Download SIRS, Sepsis, and MODS Claudio Martin, MSc, MD Programme in Critical Care

SIRS, Sepsis, and MODS
Claudio Martin, MSc, MD
Programme in Critical Care
University of Western Ontario
London, Ontario, Canada
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 24g/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
Case Presentation - Resolution
• Patient gradually stabilized and improved with
complete resolution of organ dysfunction over 5 days
• Final cultures confirmed diagnosis as
meningococcemia
Infection: Part of a bigger picture
•
Infection:
–
Presence of organisms in a
closed space or location
where not normally found
Infection
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
SIRS: Systemic Inflammatory
Response Syndrome
• SIRS: A clinical response
arising from a nonspecific
insult manifested by
2 of the following:
– Temperature
38°C or 36°C
– HR 90 beats/min
– Respirations 20/min
– WBC count 12,000/mL or
4,000/mL or >10%
immature neutrophils
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Sepsis: More Than Just Inflammation
• Sepsis:
– Known or suspected
infection
– SIRS criteria
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Severe Sepsis: Acute Organ
Dysfunction
• Severe Sepsis =
Sepsis with signs of acute
organ dysfunction in any of
the following systems:
– Cardiovascular (septic
shock)
– Renal
– Respiratory
– Hepatic
– Hemostasis
– CNS
– Unexplained metabolic
acidosis
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Sepsis: A Complex Disease
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Jargon 2002: PIRO
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
 Adult Respiratory Distress Syndrome
 Acute Tubular Necrosis
 Shock
 Metabolic encephalopathy
 Critical Illness Polyneuropathy
 Disseminated Intravascular Coagulopathy
 Gastroparesis and ileus
 Cholestasis
 Adrenal insufficiency
 Rhabdomyolysis
Specific therapy exists
Magnitude of the Problem
• Estimated 215,000 deaths from US 1995 data
• High cost for management (ICU care, diagnostic
testing, drugs)
– Estimated 20 day LOS; $22,000 cost
• Represents 9.3% of all deaths
• Equals deaths after acute myocardial infarction
Sepsis: Defining a Disease Continuum
Infection/
Trauma
SIRS
A clinical response arising
from a nonspecific insult,
including 2 of the
following:
– Temperature ≥38oC or
≤36oC
– HR ≥90 beats/min
– Respirations ≥20/min
– WBC count ≥12,000/mm3
or
≤4,000/mm3 or >10%
immature neutrophils
Sepsis Severe Sepsis
SIRS with a presumed or
confirmed infectious
process
SIRS = systemic inflammatory response
syndrome.
Bone et al. Chest. 1992;101:1644.
Sepsis: Defining a Disease Continuum
Infection/
Trauma
SIRS
Sepsis Severe Sepsis
Shock
• 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
Percent of cases within each category
18
28
24
30
35% mortality
8353 patients with LOS > 24h
4277 infections (2696 on admission)
Alberti, Int Care Med 2002
Sources of Sepsis
The International Cohort Study
Severe
Sepsis
Septic
Shock
Respiratory
66
53
Abdomen
9
20
Bacteremia
14
16
Urinary
11
11
Multiple
-
-
Microbiology of Sepsis
The International Cohort Study
Severe
Sepsis
Septic
Shock
Gram-positive
44
40
Gram-negative
47
47
Fungal
9
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
Initiation of Inflammatory Response
From Wheeler & Bernard, NEJM 1999
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.
Coagulation and Fibrinolysis
Bernard, GR. NEJM 2001;344;10:699-709
Pathogenesis of SIRS/MODS
Preoperative Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
Inadequate
Resuscitation
SIRS/MODS
Regulation of oxygen delivery
Normal
Abnormal
Cardiac
output
BP=CO * SVR
Cardiac
Output
regional distribution
regional distribution
Intra Organ Distribution
Intra Organ Distribution
Microcirculation
Microcirculation
QO2 = Flow * O2 content
Oxygen Delivery
• Delivery:Demand mismatch
• Diffusion limitation (edema)
Oxygen Consumption
H+
H+
I
Q
NADH + H+
H+
Cytc
III
H+
H+
IV
1/2 O2 + H+ H2O
NAD+
ADP + Pi
•Pyruvate Dehydrogenase (PDH) activity decreased
•Decreased delivery of Acetyl CoA to TCA cycle
•Mitochondrial dysfunction
ATP
Severe Sepsis:
The Final Common Pathway
Endothelial Dysfunction and
Microvascular Thrombosis
Hypoperfusion/Ischemia
Acute Organ Dysfunction
(Severe Sepsis)
Death
Severe Sepsis:
Management of Our Case
Endothelial Dysfunction and
Microvascular Thrombosis
rhAPC
Corticosteroids
Hypoperfusion/Ischemia
Fluids
Vasopressors
Acute Organ Dysfunction
(Severe Sepsis)
CVVHF
Enteral nutrition
Death
Survival