Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study

We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24°C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20-28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received 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 an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n = 14). In group 2 (n = 9), thiopental (variable total doses of 15-120 mg/kg) was added to the flush and given with reperfusion. In group 3 (n = 7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36°C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 (p = 0.5). Median NDS were 36% (IQR 22-62%) in group 1; 51% (IQR 22-56%) in group 2; and 55% (IQR 38-59%) in group 3 (p = 0.7). Median total HDS were 67 (IQR 56-127) in group 1; 60 (IQR 52-138) in group 2; and 76 (IQR 48-132) in group 3 (p = 1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can consistently provide 'clinically significant' cerebral preservation for 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.