Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration

Echelmeyer, Julia; Taylor, Polly; Hopster, Klaus; Rohn, Karl; Delarocque, Julien; Kästner, Sabine

doi:10.1016/j.tvjl.2019.05.012

Cited by 11 publications

(22 citation statements)

References 19 publications

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“…It appears that a value of ≥ 6.1-6.8 ng/mL provides an anti-nociceptive effect lasting 10-30 min against a thermal stimulus [31]. This concentration is remarkably higher than the analgesic plasma concentration reported in cats (>1.07 ng/mL) and dogs (>0.95 ng/mL) [32,33], probably depicting a weaker analgesic effect of opioids in horses.…”

Section: Discussionmentioning

confidence: 79%

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses

Dmitrović

Vanaga

Dupont

et al. 2021

Animals

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Controversy continues to surround the use of opioids in equine anaesthesia, with variable effects reported. This blinded clinical study aimed to investigate the influence of a low-dose fentanyl continuous rate infusion (CRI) on isoflurane requirements, parasympathetic tone activity (PTA), and anaesthetic parameters in horses during general anaesthesia. All of the twenty-two horses included in the research underwent a standard anaesthetic protocol. Eleven horses in the fentanyl group (Group F) received a loading dose of fentanyl at 6 µg/kg, followed by a CRI of 0.1 µg/kg/min during anaesthesia. A further 11 horses in the control group (Group C) received equivalent volumes of normal saline. Anaesthetic parameters and PTA index were recorded during anaesthesia. The achieved mean fentanyl plasma concentration was 6.2 ± 0.83 ng/mL. No statistically significant differences between groups were found in isoflurane requirements, MAP values, and mean dobutamine requirements. However, horses in Group F required a significantly lower dose of additional ketamine to maintain a sufficient depth of anaesthesia. Significantly higher PTA values were found in the fentanyl group. Further research is warranted to determine the limitations of PTA monitoring, and the influence of various anaesthetics on its values.

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Section: Discussionmentioning

confidence: 79%

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses

Dmitrović

Vanaga

Dupont

et al. 2021

Animals

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“…The IR remote controlled systems have now been used for formal investigations into pain and analgesics in cats [42,43], dogs [29], sheep [25] and horses [37][38][39]44].…”

Section: Discussionmentioning

confidence: 99%

Remote Controlled Nociceptive Threshold Testing Systems in Large Animals

Taylor

2020

Animals

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Nociceptive threshold (NT) testing is widely used for the study of pain and its alleviation. The end point is a normal behavioural response, which may be affected by restraint or unfamiliar surroundings, leading to erroneous data. Remotely controlled thermal and mechanical NT testing systems were developed to allow free movement during testing and were evaluated in cats, dogs, sheep, horses and camels. Thermal threshold (TT) testing incorporated a heater and temperature sensor held against the animal’s shaved skin. Mechanical threshold (MT) testing incorporated a pneumatic actuator attached to a limb containing a 1–2 mm radiused pin pushed against the skin. Both stimuli were driven from battery powered control units attached on the animal’s back, controlled remotely via infra-red radiation from a handheld component. Threshold reading was held automatically and displayed digitally on the unit. The system was failsafe with a safety cut-out at a preset temperature or force as appropriate. The animals accepted the equipment and behaved normally in their home environment, enabling recording of reproducible TT (38.5–49.8 °C) and MT (2.7–10.1 N); precise values depended on the species, the individual and the stimulus characteristics. Remote controlled NT threshold testing appears to be a viable refinement for pain research.

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“…1,2 A single intravenous (IV) bolus provides an effect lasting only 10-30 minutes in horses, therefore the injectable formulation of fentanyl requires a continuous IV infusion to maintain analgesia. 3 In addition to traditional injectable formulations, fentanyl is also formulated as a transdermal patch. Two patch designs are currently marketed: a reservoir patch and a matrix patch.…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics of a fentanyl matrix patch applied at three different anatomical locations in horses

Skrzypczak

Reed

Brainard

et al. 2021

Equine Veterinary Journal

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Background: Matrix fentanyl patches have not been investigated in horses and may represent an effective means of providing analgesia over an extended time period without venous catheterisation. Objectives:To describe the pharmacokinetics of a matrix transdermal fentanyl patch in horses. Study design:Randomised experiment, Latin-square design.Methods: Six adult horses were given each of three treatments with a 96-hour washout. For each treatment, two 100 µg/h matrix fentanyl patches were applied to the inguinal region (TXA), metacarpus (TXM) or ventral tail base (TXT) for 72 hours. Blood samples for fentanyl analysis were obtained and heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were measured at various time points for 96 hours.Fentanyl plasma concentrations were measured with LC-MS/MS for pharmacokinetic analysis. A mixed-effects model was used to analyse pharmacodynamic variables. Results:The time to maximum plasma concentration, maximum plasma concentration and area under the curve extrapolated to infinity were 10 ± 3.79, 14.3 ± 5.13 and 10.3 ± 4.8 hours; 2.07 ± 0.74, 1.55 ± 0.53 and 2.07 ± 0.72 ng/mL; and 46.6 ± 9.3, 44.6 ± 6.0 and 46.2 ± 7.68 ng hours/mL for TXA, TXM and TXT respectively. There was no significant difference among groups. There was no significant change from baseline or among treatment groups with regard to HR, RR or RT (P > .1 for all).Main limitations: There was no intravenous treatment group for determination of bioavailability.Conclusions: Fentanyl was rapidly absorbed and persisted in the plasma for up to 96 hours.No adverse effects of treatment on HR, RR or RT were observed. Further controlled prospective studies are needed to determine what plasma concentration, if any, of fentanyl achieves an analgesic effect in horses when administered via a transdermal patch system.

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Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration

Cited by 11 publications

References 19 publications

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses

Remote Controlled Nociceptive Threshold Testing Systems in Large Animals

The pharmacokinetics of a fentanyl matrix patch applied at three different anatomical locations in horses

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