Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

Haga, Henning Andreas; Lervik, Andreas; Nordgreen, Janicke

doi:10.1016/j.vaa.2020.09.007

Cited by 5 publications

(6 citation statements)

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“… 16 Given that control and actively vaccinated rats were resilient to fentanyl-induced fatal overdose particularly in the first 1–2 h after exposure, it is possible that rodents are not suitable species to test for the efficacy of medications against opioid-induced overdose because very high doses of opioids are required for lethality, which may translate into higher drug plasma concentrations than those found in humans. It is indeed possible that other species, for example, ferrets 33 or large animals (e.g., pigs 34 , 35 ) may be required to study clinically relevant overdose scenarios. Overall, these results highlight the importance of evaluating the applicability of antifentanyl vaccines in vivo both for broad efficacy against a variety of fentanyl analogues of clinical interest, and for efficacy of fentanyl vaccines against high doses of fentanyl relevant for use as a strategy for overdose prevention.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

et al. 2022

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The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has resulted in over 75 673 deaths in 2021. Immunotherapeutics such as vaccines have been investigated as a potential interventional strategy complementary to current pharmacotherapies to reduce the incidence of OUD and opioid-related overdose. Given the importance of targeting structurally distinct fentanyl analogues, this study compared a previously established lead conjugate vaccine (F 1 –CRM) to a series of novel vaccines incorporating haptens derived from alfentanil and acetylfentanyl (F 8, 9a, 9b, 10 ), and evaluated their efficacy against drug-induced pharmacological effects in rats. While no vaccine tested provided significant protection against alfentanil, lead formulations were effective in reducing antinociception, respiratory depression, and bradycardia elicited by fentanyl, sufentanil, and acetylfentanyl. Compared with control, vaccination with F 1 –CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl. These data further support investigation of F 1 –CRM as a candidate vaccine against fentanyl and selected analogues.

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Section: Discussionmentioning

confidence: 99%

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

et al. 2022

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“…Moreover, no constant pattern of reaction appearance/disappearance following eyelashes brush, corneal brush, nasal septum pinch, interdigital fold pinch, periople pinch, tail and claw clamp was found at decreasing isoflurane concentrations [ 25 ]. In a recent study, the reaction to claw clamp did not have a uniform pattern among animals when different drugs, at increasing doses, were administered in isoflurane anaesthetized pigs [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…Reflex amplitude decreased with increasing isoflurane concentrations, and reflexes evoked by single stimuli were suppressed at lower concentrations than those evoked by repeated stimuli, showing that temporal summation still occurs around MAC levels [ 23 ]. In a recent study, the NWR was shown to be influenced in a nonuniform manner by different drugs administered at increasing doses, and to give dissimilar results when compared to response to claw clamp [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

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How is depth of anaesthesia assessed in experimental pigs? A scoping review

et al. 2023

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Background Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the use of depth of anaesthesia indicators in this species. Methods Medline, Embase and CAB abstract were searched up to September 22nd 2022. No limits were set for time, language and study type. Only original articles of in vivo studies using pigs or minipigs undergoing general anaesthesia were included. The depth of anaesthesia indicators reported in the selected papers were divided in two categories: A, indicators purposely investigated as method to assess depth of anaesthesia; B, indicators reported but not investigated as method to assess depth of anaesthesia. Results Out of 13792 papers found, 105 were included after the screening process. Category A: 17 depth of anaesthesia indicators were found in 19 papers. Studies were conducted using inhalant anaesthetics as the main anaesthetic agent in the majority of the cases (13/19 = 68.4%), while 3/19 (15.8%) used propofol. The most investigated depth of anaesthesia indicators were bispectral index (8/19 = 42.1%) and spectral edge frequency 95% (5/19 = 26.3%). Contrasting results about the specific usefulness of each depth of anaesthesia indicators were reported. Category B: 23 depth of anaesthesia indicators were found in 92 papers. The most reported depth of anaesthesia indicators were: motor response following a stimulus (37/92 = 40.2%), depth of anaesthesia scores (21/92 = 23.3%), bispectral index (16/92 = 17.8%) and spectral edge frequency 95% (9/92 = 9.8%). Conclusion Results highlight the lack of scientifically valid and reliable indicators to ensure adequate depth of anaesthesia in pigs.

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“…Ketamine has been shown to increase heart rate and thereby blood pressure (21), while dexmedetomidine is known to induce bradycardia in several species, including pigs (22)(23)(24). In a previous publication in normovolemic pigs dexmedetomidine did not produce the expected decrease in heart rate (2), a finding that was later reproduced with pigs in isoflurane anesthesia (25). The reason for this surprising finding is not known.…”

Section: Discussionmentioning

confidence: 99%

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage

et al. 2021

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Background: Pigs are anesthetized when used for emergency procedures live tissue training (LTT) of civilian and military medical personnel or for experimental purposes, but there is a paucity in the literature regarding anesthesia of pigs for this purpose.Objective(s): The main goals of the study were to compare oxygen debt, macrocirculatory parameters, and time to cardiac arrest between pigs in hemorrhagic shock and anesthetized with propofol-ketamine-dexmedetomidine or alfaxalone-ketamine-dexmedetomidine.Design: A prospective, non-blinded randomized study design was used. Sixteen pigs were randomized in blocks of four to be anesthetized with either propofol-ketamine-dexmedetomidine (n = 8) or alfaxalone-ketamine-dexmedetomidine (n = 8) as a continuous infusion.Interventions: Premedication with ketamine 15 mg kg−1 and midazolam 1 mg kg−1 was given i.m. Anesthesia was maintained with propofol 8 mg kg−1 h−1 or alfaxalone 5 mg kg−1 h−1 combined with ketamine 5 mg kg−1 h−1 and dexmedetomidine 4 μg kg−1 h−1 i.v. A stepwise, volume-controlled model for hemorrhage was created by exsanguination.Main Outcome Measures: Indices of oxygen debt (lactate, base excess, and oxygen extraction), macrocirculatory (PR, SAP, DAP, MAP, and CI, SVI, and TPR) variables, and time to death was compared between groups.Results: Pigs in the alfaxalone group had significantly higher SAP than pigs given propofol. No difference in other macrocirculatory variables or indices of oxygen debt could be found. A blood loss of 50% of the total blood volume or more was possible in most pigs with both anesthetic regimes.Conclusions: Pigs anesthetized with propofol or alfaxalone combined with ketamine and dexmedetomidine tolerated substantial blood loss.

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Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

Cited by 5 publications

References 34 publications

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

How is depth of anaesthesia assessed in experimental pigs? A scoping review

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage

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