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?• 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)

SIRS = SystemicInflammatoryResponseSyndrome

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 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

• 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

• 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

• 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)

• 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)

• HIV – 163• Malaria - 58• TB - 46(LICs only; WHO, 2011)

• Severe Sepsis – 34.5 - 135

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

WHO (2008)

Global Burden of Disease Data

Mortality - Infectious and parasitic diseases

Populati

on

(000s)

Total

deaths

(000s)

Total

(000s / % total deaths)

Mortality – Lower

respiratory tract

infections

(000s / % total)

Mortality -

‘Other infectious

diseases’

(000s / % total )

World 6 737

480

56 888 8 721 / 15.3

3463 / 6.1% 1025 / 1.8%

High 1 076

797

9 071 189 / 2

347 / 3.8% 110 / 1.2%

Upper Middle 999 625 7 877 696 / 8.8

295 / 3.7% 108 / 1.3%

Lower Middle 3 834

641

30 650 4 687 / 15.3

1775 / 5.7% 424 / 1.3%

Low 826 417 9 290 3 149 / 33.9

1046 / 11.2% 383 / 4.1%

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

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

Surviving Sepsis (2004, 2008)

Sepsis Survival ResourcesMongolia (Baatar et al, 2010) Africa (Baelani et al, 2011)

Lactate measurement 13.2%, 23%

Blood Cultures 60.5%, 71%

Broad-spectrum antibiotics 65.8% 76.2%

Fluids for hypotension 92.1%, 90.7%

Central venous pressure monitoring 31.6%, 24.2% (combined elements)

ScvO2 monitoring 0%

Vasopressors 2.6%. 97.3%*

Oxygen 97.4% 93.8%*

X-ray 86.8% 90.8%*

Over the first 6 hrs after the onset ofrecurrent or persistent hypotension, eachhour of delay in initiation of effectiveantimicrobial therapy was associated withmean decrease in survival of 7.6% (range3.6 –9.9%; Fig. 1).

WHO IMAI tools

Syndromic approach to “severe sepsis” management

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.

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