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

BACKGROUND: Handling 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). RESULTS: All 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. CONCLUSIONS: We 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

Simultaneous measurement of behavior and the somatosensory-evoked potential in a rat model

Studies have shown that specific characteristics of somatosensory evoked potentials (SEPs) reflect nociception in both animals and humans. A relationship between SEPs and the unpleasantness of noxious stimulation in rats has recently been demonstrated using Pavlovian fear conditioning, consisting of a training phase in which a conditioned stimulus (CS) is paired with an unconditioned stimulus (US) to elicit the SEPs. After the training, CS-induced fear-conditioned behavior serves as a readout parameter for aversion to the US (i.e., the SEP stimulation paradigm). To prevent the animals from gnawing the stimulation cables that are necessary for generating SEPs, investigators have used a tight-fitting jacket that restrains the rats but also inhibits behavioral measurement. The use of a neck collar is an alternative technique that not only prevents cable gnawing but also allows the animals unrestricted movement while enabling investigators to assess fear-conditioned behavior and measure SEPs. The current study explores the effects of the tight-fitting jacket and the neck collar on SEPs. A within-subjects design was used for recording the SEP of each rat while the animal wore the collar or jacket. Both conditions show a similar SEP morphology, but data from the collar-wearing rats indicated an increase of the N150 peak amplitude (associated with emotional arousal) and peak latencies that appeared to be shorter. Thus the collar will be useful in future studies as it allows the simultaneous evaluation of SEPs and behavior

Simultaneous measurement of behavior and the somatosensory-evoked potential in a rat model

Studies have shown that specific characteristics of somatosensory evoked potentials (SEPs) reflect nociception in both animals and humans. A relationship between SEPs and the unpleasantness of noxious stimulation in rats has recently been demonstrated using Pavlovian fear conditioning, consisting of a training phase in which a conditioned stimulus (CS) is paired with an unconditioned stimulus (US) to elicit the SEPs. After the training, CS-induced fear-conditioned behavior serves as a readout parameter for aversion to the US (i.e., the SEP stimulation paradigm). To prevent the animals from gnawing the stimulation cables that are necessary for generating SEPs, investigators have used a tight-fitting jacket that restrains the rats but also inhibits behavioral measurement. The use of a neck collar is an alternative technique that not only prevents cable gnawing but also allows the animals unrestricted movement while enabling investigators to assess fear-conditioned behavior and measure SEPs. The current study explores the effects of the tight-fitting jacket and the neck collar on SEPs. A within-subjects design was used for recording the SEP of each rat while the animal wore the collar or jacket. Both conditions show a similar SEP morphology, but data from the collar-wearing rats indicated an increase of the N150 peak amplitude (associated with emotional arousal) and peak latencies that appeared to be shorter. Thus the collar will be useful in future studies as it allows the simultaneous evaluation of SEPs and behavior

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs

Vet Anaesth Analg. 2009 Jul;36(4):369-83. Epub 2009 May 12. Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs. Valtolina C, Robben JH, Uilenreef J, Murrell JC, Aspegrén J, McKusick BC, Hellebrekers LJ. Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands. OBJECTIVE: To compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated. STUDY DESIGN: Prospective, randomised, blinded, positive-controlled parallel-group clinical study. ANIMALS: Forty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery. METHODS: After surgery, a loading dose of either DMED (25 microg m(-2)) or MOR (2500 microg m(-2)) followed by a 24-hour CRI of DMED (25 microg m(-2) hour(-1)) or MOR (2500 microg m(-2) hour(-1)) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan-Meier methodology. RESULTS: Forty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups. CONCLUSION / CLINICAL RELEVANCE: Dexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs. PMID: 19470144 [PubMed - indexed for MEDLINE