Professional Documents
Culture Documents
Objectives
To know definitions of SIRS, sepsis, septic
shock, MODS
To become familiar with the epidemiology of
sepsis
To learn basic pathophysiology (inflammation,
cardiovascular physiology) of SIRS and sepsis
But first, a real case:
Case presentation
43-year-old male
Flu-like symptoms for 1
day
In ER
Temp 39.5
Pulse 130
Blood pressure 70/30
Respirations 32
Petechial rash
Chest, CV, Abdominal
exam normal
Case presentation - 2
Laboratory
pH 7.29, PaO2 82,
PaCO2 29
Investigations pending
Blood, urine cultures
Orally intubated and
placed on mechanical
ventilation
Central venous catheter
inserted
Cefotaxime 2 g iv
Normal saline 2 litres
initially, repeated
Admitted to ICU
Case presentation - 3
In ICU:
Noradrenaline started
to support blood
pressure
Additional fluid (saline
and pentastarch) given
based on low CVP
Pulmonary artery
catheter inserted to aid
further hemodynamic
management
Despite therapy patient
remained anuric
Continuous venovenous
hemofiltration initiated
Case presentation - 4
Early gram stain on blood revealed gram
negative rods
Patient started on:
Hydrocortisone 100 mg iv q8h
Recombinant activated protein C
24g/kg/hour for 96 hours
Enrolled in RCT (double-blind) of vasopressin
vs norepinephrine for BP support
Enteral nutrition via nasojejunal feeding tube
Prophylaxis for stress ulcers, deep venous
thromboses
Infection:
Presence of organisms in a
closed space or location
where not normally found
Infection
Infection
Inflammation
Physiologic
Biochemical
Severe
Sepsis
Specific Organ
Severity
Predisposition
Pre-existing disease
Cardiac, Pulmonary, Renal
HIV
Age (extremes of age)
Gender (males)
Genetics
TNF polymorphisms (TNF promoter high
secretor genotype)
Response
Physiology
Heart rate
Respiration
Fever
Blood pressure
Cardiac output
WBC
Hyperglycemia
Markers of Inflammation
TNF
IL-1
IL-6
Procalcitonin
PAF
Organ Dysfunction
Lungs
Kidneys
CVS
CNS
PNS
Coagulation
GI
Liver
Endocrine
Skeletal Muscle
Infection/
Trauma
SIRS
Sepsis
Severe
Sepsis
Infection/
Trauma
SIRS
Sepsis
Shock
Severe
Sepsis
Sepsis with 1 sign of organ
failure
Cardiovascular (refractory
hypotension)
Renal
Respiratory
Hepatic
Hematologic
CNS
Unexplained metabolic
acidosis
Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J Med. 1999;340:207.
Epidemiology of Sepsis
The International Cohort Study
Infection
Sepsis
Severe
Sepsis
Septic
Shock
28
24
30
35% mortality
Sources of Sepsis
The International Cohort Study
Severe
Sepsis
Respiratory
Septic
Shock
66
53
20
Bacteremia
14
16
Urinary
11
11
Multiple
Abdomen
Microbiology of Sepsis
The International Cohort Study
Severe
Sepsis
Septic
Shock
Gram-positive
44
40
Gram-negative
47
47
Fungal
13
Polymicrobial
Pathogenesis of SIRS/MODS
Preoperative Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
Inadequate
Resuscitation
SIRS/MODS
Homeostasis Is Unbalanced in
Severe Sepsis
Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock.
1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.
Pathogenesis of SIRS/MODS
Preoperative Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
Inadequate
Resuscitation
SIRS/MODS
Abnormal
Cardiac
output
BP=CO * SVR
Cardiac
Output
regional distribution
regional distribution
Microcirculation
Microcirculation
Oxygen Delivery
Delivery:Demand mismatch
Diffusion limitation (edema)
Oxygen Consumption
H+
H+
NADH + H+
H+
Cytc
III
H+
H+
IV
1/2 O2 + H+ H2O
NAD+
ADP + Pi
ATP
Severe Sepsis:
The Final Common Pathway
Endothelial Dysfunction and
Microvascular Thrombosis
Hypoperfusion/Ischemia
Death
Severe Sepsis:
Management of Our Case
Endothelial Dysfunction and
Microvascular Thrombosis
rhAPC
Corticosteroids
Hypoperfusion/Ischemia
Fluids
Vasopressors
CVVHF
Enteral nutrition
Death
Survival