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  1. Iain Mackenzie, consultant in intensive care medicine and anaesthesia1,
  2. Andrew Lever, professor of infectious diseases and honorary consultant physician2
  1. 1John Farman Intensive Care Unit, Box 17, Addenbrooke's Hospital, Cambridge CB2 2QQ
  2. 2Department of Medicine, University of Cambridge, Cambridge
  1. Correspondence to: I Mackenzie iain{at}number2.demon.co.uk
  • Accepted 17 September 2007

This is the second of two reviews—the first discussed the definition, epidemiology, and diagnosis of sepsis, whereas this one focuses on management and outcome. Management of sepsis can conveniently be divided into general supportive measures and specific treatment.

Summary points

  • A favourable outcome depends on early, aggressive, treatment

  • Antimicrobial treatment must take into account both patient susceptibilities and local resistance patterns; advice from infectious disease or microbiology colleagues is often helpful

  • Volume resuscitation and cardiovascular support should be titrated to simple clinical end points

  • Subtle signs of organ hypoperfusion should be sought in physically robust patients

  • The role of activated protein C and low dose steroids remains to be clarified

What are the general supportive measures?

Circulatory compromise arises from the combination of vasodilatation, capillary leak, and reduced myocardial contractility, and needs early correction. Whether crystalloids or colloids are better for volume resuscitation remains unresolved. Few people now use human albumin after a controversial meta-analysis concluded that albumin was associated with a 6% excess mortality.1 A subsequent randomised controlled trial found no difference in any of the outcome measures examined, including mortality.2 Another question is how to gauge the adequacy of fluid resuscitation. The pulmonary artery catheter has not been shown to be associated with either harm or benefit,3 4 and its use is declining. Clinical end points (box 1) remain useful, although some centres are also using oesophageal Doppler or pulse contour analysis. These methods provide information on the effect of fluid loading on cardiac output and stroke volume. In ventilated patients, variation in stroke volume can be used as an index of preload.

Box 1 Clinical and functional end points for titration of fluid resuscitation

  • Sustained increase in blood pressure

  • Sustained increase in central venous pressure

  • Fall in heart rate

  • Increased urine output

  • Increase in mixed venous saturation

  • Fall in base deficit

  • Fall in blood lactate concentration

Catecholamines are needed when fluids are insufficient to …

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