Anesthesia with Intraperitoneal Propofol, Medetomidine, and Fentanyl in Rats

A safe and reliable method for anesthetizing rats has long been a leading concern of biomedical researchers. We recently found that the intraperitoneal administration of propofol combined with medetomidine and fentanyl is safe for mouse anesthesia. Here we studied whether the same combination could be used for general anesthesia in rats. We used male Wistar rats to test 10 combinations of propofol, medetomidine, and fentanyl administered intraperitoneally and reversed with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia, induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate were evaluated, along with the duration and quality of induction, surgical anesthesia, and recovery. The combination of propofol and medetomidine provided a predictable induction and sufficient hypnosis and muscle relaxation, but surgical anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this protocol. The addition of fentanyl increased analgesia, making it possible to achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg), medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical technique for intraperitoneal anesthesia in rats, providing a surgical window of 25 min and restraint for 30 min, with rapid recovery after administration of atipamezole.Safe and reliable anesthesia of rats has long been a leading concern among biomedical researchers. Protocols with rapid recovery times can decrease the mortality associated with rodent anesthesia by minimizing hypothermia and hypoxia.¹⁶ Inhalant anesthesia tends to be the technique of choice for rapid recoveries. However, the necessary specific delivery equipment is not available in all facilities, and this technique is not recommended in some circumstances, such as neurosurgical and oropharyngeal procedures.^12,19Most injectable anesthetic protocols for rats are based on the combination of dissociative drugs or opiates with α2 agonists and tranquilizers or sedatives.^{13-15,17,21,23,33} Intraperitoneal barbiturates are another common technique.¹³ Unfortunately, most current injectable anesthetic protocols for rats typically lead to prolonged sedation, and full recovery of consciousness can take several hours.²³ Anesthetic combinations such as medetomidine–ketamine²⁸ and fentanyl–medetomidine²³ have the advantage of providing faster recoveries through reversal of the medetomidine effect with a specific α2 antagonist such as atipamezole.³² Nevertheless, combinations including ketamine often are associated with low-quality recoveries,^22,34 and subanesthetic treatment with ketamine can induce schizophrenic-like behavioral disturbances when applied for several consecutive days.⁷ Neuroleptanalgesic combinations of fast-acting opiates and medetomidine usually require high doses of both compounds to achieve anesthesia for surgical procedures, leading to side effects of respiratory depression and polyuria during the period of anesthesia.²³Recent studies in our laboratory showed that the combination of propofol and fast-acting opioids did not induce anesthesia in mice when administered by intraperitoneal route.² However, the addition of medetomidine resulted in an easy and reliable way to anesthetize mice by the intraperitoneal route.³ In recent studies, a single intraperitoneal dose of propofol induced general anesthesia in a single rat.^4,27 However, a large dose of propofol was necessary, which led to progressive bradypnea that persisted for more than 6 h and resulted in death from respiratory arrest. Similarly, previous studies from our group have revealed unpredictable effects from propofol and propofol–remifentanil intraperitoneal anesthesia in rats.⁴In the current study, we hypothesized that the combination of propofol with a fentanyl–medetomidine protocol would reduce the doses of all drugs required and yield appropriate anesthesia, with good muscle relaxation and analgesia and minimal respiratory depression. In addition, reversal of the medetomidine effects with atipamezole would provide a rapid recovery, leading to a safe and practical anesthetic technique.