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Definition

Sepsis is a systemic, deleterious host response to infection, manifested as multi system organ dysfunction plus hypotension, that is not readily reversible with fluid resuscitation.

Diagnostic Criteria For Sepsis (Documented/Suspected Infection Plus Inflammatory variables Plus One of The Organ Dysfunction)

General variables

• Fever > 38.3°C
• Hypothermia ( core temperature < 36°C )
• Heart rate > 90/min–1 or > 2 SD above the normal value for age
• Tachypnea
• Altered mental status
• Edema
• Positive fluid balance ( > 20 mL/kg over 24 hr)
• Hyperglycemia ( plasma glucose > 140 mg/dL or 7.7 mmol/L ) in the absence of diabetes

Inflammatory variables

• Leukocytosis ( WBC count > 12,000 µL–1 )
• Leukopenia ( WBC count < 4000 µL–1 )
• Immature WBCs forms are > 10% with normal count
• Plasma C-reactive protein > 2 SD above the normal value
• Plasma procalcitonin > 2 SD above the normal value

Hemodynamic variables

• Arterial hypotension after 30 ml/kg fluid bolus ( SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults or < 2 SD below normal for age )

Organ dysfunction variables

• Arterial hypoxemia ( Pao2/Fio2 < 300 )
• Acute oliguria ( urine output < 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation )
• Creatinine increase > 0.5 mg/dL or 44.2 µmol/L
• Coagulation abnormalities ( INR > 1.5 or aPTT > 60 Sec )
• Ileus ( absent bowel sounds )
• Thrombocytopenia ( platelet count < 100,000 µL–1 )
• Hyperbilirubinemia ( plasma total bilirubin > 4 mg/dL or 70 µmol/L )

Tissue perfusion variables

• Hyperlactatemia > 1 mmol/L
• Decreased capillary refill or mottling

Diagnostic Criteria for Severe Sepsis (sepsis induced hypoperfusion or organ dysfunction)

Includes any one of the following caused due to the infection:

• Sepsis-induced hypotension
• Lactate above upper limits laboratory normal
• Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation
• Acute lung injury with Pao2/Fio2 < 250 in the absence of pneumonia as infection source
• Acute lung injury with Pao2/Fio2 < 200 in the presence of pneumonia as infection source
• Creatinine > 2.0 mg/dL (176.8 μmol/L)
• Bilirubin > 2 mg/dL (34.2 μmol/L)
• Platelet count < 100,000 μL
• Coagulopathy (international normalized ratio > 1.5)

Management

Characterize the symptoms: Fever Hypothermia Altered mental status Mottling Ileus oliguria

Examine the patient: Tachycardia Tachypnea Edema Hyperglycemia Hypotension after an initial 30 ml/Kg bolus Decreased capillary refill

Order labs: Random blood sugar (RBS) Complete blood count (CBC) Plasma C reactie protein (CRP) Plasma procalcitonin Pulse oximetry Urinalysis/Renal function tests PT/INR Liver function tests Serum lactate Central venous pressure (CVP)

Consider alternative diagnosis: Infections Acute pancreatitis Diabetic ketoacidosis Lower gastrointestinal bleeding Myocardial infarction

Initial resuscitation: Goals to achieve in first 6 hours CVP 8-12 mm Hg Mean arterial pressure (MAP) ≥ 65 mm Hg Urine output ≥ 0/5 mL/Kg/hr Central venous O2 sat. 70%

Diangosis: 2 sets of blood cultures (aerobic and anaerobic) atleast, before starting antibiotics Drawn percutaneously Drawn through each vascular access device present for > 48 hours 1,3 beta-D_glucan assay, mannan, anti-mannan antibody assay if available Imaging studies as appropriate to locate a source

Antimicrobial therapy: Initiate within 1st hour of diagnosis Daily reassessment of regimen Low procalitonin level for prognosis Usual duration of therapy 10 days Longer in neutropenics, slow responders, undrainable foci, immunologically compromised

Choice of antibiotics

Unknown organism Empiric therapy with broad spectrum antbiotic with good tissue penetrance

Neutropenic pt with severe sepsis (goal is to cover Acinetobacter & Pseudomonas spp) Use combination empirical therapy

Severe infections + resp failure + septic shock Extended spectrum beta lactam and aminoglycoside/fluoroquinolone

Streptococcus pneumoniae Beta lactam + macrolide

Culture specific organism Shift to appropriate anti-bacterial, antiviral or antifungal

Remove source/foci of infection: Use minimally invasive process Source removal best done in first 12 hours Remove intravascular access devices if they are a possible source Oral chlorhexidine gluconate to reduce oral contamination as a risk factor for ventilator associated pneumonia

Hemodynamic support Fluid therapy: Administer crystalloids, albumin when demand for fluids is too high Use dynamic variables (change in pulse pressure, stroke volume) and static variables (arterial pressure,heart rate) to assess status Vasopressors (to achieve target MAP 65 mm Hg): Place arterial line as soon as feasible Administer norepinephrine as 1st choice drug Use epinephrine - when additional agent needed Use vasopressin 0.03 units/minute to raise MAP or decrease norepinephrine usage Selective dopamine (absolute or relative bradycardia) and phenyephrine usage Inotropic therapy: Trial of dobutamine infusion 20 μg/Kg if cardiac output low with elevated cardiac filling pressure

Corticosteroids: Use continuous flow IV hydrocortisone 200 mg/day if shock doesn’t improve with fluids & vasopressor Taper when vasopressors no longer required

Blood products: Transfuse blood when hemoglobin < 7.0 g/dL Transfuse platelets if < 10,000/mm3 or < 20,000/mm3 in those with high risk

Mechanical ventilation for sepsis induced ARDS Target tidal volume of 6 mL/Kg Target plateau pressure ≤ 30 mm Hg Use PEEP (positive end expiratory pressure) to avoid alveolar collapse Raise patients bed to 30-45° Attempt weaning when all foll criteria are met: Pt arousable Hemodynamics stable No new complications Low ventilatory/fiO2 requirements Extubate when weaning successful

Other supportive therapy Sedation & neuromuscular blockade: Use minimal sedation/neuromuscular blockade in mechanically ventilated patients Glucose control: Blood glucose target value should be ≤ 180 mg/dL Use insulin infusion and 1-2 hourly monitoring to achieve target Renal replaement therapy: May be used for management of fluid balance in hemodynamically unstable patients Use for septic patients with acute renal failure DVT prophylaxis: Do pharmacoprophylaxis with low molecular weight heparin (LMWH), if no contraindications present Use pneumatic compression devices whenever possible Stress ulcer prophylaxis Consider prophylaxis if risk factors are present Feeding: Enteral & oral feeding preferred over total parenteral feeding (TPN) Adjust calorie requirement in subsequent days, as tolerated Goals of care: Discuss goals or care, patient aspirations and future directives with family with 72 hours of admission