The Effects of Gabapentin on Acute Opioid Tolerance to Remifentanil Under Sevoflurane Anesthesia in Rats.
Journal - Anesthesia and analgesia
Background:Tolerance to remifentanil during sevoflurane anesthesia may blunt the ability of this drug to reduce anesthetic requirements. Gabapentin has been shown to be effective in reducing postoperative narcotic usage, a reduction that may be associated with a reduction in opioid-induced tolerance and hyperalgesia. We sought to determine whether gabapentin might prevent the observed acute opioid tolerance (AOT) produced by remifentanil in sevoflurane minimum alveolar concentration (MAC).Methods:Wistar rats were anesthetized with sevoflurane and the effects of gabapentin alone on sevoflurane MAC were determined at doses of 150 and 300 mg · kg(-1). In a second experiment, gabapentin 300 mg · kg(-1) was administered before remifentanil (120 and 240 µg · kg(-1) · h(-1)). The MAC was determined before gabapentin administration and 3 more times at 1.5-hour intervals after drug administration to assess AOT. MAC was determined from intratracheal gas samples using a sidestream gas analyzer; tail clamping was used as a supramaximal stimulus. Statistical analysis was performed with the 1-way analysis of variance test.Results:Remifentanil reduced MAC (2.5% ± 0.2%) by 16% ± 5% and 36% ± 6% (120 and 240 µg · kg(-1) · h(-1), respectively, P < 0.01) with a further reduction produced by coadministration with gabapentin 300 mg · kg(-1) to 39% ± 12% and 62% ± 14%, respectively (P < 0.01 versus remifentanil alone). Gabapentin given alone at 150 and 300 mg · kg(-1) reduced MAC by 26% (both doses, P < 0.01). AOT was observed with remifentanil and characterized by a lower degree of MAC reduction, approximately 1.5 hours later (P < 0.05). However, when remifentanil was administered with gabapentin, the AOT to remifentanil was not observed (P > 0.05).Conclusions:Gabapentin reduced the sevoflurane MAC and enhanced the MAC reduction produced by remifentanil. This enhancement may limit AOT in rats.
Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl.
Journal - Veterinary journal (London, England : 1997)
The objective of this study was to determine the effects of a constant rate of infusion of lidocaine and ketamine in combination with either morphine or fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) during ovariohysterectomy in dogs. Female dogs (n=44) were premedicated with acepromazine and midazolam. Anaesthesia was induced with propofol and maintained with isoflurane. Dogs received ketamine (0.6mg/kg/h) and lidocaine (3mg/kg/h) together with morphine (0.24mg/kg/h; MLK) or fentanyl (0.0036mg/kg/h; FLK). The control group received Ringer's lactate solution. A skin incision was used as the noxious stimulus. The MAC(ISO) value was obtained with Dixon's up-and-down method. MAC(ISO) was 0.7+/-0.0vol.% in the control group, 0.3+/-0.0vol.% in the MLK group (45% MAC reduction) and 0.0+/-0.0vol.% in the FLK group (97% MAC reduction). A combination of fentanyl with lidocaine and ketamine decreased the MAC(ISO) in dogs; this decrease was more pronounced than that produced by morphine, lidocaine and ketamine.Copyright © 2010 Elsevier Ltd. All rights reserved.