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Abstract
The early administration of tranexamic acid is recognised as significantly reducing mortality in traumatically injured patients with major haemorrhage, typically given via intravenous or intramuscular routes. In the context of mass casualty events, there may exist multiple traumatically injured casualties that would benefit from tranexamic acid, however, it’s administration may be delayed through the need to establish intravenous access. Additionally, if the initial assessment of the traumatically injured casualty is undertaken by an individual who cannot administer intravenous or intramuscular medications, time to administration will be further delayed. This concepts paper seeks to discuss the potential for utilising oral tranexamic acid, in the context of mass casualty events, as an alternative administration route.
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TXA is routinely administered by the intravenous or intraosseous route. However, there is good evidence of therapeutic plasma concentrations following intramuscular administration, even in patients with haemorrhagic shock. Intramuscular TXA was introduced into JRCALC guidelines in 2021, and several commercial organisations are developing intramuscular autoinjectors.3 4 The British Antarctic Survey Medical Unit has proposed an alternative administration route: oral TXA. As part of pre-deployment training for staff working across the British Antarctic Territory, all personnel are trained in the management of major haemorrhage, including the importance of TXA. In this training, personnel are also taught about its need to be administered without delay.5
This alternative position has been considered for several reasons. Oral medications do not require patient exposure (important in the extreme cold weather environment) or tolerability of intravenous access/intramuscular volume. It does not require any additional equipment or interventions, which also reduces delays in administration. It requires very little training in administration aside from knowledge of indications. There are no sharps or hazardous waste that require disposal after administration, and oral preparations are unlikely to require additional specialised storage methods.
In the context of a mass casualty event, oral TXA may present an attractive alternative to other routes (intravenous/intraosseous/intramuscular). It can be administered without any medical equipment and requires no training, therefore empowering care providers of any level to deliver effect, greatly increasing the available workforce. It can be given immediately to any patient who is conscious and able to follow instructions, which may also have the effect of increasing clinician capacity at a time of crucial need. Given this minimal requirement for resources and infrastructure, oral TXA may also have a wider impact with regard to traumatic events internationally, given its potential accessibility to low- and middle-income countries.
Oral TXA has limitations. Compared with intravenous, intraosseous and intramuscular administration, oral TXA reaches a therapeutic plasma concentration (10 mg/L) 66 min post-administration compared with immediately following intravenous administration, after 3.5 min following intramuscular administration and after 5 min following intraosseous administration.6 The above data were reported using swallowed oral TXA tablets, where it has already been used for indications such as menorrhagia or bleeding post-hip arthroplasty.7 The phenomenon of ‘dose dumping’ can occur with crushed or chewed medications that result in rapid absorption with far shorter times to peak plasma concentration.8 Therefore, there is a need for future research withpatient and public involvement to determine the time to therapeutic TXA concentrations with different oral preparations/instructions.
The use of oral TXA may be considered an additional option for the care of the conscious trauma patient. Although our current understanding indicates an obvious limitation in terms of time to therapeutic effect, further research to understand the implications of ‘dose-dumping’ from crushed or chewed TXA may mitigate this limitation.
