Desarrollo de nuevas técnicas de anestesia de roedores usando Propofol

Résumé

The synergistic interaction between propofol and short acting opioids, such as remifentanil, sufentanil or fentanyl, has been investigated in humans and animals. However, there are practical limitations associated with the technical difficulties in intravenous administration in small laboratory animals specially rodents. The objective of these studies was to develop a safe alternative method to anesthetize mice and rats by intraperitoneal route. We hypothesized that the intraperitoneal combination of propofol with sufentanil, remifentanil or fentanyl for anaesthesia would fit these requirements, based on evidence reported in studies on humans, where safe analgesia-anaesthesia protocols, with rapid anaesthetic induction and adequate muscle relaxation are observed. This work was divided in four parts. In the first part we evaluated the effects of a combination of propofol and a short-acting opioid (fentanyl, sufentanil or remifentanil), which would provide a short anaesthetic period with analgesia and a fast recovery without the use of antagonist drugs. In the second study, we compared the dose requirements of propofol administered by IP route to produce loss of consciousness in mice when associated with a fast acting opioid (fentanyl), an alpha-2 agonist (medetomidine) or alone. In the third study, we proposed that the addition of an alpha-2-agonist to the protocol used would provide a more predictable effect, reducing the necessary doses to achieve affective anaesthesia and providing a safer anaesthetic protocol. In the fourth study, the combinations tested in the previous study were also tested in rats. In conclusion, a freshly prepared combination of propofol-medetomidine (100/0.3 mg/kg) administered by IP route, provided suitable restraint for non painful procedures for a period of at least 30 minutes in rats. To provide surgical anaesthesia, the IP administration of a combination of 100/0.1/0.1 mg/kg propofol, fentanyl and medetomidine is a safe, easy and reversible technique to anaesthetize rats. It provides a surgical window of 25 to 30 minutes and restraint for over 30 minutes with a fast recovery. In mice, the same combination of 75/1/0.2 mg/kg of propofol, medetomidine and fentanyl, administered by IP route is a sae, easy and reversible technique to induce anaesthesia, providing a surgical window of 15 min and restraint for 30 min with a fast recovery.