Sepsis Syndrome By: Dr. Sabir M. Ameen. Sepsis and Septic Shock 13th leading cause of death in U.S....
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Transcript of Sepsis Syndrome By: Dr. Sabir M. Ameen. Sepsis and Septic Shock 13th leading cause of death in U.S....
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