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IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income Countries Tim Stephens, BA ( Hons ) Nursing, RGN, MSc (Global H PowerPoint Presentation
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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 CountriesTim Stephens, BA (Hons) Nursing, RGN, MSc (Global Health)
objectives of presentation to answer the following
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..?

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
bone et al 1992
Bone et al (1992)






burden of mortality
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).
sepsis as complicating factor
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)

groups at risk of sepsis in lmics
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)
lmic mortality data
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)
sepsis mortality in context
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).
estimating sepsis incidence based on adhikari et al 2010
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.
cause specific deaths per 100 000 population
Cause specific deaths(per 100,000 population)
  • HIV – 163
  • Malaria - 58
  • TB - 46

(LICs only; WHO, 2011)

  • Severe Sepsis – 34.5 - 135
take home points
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
difficulties faced in sepsis epidemiology
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
severe sepsis
Severe Sepsis
  • Difficult to define and measure.
  • Is it also difficult to treat?

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%.*


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).

urgent requirements for improving sepsis survival
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.
  • 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
references 2
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: [accessed 10th August 2011]
  • WHO (2011b) Integrated management of adolescent and adult illness / Integrated management of childhood illness. Available at: [Accessed 12th August]