Sepsis Syndrome

Bahram Hajikarim MD/MPH

ZUMS

Feb 2010

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

0 10 20 30 40 50 60

UVA Hospital

Johns Hopkins

UVA newborn ICU

UVA Enterococcus

UIHC CNS

UIHC Candida

UIHC SICU

Stages of SepsisConsensus 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)

• 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

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 Encapsulated organismsPneumococcus spp.,Haemophilus influenzae,Neisseria meningtidis,Capnocytophagiacanimorsus Babesiosis

Cirrhosis Vibrio, Yersinia, andSalmonella spp., otherGram-negative rods (GNRs),encapsulated organisms

Alcoholism Klebsiella spp.,pnemococcus

Diabetes Mucormycosis and Pseudomonas ssp.(malignant external otitis), Escherichiacoli

Steroids Tuberculosis, fungi, herpes virus

Neutropenia Enteric GNR, Pseudomonas,Aspergillus, Candida, and Mucor spp.,Staphylococcus aureus

T-cell abnortmalities

Listeria, Salmonella, and Mycobacteriaspp., herpes virus group (herpes simplexvirus, cytomegalovirus, varicella zostervirus)

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 ShockOutcomes 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