[Hepatic changes due to the administration of midazolam and ketamine--an experimental study]

The aim of the study was the investigation of the secondary effects at the hepatic level determined by anesthetics.

There were used 4 groups of 10 mature white Wistar rats, males and females. Group I was the witness group. According to the experimental protocol, group II received midazolam and ketamine, group III--carbon tetrachloride and group IV--midazolam, ketamine and carbon tetrachloride. The hepatic fragments taken from the sacrificed animals after 4 weeks were processed for light microscopy (HE, van Gieson and Gömöri stains) and also for electronic microscopy.

Midazolam in association with ketamine determined at the hepatic level a series of morphologic changes, identified in light and electronic microscopy. The light microscopy analysis revealed a significant inflammatory syndrome, and many isolated cellular necroses (acidophile bodies--apoptotic cells). Moreover, the electronic microscopy study showed marked anomalies of the cellular components, even when light microscopy indicated only minor lesions. The predominant ultrastructural changes were the mitochondrial abnormalities.

The most numerous and diverse morphologic changes were observed at the group where carbon tetrachloride was administered in association with midazolam and ketamine. We can assert that carbon tetrachloride increased the aggressive potential of ketamine, manifested even in association with midazolam.

Although each of the two anesthetics does not have an evident hepatotoxicity, when they are associated with each other or they are administered with a known hepatotoxic substance, they determine hepatic lesions of various sizes and degrees.