"War! What is it good for?"
Clinical trials in trauma treatment protocols.
Doctors are re-evaluating what mix of fluids should be given to patients that are experiencing significant hemorrhage secondary to trauma. There are several types of fluids that can be given to trauma patients, each acting for a different purpose.
Crystalloids are simple salt solutions. They have the same concentration of salts as blood. Crystalloids are cheap and easily stored. Doctors us large volume infusion of crystalloids for trauma patients to counteract the low blood pressure. In shock, vessels lose tone and the volume necessary to keep the vasculature 'full' can increase by 100-200%. Crystalloids act to fill in the newly created void in the vasculature. Being a simple salt solution, by adding large volumes of crystalloids, doctors dilute out red blood cells and important blood proteins, including clotting factors. A rapid increase in blood pressure can also dislodge tenuous clots formed at trauma sites, causing a worsening of bleeding. In addition only 25% of crystalloids remain in the vasculature after 1 hour, the rest going into tissue and the urine. In this way, the patient can quickly lose and increases in blood pressure.
Colloids are salt solutions with polymers added that act similarly to blood proteins to keep the liquid volume inside blood vessels instead of losing it to tissue. Colloids must be given in much smaller volumes than crystalloids, because at a certain volume colloids will interfere with clotting.
Doctors can give hypertonic solutions in small volumes. These solutions increase blood pressure by drawing fluids out of tissues and back into the blood vessels. The solutions are usually very concentrated salt solutions. They work well in patients with normal hydration, which most trauma patients are. There is a limit to how much hypertonic solution can be given as an increase in blood salts can occur which leads to secondary metabolic problems.
Apart from manufactured fluids, doctors can also choose from human derived fluid products. These products have the disadvantage of having specialised storage requirements and are more difficult and expensive to obtain.
Blood is composed of red and white blood cells mixed in plasma. Red blood cells carry oxygen. White blood cells include platelets which are one main component of the clotting system. Plasma contains salts, nutrients and proteins. The proteins act to keep water inside the vessels, provide important antibodies, and also are the other main component of clot formation.
Doctors can give packed red blood cells, which has had most of the plasma removed. This would increased the red cell count in an anemic patient without adding much volume, which is useful mainly in situations such as kidney failure or heart failure where an increase in blood volume could be deleterious. It is not often useful in trauma patients.
Doctors can also give whole blood. Whole blood provides some increase in fluid volume while providing all of the beneficial components of blood. If a trauma patient needs lots of volume replacement, whole blood cannot provide enough volume without causing dangerous increases in red blood cell count. Whole blood contains platelets which are important in clotting in trauma patients.
Plasma is the liquid component of blood from which the blood cells have been removed. Plasma can be given in large volumes without increasing the red cell count. Plasma provides a balanced salt solution, but also contains blood proteins to keep the volume inside of the blood vessels. Plasma contains antibodies and proteins that help 'mop up' free radicals and toxins released by damaged tissues. Plasma also contains clotting proteins, essential for trauma patients. Plasma is generally stored frozen and must be carefully thawed prior to use. This can be an issue for a trauma patient who is bleeding NOW; it can take 20-40 minutes to thaw a unit of plasma. Plasma also comes packaged in relatively small volumes. A trauma patient may need 2-3 liters of fluid rapidly to restore blood volume; plasma comes in volumes of 125-500ml bags.
A retrospective study examining survival rates of trauma victims in combat in Iraq and at trauma centers in the UK suggests that plasma should be given in much higher volumes than traditionally administered at ratios of 1:1 or 1:2 plasma:red blood cells as opposed to more conservative 1:8 ratios. Survival of trauma patients increased from 12% to 65% in patients given higher volumes of plasma. New protocols for early and aggressive administration of plasma have been implemented at UK and US combat stations in Iraq and Afghanistan and are now being implemented at domestic trauma centers in the UK.
New Blood Transfusion Protocols
From a completely non-scientific point of view, these findings are not surprising. As a veterinarian, my gut feeling evaluation of plasma is that "plasma is a goodness". Plasma is a very complex solution with proteins and small molecular components that have not been fully described but appear to have beneficial effects in any sort of critical situation. If your patient with an inflamed pancreatitis or parvovirus or liver disease isn't doing well, a plasma transfusion can cause a dramatic improvement in clinical outcomes even if the blood tests we run don't give a specific indication for plasma administration. We are even moving toward giving plasma in cases where we think the patient could develop a need for it later, rather than waiting for the need to develop. There are very few complications with the use of plasma. I have seen a single allergic reaction to plasma which was treated with standard protocols. Human plasma, like other human blood products, must obviously be carefully screened for infectious diseases. The biggest problem with plasma is that in veterinary medicine it is very very expensive. A single unit can put an owner back $400-700, and depending on the patient, several (in one case I know, over 20) units may be required. As noted above, it also has to be kept frozen and thawed carefully. Once thawed, there is a lot of debate as to whether it can be refrozen and rethawed without loss of clotting factors, so there may be issues of waste if a patient no longer needs plasma once a unit has been thawed.
An improvement of survival from 12% to 65% tells me that I need to give more plasma, and more quickly, to my trauma patients, if the owner can afford it.
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