Sepsis

By Jessica Ryon
Introduction to Sepsis
Sepsis is a metastatic infection that arises when infectious microbes in the circulatory system
overwhelms the immune system and the microorganisms can no longer be removed from
circulating blood faster than they are proliferating. The general public is relatively unaware
that sepsis exists, yet it kills approximately 120,000- 200,000 people annually in the United
States&emdash;which is more than the number of AIDS deaths nationally per year. About
40% of the people diagnosed with sepsis die, which makes it the leading cause of death in the
ICU. In fact, the medical specialty practice of Critical Care Management was specifically
developed as a result of septic mortality rates (3, 14, 12).
Means of Transmission
Sepsis, itself, is a disease process resulting from an explosive infection that is accompanied
by shock if it progresses to the final stage of end-organ damage. "Sepsis" is not
communicable. However, a number of the possible causative organisms are transmittable to
other hosts by means of contact and vehicle transmission. The most common origins of
infections that develop into sepsis are UTI, pneumonia, cellulitis, wounds and abscesses,
sinusitis, meningitis, and surgical procedures to an infected area or the abdomen (14, 23).
Etiological Agents A ten-year study of the most common causative organisms associated with
sepsis yielded the following statistics:
Gram-positive bacteria- 52.9%
Gram-negative bacteria- 41.6%
Anaerobic organisms- 1.4%
Fungi- 4.1% (15).
Gram-negatives: Proteus, Serratia, Pseudomonas aeruginosa, Neisseria meningitudis,
Escherichia coli Klebsiella pneumoniae
Gram-positives: Staphylococcus aureus, coagulase-negative Staphylococcus, Streptococcus
pyogenes, Streptococcus pneumoniae, enterococci
Fungi: Candida albicans (23, 18, 20)
Pathophysiology
Sepsis originates as an isolated infection of microorganisms that become mobile in the
circulatory system. Bacteremia is rarely associated with any signs or symptoms and most
microorganisms are readily removed from circulation by the humoral immune system. When
microbes begin to reproduce in the circulatory system and the body is unable to remove them
at an adequate rate, septicemia develops, and a systemic inflammatory response is initiated.
This syndrome, SIRS, is one of the primary disease patterns in sepsis. The progression from
sepsis to septic shock follows the significant increase in serum levels of TNF-a, IFN-a, IL1B, IL-8, and IL-6. Shock is a condition defined by inadequate tissue perfusion&emdash;in
this case resulting from vasodilation due to increased cytokine levels and intravascular fluid
shifting. TNF-a levels also increase, which is believed to be responsible for the onset of
disseminated intravascular coagulation (DIC). These conditions, together with renal and liver
failure, cause cardiac collapse and respiratory failure (ARDS). The signs and symptoms of

sepsis vary according to the associated disease processes. However, most symptomology is
universal. Sepsis is preceded by a period of altered mental status for approximately 24 hours
before other signs develop. Fatigue, malaise, myalgia, nausea, and vomiting are common
early signs. Fever initially develops, but declines to hypothermia in late stages. Elevated heart
rate and respiratory rate develop as blood pressure becomes erratic. Blood pressure
eventually declines dramatically as plasma shifts and vasodilation worsens. Impaired renal
function is evident with decreased urinary output, as is liver failure with jaundice (5, 19, 12,
22).
Laboratory Studies
Gram staining is the quickest procedure to identify the origin of infection.
Blood cultures are needed from the suspected site of origin, but samples should be taken from
two separate locations to increase likelihood of isolating the etiological agent. Any wounds,
sputum, urine, exudates, CSF, etc. should be cultured. Antibiotic sensitivity testing is
important for an absolute identification of the causative organism.
Complete Blood Count (CBC) with differential
RBC morphology patients with DIC may have hemolytic anemia with schistocytes.
WBC- greater than 15,00/mm^3 or a neutrophil band count above 1500/mm^3 indicates acute
infection
Toxic granulations, Dohle bodies
Platelets- increase initially and decrease with onset of DIC
Lipopolysaccharides (LPS)- increase up to 2000 times the normal concentration.
ABG, arterial blood gas- increased serum lactate levels indicate tissue hypoperfusion
PT/PTT- Fibin and fibrinogen are decreased and prothrombin is increased in the patients with
DIC.
Liver and renal function tests- BUN/creatinine, electrolytes, alkaline phosphate, bilirubin, and
glucose
UA- urinalysis for proteins, ketones, blood, leukocytes
Urea nitrogen- will often be increased due to bacterial metabolic waste products.
Chest x-rays- in suspected pleural origination of sepsis (pneumonia).
Lumbar Puncture- in suspected meningeal origination of sepsis.
Electrocardiogram- often reveals ectopic irregularities.
Abdominal utrasound or CT- for suspected abdominal origination of sepsis, as in perforated
or ischemic bowels, diverticulitis, and cholecystitis (21, 23, 19, 14, 22).
Predisposing Risk Factors

Overall risk factors: neonates, elderly, immunocomromised patient, such as AIDS or cancer
patients, and splenectomized patients
Gram-positive bacterial sepsis: intravenous catheters, indwelling mechanical devices, burns,
IV drug usage
Gram-negative bacterial sepsis: iatrogenic immunosupression, such as steroids and
chemotherapy, GI/GU infections, cirrhosis, cancer, alcoholism, lymphatic disease, diabetes,
parenteral nutrition (G-tubes)
Fungal sepsis: immunosupression from long-term, broad-spectrum antibiotics
Protozoans have rarely been associated with sepsis (23, 19, 4, 14, 12).
Treatment
Colloid challenge, or intravenous saline and ringers lactated, are necessary for maintenance
of blood pressure and should be given liberally. If this treatment fails to maintain blood
pressure, vasopressins such as dopamine, dobutamine, and norepinepherine are indicated.
It is important to start antibiotics as soon as sepsis is suspected. Ceftriaxone is a common
broad-spectrum antibiotic for initial treatment prior to knowing the etiology of infection.
Antibiotics are the definitive therapy for treatment of the origin of sepsis- pathogenic
microbial infection. Often, more than one antibiotic is given at once for more aggressive
treatment. The following chart provides a list of the most appropriate antibiotic regimens for
each particular microorganism.
Antibiotic Therapy
Primary Infection
Causative Organism
Classification of Organism
Recommended Antibiotic
Cathether-related
Staphylococcus aureus
Gram positive
Cefazolin or nafcillin
Cathether-related
Coagulase-negative Staph

Gram positive
Cefazolin or nafcillin
Toxic shock syndrome
Streptococcus pyogenes
Gram positive
Cefazolin or nafcillin
Pleural
S. pneumoniae
Gram positive
Cipro/amoxicillin
Urosepsis
Enterococci
Gram positive
gentamicin, ampicillin, and amoxicillin
Pleural
Klebsiella pneumoniae
Gram negative
Cipro and amoxicillin
Intra-abdominal
Proteus
Gram negative
Ampicillin/sublactam and gentamicin
Intra-abdominal
Serratia
Gram negative

Ampicillin/sublactam and gentamicin

Catheter-related
Pseudomonas aeruginosa
Gram negative
Ampicillin/sublactam and gentamicin
Meningitis
Neisseria meningitidis
Gram negative
Piperacillin and gentamicin
Urosepsis
Escherichia coli
Gram negative
vancomycin
Catheter-related
Candida albicans
Fungi
fluconazole
IV drug usage
MRSA
Gram positive
vancomycin
Anti-tumor necrosis factor- alpha, nitric oxide synthase inhibitors, anti-interleukin-1,
therapeutic catalytic, monoclonal and polyclonal, anti-endotoxin antibodies, and
immunoglobins IgG, IgM, and IgA are also available as pharmaceutical agents used to treat
the disease.
If the patient with sepsis has any indwelling mechanical devices, such as urinary or IV
catheters, they should be changed or removed. Any abscesses should be drained and all

necrotic tissue should be surgically removed. These interventions may remove the indigenous
microbial reservoir (5, 1, 2, 10, 11, 14, 12).
Prevention and Current Research
There are studies that indicate that there will be a significant success in the treatment of septic
shock that will stem from the understanding that nitric oxide, an end-product of the sepsis
cascade stimulated by inflammatory cytokines, causes profound vasodilation that results in
cardiac collapse. This drug is still in the testing phase, but is showing success in animal
subjects.
A study in which animal models were given injections of TNF-a and IL-1 concluded that
even injections of these cytokines induced shock-like presentation in the subjects, indicating
that septic shock is resultant of a cytokine overload (16). Alternately, other studies concluded
that it is not the increased level of cytokines that is detrimental to the host, but the decrease in
lymphocytes (17).
It is believed that ivIgG, which contains neutralizing and opsonizing antibodies, may increase
the bactericidal activity in the serum. Studies are difficult due to judge due to the dynamics of
the disease and the limited number of patients to each study. However, immunoglobin
therapies are yielding disappointing results, with little evidence of decreasing mortality in
severe cases.
Anti-tumor necrosis factor- alpha, and soluble receptors, nitric oxide synthase inhibitors, antiinterleukin-1, polyclonal and therapeutic catalytic, monoclonal anti-endotoxin antibodies, are
also showing little overall efficacy. Despite the lack of substantial proof that these immunefactor treatments are successful, it is still thought that they will play an important role in the
treatment of sepsis when coupled with other treatments.
Preventionof the disease is aimed at appropriate treatment of primary infections. Also,
patients with indwelling IV or urinary catheters should have them replaced every 48 hours to
avoid nosocomial disease processes (1, 21, 2, 8, 9, 6, 10, 13, 16, 7)
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