“Systemic inflammatory response syndrome (SIRS) in surgical patients.

Pathogenesis and significance in different diseases and traumas. The choice

of diagnostic and curative tactics. Algorithm of intensive therapy
implementation. Surgical sepsis, septic shock. Antibacterial therapy of
surgical infection. Surgical aspects of AIDS.”

Overview.

The inflammatory response to injury and activation of cellular processes are

inherently designed to restore tissue function and eradicate invading
microorganisms. Local injuries of limited duration are usually followed by
functional restoration with minimal intervention. By contrast, major insults to the
host are associated with an overwhelming inflammatory response that, without
appropriate and timely intervention, can lead to multiple organ failure and
adversely impact patient survival. Therefore understanding how the inflammatory
response is mobilized and ultimately controlled provides a functional framework
upon which interventions and therapeutics are formulated for the surgical patient.
The maturation of minimally invasive techniques for major surgery during the last
decade has brought complementary perspectives to the injury response paradigm,
and the immunologic benefits for these surgical approaches are undergoing
validation. Furthermore, the sequencing of the human genome and available
technology such as deoxyribonucleic acid (DNA) microarray analysis potentially
affords surgeons additional tools to profile the genetic mechanisms governing the
host response to injury.

Infections with HIV leading to acquired immune deficiency syndrome

(AIDS) have been the focus of considerable academic attention during the past 20
years. This infection is an indolent process that potentially requires a full decade,
even in the untreated patient, from the time of acute infection before
immunosuppression becomes clinically significant. Surgical problems in the HIV
patient include abnormal presentation of common illnesses but also include unique
problems that are consequences of the acquired immunosuppression.
 Educational aims:
1. Interrogation and clinical inspection of patients with SIRS, sepsis.
2. To determine the etiologic and pathogenic factors of SIRS, sepsis.
3. To develop a plan of examination of the patients with SIRS, sepsis.
4. To estimate results of laboratory data.
5. To make and formulate a diagnosis of SIRS, sepsis.
6. To estimate efficiency of treatment and prognosis of disease.
7. The stages of AIDS, clinical picture, diagnosis, surgical aspects.
A student must know:
1. Etiology and pathogenesis of SIRS, sepsis.
2. Manifestation of SIRS, sepsis.
3. Modern methods of diagnosis of SIRS, sepsis.
4. Significance in different diseases and traumas
5. The choice of diagnostic and curative tactics.
6. Algorithm of intensive therapy implementation.
7. Surgical aspects of AIDS.
A student must be able to:
1. Collect and estimate anamnesis of the patients with SIRS, sepsis.
2. Use methods of examination patients with SIRS, sepsis.
3. Set the algorithm of examination patient with SIRS, sepsis.
4. Estimate the results of laboratory, instrumental inspection of patients.
5. Determine optimum medical tactics for a concrete patient (conservative,
surgical), and in the case of SIRS, sepsis, with AIDS complicated surgical
pathology.
6. To prove necessity of pre-operation preparation of patient and to define the
operation of choice depending on localization, age, sex.
Terminology.
Term Definition
the pathologic reaction whereby fluid and circulating
Infection leukocytes accumulate in extravascular tissues in response
to injury or infection. Identifiable source of microbial insult
 are extremely complex processes involving numerous
different cell types as well as hundreds of different humoral
mediators
Two or more of following criteria
SIRS • Temperature ≥38°C or ≤36°C
• Heart rate ≥90 beats/min
• Respiratory rate ≥20 breaths/min or PaCO2 ≤32 mm
Hg or mechanical ventilation
• White blood cell count ≥12,000/L or ≤4000/L or ≥10%
band forms
Sepsis SIRS caused by infection (identifiable source of infection +
SIRS)
Severe sepsis is characterized as sepsis (defined above) combined with the
presence of new-onset organ failure.
is a state of acute circulatory failure identified by the
presence of persistent arterial hypotension (systolic blood
Septic shock pressure <90 mm Hg) despite adequate fluid resuscitation,
without other identifiable causes (sepsis + cardiovascular
collapse (requiring vasopressor support))
is a blood-borne infection that is transmitted to the
HIV susceptible host after percutaneous or a mucus membrane
exposure to infected blood or body fluids.
AIDS is infections with HIV leading to acquired immune
deficiency syndrome

Content:

Conceptually, the systemic response to injury can be broadly

compartmentalized into two phases: (1) a proinflammatory phase characterized by
activation of cellular processes designed to restore tissue function and eradicate
invading microorganisms, and (2) an anti-inflammatory or counter regulatory
phase that is important for preventing excessive proinflammatory activities as well
as restoring homeostasis in the individual. While the terminologies that describe
the various facets of systemic inflammation are often used interchangeably, there
are distinct criteria for each term.

Systemic phase of infection: sepsis

If local circumscription of infection is impossible either by removing the

bacteria or by abscess formation, micro-organisms eventually invade the
bloodstream and may reach distant organs. The presence of bacteria in the
bloodstream (bacteremia) occurs transiently in healthy individuals too. In patients,
bacteria often will be found on the intravascular portion of catheters. Nontoxin-
producing, mostly nonmultiplying bacteria can sometimes be isolated by blood
culture, but these cause no or only mild systemic symptoms. Bacteremia may,
however, progress to systemic disease, especially in immunocompromised and
postoperative patients. If the condition persists and is associated with
multiplication of bacteria in the bloodstream, and large numbers of bacteria die as
they are attacked by host defense mechanisms, then large quantities of bacterial
cell-wall structures (endotoxins) are liberated and a serious state of infection
termed sepsis ensues.

Sepsis is characterized not only by invasion and multiplication in the

bloodstream of large numbers of bacteria but also by the potential for subsequent
sudden overload of the host with endotoxins and cytokines, leading to septic shock.
Key to this process is a small molecule – nitric oxide – that when excessively
produced will block mitochondrial energy generation by inhibiting Krebs' cycle
enzymes and cells are running out of fuel for life. Clinically we then observe
sequential organ dysfunction. Sepsis is the clinical, symptomatic state resulting
from the host response to bacteremia. Liberated bacterial exo- and endotoxins are
deleterious to many organ functions; equally, cytokine mediators of host defenses
are potentially damaging if their downregulation fails. If not treated successfully,
the patient may die immediately of septic shock or later following multisystem
organ failure: 1 ng endotoxin/kg body wt results in irreversible shock and death
within 2 h. Clinical symptoms of sepsis include the following. Fever is usually is
high, spiking, and accompanied by chills. Tachycardia accompanies or precedes
the fever and is proportional to it. The total leukocyte count may not be particularly
abnormal in sepsis and may even be low, due to the consumption of polymorphs.
The differential count is more reliable: there is always a shift to the left. Petechial
lesions may be seen in the skin or conjunctiva of patients suffering from sepsis
caused by streptococci, meningococci, or pseudomonads. Anemia secondary to
hemolysis may appear rapidly when sepsis is due to staphylococci, pseudomonads,
coliforms, or clostridia. During the initial, hyperdynamic phase of septic shock the
peripheral vasodilation is explained by a circulatory response that aims to
compensate for the inability of cells to use oxygen. The last stage of septic shock is
hypodynamic, due to cell death. Shock is common in sepsis caused by Gram-
negative organisms, but occurs relatively less often with Gram-positive infections.
Metastatic abscesses, especially of the bone, brain, or spleen, are not unusual after
a septic episode: any injured tissue is easily infected during sepsis. Diagnosis is
aided by a high index of suspicion.

Thermolabile exotoxins are released by living bacteria, particularly the

Gram-positive; thermostable endotoxins are released by all bacteria after death.
Endotoxins are complex moieties of high molecular weight consisting of
phospholipids, polysaccharides, and proteins derived from the outer cell wall,
particularly of Gram-negative rods such as Escherichia coli. Clinically measurable
effects of endotoxin include fever, consumptive coagulopathy, increased
vagotonus, hyperglycemia followed by hypoglycemia, leucopenia or leukocytosis,
increased plasma lipids, release of hepatic enzymes, thrombocytopenia, and a
reduced serum iron. Low doses of endotoxin primarily affect the
reticuloendothelial system. Animal studies have shown a marked reduction in the
clearance of particulates such as colloidal carbon during endotoxemia. Mediators
such as collagenases, pyrogenic prostaglandins, and coagulation factors are
released from macrophages; after 7 days, antibodies against endotoxin are
produced. Endotoxins act directly on the hypothalamic temperature-regulation
center to cause fever, reinforcing the activity of pyrogenic substances released
from dying neutrophils. Erythropoiesis is shifted from the bone marrow to the
spleen, resulting in leucopenia followed by leukocytosis after 2 to 6 h. In small
doses, endotoxins increase phagocytic activity and bacterial killing.
Thrombocytopenia, accompanied by aggregation and lysis of thrombocytes, results
in the release of ADP, vasoactive amines, histamine, serotonin, and platelet factor
III, which in turn may lead to consumptive coagulopathy. In the extrinsic
coagulation system, endotoxins cause release of a tissue factor derived from
macrophages, as well as platelet factors and thromboplastins. In the intrinsic
system, factor XII (Hageman factor) is activated, leading to disseminated
intravascular coagulation. Endotoxin has a profound effect on metabolism. Initially
it induces hyperglycemia, which is followed after several hours by hypoglycemia.
Hyperlipidemia results from altered metabolism of free fatty acids, cholesterol,
phospholipids, and triglycerides. Protein synthesis by the liver is stimulated; lactate
dehydrogenase, transaminases, and phosphokinases are released, increasing their
serum concentrations. Release of adrenocorticotrophic hormone, cortisone, and
growth hormone is increased; thyrotropin and luteinizing hormone are not affected.
Plasma iron and total iron-binding capacity are reduced. A vagotonic effect results
in loss of thirst and appetite, stomach emptying is delayed, and diarrhea may occur.

Pathogenesis of inflammation

Central Nervous System Regulation of Inflammation. The central nervous

system, operating through autonomic signaling, has an integral role in regulating
the inflammatory response that is primarily involuntary. Classically, the autonomic
system regulates heart rate, blood pressure, respiratory rate, gastrointestinal
motility, and body temperature. An additional role of the autonomic nervous
system is to regulate inflammation in a reflex manner, much like the patellar
tendon reflex. Inflammation originating from a specific location sends afferent
signals to the hypothalamus, which in turn rapidly relays opposing anti-
inflammatory messages to the site of inflammation to reduce inflammatory
mediator release by immunocytes. Tracey and colleagues have further linked reflex
inhibition of inflammation to the parasympathetic signaling pathway whereby
acetylcholine, the primary neurotransmitter of the parasympathetic system, reduces
tissue macrophage activation. Furthermore, cholinergic stimulation directly
reduces tissue macrophage release of the proinflammatory mediators TNF-α, IL-1,
IL-18, and high mobility group protein (HMG-1), but not the anti-inflammatory
cytokine IL-10. The attenuated inflammatory response induced by cholinergic
stimuli was further validated by the identification of acetylcholine (nicotinic)
receptors on tissue macrophages. Vagal stimulation reduces heart rate, increases
gut motility, dilates arterioles, and causes pupil constriction, as well as regulates
inflammation. Unlike the humoral anti-inflammatory mediators that are released
into the circulation and allowed to travel to a site of injury, signals discharged from
the vagus nerve are precisely targeted at the site of injury or infection. Moreover,
this cholinergic signaling occurs rapidly in real time. From the available preclinical
studies, it can be proposed that impaired cholinergic activity from the vagus nerve
portends a greater proinflammatory response in patients who are critically ill.

Hormonal Response to Injury. Hormones are chemically classified as

polypeptides (e.g., cytokines, glucagon, and insulin), amino acids (e.g.,
epinephrine, serotonin, and histamine), or fatty acids (e.g., glucocorticoids,
prostaglandins, and leukotrienes). Most hormone receptors generate signals by one
of three major pathways, which overlap. Specifically, these receptor pathways are
(1) receptor kinases such as insulin and insulin-like growth factor receptors, (2)
guanine nucleotide-binding or G-protein receptors such as neurotransmitter and
prostaglandin receptors, and (3) ligand-gated ion channels which permit ion
transport when activated. Upon activation of membrane receptors, secondary
signaling pathways are often utilized to amplify the initial stimuli. Hormone
signals are further mediated by intracellular receptors with binding affinities for
both the hormone itself, as well as for the targeted gene sequence on the DNA.
These intracellular receptors may be located within the cytosol or may already be
localized in the nucleus, bound to the DNA. The classic example of a cytosolic
hormonal receptor is the glucocorticoid (GC) receptor. Intracellular GC receptors
are maintained in the cytosol by linking to the stress-induced protein, heat shock
protein (HSP). When the glucocorticoid ligand binds to the GC receptor, the
dissociation of HSP from the receptor activates the receptor-ligand complex and is
transported to the nucleus. Virtually every hormone of the hypothalamic-pituitary-
adrenal (HPA) axis influences the physiologic response to injury and stress, but
some with direct influence on the inflammatory response or immediate clinical
impact will be highlighted.

Mediators of Inflammation

Cytokines appear to be the most potent mediators of the inflammatory

response. When functioning locally at the site of injury or infection, cytokines
eradicate invading microorganisms and promote wound healing. However,
overwhelming production of proinflammatory cytokines in response to injury can
cause hemodynamic instability (i.e., septic shock) or metabolic derangements (i.e.,
muscle wasting). If uncontrolled, the outcome of these exaggerated responses is
end-organ failure and death. The production of anti-inflammatory cytokines as part
of the inflammation cascade serves to oppose the excessive actions of
proinflammatory cytokines. However, inappropriate anti-inflammatory mediator
release may render the patient immunocompromised and susceptible to
overwhelming infections.

Heat Shock Proteins. Stimuli such as hypoxia, trauma, heavy metals, local
trauma, and hemorrhage all induce the production of intracellular heat shock
proteins (HSPs). HSPs are intracellular protein modifiers and transporters that are
presumed to protect cells from the deleterious effects of traumatic stress. The
formation of HSPs requires gene induction by the heat shock transcription factor.

Reactive oxygen metabolites are short-lived, highly reactive molecular

oxygen species with an unpaired outer orbit. They cause tissue injury by oxidation
of unsaturated fatty acids within cell membranes. Oxygen radicals are produced by
complex processes that involve anaerobic glucose oxidation coupled with the
reduction of oxygen to superoxide anion. Superoxide anion is an oxygen
metabolite that is further metabolized to other reactive species such as hydrogen
peroxide and hydroxyl radicals. Activated leukocytes are potent generators of
reactive oxygen metabolites. Cells are not immune to damage by their own reactive
oxygen metabolites, but are generally protected by oxygen scavengers that include
glutathione and catalases.

Kallikrein-Kinin System. Bradykinins are potent vasodilators that are

produced through kininogen degradation by the serine protease kallikrein.
Kallikrein exists in blood and tissues as inactive prekallikrein that is activated by
various factors such as Hageman factor, trypsin, plasmin, factor XI, glass surfaces,
kaolin, and collagen. Kinins increase capillary permeability and tissue edema,
evoke pain, inhibit gluconeogenesis, and increase bronchoconstriction. They also
increase renal vasodilation and consequently reduce renal perfusion pressure. The
resulting increase in renin formation activates sodium and water retention via the
renin-angiotensin system.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) is a tryptophan

derivative that is found in chromaffin cells of the intestine and in platelets. Patients
with midgut carcinoid tumors often secrete 5-HT in excess. This neurotransmitter
stimulates vasoconstriction, bronchoconstriction, and platelet aggregation.
Serotonin is also a myocardial chronotrope and inotrope. Although serotonin is
clearly released at sites of injury, its role in the inflammatory response is unclear.

Histamine is derived from histidine and stored in neurons, skin, gastric

mucosa, mast cells, basophils, and platelets. Histamine release is activated by
increased calcium levels. There are two receptor types for histamine binding. H1
binding stimulates bronchoconstriction, intestinal motility, and myocardial
contractility. H2 binding inhibits histamine release. Both H1 and H2 receptor
activation induce hypotension, peripheral pooling of blood, increased capillary
permeability, decreased venous return, and myocardial failure. The rise in
histamine levels has been documented in hemorrhagic shock, trauma, thermal
injury, endotoxemia, and sepsis.
 Pathogens in surgical infections

This discussion of pathogens commonly responsible for surgical infections is

not intended to be a complete review. Rather, it focuses on some broad distinctions
and classifications that help organize the vast body of data concerning the usual
bacterial flora of different surgical infections and the antibiotic susceptibility
patterns of these pathogens. Bacteria important in surgical infections are broadly
divided into aerobic and facultative bacteria in one group and anaerobic bacteria in
the other; into gram-positive and gram-negative bacteria; and into bacilli (rods) and
cocci. Most infections presenting in surgical patients are caused by endogenous
bacteria. Specific bacteria are found in specific parts of the body, and the exposed
anatomic areas during a surgical procedure are usually the source of
microorganisms that cause infection. It is helpful to know the normal microbial
flora of the body, since this helps direct prophylactic antibiotics, start intelligent
empiric therapy, and suspect the origin of an unknown source of infection in
patients with positive blood cultures. It is also helpful to be familiar with the
different classifications of bacteria since it can take up to 72 hours for a final
culture to give the result as a specific bacteria; however, Gram stain and
biochemical tests can help in providing earlier guidance regarding which group of
bacteria may be responsible for an infection.

Gram-positive cocci of importance to surgeons include staphylococci and

streptococci. Staphylococci are divided into coagulase-positive and coagulase-
negative strains. Coagulase-positive staphylococci are S. aureus and are the most
common pathogen associated with infections in wounds and incisions not subject
to endogenous contamination. Coagulase-positive staphylococci should be
assumed resistant to penicillin and require treatment by a penicillinase-resistant
antibiotic. Extensive use of penicillinase-resistant β-lactam antibiotics in the past
has encouraged the emergence of MRSA. These organisms do not seem to have
intrinsic pathogenicity greater than that of other staphylococci, but they are more
difficult to treat because of antibiotic resistance. The prevalence of MRSA varies
considerably by geographic region but has been increasing during the past 2
decades. MRSA initially was seen primarily in hospitalized patients but is now
seen in an increasing number of community-acquired infections. The incidence of
MRSA recovery is increased in patients coming from long-term care facilities,
previously hospitalized or treated with antibiotics, and those with diabetes or on
dialysis. MRSA must be treated with vancomycin, quinupristin/dalfopristin, or
linezolid. Recent years have seen the introduction of S.aureus strains with
decreased susceptibility to vancomycin, and, more recently, of S. aureus strains
with high-level resistance to vancomycin. If the history of other pathogens and
antimicrobial agents repeats itself, the number of such strains will increase in the
future.

For many years, coagulase-negative staphylococci were considered

contaminants and skin flora incapable of causing serious disease. However, in the
correct clinical setting, coagulase-negative staphylococci can cause serious disease.
This is most common in patients who have been compromised by trauma,
extensive surgery, or metabolic disease and who have invasive vascular devices in
place. Coagulase-negative staphylococci are the most common organisms
recovered in nosocomial bacteremia and are frequently associated with clinically
significant infections of intravascular devices. Coagulase-negative staphylococci
are also found in endocarditis, prosthetic joint infections, vascular graft infections,
and postsurgical mediastinitis. Most coagulase-negative staphylococci are
methicillin resistant. Although most of the infections associated with intravascular
devices are cured simply by removing the device, if empiric antibiotic therapy is
indicated, vancomycin, quinupristin/dalfopristin, or linezolid should be chosen.
The streptococcal species include β-hemolytic streptococci (especially group A or
S.pyogenes), S.pneumoniae, and other α-hemolytic streptococci. These species
initially were uniformly sensitive to penicillin G and almost all other β-lactam
antibiotics. Penicillin-resistant S.pneumoniae is now found in most urban
communities. The β-hemolytic streptococci alone, although not commonly
recovered from soft tissue wounds, can cause life threatening infections. The other
α-hemolytic streptococci or viridans streptococci rarely are significant pathogens
in a surgical setting. They are commonly found on mucous membranes and skin
and may be recovered from the peritoneal cavity after upper gastrointestinal
perforations but are almost never found as the sole cause of significant surgical
infections. The precise significance of enterococci (group D streptococci) in
surgical infections is controversial. Enterococci are commonly recovered as part of
a mixed flora in intra-abdominal infections. It is rare to recover enterococci alone
from a surgical infection. Enterococcal bacteremia in association with a surgical
infection carries a grave prognosis. The stimulus for discussing the pathogenic
significance of enterococci derives from the relative resistance of these species to
antibiotic therapy. No single antibiotic is reliably effective for eradicating deep-
seated infections or bacteremia. The most effective antibiotic combination for
treating enterococcal infections is gentamicin combined with either ampicillin (or
another advanced-generation penicillin) or vancomycin.

Aerobic and Facultative Gram-Negative Rods. A great variety of gram-

negative rods are associated with surgical infections. Most fall into the family
Enterobacteriaceae. These are all facultative anaerobic bacteria and include the
familiar genera Escherichia, Proteus, and Klebsiella. These three genera (easy
gram-negative rods) are considered together because they are relatively common in
mixed surgical infections and because they are relatively sensitive to a broad
variety of antibiotics, especially second-generation cephalosporins. Other genera
within the Enterobacteriaceae that are also common in surgical infections include
Enterobacter, Morganella, Providencia, and Serratia. These genera (difficult gram-
negative rods) commonly exhibit greater intrinsic antimicrobial resistance. Empiric
antibiotic therapy directed at these organisms requires a third-generation
cephalosporin, one of the expanded-spectrum penicillin, a monobactam,
carbapenems, quinolone, or aminoglycoside. In many locales these organisms have
acquired extended-spectrum β-lactamase enzymes that are capable of inactivating
even third-generation cephalosporins. These organisms are more common in
hospital-acquired and postoperative surgical infections. Gram negative rods
recovered from infections originating in the community, such as uncomplicated
appendicitis or diverticulitis, are less likely to involve antibiotic-resistant strains.
Obligate aerobic gram-negative rods that can be found in surgical infections
include Pseudomonas and Acinetobacter species. These organisms are most
commonly found in hospital-associated pneumonias in surgical patients but may
also be recovered from the peritoneal cavity or severe soft tissue infections. These
species are often antibiotic resistant and require treatment with specific
antipseudomonal antibiotics such as ceftazidime, cefepime, aztreonam,
imipenem/cilastatin, meropenem, ciprofloxacin, an acylureido-penicillin, or an
aminoglycoside. Acinetobacter species are resistant to aztreonam. A significant
proportion of these species exhibit strains resistant even to the most effective
antibiotics, and patients with such pathogens are probably best treated empirically
with two antibiotics until in vitro susceptibility testing becomes available. Even
after susceptibility data are known, critically ill patients may benefit from
treatment with two effective agents. Bacteria from both of these genera have a
tendency to develop resistance to antibiotics during therapy. Although using two
agents may not reduce this process, it does leave the patient with at least one
effective drug when it occurs. Stenotrophomonas maltophilia (previously
Pseudomonas or Xanthomonas maltophilia) is uniformly resistant to imipenem and
meropenem and is most commonly encountered as an emerging organism when
one of these carbapenems is used for empiric treatment of a serious infection.

Anaerobic bacteria are the most numerous inhabitants of the normal

gastrointestinal tract, including the mouth. The most common anaerobic isolate
from surgical infections is Bacteroides fragilis. B.fragilis and Bacteroides
thetaiotaomicron are two common anaerobic species with significant resistance to
many β-lactam antibiotics. The most effective antibiotics against these species are
metronidazole, clindamycin, chloramphenicol, imipenem, meropenem, and
ertapenem and the combinations of a penicillin and a β-lactamase inhibitor
(ticarcillin/clavulanate, ampicillin/sulbactam, and piperacillin/tazobactam). Other
anaerobic species commonly recovered from surgical infections but with less
significant bacterial resistance patterns include Bacteroides melaninogenicus and
most of the anaerobic cocci. The other important genus of anaerobic bacteria found
in surgical infections is Clostridium, previously mentioned in the discussion of
necrotizing soft tissue infections. Although they can survive for variable periods
while exposed to oxygen, they require an anaerobic environment for growth and
invasion and for elaboration of the toxins that account for their dramatic virulence
in soft tissue infections. The Clostridium species are all gram-positive, spore-
forming rods. However, when present in human infections, they do not form
spores, so Gram-stained material from a soft tissue infection shows gram-positive
rods without spores. Clostridium difficile belongs to this family, and Clostridium
tetani is responsible for tetanus. The prevention of tetanus is accomplished solely
through active and passive immunization, not through antibiotic administration.
Anaerobic bacteria have a special importance in relation to surgical infections.
These strains grow only in settings with a low oxidation-reduction potential, which
is incompatible with the survival of mammalian tissue. Thus, the recovery of
anaerobes from a soft tissue infection or even from the blood implies their growth
and multiplication in a focus of dead tissue. The predominant source of anaerobic
bacteria is the gastrointestinal tract; thus, an anaerobic infection implies a defect in
the anatomic integrity of the gastrointestinal tract. Both of these conditions (dead
tissue and a defect in the gastrointestinal tract) require surgical correction, so most
anaerobic infections (other than lung abscess) require surgical intervention.
Certainly an anaerobic bacteremia should always prompt a search for an abscess or
for an enteric lesion that requires surgical intervention.

Diagnosis

History and physical examination The early accurate diagnosis of surgical

infections is essential: delayed treatment can result in dissemination, verwhelming
sepsis, and multisystem organ failure. The history and physical examination are the
surgeon's most important diagnostic tools. The classic signs of tumor, rubor, calor,
dolor and functio laesa are indicative of localized surgical infections. Clinical
symptoms of systemic sepsis include disturbed sensorium, tachypnea, tachycardia,
hypotension, fever, oliguria, and high-output heart failure. In postoperative
patients, the sudden appearance of tachypnea and hypotension suggests Gram-
negative sepsis. This condition has a potential mortality of 30 to 50 per cent, but
early diagnosis and treatment markedly improves the chances of survival. The
entire body must be examined; all dressings should be removed. Inspection and
palpation of a suspicious area may reveal the first three of the classical signs of
infection. Removal of the dressing around an intravenous cannula may reveal
purulent drainage or thrombophlebitis. Rectal examination may show tenderness
and induration as signs of a developing pelvic abscess. Auscultation of the chest
may reveal the presence of pneumonia before it is evident on a chest radiograph.
The patient should be examined for clues to the source of the infection, such as
pain or redness in the surgical wound or at an intravenous infusion site, or purulent
sputum, cough, pleuritic pain, rales, or dullness in the chest, diarrhea, dysuria, or
flank pain. A foul-smelling odor may lead to the site of an anaerobic infection.
Pain in the shoulder and an immobile diaphragm suggest a subphrenic abscess. A
pelvic or prostatic mass on rectal examination may indicate an abscess, and
headache or nuchal rigidity may indicate an infection of the central nervous
system.

Hematology, urinalysis, and radiologyMost bacterial infections produce

leukocytosis and, more importantly, a shift to the left in the differential count or a
relative lymphopenia. This increase in the proportion of the more immature forms
of polymorphonuclear leukocytes may signal infection before an abnormal total
leukocyte count is evident. The differential count may also reveal lymphocytosis in
viral infections, monocytosis in tuberculosis, eosinophilia in parasitic infections or
hypersensitivity reactions (drug allergy), and toxic degranulation of leukocytes in
acute bacterial infection. A low white count or a leukemoid response (a total white
count of over 25 000 cells/mm ) may be seen in sepsis in general, and in
pneumococcal pneumonia, liver abscess or cholangitis, infected pancreatic
necrosis, necrotic bowel, or retroperitoneal phlegmon in particular. Leukopenia is a
sign of overwhelming bacterial infection and carries a bad prognosis. Viral
infection, typhoid perforation of the bowel, or tuberculosis may also present with
leukopenia. Anemia may be associated with infection caused by bacteria, such as
Clostridium perfringens, group A streptococci, or coagulase-positive
staphylococci, that produce hemolytic enzymes. Routine chest films may reveal
generalized or focal atelactasis, or may indicate intra-abdominal infection through
signs of gastrointestinal leakage or free air identified under the diaphragm. In the
investigation of patients with suspected intra-abdominal infection, flat, upright, and
decubitus films may reveal a localized air–fluid level, suggesting an intra-
abdominal abscess, or a spreading air-bubble pattern suggestive of infection with a
gas-producing organism. Specialized radiologic procedures may be helpful in
confirming the diagnosis of intra-abdominal abscess. These studies include
ultrasonography and computed tomography (CT). Although a gallium scintiscan
may be helpful in special circumstances, this examination is subject to appreciable
error and is difficult to interpret in a patient who has had a recent operation.

Bacteriology Observation of exudates and secretions such as wound

drainage, urine, and sputum for odor, color, and consistency may be useful in
diagnosis. Grape-like odors occur with pseudomonal infections, urea-like odors
with Proteus infections, and feculent odors with anaerobic organisms such as
Bacteroides, fusobacteria, clostridia, and peptostreptococci. A Gram stain offers
the earliest clue to the cause of an infection, particularly when a specific
monobacterial infection is suspected. Since surgical infections are mostly due to
multiple infecting organisms that are obligate or facultative anaerobes, the Gram
stain usually shows a variety of pathogenic bacteria. Note should be taken of the
numbers of polymorphonuclear leukocytes on the slide (few, many, loaded) and
whether organisms can be seen inside them. Acid-fast and fungal stains can be
used if such infections are likely.

Technique of obtaining the specimen Purulent material from the deepest

aspect of the wound should be aspirated into a syringe and any air evacuated. Pus
is the best medium in which to preserve bacteria for transport to the laboratory.
The capped syringe is sent for aerobic and anaerobic culture, and for assay of
antibiotic sensitivity. Alternatively, a moist swab can be used to obtain bacteria
from a site of suspected infection. Ideally, anaerobic specimens should be
transported immediately in a CO -filled tube and plated within 1 h of 2 sampling;
fastidious organisms may otherwise die, resulting in a false-negative culture result.
If the specimen is held overnight, it should be placed in an anaerobic sterile vial or
tube; under no circumstances should an anaerobic specimen be refrigerated.
Generally speaking, E. coli (aerobe) and Bacteroides fragilis (anaerobe) are the
usual causes of wound infection following gastrointestinal or gynecologic
operations, while streptococci, staphylococci, and peptostreptococci are the usual
causative organisms when intra-abdominal viscera have not been resected or
opened. Blood cultures are helpful in guiding the specific antibiotic therapy of
serious infections if the empirically started, initial antibiotics fail. Following
careful disinfection of the venepuncture site with an iodophor preparation, blood
samples should be obtained for aerobic and anaerobic culture. Blood should not
ordinarily be drawn for culture through an existing intravenous needle or catheter.
It is important to obtain a number of blood cultures from different sites and at
different times. Once the patient chills and a fever spike is observed, most bacteria
have already been killed by host defense mechanisms and blood cultures will be
negative. It is possible, however, to predict the time of the next bacteremic episode,
because fever spikes occur intermittently. Drawing four blood samples at hourly
intervals before the next peak will increase the likelihood of a positive culture. If
the patient is receiving treatment with antimicrobial drugs, a drug-removing device
is helpful in obviating antimicrobial action during culture.
 Sensitivity tests need to be interpreted appropriately and with caution since
they are not always reproducible and are an oversimplification of the complex
foundations upon which antimicrobial chemotherapy is based. Disc diffusion tests
are highly sensitive to small technical and environmental changes. Their results
may not correlate well with the actual minimal inhibitory or bactericidal
concentration of an antibiotic, or with the concentration of antibiotic achieved at
the site of infection with the chosen dosage. While important for epidemiologic
purposes, routine disc sensitivity tests are generally of little value in guiding an
individual patient's antibiotic therapy. The minimal inhibitory concentration
(MIC), or the minimal bactericidal or fungicidal concentrations, are more useful
clinically, because antimicrobial dosing can be adjusted to achieve and sustain
antibiotic concentrations at the focus that are three to four times in excess of the
concentration required to kill bacteria in the test-tube.

Therapy of surgical infections

All wounds, whether made at the operating table or resulting from trauma,
expose normally sterile tissue and provide an environment for bacterial growth.
Infections can be minimized if wound management follows these principles.

1. Tissue should be handled gently, and operative trauma kept at a minimum.

2. Further contamination should be minimized by use of aseptic techniques.

3. Devitalized tissue, debris, and traumatic foreign bodies should be

removed.

4. Complete hemostasis should be achieved.

5. Blood supply is essential for healing and should not be impaired.

6. Formation of dead space should be avoided during closure.

 7. The wound should be closed by layer-to-layer approximation without
tension.

8. Operative time should be kept to a minimum to reduce the numbers of

bacteria entering the wound.

9. The wound may be irrigated with liberal amounts of sterile saline/Ringer's

lactate solution prior to closure.

Basic understanding of how the body defends itself against infection is

essential to a rational application of surgical and other therapeutic principles to the
control of infection.

General principles of therapy

Whichever antibiotics are employed, the goal of therapy is to achieve levels

of antibiotic at the site of infection that exceed the minimum inhibitory
concentration for the pathogens present. For mild infections, including most that
can be handled on an outpatient basis, this may be achievable with oral antibiotics
when appropriate choices are available. For severe surgical infections, however,
the systemic response to infection may make gastrointestinal absorption of
antibiotics unpredictable and thus antibiotic levels unreliable. In addition, for intra-
abdominal infections, gastrointestinal function is often directly impaired. For this
reason, most initial antibiotic therapy for surgical infections is begun
intravenously. Each patient with a serious infection should be evaluated daily or
more frequently to assess response to treatment. If obvious improvement is not
seen within 2 to 3 days, one often hears the question, “Which antibiotic should we
add [switch] to?” That question is appropriate, however, only after the following
question has been addressed: Why is the patient failing to improve? Likely answers
include the following:

1. The initial operative procedure was not adequate.

 2. The initial procedure was adequate but a complication has occurred.

3. A superinfection has developed at a new site.

4. The drug choice is correct, but not enough is being given.

5. Another or a different drug is needed.

The choice of antibiotics is not the most common cause for failure unless the
original choice was clearly inappropriate, such as failing to provide coverage for
anaerobes in an intra-abdominal infection. As the patient improves, one must
decide when to stop antibiotic therapy. For most surgical infections there is not a
specific duration of antibiotics known to be ideal. Antibiotics generally support
local host defenses until the local responses are sufficient to limit further infection.
When an abscess is drained, the antibiotics prevent invasive bacterial infection in
the fresh tissue planes opened in the course of drainage. After 3 to 5 days, the local
responses of new capillary formation and inflammatory infiltrate provide a
competent local defense. For deep-seated or poorly localized infections, longer
treatment may be needed. A reliable guideline is to continue antibiotics until the
patient has shown an obvious clinical improvement based on clinical examination
and has had a normal temperature for 48 hours or more.

Signs of improvement include improved mental status, return of bowel

function, resolution of tachycardia, and spontaneous diuresis. A shorter course of
antibiotics may be sufficient, but data supporting a specific duration are not
available. The recent availability of potent systemic antibiotics that can be given
orally has led to some studies demonstrating that patients with intra-abdominal and
other serious infections can be treated initially with parenteral antibiotics and then
switched to oral antibiotics to complete their antibiotic course. This has the
potential to reduce overall costs of antibiotic treatment, but it also has the risk to
increase unnecessarily the duration of antibiotic treatment. Some physicians have
succumbed to the temptation to send home patients with antibiotics by mouth
because it is easy when previously the same patient would have been sent home
without any antibiotics at all. This temptation should be resisted.

The white blood cell count may not have returned to normal when
antibiotics are stopped. If the white blood cell count is normal, the likelihood of
further infectious problems is small. If the white blood cell count is elevated,
further infections may be detected but in most cases they will not be prevented by
continuing antibiotics. Rather, a new infection requires drainage or different
antibiotics for a new, resistant pathogen in a different location. In this case, the best
approach is to stop the existing drugs and observe the patient closely for
subsequent developments. When choosing an antibiotic for empiric treatment, the
following guidelines should be followed:

1. Coverage of the presumed microorganisms involved should be ensured.

This usually means starting broad-spectrum antibiotics that can then be tailored
and narrowed to the specific microorganism isolated. Anaerobic spectrum
antibiotics should be avoided when possible since this group of bacteria plays an
important role in maintaining the gastrointestinal tract microenvironment.

2. The antibiotic chosen should be able to reach the site of the infection.
Specifically for UTI and for cholangitis, antibiotics with high renal and biliary
concentrations, respectively, should be chosen. Skin, lungs, and central nervous
system tissue concentration should also be considered for infections at these sites.

3. Toxicity should be considered, particularly in critically ill patients in

whom bioavailability and therapeutic and toxic level range are harder to predict.
Once an antimicrobial with significant toxic side effects is started, blood levels and
organ function should be closely monitored.

4. Whenever an infection that will need antibiotics is identified, these should

be dosed aggressively. The volume of redistribution of these patients is
unpredictable since they usually have aggressive fluid replacements as part of their
support or resuscitation.

5. Whenever an antibiotic regimen is started, set a time limit for the period
for which the antibiotic will be given.

A superinfection is a new infection that develops during antibiotic

treatment for the original infection. Whenever antibiotics are used, they exert a
selective pressure on the endogenous flora of the patient and on exogenous bacteria
that colonize sites at risk. Bacteria that remains are resistant to the antibiotics being
used and become the pathogens in superinfection. Respiratory tract infections are
common superinfections that occur during the treatment of intra-abdominal
infection. The greater the severity of the abdominal infection and the greater the
risk of poor outcome, the greater the risk of pneumonia as well. Careful
surveillance of hospitalized patients reveals superinfections in 2% to 10% of
antibiotic-treated patients, depending on the underlying risk factors. The best
preventive action is to limit the dose and duration of antibiotic treatment to what is
obviously required and to be alert to the possibility of superinfections. The use of

increasingly powerful and broad-spectrum antibiotics during the past 2 decades

have also led to an increasing incidence of fungal superinfections. Antibiotic-
associated colitis is another significant superinfection that can occur in hospitalized
patients with mild to serious illness. This entity is caused by the enteric pathogen
C. difficile and has been reported after treatment with every antibiotic except
vancomycin. C. difficile colitis can vary from a mild, self-limited disease to a
rapidly progressive septic process culminating in death. The most important step in
treating this disease is to suspect it. Diagnosis is best accomplished by detecting
C.difficile toxin in the stool. In severe cases, endoscopy, revealing the typical
mucosal changes with inflammation, ulceration, and plaque formation can make a
more rapid diagnosis of the severe form of the disease, pseudomembranous colitis.
Treatment is supportive with fluid and electrolytes, withdrawal of the offending
antibiotic if possible, and oral metronidazole to treat the superinfection.
Vancomycin should be reserved for metronidazole failures. In rare instances when
an overwhelming colitis does not respond to medical management, emergency
colectomy may be required.

Antibiotic resistance is an escalating problem presenting particularly in

patients in ICUs. Its implications include increased length of stay, increased costs
of care, and, more importantly, an increased morbidity and mortality derived from
infections treated unsuccessfully. Resistance has been broadly divided into two
forms: (1) intrinsic resistance, in which a specific species is inherently resistant to
a specific antibiotic (e.g., gram-negative bacteria to vancomycin) and (2) acquired
resistance, in which a change of the genetic composition of the bacteria occurs.
This acquired resistance can be the result of intrinsic changes within the native
genetic material of the pathogen or can be transferred from another species. The
molecular mechanisms by which bacteria acquire resistance to antibiotics can be
broadly classified into the following four categories:

1. Decreased intracellular concentration of antibiotic, either by decreased

influx or increased efflux— Most antibiotics are susceptible to this mechanism
(Pseudomonas/Enterobacteriaceae to β-lactams).

2. Neutralization by inactivating enzymes—This is the most common

mechanism of antibiotic resistance and affects all β-lactam antibiotics (e.g., β-
lactamases from gram-positive and gram-negative bacteria).

3. Alteration of the target at which the antibiotic will act—It affects all
antibiotics and is the main resistance mechanism for some specific bacteria
(Pneumococcus to penicillin or MSRA to all β-lactam antibiotics).

4. Complete elimination of the target at which the antibiotic will act—

Some specific bacteria develop the ability to create new metabolic pathways and
completely eliminate a specific target (e.g., VRE).

Antibiotic resistance is usually achieved by the combination of these

different mechanisms. However, the presence of one of them may confer resistance
to one or more different groups of antibiotics. The bacterial genome is divided into
chromosomal DNA, which gives specific characteristics and metabolic pathways
to the bacteria, and smaller, circular, and independent DNA elements (plasmids)
that encode information for supplemental bacterial activities such as virulence
factors and resistance mechanisms. Most resistance mechanisms are plasmid
mediated, although they can interchange with chromosomal information (with the
aid of transposons [mobile DNA elements]), conferring more fixed mechanisms
that will be transmitted vertically. However, plasmids can also be transmitted
horizontally through conjugation, transduction, and transformation processes in
which different bacteria are exposed to a specific plasmid. Risk factors for
antibiotic resistance in a specific patient include use of antibiotics, prolonged
hospital stays, use of broad-spectrum antibiotics, use of invasive devices (e.g.,
endotracheal tubes, central lines, Foley catheters) and the presence of outbreaks
that may reflect ineffective infection control policies. The populations at highest
risk are ICU patients in which the potential absence of effective antibiotic
treatments correlates with higher mortality rates. Prevention strategies have been
studied, and although it is difficult to establish a clear relation between their
practice and decreased resistance, they should be part of a discipline that not only
reduces the incidence of antibiotic resistance but also follows a logical practice for
infection control and use of antibiotics. Some of these strategies include guidelines
for use of antibiotics (hospital formulary restriction, use of narrow-spectrum
antibiotics, antibiotic cycling, use of new antibiotics), assessment of infection risk
and quantitative cultures, infectious disease specialists, and area-specific use of
antibiotics (e.g., outpatients vs. nosocomial, hospital to hospital difference).
Nonantibiotic strategies include prevention of nosocomial infections (general and
specific measures) and prevention of hospital transmission (hand washing, contact
precautions). The battle against antibiotic resistance is definitely multidisciplinary
and involves the development of new antibiotics as well as strategies in the
everyday care of patients from all the health care personnel.

A number of studies have demonstrated the importance of empiric

antimicrobial agent therapy in patients who develop severe sepsis syndrome and
subsequently are found to have developed bacteremia, concurrent with fluid
resuscitation, metabolic support, and control of any site-specific source of
infection, leading to secondary bacteremic events. Use of institutional and unit-
specific sensitivity patterns and knowledge of likely pathogens are critical in
selecting an appropriate agent for the treatment of presumed bacteremia.
Retrospective reviews demonstrate that appropriate therapy is associated with a
two- to threefold reduction in mortality. A number of new therapies for treatment
of patients with severe sepsis have recently been demonstrated to be of significant
benefit in patients with severe sepsis or septic shock. A number of investigators
have revisited the issue of corticosteroids for the treatment of septic shock. High-
dose corticosteroid therapy had been previously investigated in the late 1980s and
early 1990s with no evidence of benefit for septic patients. Recent interest has
arisen for the use of corticosteroids in patients presenting to the ICU in septic
shock subsequent to the observation that many patients in this state harbor adrenal
insufficiency. A number of randomized, controlled trials have demonstrated the
benefit of replacement doses of corticosteroids in patients with severe shock states.
In patients who develop septic shock, currently we initiate low-dose
hydrocortisone (100 mg/8 h) after performing a corticotropin stimulation test
(baseline cortisol level, corticotropin 250 μg intravenously, cortisol level 1 hour
later). Adrenal insufficiency is identified if the baseline cortisol level is less than
30 μg/dL, or if an increase of less than 9 μg/dL occurs after corticotropin
stimulation. Low-dose steroid therapy should be discontinued in patients with
normal adrenal function.

Nutrition in the surgical patient

The goal of nutritional support in the surgical patient is to prevent or reverse

the catabolic effects of disease or injury. While several important biologic
parameters have been used to measure the efficacy of nutrition regimens, the
ultimate validation for nutritional support in surgical patients should be
improvement in clinical outcome and restoration of function.

Rationale for Parenteral Nutrition The principal indications for parenteral

nutrition are found in seriously ill patients suffering from malnutrition, sepsis, or
surgical or accidental trauma, when use of the gastrointestinal tract for feedings is
not possible. In some instances, intravenous nutrition may be used to supplement
inadequate oral intake. The safe and successful use of parenteral nutrition requires
proper selection of patients with specific nutritional needs, experience with the
technique, and an awareness of the associated complications. As with enteral
nutrition, the fundamental goals are to provide sufficient calories and nitrogen
substrate to promote tissue repair and to maintain the integrity or growth of lean
tissue mass. Listed below are situations in which parenteral nutrition has been used
in an effort to achieve these goals:

1. Newborn infants with catastrophic gastrointestinal anomalies, such as

tracheoesophageal fistula, gastroschisis, omphalocele, or massive intestinal
atresia.
2. Infants who fail to thrive due to gastrointestinal insufficiency associated with
short bowel syndrome, malabsorption, enzyme deficiency, meconium ileus, or
idiopathic diarrhea.
3. Adult patients with short bowel syndrome secondary to massive small bowel
resection (<100 cm without colon or ileocecal valve, or <50 cm with intact
ileocecal valve and colon).
4. Enteroenteric, enterocolic, enterovesical, or high-output enterocutaneous
fistulas (>500 mL/d).
5. Surgical patients with prolonged paralytic ileus following major operations
(>7 to 10 days), multiple injuries, blunt or open abdominal trauma, or patients
with reflex ileus complicating various medical diseases.
6. Patients with normal bowel length but with malabsorption secondary to sprue,
hypoproteinemia, enzyme or pancreatic insufficiency, regional enteritis, or
ulcerative colitis.
7. Adult patients with functional gastrointestinal disorders such as esophageal
dyskinesia following cerebrovascular accident, idiopathic diarrhea,
psychogenic vomiting, or anorexia nervosa.
8. Patients with granulomatous colitis, ulcerative colitis, and tuberculous
enteritis, in which major portions of the absorptive mucosa are diseased.
9. Patients with malignancy, with or without cachexia, in whom malnutrition
might jeopardize successful delivery of a therapeutic option.
10. Failed attempts to provide adequate calories by enteral tube feedings or high
residuals.
11. Critically ill patients who are hypermetabolic for more than 5 days or when
enteral nutrition is not feasible.

Conditions contraindicating hyperalimentation include the following:

1. Lack of a specific goal for patient management, or in cases in which instead

of extending a meaningful life, inevitable dying is delayed.
2. Periods of hemodynamic instability or severe metabolic derangement (e.g.,
severe hyperglycemia, azotemia, encephalopathy, hyperosmolality, and fluid-
electrolyte disturbances) requiring control or correction before attempting
 hypertonic intravenous feeding.
3. Feasible gastrointestinal tract feeding; in the vast majority of instances, this is
the best route by which to provide nutrition.
4. Patients with good nutritional status.
5. Infants with less than 8 cm of small bowel, since virtually all have been
unable to adapt sufficiently despite prolonged periods of parenteral nutrition.
6. Patients who are irreversibly decerebrate or otherwise dehumanized

Rationale for Enteral Nutrition Enteral nutrition generally is preferred over

parenteral nutrition based on reduced cost and associated risks of the intravenous
route. Laboratory models have long demonstrated that luminal nutrient contact
reduces intestinal mucosal atrophy when compared with parenteral or no
nutritional support. Studies comparing postoperative enteral and parenteral
nutrition in patients undergoing gastrointestinal surgery have demonstrated
reduced infection complications and acute phase protein production when fed by
the enteral route. Yet, prospectively randomized studies for patients with adequate
nutritional status (albumin = 4 g/dL) undergoing gastrointestinal surgery
demonstrate no differences in outcome and complications when administered
enteral nutrition compared to maintenance intravenous fluids alone in the initial
days following surgery. Recent meta-analysis for critically ill patients
demonstrates a 44% reduction in infectious complications in those receiving
enteral nutritional support over those receiving parenteral nutrition. Most
prospectively randomized studies for severe abdominal and thoracic trauma
demonstrate significant reductions in infectious complications for patients given
early enteral nutrition when compared with those who are unfed or receiving
parenteral nutrition. The exception has been in studies for patients with closed-
head injury, because no significant differences in outcome are demonstrated
between early jejunal feeding compared with other nutritional support modalities.
Recommendations for instituting early enteral nutrition to surgical patients with
moderate malnutrition (albumin = 2.9 to 3.5 g/dL) can only be made by inferences
due to a lack of data directly pertaining to this population. For these patients, it is
prudent to offer enteral nutrition based on measured energy expenditure of the
recovering patient, or if complications arise that may alter the anticipated course of
recovery (e.g., anastomotic leaks, return to surgery, sepsis, or failure to wean from
the ventilator). Other clinical scenarios with substantiated benefits from enteral
nutritional support include permanent neurologic impairment, oropharyngeal
dysfunction, short bowel syndrome, and bone marrow transplantation patients.
Collectively, the data support the use of early enteral nutritional support following
major trauma and in patients who are anticipated to have prolonged recovery after
surgery. Healthy patients without malnutrition undergoing uncomplicated surgery
can tolerate 10 days of partial starvation (i.e., maintenance intravenous fluids only)
before any significant protein catabolism occurs. Earlier intervention is likely
indicated in patients with poorer preoperative nutritional status. Initiation of enteral
nutrition should occur immediately after adequate resuscitation, most readily
determined by adequate urine output. Presence of bowel sounds and the passage of
flatus or stool are not absolute requisites for initiating enteral nutrition, but
feedings in the setting of gastroparesis should be administered distal to the pylorus.
Gastric residuals of 200 mL or more in a 4- to 6-hour period or abdominal
distention will require cessation of feeding and adjustment of the infusion rate.
Concomitant gastric decompression with distal small bowel feedings may be
appropriate in certain patients such as closed-head injury patients with
gastroparesis. There is no evidence to support withholding enteric feedings for
patients following bowel resection, or in those with low-output enterocutaneous
fistulas of less than 500 mL/d, but low-residue formulations may be preferred.
Enteral feeding should also be offered to patients with short-bowel syndrome or
clinical malabsorption, but caloric needs, essential minerals, and vitamins should
be supplemented with parenteral modalities.

AIDS

HIV is a blood-borne infection that is transmitted to the susceptible host

after percutaneous or a mucus membrane exposure to infected blood or body
fluids. The virus attaches to specific receptors on the host CD4 lymphocytes. The
virus is internalized with release of the viral RNA. The unique enzyme, reverse
transcriptase, of the virus then results in the synthesis of complementary copies of
DNA to the RNA template of the virus (cDNA). This cDNA then migrates into the
nucleus of the infected cell, is incorporated into the chromosomal configuration of
the host cell, and then initiates the synthesis of new viral particles. The viral
burden within the infected cell reaches a critical level with lysis of the infected cell
and release of viral particles to infect other cells. The result of this process over
time is the systematic depletion of CD4 depressor cells with dominance of the CD8
cells and subsequent immunosuppression of the host. The natural history of HIV
infection passes through four phases. First there is the acute viral infection, which
includes fever, malaise, pharyngitis, and other symptoms that would be nonspecific
features of many viral infections. Second, there is a sustained period of
asymptomatic disease. It is during this asymptomatic disease period that active
viral replication is occurring in a slow but progressive fashion, which slowly
progresses to a state with significant reduction in CD4 cell counts. This indolent
second phase is highly variable in different patients and for many patients evolves
over a decade or longer. A third phase, which was formerly referred to as AIDS-
related complex, represents the first evidence of symptomatic AIDS. The patients
present with evidence of regional adenopathy. During this early symptomatic
period, the viral load in the patient is increasing and the CD4 count is progressively
declining. Clinical AIDS is considered to exist when the patient has an indicator
condition or has a CD4 count lower than 200. The indicator conditions may
present as problems requiring surgical care, or conventional illnesses may present
with an obscure presentation because of the patient’s immunosuppressed state, or
conventional illnesses may be mistaken for nonsurgical illnesses associated with
the primary HIV infection.

Acute Abdomen. The AIDS patient has an increased frequency of the

clinical acute abdominal pain syndrome than does the age-matched non-AIDS
population. AIDS patients undergo abdominal exploration for a host of different
reasons. It is likely that AIDS patients actually have an increased rate of
emergency abdominal procedures because they have the anticipated rates of
operation for commonly seen indications (e.g., appendicitis) but have indications in
addition to those that are specific for this disease. An increased probability of
abdominal operation but also increased nonsurgical causes for abdominal pain
means that a discriminating evaluation of these patients is always necessary. Acute
appendicitis in the AIDS patient occurs due to the conventional occlusion of the
appendiceal orifice by a fecalith but also due to occlusion of the orifice by
Kaposi’s sarcoma lesions and acute CMV infections. Accumulated appendicitis
cases in aged patients indicate that 30% are caused by complications of AIDS-
related conditions. Clinical presentation for the AIDS patient with appendicitis is
with characteristic right lower pain but is commonly associated with normal WBC
counts in most patients. Most have fever, but fever and nonspecific abdominal pain
alone are common findings among AIDS patients without surgical illness.
Although there is no clear definition in the published literature, there appears to be
an increased rate of perforation, gangrenous appendicitis, and initial appendiceal
abscess among AIDS patients. Delay in patient presentation because of frequent
abdominal pain and fever, and delay by the physician because of the numerous
nonsurgical causes of abdominal pain, may account for this apparent observation.

Perforation of the gastrointestinal tract not related to appendicitis is

certainly increased in the AIDS patient. The mean age of the clinical onset of
AIDS is in the late 30s. Other than appendicitis, this age group infrequently has a
perforated viscus. AIDS patients have perforation of the gastroduodenum, small
bowel, and colon due to CMV infection in particular. The terminal ileum and
colon are most common sites for CMV perforations. The diagnosis of CMV
perforations is confirmed by identification of the intranuclear inclusion bodies on
biopsy specimens from sites of perforation. Appropriate surgical management of
the site of perforation requires suture plication of gastroduodenal perforations,
resection and anastomosis of small bowel perforations, and colostomy for colonic
perforations. Acute antiviral chemotherapy is initiated. CMV perforation is an
indicator of advanced HIV disease and carries a grave prognosis owing to death
from peritonitis or other AIDS-related complications. Kaposi’s sarcoma,
gastrointestinal lymphoma, and severe ileocolitis from Mycobacterium avium
intracellulare are additional causes of AIDS-related perforations of the
gastrointestinal tract. Biopsies of the site of perforation at operation are necessary
to establish causation. Management of the perforated site is the same as for any
other perforation due to infectious causes.

Gastrointestinal obstruction is seen secondary to AIDS-related disease.

Causes include gastric outlet obstruction secondary to lymphoma, small bowel
obstruction due to mycobacterial disease, intussusceptions secondary to Kaposi’s
sarcoma, and an Ogilvie-like syndrome progressing to toxic megacolon due to
CMV infection. The diagnosis of the AIDS-related events needs to be
differentiated for more conventional causes of obstruction. In the usual age group
for AIDS patients, particularly when prior abdominal operation and the risk of
adhesions are not present, most intestinal obstruction events are AIDS related.

Gastrointestinal bleeding is similarly seen by the same array of disease

processes that are responsible for perforation and obstruction. When bleeding
arises from the gastroduodenum or colon, endoscopy procedures will assist
diagnosis. Operation is required only when medical measures to control
hemorrhage have failed.

Hepatobiliary disease is common in the HIV-infected patient. Chronic

hepatitis B and C infections share common routes of transmission with HIV
disease. Persistent elevation of hepatic enzymes from chronic hepatitis is common
with cirrhosis as a frequent result. Once clinical AIDS has evolved, infection of the
liver parenchyma from Candida albicans and M. avium intracellulare result in
small hepatic abscesses, which may require liver biopsy for diagnosis. Although
infections with Entamoeba histolytica among the male homosexual population with
AIDS are common, amebic abscess is much less common.
 A particularly interesting but infrequent infectious problem is AIDS-
associated cholangiopathy. This appears to be the consequence of infection of the
actual bile ducts themselves with opportunistic pathogens including
Cryptosporidium species, CMV, and Microsporidia. Inflammatory changes
secondary to invasion of the ducts result in a sclerosis-like picture. The patients
have new-onset right upper quadrant pain, fever, alkaline phosphatase elevations,
but rarely jaundice, at the time of initial presentation. Jaundice becomes more of a
feature of the disease as the process advances over time. Diagnosis is suggested by
ultrasound demonstration of thickened ducts. Endoscopic retrograde
cholangiopancreatography is used to culture the bile or obtain biopsies of the bile
ducts. Specific antimicrobial chemotherapy is used for treatment. Surgical care for
these patients is limited. An occasional patient may develop acute cholecystitis
secondary to cystic duct occlusion. Radionuclide scans are used for diagnosis, and
cholecystectomy may be necessary in the patient with acute cholecystitis.

Splenomegaly is a common finding among AIDS patients but may be the

result of multiple causes. Patients may have portal hypertension from severe liver
disease or portal fibrosis. Parenchymal infection of the spleen may be secondary to
CMV, Microbacterium, Pneumocystis carinii, and other pathogens. Splenic
enlargement may be secondary to lymphoma or Kaposi’s sarcoma. The patients
commonly have left upper quadrant pain and the spleen is palpable and quite
tender on physical examination. Splenectomy may infrequently be necessary
secondary to spontaneous rupture or to rupture from incidental trauma.

Vascular infections are reported among AIDS patients. Some infected

pseudoaneurysms are seen among the intravenous drug abuse population with
common bacteria (e.g., S. aureus). These infections among the AIDS population
are difficult to eradicate. Perhaps more interesting and somewhat unique to the
AIDS patient is Salmonella arteritis. AIDS patients have a high incidence of
Salmonella infection. Apparently Salmonella has a particular affinity for
atherosclerotic plaque. Adherence of the microbe to an atheroma of the distal aorta
or iliac arteries can result in invasive infection, pseudoaneurysm formation, and
potential rupture. Surgical management prior to rupture is desired. Reconstruction
of these patients following resection proceeds along guidelines for management of
any mycotic aneurysm infection.

Neoplasms. B-cell lymphoma occurs commonly among AIDS patients.

These malignancies are commonly undifferentiated and aggressive. Operative
intervention for the lymphoma patient is for the purpose of diagnosis of the disease
(e.g., needle biopsy). More commonly surgical intervention is for the management
of complications secondary to bleeding, obstruction, or perforation of the
gastrointestinal tract. Primary management of the lymphoma disease is medical.
Kaposi’s sarcoma is a neoplasm of the skin that was uncommon until the AIDS
epidemic. Kaposi’s sarcoma is the result of the patient having chronic infection
with human herpesvirus-8, but clinical disease occurs only when the patient’s
clinical immunosuppression reaches an advanced stage. Kaposi’s sarcoma in the
AIDS patients occurs at numerous different sites, including skin, gastrointestinal
tract, lung, liver, and even the heart. Surgical involvement is primarily for
diagnosis and the management of complications, particularly in the gastrointestinal
tract. As noted earlier, perforation, bleeding, and small bowel intussusceptions are
noted gastrointestinal complications from Kaposi’s sarcoma. Radiation and
chemotherapy are the primary treatment modalities for this neoplasm.

Anorectal Disease. The immunosuppressed AIDS patient is at increased risk

for human papillomavirus infection. Large condylomata acuminata are the result.
Very large condylomata commonly need to be surgically reduced to be followed
by local topical therapy. Squamous cell carcinoma of the anus occurs with
increased frequency presumably due to the role of papillomavirus in causing this
disease.

Occupational Risk of Infection. A major surgical concern about the HIV-

infected patient was the potential of infection being occupationally acquired during
the course of providing surgical care for these patients. Surgical exposure to patient
blood during the performance of operative procedures has been well documented.
With the knowledge that HIV is a blood-borne pathogen and that other blood-
borne pathogens (e.g., hepatitis B) have been documented to be transmitted in the
operating room, many surgeons have been concerned about this risk.

At this time it can be said that the risk of occupational transmission of HIV
disease is low, but it is not zero. As of the last available Centers for Disease
Control and Prevention report, 57 documented cases of occupational transmission
of HIV have occurred and 138 cases of probable transmission among health care
workers have been identified. No documented cases have been seen in surgeons.
Most occupational infections have come from major percutaneous injuries from
hollow needles. Solid-needle injuries have not been documented to occur in the
United States. Current rates of transmission from hollow needles are about 0.2% to
0.3%. Surgeons should feel comfortable in providing care for HIV-infected
patients but should use appropriate and standardized safeguards to prevent blood
exposure in the care of all patients.

Basic literature:
1. Oxford Textbook of Surgery (3-Volume Set) 2nd edition (January 15, 2000):
by Peter J. Morris (Editor), William C. Wood (Editor) By Oxford Press
2. Sabiston Textbook of Surgery 17th edition by Courtney M. Townsend Jr.,
Kenneth L. Mattox, B. Mark, MD Evers, Kenneth L., MD Mattox, Courtney
Townsend, Daniel Beauchamp, B. Mark Evers, Kenneth Mattox W.B.
Saunders Company (June, 2004)
3. Schwartz´s Principles of Surgery 8th Edition F. Charles Brunicardi.
Copyright ©2007 the McGraw-Hill Companies.
4. Hospital surgery/ Edited by L. Kovalchuk et al. - Ternopil: Ukrmedknyha,
2004. - 472 p.
Additional literature:
1. Bachetti T, Pasini E, Suzuki H, et al: Species-specific modulation of
the nitric oxide pathway after acute experimentally induced endotoxemia. Crit
Care Med 31:1509, 2003.
2. Briegel J, Jochum M, Gippner-Steppert C, et al: Immunomodulation
in septic shock: Hydrocortisone differentially regulates cytokine responses. J Am
Soc Nephrol 12:S70, 2001.
 3. Healy DP: New and emerging therapies for sepsis. Ann
Pharmacother 36:648, 2002. Raeburn CD, Sheppard F, Barsness KA, et al:
Cytokines for surgeons. Am J Surg 183:268, 2002.
4. Turnidge J: Impact of antibiotic resistance on the treatment of sepsis.
Scand J Infect Dis 35:677, 2003.

Tasks for final level of knowledge

1. A 62-year-old man presents with chills, fever, dysuria, urinary

frequency, diffuse low back pain, and an exquisitely tender prostate on rectal
exam.

What is it?

2. An adult woman relates that 5 days ago she began to notice

frequent, painful urination, with small volumes of cloudy and malodorous
urine. For the first 3 days she had no fever, but for the past 2 days she has been
having chills, high fever, nausea, and vomiting. Also in the past 2 days she has
had pain in the right flank. She has had no treatment whatsoever up to this
time.

What is it?

3. A 56-year-old alcoholic man is admitted with a clinical clinical

picture of acute-upper abdominal pain. The pain is constant, radiates straight
through the back, and is extremely severe. He has a serum amylase of 800, a
hematocrit of 40%, WBC count of 18,000, blood glucose of 150 mg/dL and
serum calcium of 6.5. He is given IV fluids and kept NPO with NG suction.
By the next morning, his hematocrit has dropped to 30%, the serum calcium
has remained below 7 despite calcium administration, his blood urea nitrogen
(BUN) has gone up to 32, and he has developed metabolic acidosis and a low
arterial P02.

What is it?

4. A 43-year-old obese mother of six children has severe right upper

quadrant abdominal pain that began 6 hours ago. The pain was colicky at first,
radiated to the right shoulder and around toward the back, and was accompanied
by nausea and vomiting. For the past 2 hours the pain has been constant. She
has tenderness to deep palpation, muscle guarding, and rebound in the right
upper quadrant. Her temperature is 101 °F, and she has a WBC count of 16,000.
She has had similar episodes of pain in the past brought about by ingestion of
fatty food, but they all had been of brief duration and relented spontaneously
or with anticholinergic medications.
 What is it?

5. Forty-five minutes after completion of a cystoscopy, a patient

develops chills and a fever spike of 104°F.

What is it?
Materials for the self-study of the students
Main tasks Notes (instructions)
Repeat:
-To represent the methods of HIV
1. Inflammation
diagnosis
2. Pathophysiology of
-To make the flow diagram of
inflammation
mechanisms of sepsis.
3. Stages of AIDS.

Study:
1. Stages of sepsis. -To conduct differential diagnosis
2. Methods of diagnosis. different tapes of SIRS
3. Antibiotic resistance