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Sepsis Syndrome Cynthia L. Gibert, M.D. Washington VA Medical Center Georgetown University Medical Center Sepsis and Septic Shock • • • • 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: – – – – 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 38°C 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 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 • • • • • • 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 Diaphoresis, apprehension, change in mental status History • • • • • 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 • • • • • • • 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 Myocardial depressant factor - ?? 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 • 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 • • • • • Granulocyte transfusions Recombinant colony-stimulating factors Diuretics Pentoxifylline, ibuprofen, naloxone Oral nonabsorbable antimicrobial agents