Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids

Flecknell, P. A.; Liles, J. H.; Wootton, R

doi:10.1258/002367789780863655

Cited by 65 publications

(30 citation statements)

References 14 publications

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“…These problems can be reduced if the anaesthetic regimen can be completely or partially reversed using specific antagonist drugs. A number of different combinations have been described, for example partial reversal of fentanyl/fluanisone (Flecknell et al 1989),ketamine/xylazine (Lipman et al 1987), and ketamine/medetomidine (Morris 1991).The effects of combinations of fentanyl, a /l-agonist opioid, and medetomidine, an a-adrenoceptor agonist, have been described in the rat (Hu et al 1992). This combination, however, has the disadvantages of requiring a relatively large volume of injectate (lml/lOOg i.p.)…”

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confidence: 99%

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol

Hedenqvist

Roughan²,

Flecknell³

2000

Lab Anim

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SummaryInjectable anaesthetics are widely used to anaesthetize rats, but recovery times are often prolonged. Reversible anaesthetic regimens have the advantage that animals may be recovered quickly, thus reducing the incidence of postoperative complications such as hypothermia, and also providing a means of treating inadvertent anaesthetic overdose. This study assessed and compared the characteristics of anaesthesia induced with combinations of sufentanil and medetomidine administered as a single subcutaneous or intraperitoneal dose, and reversal with butorphanol and atipamezole. Combinations of sufentanil/medetomidine at 40 /lg/150 /lg and 50 /lg/150 /lg/kg administered subcutaneously, and 80 /lg/300/lg/kg by intraperitoneal injection were found to produce surgical anaesthesia for 101± 49, 124± 45 and 76 ± 23 min (means ± SD) respectively. All three combinations produced marked respiratory depression 30min after injection « 50% of resting respiratory rate). Oxygen saturation, measured by pulse oximetry, was < 50% in all groups 30min following drug administration. Subcutaneous administration is recommended since it resulted in a more reliable and more rapid induction of anaesthesia than intraperitoneal administration. The administration of butorphanol and atipamezole (O.2/0.5mg/kg s.c.) resulted in a rapid « 7min) reversal of anaesthesia and an associated respiratory depression. The induction of anaesthesia with sufentanil/medetomidine and its reversal with a combination of atipamezole and butorphanol is an effective technique for anaesthetizing rats. However, due to the marked respiratory depression and the resulting hypoxia, we recommend that this regimen should only be used in animals which are free from respiratory disease and that oxygen should be provided during anaesthesia.

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confidence: 99%

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol

Hedenqvist

Roughan²,

Flecknell³

2000

Lab Anim

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“…Therefore, the use of mixed kappa agonists and mu antagonists like buprenorphine or nalbuphine has advantages [12]. Their ceiling effect reduces the incidence of respiratory depression and gastrointestinal side effects [13, 22]. In contrast to buprenorphine, nalbuphine is not regulated by the law on narcotics.…”

Section: Discussionmentioning

confidence: 99%

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis

Jeger

Arrigo

Hildenbrand

et al. 2017

ICMx

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BackgroundSepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis.MethodsMale Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography—high resolution mass spectrometry.ResultsIn anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats.ConclusionsIn anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis.

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“…Analgesia seems the most important aspect of the anaesthesiologic protocol 3,8,10 : even if no statistically significant difference was observed, animals treated with intraoperative fentanyl showed better intraoperative stability of vital parameters and the mean survival time was longer, even if not statistically significant, than in animals not treated with fentanyl; in this sense, perhaps the absence/ reduction of pain due to fentanyl not only allowed the an- Statistical analysis of heart rate (HR) (bpm); respiratory rate (RR) (acts per minute); systolic blood pressure (SYS) (mm Hg). Statistical analysis of heart rate (HR) (bpm); respiratory rate (RR) (acts per minute); systolic blood pressure (SYS) (mm Hg).…”

Section: Discussionmentioning

confidence: 99%

Experimental anaesthesiologic protocol for porto‐intracaval shunt for liver total vascular exclusion: Preliminary study in the rabbit

et al. 2001

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The aim of this study was to evaluate the effects and interference of different anaesthetic techniques in rabbits undergoing liver total vascular exclusion using a porto-intracaval shunt. Twenty New Zealand rabbits were divided in three groups: group A receiving diazepam as premedication, ketamine + atropine for induction and maintenance of anaesthesia and undergoing a porto-intracaval shunt operation; group B receiving midazolam as premedication, ketamine + fentanyl + atropine for induction and maintenance of anaesthesia and undergoing a porto-intracaval shunt operation; group C receiving the same drugs as group B but undergoing a simple portal and caval clamping. The following parameters were studied: efficacy of premedication, vital parameters before and after clamping and insertion of the shunt, mean time to clamp and insert the shunt, mean survival time after clamping (group C) or activation of the shunt (groups A and B). Midazolam was significantly better for premedication; there was no statistically significant difference between groups A and B for the vital parameters, for the time necessary to clamp and insert the shunt, for the intraoperative course, and for the mean survival time. The absence of a statistically significant difference between groups could be due to the low number of animals used in the study. There is actually evidence that a correct anaesthesiologic protocol, especially referring to analgesia and fluid management, improves the outcome of operated animals. Surely further studies, possibly conducted on a larger number of animals, are required to evaluate better the results observed and to consider applying these data and this experience to humans.

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Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids

Cited by 65 publications

References 14 publications

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis

Experimental anaesthesiologic protocol for porto‐intracaval shunt for liver total vascular exclusion: Preliminary study in the rabbit

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