Artificial Blood Substitutes

摘要

Haemorrhagic shock kills. The maintenance of intravascular volume is essential and resuscitation with isotonic crystalloid or volume expanders such as gelofusin or pentastarch is fundamental in the management of shock, with the addition of packed red cells when available, to restore oxygen carrying capacity and oxygen delivery to reinstate tissue perfusion - although the timing and target blood pressure for resuscitation is still not universally agreed. Donor blood however is a limited resource for which there is increasing demand. Fourteen million units of blood were used in the US alone last year. England and Wales require 8,000 units of blood per day. Currendy there are only 5.1 days' stock of O negative blood in the UK banks. 50% of RBC transfusions are used in trauma or surgery, to compensate for major blood loss. The increase in demand for blood is due to an increase in the ageing population, and decreased allogenic donation. Vamvakas et al predict an annual shortfall in the US of 4 million unitsof blood by 2030. Artificial oxygen carriers may provide a solution to the shortfall of donor blood available for transfusion.Artificial oxygen carrier infusions offer volume expansion and oxygen carriage. The advancement of artificial blood substitutes encompasses two different pathways of development. Synthetic blood substitutes are based on perfluorocarbons, whilst haemoglobin-based oxygen carriers use human or bovine haemoglobin as the core product. The aim of these products, both in the elective and trauma setting, is to reduce the need for allogenic blood transfusion and maintain tissue oxygenation.The US military have been the greatest advocates of the development of artificial blood substitutes because of the vital need and benefits in the battlefield scenario. In Vietnam, 2774 casualties received almost 20,000 units of blood, most receiving 2-5 units. Blood is currendy unavailable far forward on the battlefield for predominandy logistic reasons. Casualties may be salvageable if intervention is available far forward and earlier. Artificial oxygen carriers could provide part of the solution to this problem.Coupled with unavailability of blood far forward on the battlefield, the wastage of blood resources during war is also of great concern. 60% of the 1.3 million units of blood dispatched during the Vietnam War and 95% of 120,000 units during the Gulf War were discarded. This was largely due to the units passing their expiry date. During the same years of the Vietnam War, 15-35% of blood for civilian use was wasted. Artificial blood substitutes have been developed with this in mind, and have been engineered to have a long shelf-life. These factors have propagated the military investment in the development of these products. The U.S. military has spent approximately dollar 30 million on the enterprise to date.Allogenic blood transfusion is associated with potential significant immunomodulatory and infective complications, as outlined in Table 1. The combination of potential adverse effects of transfusion, impending shortage of blood, high cost of packed red cells storage and transfusion, and limited availability in pre-hospital scenario and battlefield, has lead to an accelerated push in the development of a clinically employable alternative.