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
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

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
38C or 36C
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
Adaptedacidosis
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

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

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
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

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+

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