Ouch! I’ve just given myself a paper cut!
*Utters a string of expletives that would make a pirate blush*
As I apply pressure to my haemorrhaging war wound, I notice that the bleeding slows down to a stop. That is because my body is able to clot at the site of this small injury according to the physiology of the clotting cascade. However, it would be a different situation if I was in a horror movie and had my arm chewed off by zombies! I would now be experiencing a massive loss of blood that would result in the need for a massive blood transfusion. The internal processes of the body to clot may not be sufficient in the setting of a massive haemorrhage, and so it will need the help of some friends in the form of other blood products to help stop the bleeding.
*Cue the Rocky theme song as I battle through a horde of zombies with one arm to find an abandoned hospital, with a fully functional blood fridge, to initiate a massive blood transfusion protocol*
What is a massive blood transfusion defined as in an adult?
Most facilities will have a protocol in place on the definition of a massive blood transfusion and the processes involved with triggering the massive blood transfusion protocol. There are some widely accepted definitions or criteria for adults that should trigger the massive blood transfusion protocol within a facilities including:
- The transfusion of one blood volume in 24 hours
- Can also be defined as more than 10 units of packed red blood cells in 24 hours, or the anticipated need to do so
- The transfusion of half of one blood volume in 4 hours
- Can also be defined as more than 4 units of packed red blood cells in 4 hours, or the anticipated need to do so
- Active bleeding of more than 150 mL per minute
Adult blood volume is approximately 70 mL/kg of ideal body weight.
A massive blood transfusion protocol has been initiated; what do I do?
There are some key interventions required for the successful management of a patient requiring a massive blood transfusion. This includes the early identification of blood loss, rectification of the cause of bleeding, restoration of the blood loss and coagulopathy management.
Unfortunately, the massive blood transfusion itself can cause problems for the patient and the active management of these adverse effects also need to be considered. We are going to remember the management principles and considerations involved with a massive blood transfusion with the acronym: REPLACE!
Replacement of intravascular volume loss
The problem with bleeding is that the loss of intravascular volume significantly decreases our blood pressure. Furthermore, the loss of blood significantly decreases circulating haemoglobin within our bodies. When you pair these two problems together without intervention, it results in the decreased perfusion of vital organs eventually leading to what we know as hypovolemic shock.
We can lose up to 15% of our blood volume without any changes in our observations, losing approximately 8-10% of our blood volume each time we donate blood. The body has processes in place to compensate for a loss of intravascular volume of up to 30% by increasing the heart rate to increase cardiac output and increasing systemic vasoconstriction to increase systolic blood pressure. After 40% of our blood volume is lost, the body cannot compensate any further reaching a point of decompensation.
The general rule of thumb is that we replace the intravascular volume with what we are losing. So if we are bleeding and losing blood, we should replace with packed red blood cells. We should consider that transfused blood is thick and may circulate a little bit better around the body when aided with a bit of dilution. So give a little crystalloid filling, but not too much! It has been found that giving more than a 1.5:1 ratio of crystalloid to packed red blood cells is independently associated with a higher risk of multi-organ failure, acute respiratory distress syndrome and acute coronary syndrome.
Our attempts to replace the blood that we are losing are futile if we do not find a way to stop the bleeding. If the bleeding is external, we can try to get control of it by compressing the bleeding site, applying a tourniquet above the bleeding extremity or packing the bleeding wound. If the bleeding is internal, there needs to be an emergent surgical intervention to find the source and get control of it. In the mean time, we can follow the remaining steps in the REPLACE acronym to attempt to stop the bleeding.
But aren’t we trying to avoid hypotension to avoid hypovolemic shock? However, your patient is already bleeding. Adding more force behind the bleed is only going to worsen it! You want blood pressure, but you don’t want too much blood pressure while the patient is still bleeding. So adopt the Goldilocks policy here; not too much, not too little…just right! Permissive hypotension of 80-100 mmHg systolic is usually recommended until the bleeding has stopped, then we can aim for a blood pressure that is normal for the patient.
Low body temperature management
We’ve heard it time and time again; cold blood doesn’t clot! That’s why we store donated blood in the fridge. A patient that is cold also has a slower heart rate, decreased myocardial contractility and impaired uptake of oxygen by the cells; leading to worsening shock. These are all things that we are trying to avoid or improve in a bleeding patient, so it is of the utmost importance that we consider the patient’s body temperature during a massive blood transfusion with packed red blood cells that have come straight from the fridge with a temperature of 8 degrees celsius.
It is easier to keep a patient warm than trying to warm them up. So if your facility has access to a blood warmer, utilise it to give all of your packed red blood cells. Also remember to put an active warming blanket on your patient to help with improving their temperature. We should aim for a temperature of more than 35 degrees celsius.
There are many reasons for why a patient develops an acidosis while actively bleeding including:
- Increased lactate production secondary to the anaerobic metabolism the body utilises when there is an insufficient blood pressure or haemoglobin to perfuse the vital organs with oxygen to allow aerobic metabolism
- The longer the vital organs remain without adequate perfusion, the worse the lactic acidosis within the body becomes
- Packed red blood cells have a base deficit of 20 mmol/L to 40 mmol/L depending on the age of the bag
- A base deficit reduces the ability of the body to buffer a worsening acidosis
- The inability for the kidneys to keep up with the buffering and removal of hydrogen ions during a massive blood transfusion
- The kidneys eliminate approximately 1 mmol/kg of hydrogen ions per day with each unit of packed red blood cells containing approximately 15 mmol of hydrogen ions
The rectification of the bleeding will improve perfusion of the vital organs and rapidly reverse the metabolic acidosis. Packed red blood cells also contains a substance known as citrate that is converted to bicarbonate by the liver, which will help buffer the acidosis. The prophylactic administration of intravenous bicarbonate is unnecessary and may cause a serious metabolic alkalosis once the bleeding has been resolved. However, we should aim for a pH greater than 7.2 and this may require the use of intravenous bicarbonate if the pH begins to fall below this.
There are various blood products that can be utilised to help the clotting process. A 1:1 ratio of coagulation products during a massive blood transfusion was once advocated, but there have been no studies that demonstrate a mortality benefit. If anything, the intravascular volume overload associated with trying to maintain a 1:1 ratio has been associated with an increased level of negative outcomes for the patient. As a result, it may be better for us to treat according to need rather than ratio.
It is important to revisit the clotting cascade to understand how various coagulation products work and to consider whether the bleeding can be rectified through the reversal of certain anticoagulant therapies:
- Fresh Frozen Plasma (FFP)
- FFP contains all the coagulation factors in normal concentrations and promotes coagulation of blood along the intrinsic, extrinsic and common pathways
- 1 unit of plasma usually contains 200-250 mL of volume, increasing most coagulation factors within the body by approximately 2.5% in a 70 kg patient
- FFP is to be given if the INR ≥ 1.5 with a dosage of 15 mL/kg, which is approximately 4 units in a 70 kg patient
- Pooled platelets
- The whole clotting cascade is pointless if there are insufficient platelets to get trapped within the fibrin fibres to thereby form a clot
- 1 adult therapeutic dose usually increases platelet count by 20,000 – 40,000 mcL
- Pooled platelets are to be given if the platelet count is < 50,ooo mcL with a dosage of 1 adult therapeutic dose (also known as 1 unit of pooled platelets)
- Cryoprecipitate contains mostly fibrinogen, factor 8, factor 13 and von Willebrand factor
- Each unit of cryoprecipate is equivalent to approximately 10-15 mL, with one unit per 10 kg of body weight resulting in an increase of fibrinogen concentration by 1.0 g/L
- Cryoprecipitate is to be given if the fibrinogen is <1.0 g/L with a dosage of 3-4 grams
- Desmopressin (DDAVP)
- DDAVP works to increase the amount of von Willebrand factor circulating within the bloodstream
- The increase of von Willebrand factor allows platelets to bind to each other and also acts as a carrier protein for coagulation factor 8 within the body, thereby playing an important role in the clotting cascade
- Tranexamic acid (TXA)
- TXA is an antifibrinolytic that works to counteract the degrading effects that plasmin has on fibrin, thereby preserving stabilised fibrin to participate in the clotting process for longer
- The recommended dose during a massive blood transfusion is a loading dose of 1 gram over 10 minutes, followed by an infusion of 1 gram over 8 hours
- Protamine reverses heparin in a ratio of 1 mg : 100 units
- If the bleeding is thought to be a result of a heparin induced coagulopathy, protamine can be given if the APTT is ≥ 1.5 the normal levels with a dosage of 25-50 mg intravenously over 5 minutes
- Vitamin K
- Warfarin affects the vitamin K dependent coagulation factors which are factors 2, 7, 9 and 10 (remember it as the old Australian television channels)
- If the bleeding is thought to be a result of a warfarin induced coagulopathy, vitamin K can be given if the INR is ≥ 1.5 with a dosage of 0.5-10 mg over at least 30 seconds
Electrolyte derangement management
As discussed earlier, packed red blood cells contain citrate that binds to ionised calcium thereby preventing the clotting cascade from progressing further. The body is able to convert citrate to bicarbonate in the liver, however rapid administration of packed red blood cells overwhelms this process. When this happens, we are effectively giving blood that won’t clot to a bleeding patient. For this reason, the replacement of calcium needs to be considered during a massive blood transfusion to maintain an ionised calcium level of ≥ 1.1 mmol/L. There are usually two choices for calcium replacement; calcium chloride and calcium gluconate. A 10% calcium chloride solution has 27 mg/mL of calcium whereas a 10% calcium gluconate solution has 9 mg/mL of calcium. Despite having more bang for your buck in terms of increasing calcium, calcium chloride tends to be more irritating to the veins and the chloride concentration may worsen the acidosis of the patient. Therefore, calcium gluconate is usually the calcium replacement of choice.
Packed red blood cells leak potassium proportionately throughout their storage life. There will be more circulating potassium in an older bag of packed red blood cells, with the average age of most packed red blood cells being 20 days. Hyperkalaemia can be avoided by utilising packed red blood cells that are less than 7 days old in massive blood transfusions. In the event that this is not feasible, an insulin and glucose infusion may need to be commenced to lower potassium levels within the blood. Insulin works as a carrier molecule to move potassium from the extracellular space into the intracellular space. It also reduces the glucose levels within the body, which is why a concurrent glucose infusion is necessary to avoid hypoglycaemia.
Do I have a massive blood transfusion protocol in my facility?
Most facilities will have a massive blood transfusion protocol in place, so have a look next time you are at work. If your facility doesn’t or it is not a very comprehensive document, the National Blood Authority of Australia has a great template that I have added here:
They also have a great resource for suggested criteria for activating a massive blood transfusion protocol along with some management and dosage principles:
There is a lot of information within this post, but the most important thing to remember is the basic principles associated with the REPLACE acronym when dealing with a massive blood transfusion!
Low temperature management
The next time you are involved in a massive blood transfusion, just think about whether all of these things have been considered and speak up if something has been missed! *Hint: it’s usually calcium*
- Hess, J. R. (2015). Massive blood transfusion. Retrieved from: http://www.uptodate.com/contents/massive-blood-transfusion
- Maxwell, M. J., & Wilson, M. J. A. (2006). Complications of blood transfusion. Continuing education in anaesthesia, critical care and pain, 6(6), 225 – 229. doi: 10.1093/bjaceaccp/mkl053
- National Blood Authority Australia. (2011). Patient blood management guidelines: Critical bleeding massive transfusion. Retrieved from: https://www.blood.gov.au/pubs/pbm/module1/contents.html
- Reading, J. (2016). REPLACE: Seven steps to remember during a massive blood transfusion. Retrieved from: https://www.ausmed.com/articles/massive-blood-transfusion/
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