The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in Rhesus Macaques

BackgroundHandling of common marmoset (Callithrix jacchus) usually requires chemical restraint. Ketamine has been associated with muscle damage in primates, while common marmosets, compared to other primates, additionally display an exceptional high sensitivity to ketamine-associated side-effects. Notably, muscle twitching movements of limbs and hands, and a marked increase in salivation are observed. We investigated two alternative intramuscular (i.m.) immobilisation protocols against ketamine (50 mg/kg; protocol 1) in a double-blind randomised crossover study in ten healthy adult common marmosets for use as a safe reliable, short-term immobilisation and sedation. These protocols comprised: alphaxalone (12 mg/kg; protocol 2) and 25 mg/kg ketamine combined with 0.50 mg/kg medetomidine (reversal with 2.5 mg/kg atipamezole; protocol 3A). Following completion and unblinding, the project was extended with an additional protocol (3B), comprising 25 mg/kg ketamine combined with 0.05 mg/kg medetomidine (reversal with 0.25 mg/kg atipamezole, twice with 35 min interval).ResultsAll protocols in this study provided rapid onset (induction times <5 min) of immobilisation and sedation. Duration of immobilisation was 31.23 ± 22.39 min, 53.72 ± 13.08 min, 19.73 ± 5.74 min, and 22.78 ± 22.37 min for protocol 1, 2, 3A, and 3B, respectively. Recovery times were 135.84 ± 39.19 min, 55.79 ± 11.02 min, 405.46 ± 29.81 min, and 291.91 ± 80.34 min, respectively. Regarding the quality, and reliability (judged by pedal withdrawal reflex, palpebral reflex and muscle tension) of all protocols, protocol 2 was the most optimal. Monitored vital parameters were within clinically acceptable limits during all protocols and there were no fatalities. Indication of muscle damage as assessed by AST, LDH and CK values was most prominent elevated in protocol 1, 3A, and 3B.ConclusionsWe conclude that intramuscular administration of 12 mg/kg alphaxalone to common marmosets is preferred over other protocols studied. Protocol 2 resulted in at least comparable immobilisation quality with acceptable and less frequent side effects and superior recovery quality. In all protocols, supportive therapy, such as external heat support, remains mandatory. Notably, an unacceptable long recovery period in both ketamine/medetomidine protocols (subsequently reversed with atipamezole) was observed, showing that α-2 adrenoreceptor agonists in the used dose and dosing regime is not the first choice for sedation in common marmosets in a standard research setting.

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“…In addition, as described in other studies [32,35], a combination of medetomide and ketamine provides more muscle relaxation than ketamine alone.…”

Section: Discussionsupporting

confidence: 54%

“…However, retching and vomiting were not seen in macaques given ketamine-medetomidine [35]. The observed retching and vomiting during recovery, could also be due atipamezole, however, no information is available about the side effects of atipamezole in primates [28-30,32-35]. …”

Section: Discussionmentioning

confidence: 99%

Comparison of three different sedative-anaesthetic protocols (ketamine, ketamine-medetomidine and alphaxalone) in common marmosets (Callithrix jacchus)

et al. 2013

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“…Other authors have suggested that the benzodiazepines reduce rates of glomerular filtration and urine production in humans, so that these changes in electrolytes could be related to the use of the tranquilizers and sedatives applied in this study. It is important to emphasize that while our results reveal significant differences among the different anesthetic mixtures compared to controls, they remained within the ranges of normality published previously …”

Section: Discussionsupporting

confidence: 85%

“…In addition, this has been shown to decrease the number of respirations per minute by depressing the respiratory centers of the CNS, findings that are consistent with the reduction in SpO 2 observed in Group 5 . According to Settle et al, depression of the HR due to administration of xylazine can be attributed to the combined action of the baroreceptor reflex and vasoconstriction mediated by the α2 receptor. The vasopressor effect of the α2 adrenoceptors produces greater vagal activity while inhibiting central sympathetic activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of different anesthetic mixtures—ketamine‐xylazine, ketamine‐acepromazine and tiletamine‐zolazepam—on the physiological and blood biochemistry parameters of male rhesus monkeys (Macaca mulatta) at different ages

Hernández-Godínez

Jaime²,

Poblano

et al. 2019

Anim Models and Exp Med

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Background Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta . Methods Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every 5 minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion These findings contribute to standardizing this animal model in biological research.

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“…The main advantage of this approach is the ability to maintain normal physiology. Important drawbacks include sedative medication side effects, the stress of anaesthesia and lack of flexibility in sampling times 25 . An alternate approach involves training NHPs, for example using the Positive Reinforcement Technique, to present themselves for sampling.…”

Section: Discussionmentioning

confidence: 99%

Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness

Poliquin

Biondi

Ranadheera

et al. 2017

Sci Rep

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Critical care needs have been rising in recent decades as populations age and comorbidities increase. Sepsis-related admissions to critical care contribute up to 50% of volume and septic shock carries a 35–54% fatality rate. Improvements in sepsis-related care and mortality would have a significant impact of a resource-intensive area of health care delivery. Unfortunately, research has been hampered by the lack of an animal model that replicates the complex care provided to humans in an intensive care unit (ICU). We developed a protocol to provide full ICU type supportive care to Rhesus macaques. This included mechanical ventilation, continuous sedation, fluid and electrolyte management and vasopressor support in response to Ebolavirus-induced septic shock. The animals accurately recapitulated human responses to a full range of ICU interventions (e.g. fluid resuscitation). This model can overcome current animal model limitations by accurately emulating the complexity of ICU care and thereby provide a platform for testing new interventions in critical care and sepsis without placing patients at risk.

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The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in Rhesus Macaques

Abstract: These findings demonstrate repeated anesthesia with ketamine can initiate changes suggesting a tolerance effect.

Cited by 21 publications

References 8 publications

Comparison of three different sedative-anaesthetic protocols (ketamine, ketamine-medetomidine and alphaxalone) in common marmosets (Callithrix jacchus)

Comparison of three different sedative-anaesthetic protocols (ketamine, ketamine-medetomidine and alphaxalone) in common marmosets (Callithrix jacchus)

Effect of different anesthetic mixtures—ketamine‐xylazine, ketamine‐acepromazine and tiletamine‐zolazepam—on the physiological and blood biochemistry parameters of male rhesus monkeys (Macaca mulatta) at different ages

Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness

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