C.R.A.S.H. study: A randomised study of tissue oxygenation in an ovine model of haemorrhagic shock comparing the effect of colloid, fresh red cells, aged red cells and saline.

We will assess the amount of oxygen getting to the key organs (heart, brain and kidney) and how well the different fluids achieve their aim – namely to improve organ function, using other tests to show how well these organs function after fluid administration.

Grant ID: PROJ-2009-015-STAIB-CRASH

Project Summary

Blood loss is a major cause of early deaths after trauma, accounting for 51% of the deaths occurring during the initial 48 hours after hospital admission. Decisions made in the early treatment of severe blood loss have important consequences for patient survival and length of time in the Intensive Care Unit. Red blood cell (RBC) transfusion is a key component of the management in acute haemorrhagic shock, based on the assumption that transfused RBCs improve delivery of oxygen to the tissues. However existing evidence suggests this may not be the case. Recent studies suggest however that transfusion of older blood may worsen both morbidity and mortality in certain patient subgroups. The aetiology behind this association shown in this retrospective study is unclear, but seems related to an alteration in risk/benefit profile of old vs new blood. Hence, this project will investigate the ability of typical fluids used in haemorrhagic shock in ED departments to improve oxygen delivery to vital organs following severe haemorrhage.

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Outcomes

i. In looking at biomarkers to measure haemorrhagic shock, the research team concluded that the measurement of serum lactate and other global markers underestimate the severity of end organ hypoxia and hypoperfusion in haemorrhagic shock.
ii. Transfusion of selenium-poor packed red blood cell (PRBC) transfusions can dilute selenium levels and compromise glutathione peroxidase antioxidant activity and thereby allow lipid peroxidation. As there was no evidence that aged PRBC induced more severe oxidative injury this suggests that selenium dilution is a key underlying mechanism.
iii. Transfusion of stored ovine blood induced (1) transient pulmonary arterial hypertension but no oedema and (2) reduced fibrinogen levels more than fresh blood, but neither induced coagulopathy. Thus, transfusion of stored blood affected pulmonary function even in the absence of overt organ injury.
iv. The team also demonstrated the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

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Dissemination

Fung, Y.L., Simonova, G. and Tung, J.P., 2016. Lessons from sheep models of transfusion. ISBT Science Series, 11(S2), pp.73-78.

Ng, M.S.Y., Ng, A.S.Y., Chan, J., Tung, J.P. and Fraser, J.F., 2015. Effects of packed red blood cell storage duration on post-transfusion clinical outcomes: a meta-analysis and systematic review. Intensive care medicine, 41(12), pp.2087-2097.

Chemonges, S., Shekar, K., Tung, J.P., Dunster, K.R., Diab, S., Platts, D., Watts, R.P., Gregory, S.D., Foley, S., Simonova, G. and McDonald, C., 2014. Optimal management of the critically ill: anaesthesia, monitoring, data capture, and point-of-care technological practices in ovine models of critical care. BioMed Research International, 2014.

Milford, E.M., Reade, M.C., Shekar, K., Tung, J.P. and Fraser, J.F., 2014. An age-of-blood transfusion trial in the trauma setting is crucial and animal models may help inform trial design. Crit Care Resusc, 16(2), pp.149-150.

McDonald, C.I., Fraser, J.F., Shekar, K., Dunster, K.R., Thom, O. and Fung, Y.L., 2014. Transfusion of packed red blood cells reduces selenium levels and increases lipid peroxidation in an in vivo ovine model. Transfusion Medicine, 24(1), pp.50-54.

Simonova, G., Tung, J.P., Fraser, J.F., Do, H.L., Staib, A., Chew, M.S., Dunster, K.R., Glenister, K.M., Jackson, D.E. and Fung, Y.L., 2014. A comprehensive ovine model of blood transfusion. Vox Sanguinis, 106(2), pp.153-160.

Fung, Y.L., Tung, J.P., Foley, S.R., Simonova, G., Thom, O., Staib, A., Collier, J., Dunster, K.R., Solano, C., Shekar, K. and Chew, M.S., 2013. Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage. Vox sanguinis, 105(2), pp.150-158.

Fung, Y.L., Do, H.L., Tung, J.P., Collier, J. and Fraser, J.F., 2011. A validated ovine model for blood collection, processing, compatibility testing and transfusion. Vox Sanguinis, 101, pp.134-134.

Conference:
-Fung Y.L., Do H.L., Tung J., Collier J., Fraser J.F., "A validated ovine model for blood collection, processing, compatibility testing and transfusion", 22nd Regional Congress of the ISBT, Asia, Nov 19 - 23, 2011,Taiwan
- Fung YL, Foley R., Varzeshi M., Simonava G., Do H.L., Staib A., Fraser J.F., "Red cell and albumin resuscitation following acute massive haemorrhage alters haemostasis", 22nd Regional Congress of the ISBT, Asia, Nov 19 - 23, 2011, Taiwan
- Fung YL, McDonald Cl., Thom O., Fraser J.F., "Transfusion of fresh or aged red cells after haemorrhagic shock reduces selenium and glutathione peroxidase", 22nd Regional Congress of the ISBT, Asia, Nov 19 - 23, 2011, Taiwan
- Foley R., Fung Y.L., Varzeshi M., Simonava G., Do h.L.,Staib A., Fraser J.F., "Massive Haemorrhage and Transfusions each change Coagulation Plasma Factors," Australia New Zealand Intensive Care Society Annual Scientific Meeting, 2011
- Staib A., Collier J., Fung Y.L., Do H.L., Thom O., Dunster K., Fraser J.F., "What are the best markers of essential tissue hypoperfusion in haemorrhagic shock?", 28th Australasian College for Emergency Medicine Annual Scientific Meeting, 2011; 24(1):18

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