SIRS and the Septic
Response
Manoj Sayal, MD FRCSC
March 5, 2008
Agenda
1.
2.
3.
4.
A brief review of SIRS (systemic
inflammatory response syndrome)
SIRS and it’s role in sepsis
Definitions of the sepsis syndrome
Current sepsis guidelines
Case 1
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67yo male, presents to ER with 2 day
history of N+V, abdo pain
In ER, looks unwell: HR 130, BP 80/60
RR 36 SPO2 84% on room air;
supplemental O2 applied, sats increase to
92%
Diffusely tender abdomen, coarse air entry
bilaterally
What now?
Case 1

2 large bore IV’s—normal saline 1 litre
Labs drawn
CXR (portable), EKG, ABGs
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Diagnosis?
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Case 1
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CXR: RLL infiltrate
WBC 22.4 Hb 108 Pl 98
Lytes normal; transaminases normal
Amylase 700
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What now?
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Case 2
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Same patient, but normal amylase
Case 3
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Same patient but involved in a major
house fire, normal amylase
What’s wrong with each of these patients?
Does their management differ significantly
(initially)?
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They are all manifesting evidence of the
SIRS response
SIRS for Dummies (or Surgeons)
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Dysregulation of the normal response with
massive and uncontrolled release of
proinflammatory mediators creating a
chain of events that leads to widespread
tissue injury
Results in MODS (Multiple Organ
Dysfunction Syndrome) that causes the
extremely high morbidity and mortality in
this situation
SIRS
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SIRS is a clinical diagnosis, recognized
by 2 or more of the following (in the
appropriate setting):
1.
2.
3.
4.
Temp >38ºC or <35ºC
HR>90bpm
RR>20bpm or PaCO2<32mmHg
WBC>12, <4 or >10% immature (band)
forms
SIRS
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Causes
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Acute pancreatitis, autoimmune disorders,
vasculitis, thromboembolism, burns, surgery,
pulmonary contusion, SEPSIS)
SIRS
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How does this relate to infection or the
response to infection?
Definitions
Infection

an inflammatory response to microorganisms
or the invasion of normally sterile host tissue
by these organisms
Bacteremia
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viable bacteria in the blood
Definitions
Sepsis
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In sepsis, clinical signs of SIRS are present
and are due to either a culture proven
infection or a suspected infection
Clinical syndrome that complicates severe
infection and represents the systemic
response to the infection
Definitions
Severe Sepsis
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Sepsis plus at least one of the following:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Areas of mottled skin
Capillary refill > 3 seconds
Urine output < 0.5cc/kg/hr for at least one hour or renal
replacement therapy
Elevated lactate (>2 to 3)
Abrupt change in mental status
Abnormal EEG findings
Platelet count <100, 000
DIC
ARDS
Cardiac dysfunction
Definitions
Septic Shock

Severe sepsis plus at least one of the
following:
1.
2.
MAP<65mmHg despite adequate fluid
resuscitation
Maintaining MAP>60-65mmHg requires
vasopressors:
•
•
•
Dopamine > 5μg/kg/min
Norepinephrine < 0.25μg/kg/min
Epinephrine < 0.25mg/min
Definitions
Refractory Septic Shock

Septic shock that requires higher doses of the
ionotropes to keep the MAP>65mmHg:
Dopamine > 15μg/kg/min
 Norepinephrine > 0.25μg/kg/min
 Epinephrine >0.25mg/min
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Definitions
Multiple Organ Failure/MODS

Presence of altered organ functions in an
acutely ill patient such that homeostasis
cannot be maintained without intervention
Primary: secondary to a well defined insult in
which organ dysfunction occurs early and can be
directly attributable to the insult itself (eg ARF
from rhabdomyolysis)
 Secondary: organ failure not in direct response to
the insult itself but as a consequence of a host
response to the insult (eg ARDS in pancreatitis)
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Definitions
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Note that NO positive blood cultures are
needed in the definition
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You only get positive cultures in 17-69% of all
septic/septic shock patients
Sepsis
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Getting more frequent (increasing by 8% per
year since the 1970’s) with increasing severity
2% of all hospitalized patients
Up to 75% of all ICU patients
20-50% mortality, depending on the degree:
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SIRS alone 7%
Sepsis 16%
Severe sepsis 20%
Septic shock 46%
Rangud-Feausto, MS et al,
JAMA 1995; 273:117
Sepsis
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Characteristics that influence outcome in the septic
patient include:
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Host response: is the host able to mount a fever or WBC
response?
Underlying disease: comorbidities (NIDDM, kidney failure,
hepatic failure, cancer, EtOH abuse, immune suppression)
APACHE II score
Advanced age
Site of infection: Lung/gut 50% Urine 30%
Community acquired vs healthcare acquired
Organism involved
Antibiotics—timing and type
Rapidity and adequacy of response
Sepsis--Pathogenesis
Pathogenesis
 Process of malignant intravascular
inflammation
 Uncontrolled, unregulated, self-sustaining
 Exaggerated response of the normal
inflammatory response
Sepsis--Pathogenesis
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When tissue is injured, or infected, there
is the simultaneous release of
proinflammatory and antiinflammatory
elements—the balance of these helps
facilitate tissue repair and healing
Remote tissue injury may ensue when this
equilibrium in the inflammatory process is
lost and these mediators exert systemic
effects
Sepsis--Pathogenesis
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The significant consequences of a
systemic proinflammatory reaction include
endothelial damage, microvascular
dysfuntion, impaired tissue oxygenation
and subsequent organ damage or injury
The consequences of an excessive
antiinflammatory response include anergy
and immunosuppression
Sepsis--Pathogenesis
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Normal inflammation involves the
regulation of PMN rolling, adhesion,
diapedesis, chemotaxis, phagocytosis and
killing of invading bacteria
These processes are highly controlled
through proinflammatory and
antiinflammatory cytokines released by
activated macrophages
Sepsis--Pathogenesis
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As a result of dysregulation of this
process, an autodestructive process
ensues to involve otherwise remote
normal tissue and results in the sepsis
syndrome
Sepsis--Pathogenesis
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This involves many factors:
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Proinflammatory cytokines (TNFα, IL-6 etc)
Bacterial factors—direct effect of invading
microorganisms or their toxic products:
Endotoxin (gm neg bacteria)
 Cell wall components (peptoglycans, muramyl
dipeptide, lipoteichoic acid)
 Enterotoxins (staph), exotoxin (pseudomonas), M
protein (GAS), toxic shock toxin etc
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Complement activation (C5a)
Sepsis--Pathogenesis
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This results in cellular injury and
subsequent organ dysfunction
The precise mechanism is not known, but
proposed mechanisms include:
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Cellular ischemia (O2 lack relative to need)
Direct cell injury by inflammatory mediators
and other products of inflammation
Increased rate of apoptosis (programmed cell
death)
Sepsis--Pathogenesis
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If the mediators balance each other out
and the initial infectious insult is
overcome, homeostasis will be restored
The initial insult may be so severe that it
directly induces SIRS and MODS
In most patients, a balance is not
established and one of the 2 predominates
Specific Organ Involvement
Circulation
 Derangement in metabolic autoregulation
occurs (process that matches O2
availability to need)
 Vasoactive mediators are released that
cause microvascular permeability and
vasodilation (prostacyclin and NO)
 Impaired compensatory secretion of ADH
(vasopressin) may also contribute
Circulation
 In central circulation, early manifestations
include changes in systolic and diastolic
ventricular function
 Initially, CO increases to compensate for
the vasodilation until the patient is no
longer able to do so
Circulation
 In the regional circulation, there is heterogeneity
in normal distribution of blood flow and loss of
regulation
 The microcirculation is a key (if not the most
important) target organ for injury in the sepsis
syndrome
 There is a decrease in the number of functional
capillaries which causes an inability to extract O2
maximally
Circulation
 Panendothelial activation leads to widespread
tissue edema, which is rich in protein
 Hypotension is the most serious expression of
the circulatory dysfunction that results (reduced
arterial tone, increased permeability)
 Other changes include venous dilatation
(decreasing venous return to the heart) and the
release of myocardial depressant factors
Lung
 Endothelial injury leads to disturbed
capillary blood flow and enhanced
microvascular permeability and
subsequent interstitial and alveolar edema
 PMN entrapment amplifies this damage
 ALI/ARDS
GI Tract
 May provided positive feedback loop in
injury from sepsis from various sources:
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Bacterial overgrowth in UGI tract leading to
VAP if patients not fed or prophylaxed
Translocation through gut wall of bacteria
from circulatory abnormalities depressing the
gut’s barrier funtion
Liver
 Liver dysfunction can worsen sepsis by
preventing bacterial clearance
 Can get reticuloendothelial system
dysfunction from the sepsis syndrome
 Increased LFT’s/transaminases
Kidney
 ATN (systemic hypotension, direct renal
vasoconstriction, cytokine release etc may
all cause)
 Likelihood of death increases dramatically
if renal failure accompanies sepsis
Nervous System
 CNS: altered sensorium
 PNS: peripheral neuropathy
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Limb muscle weakness and atrophy
Reduced DTR’s
Loss of peripheral sensation to light touch and pin prick
Preservation of cranial nerve function
Blood
 Thrombocytopenia
 DIC
 Hyponatremia
 Anemia
 Elevated or decreased WBC
Treatment
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Try to get the patient back to homeostasis
as quickly and safely as possible
Fluid is your best ionotrope…do not be
afraid of it
“Hit them early, hit them hard”
Treatment
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Early Goal Directed Therapy in the
Treatment of Severe Sepsis and Septic
Shock
Emmanuel Rivers, NEJM 2001
Treatment

Surviving Sepsis Campaign: International
Guidelines for Management of Severe
Sepsis and Septic Shock: 2008
Crit Care Med 2008 Vol 36 No 1
Treatment
Initial resuscitation (within first 6h)
 Begin resuscitation immediately in patients with
hypotension or elevated lactate (>4)—do not
delay until pending ICU admission
 Resuscitation goals
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CVP 8-12 mmHg
MAP >65 mmHg
U/O > 0.5ml/kg/hr
SVC O2 sat >70%
If venous O2 sat not achieved, consider futher
fluid, PRBC (to keep Hct >30%) or dobutamine
Treatment
Diagnosis
 Obtain appropriate cultures providing it
does not delay antibiotic administration
 2 or more BCs
 One BC from each access device >48hr
old
 Other sites as indicated
Treatment
Antibiotics
 As early as possible and always within 1hr
 Broad spectrum, covering all likely
pathogens then narrow as clinically
indicated
 Stop if not infectious cause, otherwise 710 days
Treatment
Source Control
 Identify anatomic site of infection as soon
as possible (within 6hr of presentation)
 Choose source control with max efficacy
and min physiologic upset
 Remove all intravascular devices if
potentially infected
Treatment
Fluid Therapy
 Crystalloid or colloid
 Use fluid challenge technique while associated
with hemodynamic improvement
 1000cc crystalloid or 300-500cc colloid over 30
mins
 Rate of fluid administration should be reduced if
cardiac filling pressures increase without
concurrent hemodynamic improvement
Treatment
Vasopressors
 Maintain MAP > 65mmHg
 Norepinephrine or dopamine initially
 Then can add epinephrine or vasopressin
 Art line when practical
 No low-dose dopamine for renal protection
Ionotropes
 Dobutamine in patients with depressed
myocardial function
Treatment
Steroids
 Low dose in patients who respond poorly
to fluids and vasopressors
 No ACTH stim test needed
 Use HC with or without FC
 Stop once patient is off vasopressors
Treament
Activated Protein C
 Consider in patients with sepsis induced
organ dysfunction and high risk of death
(APACHE II >24 or MODS) if there are no
contraindications
Treatment
Blood Product Administration
 Give RBC if Hb < 70 to target 70-90
 Do not use FFP unless there is bleeding or
planned invasive procedures
 Give platelets when counts are <5000, or
between 5000 and 30000 and there is
significant bleeding risk
Treatment
Mechanical Ventilation
 Lung protective strategies, using ARDSnet
guidelines
 SBT’s once patient ready for them
 HOB at 30-45 degrees
Treatment
Others
 Sedation as necessary
 DVT/Stress ulcer prophylaxis
 Glucose control (keep 5-8.3)
Summary
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A large and diverse topic
Will be a common occurrence in any
surgical practice
Needs to be recognized and dealt with
quickly to minimize morbidity and
mortality
Treatment