The antiinflammatory effects of ketamine in endotoxemic rats during moderate and mild hypothermia.

Abstract

Endotoxemia is a common problem among critically-ill patients. We previously found that ketamine inhibited hypotension, metabolic acidosis, and increase of plasma cytokines during endotoxemia in rats. Although endotoxic patients often develop hypothermia, it has not been determined whether ketamine retains its antiinflammatory effects during hypothermia. We investigated the effects of ketamine on endotoxemic rats subjected to moderate and mild hypothermia. Male Wistar rats (n = 100) were anesthetized intraperitoneally with pentobarbital sodium and assigned to one of two protocols: one representing moderate hypothermia (30 degrees C-32 degrees C) and the other, mild hypothermia (33 degrees C-35 degrees C). Each protocol included 5 equal groups: 1). Escherichia coli endotoxin (15 mg/kg IV) in normothermia, 2). ketamine (10 mg x kg(-1) x h(-1) IV) during and after endotoxin injection in normothermia, 3). saline in hypothermia, 4). endotoxin (15 mg/kg IV) in hypothermia, and 5) ketamine (10 mg x kg(-1) x h(-1) IV) in hypothermia after endotoxin injection. Rats were then warmed or cooled to maintain rectal temperatures as above for 6 h. We assessed hemodynamics, acid-base status, and plasma concentrations of tumor necrosis factor-alpha, and interleukin-6. Endotoxemic rats developed hypotension and metabolic acidosis as well as increased plasma cytokine concentrations. At 6 h after endotoxin injection, the mean systolic arterial blood pressure decreased by 71% in the saline/normothermia/endotoxin group, whereas it decreased by only 6%, 41%, and 29% in the ketamine/normothermia/endotoxin, saline/moderate hypothermia/endotoxin, and ketamine/moderate hypothermia/endotoxin groups, respectively. Ketamine administration to endotoxemic rats with hypothermia, whether moderate or mild, also attenuated hypotension, metabolic acidosis, and cytokine increase, but these effects were not superior to those of hypothermia alone. Our findings suggest that, during hypothermia, ketamine administration may not have additive beneficial antiinflammatory effects. Although ketamine administration decreased the severity of hypotension and acidosis in endotoxemic rats, ketamine administration may not have additive beneficial antiinflammatory effects during hypothermia.