Harborview Medical Center Guidelines

Sepsis: Early Goal Directed Therapy (EGDT)

Step 1:  Is an infection suspected?

Step 2:  Does the patient exhibit 2 or more of the following:

  • Temperature > 38° C or < 36° C
  • Heart rate > 90 beats/min.
  • Respiratory rate > 20 breaths/min., PaCO2 < 32 or intubation for respiratory failure
  • WBC count > 12,000/mm3, < 4000/mm3 or > 10% immature (band) forms

Step 3:  If the answer is yes to step 1 & 2, proceed with this protocol.

Initial Resuscitation Period (First hour):

  • Obtain serum lactate level STAT (venous or arterial in a blood gas syringe)
  • CBC with differential STAT
  • Obtain 2 sets of blood cultures prior to antibiotic administration (one set from a peripheral site)
  • Administer antibiotics within 3 hours of ED presentation or 1 hour for in-patient presentation
        (See pages 3 - 5 for antibiotic administration guidelines)
  • Initiate fluid resuscitation with 20 mL/kg of:
    • Normal Saline
    • Lactated Ringers

      Weight (estimated):  ____________ kg x 20 mL = ____________ mL fluid bolus
  • Repeat lactate level after fluid administration

    If the repeat lactate level is ≥ 4 mmol/L OR the patient is hypotensive (MAP < 65 mmHg), initiate “Code Sepsis” by dialing 222.
  • Initiate admission to the Intensive Care Unit

For persistent hypotension (MAP < 65 mmHg) or lactate ≥ 4 mmol/L after initial fluid bolus (First 6 hours):

  1. Fluid Resuscitation:
    • If MAP < 65 mmHg or initial lactate > 4 mmol/L, administer additional 500 mL fluid bolus.
    • When central is placed, transduce Central Venous Pressure (CVP) with goal: < 8 mmHg (if not mechanically ventilated) or < 12 mmHg (if mechanically ventilated).
    • Repeat assessment for fluid bolus every 30 minutes

      Note :  If signs of intravascular volume excess develop (JVD, crackles, or SpO2 drop by more than 5% points) stop fluid boluses and notify MD.
  2. Central Intravenous Access:
    • Oximetric ScvO2 catheter and measure CVP and ScvO2
      OR
    • Central venous catheter and measure central venous pressure
      • Obtain mixed venous oxygen saturation
    • If ScvO2 is < 70% and CVP < 8 – 12 mmHg, return to #1 and administer fluids
    • Repeat lactate & mixed venous oxygen levels a minimum of every 2 hours & after interventions.
  3. Vasopressor Support:
    For hypotension not responding to repeat fluid boluses (MAP ≥ 65 mm Hg or SBP ≥ 90 mm Hg), start:
    • Norepinephrine – Start infusion at 5 mcg/min; titrate up by doubling dose every 5 min.
      If dose exceeds 30 mcg/min, notify MD.
    • Dopamine – Start infusion at 2 mcg/kg/min; titrate up by 2.5 mcg/kg/min every 5 min.
      If dose exceeds 20 mcg/kg/min, tachycardia worsens or ventricular ectopy develops, notify MD.
    • Vasopressin – Start infusion at 0.04 units/min; utilize as a second line agent in addition to Norepinephrine or Dopamine.  Do not titrate.
  4. Additional Support:
    • If ScvO2 is < 70% and CVP > 8 – 12 mmHg and Hct > 30%, start Dobutamine at 5 mcg/kg/min.  Increase dose by 2.5 mcg/kg/min every 15 minutes if ScvO2 < 70%.  Maximum dose 20 mcg/kg/min.  Decrease dose if MAP < 65 mmHg or heart rate > 120 bpm.
    • If ScvO2 is < 70% and Hct < 30%, give PRBC
      (consider potential sources of blood loss)
    • Insert arterial pressure line
    • Evaluate for Drotrecogin (Xigris) using Drotrecogin (Xigris) orders.

Initial Empiric Antimicrobial Therapy in Sepsis
Based on Suspected Primary Source

Principles:

  • Recommendations are for septic patients requiring critical care, not uncomplicated infections
  • Review past microbiology for known colonization with resistant organisms
  • Broad empiric coverage based on local microbiology and antimicrobial resistance patterns
  • De-escalate (narrow coverage) once cultures and susceptibilities available
  • Consult with pharmacy for renal dosing adjustment if CrCl < 50 mL/min or creatinine > 1.2

Allergies:  ______________________________________________________________

1.  Sepsis: site unknown

(MRSA, Resistant Gram-negative bacilli)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    PLUS
  • Imipenem 500 mg IV every 6 hours

    If previous colonization or concerns for highly resistant Gram-negative pathogen such as Acinetobacter, Pseudomonas, or ESBL, consider addition of:
  • Amikacin ________ mg (7.5 mg/kg) IV every 12 hours
    OR
  • Ciprofloxacin 400 mg IV every 12 hours (if renal impairment)

2.  Pneumonia

A.  Community-acquired, non-aspiration risk (MRSA, S. pneumonia, Legionella)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    OR
  • Linezolid 600 mg IV every 12 hours or Linezolid 600 mg PO every 12 hours
    PLUS
  • Ceftriaxone 1 Gram IV every 24 hours
    PLUS
  • Azithromycin 500 mg IV every 24 hours
               
    If aspiration risk:
  • Ampicillin-sulbactam 3 Grams IV every 6 hours (to replace Ceftriaxone)

B.  Healthcare-associated (MRSA, Gram-negative bacilli)

(Skilled Nursing Facility or hospital non-ICU, not known to be colonized with Acinetobacter)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    OR
  • Linezolid 600 mg IV every 12 hours or Linezolid 600 mg PO every 12 hours
    PLUS
  • Piperacillin-tazobactam 4.5 Grams IV every 6 hours

C.  Late-onset ventilator-associated (> 4 days of MV or hospitalization)

(MRSA, Resistant Gram-negative bacilli including Acinetobacter, Pseudomonas, ESBL)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    OR
  • Linezolid 600 mg IV every 12 hour or Linezolid 600 mg PO every 12 hour
    PLUS
  • Imipenem 500 mg IV every 6 hours

    If previous colonization or concern for highly resistant Gram-negative pathogen such as Acinetobacter, consider addition of:
  • Amikacin ________ mg (7.5 mg/kg) IV every 12 hours
    OR
  • Ciprofloxacin 400 mg IV every 12 hours (if renal impairment)

3.  Bloodstream

A.  Community (Injection drug use) or Hemodialysis; (MRSA, Gram-negative bacilli)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    PLUS
  • Gentamicin ________ mg (5 mg/kg) IV every 24 hours
    OR
  • Gentamicin ________ mg (1 mg/kg) every 48 hours after hemodialysis

B.  Hospital-acquired, Gram stain available

Gram positive awaiting culture identification:

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours   

Gram-negative awaiting culture identification:

  • □ Imipenem 500 mg IV every 6 hours

4.  Necrotizing Skin and Soft Tissue Infection

(MRSA, Group A strep, Clostridium sp and mixed anaerobes, Gram-negative bacilli)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    PLUS
  • Penicillin 4 million units IV every 4 hours
    PLUS
  • Clindamycin 1200 mg IV every 6 hours
    PLUS
  • Gentamicin ________ mg (5 mg/kg) IV every 24 hours

    If renal impairment:
    OR
  • Ciprofloxacin 400 mg IV every 12 hours (to replace Gentamicin)

5.  Intra-abdominal

A.  Community (Enteric Gram-negative bacilli, anaerobes)

  • Ampicillin-sulbactam 3 Grams IV every 6 hours

B.  Hospital-acquired (Resistant Gram-negative bacilli, anaerobes)

  • Piperacillin-tazobactam 3.375 Grams IV every 6 hours
    OR
  • Imipenem 500 mg IV every 6 hours

    If GPC in clusters on gram stain or concern for MRSA,
    add
  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours

6.  Neutropenic fever (oncology patients) and sepsis

(MRSA, Resistant Gram-negative bacilli including Acinetobacter, Pseudomonas, ESBL)

  • Vancomycin ________ Gram (15 mg/kg) IV every 12 hours
    PLUS
  • Imipenem 500 mg IV every 6 hours
    PLUS
  • Amikacin ________ mg (7.5 mg/kg) IV every 12 hours
    OR If renal impairment:
  • Ciprofloxacin 400 mg IV every 12 hours (to replace Amikacin)

    Empiric therapy with micafungin for suspected candidemia should be considered in septic patients with any of the following risk factors: total parenteral nutrition, prolonged broad-spectrum antibiotics, hematologic malignancy or transplant, femoral catheterization, or Candida colonization at multiple sites.
  • Micafungin 100 mg IV every 24 hours

Additional Orders:

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Read also: Sepsis: Initial Resuscitation Orders (For adult patients only)