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Transcript
Sepsis Syndrome
Cynthia L. Gibert, M.D.
Washington VA Medical Center
Georgetown University Medical Center
Sepsis and Septic Shock
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13th leading cause of death in U.S.
500,000 episodes each year
35% mortality
30-50% culture-positive blood
Mortality Percentage
UIHC SICU
UIHC Candida
UIHC CNS
UVA Enterococcus
UVA newborn ICU
Johns Hopkins
UVA Hospital
0
10
20
30
40
50
60
Stages of Sepsis
Consensus Conference Definition
• Systemic Inflammatory Response Syndrome (SIRS)
Two or more of the following:
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Temperature of >38oC or <360C
Heart rate of >90
Respiratory rate of >20
WBC count >12 x 109/L or <4 x 109/L or 10% immature forms (bands)
• Sepsis
SIRS plus a culture-documented infection
• Severe Sepsis
Sepsis plus organ dysfunction, hypotension, or hypoperfusion
(including but not limited to lactic acidosis, oliguria, or acute mental
status changes)
• Septic Shock
Hypotension (despite fluid resuscitation) plus hypoperfusion
Multiple Organ Dysfunction
Syndrome
• Dysfunction of 2 or more systems
• Four or more systems - mortality near
to 100 percent
Factors Associated with
Highest Mortality
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Respiratory > abdominal > urinary
Nosocomial infection
Hypotension, anuria
Isolation of enterococci or fungi
Gram-negative bacteremia, polymicrobial
Body temperature lower than 38°C
Age greater than 40
Underlying illness: cirrhosis or malignancy
Predisposing Underlying
Diseases
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Heart disease-rheumatic or congenital
Splenectomy
Intraabdominal sepsis
Septic abortion or pelvic infection
Intravenous drug abuse
Immunocompromised
Organisms Responsible for Septic
Shock in Relation to Host Factors
Asplenia
Cirrhosis
Alcoholism
Encapsulated organisms
Pneumococcus spp.,
Haemophilus influenzae,
Neisseria meningtidis,
Capnocytophagia
canimorsus Babesiosis
Vibrio, Yersinia, and
Salmonella spp., other
Gram-negative rods (GNRs),
encapsulated organisms
Klebsiella spp.,
pnemococcus
Diabetes
Steroids
Mucormycosis and Pseudomonas ssp.
(malignant external otitis), Escherichia
coli
Tuberculosis, fungi, herpes virus
Neutropenia
Enteric GNR, Pseudomonas,
Aspergillus, Candida, and Mucor spp.,
Staphylococcus aureus
T-cell
abnortmalities
Listeria, Salmonella, and Mycobacteria
spp., herpes virus group (herpes simplex
virus, cytomegalovirus, varicella zoster
virus)
Bacteremia in the Preantibiotic Era
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Streptococcus pneumoniae
Group A streptococcus
Staphylococcus aureus
Haemophilus influenzae
Neisseria mennigitidis
Salmonella spp.
Emergence of
Gram-Negative Organisms
• Antibiotic pressure on normal flora
• Use of invasive devices
• Immune suppression
Differential Diagnosis
of Fever and Shock
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Purulent bacterial pericardial effusion
Peritonitis
Pneumonia with severe hypoxia
Mediastinitis
Anaphylaxsis
Staphylococcal toxic shock syndrome
Streptococcal toxic shock syndrome
Clinical Manifestations
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Fever, chills, hypotension
Hypothermia, especially in the elderly
Hyperventilation - respiratory alkalosis
Diaphoresis, apprehension, change in mental
status
History
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Community versus hospital-acquired
Prior or current medications
Recent manipulations or surgery
Underlying diseases
Travel history
Approach to Septic Patient
• Seek primary site of infection
• Direct therapy to primary site
• Repeated examination
Skin
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Furuncles, cellulitis, bullous lesions
Intravenous sites, phlebitis
Erythema multiforme
Ecchymotic or purpuric lesions
DIC, petechiae
Ecthyma gangrenosum
Purpura fulminans
Cardiovascular Signs
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“Warm shock” -  CO,  SVR
“Cold shock” -  CO,  SVR
Anaerobic metabolism - lactic acidemia
Myocardial depressant factor - ??
Pulmonary Signs
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Tachypnea
Hyperventilation, respiratory alkalosis
ARDS, respiratory failure
Ventilation-perfusion mismatch
Widened alveolar-arterial oxygen gradient
Reduced lung compliance
Hematologic Findings
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Neutrophilic leukocytosis
Leukemoid reaction
Neutropenia
Thrombocytopenia
Toxic granulations
DIC
Renal and
Gastrointestinal Signs
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Acute tubular necrosis, oliguria, anuria
Upper GI bleeding
Cholestatic jaundice
Increased transaminase levels
Hypoglycemia
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
Laboratory Studies
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Blood cultures
Infected secretions/body fluids
Stool for WBC, C. difficile
Aspirate advancing edge of cellulitis
Skin biopsy/scraping
Buffy coat
Therapy of Septic Shock
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Correct pathologic condition
Optimize intravascular volume
Administer empiric antimicrobial therapy
Administer vasoactive drugs
Failure of Fluid Replacement
and Vasopressors
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acidosis - pH<7.3
hypocalcemia
adrenal insufficiency
hypoglycemia
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
• Hospital-acquired
– Nonneutropenic: 3rd generation cephalosporin +
metronidazole, -lactam / -lactamase inhibitor,
menopenem all + AG
– Neutropenic: Timentin + AG, meropenem + AG;
ceftazidime + metronidazole + AG
Septic Shock
Outcomes for Patients on
Hospital Wards versus ICU’s
• 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. 26:1020; 1998
Immunotherapies for
Septic Shock
• Corticosteroids
• Antiendotoxin monoclonal antibodies
E-5, HA-1A
• Anti-TNF antibodies
• IL-1 receptor antagonists
Other Treatment Modalities
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Granulocyte transfusions
Recombinant colony-stimulating factors
Diuretics
Pentoxifylline, ibuprofen, naloxone
Oral nonabsorbable antimicrobial agents