Sepsis

1. See Also
   1. Sepsis in Children
   2. Bacteremia in Children
   3. Systemic Inflammatory Response Syndrome (SIRS)
2. Signs: Sepsis
   1. Hypotension
      1. Systolic Blood Pressure <90 mmHg or
      2. Mean arterial pressure <65 mmHg or
      3. Systolic Blood Pressure drop >40 mmgHg from baseline
   2. Decreased urine output (<0.5 ml/kg)
   3. Hypoxia
   4. Body Temperature abnormality
      1. Fever
      2. Hypothermia (<36 C): Poor prognostic sign
   5. Tachypnea
   6. Tachycardia
   7. Mental status changes
   8. Mottling of skin
3. Diagnosis: Criteria
   1. Sepsis
      1. Infection and
      2. Systemic Inflammatory Response Syndrome (SIRS) criteria positive (2 of 4 present)
   2. Septic Shock
      1. Infection and SIRS and
      2. Hypotension despite what should be adequate fluid Resuscitation (e.g. 2 Liters in an adult patient)
   3. Severe Sepsis
      1. Infection and SIRS and
      2. Markers of poor organ perfusion
         1. Increased serum lactate (>2 mmol/L)
         2. Capillary Refill >3 seconds
         3. Mottled skin
         4. Urine output <0.5 ml/kg for 1 hour or more
         5. Altered Mental Status or abnormal EEG
         6. Disseminated Intravascular Coagulation
         7. Acute Lung Injury or ARDS
         8. Platelet Count <100,000/ml
         9. Cardiac dysfunction
   4. Multiple Organ Dysfunction Syndrome (MODS)
      1. Most severe Sepsis with progressive organ dysfunction
      2. Parameters demonstrating progressive organ dysfunction
         1. Serum Creatinine
         2. Serum Bilirubin
         3. PO2 to FIO2 ratio
         4. GCS Score
         5. Platelet Count
4. Evaluation: Predictors of positive Blood Cultures (each doubles risk)
   1. Age over 30 years
   2. Heart Rate >90 bpm
   3. Temperature >37.8 C (>100 F)
   4. White Blood Cell count >12,000
   5. Central venous catheter
   6. Hospital stay >10 days
5. Evaluation: Occult source identification
   1. Meningitis
      1. Consider Lumbar Puncture
   2. Bacterial Endocarditis
      1. Consider Echocardiogram
   3. Acute Sinusitis
      1. Consider Sinus CT
   4. Cholecystitis
      1. Consider RUQ Ultrasound
6. Labs
   1. Blood Culture
   2. Urine Culture
   3. Complete Blood Count
      1. Leukocytosis (>12,000) or Leukopenia (<4000)
      2. Thrombocytopenia
   4. Chemistry panel
   5. Liver Function Tests
   6. Thyroid Stimulating Hormone
      1. Consider in refractory cases
   7. Serum Lactate (Lactic Acid)
      1. Marker of poor organ perfusion (see definition of severe Sepsis above)
      2. Obtain on all septic patients, when obtaining Blood Cultures and for those admitted with infection
      3. Serum Lactate >4 mmol/L is associated with increased mortality
      4. Higher serum lactates should be met with more aggressive management
7. Management: Antibiotics
   1. General
      1. Appropriate antibiotic choice and delivery
         1. Establish Emergency Department first dose protocols based on local sensitivities and infectious disease recommendations
         2. Simultaneous antibiotics without delay is ideal (obtain additional IV sites if needed)
      2. Start as early as possible (within 1 hour is goal)
         1. Early antibiotic delivery is most critical in severe Sepsis and Septic Shock
         2. Kumar (2006) Crit Care Med 34(6): 1589-96
         3. Gaieski (2010) Crit Care Med 38(4): 1045-53
      3. Consider source, but start broad spectrum antibiotic
         1. Source not identified in 20-30% of cases
      4. Remove obvious source within 6 hours (e.g. infected lines, drain abscess)
         1. Culture the tip of infected device
   2. Community acquired Pneumonia
      1. Ceftriaxone 1 gram IV (consider 2 grams IV in younger patients) and
      2. Macrolide or Fluoroquinolone such as Ciprofloxacin (Legionella coverage) and
      3. Vancomycin (MRSA coverage) indicated in Pneumonia with severe Sepsis
   3. Nosocomial Pneumonia (recent hospitalization)
      1. Cefepime or Imipenem or Piperacillin-Tazobactam (Zosyn) and
      2. Macrolide or Fluoroquinolone and
      3. Vancomycin (MRSA coverage)
   4. Urinary tract source
      1. Third generation Cephalosporin (e.g. Ceftriaxone) or
      2. Fluoroquinolone (growing resistance rates)
   5. Empiric therapy without obvious source (broad spectrum coverage)
      1. Piperacillin-Tazobactam (Zosyn) or Imipenem (or Cefepime with Metronidazole) and
      2. Vancomycin
   6. Gastrointestinal source suspected
      1. Beta-lactam/lactamase inhibitor and
      2. Metronidazole
      3. Consider Fluoroquinolone
   7. Central nervous system source
      1. Cephalosporins and
      2. Consider Vancomycin and
      3. Consider Acyclovir
8. Monitoring: Serum Lactate
   1. Serial serum lactate levels can help guide Resuscitation and response to management
      1. Consider obtaining at presentation and again at 3 and 6 hours
      2. Lactate clearance can drive goal directed therapy
      3. Jones (2010) JAMA 303(8):739-46
   2. Indications for more aggressive Sepsis management and monitoring with serial serum lactate levels
      1. Serum lactate >4 mmol/L
      2. Hypotension despite 2 Liters of IV fluids
      3. Hypotension responsive to IV fluids (may be a harbinger of later more severe episodes)
9. Management: Stabilization
   1. Oxygenation
      1. Maintain Oxygen Saturation >90%
   2. Ventilation (BIPAP or Mechanical Ventilation)
      1. Indicated for septic patients with Oxygen Saturation <90% or significant Tachypnea despite High Flow Oxygen
      2. Use a low threshold for intubation of the elderly patient with severe Sepsis
      3. Tidal Volumes 6 cc/kg of ideal body weight (up to 8 cc/kg/IBW)
   3. Volume Resuscitation (Total of 2-10 liters NS or LR)
      1. Start with 1 liter of isotonic crystalloid (NS or LR) in first 30 minutes
      2. Goals
         1. Inferior Vena Cava Ultrasound with <50% collapse on inspiration
         2. Serial serum lactate decrease (see above)
         3. Central Venous Pressure >8 (>12 if on mechanical Ventilator)
         4. Central venous oxygen level >70 mmHg
         5. Systolic Blood Pressure >90 mmHg or mean arterial pressure >65-70 mmHg
            1. Blood Pressure is an unreliable marker of Sepsis severity and response to therapy
            2. Blood Pressure can be normal or high immediately before decompensated shock
            3. Patient positioning is also an unreliable marker to predict fluid Resuscitation response
               1. Technique involves raising legs and observing for increase in Blood Pressure
   4. Transfusion
      1. Indications are controversial
         1. Most current guidelines suggest transfusion for Hemoglobin <7 g/dl (Hematocrit <21)
         2. Other studies suggest transfusion for Hemoglobin <10 g/dl (Hematocrit <30)
      2. More important after the initial stabilization
      3. Mortality increases for transfusion for mild Anemia
      4. Herbert (1999) N Engl J Med 340:409-17
   5. Blood Sugar management
      1. Conventional therapy (non-intensive Blood Sugar management: 144-180) is safer in critically ill
         1. (2009) N Engl J Med 360:1283-97
   6. Corticosteroids
      1. Hydrocortisone at physiologic dose (200-300 mg)
      2. Indicated for severe Sepsis (e.g. requiring 2 pressors)
      3. Efficacy (variable evidence)
         1. Marked mortality benefit from Corticosteroids in severe Sepsis
            1. Annane (2002) JAMA 288(7):862-71
         2. Has short-term benefit in duration and severity
            1. Annand (2009) JAMA 301:2362
         3. CORTICUS trial found no benefit to Corticosteroids
            1. Sprung (2008) NEJM 358(2): 111-24
   7. Central venous access indications (e.g. internal jugular venous catheterization)
      1. Vasopressor delivery (Norepinephrine, Epinephrine)
      2. Monitoring
         1. Sepsis catheters (e.g. Vigileo) can monitor central venous Oxygen Saturation (ScvO2)
         2. Monitoring may be done instead non-invasively (e.g. follow IVC Ultrasound)
   8. Vasopressors
      1. Target perfusion
         1. Central venous pressure 8-12 mmHg
         2. Mean arterial pressure >65 mmHg
         3. Urine output >0.5 ml/kg/h
         4. Mixed venous Oxygen Saturation >70%
      2. First agent
         1. Norepinephrine (preferred first line)
            1. Start at 0.2 mcg/kg/min (range 0.1 to 1 mcg/kg/min)
         2. Phenylephrine
            1. Indicated if pressors needed prior to securing central venous access
            2. Can bridge with less peripheral vein complications than Norepinephrine until central access is obtained
      3. Second agent (added to first)
         1. Indicated for Hypotension despite fluid bolus and other additional measures listed below
         2. Epinephrine
            1. Indicated for combined Vasopressor and inotropic support
         3. Vasopressin 0.04 units/minute
            1. Indicated for additional Vasopressor support
      4. Pressors to avoid in Sepsis
         1. Dopamine
            1. No longer recommended in Sepsis
            2. Dosing range: 2-20 mcg/kg/min
            3. Do not use "renal dose" Dopamine - misnomer
   9. Additional measures when poor response to Resuscitation efforts
      1. Consider additional intravenous fluids (if suspect still volume down)
         1. Give additional 1-2 Liters on top of already administered 2 liters
      2. Manage Hypocalcemia (based on Ionized Calcium or Corrected Serum Calcium for albumin)
         1. Replace with Calcium Gluconate or Calcium Chloride if hypocalcemic
      3. Occult Hemorrhage (e.g. Gastrointestinal Bleeding)
         1. Stop bleeding and Consider pRBC transfusion if actively bleeding or Hemoglobin <7.0 mg/dl
      4. Consider inotrope for CHF
         1. Dobutamine 2.5 mcg/kg/min
         2. Obtain beside Echocardiogram if available
         3. Indicated for poor perfusion
            1. SvcO2 <70% or Lactic Acid fails to improve
            2. Despite o2sat >90% and MAP>65
      5. Consider Hypothyroidism
   10. Other agents
       1. Activated Protein C
       2. Drotecogin Alfa (Xigris)
10. Prognosis
    1. Positive Blood Culture
       1. Confers 150% increase in mortality risk
11. Resources
    1. Surviving Sepsis Protocol
       1. http://www.annalsofintensivecare.com/content/pdf/2110-5820-1-17.pdf
12. References
    1. Orman and Weingart in Majoewsky (2012) EM:RAP 12(10): 4-7
    2. Khoujah (2013) Crit Dec Emerg Med 27(4):12-21
    3. Marik (2011) Annals of Intensive Care 1:17
    4. Jaimes (2004) Clin Infect Dis 38:357-62