Intravenous fish oil in critically ill and surgical patients - Historical remarks and critical appraisal.

The purpose of this review is to explain the historical and clinical background for intravenous fish oil administration, to evaluate its results by using a product specific metaanalysis, and to stimulate further research in the immune-modulatory potential of fish oil. Concerning the immune-modulatory effects of fatty acids, a study revealed that ω-3 as well as ω-6 fatty acids would prolong transplant survival, and only a mixture with an ω-6:ω-3 ratio of 2.1:1 would give immune-neutral results. In 1998, the label of a newly registered fish oil emulsion also acknowledged this immune-neutral ratio in conjunction with ω-6 lipids. Also, two fish oil-supplemented fat emulsions, registered in 2004, used a similar ω-6:ω-3 ratio. Such an immune-neutral ω-6:ω-3 ratio denoted progress for most patients compared to pure ω-6 lipid emulsions. However, this immune-neutrality might on the other hand be responsible for the limited positive clinical results gained so far in critically ill and surgical patients where in most cases significance could only be shown for the pooled effect of numerous trials. Our product specific metaanalysis also did not reveal any differences, neither in infections rates nor in ICU or hospital length of stay. To evaluate the immune-modulatory effect of fish oil administered alone, new dose finding studies, reporting relevant clinical outcome parameters, are required. Precise mechanistic or physiological biomarkers for the indication of such a therapy should also be developed and validated.