Sepsis Syndrome

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Sepsis Syndrome

• Cynthia L. Gibert, M.D.
• Washington VA Medical Center
• Georgetown University Medical Center

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Sepsis and Septic Shock

• 13th leading cause of death in U.S.
• 500,000 episodes each year
• 35 mortality
• 30-50 culture-positive blood

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Mortality Percentage
UIHC SICU
UIHC Candida
UIHC CNS
UVA Enterococcus
UVA newborn ICU
Johns Hopkins
UVA Hospital
0 10 20 30 40 50 60
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Stages of SepsisConsensus Conference Definition

• Systemic Inflammatory Response Syndrome
  (SIRS)Two or more of the following
• Temperature of gt38oC or lt360C
• Heart rate of gt90
• Respiratory rate of gt20
• WBC count gt12 x 109/L or lt4 x 109/L or 10
  immature forms (bands)
• SepsisSIRS plus a culture-documented infection
• Severe SepsisSepsis plus organ dysfunction,
  hypotension, or hypoperfusion(including but not
  limited to lactic acidosis, oliguria, or acute
  mental status changes)
• Septic ShockHypotension (despite fluid
  resuscitation) plus hypoperfusion

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Multiple Organ Dysfunction Syndrome

• Dysfunction of 2 or more systems
• Four or more systems - mortality near to 100
  percent

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Factors Associated with Highest Mortality

• Respiratory gt abdominal gt urinary
• Nosocomial infection
• Hypotension, anuria
• Isolation of enterococci or fungi
• Gram-negative bacteremia, polymicrobial
• Body temperature lower than 38C
• Age greater than 40
• Underlying illness cirrhosis or malignancy

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Predisposing Underlying Diseases

• Heart disease-rheumatic or congenital
• Splenectomy
• Intraabdominal sepsis
• Septic abortion or pelvic infection
• Intravenous drug abuse
• Immunocompromised

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Organisms Responsible for Septic Shock in
Relation to Host Factors
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Bacteremia in the Preantibiotic Era

• Streptococcus pneumoniae
• Group A streptococcus
• Staphylococcus aureus
• Haemophilus influenzae
• Neisseria mennigitidis
• Salmonella spp.

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Emergence of Gram-Negative Organisms

• Antibiotic pressure on normal flora
• Use of invasive devices
• Immune suppression

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Differential Diagnosis of Fever and Shock

• Purulent bacterial pericardial effusion
• Peritonitis
• Pneumonia with severe hypoxia
• Mediastinitis
• Anaphylaxsis
• Staphylococcal toxic shock syndrome
• Streptococcal toxic shock syndrome

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Clinical Manifestations

• Fever, chills, hypotension
• Hypothermia, especially in the elderly
• Hyperventilation - respiratory alkalosis
• Diaphoresis, apprehension, change in mental status

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History

• Community versus hospital-acquired
• Prior or current medications
• Recent manipulations or surgery
• Underlying diseases
• Travel history

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Approach to Septic Patient

• Seek primary site of infection
• Direct therapy to primary site
• Repeated examination

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Skin

• Furuncles, cellulitis, bullous lesions
• Intravenous sites, phlebitis
• Erythema multiforme
• Ecchymotic or purpuric lesions
• DIC, petechiae
• Ecthyma gangrenosum
• Purpura fulminans

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Cardiovascular Signs

• Warm shock - ? CO, ? SVR
• Cold shock - ? CO, ? SVR
• Anaerobic metabolism - lactic acidemia
• Myocardial depressant factor - ??

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Pulmonary Signs

• Tachypnea
• Hyperventilation, respiratory alkalosis
• ARDS, respiratory failure
• Ventilation-perfusion mismatch
• Widened alveolar-arterial oxygen gradient
• Reduced lung compliance

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Hematologic Findings

• Neutrophilic leukocytosis
• Leukemoid reaction
• Neutropenia
• Thrombocytopenia
• Toxic granulations
• DIC

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Renal and Gastrointestinal Signs

• Acute tubular necrosis, oliguria, anuria
• Upper GI bleeding
• Cholestatic jaundice
• Increased transaminase levels
• Hypoglycemia

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Acute Physiology and Chronic Health Evaluation

• APACHE II
• Temp Arterial pH
• MAP Serum Na Serum Cr
• Heart rate Hematocrit
• Resp. rate WBC
• Oxygenation Glasgow Coma Score
• Acute physiology score Age Chronic health
  points

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Laboratory Studies

• Blood cultures
• Infected secretions/body fluids
• Stool for WBC, C. difficile
• Aspirate advancing edge of cellulitis
• Skin biopsy/scraping
• Buffy coat

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Therapy of Septic Shock

• Correct pathologic condition
• Optimize intravascular volume
• Administer empiric antimicrobial therapy
• Administer vasoactive drugs

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Failure of Fluid Replacement and Vasopressors

• acidosis - pHlt7.3
• hypocalcemia
• adrenal insufficiency
• hypoglycemia

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Empiric Antimicrobial Regimens for Sepsis Syndrome

• Community-acquired non-neutropenic
• Urinary tract 3rd generation cepholosporin,
  piperacillin, quinolone AG
• Non-urinary tract 3rd generation cepholosporin
  metronidazole, ?-lactam/ ?-lactamase inhibitor
  AG

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• Hospital-acquired
• Nonneutropenic 3rd generation cephalosporin
  metronidazole, ?-lactam / ?-lactamase inhibitor,
  menopenem all AG
• Neutropenic Timentin AG, meropenem AG
  ceftazidime metronidazole AG

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Septic ShockOutcomes for Patients on Hospital
Wards versus ICUs

• Ward patients Delays in ICU transfer (67 mins.)
• IV fluid boluses (27 vs 15 mins.)
• Inotropic agents (310 vs 22.5 mins)
• Mortality Wards (70) vs ICUs (39)
• Apache II scores (18.5 vs 24)
• Candidemia

JS Lunberg, Crit. Care Med. 261020 1998
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Immunotherapies for Septic Shock

• Corticosteroids
• Antiendotoxin monoclonal antibodies E-5, HA-1A
• Anti-TNF antibodies
• IL-1 receptor antagonists

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Other Treatment Modalities

• Granulocyte transfusions
• Recombinant colony-stimulating factors
• Diuretics
• Pentoxifylline, ibuprofen, naloxone
• Oral nonabsorbable antimicrobial agents