More on additives to EVLP perfusate: Methylprednisolone

A recent Dutch study shows that adding methylprednisolone to the EVLP perfusate improved the quality of donor lungs.

Although the concept of the inflammatory cytokine storm has now become a familiar feature of severe Covid-19 infection, it has also long been recognized as an inherent complication of organ donation after brain-stem death(12).

This storm-like surge of pro-inflammatory cytokines can be attenuated to some extent already during donor management, prior to organ retrieval, by the judicious use of corticosteroids, primarily methylprednisolone.

Some groups have also shown that the combined effects of methylprednisolone use during both donor management and subsequent EVLP are beneficial, even in DCD donors(13).

However, no-one had investigated the effects of methylprednisolone when used only during EVLP until a recent Dutch study(14) in which groups of rat lungs from brain-dead donors were subjected to prolonged (six-hour) acellular EVLP. One group received methylprednisolone in the perfusate while the others did not.

Not surprisingly, the quality of the lungs receiving methylprednisolone improved significantly on several fronts after six hours of EVLP: the positive inspiratory pressures needed to maintain tidal volumes decreased, lung compliance and lung edema improved, lactate production decreased and pro-inflammatory gene expression levels of IL-1β, IL-6 and MCP-1, and IL-6 perfusate levels all decreased. There was some deterioration in quality over time which the authors attribute to the small organ size of their rat lung model.

However, all in all, the results clearly suggest that methylprednisolone downregulates pro-inflammatory gene expression during EVLP in lungs derived from brain dead donors.

XVIVO Insights PB-2021-04-20

References:

12. Avlonitis VS, et al: The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant, 2005, vol. 5, 4 Pt 1 (pg. 684 93 ) Google Scholar Crossref  PubMed
13. Martens A, et al. Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation. Transpl Int. 2016;29:1237–1246.
14. Van Zanden J E, et al. Ex Vivo Perfusion With Methylprednisolone Attenuates Brain Death-induced Lung Injury in Rats. Transplant Direct . 2021 Mar 16;7(4):e682. doi: 10.1097/TXD.0000000000001141. eCollection 2021 Apr. (link to Abstract)