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Sepsis Syndrome

Continuum of clinical pathophysiology and severity Process rather than an event Mild dysfunction to frank organ failure Changes in the function of every organ system mediated by the host immune system.

Systemic Inflammatory Response SyndromeACCP/SCCM Consensus Temperature >38C or <36 Heart rate >90 bpm Respiratory Rate>20 or PaCO2<32mmHg WBC>12,000/l or <4,000/l

Sepsis: 2 or more Tachycardia >90bpm Rectal temp>38C or <36C Tachypnea(>20bpm) With 1 or more Alteration in mental status Hypoxemia (PaO2<72mmHG at FiO20.21) Elevated plasma lactate Oligouria

Severe Sepsis
Tachycardia >90bpm Rectal temp>38C or <36C Tachypnea(>20bpm) or PaCO2<32mmHg Hypotension despite fluid resuscitation Presence of perfusion abnormalities: lactic acidosis, oligouria, alteration in mental status

Mediators of Sepsis
Lipospolysaccharide (gram-negative bacteria) Lipoteichoic acid (gram-positive bacteria Peptidoglycan Cytokines
IL-1 mediates systemic effects of infection IL-6 effects liver function TNF-- potentiates the activation of neutrophils and macrophages IL-8 regulates neutrophil function, mediates lung injury in sepsis

Sepsis and Septic Shock

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

Stages of Sepsis Consensus Conference Definition

Systemic Inflammatory Response Syndrome (SIRS) Two or more of the following:
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

Respiratory > abdominal > urinary Nosocomial infection Hypotension, anuria Isolation of enterococci or fungi Gram-negative bacteremia, polymicrobial Body temperature lower than 35C Age greater than 40 Underlying illness: cirrhosis or malignancy

Predisposing Underlying Diseases

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 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




Steroids Neutropenia

Mucormycosis and Pseudomonas ssp. (malignant external otitis), Escherichia coli Tuberculosis, fungi, herpes virus Enteric GNR, Pseudomonas, Aspergillus, Candida, and Mucor spp., Staphylococcus aureus Listeria, Salmonella, and Mycobacteria spp., herpes virus group (herpes simplex virus, cytomegalovirus, varicella zoster virus)

T-cell abnortmalities

Bacteremia in the Preantibiotic Era

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

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

Clinical Manifestations
Fever, chills, hypotension Hypothermia, especially in the elderly Hyperventilation - respiratory alkalosis Change in mental status

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

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

Cardiovascular Signs
Warm shock - CO, SVR Cold shock - CO, SVR Anaerobic metabolism - lactic acidemia

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

Hematologic Findings
Neutrophilic leukocytosis Leukemoid reaction Neutropenia Thrombocytopenia Toxic granulations DIC

Renal and Gastrointestinal Signs

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
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

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

Failure of Fluid Replacement and Vasopressors

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

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 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. 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

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