Presence of Sepsis in Republic of Macedonia

1. Presence of Sepsis in Republic of Macedonia Panova G., Zisovska E., Zdravkova V. Panova B. PanovN. Stojanov H. Nikolovska L. Shumanov G.

2. Bacterial sepsis is a clinical term used to describe symptomatic bacteremia, with or without organ dysfunction. Currently, sepsis is commonly defined as the presence of infection in conjunction with the systemic inflammatory response syndrome (SIRS), with severe sepsis understood as sepsis complicated by organ dysfunction and septic shock understood as sepsis-induced acute circulatory failure characterized by persistent arterial hypotension despite adequate volume resuscitation and not explained by other causes.[2]

3. The term sepsis is often misused and misapplied to patients with fever, leukocytosis, and hypotension due to other causes (pseudosepsis). True sepsis is a common cause of hospitalization in almost all countries, including in elderly men who are more likely to develop urosepsis as a result of benign urinary tract obstruction caused by prostatic hypertrophy. Patients who have diabetes, systemic lupus erythematosus (SLE), or alcoholism or who are taking steroids are also at increased risk for bacteremia.

4. Sustained bacteremia, in contrast to transient bacteremia, may result in a sustained febrile response that may be associated with organ dysfunction. The term septicemia refers to the active multiplication of bacteria in the bloodstream that results in an overwhelming infection; the term bloodstream infection (BSI) is also commonly used. • The most important medicolegal concerns regarding sepsis treatment include the following: • Ensuring that the patient indeed does have sepsis • Rapidly identifying its source • Implementing effective treatments

5. Most cases of sepsis occur as a result of infection of the urinary tract, lungs or peritoneum . Other sources of infection include skin infections, soft tissues and the central nervous system. Approximately 50 % of cases of sepsis caused by gram - negative bacteria, and less than 50 % are caused by gram-positive bacteria. Less common causes of sepsis are bacterial infections and viruses such as HIV and protozoa.

6. Sepsis or septic shock may be associated with the direct introduction of microbes into the bloodstream via intravenous (IV) infusion (eg, IV line infections and other device-associated infections). Meningococcemia from a respiratory source may also result in sepsis, with or without associated meningitis.

7. Bacteriemia due to bacteriuria (urosepsis) may complicate cystitis in compromised hosts, and sepsis may be caused by overwhelming pneumococcal infection in patients with impaired or absent splenic function.[5] • The pathophysiology of sepsis is complex and results from the effects of circulating bacterial products, mediated by cytokine release, caused by sustained bacteremia.

8. Cytokines are responsible for the clinically observable effects of the bacteremia in the host.[6,7,8,9] Impaired pulmonary, hepatic, or renal function may result from excessive cytokine release during the septic process. • Multiple organ dysfunction syndrome (MODS) is a continuum, with incremental degrees of physiologic derangements in individual organs; it is a process rather than a single event. Alteration in organ function can vary widely from a mild degree of organ dysfunction to completely irreversible organ failure. The degree of organ dysfunction has a major clinical impact.

9. In a classic 1975 editorial by Baue, the concept of “multiple, progressive or sequential systems failure” was formulated as the basis of a new clinical syndrome.[1] Several different terms were proposed thereafter (eg, multiple organ failure, multiple system organ failure, and multiple organ system failure) to describe this evolving clinical syndrome of otherwise unexplained progressive physiologic failure of several interdependent organ systems.

10. Eventually, the term MODS was proposed as a more appropriate description. MODS is defined as a clinical syndrome characterized by the development of progressive and potentially reversible physiologic dysfunction in 2 or more organs or organ systems that is induced by a variety of acute insults, including sepsis. • Sepsis is a clinical syndrome that complicates severe infection and is characterized by systemic inflammation and widespread tissue injury. A continuum of severity from sepsis to septic shock and MODS exists. The clinical process usually begins with infection, which potentially leads to sepsis and organ dysfunction.[2] A consensus panel of the American College of Chest Physicians and the Society of Critical Care Medicine developed definitions of the various stages of this process. [3]

12. Infection is a microbial phenomenon in which an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by these organisms is characteristic. • Bacteremia is the presence of viable bacteria in the blood.

13. Systemic inflammatory response syndrome (SIRS) may follow a variety of clinical insults, including infection, pancreatitis, ischemia, multiple trauma, tissue injury, hemorrhagic shock, or immune-mediated organ injury. SIRS is defined by the presence of 2 or more of the following: • Temperature greater than 38.0°C or less than 36.0°C • Heart rate higher than 90 beats/min • Respiratory rate higher than 20 breaths/min or arterial carbon dioxide tension below 32 mm Hg • White blood cell (WBC) count higher than 12,000/µL, lower than 4000/µL, or including more than 10% bands

14. Sepsis is a systemic response to infection. It is identical to SIRS, except that it must result specifically from infection rather than from any of the noninfectious insults that may also cause SIRS (see the image below).

16. Sepsis is a common cause of mortality and morbidity worldwide. The prognosis depends on underlying health status and host defenses, prompt and adequate surgical drainage of abscesses, relief of any obstruction of the intestinal or urinary tract, and appropriate and early empiric antimicrobial therapy with the drug spectrum appropriate to the presumed septic source. Thus, early and appropriate empiric antimicrobial therapy and surgical intervention are critical in decreasing mortality and morbidity.

18. The prognosis in most patients is good, except in those with intra-abdominal or pelvic abscesses due to organ perforation. The underlying physiologic condition of the host is the primary determinant of outcome. • A systematic review by Winters et al suggested that beyond the standard 28-day in-hospital mortality endpoint, ongoing mortality in patients with sepsis remains elevated up to 2 years and beyond.[10] In addition, survivors consistently demonstrate impaired quality of life.[11]

19. Purpose of the study: • Taking into consideration the severe consequences of sepsis and septic shock, the aim of this study was to evaluate the statistical reports on the number of cases of sepsis, increased morbidity and mortality and causes of their occurrence, in order to give a contribution in any segment of the problems associated with this disease, and their impact on patients and staff working in health facilities.

20. Material and methods :Statistical data obtauined by the Institute of Public health in Skopje was analyzed and processed. In order to answer the questions formulated as a goal of this effort, the analyzis was performed showing the trends of sepsis and the number of the cases in Macedonia through statistical data processing. In the preparation of this paper descriptive method was applied through collection and processing of data tables showing the results.

21. Results: The results of the Institute of Public helath in Skopje (Republic of Macedonia) with encrypted diagnosis from 2012 godina, as A40 and A41 (septicemia), 75 people were treated with these codes and diagnosis, of whom 54 were men, 21 were women, at the age from 0-89 years. On average, they were treated about 15 days, and all of them (75 patients) had 1130 hospital days. The average length of stay was 15,07 days. Patients were from Prilep, Ohrid, Tetovo, Kavadarci, Kocani, and Strumica.

22. Patients were treated in the following hospitals: The Special hospital Kozle- Skopje, Clinic for Childfren’s diseases, the Departments of Infeciytous diseases , the City Hospital 8mi Septemvri – Skopje, and the most severe cases 35/75) were treated at the Clinic for Infectious Diseases-Skopje – Skopje. All these cases have endangered the health of the patients and were great therats to their lives. The probable source of the sepsis was uroinfection in 37%, 29% were abdominal infections, 12% were skin infections, and the rest had unclear (unconfirmed) origin.

23. Discussion: Centers for Public Health and their organizational units perform regular activities in collecting data about the septic cases in the country. During the data collection in 2012 in the Republic of Macedonia regarding the implementation of measures and activities to monitor, prevent and suppress the occurrence of sepsis in medical facilities on its territory, they have recorded (reported to them) the presented 75 cases.

24. The Institute for Public Health - Skopje received written reports, information and therefore published the Annual reports (specific or aggregated), compared by year, and presenting the trends. This kind of activity is very important for the country in the process of the follow uo of this very dangerous state of ill/health. Deeper analysis is necessary to find out the causes of sepsis, the source of infection and to plan measures of prevention, in terms of improving the health and prevention of nosocomial infections which are usually the main mode of systemic infections. The special attention should be put in the Intensive care units in the country.

25. Conclusion: Sterilization and the insuficient preventive measures are still unsatisfactory in Macedonian health institutions. It is unacceptable in the 21st century sepsis to be the cause of serious complications in patients . Sepsis pose a very serious problem in the world and in our country, and in many cases more difficult problem than the patient's underlying disease. Thes sepsis appearance is directly related to medical procedures for diagnostic studies, treatment, health care, rehabilitation, and other health care procedures .

26. On September 13, the World Day Sepsis would die ten times greater than that of a heart attack:iswhy it is important to know. Little known, diagnosed with difficulty, it is actually one of the most common and deadly diseases.

27. References: • McNamara D. Severe sepsis strategy significantly reduces mortality. Medscape Medical News. October 16, 2013. Available at http://www.medscape.com/viewarticle/812674. Accessed December 22, 2013. • Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. Apr 2003;31(4):1250-6.  • Merrell RC. The abdomen as source of sepsis in critically ill patients. Crit Care Clin. Apr 1995;11(2):255-72.  • Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. Apr 2003;31(4):1250-6.  • William BM, Corazza GR. Hyposplenism: a comprehensive review. Part I: basic concepts and causes.Hematology. Feb 2007;12(1):1-13. . • Bone RC. Sepsis and its complications: the clinical problem. Crit Care Med. Jul 1994;22(7):S8-11. • Siegel JP, Stein KE, Zoon KC. 41 anti-endotoxin monoclonal antibodies. N Engl J Med. 1992;327:890. • Warren HS, Danner RL, Munford RS. Anti-endotoxin monoclonal antibodies. N Engl J Med. Apr 23 1992;326(17):1153-7.  • Kobayashi M, Tsuda Y, Yoshida T, et al. Bacterial sepsis and chemokines. Curr Drug Targets. Jan 2006;7(1):119-34.  • [Best Evidence] Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med. May 2010;38(5):1276-83. • Sarikonda KV, Micek ST, Doherty JA, et al. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med. Oct 2010;38(10):1991-5.  • Price CS, Hacek D, Noskin GA, et al. An outbreak of bloodstream infections in an outpatient hemodialysis center. Infect Control Hosp Epidemiol. Dec 2002;23(12):725-9.  • Cunha BA. Central intravenous line infections in the critical care unit. In: Cunha BA, ed. Infectious Diseases in Critical Care Medicine. 2nd ed. New York, NY: Informa Healthcare, Inc.; 2007:283-7/13. • Jenny-Avital ER. Catheter-related bloodstream infections. N Engl J Med. Mar 22 2007;356(12):1267; author reply 1268.  • Lange D, Zappavigna C, Hamidizadeh R, Goldenberg SL, Paterson RF, Chew BH. Bacterial Sepsis After Prostate Biopsy-A New Perspective. Urology. Oct 6 2009; • Sacks-Berg A, Calubiran OV, Epstein HY, et al. Sepsis associated with transhepaticcholangiography. J Hosp Infect. Jan 1992;20(1):43-50.  • Girard TD, Ely EW. Bacteremia and sepsis in older adults. ClinGeriatr Med. Aug 2007;23(3):633-47, viii. • Faro S. Sepsis in obstetric and gynecologic patients. CurrClin Top Infect Dis. 1999;19:60-82.  • Cunha BA, Shea KW. Fever in the intensive care unit. Infect DisClin North Am. Mar 1996;10(1):185-209. • Cunha BA. Sepsis and its mimics. Intern Med. 1992;13:48-55. • Sepsis and its mimics in the critical care unit. In: Cunha BA, ed. Infectious Diseases in Critical Care Medicine. 2nd Ed. New York, NY: Informa Healthcare, Inc; 2007:73-8/4.

28. Тhanks for your attention