• Severe sepsis affects 500,000 annually in the United States
• Despite improvements in critical care mortality of 20-50% remains unchanged

Definitions

Condition	Definition
Bacteraemia	The presence of viable bacteria in the bloodstream
SIRS	The systemic inflammatory response to a variety of clinical insults manifest by two or more of the following: Temperature >38°C or <36° Heart Rate > 90 bpm Respiratory Rate > 20 breaths per minute or PaCO2 > 4.3 kPa White Cell Count > 12,000 or <4,000 per mm3
Sepsis	SIRS with documented infection
Severe SIRS	SIRS with documented infection and hypoperfusion, hypotension and organ dysfunction
Septic Shock	Sepsis with hypotension despite adequate fluid resuscitation

Clinical features of sepsis and SIRS

• Cardiorespiratory effects
  • Increased cardiac output
  • Decreased vascular resistance
  • Increased oxygen consumption
  • Fever or hypothermia
  • Tachycardia
  • Tachypnoea
• Metabolic or haematological effects
  • Respiratory alkalosis
  • Deranged liver function
  • Deranged renal function
  • Altered whit cell count  and platelets
  • Disseminated intravascular coagulation

Aetiology of SIRS

SIRS can arise from a number of aetiological triggers

• Infection – bacterial, viral, fungal
• Hypovolaemic shock
• Trauma
• Burns
• Tissue ischaemia
• Pancreatitis

Bacterial Infection is commonest cause

• 50% due to gram-negative organisms
• 40% due to gram-positive organisms

Mechanisms in the pathology of SIRS

• Over-production of inflammatory mediators
• Under-production of anti-inflammatory mediators
• Receptor abnormalities
• Decreased destruction of inflammatory mediators
• Abnormal leukocytes

Major inflammatory mediators involved in SIRS

• Platelet activating factor
• Tumour necrosis factor -alpha
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Interleukin-10

Bibliography

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Boontham P,  Chandran P,  Rowlands B,  Eremin O.  Surgical sepsis:  dysregulation of immune function and therapeutic implications.  Surg J R Coll Surg Edinb Irel 2003;  1:  187-206.

Cohen J.  The immunopathogenesis of sepsis.  Nature 2002;  420:  885-891.

Parker S J,  Watkins P E.  Immunomodulatory therapies of sepsis and SIRS.  In:  Johnson C D,  Taylor I eds.  Recent advances in surgery 23.  Edinburgh, Churchill Livingston 2000:  55-68.

Paterson R L,  Webster N R.  Sepsis and the systemic inflammatory response syndrome.  J R Coll Surg Ed 2000;  45:  178-182.

Russell J A.  Management of sepsis.  N Engl J Med 2006;  355: 1699-1713.

Vincent J L,  de Carvalho F B,  de Backer D.  Management of septic shock.  Ann Med 2002;  34:  606-613.

Wheeler A P,  Bernard G R.  Treating patients with severe sepsis.  N Eng J Med 1999;  340:  207-214.