# Storage duration of packed red blood cells transfused during veno-venous extracorporeal membrane oxygenation is associated with elevated pulmonary artery pressure and lung injury in a sheep model

## TL;DR

Older stored red blood cells used during ECMO in a sheep model caused higher lung injury and increased pulmonary artery pressure compared to fresh blood.

## Contribution

This study is the first to show that stored red blood cells during ECMO may worsen lung injury and hemodynamics in a sheep model.

## Key findings

- Stored RBC transfusion increased pulmonary artery pressure compared to fresh RBC and control groups.
- Stored RBC transfusion caused greater lung injury marked by inflammation and edema.
- Coagulation profiles changed with faster clot formation in transfused groups.

## Abstract

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is associated with a high transfusion burden. While trials have concluded that red blood cell (RBC) storage does not impact patient morbidity and mortality in the critically ill or cardiac surgical cohorts, evidence is sparse for ECMO cohorts. A sheep model was to investigate this question. On an underlying injury of smoke inhalation, we compared fresh (< 5 days) or stored (35–42 days) RBC transfusion with no transfusion. Clinically relevant outcomes included pulmonary artery pressure as well as biochemical or histopathological markers of lung, liver, and renal injury.

Twenty-four female Merino/Samm Border Leicester Cross sheep were anaesthetised and placed on pressure-controlled ventilation. They were instrumented for continuous haemodynamic monitoring. They then underwent smoke inhalation injury, followed two hours later by veno-venous ECMO. Sheep were randomised to three groups: control (no transfusion (n = 8)), fresh RBC (n = 8) and stored RBC (n = 8) transfusion occurring six hours after ECMO initiation. Blood samples were taken regularly, and 24 h post-ECMO, animals were sacrificed. Post-mortem samples of lung and kidney were collected for post-mortem analyses.

Following ECMO initiation and transfusion, pulmonary artery pressure increased in the stored RBC group. Histopathological analysis also demonstrated a significantly elevated lung injury in this group. This lung injury was characterised by greater extravasation of inflammatory cells as well as bronchiole damage and oedema. Renal histopathology showed no significant differences between groups. Alanine aminotransferase, aspartate aminotransferase and bilirubin levels increased in a time dependent manner post-transfusion but there were no treatment-associated differences. During experimentation, the coagulation profile changed with firmer clots forming more quickly. Differences were observed between both transfusion groups and controls.

Transfusion of stored RBC elevated pulmonary artery pressure when compared to fresh RBC transfusion and controls. This change was correlated with a greater post-transfusion lung injury in the stored RBC group. Further investigation assessing whether insufficient nitric oxide had a role in these findings is warranted, as is consideration of longer ECMO durations and greater transfusion volumes.