Therapeutics - Sepsis 1

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Therapeutics - Sepsis 1
2014-11-16 15:07:30
Therapeutics Sepsis
Therapeutics - Sepsis
Therapeutics - Sepsis
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  1. What is SIRS?
    • A clinical response arising from a nonspecific insult, with at least 2 of the following:
    • Temperature > or = to 38oC or < or = to 36oC
    • HR >/=90 beats/min
    • Respirations >/=20/min
    • WBC >/=12,000 or 10% immature neutrophils (bands)
  2. What is Sepsis?
    SIRS with a presumed or confirmed infectious process
  3. What constitutes severe sepsis?
    • Sepsis with at least one organ system failing
    • [Cardiovascular (refractory hypotension), Renal, Respiratory, Hepatic, Hematologic, CNS,Metabolic acidosis]
    • Leading to shock
  4. What age group is most susceptible to sepsis?
    • Elderly 60/70/80s
    • Young people with considerable co-morbidities
  5. What are the GENERAL VARIABLE diagnostic criteria for Sepsis?
    • Fever (> 38.3°C) OR Hypothermia (core temperature < 36°C)
    • Heart rate > 90/min–1 or more than two SD above the normal value for age
    • Tachypnea
    • Altered mental status
    • Significant edema or 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
  6. What are the Inflammatory diagnostic criteria for sepsis?
    • Leukocytosis (WBC count > 12,000 µL–1) OR Leukopenia (WBC count < 4000 µL–1)
    • Normal WBC count with greater than 10% immature forms (bands)
    • Plasma C-reactive protein more than two SD above the normal value
    • Plasma procalcitonin more than two SD above the normal value
  7. What are the Inflammatory diagnostic criteria for sepsis?
    Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults or less than two SD below normal for age)
  8. What are the Hemodynamic diagnostic criteria for sepsis?
    Arterial hypoxemia (Pao2/FIO2 < 300)
  9. What are the Organ dysfunction diagnostic criteria for sepsis?
    • 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 s)
    • Ileus (absent bowel sounds)
    • Thrombocytopenia (platelet count < 100,000 µL–1)
    • Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 µmol/L)
  10. What are the Tissue perfusion diagnostic criteria for sepsis?
    • Hyperlactatemia (> 1 mmol/L)
    • Decreased capillary refill or mottling
  11. What are the diagnostic criteria for Severe sepsis?
    • 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)
  12. In Grading of evidence, an “A” means what?
    (high) RCTs (randomized controlled trial)
  13. In Grading of evidence, an “B” means what?
    • Moderate
    • Down-graded RCTs or
    • Up-graded observational studies
  14. In Grading of evidence, an “C” means what?
    (low) Observational studies
  15. In Grading of evidence, an “D” means what?
    (very low) Case series and expert opinion
  16. In Grading of evidence, an “UG” means what?
    UG is ungraded (recommendation not conducive for Grade process)
  17. What is the basic framework for treating sepsis?
    • Initial resuscitation
    • Screening for sepsis and performance improvement
    • Diagnosis
    • Antimicrobial therapy
    • Source control
    • Infection prevention
  18. What are the goals for the first 6 hours of therapy in a sepsis patient with sepsis induced hypoperfusion?
    • Goals during the first 6 hrs of resuscitation:
    • Central venous pressure 8–12 mm Hg
    • Mean arterial pressure (MAP) ≥ 65 mm Hg
    • Urine output ≥ 0.5 mL/kg/hr
    • Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C)
  19. What constitutes sepsis induced hypoperfusion?
    Hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L
  20. Does early goal directed therapy for sepsis decrease 28 day mortality?
    Yes, though results have been hard to copy
  21. What should be done to diagnose sepsis once it is suspected?
    • 1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins/ within 1st hour of presentation) in the start of antimicrobial(s) (grade 1C)
    • At least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C)
    • 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available and invasive candidiasis is in differential diagnosis of cause of infection
    • Imaging studies performed promptly to confim a potential source of infection (UG)
  22. In general, how should antimicrobial therapy should be administered once sepsis is suspected?
    • Antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C)
    • Initial empiric anti-infective therapy (broad spectrum=bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source (grade 1B)
    • Antimicrobial regimen should be reassessed daily for deescalation (grade 1B)
    • Use of low procalcitonin levels or similar biomarkers in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C)
    • Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, MDR bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B)
    • De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known
  23. What are the normal empiric anbiotic therapies for Sepsis?
    Zosyn, vanco and quinolone
  24. Severe infections associated with respiratory failure and septic shock caused by P. aeruginosa bacteremia, should be treated with what general antibiotic regimen?
    Combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone
  25. Patients with septic shock from bacteremic Streptococcus pneumonia, should be treated with what general antibiotic regimen?
    Combination of beta-lactam and macrolide