Sepsis and Early Goal Directed Therapy

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

Sepsis Infection Severe Sepsis SIRS 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 SIRS is a sign of inflammation, not infection

Basic Definitions Sepsis: Severe 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: Hypotension: Refractory Hypotension: 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% 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

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 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

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 Challenge Pressors

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

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

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)

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