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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 Standard deviation (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 (Systolic blood pressure (SBP) < 90 mm Hg, mean arterial pressure (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 reactive 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
❑ Central venous pressure (CVP) 8-12 mm Hg
❑ Mean arterial pressure (MAP) ≥ 65 mm Hg
❑ Urine output ≥ 0/5 mL/Kg/hr
❑ Central venous O₂ sat. 70%
❑ If lactate levels elevated, target is normalization

Diagnosis:
❑ Perform 2 sets of blood cultures (aerobic and anaerobic) atleast, before starting antibiotics

Drawn percutaneously
Drawn through each vascular access device present for > 48 hours

❑ Perform 1,3 beta-D-glucan assay, mannan, anti-mannan antibody assay if available
❑ Perform imaging studies as appropriate to locate a source

Antimicrobial therapy:
❑ Initiate within 1st hour of diagnosis
Reassess regimen daily
❑ Use low procalitonin levels 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, use 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 phenylephrine 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

Do's

Patients who are suspected of being severely infected, should be routinely screened for sepsis.

Administer antimicrobial therapy within 1 hour of diagnosis of sepsis.

Delay intervention, if source/foci of infection is peri-pancreatic necrosis.

Dont's

Antimicrobial Therapy:

Do not use empiric combination therapy for more than 3-5 days.

Do not use antimicrobial agents in severely inflamed patients, from a non-infectious cause.

Fluid therapy:

Do not use hydroxyethyl starch for resuscitation of severe sepsis and septic shock.

Vasopressors:

Do not use low dose vasopressin/dopamine/phenylephrine as monotherapy.

Do not use low dose dopamine for renal protection.

Corticosteroids:

Do not use corticosteroids in absence of shock.

Blood products:

Do not use erythropoietin as a specific treatment of anemia associated with sepsis.

Do not use antithrombin.

Do not use fresh frozen plasma to correct clotting abnormalities in the absence of bleeding or planned invasive procedure.

Other supportive therapy:

Do not use following therapies as their role is not clear:

IV immunoglobulins

IV selenium

Do not use pulmonary artery catheters routinely.

Do not use bicarbonate therapy as prophylaxis of hypoperfusion induced lactic acidosis if pH > 7.15.