There are several additional therapies which have been advocated in severe sepsis.

Recombinant Human Activated Protein C (rh-APC)

This drug has now been withdrawn following a repeat trial which demonstrated no effect.

rh-APC is thought to control thrombosis and improve microcirculatory flow in severe sepsis.

A worldwide evaluation (PROWESS study) was associated with a reduction in mortality and further weight was added by the ENHANCE study, an open label extended evaluation.

However, the subsequent ADDRESS study in which rh-APC was given to patients with less severe disease was stopped because of no apparent mortality benefit.

Potential risks of administration of rh-APC include bleeding and this should be considered before and during use.

rh-APC is currently not recommended in the treatment of sepsis and has been withdrawn from the market.

Low dose steroids

IV hydrocortisone (200mg once/day) could be considered if adequate fluid resuscitation and vasopressor therapy do not sufficiently restore haemodynamic stability.

Glucose control

Target upper blood glucose levels <10mmol/L (180mg/dl). https://journals.lww.com/ccmjournal/Fulltext/2017/03000/Surviving_Sepsis_Campaign___International.15.aspx

Rrenal replacement

This treatment has no rationale outwith the normal indications for renal replacement therapy. There is one trial indicating a worse outcome when used for sepsis, and no trials indicating a positive effect.

Renal replacement therapy should be offered to patients with acute kidney injury if appropriate.

There is currently no evidence favouring intermittent haemodialysis over continuous haemofiltration.

The use of high dose haemofiltration had once been hypothesised to remove pro-inflammatory mediators with potential benefit; however, there is currently no evidence or indeed rationale to support the use of this therapy. The only trial in the literature had a higher mortality in the treatment group.

Two recent randomised controlled trials have failed to show benefit using higher dose RRT, but work is ongoing to investigate the dose of RRT.