Early goal direct therapy

2.  Definition of spectrum of sepsis
 Pathophysiology of sepsis
 Early Goal Directed Therapy

3. Infection SIRS
Sepsis
Severe
Sepsis
Septic
Shock

4.  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

5.  Sepsis:
 Presence of infection + SIRS
 Documented OR presumed infection
 Severe Sepsis:
 Sepsis + end organ dysfunction

6.  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:
 Sepsis + refractory hypotension
 Hypotension:
 SBP < 90
 MAP < 65
 Decrease of 40 mm Hg SBP off baseline
 Refractory Hypotension:
 Hypotension despite 20 - 40 mL/kg crystalloid
challenge

8.  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.  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.  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% 16% Absolute
reduction in
mortality

11.  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.  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.  CVP of 8 – 12 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.  20-40ml/kg bolus
 Looking for recruitable CO
 Increase in BP with fluid challenge
 Pressors only after adequate fluid challenge

15. MAP <65 Fluid
Challenge
Pressors

16.  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

17. ScvO2
<70
Transfuse
to HCT 30
Inotropes

18.  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

19.  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.  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.  Within 3 hours:
 Get lactate level
 Blood cx
 Abx (within 1hour)
 Fluid resuscitation

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