Study Design: Prospective controlled in vivo swine model.
PICO:
- Population: 10 healthy yorkshire swine under general anesthesia with controlled hemorrhage, simulated hyperfibrinolysis, and acidosis (discussed in more detail below).
- Intervention: 1000mg IV TXA (n=5).
- Control: No TXA (n=5).
- Outcome: Resolution of fibrinolysis as measured by ROTEM Maximum Lysis (ML) directly after TXA administration.
What they did:
The pigs were intubated and placed on invasive monitors (PA + arterial) under general anesthesia. Blood samples were then drawn at baseline and repeated at 30 minutes, 1 hour, and 4 hours post-resuscitation. To achieve simulated hemorrhage ischemic-reperfusion injury, all pigs were bled 35% of their total circulating volume (26ml/kg) through their inferior vena cava via a midline laparotomy. Immediately after, the aorta was cross-clamped and pigs were left for 50 minutes to create a "severe truncal ischemia". Resuscitation phase began after a 5 minute controlled release of the aortic clamp. 30 minutes into the resuscitation, all pigs were given 100mg tPA. At 35 minutes, the intervention group was given 1000mg TXA. Crystalloid was given to all animals who's MAP < 40 and PCWP < 150% baseline. Epinephrine was given if MAP < 40 mmHg and PCWP > 150% of baseline.
The pigs were intubated and placed on invasive monitors (PA + arterial) under general anesthesia. Blood samples were then drawn at baseline and repeated at 30 minutes, 1 hour, and 4 hours post-resuscitation. To achieve simulated hemorrhage ischemic-reperfusion injury, all pigs were bled 35% of their total circulating volume (26ml/kg) through their inferior vena cava via a midline laparotomy. Immediately after, the aorta was cross-clamped and pigs were left for 50 minutes to create a "severe truncal ischemia". Resuscitation phase began after a 5 minute controlled release of the aortic clamp. 30 minutes into the resuscitation, all pigs were given 100mg tPA. At 35 minutes, the intervention group was given 1000mg TXA. Crystalloid was given to all animals who's MAP < 40 and PCWP < 150% baseline. Epinephrine was given if MAP < 40 mmHg and PCWP > 150% of baseline.
Results:
- All pigs survived.
- At the time of TXA administration, average pH was 7.2.
- In intervention group, Maximum Lysis returned to baseline 10 minutes after administration of TXA (92% vs 9%, p<0.001).
- Swine model does not directly represent human model of coagulation. Authors acknowledge that swine coagulation profile is much more robust and, because of this, both groups returned to baseline at the end of resuscitation at 4 hours.
- Serum lactate was significantly higher in the TXA group (3.5mmol/L vs 7.0mmol/L) → authors state this may be due to a higher epinephrine requirement in intervention group (unable to know for sure as it was not powered to answer that question).
- Simulated model of "trauma-induced coagulopathy" is not consistent with actual traumatic coagulopathy.
What can we take home from this study?
- While this certainly is not practice changing by any means, it does seem to show effectiveness of TXA in an acidic environment.
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