Use of Polyclonal Ig as Adjuvant Therapy for Sepsis/Severe Sepsis K Georg. Kreymann et al CCM 2007 35(12) 2677-

This important paper is a meta analysis of all trials including the use of IVIG in patients (adult and Children-including neonates) with sepsis and severe sepsis. IVIG bind up toxins, allow oponisation and bind toxins and superantigens Previous papers from the Cochrane group have apparently not included all studies which this meta analysis has tried to do.
The search criteria was vigorous, including peer reviewed articles as well as personal communications, letters etc. They particularly included studies which used mortality as an end point. They graded papers on strict guidelines as there was a paucity of double blinded randomised placebo controlled trials (DBRPCT) to try and add some power to the meta analysis.

In all 27 trials were included. In 15 trials, including 1492 patients (adults and children) showed the use of IVIG created a RR of 0.79 (significant). When split into type of IVIG, the IVIGAM (immunoglobulins containing predominantly IVIG A and M) were used in 560 patients with a significant RR of 0.66. With just IVIG, including 932 patients, RR was 0.85 (significant). IVIG A and M showed further benefit over just IVIG. It is interesting to note many studies showed a positive trend but these trials were rated as significantly heterogeneous on tests. The largest trial showed no difference between those treated with IVIG and these not. 12 trials included neonates and are not discussed further here.

In conclusion they stated the use of IVIG A+M reduce mortality by 34% in sepsis or severe sepsis from all cause with, a 15% reduction if IVIG is used in adults or children.

This is an interesting paper. There are always faults in trying to draw conclusions from heterogeneous papers, with poor methodology and small patient numbers, particularly as some involve children with different pathologies. The grading of papers if not large DBRPCT to allow recommendations and comparisons will only be as good as the criteria used to grade papers.
That said there is good reason for IVIG to work, yet they have not received publicity in the sepsis care bundles, not being included in the original and the re written sepsis bundles. A few points need to be considered;-

1. Most of the studies are European. The sepsis guidelines are American.

2. Vast heterogenocity in the trials both in numbers patients used, definition of sepsis, dose and type of IG used.

4. Few DBPRCT. The ones that exist suggest no difference in outcome. Smaller studies suggest bigger differences.

Bearing all this in mind, the poor evidence behind most of the surviving sepsis guidelines, then the absence of IVIG as at least a consideration is note worthy. Other problems MAY exist with IVIG, for example IVIG may be immunosuppressant and could have long term problems (not examined in these studies). They could increase nosocomial infections and therefore late mortality BUT steriods do the same and they are included and the evidence is poorer.

Therefore why is IVIG not even considered as part of the surviving sepsis guideleins and should we be using them in patients with severe sepsis/septic shock?

Dr. Andy Sharman

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1 comment so far

  1. danharvey on

    I noticed that IVIG is recommended by the DOH for the treatment of MRSA PVL necrotising pneumonia (in this useful review). I guess the basis for this will be grade D or at best C evidence. So treatments remain in the guidelines on the basis of case series or uncontrolled trial evidence for specific rare sub types of conditions, but are rejected for broader condition definitions. This appears to me to be a double standard.


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