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IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income Countries Tim Stephens, BA ( Hons ) Nursing, RGN, MSc (Global H

IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income Countries Tim Stephens, BA ( Hons ) Nursing, RGN, MSc (Global Health). Objectives of presentation – to answer the following: . What is sepsis? What is the burden of sepsis and it’s associated mortality?

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IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income Countries Tim Stephens, BA ( Hons ) Nursing, RGN, MSc (Global H

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  1. IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income CountriesTim Stephens, BA (Hons) Nursing, RGN, MSc (Global Health)

  2. Objectives of presentation – to answer the following: • What is sepsis? • What is the burden of sepsis and it’s associated mortality? • In resource poor settings, what could be done to reduce mortality.? • What is currently happening and what more could be done..?

  3. Sepsis – When the bodies reaction to infection moves from a localised to a generalised response • e.g. A cut becomes infected, there is some swelling and redness around the injury – local inflammatory processes cause this...sepsis is the continuation of these processes at a systemic (whole body) level • Final common pathway of many infectious processes e.g. Bacterial, viral, fungal and parasitic infection

  4. Bone et al (1992) SIRS = Systemic Inflammatory Response Syndrome

  5. Burden of Mortality • USA - it is the 10th leading cause of death (Minino et al, 2010) and is estimated to kill in excess of 215,000 people per year (Angus et al, 2001). • The incidence of sepsis in LMICs, and its consequent burden of mortality, is currently not known (Adhikari et al, 2010).

  6. Sepsis as complicating factor • Sepsis is not a disease in itself but a component cause of morbidity and mortality in association with diseases such: • HIV, • Blood stream infection (BSI) and • Pneumonia • Malaria • Diabetes • Chronic Renal Failure and • Cancer (N.B. Increasing concern about rise of NCDs in LMICs)

  7. Groups at risk of sepsis in LMICs • HIV (OR for BSI = 3.4, Reddy et al, 2010) • Maternal complications (approx. 10% of all maternal mortality, Khan et al, 2006) • Diabetes (25-75% increased risk of sepsis, Hall et al, 2011) • HAIs (15 /100 in-patients will contract a nosocomial infection in LMICs, Allegranzi et al, 2010)

  8. LMIC mortality data • Median (and mean) mortality rates for severe sepsis and septic shock can be calculated as 44.95% (45.67%) and 53.35% (62.86%) respectively. • Severe sepsis mortality USA - mortality rate of 28.6% (Angus et al, 2001)

  9. Sepsis mortality in context • Brazil - Overall mortality vs. severe sepsis mortality (21-29% for all cause in hospital mortality vs. 51.6 – 56.8% with severe sepsis; Kauss et al, 2011, Silva et al, 2004). • Uganda - all cause in-hospital mortality of 15.4% compared to an in-hospital mortality of 23.7% and a 28 day-mortality of 43.0% for patients with severe sepsis (Jacob et al, 2009).

  10. Estimating sepsis incidence – based on Adhikari et al (2010) • Population incidence of 77 to 300 per 100,000; (Finfer et al, 2004; Angus et al, 2001) for severe sepsis applied to population data for LMICs • Caveat 1 – this is a very rough estimate as in LMICs there are many more deaths are caused by infection • Caveat 2 – Angus et al data very inclusive – likely to overestimate incidence of severe sepsis. Finfer et al data only ICU population, not total population.

  11. Cause specific deaths(per 100,000 population) • HIV – 163 • Malaria - 58 • TB - 46 (LICs only; WHO, 2011) • Severe Sepsis – 34.5 - 135

  12. Take home points... • With the conservative estimates, severe sepsis may have a mortality similar to that of TB and at most worst, it may be very similar to that of HIV • The problem is...we don’t actually know. • Very hard therefore to mobilise resources against an invisible foe

  13. Difficulties faced in sepsis epidemiology • No single test • Short prodrome followed by resolution or death • Clinical diagnosis – current criteria over sensitive / lacking in specificity, especially in context of LMICs • Diagnosis supported by blood or other microbiological cultures – limited availability in LMICS • Clinical Coding unreliable in many LMICs

  14. Severe Sepsis • Difficult to define and measure. • Is it also difficult to treat?

  15. Surviving Sepsis (2004, 2008)

  16. Sepsis Survival Resources

  17. Sepsis Resuscitation Bundle (adapted from Levy et al, 2010) (To be accomplished as soon as possible and scored over first 6 hours): 1. Serum lactate measured. 2. Blood cultures obtained prior to antibiotic administration. 3. From the time of presentation, broad-spectrum antibiotics administered within 3 hours for ED admissions and 1 hour for non-ED ICU admissions. 4. In the event of hypotension and/or lactate > 4 mmol/L (36 mg/dl): a) Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent). b) Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) > 65 mm Hg. 5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dl): a) Achieve central venous pressure (CVP) of > 8 mm Hg. b) Achieve central venous oxygen saturation (ScvO2) of > 70%.*

  18. Over the first 6 hrs after the onset of recurrent or persistent hypotension, each hour of delay in initiation of effective antimicrobial therapy was associated with mean decrease in survival of 7.6% (range 3.6 –9.9%; Fig. 1).

  19. WHO IMAI tools

  20. Syndromic approach to “severe sepsis” management

  21. Urgent requirements for improving sepsis survival • Prospective epidemiological studies to identify the sepsis burden within LMICs. • Randomised controlled trials (RCT) based of protocol based care for severe sepsis in adults, using low cost and widely available interventions to generate a new evidence base that is relevant to LMIC contexts.

  22. References • Adhikari, N. K., Fowler, R., Bhagwanjee, S., & Rubenfeld, G. D. (2010). Critical care and the global burden of critical illness in adults. The Lancet, 376(9749), 1339-1346 • Allegranzi, B., Nejad, S. B., Combescure, C.,et al. (2010). Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. The Lancet, 377(9761), 228-241. • Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001). Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical care medicine, 29(7), 1303-10. • Baelani, I., Jochberger, S., Laimer, T., Otieno, D., Kabutu, J., Wilson, I.. Baker, T & Dünser, M (2011). Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers. Critical care, 15(1), R10 • Bataar, O., Lundeg, G., Tsenddorj, G., et al (2010). Nationwide survey on resource availability for implementing current sepsis guidelines in Mongolia. Bulletin of the World Health Organization, 88(11), 839-46. • Bone, RC., Balk, RA.,Cerra, R., Dellinger, R Fein, AM, Knaus, M.,Schein R and Sibbald W (1992)Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.The ACCP/SCCM Consensus Conference Committee / American College of Chest Physicians/Society of Critical Care Medicine. Chest 101, 1644-45 • Dellinger, R. P., Levy, M. M., Carlet, J. M., et al (2008). Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive care medicine, 34(1), 17-60. • Finfer, S., Bellomo, R., Lipman, J., French, C., Dobb, G., & Myburgh, J. (2004). Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive care medicine, 30(4), 589-96. • Hall, V., Thomsen, R. W., Henriksen, O., & Lohse, N. (2011). Diabetes in Sub Saharan Africa 1999-2011: Epidemiology and Public Health Implications. A systematic review. BMC public health, 11(1), 564. • Jacob, S. T., Moore, C. C., Banura, P et al (2009). Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PloS one, 4(11), e7782

  23. References 2 • KaussI.,Cintia MC., Cardoso, LT., et al(2003). The epidemiology of sepsis in a Brazilian teaching hospital. Braz J Infect Dis 2010;14(3):264-270 • Khan, K. S., Wojdyla, D., Say, L., Gülmezoglu, M., & Van Look, P. F. (2006). WHO analysis of causes of maternal death: a systematic review. Lancet, 367(9516), 1066-74. • Kumar, Anand, Roberts, D., Wood, K. E., et al (2006). Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical care medicine, 34(6), 1589-96. • Levy, M. M., Dellinger, R. P., Townsend, S. R., et al (2010). The Surviving Sepsis Campaign: results of an  international guideline-based performance improvement program targeting severe sepsis. Intensive care medicine, 36(2), 222-31. • Maitland, K., Kiguli, S., Opoka, R. O., et al(2011). Mortality after Fluid Bolus in African Children with Severe Infection. The New England journal of medicine, May 26, 1-13 • Miniño AM, Xu JQ, Kochanek KD. (2010) Deaths: Preliminary data for 2008. National Vital Statistics Reports; vol 59 no 2. Hyattsville, MD: National Center for Health Statistics. • Namas, Rami, Zamora, R., Namas, Rajaie, An, G., Doyle, J., Dick, T. E. (2011). Sepsis: Something old, something new, and a systems view. Journal of critical care. doi: 10.1016/j.jcrc.2011.05.025. • Silva, E., Pedro, M. D. A., Sogayar, A. C. B., et al (2004). Brazilian Sepsis Epidemiological Study (BASES study). Critical care, 8(4), R251-60. • Reddy, E. a, Shaw, A. V., & Crump, J.(2010). Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis. The Lancet Infectious Diseases, 10(6), 417-432. • WHO (2008) The Global Burden of Disease: 2004 Update. Geneva: World Health Organisation. Available at: http://www.who.int/healthinfo/global_burden_disease/en/ [accessed 10th August 2011] • WHO (2011b) Integrated management of adolescent and adult illness / Integrated management of childhood illness. Available at: http://www.who.int/hiv/topics/capacity/en/ [Accessed 12th August]

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