The Effect of Repetitive Intraperitoneal Anesthesia by Application of Fentanyl-Medetomidine and Midazolam in Laboratory Rats

Background: Literature reviews show numerous options for anesthesia in the small laboratory animals. Many methods are associated with complications, such as high technical effort, difficult monitoring, respiratory and cardiovascular depression, and prolonged sedation. In the present study, we report first time results after repeated use of an intraperitoneal combined anesthesia with a high tolerability. Methods: Three hundred and seventy-four anesthesias were performed on 38 adult male lewis rats (280-460g). Each animal was anesthetized repeatedly over a period of three months, using an intraperitoneal combination of Fentanyl-Medetomidine and Midazolam (FMM). The time required for the animals to lose ear pinch response and the ability to perform a righting and pedal withdrawal reflex was measured. For evaluation of the clinical state, a four-point vitality scale was developed. The anesthesia was antagonized with Naloxone, Flumazenil, and Atipamezole (s.c.). Results: The animals lost all three reflex responses within 5 (+/- 2.4) min of injection. Without antagonism of anesthesia, the ear pinch response returned on average within 125 (+/- 21.5) min. After antagonism of anesthesia, the rats needed 5 (+/- 2.9) min to regain all three reflex responses. No significant differences of vitality-index were measured after repeated use of FMM during the investigation period. Conclusions: A repeatable and secure anesthesia is indispensable for any experimental studies that require multiple anesthesia of a single animal. Intraperitoneal combination of FMM provides an adequate procedure to induce a well tolerable, repeatable state of anesthesia, which conforms to all the necessary requirements for laboratory rats.