Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study

Abstract

We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading, and even more so with the further addition of phenytoin and methylprednisolone. Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1=normal, OPC 5=brain death) were better in group 2 than group 1 (<0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 ( P<0.05 group 4 vs. 2). Best NDS were 44±3% in group 1; 20±14% in group 2 ( P=0.002); 21±15% in group 3 (NS vs. group 2); and 7±8% in group 4 ( P=0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156±38 in group 1; 81±12 in group 2 ( P<0.001 vs. group 1); 53±25 in group 3 ( P=0.02 vs. group 2); and 48±5 in group 4 ( P=0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone.