SIRS

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SIRS

• Dr. Jonathan R. Goodall
• M62 Coloproctology Course
• 31st March 2006

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SIRS
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SIRS

• Definitions
• Recognising the patient with SIRS
• Management of the patient with SIRS
• Activated Protein C
• Use of Steroids
• Glucose Control

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SIRS
pring s eluctantly tarting to happen
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SIRS
omething ntrinsically elated to epsis
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SIRS
omething ntensivists are eliably mug about
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SIRS
yndrome nstictively ecognised by urgeons
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SIRS
omething nfrequently ecognised by HOs
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Definitions

• Systemic Inflammatory Response Syndrome (SIRS)
• Severe Sepsis
• Septic Shock
• Refractory Shock

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Definitions

• SIRS 2 or more of
• Temperature gt 38C or lt 36C
• Heart rate gt 90 bpm
• Resp rate gt 20 breaths.min -1 or PaCO2 lt 4.3kPa
  (32mmg)
• WBCs gt 12 or lt 4 (or gt10 immature forms)

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Definitions

• Sepsis
• SIRS with documented infection site
• Severe Sepsis
• Sepsis organ dysfunction, hypoperfusion or
  hypotension
• Septic Shock
• Severe sepsis (SBP lt 90mmHg) despite adequate
  fluid resuscitation

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Crit Care Med 2004 Vol. 32 No 3
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• Experts from 11 international organisations
  (2003)
• Management guidelines that would be of practical
  use for the bedside clinician
• International effort to increase awareness
  improve outcome

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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Key Recommendations

• Recommendations on groups of treatments
• Total consensus reached on all but two of
  recommendations
• Most of recommendations are not supported by
  high-level evidence

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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A. Initial Resuscitation

• Resuscitation should begin as soon as condition
  is recognised
• In first 6 hours should include all of the
  following
• CVP 8-12mmHg
• MAP gt 65mmHg
• UO gt 0.5ml.kg-1.hr-1
• CvO2 gt 70
• Grade B Early Goal Directed Therapy in the
  Treatment of Severe Sepsis. Rivers et al NEJM
  2001 3451368-77

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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B. Diagnosis

• Appropriate cultures should always be obtained
  before antimicrobial therapy
• At least 2 blood cultures
• One from each IV device gt48 hours old
• Other cultures as appropriate
• Grade D/E

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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C. Antibiotic Therapy

• Appropriate antimicrobial therapy should be
  started within 1 hour of onset Grade E
• Initial empirical therapy Grade D
• Focussed after 48-72 hours
• ? Monotherapy
• 7-10 day course Grade E
• Stop if non-infective cause found Grade E

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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D. Source control

• Evaluate all patients for the presence of a focus
  of infection amenable to source control
  measures (SCM) (Grade E)
• Method of SCM must weigh benefits risks (Grade
  E)
• Once a source of infection identified, SCM should
  be instituted as soon as possible (Grade E)
• IV access devices should be removed promptly
  (Grade E)

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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E. Fluid Therapy

• Fluid resuscitation may consist of natural or
  artificial colloids or crystalloids. There is no
  evidence-based support for one type of fluid over
  another.
• Rates
• 500-1000ml crystalloids over 30 mins
• 300-500ml colloids over 30 mins
• Grade C

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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F G Vasopressors Inotropes

• Use when appropriate fluid resuscitation fails to
  restore adequate MAP
• Noradrenaline or dopamine dobutamine (Grade D)
• Low-dose (renal) dopamine should not be used.
  (Grade B) Bellomo et al Lancet 2000
  3562139-2143

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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H. Steroids

• IV hydrocortisone (200-300mg/day) should be used
  for 7 days in patients requiring vasopressor
  therapy (Grade C)
• gt 300mg/day should not be used
• Steroids should not be for the treatment of
  sepsis in the absence of shock (Grade E)

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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I. Activated Protein C

• Recommended in patients at high risk of death
  without contraindications (Grade B) Bernard GR et
  al, N Engl J Med 2001344699-709

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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Activated Protein C - properties

• Anticoagulant
• Degrades factor Va VIIIa thereby inhibiting
  generation of thrombin
• Pro-fibrinolytic
• Promoted fibrinolysis by inhibiting plasminogen
  activator inhibitor
• Anti-inflammatory
• Direct effects on endothelium and neutrophils

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PROWESS Study Group

• 1690 patients with sepsis enrolled
• Mortality rate 30.8 in placebo group vs 24.7 in
  APC group
• Relative risk of death reduction 19 absolute
  risk reduction 6 (P0.005)
• Increased incidence serious bleeding (3.5 vs 2 )

• Bernard GR et al, N Engl J Med 2001344699-709

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M. Glucose Control

• Following initial stablisation maintain blood
  glucose lt 8.3 mmol/l
• (Grade B) Intensive Insulin Therapy in
  Critically Ill Patients. van den Berghe et al N
  Engl J Med 20013451359

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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Intensive Insulin Therapy

• 1548 patients admitted to ICU
• Intensive Treatment Group
• Insulin started if glucose gt 6.1 mmol.l-1
• Glucose controlled 4.4 - 6.1 mmol.l-1
• Conventional Treatment Group
• Insulin started if glucose gt 12 mmol.l-1
• Glucose controlled 10.0 11.1mmol.l-1

van den Berghe NEJM 20013451359
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Intensive Insulin Therapy

• Mortality Rates
• Treatment Group 4.6
• Conventional Group 8.0
• Unbiased risk reduction 32
• Also reduced incidence of complications (eg
  septicaemia, acute renal failure)

van den Berghe NEJM 20013451359
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M. Glucose Control

• There is no reason to think these data are not
  generalisable to all severely septic patients
• Intensive Insulin Therapy in the Medical ICU. van
  den Berghe et al N Eng J Med 2006 354 449-461

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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P. DVT Prophylaxis

• Use unfractionated or LMW heparin
• For patients with contraindication to heparin,
  use of a mechanical prophylactic device is
  recommended
• In very high risk patients, use both
  pharmacological and mechanical prophylaxis
• Grade A

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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Q. Stress Ulcer Prophylaxis

• H2 receptor antagonsists are more efficacious
  than sucralfate and are the preferred agents
• Proton pump inhibitors have not been assessed in
  a direct comparison to H2 receptor antagonsists,
  and their relative efficacy is not known.
• Grade A

Dellinger et al, Crit Care Med 2004 Vol 32, No 3
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Summary

• SIRS is very common
• SIRS is a difficult problem
• It is a complex disease
• It is not easy to recognise
• Steroids probably useful
• APC is useful
• Tight glucose control is useful (in surgical
  patients)

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