Sepsis Syndrome By: Dr. Sabir M. Ameen

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

What is SIRS? A systemic response to a nonspecific insult Infection, trauma, surgery, massive transfusion, etc Defined as 2 of the following: Temperature >38.3 or <36 0C Heart rate >90 min-1 Respiratory rate >20 min-1 White cells <4 or >12 Acutely altered mental state Hyperglycaemia (BM>7.7) in absence of DM SIRS SEVERE SEPSIS 3

Definitions Sepsis = SIRS + Infection Infection = either Bacteraemia (or viraemia / fungaemia /protozoan) Septic focus (abscess / cavity / tissue mass)

SIRS = systemic inflammatory response syndrome The Sepsis Continuum Sepsis SIRS Severe Septic Shock A clinical response arising from a nonspecific insult, with 2 of the following: T >38oC or <36oC HR >90 beats/min RR >20/min WBC >12,000/mm3 or <4,000/mm3 or >10% bands SIRS with a presumed or confirmed infectious process Sepsis with organ failure Refractory hypotension SIRS = systemic inflammatory response syndrome Chest 1992;101:1644. 5

Definitions Cont. Severe sepsis = Sepsis + Organ Dysfunction Organ Dysfunction = Any of SBP <90 or inotrope to get MAP 90 BE <-5mmol/L Lactate >2mmol/L Oliguria <30ml/hr for 1 hour Creatinine >0.16mmol/L Toxic confusional state FIO2 >0.4 and PEEP >5 for oxygenation

Definitions Cont. Septic Shock = Severe sepsis + Hypotension Hypotension = either SBP <90 Inotrope to get MAP >90

Pathophysiology Infection of bacterial, viral or fungal origin Nidus of infection through multiplication of infective organism, releasing various mediators which consist of structural components of the organism and/or exotoxins and endotoxins (from the dead invading organism) Over 100 mediators have been identified (include: tissue necrosis factors, interleukins) Circulatory & cardiac ‘toxic’

Circulatory changes: Cardiac Dysfunction Nitric oxide overproduction in response to these mediators results in peripheral vasodilatation, decreased systemic vascular resistance, fluid leak from capillaries Capillary blood flow is reduced Cardiac Dysfunction Ventricular dilatation with decreased ejection fraction, decreased stroke volume Leads to increased heart rate (& O2 demand)

Where’s the infection ? Bernard & Wheeler NEJM 336:912, 1997 10

High Risk Patients For Sepsis For Dying For Both Post op / post procedure / post trauma Post splenectomy (encapsulated organisms) Cancer Transplant / immune suppressed Alcoholic / Malnourished For Dying Genetic predisposition (e.g. meningococcus) Delayed appropriate antibiotics Yeasts and Enterococcus Site For Both Cultural or religious impediment to treatment

CLINICAL EFFECTS OF INFECTION ON THE BODY Acute Fever; anorexia, protein catabolism, acute-phase protein response, hypoalbuminaemia, low serum iron, anemia, neutrophilia Inflammation; pain, dysfunction, tissue damage Convulsions; especially in children Confusion; especially in the elderly Shock; fall in circulating blood volume associated with lowered systemic vascular resistance Blood; hemorrhage, haemolytic anemia, intravascular coagulation Organ failure; kidneys, liver, lung, heart, brain, necrosis of skin

Multiple Organ Dysfunction Syndrome Dysfunction of 2 or more systems Four or more system dysfunction - mortality near 100 %

Factors Associated with Highest Mortality Respiratory > abdominal > urinary Nosocomial infection Hypotension, anuria Isolation of enterococci or fungi Gram-negative bacteremia, polymicrobial Body T° < 38°C Age > 40 Underlying illness: cirrhosis or malignancy

Fig. 56.1 Potential risk factors leading to sepsis. 15

Fig. 56. 2 Positive blood cultures in severe sepsis Fig. 56.2 Positive blood cultures in severe sepsis. Data from Bochud et al.42 16

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 Empiric antimicrobial therapy Vasoactive drugs

Initial resuscitation of sepsis: therapeutic goals Central venous pressure: 8 – 12 mmHg Mean arterial pressure: ≥ 65 mmHg Urine output: 0.5 ml/kg/h Central venous (SVC) or mixed venous oxygen saturation: ≥ 70%

Failure of Fluid Replacement and Vasopressors acidosis – pH <7.3 hypocalcemia adrenal insufficiency hypoglycemia

Choosing antibiotics in sepsis There is no, single, “best” regimen Consider the site of the infection Consider which organisms most often cause infection at that site Choose antibiotic(s) with the appropriate spectrum After obtaining cultures, give antibiotics quickly and empirically at appropriate dose

Empiric Antimicrobial Regimens for Sepsis Syndrome Community-acquired non-neutropenic UTI: 3rd generation cepholosporin Non-urinary tract: 3rd generation cepholosporin + metronidazole

Hospital-acquired Non-neutropenic: 3rd generation cephalosporin + metronidazole + aminoglycoside Neutropenic: meropenem + aminoglycoside

Immunotherapies for Septic Shock Corticosteroids Anti-endotoxin monoclonal antibodies Anti-TNF antibodies IL-1 receptor antagonists

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