A combat casualty relevant dismounted complex blast injury model in swine

Abstract

Background: Improvised explosive devices have resulted in a unique polytrauma injury pattern termed dismounted complex blast injury (DCBI), which is frequent in the modern military theater. Dismounted complex blast injury is characterized by extremity amputations, junctional vascular injury, and blast traumatic brain injury (bTBI). We developed a combat casualty relevant DCBI swine model, which combines hemorrhagic shock (HS) and tissue injury (TI) with a bTBI, to study interventions in this unique and devastating military injury pattern.

Methods: A 50-kg male Yorkshire swine were randomized to the DCBI or SHAM group (instrumentation only). Those in the DCBI group were subjected to HS, TI, and bTBI. The blast injury was applied using a 55-psi shock tube wave. Tissue injury was created with bilateral open femur fractures. Hemorrhagic shock was induced by bleeding from femoral arteries to target pressure. A resuscitation protocol modified from the Tactical Combat Casualty Care guidelines simulated battlefield resuscitation for 240 minutes.

Results: Eight swine underwent the DCBI model and five were allocated to the SHAM group. In the DCBI model the mean base excess achieved at the end of the HS shock was -8.57 ± 5.13 mmol·L -1 . A significant coagulopathy was detected in the DCBI model as measured by prothrombin time (15.8 seconds DCBI vs. 12.86 seconds SHAM; p = 0.02) and thromboelastography maximum amplitude (68.5 mm DCBI vs. 78.3 mm in SHAM; p = 0.0003). For the DCBI models, intracranial pressure (ICP) increased by a mean of 13 mm Hg, reaching a final ICP of 24 ± 7.7 mm Hg.

Conclusion: We created a reproducible large animal model to study the combined effects of severe HS, TI, and bTBI on coagulation and ICP in the setting of DCBI, with significant translational applications for the care of military warfighters. Within the 4-hour observational period, the swine developed a consistent coagulopathy with a concurrent brain injury evidenced by increasing ICP.

Figure 1.. Graphical representation of experiment.

Following anesthesia and initial vascular and intracranial access, swine were either subjected a SHAM model (consisting of surgical access and instrumentation only) or to the dismounted complex blast injury (DCBI: consisting of blast TBI, tissue injury caused by bilateral femur fractures, and then a pressure targeted hemorrhagic shock phase). The SHAM group remained under anesthesia and monitored during the time it takes to complete the entire DCBI series. At the end of the hemorrhagic shock phase, DCBI swine are monitored for 240min during which resuscitation occurs. SHAM swine complete 240min of observation with normal saline for fluid replacement for insensible losses.

Figure 2.. The MAP, EtCO₂, and heart rate changes monitored throughout the model are shown.

DCBI swine are subjected to blood removal to until MAP reaches 15-20mmHg and EtCO₂ decreased to 20mmHg. Heart rate subsequently increases during the hemorrhagic shock phase but returns to a similar rate as SHAM models at the completion of the experiment.

Figure 3.. Measure or organ function throughout model.

Troponin, total bilirubin, lipase, and creatinine were measured at baseline, 60min after injury, and at model completion after 240min of observation. There were no significant changes in these labs in the SHAM group. Troponin increased significantly in the DCBI group and was significantly higher than the SHAM group at 240min. Total bilirubin increased significantly in the DCBI group and was significantly higher than the SHAM group at 240min. DCBI final creatinine level was significantly higher than baseline and the corresponding final SHAM level. Lipase trended slightly lower at 240min compared to baseline in the DCBI group, but the final lipase level was significantly lower than the SHAM group.

Figure 4.. Changes in intracranial pressure and cerebral perfusion pressure.

ICP increased significantly in the DCBI model but did not change in the SHAM model. Calculated CPP was significantly lower than baseline at all timepoints once hemorrhagic shock occurred.

Figure 5.. Changes in CN Thromboelastographry results.

R time, angle, and LY30 remained at similar levels to baseline for both models. Maximum amplitude decreased significantly in the DCBI model and was significantly lower than the SHAM group at 30min post injury and later.

Figure 6.. Changes in PT and the tPA Challenge TEG LY30.

The tPA challenge TEG showed significantly elevated LY30 percentages in the DCBI model compared to the SHAM at 30min and 60min post injury. Significant elevations in PT were detected in the DCBI model compared to the SHAM model at 30min post injury.