Less common means of transmission are drinking or swimming in contaminated water, from animal scratches or bites of animals contaminated from eating infected animals, and inhaling dust from contaminated soil or handling contaminated pelts or paws of animals. Tularemia is not directly transmitted from person to person. Laboratory workers exposed to the bacteria are at higher risk.

The clinical form of disease reflects the mode of transmission. Some authors classify the disease as typhoidal (predominance of systemic symptoms), pneumonic (pulmonary findings), or ulceroglandular (regional symptoms).

Weaponized tularemia is most likely acquired by inhalation or consumption of contaminated food. The most common form of tularemia is usually acquired through the bite of blood-sucking arthropods or from contact with infected animals. Inhalation of the organism will result in sudden chills, fever, weight loss, abdominal pain, fatigue, and headaches. Inhalation of F. tularensis may result in tularemic pneumonia. Patchy, ill-defined infiltrates appear in one or more lobes on chest radiography. Bilateral hilar adenopathy may be present. Bloody pleural effusions are characteristic and demonstrate a mononuclear cellular response. This may progress to ARDS. Ingestion of the organism in contaminated food or water may result in painful pharyngitis, abdominal pain, diarrhea, and vomiting. As many as 20% of patients have a rash that may begin as blotchy, macular, or maculopapular and progress to pustular lesions. Erythema nodosum and erythema multiforme rarely occur. Other systems may also be involved, leading to meningitis, pericarditis, peritonitis, and osteomyelitis.

Symptoms generally appear between 1 and 14 days, but usually within 3 to 5 days. Diagnosis is exceedingly difficult to make. It is usually based on serology (the tularemia tube agglutination test). However, there is a 12- to 14-day delay in receiving the result of this test. Treatment is with gentamicin or streptomycin. Otherwise therapy is supportive. Mortality in untreated patients is 5% to 15%; in treated patients it is 1% to 3%.

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Yersinia pestis is a gram-negative bacillus that causes plague. Like anthrax, it primarily infects animals, particularly rodents. The disease is spread to humans via bites from infected rodent fleas. In this form, known as bubonic plague, approximately 10 cases per year are reported in the United States ( Table 12-18 ).

TABLE 12-18   -- Clinical Presentations and Syndromic Differential Diagnoses of Selected Agents of Bioterrorism

Clinical Presentation


Differential Diagnosis

Nonspecific “flu-like” symptoms with nausea, emesis, cough with or without chest discomfort, without coryza or rhinorrhea, leading to abrupt onset of respiratory distress with or without shock, mental status changes, with chest radiographic abnormalities (wide mediastinum, infiltrates, pleural effusions)

Inhalational anthrax

Bacterial mediastinitis, tularemia, Q fever, psittacosis, legionnaires' disease, influenza,Pneumocystis carinii pneumonia, viral pneumonia, ruptured aortic aneurysm, superior vena cava syndrome, histoplasmosis, coccidioidomycosis, sarcoidosis

Pruritic, painless papule, leading to vesicle(s), leading to ulcer, leading to edematous black eschar with or without massive local edema and regional adenopathy and fever, evolving over 3 to 7 days

Cutaneous anthrax

Recluse spider bite, plague, staphylococcal lesion, atypical Lyme disease, orf, glanders, tularemia, rat-bite fever, ecthyma gangrenosum, rickettsialpox, atypical mycobacteria, diphtheria

Rapidly progressive respiratory illness with cough, fever, rigors, dyspnea, chest pain, hemoptysis, possible gastrointestinal symptoms, lung consolidation with or without shock

Primary pneumonic plague

Severe community-acquired bacterial or viral pneumonia, inhalational anthrax, inhalational tularemia, pulmonary infarct, pulmonary hemorrhage

Sepsis, disseminated intravascular coagulation, purpura, acral gangrene

Septicemic plague

Meningococcemia; gram-negative, streptococcal, 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 followed by development of synchronous, progressive papular leading to vesicular and then pustular rash on face, mucous membranes (extremities more than the trunk); the rash may become generalized, with a hemorrhagic component and systemic toxicity.


Varicella, drug eruption, Stevens-Johnson syndrome, measles, secondary syphilis, erythema multiforme, severe acne, meningococcemia, monkeypox (with African travel history), generalized vaccinia, insect bites, coxsackievirus infection, vaccine reaction

Nonspecific flu-like, febrile illness with pleuropneumonitis, bronchiolitis with or without hilar lymphadenopathy; variable progression to respiratory failure

Inhalational tularemia

Inhalational anthrax, pneumonic plague, influenza, mycoplasma pneumonia, legionnaires' disease, Q fever, bacterial pneumonia

Acute onset of afebrile, symmetrical, descending flaccid paralysis that begins in bulbar muscles, dilated pupils, diplopia or blurred vision, dysphagia, dysarthria, ptosis, dry mucous membranes, leading to airway obstruction with respiratory muscle paralysis. Clear sensorium and absence of sensory changes


Myasthenia gravis, brain stem cerebrovascular accident, polio, Guillain-Barré syndrome variant, tick paralysis, chemical intoxication

Acute onset fevers, malaise, prostration, myalgias, headache, gastrointestinal symptoms, mucosal hemorrhage, altered vascular permeability, disseminated intravascular coagulation, hypotension, leading to shock, with or without hepatitis and neurologic findings

Viral hemorrhagic fever

Malaria, meningococcemia, leptospirosis, rickettsial infection, typhoid fever, borrelioses, fulminant hepatitis, hemorrhagic smallpox, acute leukemia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, systemic lupus erythematosus



Numerous epidemics of bubonic plague have swept the world during the course of the last 1000 years. It is believed that one third of the population of Europe succumbed in the 14th century to plague, commonly known as the “Black Death.”

Plague was used as a biological weapon during World War II by the Japanese in China, when infected fleas were released. It is known that the United States and the Soviet Union developed an aerosolized version during the Cold War and maintain stockpiles to this day.

The bubonic plague typically presents 2 to 8 days after exposure, with sudden onset of fever, chills, weakness, and acutely swollen lymph nodes, termed buboes. These are usually located in the groin, axilla, or cervical regions. Buboes are egg shaped, 1 to 10 cm in length, and often exquisitely tender. The patient develops acute severe sepsis, progressing to multiorgan failure, characterized by microvascular thrombosis, over a 2-day period. Peripheral tissue necrosis, similar to that seen in meningococcemia (i.e., necrotitis fulminans) is seen. Person-to-person spread of bubonic plague does not occur.

When Yersinia is spread by aerosolized droplets, the subsequent disease is known as pneumonic plague. It is highly contagious. This would be the route of attack by terrorists or the military.

After exposure there is an incubation period of 2 to 4 days, with sudden onset of fever, rigors, and muscular pain. Within 24 hours the patient develops hemoptysis, owing to the production of coagulase and fibrolysin by the bacterium, leading to tissue necrosis. The patient may complain of abdominal pain, chest pain, nausea, and vomiting. The disease progresses to ARDS, with severe hypoxemia, and to septic shock. Without appropriate antibiotics within 18 hours, the disease is fatal.

The diagnosis of plague may be difficult in isolated cases: the symptoms and signs may be indistinguishable from other forms of acute severe sepsis (e.g., meningococcemia or pneumococcal pneumonia). A history of hemoptysis on presentation should alert the clinician to the possibility of plague. Moreover, if a biological attack is carried out with Yersinia, multiple patients will begin presenting to the emergency department with symptoms of rapidly progressing pneumonia and hemoptysis. Sputum Gram stain reveals gram-negative rods. Blood cultures are usually positive, but the diagnosis is usually retrospective because, by the time the cultures emerge, without treatment the patient will be dead.

The treatment of choice for plague is streptomycin, gentamicin, doxycycline, or ciprofloxacin. These agents are not routinely used or recommended for community-acquired pneumonia. If the patient has symptoms or signs of meningitis, chloramphenicol should be used. Strict isolation with droplet precautions should be enforced for 48 hours.

Anesthesia Implications.

The anesthesiologist may be involved with airway management and commencement of mechanical ventilation. Extreme precautions should be taken to avoid contact with patients‚ secretions. The anesthesiologist should wear a gown, mask, and eye protection because of the potential for contagion. All health care workers involved in face-to-face contact must be given chemoprophylaxis with doxycycline for at least 7 days. Patients are managed supportively in the ICU. There are no indications for surgery in the early stages. In particular, buboes should not be incised or débrided owing to the risk of spreading the infection. Peripheral necrosis requires surgical débridement or amputation, but this is delayed until the patient is in the recovery stage of the disease.

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Sarin (GB) is an organophosphate nerve agent first developed by Nazi scientists in 1938. A number of similar agents exist, such as tabun (GA), soman (GD), cyclosarin (GF), and VX toxin. VX is the most potent known biotoxin. Sarin is one of the few biological weapons known to have been used in military and terrorist attacks. It is widely believed that sarin was used by the Iraqi military against Kurdish villagers in 1988 as well as during the Iraq-Iran War.[94] A Japanese terrorist cult known as Aum Shinrikyo used sarin against civilians in Japan, first in Matsumoto in 1994, killing 8 people, then in the Tokyo Subway in 1995, killing 13 and injuring hundreds.[95]

Clinical and Pathologic Features.

At room temperature, sarin is a volatile liquid that can be aerosolized by explosive devices. Exposure to sarin occurs by one of two routes: topically/transdermally or inhaled into the lungs.[96] Once acquired, organophosphate nerve agents bind to and inactivate acetylcholinesterase (AchE). This leads to toxic accumulation of acetylcholine at nicotinic, muscarinic, and CNS synapses. Thus, sarin is a noncompetitive agonist at neuromuscular junctions, parasympathetic nerve terminals, and nicotinic adrenergic receptors. The result is a medley of symptoms ( Table 12-19 )[97]:

TABLE 12-19   -- Symptoms Associated with Sarin or Organophosphate Poisoning



Respiratory: Dyspnea, cough, chest tightness, wheezing (bronchospasm)



Cardiovascular (adrenal medullary stimulation): tachycardia, hypertension



Neurologic: Headache, weakness, fasciculations, extremity numbness, decreased level of consciousness, vertigo, dizziness, convulsions



Ophthalmic: Eye pain, blurred vision, dim vision, conjunctival injection, tearing



Ear, nose, throat: Rhinorrhea



Gastrointestinal: Nausea, vomiting, diarrhea, tenesmus, fecal incontinence



Genitourinary: Urinary incontinence



Dermal: Sweating



Psychological: Agitation



General: Fatigue

Data from Lee EC: Clinical manifestations of sarin nerve gas exposure. JAMA 2003;290:659-662.




Initial symptoms and signs depend on the route of exposure and quantity of agent involved.[96] Transdermal poisoning causes insidious symptoms—initially vasodilatation, sweating, localized muscle fasciculations, and paralysis and then generalized muscle weakness, paralysis, and respiratory depression.

Inhalation of large quantities of nerve agent leads to acute respiratory distress, loss of consciousness, flaccid paralysis, convulsions, and coma.

Physical signs include dyspnea, tachypnea, and wheezing. There may be tachycardia or bradycardia, reduced levels of consciousness, weakness, muscle fasciculation, flaccid paresis. Examination of the eyes reveals miosis and lacrimation.

If a sarin gas attack is suspected it is imperative that health care providers take extraordinary personal protective measures. Protective equipment includes protective suits, heavy butyl rubber gloves, and self-contained breathing apparatus. Aggressive decontamination of victims is required to prevent further exposure to them and others

Goals of decontamination are to prevent further absorption of nerve agents by victims and to prevent the spread of nerve agents to others. Decontamination is necessary only with topical exposure. The skin should be washed with an alkaline solution of soap and water or 0.5% hypochlorite solution (made by diluting household bleach 1:10). This chemically neutralizes the nerve agent.

Anesthesia Implications.

The anesthesiologist's involvement in the emergency care of patients poisoned with organophosphates usually involves securing the airway, commencing mechanical ventilation, and transferring the patient to the ICU. The patient should be treated with supplemental oxygen before intubation. A hypnotic agent is administered to facilitate intubation. Succinylcholine should be avoided because it is metabolized 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 and airway secretions.

Two essential antidotes are required to treat organophosphate poisoning: atropine and pralidoxime.[96] Atropine reverses the muscarinic effects of the poison, which include bronchoconstriction, abdominal pain, nausea, vomiting, and bradycardia. Pralidoxime acts by disrupting covalent bonds between nerve agent and AChE before they become permanent; thus, AChE is reactivated and skeletal muscle weakness is reversed. Convulsions are treated with benzodiazepines.[97]

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Ricin is a plant carbohydrate binding protein (lectin) found in high concentration in castor beans. Ricin is active orally or on inhalation and thus could be aerosolized or used to poison food. Ricin has relatively low potency, although it has been used as a biological weapon, most famously in the assassination of Georgi Markov in 1978 after skin perforation with the tip of an umbrella. A recent find of ricin and castor bean extraction equipment during a police raid of an apartment in the United Kingdom and in a postal facility in the United States indicates interest in this agent by terrorists.

Ricin is composed of two hemagglutinins and two toxins. The toxins, RCL III and RCL IV, are dimers of approximately 66,000 daltons. The toxins have an A and a B chain, which are polypeptides and joined by a disulfide bond. The B chain binds to cell surface glycoproteins and affects entry into the cell by an unknown mechanism. The A chain acts on the 60S ribosomal subunit and prevents the binding of elongation factor-2. This inhibits protein synthesis and leads to cell death.

Clinical and Pathologic Features.

After inhalation exposure there is an incubation period of 4 to 8 hours, followed by fever, cough, dyspnea, nausea, and the development of ARDS. By the oral route there is necrosis of the gastrointestinal tract and significant bleeding. In parenteral exposure there is induration, erythema, and gradual development of systemic symptoms.

Mortality and morbidity depend on the route and amount of exposure. Therapy is supportive. The airway is secured, and ventilation is ensured. Decontamination is carried out similar to sarin infection.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Botulism is caused by the toxin of Clostridium botulinum, an aerobic, spore-forming bacterium. The bacterium occurs naturally in soil. Botulism is a neuroparalytic disease. Although manufactured as a bioweapon, botulinum toxin has never been used as such. The most likely bioterrorism dissemination scenarios include contamination of food and aerosolization.

Clinical and Pathologic Features.

Following infection, the neurotoxin is absorbed through the intestinal mucosa and is widely distributed throughout the body. Initial presentation includes gastrointestinal problems that rapidly progress to cranial nerve abnormalities (e.g., diplopia, dysphagia, dysarthria) and, particularly, bulbar deficits. A progressive, bilateral, descending motor neuron flaccid paralysis ensues, followed by respiratory failure and death. The toxin combines irreversibly with peripheral cholinergic synapses, preventing acetylcholine release[98] and leading to flaccid paralysis not dissimilar to that seen with neuromuscular blocking drugs. There are no antiadrenergic effects. Blockade of neurotransmitter release at the terminal is permanent, and recovery only occurs when the axon sprouts a new terminal to replace the toxin-damaged one. Mortality is less than 5% if the infection is treated but approaches 60% if it is untreated ( Table 12-20 ).

TABLE 12-20   -- Differential Diagnosis of Botulism


Features that Distinguish Each Condition from Botulism

Guillain-Barré syndrome (GBS) (particularly Miller Fisher variant)

Usually an ascending paralysis, although Miller Fisher variant may be descending and may have pronounced cranial nerve involvement

Abnormal cerebrospinal fluid protein 1 to 6 weeks after illness onset (although may be normal early in clinical course)

Paresthesias commonly 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 hr after tick removal.

EMG shows abnormal nerve conduction velocity and unresponsiveness to repetitive stimulation.

Usually does not involve cranial nerves

Lambert-Eaton syndrome

Commonly 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 20-50 Hz.

Increased strength with sustained contraction

Deep tendon reflexes often absent; ataxia may be present.

Usually does not involve cranial nerves

Stroke or CNS mass lesion

Paralysis usually asymmetrical.

Brain imaging (CT or MRI) usually abnormal.

Sensory deficits common.

Altered mental status may be present.


Febrile illness

CSF shows pleocytosis and increased protein.

Altered mental status may be present.

Paralysis often asymmetrical.

Paralytic shellfish poisoning or ingestion of puffer fish

History of shellfish (i.e., clams, mussels) or puffer fish ingestion within several hours before symptom onset

Paresthesias of mouth, face, lips, extremities commonly occur.

Belladonna toxicity

History of recent exposure to belladonna-like alkaloids



Altered mental status

Aminoglycoside toxicity

History of recent exposure to aminoglycoside antibiotics

More likely to occur in the setting of renal insufficiency

Most commonly seen with neomycin

Most commonly associated with other neuromuscular blocking agents such as succinylcholine and paralytics

Other toxicities (hyper-magnesemia, organo-phosphates, nerve gas, carbon monoxide)

History of exposure to toxic agents

Carbon monoxide toxicity: altered mental status may occur, cherry-colored skin

Hypermagnesemia: history of use of cathartics or antacids may be present, elevated serum magnesium level

Organophosphate toxicity: fever, excessive salivation, altered mental status, paresthesias, miosis

Other conditions

CNS infections (particularly brain stem infections)

Inflammatory myopathy


Diabetic neuropathy

Viral infections

Streptococcal pharyngitis (pharyngeal erythema and sore throat can occur in botulism owing to dryness caused by parasympathetic cholinergic blockade)

From Infectious Disease Society of North America. Available at http://www.cidrap.umn.edu/cidrap/content/bt/botulism/biofacts/botulismfactsheet.html.

CSF, cerebrospinal fluid; EMG, electromyogram; CT, computed tomography; MRI, magnetic resonance imaging.




Anesthesia Implications.

Treatment of botulism involves immediate administration of antitoxin, respiratory monitoring, and administration of mechanical ventilation. Once forced vital capacity falls below 30% of predicted,intubation is necessary. No specific interventions are required for intubation. The administration of neuromuscular blocking agents is unnecessary. Patients may require mechanical ventilation for up to 6 weeks. Full recovery may take 1 year.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


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