Sepsis resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

Definition

Sepsis is a systemic inflammatory response syndrome (SIRS) following an infection, and it is manifested by multi-system organ dysfunction in addition to hypotension that is not readily reversible with fluid resuscitation.

Systemic inflammatory response syndrome (SIRS) is the occurrence of at least two of the following criteria:

• Fever > 38.0°C or hypothermia < 36.0°C,
• Tachycardia > 90 beats/minute
• Tachypnea > 20 breaths/minute or PaCO₂ lower than 32 mm Hg.
• Leucocytosis > 12,000/mm³ or leucopoenia < 4,000/mm³

Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation (infusion of 30 mL/kg of crystalloids/albumin equivalent).

Diagnostic Criteria For Sepsis

(Documented/Suspected Infection plus some of the following:)

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

Severe Sepsis

Severe sepsis refers to sepsis-induced tissue hypoperfusion or organ dysfunction with one of the following, due to infection:

• Sepsis-induced hypotension - systolic blood pressure (SBP) <90 mmHg or mean arterial pressure (MAP) <70 mmHg or a SBP decrease >40 mmHg or less than two standard deviations below normal for age in the absence of other causes of 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)

Causes

Life Threatening Causes

• Bacteremia: 95% of positive blood cultures were associated with sepsis, severe sepsis, or septic shock.. However septic shock can occur without bacteremia "viable bacteria in the blood". In fact, septic shock is associated with culture-positive bacteremia in only 30-50% of cases.

Common Causes

• Community acquired pneumonia: 48% develop severe sepsis.
• Diabetes and renal disease may explain the higher rates of infection related septic shock.
• Immunosuppression

Management

The following guidelines are based on 'Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012'.

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 andaminoglycoside/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 IVhydrocortisone 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 withacute 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

• 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.

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

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

• Do not use low dose dopamine for renal protection.

• Do not use corticosteroids in the absence of shock.

• 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.

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

IV immunoglobulins

IV selenium

• Do not routinely use pulmonary artery catheters.

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