Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection.The definition of sepsis was updated in 2016 following publication of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). This recommended that organ dysfunction should be defined using the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria or the "quick" (q)SOFA criteria.

1. What’s New in Sepsis
Dr Kamal Bharathi. S
Department of Pulmonary Medicine
Sri Manakula Vinayagar Medical college and Hospital

6. SEPSIS
• The clinical criteria for sepsis include suspected
or documented infection and an acute increase of
two or more Sequential Organ Failure Assessment
(SOFA) points as a proxy for organ dysfunction.
• This new definition emphasizes the primacy of
the non-homeostatic host response to infection,
the potential lethality that is considerably in
excess of a straightforward infection, and the
need for urgent recognition.

7. Sepsis vs Septic Shock

8. The Sequential Organ Failure
Assessment (SOFA) Score
• A clinical evaluation of the patient that includes
laboratory values is needed to calculate a SOFA
score. The SOFA score is most commonly used in the
ICU practice setting.
The following are the abnormal physiologic SOFA
parameters, each of which receives a score of 2 or higher:
• PaO2:FiO2, < 300 mmHg
• Platelets < 100 × 103/mm3
• Bilirubin ≥ 2 mg/dL
• Hypotension requiring vasopressor support
• Glasgow Coma Scale score ≤ 12
• Creatinine ≥ 2 mg/dL, or urine output < 500 mL/day.

9. SOFA Score

10. The Quick Sequential Organ Failure
Assessment (qSOFA) Score
The following are the abnormal physiologic qSOFA parameters:
• systolic blood pressure, ≤ 100 mmHg
• respiratory rate, ≥ 22 breaths per minute
• any change in mental status
Non-ICU patients with a total score of 2 or 3 are considered at elevated
risk for an extended ICU stay or death and should be assessed for
evidence of organ dysfunction using the SOFA.

11. MEWS & NEWS

12. Logistic Organ Dysfunction Score

13. SIRS versus SOFA and qSOFA in Sepsis
• Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, Pilcher DV. Prognostic accuracy of the SOFA score, SIRS
criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit.
Jama. 2017 Jan 17;317(3):290-300.

14. "Time zero” or “time of presentation” is defined as the time of
triage in the emergency department or, if referred from another
care location, from the earliest chart annotation consistent with
all elements of sepsis (formerly severe sepsis) or septic shock
ascertained through chart review."

15. Surviving Sepsis Campaign Bundle:
2018 Update
HOUR-1 BUNDLE
• The most important change in the
revision of the SSC bundles is that the 3-h
and 6-h bundles have been combined
into a single “hour-1 bundle” with the
explicit intention of beginning
resuscitation and management
immediately.

16. HOUR-1 BUNDLE
• Measure lactate level. Re-measure if initial
lactate is >2 mmol/L.
• Obtain blood cultures prior to administration of
antibiotics.
• Administer broad-spectrum antibiotics.
• Begin rapid administration of 30m1/kg crystalloid
for hypotension or lactate > 4 mmol/L.
• Apply vasopressors if patient is hypotensive
during or after fluid resuscitation to maintain
MAP 65 mm Hg.

17. 3-h and 6-h bundles
TO BE COMPLETED WITHIN 3 HOURS:
1) Measure lactate level
2) Obtain blood cultures prior to administration of antibiotics
3) Administer broad spectrum antibiotics
4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L
TO BE COMPLETED WITHIN 6 HOURS:
5) Apply vasopressors (for hypotension that does not respond to initial fluid
resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg)
6) In the event of persistent arterial hypotension despite volume resuscitation
(septic shock) or initial lactate ≥ 4 mmol/L (36 mg/dL):
- Measure central venous pressure (CVP)
- Measure central venous oxygen saturation (ScvO2)
7) Re-measure lactate if initial lactate was elevated.

18. Measure Lactate Level
• Increases may represent tissue hypoxia,
accelerated aerobic glycolysis driven by excess
beta-adrenergic stimulation, or other causes
associated with worse outcomes.
• A significant reduction in mortality with lactate
guided resuscitation (24−28).
• If initial lactate is elevated (> 2mmol/L), it should
be remeasured within 2−4 h to guide
resuscitation to normalize lactate in patients with
elevated lactate levels as a marker of tissue
hypoperfusion.

19. Blood Cultures
• Sterilization of cultures can occur
within minutes of the first dose of
an appropriate antimicrobial, so
cultures must be obtained before
antibiotic administration to
optimize the identification of
pathogens and improve outcomes.
• Appropriate blood cultures
include at least two sets (aerobic
and anaerobic).
• 1 -percutaneously
1 -drawn through each vascular
access device

21. Hemodynamic Support
and Adjunctive
Therapy

22. Antimicrobial Therapy
• Administration of effective IV antimicrobials
within the 1st hour of recognition.
a) Initial empiric anti-infective therapy of one or
more drugs that have activity against all likely
pathogens & that penetrate in adequate
concentrations into tissues.
b) Empiric combination therapy should not be
administered for more than 3–5 days
c) Antimicrobial regimen should be reassessed
daily for potential de-escalation.

23. Procalcitonin
• Rises with bacterial infections (not viral!!!)
• Precursor to calcitonin (responsible for calcium homeostasis)
• Normal level is < 10 pg/ml (< 0.5 ng/ml)
• 0.5 – 2 ng/ml “grey zone” (repeat level in 6 – 24 hrs)
• > 10 ng/ml associated with severe sepsis/shock
• Half life of 25 – 30 hours
• Discontinue/ taper antibiotics
• 2 meta-analysis CAP
• 6 days antibiotics (treatment group) vs 10 days (control)
We suggest that measurement of procalcitonin levels can be used to
support shortening the duration of antimicrobial therapy

24. Combination empirical therapy
• Beta-lactam and either an aminoglycoside or a
fluoroquinolone is for P. aeruginosa
bacteremia.
• Beta-lactam and macrolide for bacteremic
Streptococcus pneumoniae infections.

25. Fluid Therapy
• Crystalloids as the initial fluid of choice in the
resuscitation of severe sepsis and septic shock.
• Albumin - when patients require substantial amounts
of crystalloids.
• Initial fluid challenge in patients with sepsis-induced
tissue hypoperfusion with suspicion of hypovolemia to
achieve a minimum of 30 mL/kg of crystalloids (a
portion of this may be albumin equivalent).
• Continued as long as there is hemodynamic
improvement either based on dynamic (eg, change in
pulse pressure, stroke volume variation) or static (eg,
arterial pressure, heart rate) variables.

26. Vasopressors
• Vasopressor therapy initially to target a mean arterial
pressure (MAP) of 65 mm Hg.
• Norepinephrine as the first choice vasopressor.
• Epinephrine (added to and potentially substituted for
norepinephrine) when an additional agent is needed to
maintain adequate blood pressure.
• Vasopressin 0.03 units/minute can be added to
norepinephrine (NE) with intent of either raising MAP or
decreasing NE dosage.
• Dopamine as an alternative vasopressor agent to
norepinephrine only in highly selected patients (eg,
patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)

27. Inotropic Therapy
• A trial of dobutamine infusion up to 20
micrograms/kg/min be administered or added
to vasopressor (if in use) in the presence of
(a) myocardial dysfunction as suggested by
elevated cardiac filling pressures and low cardiac
output, or
(b) ongoing signs of hypoperfusion, despite
achieving adequate intravascular volume and
adequate MAP.

28. Supportive Therapy of
Severe Sepsis

29. Mechanical Ventilation of Sepsis-
Induced ARDS
• Target a tidal volume of 6 mL/kg predicted
body weight in patients with sepsis-induced
ARDS.
• Initial upper limit goal for plateau pressures in
a passively inflated lung be ≤30 cm H2O.
• PEEP be applied to avoid alveolar collapse at
end expiration.

30. Blood Product Administration
• Hemoglobin concentration decreases to <7.0
g/dL to target a hemoglobin concentration of
7.0 –9.0 g/dL in adults.
• Prophylactic platelet transfusion when counts
are < 20,000/mm3 (20 x 109/L) if the patient
has a significant risk of bleeding.

31. Sedation, Analgesia, and
Neuromuscular Blockade
• Continuous or intermittent sedation be
minimized in mechanically ventilated sepsis
patients, targeting specific titration endpoints.
• A short course of NMBA of not greater than 48
hours for patients with early sepsis-induced
ARDS and a Pao2/Fio2 < 150 mm Hg

32. • Glucose Control: Target an upper blood
glucose ≤180 mg/dL rather than an upper
target blood glucose ≤ 110 mg/dL.
• Renal Replacement Therapy (RRT):
Continuous RRT and intermittent hemodialysis
are equivalent in patients with severe sepsis
and acute renal failure.
• Bicarbonate Therapy: in hypoperfusion-
induced lactic acidemia with pH ≥7.15

33. • Deep Vein Thrombosis Prophylaxis: daily
subcutaneous (LMWH) against venous
thromboembolism (VTE).
• Stress Ulcer Prophylaxis: using H2 blocker or proton
pump inhibitor.
• Prone position for sepsis-induced ARDS with
PaO2/FiO2 ratio <150.
• Elevate head of bed 30–45 degrees in mechanically
ventilated patients, spontaneous breathing trials, and a
weaning protocol.
• Early enteral nutrition, against parenteral nutrition in
the first 7 d

34. SSC recommends AGAINST
• Low dose Dopamine for renal protection
• Steroids (Only if on vasopressors – hydrocortisone
200mg/day)
• Erythropoietin for sepsis related anemia
• IV Immunoglobulins for sepsis or septic shock
• High frequency oscillatory ventilation (HFOV) for sepsis
induced ARDS
• ß2 agonists for sepsis-induced ARDS without
bronchospasm
• PA Catheter for patients with sepsis-induced ARDS

35. • Sodium bicarb therapy to improve
hemodynamics or to reduce vasopressor
requirements
• Stress ulcer prophylaxis in patients without risk
factors for GI bleeding!
• Parenteral nutrition alone or in combination with
enteral feedings
• Monitoring gastric residual volumes (only in
feeding intolerance or high risk aspiration)
• IV selenium, glutamine or arginine

36. Thank you…!!!