Ketamine reduces mortality of severely burnt rats, when compared to midazolam plus fentanyl

Abstract 

Ketamine can provide protective effects, through its anti-inflammatory properties, as shown in animal models of septic shock and endotoxemia, and has elicited the heat-shock response (HSR) in experimental studies. The HSR has reduced the mortality after severe burns in rats. This study has tested the hypothesis that ketamine could be protective in experimental burns and that it could generate the HSR. One hundred and twenty adult male Fischer rats were randomly divided into five groups. Rats in the first group (n=20) were sham-anesthetized. In the second group (n=20), rats were anesthetized with ketamine and shaved. In the third group (n=20) rats were anesthetized with midazolam plus fentanyl and shaved. In the fourth group (n=30), rats were anesthetized with ketamine, shaved and submitted to 29% body surface third-degree burns using a brass bar. In the fifth group (n=30), rats were anesthetized with midazolam plus fentanyl, shaved and submitted to 29% body surface third-degree burns using a brass bar. Mortality rates were measured at 1, 2, 3, 5, 7, 10, 15 and 25 days. Liver and lung samples were collected from all groups for heat-shock protein 70 (HSP70) detection. No animals died in the first, second or third group. Animals anesthetized with ketamine showed significantly decreased mortality, as compared to those anesthetized with midazolam plus fentanyl, from day 2 to day 10 (P<0.01, Fischer’s exact test) and from day 10 to day 25 (P<0.05). HSP70 was positive in the lungs of animals from all groups, without any differences among them, and was found in none of the liver samples. In conclusion, the mortality was significantly lesser in ketamine-anesthetized burnt rats than in burnt animals anesthetized with midazolam plus fentanyl. Ketamine has not elicited the HSR in this model of experimental burns and, therefore, its protective effects were not shown to be mediated through this mechanism.

Keywords:  Heat-shock response, Burns, Protection, Ketamine, Midazolam, Fentanyl