J Trauma Acute Care Surg. 2019 Apr 12; Epub ahead of print

# Pre-hospital adenosine, lidocaine and magnesium has inferior survival compared to tactical combat casualty care resuscitation in a porcine model of prolonged hemorrhagic shock.

How R, Glaser J, Schaub L, Fryer D, Ozuna K, Morgan C, Sams V, Cardin S

BACKGROUND: Adenosine, lidocaine, and magnesium (ALM) is a cardioplegic agent shown to improve survival by improving cardiac function, tissue perfusion, and coagulopathy in animal models of shock. We hypothesized pre-hospital ALM treatment in hemorrhagic shock would improve survival compared to current Tactical Combat Casualty Care (TCCC) resuscitation beyond the Golden Hour.

METHODS: Swine were randomized to: 1) TCCC, 2) 2cc/kg vehicle control (VC), 3) 2cc/kg ALM+drip, 4) 4cc/kg ALM+drip, 5) 4cc/kg ALM+delayed drip at 0.5cc/kg/hr, 6) 4cc/kg vehicle control, 7) 4cc/kg ALM for 15 mins + delayed drip at 3cc/kg/hr. Animals underwent pressure controlled hemorrhage to MAP of 30mmHg (S=0). Treatment was administered at T=0. After 120 minutes of simulated pre-hospital care (T=120) blood product resuscitation commenced. Physiologic variables were recorded and labs were drawn at specified time points.

RESULTS: TCCC demonstrated superior survival to all other agents. VC and ALM groups had lower mean arterial pressures (MAPs) and systolic blood pressures (SBPs) compared to TCCC. Except for the vehicle control groups, lactate levels remained similar with correction of base deficit after pre-hospital resuscitation in all groups. Kidney function and liver function remained comparable across all groups. Compared to baseline values, TCCC demonstrated significant hypocoagulability.

CONCLUSION: ALM, as administered in this study, is inferior to current Hextend®-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower SBPs and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. ALM does not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct.