The uptake of transdermal fentanyl in a pregnant sheep model

Self Cite

The aim of this study was to document the packed cell volume (PCV), haemoglobin concentration and total protein concentration of maternal blood before, during and after anaesthesia. Six singleton Merino-cross pregnant ewes at 116-117 days of gestation were premedicated with intramuscular acepromazine (0.02 mg/kg) and buprenorphine (0.01 mg/kg), and anaesthesia was induced with intravenous midazolam and ketamine. Anaesthesia was maintained with isoflurane in 100% oxygen. Serial blood samples were collected the day before anaesthesia (baseline), immediately prior to induction of anaesthesia (pre-op), at the end of the procedure (intra-op) and the following day (post-op). There was a significant change in the PCV during the study (p = 0.003) with an initial decrease of 12.5% from the baseline (0.36 (0.36–0.4) to 0.315 (0.29–0.34), p = 0.044), a further intraoperative decrease of 41.7% from the baseline (0.21 (0.195–0.245), p = 0.002) and an increase the day afterwards (0.3 (0.285–0.35), p > 0.99 compared with baseline). The haemoglobin concentration also changed (p < 0.0001) (baseline: 114 (111.8–123); pre-op: 97 (77.25–104.5), 14.9% decrease, p = 0.022; intra-op: 70 (61.5–83.25), 38.5% decrease, p = 0.0009; post-op: 101.5 (96.25–114) g/L, p > 0.99). Likewise the change in total protein during the study was significant (p = 0.0003) and decreased from the baseline [70 (67.25–70.75) g/L] prior to anaesthesia (61 (58.25–64.5) g/L, 12.9% decrease, p = 0.0437) and further during anaesthesia (55.5 (53.75–63.25) g/L, 20.7% decrease, p = 0.0021) with an increase [63 (61.25–67) g/L, p > 0.99] on the first post-op day. In conclusion, intraoperative anaemia and hypoproteinaemia occurred in this study. These alterations are attributed to a combination of the side effects of acepromazine and haemodilution.

Section: Methodsmentioning

confidence: 99%

Anaemia and Hypoproteinaemia in Pregnant Sheep during Anaesthesia

Musk

Kershaw

Kemp³

2019

Self Cite

“…In another study, Musk et al reported a sufficient analgesia applying the TFP at the groin region of pregnant sheep undergoing a hysterotomy and laparotomy. The efficacy of analgesia was assessed via a pain score postoperatively [36]. These two examples as well as the present study highlight differences in fentanyl uptake when patches are applied at different locations in sheep and thereby enabling scientists to use these differences to refine their analgesic protocols.…”

Section: Discussionmentioning

confidence: 78%

Transdermal Fentanyl Uptake at Two Different Patch Locations in Swiss White Alpine Sheep

Buchholz

Hildebrand

Heider³

et al. 2020

When using animals in biomedical research, investigators have the responsibility to ensure adequate analgesia. Currently, transdermal fentanyl patches (TFP) are often used to provide postoperative analgesia in large laboratory animals. The aim of this study was to compare the fentanyl uptake resulting from TFP applied at two different locations, namely the foreleg and the thorax, in healthy adult sheep. Twelve sheep received a TFP with an intended dosage of 2 ug/kg/h. Blood samples were taken at different time points over a period of five days and the fentanyl plasma levels were measured. The TFP applied on the foreleg allowed a faster fentanyl uptake with higher peaks and a longer time within or above the target concentration of 0.6–1.5 ng/mL, shown to be analgesic in humans, when compared to the one on the thorax. Assuming that the effective plasma concentration described for humans is providing analgesia in sheep as well, the present findings suggest that it should be sufficient to apply the TFP 3–6 h before the painful insult and that its effect should last at least 48 h. Furthermore, when TFP are used to provide postoperative analgesia in sheep, they should be placed on the foreleg rather than on the thorax.

“…The sedation aspect would pose challenges in terms of moving animals post-procedure in a commercial situation. In pregnant animals, the use of fentanyl patches may be contraindicated by the fact that the agent is transferred across the placenta into the foetus [398]. De Souza et al [399] investigated the pharmacokinetics of 2 mg/kg tramadol in goats following either oral or intravenous administration, and found that oral administration was likely to be ineffective in goats, while intravenous injection would need to be repeated every 6 h to maintain plasma levels equivalent to those found to provide effective pain relief in humans.…”

Section: Opioidsmentioning

confidence: 99%

Analgesia for Sheep in Commercial Production: Where to Next?

Small

Fisher

et al. 2021

Increasing societal and customer pressure to provide animals with ‘a life worth living’ continues to apply pressure on livestock production industries to alleviate pain associated with husbandry practices, injury and illness. Over the past 15–20 years, there has been considerable research effort to understand and develop mitigation strategies for painful husbandry procedures in sheep, leading to the successful launch of analgesic approaches specific to sheep in a number of countries. However, even with multi-modal approaches to analgesia, using both local anaesthetic and non-steroidal anti-inflammatory drugs (NSAID), pain is not obliterated, and the challenge of pain mitigation and phasing out of painful husbandry practices remains. It is timely to review and reflect on progress to date in order to strategically focus on the most important challenges, and the avenues which offer the greatest potential to be incorporated into industry practice in a process of continuous improvement. A structured, systematic literature search was carried out, incorporating peer-reviewed scientific literature in the period 2000–2019. An enormous volume of research is underway, testament to the fact that we have not solved the pain and analgesia challenge for any species, including our own. This review has highlighted a number of potential areas for further research.