It is the first kind of cases that I had to learn to manage. The cases ere so abundant and management so rapid that it took me a while to wrap my head around it. I did not sepsis from septic shiock, I did not know the signs and symptoms and I definitely did not how it all came together. Sepsis bundles included in the presentation need to be updated.

1. Sepsis
Dr. Muhammad Muneeb Riaz
PGR Anaesthesia/ICU
JHL

2. • Best Practice statements
– Strong but ungraded statements

3. Evidence-based
guidelines/recommendations
• Systematically developed statements to assist
practitioner decisions about appropriate
health care for specific clinical circumstances.
(Greenhalgh 2014)

4. Hierarchy of Evidence
Grade Type of evidence
Ia Evidence from meta analysis of RCT’s
Ib Evidence from at least one RCT
IIa Evidence from at least one trial not randomized
IIb Evidence from at least one other type of quasi-experiment study
III Evidence from observational study
IV Evidence from expert committee reports or experts

5. Sepsis
• A life-threatening organ dysfunction due to a
dysregulated host response to infection.
• Word sepsis is used in place of sever sepsis in
2016 recommendations.

6. • Mortality of 55%
• Mortality progresses by 10% for each hour of
treatment delay

7. • Common foci of sepsis
– Respiratory tract
– Urogenital tract
– Device related infections
– Wound infection
– Peritonitis

8. It will be further discussed under following
subtopics:
– Pathophysiology
– Diagnosis
– Management
– Scoring Systems

9. PATHOPHYSIOLOGY
• Microbiological stimulus
• Immunological response
• Loss of hemostatic balance
• Endothelial dysfunction
• Cardiovascular dysfunction
• Endocrine dysfunction
• Multiorgan Dysfunction

10. Microbiological Stimulus
• Gram Negative
– LPS produce PAMP’s which are recognized by TLR
which induce immune modulators.
• Gram Positive
– LTA produce PAMP’s which are receognized by TLR
which induce immune modulators.

11. Immunological response
• Within first hour TNF and IL-1
• Complement system activation C5a, after
three hours.
• Migration inhibition factor after 8 hours
• Initiation of sepsis after 24 hours

13. Loss of Homeostatic Balance

14. Endothelial dysfunction
• Mediator stimulated increased production of
iNOS which cause vasodilation.
• Remote expression of adhesion molecules on
endothelial surface leading to leucocyte
adhesion and rolling.
• Respiratory burst characterized by elastases,
myeloperoxidases and ROS.

15. Cardiovascular dysfunction
• Cardiac dysfunction characterized by
increased filling pressures and shifting of
Frank Starling curve to right.
• Vascular dysfunction due to NO medicated
vasodilation.
• Hypovolemia due to capillary leakage.
• Microcirculatory shunting due to micro
vascular blockage.

16. Endocrine dysfunction
• Relative adrenal insufficiency.
• Decreased vasopressin production due to
blunted sympathetic response
• Hyperglycemia due to decreased insulin
production, insulin resistance and increased
production of hyperglycemia causing
hormones.

18. Septic Shock
• Subset of sepsis associated with circulatory
and cellular/metabolic dysfunction associated
with higher mortality rate.

19. Multiorgan dysfunction
• Parallel or sequential failure of at least two
organs.
• Caused by tissue hypoxia:
– Decreased perfusion
– Disturbance of mitochondrial oxygen utilization
• Caused by Apoptosis via Caspase 3:
– Extrisic pathway; Fas receptor activate procaspase 8
– Intrinsic pathway; p53 which activate procaspase 9
• Two hit theory

22. Diagnosis
SIRS and a source of infection constitute sepsis.

23. SIRS
• Fever of more than 38°C (100.4°F) or less than
36°C (96.8°F)
• Heart rate of more than 90 beats per minute
• Respiratory rate of more than 20 breaths per
minute or arterial carbon dioxide tension
(PaCO2) of less than 32 mm Hg
• Abnormal white blood cell count (>12,000/µL
or <4,000/µL or >10% immature [band] forms)

26. Laboratory variables
• C- reactive protein
• Procalcitonin > 2ng/mL are indicative of
bacterial infection.
– May also be increased in major trauma and
surgical procedures.

27. qSOFA
• It uses three criteria, assigning one point for:
– low blood pressure (SBP≤100 mmHg),
– high respiratory rate (≥22 breaths per min), or
– altered mentation (Glasgow coma scale<15).
• A score of two or more constitute sepsis

28. Management
• One hour bundle

29. Limitations
• Clinical judgment is not taken into account for
patients can have many comorbid.

30. • Identification of organism is dependent on
cultures and positive only 30% of times.
• 10 ml of Blood is taken from two locations
under sterile conditions and incubated in
aerobic and anaerobic culture bottles.
• Moreover, BAL, urine sample and suspected
tissue samples be taken.

31. After 1st hour
• Source control with complete surgical removal
of infected tissue is a key element for effective
treatment.
• Reevaluation of antimicrobial therapy.
– Depending on local bacterial prevalence.

32. • Monitoring
– Lactate levels which may be raised due to
increased metabolism or dehydrogenase enzyme
inhibition
– Svo2 70% to 85%

33. Nutritional support
• If can be fed, should be fed.
• Feeding as soon as possible
• IV glucose alone is not recommended.
• Maintain normoglycemia.

34. Organ support
• Cardiovascular support
• Respiratory system
• Renal system

35. CVS
• MAP > 65 mmg
• Norphine then adrenaline
• Dobutamine if heart contractility is
compromised.

36. Respiratory system
• On Mechanical ventilation
– Low tidal
– High PEEP
– Recommend against beta 2 agonist use for sepsis
induced ARDS

37. Renal Support
• UOP >o.5 mL/kg/hr
• No RRT in raised createnine and oliguria in the
absence of other indications of dialysis.

38. Fluid management
• Aggressive fluid therapy for first 24 hours.
• Maintain CVP between 8 to 12.
• Albumin is beneficial.
• Svo2 above 70%
• Goal directed fluid therapy

39. Regarding Blood
• Values of 10-12 g/dL are superior to 7-9 g/dL
• BUT
– If Svco2 <70%, raising Hb to 10g/dL improved
survival

40. Regarding Steroids
• If fluid resuscitation and vasopressin therapy
fails to bring in hemodynamic stability.
• Hydrocortisone 200 mg per day.

41. Scoring systems
• SOFA
• MODS
• LODS

43. SOFA

44. Maximum
SOFA Score
Mortality
0 to 6 < 10%
7 to 9 15 - 20%
10 to 12 40 - 50%
13 to 14 50 - 60%
15 > 80%
15 to 24 > 90%

45. Time course of disease
• Admission SOFA
• Daily SOFA
• Maximum Daily SOFA
• Maximum organ failure score
• Delta SOFA
• Discharge SOFA

46. • A high total SOFA score (SOFA max) and a high
delta SOFA (the total maximum SOFA minus
the admission total SOFA) have been shown to
be related to a worse outcome
• The total score has been shown to increase
over time in non-survivors compared with
survivors.

47. Thank you