A 6 year old male is bought to your ED by local ambulance following a 5-6 metre fall from the roof of his family home. He had been trying to get his tennis ball that was stuck in the second story gutter when he slipped and fell to the concrete ground below, landing on his left hand side. On examination, he is speaking in short sentences without evidence of head injury. His observations are P 168, BP 72/-, SaO2 99% (on O2), RR 36, GCS 14. Air entry is equal but he has clinical left lower rib fractures with marked tenderness and local chest wall contusion. He is cool and clammy with a capillary refill time of 5-6 seconds. There are no obvious long bone fractures or evidence of external haemorrhage. He has marked left upper quadrant tenderness with features of peritonism. There is a pelvic binder in situ with adequate positioning. His initial investigations reveal gross haemoperitoneum on bedside FAST exam with a lateral compression injury to his pelvis. As the decision is made to proceed to theatres for laparotomy you wonder how the team should manage his volume resuscitation…

Trauma related injuries are a leading cause of death in paediatric patients with exsanguination accounting for ~39% of all traumatic deaths. Coagulopathy of trauma is at least as prevalent in paediatric trauma patients as in adults and carries with it increased morbidity and mortality.

Paediatric massive transfusion is a rare entity with an incidence of ~3%. This typically is associated with severe traumatic injuries plus a myriad of complications. Not surprisingly, it is predictive of higher in-hospital mortality.

What is the definition of ‘massive transfusion’?

Massive transfusion is defined as:

“the replacement (or anticipation of replacement) of greater than one circulating blood volume within the first 24 hours of resuscitation”

Studies often use cut offs of 40 mL/kg of PRBC (over 24 hours). The common trigger for initiating massive transfusion protocols is a requirement of >40 mL/kg of PRBC (or >20mL/kg in 2 hours with ongoing losses anticipated).

Massive transfusion protocols (MTP) are designed to provide the right amount and balance of blood products, mimicking ‘whole blood’, to critically injured patients in order to prevent and treat haemorrhagic shock and coagulopathy. Not only does MTP guide resuscitation; it facilitates communication and logistical support between treating clinicians, blood bank and support staff.

MTPs are based on the ‘recently’ developed concept of damage control resuscitation, which advocates for early blood component therapy (with minimisation of crystalloid use) combined with rapid surgical control of haemorrhage.

Early administration of predefined, balanced ratios of RBC, FFP and PLTs have been shown to be associated with improved patient outcomes in adult trauma patients. Recently the PROPPR trial demonstrated improved haemostasis and a reduction in death from exsanguination in patients receiving 1:1:1 transfusion (vs 1:1:2).

Considerations include:

Normal circulating blood volume in children is ~80 mL/kg

~90 mL/kg in infants <3 months of age

~70 mL/kg in older children (65 mL/kg in obese children)

Children have higher oxygen consumption & higher CO:blood volume ratio than adults

Clinical signs of hypovolaemia in children vary from adults due to their substantial physiologic reserve

Hypotension remains a LATE sign of shock

Narrow pulse pressure is a more sensitive marker of hypovolaemia

In addition to typical sites of blood loss (long bone fractures, peritoneal and pelvic trauma) substantial bleeding can occur in children from closed head injuries

What are the basic principles for managing this patient?

1. Arrest external haemorrhage

Direct compression

Sutures or staples

Arterial tourniquets

Foley catheter (penetrating junctional injuries)

2. Pelvic splinting

Low threshold for application in shocked trauma patient

Either sheeting or proprietary product; application at level of greater trochanters

3. Realignment of long bone fractures

4. Fluid warmers

The products

Ideally (and in non-time critical scenarios) blood component transfusion is prescribed in a weight-based manner. Given the time-pressures and urgent fashion in which these are required for the resuscitation of haemorrhage shock, many massive transfusion protocols will administer these components based on weight zones with products bundled in “packs”. The Sydney Children’s Hospitals Network delivers their products in the following “packs”.

What about the adjuncts?

Tranexamic acid

The early administration of tranexamic acid (TXA) has been associated with a reduction in mortality & blood product requirements in severely injured adults. Recent registry data suggests that the administration of TXA to severely injured children (standard adult dosing of 1 gram) is associated with decreased mortality without significant differences in thromboembolic events.

The Sydney Children’s Hospitals Network recommends a dose of 15 mg/kg over 10-15 mins

Range of 10-20 mg/kg

Maximum dose of 1g

Ideally within 3 hours of injury

Calcium

Calcium is intimately involved in the clotting cascade & crucial for adequate inotropy and vasoconstriction. Hypocalcaemia is a common occurrence in patients requiring massive transfusion, typically as a result of citrate overload. It is important to regularly monitor ionised calcium and correct it accordingly.

Dose: ~0.3 mL/kg of 10% calcium gluconate.

Factor VII

In trauma patients with critical bleeding requiring massive transfusion, administration of rFVIIa has no effect on 48-hour or 30-day mortality. It is not for routine use in trauma patients.

Much of the current use of rFVIIa is for patients with critical bleeding unresponsive to conventional measures of surgical haemostasis and adequate component therapy. This use remains controversial, particularly because of concerns about the risk of potential thrombotic complications.

Dose: 90 μg/kg

Typically this is guided by Haematology consultation during MTP.

The following is an example of the Children’s Hospital Westmead Massive Transfusion Protocol.

The targets are:

And finally, what are the complications?

Massive transfusion carries with it a high rate of complications. These can result from physiologic sequelae of the underlying injury or as an iatrogenic consequence of the blood products themselves.

They include, but are not limited to:

Immune

Acute haemolytic transfusion reaction: ABO-incompatibility; induces intravascular haemolysis

Febrile transfusion reaction – unexpected temperature rise (>38oC or >1oC from baseline)

Allergic Reaction (including anaphylaxis)

Transfusion-related acute lung injury: non-cardiogenic pulmonary oedema; leading cause of transfusion-related mortality; occurs within 6 hours of transfusion

Non immune

Transfusion-associated circulatory overload

Transfusion associated sepsis (bacterial contamination): 1:75,000 (PLT), 1:500,000 (pRBC); early antibiotics and haemodynamic support

Viral transmission: HIV <1 in 1 million; hep C < 1 in 1 million; hep B ~ 1 in 700,000

Electrolyte disturbance: hypocalcaemia; hyperkalaemia; hypomagnesaemia

Air embolism

Infection – resulting from immunomodulation

References

Literature

National Blood Authority. Patient Blood Management Guidelines: Module 1 – Critical Bleeding/Massive Transfusion. [cited April 23, 2015]. Available from: https:// www.nba.gov.au The Sydney Children’s Hospitals Network. Massive Transfusion Protocol (MTP) – CHW Procedure. [cited April 23, 2015] Neff, L. P., et al. (2015). Clearly defining pediatric massive transfusion: cutting through the fog and friction with combat data. The journal of trauma and acute care surgery, 78(1), 22–8– discussion 28–9. doi:10.1097/TA.0000000000000488 Nystrup, K. B., et al. (2015). Transfusion therapy in paediatric trauma patients: a review of the literature. Scandinavian journal of trauma, resuscitation and emergency medicine, 23(1), 21. doi:10.1186/s13049-015-0097-z Holcomb, J. B., et al. (2013). The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA surgery, 148(2), 127–136. doi:10.1001/2013.jamasurg.387 Holcomb, J. B., et al. (2015). Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA: the journal of the American Medical Association, 313(5), 471–482. doi:10.1001/jama.2015.12 Livingston, M. H., Singh, S., & Merritt, N. H. (2014). Massive transfusion in paediatric and adolescent trauma patients: Incidence, patient profile, and outcomes prior to a massive transfusion protocol. Injury, 45(9), 1301–1306. doi:10.1016/j.injury. 2014.05.033 Diab, Y. A., Wong, E. C. C., & Luban, N. L. C. (2013). Massive transfusion in children and neonates. British journal of haematology, 161(1), 15–26. doi:10.1111/bjh.12247 Barcelona, S. L., Thompson, A. A., & Cote, C. J. (2005). Intraoperative pediatric blood transfusion therapy: a review of common issues. Part I: hematologic and physiologic differences from adults; metabolic and infectious risks. Pediatric Anesthesia, 15(9), 716–726. doi:10.1111/j.1460-9592.2004.01548.x Barcelona, S. L., Thompson, A. A., & Cote, C. J. (2005). Intraoperative pediatric blood transfusion therapy: a review of common issues. Part II: transfusion therapy, special considerations, and reduction of allogenic blood transfusions. Paediatric anaesthesia, 15(10), 814–830. doi:10.1111/j.1460-9592.2004.01549.x Eckert, M. J., et al. (2014). Tranexamic acid administration to pediatric trauma patients in a combat setting: the pediatric trauma and tranexamic acid study (PED-TRAX). The journal of trauma and acute care surgery, 77(6), 852–8– discussion 858. doi:10.1097/TA.0000000000000443 Shakur, H., et al. (2010). Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. The Lancet, 376(9734), 23–32. doi:10.1016/S0140-6736(10)60835-5 Davenport, R. (2013). Pathogenesis of acute traumatic coagulopathy. Transfusion, 53 Suppl 1, 23S–27S. doi:10.1111/trf.12032

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