Reference : Anaesthesia refinement for the laboratory rhesus macaque
Dissertations and theses : Doctoral thesis
Life sciences : Veterinary medicine & animal health
Anaesthesia refinement for the laboratory rhesus macaque
[fr] Raffinement de l’anesthésie pour le macaque rhésus de laboratoire
Bertrand, Henri mailto [Université de Liège - ULiège > > > Doct. sc. vété. (paysage)]
Université de Liège, ​Liège, ​​Belgique
Docteur en Sciences Vétérinaires
Sandersen, Charlotte mailto
[en] Anaesthesia ; Refinement ; Primate
[en] Non-human primates (NHPs) are considered an optimal model for some areas of biomedical research. However, their use raises major ethical concerns and NHPs should only be used when other animal models are considered unsuitable. Providing anaesthesia for experimental invasive procedures in laboratory animals, including NHPs is a legal and ethical obligation in Europe (Article 14 of European Directive 2010/63/10). However, the nature of anaesthetics can not only negatively influence the scientific data that is being collected but also the primates’ welfare by depressing their vital functions and possibly delaying reintroduction in social group. Hence, the anaesthesia protocol should consider both the welfare of the animal, and the scientific objectives of the study.
A review of the scientific literature from 2010 to 2015 was performed to identify current anaesthesia methods used in NHPs for experimental invasive procedures. This review highlighted that isoflurane and ketamine (alone or combination with other anaesthetics) were the most frequently used anaesthetics in NHPs. However, this review also showed an underreporting, of details of the anaesthetic protocols used. This information that should be considered critical not only from a scientific perspective but also because of public concerns related to the use of NHPs. Ketamine has a wide therapeutic index in NHPs but is associated with dysphoria and delirium during emergence, tissue irritation and can cause long-term neurological impairment. Isoflurane, with its low cost and low toxicity, is widely for general anaesthesia in a range of laboratory animal species. Isoflurane anaesthesia is associated with a relatively rapid recovery, which enables an early initial neurological assessment to be carried out, and supportive treatment to be implemented if necessary. Refinement of the use of anaesthetics that have less prolonged depressant effects, or are reversible with specific antagonists could therefore be beneficial for primate welfare.
Three alternative combinations of injectable agents, which would avoid the use of ketamine, were assessed. The choice of the agents was based on the potiential for reversing their activity, their short duration of action and also their safety for tissues. A combination of fentanyl-midazolam- medetomidine (10μg/kg-1;; 20μ by the intramuscular route provided an easily reversible immobilization with a rapid and good quality recovery. Cardiovascular and respiratory parameters were moderately depressed compared to ketamine; Heart rate (beats/min) (Ket=119±18; FMM=89±17; p=0.0066), systolic blood pressure (mmHg) (Ket=109±10; FMM=97±10; p=0.0313), and respiratory rate (breaths/min) (Ket=39±9; FMM=29±10; p=0.0416). Two other combinations: fentanyl-fluanisone-midazolam (;; 0.5 and alfaxalone-medetomidine- midazolam (; 20μ; were also assessed. These two combinations were either less reliable or provided a prolonged sedation that was not reversible with current available antagonists.
The volatile agents most recently introduced into clinical practice, such as sevoflurane and desflurane, have a lower solubility in the blood associated with shorter recovery and a possible better recovery than isoflurane. General anaesthesia with either sevoflurane or desflurane had similar cardiovascular effects, mainly a moderate hypotension that was easily manageable with administration of additional intravenous fluids or by administration of vasopressor agents. Recovery from sevoflurane and desflurane was more rapid than isoflurane, however no significant difference between sevoflurane and desflurane was found. The quality of recovery was assessed using a clinical scoring scheme, but despite a trend showing a better recovery profile with desflurane, no significant statistical difference was found between the treatment groups.
The combination of fentanyl-medetomidine-midazolam and the use of modern volatile agents resulted in a rapid recovery and hence a more rapid resumption of normal food and water intake as well as a faster reintroduction to the animal’s social group, potentially decreasing the risk of violent hierarchical conflict. However further studies to evaluate the possible interference of these alternative regimens with different types of neurophysiological research should be performed, to enable better interpretation of scientific data obtained from animals.

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