Reduction of isoflurane MAC by fentanyl or remifentanil in rats.
OBJECTIVE
The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration (MAC) of isoflurane in the rat. A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs.


METHODS
Thirty-seven male Wistar rats were randomly allocated to one of six treatment groups.


METHODS
For all treatment groups anaesthesia was induced with 5% isoflurane in oxygen using an induction chamber. A 14-gauge catheter was used for endotracheal intubation, and anaesthesia was maintained with isoflurane delivered in oxygen via a T-piece breathing system. A baseline determination of the minimum alveolar concentration of isoflurane (MACISO) was made for each animal. Fentanyl (15, 30, 60 micro g kg-1 hour-1) or remifentanil (60, 120, 240 micro g kg-1 hour-1) were infused intravenously into a previously cannulated tail vein. Thirty minutes after the infusion started, a second MACISO (MACISO+drug) was determined. The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements. Cardiovascular (heart rate and arterial pressure) and respiratory (respiratory rate and presence/absence of apnoea) effects after opioid infusion were also recorded.


RESULTS
Fentanyl (15, 30, 60 micro g kg-1 hour-1) and remifentanil (60, 120, 240 micro g kg-1 hour-1) similarly reduced isoflurane MAC in a dose-dependent fashion: by 10% at lower doses, 25% at medium doses and by 60% at higher doses of both the drugs. Both opioids reduced the respiratory rate in a similar way for all doses tested. No episodes of apnoea were recorded in the remifentanil groups, while administration of fentanyl resulted in apnoea in three animals (one at each dose level). The effects on the cardiovascular system were similar with both drugs.


CONCLUSIONS
We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane, and that this anaesthetic sparing effect is dose-dependent and similar to that produced by fentanyl at the doses tested.


CONCLUSIONS
The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl, providing similar reduction in isoflurane requirements. Due to its rapid offset, it is recommended that alternative pain relief be instituted before it is discontinued.
Criado
Ana B
AB
LAS Department, GlaxoSmithKline, UK. ana.b.criado@gsk.com
Gómez e Segura
Ignacio A
IA
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia / Q000662:veterinary; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous / Q000662:veterinary; D007530:Isoflurane / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats / Q000502:physiology*; D017208:Rats, Wistar; D000077208:Remifentanil
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D010880:Piperidines; D007530:Isoflurane; D000077208:Remifentanil; D005283:Fentanyl