Dr.Nannika Pradhan

1. SIRS and SEPSIS
Presenter : Srijana Pradhan
Chairperson : Dr Sandip Saha

2. Definition
• SIRS (Systemic inflammatory Response
Syndrome)
– 2 of the following
• Temperature >38⁰C or <36⁰C
• Heart >90 beats/min
• Respiratory rate >20 breaths/min
• WBC count >12000/cumm or <4000/cumm

3. • Prior to Sepsis 3
– Sepsis
– Severe sepsis
– Septic shock
• After sepsis 3
– Sepsis
– Septic shock
Changes in Sepsis 3 update

4. • Sepsis
– Life threatening organ dysfunction caused by a
dysregulated host response to infection
• Septic shock
– Subset of sepsis in which underlying circulatory
and cellular/metabolic abnormalities lead to
substantially increased mortality risk
Definition

5. Criteria in 2016 (Sepsis-3)
• Sepsis
– Suspected (or documented) infection
– Acute increase in ≥2 sepsis related organ failure
assessment (SOFA) points
• Septic shock
– Suspected (or documented) infection
– Vasopressor therapy needed to maintain
MAP≥65mmHg
– serum lactate >2 mmol/L despite adequate fluid
resusitation

6. SOFA

7. qSOFA
– Respiratory rate ≥22/min
– Altered mentation
– Systolic blood pressure ≤100 mmHg
– ≥2 variables - qSOFA positive

8. • qSOFA no longer recommended as screening tool for
sepsis
• Consider non infectious causes and delay
antimicrobials administration in patients at low risk
of sepsis
• Use procalcitonin only for antibiotic de-escalation
Changes in the 2021 update

9. Pathogenesis

10. Lactic acidosis in Sepsis
• impaired regional microvascular blood flow
• mitochondrial dysfunction with impaired pyruvate
oxidation
• excess catecholamines may impair hepatic lactate
extraction
• lactate clearance is decreased because pyruvate
dehydrogenase activity is reduced in both skeletal muscle
and liver

11. Main goals of management
• Early recognition, prompt disease stratification
and rapid treatment initiation
• Prevention and support of organ dysfunction
• Rapid infection source control
– Adequate antimicrobial therapy
– Surgical/ instrumental intervention

12. Elements of Care
• Resuscitation
• Infection control
• Respiratory support
• General supportive care

13. Surviving Sepsis Campaign

14. Initial Resustitation
• Sepsis and septic shock –medical emergencies
– Recommendation: treatment to be started
immediately
• IV crystalloid fluid 30 mL/kg of should be given
within the first 3 hr of resuscitation
• Crystalloids as first-line fluid for resuscitation. Strong
recommendation, moderate quality of evidence.

15. Fluid therapy
• Albumin in patients who received large volumes of
crystalloids over using crystalloids alone. Weak
recommendation, moderate quality of evidence.
• Recommends against using starches for resuscitation.
Strong recommendation, high quality of evidence.
• Suggests against using gelatin for resuscitation. Weak
recommendation, moderate quality.
• Dynamic measures to guide fluid resuscitation, over
physical examination, or static parameters alone.

16. Vasoactive medications
• Norepinephrine as the first-line agent over other
vasopressors. Strong recommendation
• Septic shock on norepinephrine with inadequate
MAP levels- suggests adding vasopressin instead of
escalating the dose of norepinephrine. Weak
recommendation, moderate-quality evidence.
• Inadequate MAP levels despite norepinephrine and
vasopressin - suggests adding epinephrine

17. Ionotropes
• Cardiac dysfunction with persistent hypoperfusion
despite adequate volume status and arterial blood
pressure – suggests either adding dobutamine to
norepinephrine or using epinephrine alone. Weak
recommendation, low quality of evidence.

18. Summary of vasoactive agents
recommendation

19. • Elevated serum lactate levels - resuscitation should
be guided towards normalizing these levels when
possible
• Capillary refill time to guide resuscitation as an
adjunct to other measures of perfusion. Weak, low
quality of evidence
Initial Resustitation

20. Andromeda Shock Study 2015
• Evaluated whether a resuscitation strategy targeting
CRT normalization was more effective than a
resuscitation strategy aiming at normalization or
decreasing lactate levels by 20%
• At day 3, the CRT group had significantly less organ
dysfunction as assessed by SOFA score
• Using CRT during resuscitation has physiologic
plausibility and is easily performed, noninvasive, and
no cost.

21. Early Goal-Directed Therapy

22. Early Goal-Directed Therapy

23. Newer Trials deemphasized EGDT
• ProCESS (2014)
– 3 arms
• Bundle of care described by Rivers trial
• Similar arm without the use of ionotropes or blood transfusions
• Usual care
– No mortality benifit
• ARISE (2014)
– No mortality benefit
• ProMIse (2015)
– No mortality benifit

24. CLOVERS trial
• Restrictive fluid vs liberal fluid strategy
• Less intravenous fluids in restructive group than in
liberal group
• No difference in 90 day mortality between the two
strategies

25. Infection Control
• Early administration of appropriate antimicrobials -
most effective intervention to reduce mortality in
patients with sepsis.
• Delivering antimicrobials to patients with sepsis or
septic shock - treated as an emergency
• Suggests against using procalcitonin to decide when
to start antimicrobials. Weak recommendation, very
low quality of evidence

26. Timing of antibiotic administration

27. Choice of Antimicrobial therapy
• 2016
– Empirical broad-spectrum therapy with one or
more antimicrobials for patients presenting with
sepsis or septic shock to cover all likely pathogens
(including bacterial and potentially fungal or viral
coverage).

28. • 2021
– low risk of MRSA- suggests against using empiric
antimicrobials with MRSA coverage
– Suggests against using double gram-negative coverage
once the causative pathogen and the susceptibilities
are known.
– High risk of fungal infection - suggests using empiric
antifungal therapy over no antifungal therapy
– no recommendation on the use of antiviral agents.
Choice of Antimicrobial therapy

29. Antimicrobial therapy
• Unconfirmed infection - recommends continuously re-
evaluating and searching for alternative diagnoses and
discontinuing empiric antimicrobials.
• High likelihood for sepsis - administering antimicrobials
immediately, ideally within 1 hr of recognition.
• Suggests using prolonged infusion of beta-lactams for
maintenance (after an initial bolus) over conventional
bolus infusion. Weak recommendation, moderate quality
of evidence

30. • Source control should be undertaken as soon as is medically
and logistically possible. Best practice statement
• Prompt removal of intravascular access devices that are a
possible source of sepsis or septic shock after other vascular
access has been established. Best practice statement
• Suggests using shorter over longer duration of antimicrobial
therapy. Weak recommendation, very low quality of evidence.
• Daily assessment for de-escalation of antimicrobial therapy
should be conducted
Antimicrobial therapy

31. Antimicrobial therapy

32. Respiratory Support
• A target tidal volume of 6ml/kg is recommended in
sepsis induced ARDS
• In severe ARDS, prone positioning is recommended
• Suggests the use of high flow nasal oxygen over
noninvasive ventilation. Weak recommendation, low
quality of evidence.

33. Corticosteroids
• Ongoing requirement for vasopressor therapy -
suggests using IV corticosteroids. Weak
recommendation; moderate quality of evidence.
• Indication
– dose of norepinephrine or epinephrine ≥ 0.25
mcg/kg/min at least 4 hours after initiation.
• Dose
– IV hydrocortisone at a dose of 200 mg/d given as 50
mg every 6 hours or as a continuous infusion.

34. • 200mg of hydrocortisone administed by infusion or
by matched placebo
• No statistically significant difference in 90 day
mortality between the two groups
• Secondary outcomes in hydrocortisone group
– Earlier shock reversal
– Faster liberation from mechanical ventilation
– Earlier discharge from ICU
ADRENAL study (2018)

35. APROCCHSS study
• Hydrocortisone combined with fludricortisone vs
placebo
• Mortality was significantly lower in the group that
received steroids

36. Blood products
• Recommends using a restrictive (over liberal) transfusion
strategy. Strong recommendation; moderate quality of
evidence.
• Red blood cell transfusion is recommended only when the Hb
<7g/dl in the absence of myocardial infraction, severe
hypoxemia or acute hemorrhage
• Suggests against using IV immunoglobulins. Weak, low quality
of evidence

37. Stress Ulcer Prophylaxis
• For adults with sepsis or septic shock, and who have
risk factors for gastrointestinal (GI) bleeding -
suggests using stress ulcer prophylaxis. Weak
recommendation, moderate quality of evidence.

38. Venous Thromboembolism
• Recommends using pharmacologic VTE prophylaxis unless
a contraindication to such therapy exists. Strong
recommendation, moderate quality of evidence.
• Recommends using low molecular weight heparin(LMWH)
over unfractionated heparin (UFH) for VTE prophylaxis.
Strong recommendation, moderate quality of evidence.
• Suggests against using mechanical VTE prophylaxis in
addition to pharmacological prophylaxis, over
pharmacologic prophylaxis alone. Weak recommendation,
low quality of evidence.

39. Renal Replacement Therapy
• In adults with sepsis or septic shock and AKI
– who require renal replacement therapy, we suggest using
either continuous or intermittent renal replacement
therapy. Weak recommendation, low quality of evidence.
– no definitive indications for renal replacement therapy, we
suggest against using renal replacement therapy. Weak
recommendation, moderate quality of evidence

40. Additional therapies
• Glucose Control
– recommends initiating insulin therapy at a glucose level of
≥ 180 mg/dL (10 mmol/L). Strong recommendation;
moderate quality of evidence.
– Following initiation of an insulin therapy, a typical target
blood glucose range is 144−180 mg/dL (8−10 mmol/L).
• Recommendation to commence insulin when two consecutive
blood glucose levels are > 180 mg/dL derived from the NICE-
SUGAR trial

41. • Suggests against using IV vitamin C. Weak
recommendation, low quality of evidence
• Suggest early (within 72 hours) initiation of enteral
nutrition. Weak recommendation; very low quality of
evidence.
– Advantages
• maintenance of gut integrity
• prevention of intestinal permeability
• dampening of the inflammatory response
• modulation of metabolic responses that may reduce
insulin resistance
Additional therapies

42. Additional therapies
• Sodium bicarbonate therapy
– Hypoperfusion induced lactic acidemia - suggests against
using sodium bicarbonate therapy to improve
hemodynamics or to reduce vasopressor requirements.
Weak recommendation, low quality of evidence.
– For severe metabolic acidemia (pH ≤ 7.2) and AKI - suggest
using sodium bicarbonate therapy. Weak
recommendation, low quality of evidence.

43. • Acetaminophen
– reduces temperature in non-critically ill patients but does
not change mortality or other outcomes
– should not be considered one of the main pillars of sepsis
treatment
Additional therapies

44. Goals of Care
• For adults with sepsis or septic shock - recommends
discussing goals of care and prognosis with patients and
families over no such discussion.
• Addressing goals of care early (within 72 hours) Weak
recommendation, low-quality evidence.

45. Take Home Message
• qSOFA no longer recommended as screening tool for sepsis
• Consider non infectious causes and delay antimicrobials
administration in patients at low risk of sepsis
• Elements of Care
– Resuscitation
– Infection control
– Respiratory support
– General supportive care
• 5 steps of the 1hr Bundle according to the Surviving Sepsis
Campaign