SEPSIS AND EARLY GOAL DIRECTED

THERAPY

Goals of this didactic

Definition of spectrum of sepsis Pathophysiology of sepsis Early Goal Directed Therapy

Infection SIRS

Sepsis

Severe Sepsis

Septic Shock

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

Basic Definitions

Sepsis: Presence of infection + SIRS

Documented OR presumed infection

Severe Sepsis: Sepsis + end organ dysfunction

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

Septic Shock

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

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

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

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%

16% Absolute reduction in mortality

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

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

Specific Targets 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

Optimize Preload

20-40ml/kg bolus

Looking for recruitable CO Increase in BP with fluid challenge

Pressors only after adequate fluid challenge

MAP Management

MAP <65

Fluid Challeng

ePressors

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

ScvO2 Management

ScvO2 <70

Transfuse to HCT

30

Inotropes

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

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

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

Time Frame

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

Conclusion

Early recognition of sepsis is key in lowering mortality

Early antibiotics Early Goal Directed Therapy in

appropriate patients Appropriate access Being Aggressive