Infectious Disease Book



Aka: Sepsis, Septic Shock, Septicemia, Bacteremia in Adults, Septicemia in Adults, Surviving Sepsis Campaign, Sepsis Bundle, Early Goal Directed Therapy
  1. See Also
    1. Sepsis in Children
    2. Bacteremia in Children
    3. Systemic Inflammatory Response Syndrome (SIRS)
    4. Sequential Organ Failure Assessment Score (SOFA Score)
    5. qSOFA Score
  2. Epidemiology: United States
    1. Incidence: 750,000/year
    2. Prevalence: 3 cases per 1000
    3. In-Hospital Mortality: 200,000/year (20%)
  3. Pathophysiology
    1. Inflammatory response (and antagonizing anti-inflammatory response)
    2. Endothelial damage
    3. Increased vascular permeability
    4. Coagulation Pathway activation
    5. Impaired tissue oxygenation
    6. Decreased vasopressin, Thyroxine, cortisol and Growth Hormone
  4. Risk Factors
    1. Age over 65 years
      1. Sepsis risk >13 fold increased risk
      2. Sepsis mortality risk >2 fold increased risk
    2. Malnutrition
    3. Chronic illness
    4. Immunosuppression
    5. Recent surgery or hospitalization
    6. Indwelling catheter or other device
  5. Signs: Sepsis
    1. Constitutional changes
      1. Body Temperature abnormality
        1. Fever
        2. Hypothermia (<36 C): Poor prognostic sign
      2. Diaphoresis
      3. Rigors
      4. Myalgias
      5. Malaise
    2. Cardiovascular changes
      1. Occurs with myocardial depression and intravascular fluid redistribution
      2. Hypotension
        1. Systolic Blood Pressure <90 mmHg or
        2. Mean arterial pressure <65 mmHg or
        3. Systolic Blood Pressure drop >40 mmgHg from baseline
        4. Hypotension at presentation confers a 2 fold increased mortality risk
      3. Cold and clammy skin
      4. Mottling of skin
      5. Decreased Capillary Refill 3 seconds or greater
      6. Tachycardia
      7. Decreased Urine Output (<0.5 ml/kg)
    3. Respiratory Findings
      1. Hypoxia, Dyspnea or Tachypnea
      2. Pharyngitis, Dysphagia or Stridor
      3. Cough, Pleuritic Chest Pain
      4. Abnormal lung auscultation (consolidation)
    4. Gastrointestinal findings
      1. Abdominal Pain, distention and rigidity
      2. Decreased Bowel Sounds
      3. Upper Gastrointestinal Bleeding (significant blood loss in Sepsis is rare)
      4. Vomiting
      5. Diarrhea
    5. Genitourinary Findings
      1. Dysuria, frequency, Hematuria, pyuria
      2. Costovertebral Angle Tenderness
      3. Pelvic Pain
      4. Vaginal Discharge or Vaginal Bleeding
    6. Neurologic changes
      1. Mental status changes
      2. Agitation may be only presenting neurologic change in elderly
      3. Headache
    7. Dermatologic changes
      1. Direct Bacterial Infection (responsible for Sepsis)
        1. Abscess
        2. Cellulitis
        3. Necrotizing Fasciitis
      2. Vasculitis, microembolic, or Disseminated Intravascular Coagulation (DIC) induced lesions
        1. Ecchymosis
        2. Petechiae or Purpura
          1. Consider Neisseria Meningitidis
          2. Consider Rocky Mountain Spotted Fever
  6. Diagnosis: Criteria
    1. Sepsis
      1. Infection AND
      2. Systemic Inflammatory Response Syndrome (SIRS criteria) positive (2 of 4 present)
        1. SOFA Score and qSOFA Score are recommended to replace SIRS Criteria in Sepsis-3 Guidelines
        2. SOFA Score 2 or more is consistent with Sepsis
        3. qSOFA Score 2 or more is consistent with Sepsis
    2. Severe Sepsis
      1. Infection and SIRS (or SOFA Score or qSOFA Score) AND
      2. Markers of poor organ perfusion
        1. Increased serum lactate (>4 mmol/L cut-off)
        2. Capillary Refill 3 seconds or greater
        3. Mottled skin
        4. Urine Output <0.5 ml/kg for 1 hour or more (or renal replacement therapy)
        5. Abrupt onset of Altered Level of Consciousness or abnormal EEG
        6. Disseminated Intravascular Coagulation
        7. Acute Lung Injury or ARDS
        8. Platelet Count <100,000/ml
        9. Cardiac dysfunction (based on Echocardiogram)
    3. Septic Shock
      1. Infection and SIRS (or SOFA Score or qSOFA Score) AND
      2. Full fluid Resuscitation trial (e.g. 40-60 ml/kg or 2 Liters in an adult patient or wedge pressure 12-20 mmHg) AND
      3. Hypotension despite what should be adequate fluid Resuscitation
        1. Mean arterial pressure <60 mmHg (<80 mmHg if prior Hypertension) or
        2. Vasopressor (Dopamine, Norepinephrine, Epinephrine) required for pressure support
    4. Refractory Septic Shock
      1. Septic Shock AND
      2. High Vasopressor dose required to maintain Mean arterial pressure <60 mmHg (<80 mmHg if prior Hypertension)
        1. Dopamine >15 mcg/kg/min OR
        2. Norepinephrine or Epinephrine >0.25 mcg/min
    5. 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
  7. Differential Diagnosis
    1. Hypovolemia
    2. Acute blood loss
    3. Acute Myocardial Infarction
    4. Acute Pancreatitis
    5. Transfusion Reaction
    6. Diabetic Ketoacidosis
    7. Adrenal Insufficiency
    8. Acute Pulmonary Embolism
      1. Consider evaluation early in course
  8. 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
  9. Evaluation: Sources
    1. Most common organisms
      1. Bacteria are responsible for most Sepsis cases
      2. Gram-positive Bacteria account for up to 50% of all Sepsis cases
    2. Most common sources (80% of cases)
      1. Respiratory infection
        1. Pneumonia is most common cause of Sepsis
      2. Genitourinary infection
        1. Urinary Tract Infection (Pyelonephritis)
        2. Consider Septic Abortion in pregnancy or Chorioamnionitis in postpartum patients
      3. Gastrointestinal infection
      4. Skin and Soft Tissue Infection
    3. Occult sources
      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
  10. Labs
    1. Cultures
      1. Obtain within 45 minutes of presentation
      2. Do not delay antibiotics if cultures cannot be obtained within 45 minutes
      3. If surgical source culture is required, percutaneous, minimally invasive approach is preferred
        1. Consult with local surgery or Interventional Radiology
      4. Sources
        1. Blood Culture
          1. Rigors, high fever, and appetite loss are most predictive of positive Blood Cultures
        2. Urine Culture
        3. CSF Culture (if indicated)
        4. Central Line or PICC Line (if present, draw a culture through the line prior to removal)
    2. Complete Blood Count
      1. Leukocytosis (>12,000) or Leukopenia (<4000)
        1. Neutrophil predominance is typical
        2. Neutropenia is uncommon (except for chronic Alcoholism and the elderly)
      2. Thrombocytopenia
        1. Typically precedes DIC
        2. Platelet Count drop >30% is associated with increased ICU-mortality
      3. Hemolytic Anemia (microangiopathic)
        1. Present in DIC
    3. Coagulation Studies (INR, PTT)
      1. Coagulopathy in DIC
    4. Chemistry panel
      1. Hyperglycemia (Sepsis-induced Insulin Resistance)
      2. Acute Renal Failure
    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
      5. Measurement of serial Lactic Acid levels should be performed on the same machine
        1. Most accurate methods are with Arterial Blood Gas machine (even for venous sample)
        2. Weingart and Orman in Majoewsky (2013) EM:Rap 13(10):5
    8. Urinalysis
      1. Urinary sediment (in association with Anuria or Oliguria)
        1. Acute Tubular Necrosis
  11. Imaging
    1. Chest XRay
    2. CT Abdomen and Pelvis
      1. Indicated for intraabdominal or pelvic findings or suspected GI Source
    3. Echocardiogram
      1. Indicated for suspected endocarditis with septic emboli (e.g. IVDA)
  12. Management: Sepsis Decision Pathway
    1. Indications
      1. Modified SIRS Criteria 2 or more AND suspected infection
    2. Step 1: Emergency Department triage measures
      1. Serum Lactic Acid
      2. Mean arterial pressure
      3. Triage may also draw rainbow lab tubes and one Blood Culture bottle and set aside
        1. Triage Sepsis alert in the EMR significantly reduces time to fluids and antibiotics
        2. Hayden (2016) Am J Emerg Med 34(1): 1-9 +PMID:26386734 [PubMed]
    3. Step 2: Mean Arterial Pressure <65 mmHg
      1. Immediate rooming
      2. Initial stabilization
        1. Initiate 30 cc/kg IV crystalloid bolus over 30 minutes
        2. Obtain 2 sets of Blood Cultures as well as specific source cultures
        3. Initiate broad spectrum antibiotics
      3. Reassess mean arterial pressure and consider IVC Ultrasound
        1. Go to Steps 3a-d
    4. Step 3a: Mean Arterial Pressure <65 mmHg despite 2 Liters crystalloid in Step 2 (Septic Shock)
      1. Obtain Central Line access
      2. Empiric second round of fluid Resuscitation (or base on IVC Ultrasound)
        1. Age <75 AND no history of CHF: Give 4 L IV fluids within first 6 hours
        2. Age >75 OR history of CHF: Give 3 L IV fluids within first 6 hours
      3. Start Vasopressors (e.g. Norepinephrine)
        1. Target mean arterial pressure (MAP) >65 mmHg
      4. Disposition to Intensive Care Unit
    5. Step 3b: Mean Arterial Pressure >65 mmHg AND Serum Lactic Acid 4 mmol/L or more (Severe Sepsis)
      1. Obtain 2 peripheral IVs
        1. A single large gauge IV (e.g. 16g) may be sufficient
        2. Central Line access may be considered (optional)
      2. Initiate 2 Liter crystalloid bolus
        1. Empiric second round of fluid Resuscitation (or base on IVC Ultrasound)
        2. Age <75 AND no history of CHF: Give 4 L IV fluids within first 6 hours
        3. Age >75 OR history of CHF: Give 3 L IV fluids within first 6 hours
      3. Obtain 2 sets of Blood Cultures as well as specific source cultures
      4. Initiate broad spectrum antibiotics
      5. Admit to intensive care unit
      6. Repeat serum Lactic Acid after fluid Resuscitation
    6. Step 3c: Mean Arterial Pressure >65 mmHg AND Serum Lactic Acid 2-4 mmol/L (Sepsis)
      1. Initiate 2 Liter crystalloid bolus
      2. Obtain specific source cultures
        1. Consider 2 sets of Blood Cultures (per hospital policy, discuss with admitting hospitalist)
      3. Initiate targeted antibiotics for suspected source
      4. Repeat serum Lactic Acid after initial crystalloid bolus
        1. Serum lactate clearance >10% (percent drop in lactate from first value)
          1. Admit to regular medical ward
        2. Serum lactate clearance <10% (percent drop in lactate from first value)
          1. Repeat crystalloid bolus 1 Liter
          2. Admit to intensive care
    7. Step 3d: Mean Arterial Pressure >65 mmHg AND Serum Lactic Acid <2 mmol/L (Uncomplicated Sepsis)
      1. Antibiotics as indicated
      2. Fluid Resuscitation as indicated
    8. References
      1. Berg and Orman in Herbert (2015) EM:Rap 15(8): 8-11
  13. Management: Antibiotic Overall Approach
    1. Appropriate antibiotic choice and delivery
      1. Establish Emergency Department first dose protocols
        1. Based on local sensitivities and infectious disease recommendations
      2. Simultaneous antibiotics without delay is ideal (obtain additional IV sites if needed)
      3. Vancomycin dosing should be calculated based on weight
        1. Dose: 15-20 mg/kg total body weight (up to 2 grams)
    2. Start antibiotics as early as possible (within 1 hour is goal)
      1. Early antibiotic delivery is most critical in severe Sepsis and Septic Shock
      2. Mortality increases with each hour of antibiotic delay
      3. Kumar (2006) Crit Care Med 34(6): 1589-96 [PubMed]
      4. Gaieski (2010) Crit Care Med 38(4): 1045-53 [PubMed]
      5. Seymour (2017) N Engl J Med 376(23):2235-44 [PubMed]
    3. Consider source, but start broad spectrum antibiotic
      1. Source not identified in 20-30% of cases
      2. Re-evaluate antibiotic selection daily
    4. Empiric therapy without obvious source (broad spectrum coverage)
      1. Vancomycin 15-20 mg/kg (up to 2 g) every 12 hours AND
      2. Choose one of the following
        1. Piperacillin-Tazobactam (Zosyn, if low Prevalence ESBL) OR
        2. Imipenem 1 g IV every 8 hours (or Meropenem or Doripenem) OR
        3. Cefepime 2 g IV every 8 hours with Metronidazole
      3. Consider adding Aminoglycoside (e.g. Gentamicin)
    5. Remove obvious source within 6 hours (e.g. infected lines, drain abscess)
      1. Culture the tip of infected device
    6. Consider risk factors for multi-drug resistance
      1. Recent antibiotics
      2. Recent wound care
      3. Hospitalization in last 3 months
    7. Consider initial antibiotics that may be given as IV bolus
      1. Some beta-lactams, Cephalosporins and Aminoglycosides may be administered IV bolus
      2. Larger molecule antibiotics (e.g. Vancomycin, Quinolones) may not be given IV bolus
        1. Risk of adverse reactions
      3. References
        1. Lin and Spaulding in Herbert (2016) EM:Rap 16(3): 6-7
        2. Garrelts (1992) Pharmacoeconomics 1(2): 116-23 +PMID:10172048 [PubMed]
    8. Avoid delay in subsequent antibiotic doses
      1. Antibiotic second dose delays are common in transition from the Emergency Department to admission
      2. Leisman (2017) Crit Care Med 45(6): 956-65 +PMID:28328652 [PubMed]
  14. Management: Antibiotics - Empiric by Site of Infection and Risk Factors
    1. Unknown source
      1. See empiric therapy described above
    2. Community Acquired Pneumonia
      1. See Pneumonia Management
      2. Empiric Antibiotic Regimen
        1. Piperacillin-Tazobactam 4.5 g IV q6-8h or Aztreonam 2 g IV q8h (or Ceftriaxone) AND
        2. Azithromycin or Levofloxacin 750 IV q24h, Moxifloxacin 400 IV q24h for Legionella AND
        3. Vancomycin (or Linezolid) for MRSA coverage in Pneumonia with severe Sepsis
      3. Evaluate Pleural Fluid
        1. Drain empyema if present
    3. Nosocomial Pneumonia (recent hospitalization)
      1. See Nosocomial Pneumonia
      2. Vancomycin (MRSA coverage) AND
      3. Cefepime or Meropenem or Piperacillin-Tazobactam (Zosyn) AND
      4. Consider adding Tobramycin or Levofloxacin or Ciprofloxacin (if dictated by local resistance)
    4. Urinary tract source
      1. See Acute Pyelonephritis
      2. Cover organisms associated with complicated Urinary Tract Infection
        1. Enterococcus
        2. Pseudomonas aeruginosa
        3. Staphylococcus aureus
      3. Empiric antibiotics
        1. Piperacillin/Tazobactam (Zosyn) 4.5 g every 6-8 hours (or Aztreonam 2 g IV q8h) AND
        2. Gentamicin 7 mg/kg every 24 hours
          1. If Enterobacteriaceae (nitrate positive or by Gram Stain)
            1. May subsititue Ciprofloxacin or Third generation Cephalosporin
          2. Otherwise avoid fluouroquinolones in UTI with Sepsis due to increasing resistance
      4. Imaging indications
        1. Evaluate for obstruction (Nephrolithiasis)
    5. Intra-abdominal or pelvic source suspected
      1. Empiric antibiotic coverage
        1. First-line single agents (choose one)
          1. Piperacillin-Tazobactam (Zosyn) 4.5 g every 6-8 hours OR
          2. Imipenem/Cilastin 250-500 mg IV every 6-8 hours OR
          3. Meropenem 1 g IV every 8 hours OR
          4. Cefepime 2 g IV every 12 hours (alternative option)
        2. Consider adding additional Gram Negative coverage
          1. Gentamicin 7 mg/kg every 24 hours OR
          2. Ciprofloxacin 400 mg IV every 12 hours
        3. Consider Metronidazole 500 mg IV every 6-8 hours
        4. Consider Vancomycin if MRSA suspected
      2. Early surgical Consultation
        1. Consider percutaneous or open drainage of infection source
    6. Meningitis Suspected
      1. See Bacterial Meningitis Management
      2. Vancomycin 15-20 mg/kg (up to 2 g) every 12 hours AND
      3. Ceftriaxone 2 g every 12 hours (or Cefotaxime)
      4. Consider Ampicillin 2 g every 4 hours (for listeria if immunocompromised or over age 50 years)
      5. Consider adding Dexamethasone 10 mg every 6 hours (for pneumococcal Meningitis)
      6. Consider adding Acyclovir 10 mg/kg every 8 hours (if herpes Encephalitis suspected)
      7. Consider adding Rifampin
    7. Skin and Soft Tissue Infection or Necrotizing Fasciitis
      1. See Cellulitis
      2. See Necrotizing Fasciitis
      3. Empiric antibiotics
        1. Vancomycin 15-20 mg/kg (up to 2 g) every 12 hours AND
        2. Piperacillin/Tazobactam (Zosyn) 4.5 g every 6-8 hours AND
        3. Clindamycin 900 mg every 8 hours (esp. if toxin release, e.g. Necrotizing Fasciitis, gangrene)
      4. Surgical Consultation indications
        1. Necrotizing Fasciitis suspected
        2. Deep abscess
    8. Post-splenectomy
      1. Ceftriaxone 2 g IV every 24 hours (every 12 hours if Meningitis) OR
      2. Piperacillin-Tazobactam (Zosyn) 4.5 g IV every 6-8 hours OR
      3. Carbapenem (e.g. Meropenem) OR
      4. Clindamycin OR
      5. Fluoroquinolone (e.g. Levofloxacin OR Moxifloxacin)
        1. Do not use in Dog Bite (risk of Capnocytophagia, with Fluoroquinolone resistance)
    9. Febrile Neutropenia
      1. See Febrile Neutropenia
      2. Vancomycin 15-20 mg/kg (up to 2 g) IV every 12 hours AND
      3. Zosyn 4.5 g IV q6-8 hours (or Aztreonam 2 g IV q8 hours) AND
      4. Gentamycin 7 mg/kg every 24 hours (or Levofloxacin 750 mg IV q24 h)
    10. Vascular Device Infection
      1. Vancomycin 15-20 mg/kg (up to 2 g) IV every 12 hours AND
      2. Piperacillin-Tazobactam (Zosyn) 4.5 g IV q6-8 hours (or Aztreonam 2 g IV q8 hours) AND
    11. Illicit Drug use
      1. Include Vancomycin in regimen (to cover MRSA)
    12. Petechial rash
      1. Include Ceftriaxone 2 g IV q12 hours
      2. Cover Neisseria Meningitidis and Rocky Mountain Spotted Fever (also consider DIC)
    13. Acute Diarrheal Syndrome
      1. Metronidazole 500 mg IV every 6 hours AND
      2. Vancomycin 250 mg orally every 6 hours (OR enema 1 g/500 ml rectally every 8 hours)
  15. 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 [PubMed]
    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)
  16. Management: Stabilization - General Measures
    1. Surviving Sepsis Guidelines in 2018
      1. Criticism that prior 3 and 6 hour bundles have been compressed into 1 hour
      2. Weak evidence to support the aggressive changes and increased risk of adverse effects
      3. Swaminathan, Spiegel, Farkas in Herbert (2018) EM:Rap 18(10): 1-2
    2. Precautions: ProCESS Trial results (2014)
      1. Pragmatic aggressive care (fluids, antibiotics, pressors)
        1. As effective as Early Goal Directed Therapy (with Svo2 monitoring)
      2. Emphasis
        1. Aggressive fluid hydration starting with 30 cc/kg bolus (4.4 Liters on average)
        2. Early antibiotics
        3. Vasopressors (44%)
        4. Central Lines (>50% of cases)
      3. However, specialized Sepsis catheters with Svo2 monitoring are not required
        1. Did not improve outcomes beyond otherwise aggressive care
      4. References
        1. (2014) N Engl J Med 370(18): 1683-93 [PubMed]
    3. Oxygenation
      1. Maintain Oxygen Saturation >90%
      2. Maintain superior vena cava Oxygen Saturation (Scvo2) >70%
      3. Maintain mixed venous Oxygen Saturation (Svo2) >65%
    4. 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)
      4. Maintain median inspiratory plateau pressure (IPP) <30 cm H2O in ventilated patients
      5. Be alert for transient Hypotension with intubation in Sepsis (consider Push Dose Pressor)
    5. Central venous access indications (e.g. internal jugular venous catheterization)
      1. Vasopressor delivery (Norepinephrine, Epinephrine)
      2. Unreliable Intravenous Access
      3. Monitoring (controversial - see above)
        1. Monitoring may be done instead non-invasively (e.g. follow IVC Ultrasound)
        2. Sepsis catheters (e.g. Vigileo) can monitor central venous Oxygen Saturation (ScvO2)
          1. ProCESS Trial showed no added benefit to otherwise aggressive Sepsis management (see above)
  17. Management: Stabilization - Volume Resuscitation
    1. Crystalloid selection
      1. Consider Lactated Ringers instead of NS or consider Plasma-Lyte after several liters of NS have been given
      2. Normal Saline (NS) increases acidosis in contrast to Lactated Ringers (LR)
        1. NS in the large quantities used for Sepsis, may have adverse renal and inflammatory effects
    2. Crystalloid volume
      1. Start with 1 liter of isotonic crystalloid (NS or LR) in first 30 minutes
        1. Improved survival when crystalloid bolus started within first 30 minutes
        2. Liesman (2016) Ann Emerg Med 68(3): 298-311 +PMID:27085369 [PubMed]
      2. Typical total initial crystalloid bolus of 30cc/kg (2-3L in 70-100 kg adult) within first 3 hours
      3. Typical total crystalloid fluid over first 24-48 hours may approach 5-7 Liters
      4. Overall Crystalloid Total: 2-4 Liters initially of NS or LR (up to 10 L have been used in some cases)
    3. 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. Precautions
      1. Aggressive fluid hydration is key to Sepsis management, even in those at risk of Fluid Overload (CHF, CKD)
        1. CHF and CKD patients have decreased mortality with aggressive fluid hydration in Sepsis
        2. Aggressive fluid hydration offers significant benefit even if Lactic Acid 2-4 (intermediate range)
        3. Levy (2016) Am J Respir Crit Care Med 193(11):1195-6 +PMID:27248586 [PubMed]
        4. Liu (2016) Am J Respir Crit Care Med 193(11): 1264-70 +PMID:26695114 [PubMed]
      2. Avoid Albumin 5% (500 ml bolus) or similar colloid (lack of efficacy)
        1. Previously indicated for high volume crystalloid Resuscitation (e.g. >4-6 Liters)
        2. Was postulated to help prevent fluid third spacing
        3. No benefit to albumin over isotonic saline in Sepsis (as of 2014)
          1. Caironi (2014) N Engl J Med 370(15): 1412-21 [PubMed]
      3. Avoid hyroxyethyl starch
        1. Initially promoted to correct Metabolic Acidosis from high volume crystalloid Resuscitation
        2. Hydroxyethyl starch is associated with increased risk of bleeding and Renal Failure
    5. Transfusion: pRBC Indications
      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)
          1. Goal Hematocrit >30% if central venous Oxygen Saturation <70% after restoring mean arterial pressure
      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 [PubMed]
      5. Rivers (2001) N Engl J Med 345(19): 1368-77 [PubMed]
    6. Transfusion: Platelet Indications
      1. Platelet Count <5,000/ul or
      2. Platelet Count 5,000 to 30,000/ul and significant bleeding risk or
  18. Management: Stabilization - Vasopressors
    1. Precaution
      1. Intravenous Fluids should be maximized prior to starting first pressor (>2 L) and second pressor (4 L)
      2. Vasopressors ultimately require central venous access
        1. Vasopressors may be initiated peripherally during stabilization
          1. Temporize until Central Line access is obtained (typically <1-2 hours)
          2. Complication rates are higher with peripheral Vasopressor (but not life threatening)
          3. Risk outweighed by the benefit of initiating Vasopressors without delay
            1. Indicated after failed response to aggressive hydration
          4. Ricard (2013) Crit Care Med 41(9): 2108-15 [PubMed]
        2. Peripheral extravasation of Vasopressors may result in severe local tissue necrosis
          1. Potential with risk of Compartment Syndrome
          2. Vasopressors in peripheral lines must be observed very closely
            1. Frequently recheck for extravasation (e.g. q10-15 min)
          3. Plan for immediate response to extravasation including available antidote (e.g. phentolamine)
    2. Target perfusion
      1. Central Venous Pressure (CVP) 8-12 mmHg
      2. Mean arterial pressure (MAP) >65 mmHg
      3. Urine Output >0.5 ml/kg/h
      4. See venous oxygenation goals (Scvo2 or Svo2) above
    3. First agent
      1. Norepinephrine (preferred first line)
        1. Start at 0.2 mcg/kg/min (range 0.1 to 1 mcg/kg/min)
        2. Titrate to adequate perfusion parameters including MAP (doses up to 1 mcg/kg/min may be required)
        3. May be initiated via peripheral access (while awaiting central access)
          1. Observe closely for extravasation and move to Central Line within 1-2 hours
          2. With large bore, reliable peripheral IVs, Norepinephrine has been used peripherally for 24 hours
    4. 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
        2. Indicated when bedside Echocardiogram demonstrates poor cardiac contractility (Cardiomyopathy)
      3. Vasopressin 0.03 units/minute (previously 0.04 units/min was recommended)
        1. Indicated for additional Vasopressor support
        2. Indicated when bedside Echocardiogram demonstrates good cardiac contractility with adequate inotropy
    5. Agents to generally avoid in most Sepsis cases
      1. Avoid Dopamine in Sepsis
        1. Dosing range: 2-20 mcg/kg/min
        2. Do not use "renal dose" Dopamine - misnomer
        3. No longer recommended in Sepsis due to less effective than Norepinephrine and arrhythmogenic
        4. De Backer (2010) N Engl J Med 362(9): 779-89 [PubMed]
      2. Avoid Phenylephrine in Sepsis
        1. Lacks inotropic activity and overall efficacy in Sepsis shock when compared with Norepinephrine
        2. Has been used to bridge Vasopressor use until securing central venous access
          1. However Norepinephrine can be safely used for hours until central access has been obtained
        3. Has also been used to avoid Norepinephrine in Tachycardia
          1. However, Norepinephrine may still be used despite Tachycardia
        4. References
          1. Orman and Weingart in Herbert (2016) EM:Rap 16(8):7-8
  19. Management: Stabilization - Adjunctive measures
    1. Nutrition
      1. Maintain adequate nutrition
        1. Consider oral Gastric Tube or nasal Gastric Tube
        2. Consider TPN
      2. Blood Glucose
        1. Conventional therapy (non-intensive Blood Sugar management: 144-180) is safer in critically ill
        2. Tight Glucose control is associated with Hypoglycemia and increased mortality
        3. Hyperglycemia is associated with apoptosis, ischemia and delayed healing
        4. Ideally mean Glucose of 150 mg/dl is preferred
        5. (2009) N Engl J Med 360:1283-97 [PubMed]
    2. Corticosteroids
      1. Hydrocortisone at physiologic dose
        1. Hydrocortisone 50 mg IV every 6 hours (some give 100 mg as initial dose)
      2. Indicated for severe Sepsis refractory to aggressive fluid Resuscitation and Vasopressor therapy
        1. Consider if patient is requiring 2 pressors for support (e.g. Norepinephrine and Epinephrine or vasopressin)
        2. Benefit may be limited to early administration
      3. Efficacy (variable evidence)
        1. Surviving Sepsis Campaign downgraded Corticosteroid recommendation to weak evidence in 2012
        2. Marked mortality benefit from Corticosteroids in severe Sepsis
          1. Annane (2002) JAMA 288(7):862-71 [PubMed]
        3. Has short-term benefit in duration and severity
          1. Annand (2009) JAMA 301:2362 [PubMed]
        4. CORTICUS trial found no benefit to Corticosteroids overall
          1. However of those who did respond to shock reversal, those on Corticosteroids improved faster
          2. Sprung (2008) NEJM 358(2): 111-24 [PubMed]
        5. ADRENAL Study found no significant benefit
          1. However some argue higher doses given earlier in course are beneficial
          2. Swaminathan and Weingart in Herbert (2018) EM:Rap 18(8): 9
          3. Venkatesh (2018) N Engl J Med 378(9): 797-808 [PubMed]
    3. Additional measures when poor response to Resuscitation efforts
      1. Consider Hypothyroidism
      2. Consider additional Intravenous Fluids (if suspect still volume down)
        1. Give additional 1-2 Liters on top of already administered 2 liters
      3. Manage Hypocalcemia (based on Ionized Calcium or Corrected Serum Calcium for albumin)
        1. Replace with Calcium Gluconate or Calcium Chloride if hypocalcemic
      4. Stress Ulcer or peptic ulcer prophylaxis
        1. Indications
          1. Thrombocytopenia
          2. Multiorgan failure
          3. Mechanical Ventilation
        2. Agents (either are equivalent)
          1. H2 Blocker (e.g. Ranitidine) or
          2. Proton Pump Inhibitor (e.g. Protonix)
      5. Occult Hemorrhage (e.g. Gastrointestinal Bleeding)
        1. Stop bleeding and Consider pRBC transfusion if actively bleeding or Hemoglobin <7.0 mg/dl
      6. DVT Prophylaxis
        1. Low molecular-weight Heparin (preferred) or
        2. Low dose Unfractionated Heparin or
        3. Mechanical compression devices if Heparin contraindicated
      7. Inotropes (e.g. Dobutamine)
        1. Consider for inotropic support when inadequate tissue perfusion/oxygenation
          1. Especially where myocardial dysfunction is suspected
        2. Consider when perfusion markers fail to improve despite MAP >65 mmHg and Oxygen Saturation >90%
          1. SvcO2 <70% or
          2. Lactic Acid fails to improve or
          3. Serum Creatinine fails to improve
        3. Approach
          1. Dobutamine 2.5 mcg/kg/min
          2. Obtain beside Echocardiogram if available
    4. Other agents
      1. Activated Protein C
      2. Drotecogin Alfa (Xigris)
        1. No survival benefit
        2. Removed from the U.S. market in october 2011 (as well as surviving Sepsis guidelines)
      3. Bicarbonate
        1. Not generally recommended
        2. Acidosis improves with improved perfusion
  20. Management: End Stage Renal Disease (ESRD) and Sepsis
    1. Precautions
      1. Septic Shock in ESRD is of the highest risk
      2. ESRD patients have decreased mortality with aggressive fluid hydration in Sepsis (see above)
    2. Fluid management
      1. All septic patients with Hypotension or Lactic Acidosis will typically need upwards of 30 cc/kg replacement
        1. Early intubation may be preferred
        2. If monitoring (e.g. Ultrasound, CVP) is unreliable or unavailable
          1. Aim for 3-4 Liter IV fluid Resuscitation (in 500 cc increments)
      2. Emergency Dialysis may be required to manage Fluid Overload
        1. Aggressive fluid Resuscitation needed in Sepsis
      3. Use Inferior Vena Cava Ultrasound to drive fluid Resuscitation
        1. See Inferior Vena Cava Ultrasound for Volume Status
        2. Hypotension or Lactic Acidosis
          1. Vena cava collapses with inspiration: Give 500 cc IV bolus of fluid
          2. Vena cava does not collapse: Start Vasopressors (e.g. Norepinephrine)
        3. Repeat cycle of fluid bolus or pressors followed by Ultrasound until Hypotension and Lactic Acidosis resolve
          1. Once IVC does not collapse with inspiration, move to Vasopressors
          2. Consider starting Vasopressors earlier to help increase Preload
          3. Consider monitoring Central Venous Pressure (CVP) to confirm that it remains low following fluid bolus
    3. Airway management
      1. Early intubation is preferred over crash airway management
      2. BIPAP or intubation may be needed with fluid Resuscitation related to Fluid Shifts and pulmonary edema (expected)
    4. Labs
      1. Serum lactate is an accurate reflection of Sepsis status in ESRD (lactate undergoes hepatic clearance)
    5. References
      1. Weingart and Orman in Majoewsky (2013) EM:Rap 13(10): 6
  21. Management: Pregnancy and Sepsis
    1. Sepsis Criteria in pregnancy
      1. SIRS Criteria and qSOFA Criteria do NOT apply to pregnant patients
      2. No obstetric Sepsis scoring system (MEWS, MOEWS, SOS) has been found accurate enough for clinical use
        1. Edwards (2015) Am J Obstet Gynecol 212(4):536.e1-8 +PMID:25446705 [PubMed]
        2. Albright (2017) Obstet Gynecol 120(4):747-55 +PMID:28885400 [PubMed]
      3. Blood Pressure, Heart Rate, Respiratory Rate are unreliable markers of serious infection or instability in pregnancy
      4. Lactic Acid cutoffs do not apply well to pregnancy, but higher Lactic Acids are associated with worse outcomes
        1. Albright (2015) Am J Perinatol 32(5):481-6 [PubMed]
    2. General measures
      1. Left lateral decubitus position
      2. Aggressive fluid Resuscitation (as with other Sepsis cases)
      3. Blood Products as needed
      4. Early antbiotics
      5. No clear evidence for one Vasopressor over another in pregnancy (Norepinephrine is reasonable)
    3. References
      1. Swadron, Schmitz, Bridwell, Carius in Herbert (2019) EM:Rap 19(3): 12-4
  22. Prognosis
    1. Positive Blood Culture
      1. Confers 150% increase in mortality risk
    2. Mortality
      1. Severe Sepsis: 25-30%
      2. Septic Shock: 40-70%
  23. Resources
    1. Surviving Sepsis Protocol
  24. References
    1. (2016) CALS, 14th ed, 1:46
    2. Goldberg (2015) Crit Dec Emerg Med 29(3): 9-19
    3. Guirgis and Khadpe (2017) Crit Dec Emerg Med 31(12): 3-8
    4. Swadron and Goldberg in Majoewsky (2013) EM:RAP 13(6): 2-4
    5. Weingart and Orman in Majoewsky (2014) EM:RAP 14(8): 3-5
    6. Orman and Weingart in Majoewsky (2012) EM:RAP 12(10): 4-7
    7. Khoujah (2013) Crit Dec Emerg Med 27(4):12-21
    8. Marik (2011) Annals of Intensive Care 1:17
    9. Angus (2013) N Engl J Med 369(9): 840-51 +PMID:23984731 [PubMed]
    10. Annane (2005) Lancet 365(9453): 63-78 [PubMed]
    11. Cunha (2008) Crit Care Clin 24(2): 313-34 [PubMed]
    12. Dellinger (2013) Crit Care Med 41(2):580-637 [PubMed]
    13. Gauer (2013) Am Fam Physician 88(1): 44-53 [PubMed]
    14. Jaimes (2004) Clin Infect Dis 38:357-62 [PubMed]
    15. Lever (2007) BMJ 335(7625): 879-83 [PubMed]

Septicemia (C0036690)

Definition (MSHCZE) Dř. tak byl označován stav, při němž v krvi dochází k rozsevu bakterií ve shlucích, které se obv. uvolňují z infikované krevní sraženiny (trombu při hnisavém zánětu žil či endokarditidě) a embolizací mohou vést k septickému infarktu a dalšímu šíření infekce do jiných orgánů. Též septikopyemie, pyemie. Dnes ztotožňováno s pojmem sepse. (cit. Velký lékařský slovník online, 2013 )
Definition (NCI_CTCAE) A disorder characterized by the presence of pathogenic microorganisms in the blood stream that cause a rapidly progressing systemic reaction that may lead to shock.
Definition (NCI_NCI-GLOSS) Disease caused by the spread of bacteria and their toxins in the bloodstream.
Definition (NCI) The presence of pathogenic microorganisms in the blood stream causing a rapidly progressing systemic reaction that may lead to shock. Symptoms include fever, chills, tachycardia, and increased respiratory rate. It is a medical emergency that requires urgent medical attention.
Definition (CSP) systemic disease associated with presence and persistance of pathogenic microorganisms or their toxins in the blood.
Definition (MSH) Systemic disease associated with the presence of pathogenic microorganisms or their toxins in the blood.
Concepts Disease or Syndrome (T047)
MSH D018805
ICD9 038.9, 038
ICD10 A41.9
SnomedCT 187333004, 266089004, 186392004, 40555009, 154313001, 105592009, 91302008
LNC MTHU020833
English Unspecified septicemia, SEPTICAEMIA, SEPTICEMIA, Septicaemia, Septicaemia NOS, Septicaemia, unspecified, Septicemia, unspecified, [X]Septicaemia, unspecified, [X]Septicemia, unspecified, Blood Poisoning, Poisoning, Blood, Septicemia NOS, POIS BLOOD, BLOOD POIS, septicemia (diagnosis), septicemia, Poisonings, Blood, Blood Poisonings, Septicemias, Septicemia [Disease/Finding], Blood poisoning, poisoning blood, blood poisoning, septicaemia, [X]Septicemia, unspecified (disorder), Septicaemia (disorder), (Septicaemia NOS) or (sepsis) (disorder), (Septicaemia NOS) or (sepsis), (Septicemia NOS) or (sepsis), Septicemia NOS (disorder), Septicemia (disorder), sepsis, SEPSIS, toxemia, Sepsis Syndrome, Unspecified septicaemia, Septicemia, intoxication; septic, general, intoxication; septic, septic; intoxication, general, septic; intoxication, Blood poisoning, NOS, Septicemia, NOS, Septicaemia, NOS, Sepsis
French SEPTICEMIE, Septicémie SAI, Septicémie non précisée, Septicémie
Portuguese SEPTICEMIA, Septicemia NE, Septicémia NE, Septicemia não especificada, Septicemia
Spanish SEPTICEMIA, Septicemia NEOM, Septicemia, Septicemia por organismo indeterminado, Septicemia no especificada, [X]septicemia, no especificada, septicemia, SAI, [X]septicemia, no especificada (trastorno), septicemia, SAI (trastorno), septicemia, septicemia (trastorno)
German SEPTIKAEMIE, unspezifische Septikaemie, Septikaemie NNB, Septikaemie ohne weitere Angabe, Septikämie, Sepsis, nicht naeher bezeichnet, Septhämie, Septisches Fieber, Septikaemie, Septikhämie, Septikhaemie
Dutch septikemie, septikemie NAO, niet-gespecificeerde septikemie, intoxicatie; septisch, gegeneraliseerd, intoxicatie; septisch, septisch; intoxicatie, gegeneraliseerd, septisch; intoxicatie, Sepsis, niet gespecificeerd
Italian Setticemia NAS, Setticemia non specificata, Setticemia
Japanese 敗血症, 敗血症NOS, 詳細不明の敗血症, ハイケツショウ, ショウサイフメイノハイケツショウ, ハイケツショウNOS
Czech septikémie, Septikemie, Septikemie NOS, Blíže neurčená septikemie, otrava krve, septikemie
Korean 상세불명의 패혈증
Hungarian septicaemia, nem meghatározott septicaemia, nem meghatározott szeptikémia, septicaemia k.m.n.
Norwegian Blodforgiftning, Septikemi
Derived from the NIH UMLS (Unified Medical Language System)

Septic Shock (C0036983)

Definition (NCI) A state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion unexplained by other causes.(NICHD)
Definition (CSP) shock caused by infection; frequently caused by gram negative bacteria, although some cases have been caused by other bacteria, viruses, fungi, and protozoa; characterized by fever, chills, tachycardia, tachypnea, and hypotension.
Definition (MSH) Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.
Concepts Pathologic Function (T046)
MSH D012772
ICD9 785.52
SnomedCT 207031008, 158359009, 76571007
English Shock, Septic, [D]Septic shock, [D]Septicaemic shock, [D]Septicemic shock, [D]Septic shock (context-dependent category), SHOCK SEPTIC, septic shock (diagnosis), septic shock, Shock septic, Shock, Septic [Disease/Finding], septicemic shock, [D]Septic shock (situation), SEPTIC SHOCK, SHOCK, SEPTIC, Septic shock, Septicaemic shock, Septicemic shock, Sepsis-associated hypotension, Septic shock (disorder), Septic Shock, septic; shock, shock; septic
Dutch shock septisch, septisch; shock, shock; septisch, septische shock, Septische shock, Shock, septische
German Schock septisch, Septischer Schock, Schock, septischer
Swedish Chock, septisk
Spanish [D]choque séptico (categoría dependiente del contexto), choque septicémico, Shock Séptico, Choque Séptico, [D]choque séptico, [D]shock séptico, [D]choque séptico (situación), Síndrome de Shock Tóxico, Síndrome de Choque Tóxico, Shock Tóxico, Síndrome del Shock Tóxico, Shock Endotóxico, Shock séptico, choque septicémico (trastorno), shock septicémico, choque séptico (trastorno), choque séptico, shock séptico
Japanese ハイケツショウセイショック, ショック-中毒性, 中毒性ショック, 内毒素ショック, 中毒性ショック症候群, ショック-内毒素, 敗血症性ショック, 敗血性ショック, ショック-エンドトキシン, 細菌性ショック, 感染性ショック, エンドトキシンショック, ショック-敗血症性
Finnish Septinen sokki
Czech Septický šok, septický šok, šok septický
Polish Wstrząs septyczny, Wstrząs endotoksyczny
Hungarian septicus shock, Septicus shock
Norwegian Sjokk, septisk, Septisk sjokk
Portuguese Choque séptico, Choque Séptico
French Choc septique
Italian Shock settico
Derived from the NIH UMLS (Unified Medical Language System)

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