sepsis ever expanding subject. 2014 was the milestone year in management of sepsis.

1. Sepsis update
Dr. Harshil Mehta
Associate Consultant
Accident and Emergency
Kokilaben Dhirubhai Ambani Hospital, Mumbai

2. Definitions
• Infection
• Bacteremia
• SIRS
• Sepsis
• Severe sepsis
• Septic shock
• MODS / p- MODS

6. •Emergency physician at Henry
ford Hospital, Detroit
•Study was conducted in 2001
•Aim was to evaluate efficacy of
EGDT before ICU admission

10. Supportive Evidence
Quality / Grade A B C D E F
Outstanding • Rivers,NEJM,
2001
Good Nguyen,CCM,2007;
Ferrer, JAMA 2008
Adequate Micek, CCM, 2006; Kortgen,
El Sohl, J Am Ger CCM,
Soc, 2008 2006

11. Surviving sepsis campaign

12. SSC partners

13. SSC 3 hour bundle
1. Measure lactate level
2. Obtain blood culture prior to administration
of antibiotics
3. Administer broad spectrum antibiotic
4. Administer 30 ml/kg crystalloids for
hypotension and lactate > 4 mmol/l

14. SSC 6 hour bundle
1. Apply vasopressors to maintain MAP > 65
mmHg
2. In persistent hypotension despite volume
resuscitation or initial lactate > 4 mmol/l
• Measure CVP
• Measure ScvO2
3. Remeasure lactate if initial lactate was
elevated

15. 3 hour bundle
1. Measure lactate level:
– Essential to identify tissue hypoperfusion
– Limiatation:
• Raised in cellular metabolic failure
• Elevated in hepatic clearance failure
– Implication:
• Mortality is high in hypotension, raised lactate level or in
both
• Lactate > 4 mmol/L – 6 hour bundle patient
– Turnaround time:
– Arterial v/s venous??

18. 0
5
10
15
20
25
Intent to treat Per protocol
Lactate group
ScvO2 group

19. 2. Obtaining blood cultures before administering
antibiotics:
– Collection strategy:
• Two or more culture from percut and veach vascular
access device
• Wound, urine, sputum, CSF, ascitic fluid, pleural fluid
– Indications:
• Fever, chills, hypothermia, leukocytosis, renal failure,
hemodynamic compromise, other unexplained organ
dysfunction

20. 3. Administer broad spectrum antibiotics:
– Timing of antibiotic:
• Once sepsis is identified, antimicrobial agent should be
administered as soon as possible.
• Adequate antibiotic therapy is required.
– Choice of antibiotic:
• Use broad spectrum antibiotics until specific pathogen is
identified
• Use combination of antibiotics initially
– Re-evaluation after 24-48 hours:
• Once organism is identified, restrict antibiotic to specific
pathogen narrow the spectrum

23. 4. Administer 30 ml/kg crystalloid for
hypotension and lactate > 4 mmol/L:

24. • Initial fluid resuscitation
– 30 ml/kg, as early as possible after diagnosis
– Requirement is not easy calculate, so repeated
boluses should be given
– Target : CVP > 8 mmHg
Lactate clearance
ScvO2 > 70%

25. t
• SSC recommends MAP of
at least 65 mmHg.
•Whether this is effective
or not in unknown
•Aim of this trial was to
study significant difference
between high target blood
pressure and low target
blood pressure group

27. Lower v/s higher hemoglobin threshold
for blood transfusion in septic shock
• Multicenter, RCT
• To establish harms and benefits of blood
transfusion in patients with high and low
threshold level
• High threshold <9 g/dl
• Low threshold < 7 g/dl
• Primary outcome – 90 days mortality
Published in NEJM.org on October 1, 2014

28. •Total 1545 blood transfusion
were given to low threshold
group v/s 3040 to high
threshold group (p<0.001)
•176 patients (36.1%) in low
threshold group didn’t undergo
transfusion as compared to only
6 patients (1.2%) in high
threshold.

29. International trials on sepsis

30. • Aim : whether River’s findings were
generalized and whether all aspects of
protocol were necessary.
• Patients were divided in three groups:
– Protocol based EGDT
– Protocol based standard therapy
– Usual care

32. •No benefit of CV line and central
monitoring in all patients
•Two protocol based
management lead to initial
transient improvement in blood
pressure, but a higher
requirement of intensive care
and renal replacement therapy.
•No significant difference in
mortality

35. • Question: Does EGDT compared with standard
care decrease mortality at 90 days?
• Design:
– Multi centered, RCT
– 51 hospitals from 2008-2014
– Around 1600 patients

38. • Strength of the study:
– Clinical relevance
– Large multi center study
– Use of original EGDT algorithm
– No confounding effect of antibiotic administration
– Statistical analysis
• Bottom line:
– Contradictory to EGDT, continuous central venous
oximetry, liberal blood transfusion policy and
dobutamine
– Early recognition, source control, early antimicrobial
therapy, fluid resuscitation and escalation remain
fundamental goals

39. • ARISE and PROCESS have not demonstrated
any adverse outcome in groups using CVP and
ScvO2 monitoring. So no harm in continuing
SSC bundle
• SSC will review their bundle and treatment
plan and update accordingly
• For now, no change in 3 hour bundle pattern

40. • Objective:
– Determine the association between compliance
with SSC bundle and mortality
• Design:
– Based on 2004 SSC guidelines
– Data collection from 2005 to 2012
– 218 hospitals from US, South America and Europe

41. • Results:
– Hospital mortality rate dropped 0.7% per site for
every 3 months of participation (p<0.001)
– Hospital and ICU LOS decreased 4% (p-0.012) for
every 10% increase in site compliance with
resuscitation bundle.
Compliance High Low P value
Resuscitation bundle 29.0% 38.6% <0.001
Management bundle 33.4% 32.3% 0.039

42. • Purpose:
– To describe and compare the design of three multi
centered independent trials on EGDT for severe
sepsis and septic shock
• Conclusion:
– Harmonization is feasible
– Facilitate pooling of data on completion of trials

43. Duration for first bolus

44. Duration of third bolus
Duration of first dose of
antibiotic