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Three Part Question

In [adult patients requiring trauma resuscitation] can a [single bolus of tranexamic acid] be [administered using an intraosseous route compared to intravenous or intramuscular access]?

Clinical Scenario

A 28-year-old male with a history of IV drug use presents to the emergency department for injuries sustained during a motor vehicle collision. The patient was non-ambulatory at the scene with multiple injuries to his extremities including an obvious right-sided femur fracture. Upon arrival, the patient is hypotensive with weak distal pulses. Nurses are unable to obtain IV access but you successfully place an intraosseous (IO) line in the left proximal tibia. You consider whether administering tranexamic acid (TXA) via IO will have the same efficacy as IV or intramuscular (IM) administration.

Search Strategy

Medline 1966-05/20 using PubMed, Cochrane Library (2020), and Embase
[(exp Intraosseous OR IO access) AND (exp trauma or exp hemorrhagic shock) AND (exp tranexamic acid)]

Search Outcome

96 studies were identified; four studies addressed the clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Boysen S, et al. Feb 2017 Canada	16 male swine	Animal study	Plasma levels of TXA when administered IO versus IV	IV route reached peak concentration 1 minute earlier than IO. No significant difference in bioequivalence of TXA	Use of normovolemic, anesthetized animal model. IO TXA was injected into red marrow while adult long bones are almost exclusive yellow marrow. Proximity to sampling site (jugular) varied; auricular venous circulation (IV) versus tibial circulation (IO).
Lewis P, et al. June 2014 UK	Eighty-two patients received TXA via IO access	Retrospective cohort	Survival rate and complications	survival rate of patients receiving TXA was 69.2%; there were no complications	Retrospective; no comparison group; limited clinical outcomes
Lallemand M, et al. Feb 2018 USA	18 adult swine undergoing hemorrhage and ischemia-perfusion protocol	Animal study	Serum concentrations in IO vs. IV administration	No significant difference in serum drug concentrations	Non-blinded, animal model. Ischemia-perfusion model induces hyperfibrinolysis rather than physiologic fibrinolysis. No postportem tissue analysis of bone through TXA was infused was performed.
			Efficacy of TXA when administered IO vs. IV	Correction of hyperfibrinolysis at 30 minutes similar in IV and IO
DeSourcy E, et al. Winter 2019 USA	15 Yorkshire-cross pigs undergoing controlled hemorrhagic shock (35% of blood volume lost)	Animal study	Serum concentrations in IO, IV and IM administration	Peak concentrations (Cmax) in IV was slightly higher than IO with similar time to Cmax but both concentrations were significantly higher than IM.	Animal model. Controlled hemorrhagic shock produced hypotension but did not induce tissue injury likely seen in setting of severe trauma thus producing different coagulation profile.

Comment(s)

Intraosseous (IO) administration of TXA does not show any significant difference in peak serum concentration (Cmax) or time to Cmax when compared to IV administration. Both IV and IO administration appear to be superior to IM administration in terms of Cmax and time to Cmax. However, these were mostly animal studies and there is currently a lack of prospective human studies. Intraosseous administration may be more suited in field conditions when a bolus is more feasible than IV administration that requires a gravity drip or when IV access cannot be obtained.

Clinical Bottom Line

In adult patients in hemorrhagic shock, there is no significant difference between IO and IV administration of TXA for reversal of trauma-induced coagulopathy. However, IO administration is preferable to IM administration when IV access cannot be obtained or in situations that are not conducive to IV infusion.

References

1. Boysen SR, Pang JM, Mikler JR, Knight CG, Semple HA, Caulkett NA. Comparison of tranexamic acid plasma concentrations when administered via intraosseous and intravenous routes. Am J Emerg Med 2017 Feb;35(2):227-233
2. Lewis P, Wright C. Saving the critically injured trauma patient: a retrospective analysis of 1000 uses of intraosseous access Emerg Med J 2015 Jun;32(6):463-7
3. Lallemand MS, Moe DM, McClellan JM, Loughren M, Marko S, Eckert MJ, Martin MJ No intravenous access, no problem: Intraosseous administration of tranexamic acid is as effective as intravenous in a porcine hemorrhage model. J Trauma Acute Care Surg 2018 Feb;84(2):379-385.
4. DeSoucy ES, Davidson AJ, Hoareau GL, Simon MA, Tibbits EM, Ferencz SE, Grayson JK, Galante JM. Pharmacokinetics of Tranexamic Acid via Intravenous, Intraosseous, and Intramuscular Routes in a Porcine (Sus scrofa) Hemorrhagic Shock Model. J Spec Oper Med 2019 Winter;19(4):80-84