Transcript IMPROVING ADULT SEPSIS SURVIVAL in Low and Middle Income

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 =
Systemic
Inflammatory
Response
Syndrome
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)
Mortality - Infectious and parasitic diseases
Global Burden of Disease Data
World
Populati
Total
Total
on
deaths
(000s / % total deaths)
(000s)
(000s)
6 737
56 888
1 076
999 625
Lower Middle
3 834
9 071
826 417
‘Other infectious
infections
diseases’
(000s / % total)
(000s / % total )
7 877
30 650
9 290
6.1%
1025 / 1.8%
189 / 2
347 / 3.8%
110 / 1.2%
295 / 3.7%
108 / 1.3%
1775 / 5.7%
424 / 1.3%
1046 / 11.2%
383 / 4.1%
696 / 8.8
4 687 / 15.3
641
Low
respiratory tract
3463 /
797
Upper Middle
Mortality -
8 721 / 15.3
480
High
Mortality – Lower
3 149 / 33.9
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 Resources
Mongolia (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%*
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 nonED 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).
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.
References
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