Specific treatments for severe sepsisseptic shock

1. Activated protein C significantly improves outcome in patients with >2 organ dysfunctions if commenced within 48h of onset of severe sepsis. The PROWESS study mainly included patients presenting from the community and had numerous exclusion criteria, particularly related to those at increased risk of bleeding. Subsequent studies revealed <15% of septic patients presenting to ICUs meet both inclusion and exclusion criteria.

2. 'Low-dose' hydrocortisone (50mg qds) given for 7 days improved outcomes if commenced within 8h of septic shock presentation, though only in the subset with an abnormal cortisol response to synthetic ACTH. Our current practice is to start hydrocortisone after performing a Synacthen test and to discontinue this therapy if the test is normal.

3. For norepinephrine (NEPI)-resistant septic shock, i.e. high-output severe hypotension not responding to adequate fluid loading and a NEPI dose >0.4pg/kg/min, we consider careful administration of terlipressin or methylthioninium chloride. Until more data are forthcoming, these agents should be viewed as rescue therapies rather than a straight alternative for NEPI.

4. We occasionally use plasmapheresis, prostaglandins or high-output haemofiltration for resistant cases of septic shock, particularly those with low cardiac outputs. We readily acknowledge the evidence base for these therapies is slight and our use is based on anecdotal success.

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