1. Associate Prof. Dr
Huda Nasser
MD, FARCSI
Faculty of Medicine –Aleppo University

3. Agenda
 Clinical syndromes related to sepsis
 Septic shock, pathogenesis, manifestations
 Goals of treatment of septic shock
 Initial resuscitation with fluid
 Stabilize hemodynamics with pressors
 Antibiotics
 Interruption of inflammatory mediators
 Early goal directed therapy

5. Bacteremia
Transient Infection in the blood

6. Systemic Inflammatory Response Syndrome
(( SIRS
 Trigger: infectious or non-infectious (e.g.,
pancreatitis, crush injuries, and certain drug
ingestions such as salicylates)
 Cause: release of inflammatory mediators
 Can be self limited or can progress to severe
sepsis and septic shock

7. Systemic Inflammatory Response Syndrome

9. Sepsis
SIRS + Blood Infection

10. Severe Sepsis
SIRS + Blood Infection
Plus
Organ Failure

11. Septic Shock
SIRS or Sepsis
Plus
Hypotension (SBP< 90) or Lactate ≥ 4 mmol/L

12. Refractory Hypotension
 Systolic blood pressure < 90 mm Hg after a
crystalloid-fluid challenge.
 Dose of fluid Challenge: 20 to 30 ml per
kilogram of body weight over 60 minutes
 Example: (70 kg) fluid challenge= 1.5-2.0 L

14. Septic Shock
 Is caused by the systemic release of
mediators that usually are triggered by
circulating bacteria or their products
 Or caused by systemic mediators triggered
by noninfectious causes
 Refractory Hypotension MUST be present

15. Clinical Manifestation of
Shock

16. Septic Shock: Goals of Treatment

17. Septic Shock-Initial
Resuscitation
 Appropriate large-volume fluid administration to
compensate for the decrease in vascular tone
and dilated ventricular capacity.
 First Goal: CVP = 8-12 cm H2O
a) Crystalloid fluid Administration
b) Central venous pressure monitor
c) During first 6 hours

18. Fluid Therapy
 We recommend fluid resuscitation with either
natural/artificial colloids or crystalloids.
 There is no evidence-based support for one type of
fluid over another (grade 1B).
A comparison of albumin and saline for fluid resuscitation in the intensive care unit.
N Engl J Med 2004; 350:2247-2256.

19. Stabilize Hemodynamics
 Second goal is: 65 ≤ MAP ≤ 90
a) Norepinephrine or Dopamine IV drip
b) Arterial line monitor
c) During first 6 hours
 Third goal is: ScvO2 ≥ 70 %
a) Blood transfusion to keep Hct ≥ 30 %
b) Use Inotropic agent to improve cardiac index
c) Central venous monitor of O2 saturation
d) During first 6 hours

20. Blood Product
Administration
 Give red blood cells when hemoglobin
decrease to < 7 g/dl to target a hemoglobin of
7.0-9.0 g/dl in adults
 Do not use erythropoietin to treat sepsis
related anemia

21. Norepinephrine Dose
 0.2-1.5 mcg/kg/min
 Large dose: 3.3 mcg/kg/min have been used
because of the alpha-receptor down-regulation
in sepsis.

22. Norepinephrine versus Dopamine
 Two recent trials have shown that a significantly greater
proportion of patients treated with norepinephrine were
resuscitated successfully, as opposed to the patients treated
with dopamine.
 Norepinephrine should be used early and should not be
withheld as a last resort in patients with severe sepsis who are
in shock.
Critical Care Medicine 2000;28,2758-2765
Chest 1993;103,1826-1831

23. Dopamine
Dopamine is capable of stimulating:
1. Cardiac ß1-receptors
2. Peripheral α-receptors
3. Dopaminergic receptors in renal, splanchnic,
and other vascular beds.

24. Bicarbonate Therapy
 Do not use bicarbonate for the purpose of
improving hemodynamics or reducing
vasopressor requirements when treating
hypoperfusion-induced lactic acidemia with
PH ≥ 7.15

25. Control of Underlying Infection
Replacement of Central and Arterial lines:
1) Infected lines or old lines ( ≥ 7 days )
2) Avoid Femoral Vein if possible
3) Full sterile technique ( mask, gown, gloves )
4) Antibiotics
Treatment of Pneumonia:
1) Good Oral Hygiene
2) Aspiration Precaution: ↑ HOB 45 ˚
3) Antibiotics
Treatment of Intra-abdominal infections:
1) Cholecystitis, diverticulitis, gut ischemia, abscess, pancreatitis, appendicitis,
UTI ( change catheter )
2) Mini-invasive surgery vs. surgery
3) Antibiotics

26. (Blood Cultures ( BCs
 Obtain ≥ 2 BCs
 ≥ 1 BC should be percutaneous
 One BC from each vascular access device in
place > 48
 Should be obtained very early
 Obtain Lactate level with blood culture

27. Empiric Antibiotics: Broad Spectrum
 Must be broad-spectrum agents and must cover
gram-positive, gram-negative, and anaerobic
bacteria.

28. Empiric Antibiotics: First
Hour
 Should be started within the first hour of
recognition of septic shock and severe sepsis
 Appropriate cultures should be obtained
before initiating antibiotic therapy
 Blood cultures should not significantly delay
antibiotic therapy

29. Empiric Antibiotics: Selection
 Host defenses, potential sources of infection,
and most likely organisms
 Antibiotic experienced patient: use
aminoglycoside rather than a quinolone or
cephalosporin for gram-negative coverage
 Antibiotic resistance patterns of both the
hospital itself and its referral base (i.e., nursing
homes)

30. Empiric Antibiotics: Duration
 Should not be administered for > 3-5 days
 De-escalation to the most appropriate single
therapy should be performed as soon as the
susceptibility profile is known

31. Anti-Fungal
 If candidemia is a likely cause
 Risk factors for Candidemia: TPN, Propofol,
DM, HIV, Chemotherapy
 Empirical antifungal therapy (e.g.,
fluconazole, amphotericin B, or
echinocandin)

32. Specific Antibiotics: Duration
 Typically 7-10 days
 Longer courses in patients:
1. Slow clinical response
2. Undrainable foci of infection
3. Immunologic deficiencies
4. Neutropenia

33. Interrupt Inflammatory
Mediators
Activated Protein C:
1) Reduced mortality rate in sever sepsis and septic
shock
2) Very expensive therapy
Corticosteroid therapy:
1) Persistent Hypotension
2) Non responder to ACTH stimulation test
Glucose control:
1. Keep glucose < 150 mg/dl
2. Use Intravenous insulin protocol

34. Activated Protein C

35. Drotrecogin alfa Dose
Continuous infusion of 24 mcg/kg/hour for
96 hours

36. Contraindications to Use of
Recombinant Human Activated Protein C
( (rhAPC
 Active internal bleeding
 Recent (within 3 months) hemorrhagic stroke
 Recent (within 2 months) intracranial or intraspinal surgery, or severe head
trauma
 Trauma with an increased risk of life-threatening bleeding
 Presence of an epidural catheter
 Intracranial neoplasm or mass lesion or evidence of cerebral herniation
 Known hypersensitivity to rhAPC or any component of the product
 The committee recommends that platelet count be maintained at ≥30,000 during
infusion of rhAPC.
Physicians' Desk Reference, 61st Edition. Montvale, NJ, Thompson PDR, 2007, Page
1829

37. EARLY GOAL-DIRECTED THERAPY
( ( EGDT
Early detection and treatment:
Decreases mortality rate

38. Septic Shock

39. Fluid Dose: First Golden 6
Hours
 A 500-ml bolus of crystalloid ( NS ) was given
every 30 minutes to achieve a central venous
pressure of 8 to 12 mm Hg
 Central venous catheter capable of
measuring central venous oxygen saturation
(Edwards Lifesciences, Irvine, Calif.)

41. Sepsis Bundle
Is defined as a group of interventions
related to a disease process that, when
executed together, result in better
outcomes than when implemented
individually

42. Sepsis Bundle
Reduces mortality and ICU stay
if implemented within 6 hours

43. Thank you