Sepsis is a serious condition caused by infection that can lead to tissue damage, organ failure and death. It has high mortality rates of 30-50% for severe sepsis and septic shock. The document outlines definitions of sepsis, severe sepsis, septic shock and related organ dysfunction. It discusses the complex pathophysiology and recommends treatment bundles that should be completed within 3-6 hours and 24 hours to help combat sepsis, including administering antibiotics and fluids, monitoring lactate levels, achieving hemodynamic and oxygenation targets, and managing ventilation, glucose and steroids. Outcomes can be improved by early goal directed therapy and tight control of factors like sugars and ventilation parameters.

1. BY
DR MUHAMMAD AKRAM KHAN
MATERNITY AND CHILDREN HOSPITAL
MAUSADIA, JEDDAH
DECEMBER 2015

2. Sepsis Overview
 Severe sepsis and septic shock have mortality rates of
30-50%
 Account for up to 45% of ICU admissions
 Higher mortality and incidence than STEMI and
stroke
 Complex pathophysiology which routinely causes
shock without significantly abnormal vital signs

4. INFECTION
 microbial phenomenon characterised by an
inflammatory response to the presence of micro
organisms or the invasion of normally sterile host
tissue by these organisms

5. Definitions
The ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and guidelines for the use of
innovative therapies in sepsis. Chest 1992.
 SIRS
 Widespread inflammatory response
 Two or more of the following
 Temp>38 C<36 C
 Heart Rate >90 bpm
 Tachypnea RR>20 or hyperventilation PaCO2 <32 mmHg
 WBC >12,000<4000 or presence of >10% immature neutrophils.
 Sepsis: SIRS + definitive source of infection

6. SEVERE SEPSIS
 Sepsis associated with organ dysfunction,
hypoperfusion or hypotension
 May include lactic acidosis,oliguria,altered mentation

7. SEVERE SEPSIS
 Sepsis associated with organ dysfunction,
hypoperfusion or hypotension
 May include lactic acidosis,oliguria,altered mentation
 Systemic response to infection manifested by ≥
2 of:
 Temp > 38oC or < 36oC
 HR > 90 bpm
 RR > 20 bpm or PaCO2 < 32 mmHg
 WBC > 12 x 109/L, < 4 x 109/L or >10% band form

8. ORGAN DYSFUNCTION
 Arterial hypotension
SBP<90 MAP<70 x 1hour
despite fluid resuscitation
perfusion abnormalities
(that could include,lactic acidosis, oliguria, and/or
acute change in mental status).
 Thrombocytopenia
drop by >30% within 24 hrs OR count <100K

9. ORGAN DYSFUNCTION
 Arterial hypoxaemia
PaO2 < 75 mm of Hg (room air) OR
PaO2 /FiO2 < 250 (oxygen supplimentation)
 Renal dysfunction
Urine output < 0.5 ml/ kg x 2 hrs despite fluid loading
OR S. creatinine > 2x reference range
 Metabolic acidosis
BE > 5 mmol/L OR S.lactate > 1.5 x upper value

10. MODS
 Presence of altered organ function lasting for > 24 hrs
in an acutely ill patient, such that homeostasis cant be
maintained without intervention.

11. MODS
0
10
20
30
40
50
60
70
80
PercentofPatients
Shock
Respiratory
Renal
Metabolic
Coag
DIC

12. Surviving Sepsis Campaign 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 ≥4 mmol/L
TO BE COMPLETED WITHIN 6 HOURS:
5) Apply vasopressors (for hypotension that does not respond to initial
fluid resuscitation) to maintain a MAP ≥65 mmHg
6) In the event of persistent arterial hypotension despite volume
resuscitation (septic shock) or initial lactate ≥4 mmol/L :
– Measure CVP
– Measure ScvO2
7) Remeasure lactate if initial lactate was elevated

13. Liver (& Lung) disease
Accelerated glycolysis
Congenital disorders
Thiamine deficiency
Anaerobic metabolism
Toxic and drug effects
Extracellular movement in alkalosis
Sepsis
Glucose
Pyruvate
Lactate
Acetyl
CoA

Adrenaline, salbutamol
Cori
cycle

14. Lactate Testing
Lactate > 4mmol/L is associated with much higher
mortality rates
Lactate has been proven to be a better indicator of
shock, risk, prognosis and mortality than any other
vital sign in sepsis
0
10
20
30
40
50
Non-sShock Shock
Low Int High Low Int High
Non-shock Shock
28daymortality(%)
http://www.laktate.com/wp-content/uploads/2013/09/lactate-plus-
meter1.png
p=0.001
p<0.001

15. INITIAL RESUSCITATION [1st 6 hrs]
 Central venous pressure (CVP): 8–12 mm Hg / 12-15 if
mechanical ventilation
 Mean arterial pressure (MAP) >65 mm Hg
 Urine output >0.5 mL/kg/hour
 Central venous (superior vena cava) or mixed venous
oxygen saturation >70% or >65%, respectively

16. IF CENTRAL VENOUS OXYGEN
SATURATION NOT ACHIEVED
 FLUID
 PRBC ( Hct >30)
 Vasopressors

17. DIAGNOSIS

18. ANTIBIOTICS

19. HEMODYNAMIC SUPPORT

20. CVP
MAP
ScvO2
<8 mmHg
<65mmHg
<70%
IVF
Pressors
PRBCs

21. VASOPRESSORS
NOREPINEPHRINE / DOPAMINE
EPINEPHRINE ADDED
IF POOR RESPONSE
VASOPRESSIN
0.03 UNITS/MIN
No low dose
Dopamine!
MAP >65
Arterial catheter

22. LeDoux D et al.
Crit Care Med 2000
Bourgoin A et al.
Crit Care Med 2005
10 Patients
28 Patients
MAP
65mmHg
75mmHg
85mmHg
Lactate
Renal Fxn
UOP

23. 29 Centers in France
with 776 Patients

24. SEPSISPAM Trial was published along side ProCESS (Protocol-
Based Care for Early Septic Shock)
trial April 2014
•Multicenter, open label trial of 776 patients with septic
shock from 29 hospitals in France
•Septic Shock = Sepsis with Refractory Hypotension after
30cc/kg bolus of IVF
•Primary Outcome: 28 day mortality
•Also looked to see if higher MAP beneficial in patients with
chronic HTN

25. Low Target
Group
MAP
65 – 70 mmHg
High Target
Group
MAP
80 – 85 mmHg

26. Difference
NO
Difference
28 or 90 Day
Mortality
28 Day Survival
w/o Organ Support
More
Atrial
Fibrillation
Longer
Pressor
Duration &
Dose

27. 3L IVF in 24h
then
Pressors
Mortality = 34 – 36.6%

28. Don’t Chase
MAP ≥65mmHg
Bottom Line
Give Fluids
Early

29. STEROIDS
 Poorly responsive hypotension
 Hydrocortisone > dexamethasone
 Hydrocortisone <300 mg / day
 Fludrocortisone 50 µg OD optional
 Weaned when no vasopressors
 No steroid if no shock

30. RECOMBINANT ACTIVATED Protein
C
 APACHE II >25

31. Activated Protein C Guidelines

32. BLOOD PRODUCTS
Hb: 7-9g
Sepsis related
anemia- no
erythropoetin
FFP: only if
bleeding /
invasive
procedures
FFP not a
nutrient!
No antithrombin

33. 32 Centers in Europe
with 998 Patients

34. Transfusion
Requirements
In
Septic Shock
(TRISS)

35. 50% Less
Transfusions
36% No
Transfusions
No 90 Day Mortality Difference

36. Liberal
Transfusion
Hb ≤9g/dL
Restrictive
Transfusion
Hb ≤7g/dL

37. Bottom Line
Use A
Restrictive
Transfusion
Strategy

38. PLATELETS

39. MECHANICAL VENTILATION-ARDS
TIDAL VOLUME: 6 ML/KG
PLATEAU PRESSURE MAX 30 CM H2O
PERMISSIVE HYPERCAPNEA
PEEP
PRONE POSITION VENTILATION
SEMIRECUMBENT : 30-45º
STABLE/AROUSABLE/REFLEXES/FAST RECOVERY NIV

40. MECHANICAL VENTILATION-ARDS
WEANING PROTOCOL
SBT: LOW LEVEL PS † PEEP-5 CM H2O OR T-PIECE
AROUSABLE
STABLE HEMODYNAMICS
NO NEW SERIOUS CONDITIONS
LOW PEEP REQUIREMENT
LOW FiO2 REQUIREMENT

41. SEDATION- ANALGESIA- NMB

42. GLUCOSE CONTROL

43. GLUCOSE CONTROL

44. RENAL REPLACEMENT
 Intermittent HD = CVVH
 CVVH if hypotension

45. BICARBONATE THERAPY
 Not for hypoperfusion induced lactic acidemia with
pH >7.15

46. DVT PROPHYLAXIS

47. STRESS ULCER PROPHYLAXIS
GI BLEED
VAP

48. SEPSIS RESUSCITATION BUNDLE- 6 h

49. SEPSIS MANAGEMENT BUNDLE – 24HR
STEROID
DROTECOGEN
α
GLUCOSE <150 PIP<30 CM

50. OUTCOME IMPROVED BY
 Early goal directed therapy
 Lung protective ventilation
 Appropriate antibiotic coverage
 Activated protein C
 Tight control of sugars 80-100mg/dl
 Steroids

51. A clinician, armed with the sepsis bundles, attacks the three heads of severe
sepsis: hypotension, hypoperfusion and organ dysfunction