Sepsis SyndromeSepsis Syndrome

By: Dr. Sabir M. AmeenBy: Dr. Sabir M. Ameen

Sepsis and Septic ShockSepsis and Septic Shock

• 13th leading cause of death in U.S.

• 500,000 episodes each year

• 35% mortality

• 30-50% culture-positive blood

A systemic response to a nonspecific insultInfection, 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

SIRSSEVERE SEPSIS

What is SIRS?What is SIRS?

DefinitionsDefinitions

• Sepsis = SIRS + Infection• Infection = either

• Bacteraemia (or viraemia / fungaemia /protozoan)• Septic focus (abscess / cavity / tissue mass)

The Sepsis ContinuumThe Sepsis Continuum

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 = systemic inflammatory response syndrome

SIRS with a presumed or confirmed infectious process

Chest 1992;101:1644.

SepsisSIRSSevere Sepsis

SepticShock

Sepsis with organ failure

Refractoryhypotension

Definitions Cont.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.Definitions Cont.

• Septic Shock = Severe sepsis + Hypotension

• Hypotension = either• SBP <90 • Inotrope to get MAP >90

PathophysiologyPathophysiology

• 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:– 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 ?Where’s the infection ?

Abdomen15%

Culture Negative

20%

Lung47%

Urine 10%

Other8%

Bernard & Wheeler NEJM 336:912, 1997

High Risk PatientsHigh Risk Patients• For Sepsis

– 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 CLINICAL EFFECTS OF INFECTION ON THE BODYON 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 Multiple Organ Dysfunction SyndromeSyndrome

• Dysfunction of 2 or more systems

• Four or more system dysfunction - mortality near 100 %

Factors Associated with Factors Associated with Highest MortalityHighest 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

Laboratory StudiesLaboratory 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 ShockTherapy of Septic Shock

• Correct pathologic condition

• Optimize intravascular volume

• Empiric antimicrobial therapy

• Vasoactive drugs

Initial resuscitation of sepsis: Initial resuscitation of sepsis: therapeutic goalstherapeutic 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 Failure of Fluid Replacement and VasopressorsVasopressors

• acidosis – pH <7.3

• hypocalcemia

• adrenal insufficiency

• hypoglycemia

Choosing antibiotics in sepsisChoosing 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 Empiric Antimicrobial Regimens for Sepsis Syndromefor 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 forImmunotherapies for Septic Shock Septic Shock

• Corticosteroids

• Anti-endotoxin monoclonal antibodies

• Anti-TNF antibodies

• IL-1 receptor antagonists

Other Treatment ModalitiesOther Treatment Modalities

• Granulocyte transfusions

• Recombinant colony-stimulating factors

• Diuretics

• Pentoxifylline, ibuprofen, naloxone

• Oral nonabsorbable antimicrobial agents