1. Sepsis and Early Goal Directed Therapy

2. Goals of this didactic Definition of spectrum of sepsis
Pathophysiology of sepsis
Early Goal Directed Therapy

3. Sepsis
Infection
Severe Sepsis
SIRS
Septic Shock

4. Basic Definitions Infection:
Pathophysiologic abnormality caused by a microbial pathogen
Systemic Inflammatory Response Syndrome (SIRS)
> 2 of the following:
Temp > 380C (100.4 F) or < 360C (96.8 F)
Pulse > 90
RR > 20 (or PaCO2 < 32)
WBC > 12,000 or < 4,000 or > 10% bands
CRP or procalcitonin > 2 SD above normal
SIRS is a sign of inflammation, not infection

5. Basic Definitions Sepsis: Severe Sepsis: Presence of infection + SIRS
Documented OR presumed infection
Severe Sepsis:
Sepsis + end organ dysfunction

6. End-Organ Dysfunction
Signs of Hypoperfusion
Lactic acidosis or Mottling
Altered Mental Status
Arterial Hypoxemia (PaO2:FiO2 < 300)
Coagulation abnormalities (INR > 1.5)
Thrombocytopenia (Platelets < 100,000)
Ileus
Renal, liver, cardiac failure
Lab or vital sign abnormalities

7. Septic Shock Septic Shock: Hypotension: Refractory Hypotension:
Sepsis + refractory hypotension
Hypotension:
SBP < 90
MAP < 65
Decrease of 40 mm Hg SBP off baseline
Refractory Hypotension:
Hypotension despite mL/kg crystalloid challenge

8. Pathophysiology of Sepsis
Lipopoloysaccharides and other bacterial components activate neutrophils and vascular endothelium
Cytokines and complement activation lead to vascular instability
Increase in tissue factor leads to microvascular occlusion
Combination leads to coagulopathy, vasodilation and capillary leak

9. Antimicrobial Therapies – ASAP!
Early antibiotic therapy (within 1 hour of presentation) decreases mortality
Check hospital antibiogram
Target the most likely source
Start broad, narrow later
When all else fails:
Cefepime 1 gm IV and Vancomycin 15mg/kg
Note: generally, anaerobes are NOT a cause of sepsis except in rare intraabdominal cases

10. Early Goal-Directed Therapy
Algorithmic approach to management of severe sepsis
Inclusion: 2/4 SIRS, SBP ≤90 after fluids or serum lactate >4
Then randomly assigned to standard therapy or EGDT
With their EGDT protocol:
Reduction in sudden cardiovascular collapse
Mortality reduction:
Standard therapy in-hospital mortality: 46.5%
EGDT in-hospital mortality: 30.5%
EGDT added TLC with measurement and management of SvO2
In hospital as well as 28 and 60 day mortality was reduced
16% Absolute reduction in mortality

11. Who’s eligible for EGDT?
Patients with severe sepsis with signs of hypoperfusion/end-organ dysfunction
Lactate > 4 mmol/L
(The patient does NOT need to be hypotensive)
Patients with septic shock

12. EGDT: Basic Principles
Goal-directed hemodynamic resuscitation of severe sepsis / septic shock:
Optimize CO: preload, afterload, and contractility
Restore systemic oxygen content
Oxygen Delivery (DO2) = CO x CaO2
DO2 = CO x (1.34 * Hb * SaO2) + (0.003 * PaO2)
Preserve tissue perfusion
Avoid increases in myocardial O2 consumption

13. Specific Targets CVP of 8 – 12 mm Hg MAP of >65 mm Hg
Controversy about using CVP as no direct correlation to volume responsiveness
MAP of >65 mm Hg
UOP ≥ 0.5 ml/kg/h
Normalization of Lactate
ScvO2 ≥ 70%
ScvO2 = from CVP
SvO2 = from PA catheter

14. Optimize Preload 20-40ml/kg bolus Looking for recruitable CO
Increase in BP with fluid challenge
Pressors only after adequate fluid challenge

15. MAP Management
MAP <65
Fluid Challenge
Pressors

16. MAP Management Vasopressors to MAP of > 65
Once initial fluid resuscitation has been completed*
Arterial line placement is needed at some point
Pressors of choice
Norepi +/- Vasopressin
Epi
If patient does not respond to fluids and pressors, Hydrocortisone should be given
*hypovolemia still may not be resolved but may require pressors after initial fluid challenge

17. ScvO2 Management ScvO2 <70 Transfuse to HCT 30 Inotropes
HCT 30 goal only for first 6 hours of resus  then goal transfusion goal <7 unless patient with ongoing ischemia, hemorrhage or severe hypoxemia and resolution of tissue hypoperfusion

18. ScvO2 Management Achieve ScvO2 ≥ 70% Initial fluid resuscitation
Blood transfusions to HCT > 30%**
1 U PRBC will raise HCT ~ 3% or Hgb 1 gram
Inotropic therapy
Decrease O2 consumption
Major users are muscles of respiration
Intubation, sedation, and paralysis may be needed
SvO2 - True mixed venous oxygen saturation from PA catheter,  ScvO2 - Central venous oxygen saturation from TLC
Target >65% for SvO2 (5% difference due to the mixing of venous blood from the atrial and coronary sinus blood)

19. Inotropic therapy Dobutamine
Use when ScvO2 < 70% despite fluids and HCT > 30%
Improves contractility
Use in combination with vasopressor because of vasodilatory effect
Dose: 2.5 to 20 mcg/kg/min
Major adverse effect: dysrhythmias

20. Access Central Access in order to follow ScvO2
Arterial Line: especially if patient requires pressors
Intubation if patient hypoxemic or with significant altered mental status
Early intubation can decrease oxygen consumption by decreasing work of breathing

21. Time Frame Within 3 hours: Get lactate level Blood cx
Abx (within 1hour)
Fluid resuscitation

22. Conclusion Early recognition of sepsis is key in lowering mortality
Early antibiotics
Early Goal Directed Therapy in appropriate patients
Appropriate access
Being Aggressive