Combination treatment of phenytoin and thiopental by aortic arch flush for cerebral preservation during 20 min exsanguination cardiac arrest (EXCA) in dogs. Exploratory experiments

Objectives: We are systematically exploring suspended animation (SA) for cerebral preservation during transport and resuscitative surgery in exsanguinated trauma victims. We have shown previously that inducing moderate cerebral hypothermia with cold (4°C) saline aortic arch flush at start of ExCA of 20 min no-flow leads to normal functional outcome in dogs. For combat casualties, flush at ambient temperature would be available. We hypothesized that Phenytoin (Ph) combined with Thiopental (Th), given by aortic arch flush of saline at 24°C at start of 20 min ExCA will have the same beneficial effect as aortic arch flush at 4°C without drug. Methods: 15 dogs (20-25 kg) were exsanguinated over 5 min to CA of 20 min, resuscitated by closed-chest cardiopulmonary bypass, followed by assisted circulation to 2 h, 34°C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received saline aortic arch flush 25 ml/kg by a balloon-tipped catheter, inserted through the femoral artery. In the treatment dogs, Ph plus Th was dissolved in the flush and in addition infused during reperfusion. Results: In the Ph/Th group with Ph 30 mg/kg plus Th 15 mg/kg by flush and Ph 20 mg/kg plus Th 30 mg/kg i.v. at reperfusion (n=5), 1 dog achieved overall performance category (OPC) at 72 h 1 (normal), 1 dog OPC 3 (severe disability), and 3 dogs OPC 4 (coma). One dog with Ph 30 mg/kg plus Th 15 mg/kg by flush alone achieved OPC 4. One dog with Th 15 mg/kg by flush and Ph 20 mg/kg plus Th 30 mg/kg i.v. at reperfusion achieved OPC 3. In the control group (n=8), 2 dogs achieved OPC 2 (moderate disability), 2 dogs OPC 3, and 4 dogs OPC 4 (NS). Neurologic deficit scores (0-10%=normal, 100%=brain death) (median [inter-quartile range]) were 56% (29-65) with Ph/Th (combined all doses) vs. 55% (28-59) in controls (NS). Total brain histologic damage scores were 76 (48-132) with Ph plus Th vs. 98 (58-136) in controls (NS). Conclusion: Ph plus Th by aortic arch flush in this SA model, in different dosing strategies, does not reproducibly provide cerebral preservation.