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:

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, IL-1B, 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

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, anti-interleukin-1, polyclonal and therapeutic catalytic, monoclonal anti-endotoxin antibodies, are also showing little overall efficacy. Despite the lack of substantial proof that these immune-factor 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)

Works Cited

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2. Holzheimer, R.G.. "Immunoglobulins for Prophylaxis and Treatment of Sepsis: New Experience with a Natural Immunodulatory Compound." 1999;3:193-196. 25 April 2002.

3. Phillips, Danny. "KU Med researchers granted sepsis patent." 04 Feb. 2002 http://www.research.ukans.edu/newsmenu/2000_04/sepsis.html 25 April 2002.

4. "Clinical Sepsis and Death in a Newborn Nursery Associated with Contaminated Parenteral Medications &endash; Brazil, 1996." 02 May 2002 http://www.cdc.gov/mmwr/preview/mmwrhtml/00054058.html 24 April 2002.

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11. "University of Pennsylvania Medical Center Guidelines for Antimicrobial Therapy. Sepsis." 2002. http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/sepsis.html 24 April 2002.

12. Chamberlain, Neal R., PhD. "From Systemic Inflammatory Response Syndrome (SIRS) to Bacterial Sepsis with Shock." 31 July 2001. http://www.kcom.edu/faculty/chamberlain/Website/lectures/lecture/sepsis.html 24 April 2002.

13. Manson, W.L. "Prevention and Reduction of the Consequences of Septic Shock." June1997. http://www.isgnas.org/docs/consequences_septic_shock.html 25 April 2002.

14. "Bacteremia and Septic Shock." The Merck Manual. Section 17. Infections Ch. 176. 2002. http://www.merck.com/pubs/mmanual_home/sec17/176.html 25 April 2002

15. "Ten-Year study finds increased incidence of sepsis in U.S." 06 November 2001. http://www.chestnet.org/publications/media/press.releases/sepsis.html 25 April 2002

16. "Cytokines & Sepsis: Background information." 22 May 1998. http://www.researchd.com/cytokines/sepsis.html 25 April 2002

17. Karl, Irene E. PhD., Hotchkiss, Richard S. M.D. "Pathogenesis of sepsis and multiorgan dysfunction." http://www.research.medicine.wustl.edu/ocfr.Research.nsf/c517b7f273394130862567970055bff2/f5036c661f97004e8625677d00592e0e 25 April 2002

18. Jenson, Hal B. M.D. and Baltimore, Robert S. M.D. "Bacteria." 13 April 2002. http://www.pediduthscsa.edu/Bacteria.html 25 April 2002.

19. Suner, Selim M.D. M.S. "Sepsis." eMedicine Consumer Journal, May 8, 2001, Volume 2, Number 5. http://www.emidicine.com/aaem/topic392.html 24 April 2002.

20. "Notice to Readers Bacterial Sepsis Associated with Receipt of Albumin." October 11, 1996/45(40);866-7. http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/000440008.htm 24 April 2002.

21. Moulin, Frederic. "Lipopolysaccharides and the multiple organ failure syndrome." 01 January 1997. http://www.msu.edu/user/moulinfr/lps.html 25 April 2002

22. Stapczynski, J. Stephen, MD. "Shock, Septic." eMedicine Journal, July 16,2001, Volume 2, Number 7. http://www.emedicine.com/EMERG/topic533.html 25 April 2002

23. Polgreen, Philip M., MD. "Infectious Disease: Sepsis." 10 January 2002. http://www.vh.org/Providers/ClinRef/FPHandbook/Chapter10/05-10.html 25 April 2002.