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This article reports on respiratory function in white rhinoceros (Ceratotherium simum) immobilized with etorphine-azaperone and the changes induced by butorphanol administration as part of a multifaceted crossover study that also investigated the effects of etorphine or etorphine-butorphanol treatments. Six male white rhinoceros underwent two immobilizations by using 1) etorphine-azaperone and 2) etorphine-azaperone-butorphanol. Starting 10 min after recumbency, arterial blood gases, limb muscle tremors, expired minute ventilation, and respiratory rate were evaluated at 5-min intervals for 25 min. Alveolar to arterial oxygen gradient, expected respiratory minute volume, oxygen consumption, and carbon dioxide production were calculated. Etorphine-azaperone administration resulted in hypoxemia and hypercapnia, with increases in alveolar to arterial oxygen gradient, oxygen consumption, and carbon dioxide production, and a decrease in expired minute ventilation. Muscle tremors were also observed. Intravenous butorphanol administration in etorphine-azaperone–immobilized white rhinoceros resulted in less hypoxemia and hypercapnia; a decrease in oxygen consumption, carbon dioxide production, and expired minute ventilation; and no change in the alveolar to arterial oxygen gradient and rate of breathing. We show that the immobilization of white rhinoceros with etorphine-azaperone results in hypoxemia and hypercapnia and that the subsequent intravenous administration of butorphanol improves both arterial blood oxygen and carbon dioxide partial pressures. [ABSTRACT FROM AUTHOR]

Black-faced impala (Aepyceros melampus ssp. petersi) are endemic to Namibia where conservation management involves immobilisation and translocation, and mortality with current protocols is common. Critically evaluated field immobilisation protocols are needed to maximise animal safety. This prospective study was done in two phases: the first compared etorphine- and thiafentanil-based combinations, the second evaluated the influence of oxygen in impala receiving the thiafentanil-based combination. Animals (10 per group) received 50 mg ketamine (K) and 10 mg butorphanol (B), with either 2.0 mg etorphine (E) or 2.0 mg thiafentanil (T). A third group of ten impala were anaesthetised using TKB with supplemental nasal oxygen (O) at a rate of 5 L/minute. Behavioural, metabolic and physiological variables were assessed within five minutes of recumbency and at 10, 15, and 20 minutes post-recumbency. Statistical analyses for non-parametric data were performed to compare the treatment groups as well as time points; p ≤ 0.05 considered significant. Following darting, 7/10 EKB animals were standing when approached, compared to 2/20 in the thiafentanil treatment groups. Time to first effect was significantly higher for EKB (155 ± 105.7 seconds) compared to TKBO (61.5 ± 21.4 seconds). Time to sternal after darting was significantly higher with EKB (411.6 ± 174 seconds) compared to TKB (160.5 ± 85.4 seconds) and TKBO (166 ± 77.3 seconds). This study builds on previous work investigating the effects of potent opioids on impala and is the first evaluating their use in a field setting. The thiafentanil combination had a faster onset and resulted in a smoother induction than the etorphine combination. Additionally, oxygenation improved in animals receiving oxygen supplementation. [ABSTRACT FROM AUTHOR]

Numerous G-protein-coupled receptors (GPCRs) display ligand-free basal signaling with potential physiological functions, a target in drug development. As an example, the μ opioid receptor (MOR) signals in ligand-free form (MOR-μ*), influencing opioid responses. In addition, agonists bind to MOR but can dissociate upon MOR activation, with ligand-free MOR-μ* carrying out signaling. Opioid pain therapy is effective but incurs adverse effects (ADRs) and risk of opioid use disorder (OUD). Sustained opioid agonist exposure increases persistent basal MOR-μ* activity, which could be a driving force for OUD and ADRs. Antagonists competitively prevent resting MOR (MOR-μ) activation to MOR-μ*, while common antagonists, such as naloxone and naltrexone, also bind to and block ligand-free MOR-μ*, acting as potent inverse agonists. A neutral antagonist, 6β-naltrexol (6BN), binds to but does not block MOR-μ*, preventing MOR-μ activation only competitively with reduced potency. We hypothesize that 6BN gradually accelerates MOR-μ* reversal to resting-state MOR-μ. Thus, 6BN potently prevents opioid dependence in rodents, at doses well below those blocking antinociception or causing withdrawal. Acting as a 'retrograde addiction modulator', 6BN could represent a novel class of therapeutics for OUD. Further studies need to address regulation of MOR-μ* and, more broadly, the physiological and pharmacological significance of ligand-free signaling in GPCRs. [ABSTRACT FROM AUTHOR]

The study compared immobilisation of blesbok (Damaliscus pygargus phillipsi) with etorphine and azaperone vs etorphine and midazolam. Twelve female blesbok, weighing 59.4 ± 2.8 kg, were used. Each animal randomly received Treatment 1 (T1) (etorphine, 0.07 ± 0.003 mg/kg + azaperone, 0.36 ± 0.02 mg/kg) and Treatment 2 (T2) (etorphine, 0.07 ± 0.003 mg/kg + midazolam, 0.20 ± 0.01 mg/kg) with a one-week washout period between treatments. Induction times were recorded followed by physiological monitoring for 45 minutes of immobilisation. Immobilisation was reversed with naltrexone (20 mg per mg etorphine). Recovery times were also recorded. Induction, immobilisation and recovery were scored with subjective measures. Inductions and recoveries did not differ between combinations, but the quality of immobilisation was significantly better with T1. Rectal temperature and blood pressure were significantly lower during T1. Both treatments resulted in severe hypoxaemia and impaired gas exchange, although overall hypoxaemia was more pronounced for T1. Animals treated with T2, however, exhibited a deterioration in respiration as the monitoring period progressed, possibly as a result of impaired ventilatory muscle function due to the effects of midazolam. Both combinations are suitable for adequate immobilisation of blesbok and should be selected based on the specific capture situation. Supplementation with oxygen is highly recommended. [ABSTRACT FROM AUTHOR]

Sixteen captive Persian fallow deer (Dama dama mesopotamica) scheduled for translocation were immobilized with a combination of 30±5µg/kg etorphine and 3±0.6µg/kg medetomidine administered by a remote intramuscular injection. Induction and recovery times and physiologic parameters were recorded, and the quality of induction, immobilization and recovery were scored. Naltrexone and atipamezole were administered for recovery. Mean induction time was 4.9±3.1 minutes, and induction quality was considered very good. The quality of immobilization was fair, due to the light immobilization plane and constant limb movement. Severe hypoxemia was observed (oxygen saturation at 70%). Following reversal, mean recovery time was 3.8±2.4 minutes, and recovery quality was excellent. The combination of etorphine-medetomidine at the doses reported here did not result in optimal immobilization and is likely to produce severe hypoxemia, however, recovery is quick. Other anesthetic combinations should be investigated for immobilization of Persian fallow deer. [ABSTRACT FROM AUTHOR]

Background and purposeThe opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception.Experimental approachWe used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception.Key resultsEtorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg(-1) ), unmasked etorphine (3 mg·kg(-1) ) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg(-1) ) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg(-1) ) and diazepam (1 mg·kg(-1) ).Conclusions and implicationsSystemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation.Linked articlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Chemical immobilisation is essential for veterinarians to perform medical procedures in wild African ungulates. Potent opioids combined with neuroleptic drugs are most often used for this purpose. The present study aimed at comparing the quality of immobilisation and effects on physiological variables between a high (high etorphine-azaperone [HE]: 0.09 mg kg–1) and low etorphine dose (low etorphine-azaperone [LE]: 0.05 mg kg–1), both combined with azaperone (0.35 mg kg–1), in 12 adult female boma-acclimatised blesbok. It was hypothesised that a reduction in etorphine's dose in combination with azaperone would result in less cardiorespiratory impairment but likely worsen the quality of immobilisation. Both treatments resulted in rapid induction and recovery times. Overall inter-treatment differences occurred in pulse rate (HE and LE: 52 ± 15 and 44 ± 11 beats minute–1, p < 0.0001), respiratory rate (HE and LE: 15 ± 4 and 17 ± 4 breaths minute–1, p < 0.006), partial pressure of exhaled carbon dioxide (HE and LE: 62.0 ± 5.0 and 60.0 ± 5.6 millimetre of mercury [mmHg], p < 0.028) and arterial carbon dioxide (HE and LE: 58.0 ± 4.5 and 55.0 ± 3.9 mmHg, p < 0.002). Both HE and LE led to bradycardia, hypertension and marked hypoxia to a similar extent. Furthermore, quality of induction, immobilisation and recovery were similar in both treatments. The role of azaperone in the development of cardiorespiratory compromise and gas exchange impairment that occurred when these combinations were used is still unclear. Further studies are recommended to elucidate drug- and dose-specific physiological effects in immobilised antelope. [ABSTRACT FROM AUTHOR]

To compare the cardiopulmonary effects of the opioids etorphine and thiafentanil for immobilization of impala. Two-way crossover, randomized study. A group of eight adult female impala. Impala were given two treatments: 0.09 mg kg–1 etorphine or 0.09 mg kg–1 thiafentanil via remote dart injection. Time to recumbency, quality of immobilization and recovery were assessed. Respiratory rate, heart rate (HR), mean arterial blood pressure (MAP) and arterial blood gases were measured. A linear mixed model was used to analyse the effects of treatments, treatments over time and interactions of treatment and time (p < 0.05). Time to recumbency was significantly faster with thiafentanil (2.0 ± 0.8 minutes) than with etorphine (3.9 ± 1.6 minutes; p = 0.007). Both treatments produced bradypnoea, which was more severe at 5 minutes with thiafentanil (7 ± 4 breaths minute–1) than with etorphine (13 ± 12 breaths minute–1; p = 0.004). HR increased with both treatments but significantly decreased over time when etorphine (132 ± 17 to 82 ± 11 beats minute–1) was compared with thiafentanil (113 ± 22 to 107 ± 36 beats minute–1; p < 0.001). Both treatments caused hypertension which was more profound with thiafentanil (mean overall MAP = 140 ± 14 mmHg; p < 0.001). Hypoxaemia occurred with both treatments but was greater with thiafentanil [PaO 2 37 ± 13 mmHg (4.9 kPa)] than with etorphine [45 ± 16 mmHg (6.0 kPa)] 5 minutes after recumbency (p < 0.001). After 30 minutes, PaO 2 increased to 59 ± 10 mmHg (7.9 kPa) with both treatments (p < 0.001). The shorter time to recumbency with thiafentanil may allow easier and faster retrieval in the field. However, thiafentanil caused greater hypertension, and ventilatory effects during the first 10 minutes, after administration. [ABSTRACT FROM AUTHOR]

To determine the cardiopulmonary effects of etorphine and thiafentanil for immobilization of blesbok. Blinded, randomized, two-way crossover study. A group of eight adult female blesbok. Animals were immobilized twice, once with etorphine (0.09 mg kg–1) and once with thiafentanil (0.09 mg kg–1) administered intramuscularly by dart. Immobilization quality was assessed and analysed by Wilcoxon signed-rank test. Time to final recumbency was compared between treatments by one-way analysis of variance. Cardiopulmonary effects including respiratory rate (ƒ R), arterial blood pressures and arterial blood gases were measured. A linear mixed model was used to assess the effects of drug treatments over the 40 minute immobilization period. Significant differences between treatments, for treatment over time as well as effect of treatment by time on the variables, were analysed (p < 0.05). There was no statistical difference (p = 0.186) between treatments for time to recumbency. The mean ƒ R was lower with etorphine (14 breaths minute–1) than with thiafentanil (19 breaths minute–1, p = 0.034). The overall mean PaCO 2 was higher with etorphine [45 mmHg (6.0 kPa)] than with thiafentanil [41 mmHg (5.5 kPa), p = 0.025], whereas PaO 2 was lower with etorphine [53 mmHg (7.1 kPa)] than with thiafentanil [64 mmHg (8.5 kPa), p < 0.001]. The systolic arterial pressure measured throughout all time points was higher with thiafentanil than with etorphine (p = 0.04). The difference varied from 30 mmHg at 20 minutes after recumbency to 14 mmHg (standard error difference 2.7 mmHg) at 40 minutes after recumbency. Mean and diastolic arterial pressures were significantly higher with thiafentanil at 20 and 25 minute measurement points only (p < 0.001). Both drugs caused clinically relevant hypoxaemia; however, it was less severe with thiafentanil. Ventilation was adequate. Hypertension was greater and immobilization scores were lower with thiafentanil. [ABSTRACT FROM AUTHOR]

This study used electrical impedance tomography (EIT) measurements of regional ventilation and perfusion to elucidate the reasons for severe gas exchange impairment reported in rhinoceroses during opioid-induced immobilization. EIT values were compared with standard monitoring parameters to establish a new monitoring tool for conservational immobilization and future treatment options. Six male white rhinoceroses were immobilized using etorphine, and EIT ventilation variables, venous admixture, and dead space were measured 30, 40, and 50 min after becoming recumbent in lateral position. Pulmonary perfusion mapping using impedance-enhanced EIT was performed at the end of the study period. The measured impedance (∆Z) by EIT was compared between pulmonary regions using mixed linear models. Measurements of regional ventilation and perfusion revealed a pronounced disproportional shift of ventilation and perfusion toward the nondependent lung. Overall, the dependent lung was minimally ventilated and perfused, but remained aerated with minimal detectable lung collapse. Perfusion was found primarily around the hilum of the nondependent lung and was minimal in the periphery of the nondependent and the entire dependent lung. These shifts can explain the high amount of venous admixture and physiological dead space found in this study. Breath holding redistributed ventilation toward dependent and ventral lung areas. The findings of this study reveal important pathophysiological insights into the changes in lung ventilation and perfusion during immobilization of white rhinoceroses. These novel insights might induce a search for better therapeutic options and is establishing EIT as a promising monitoring tool for large animals in the field. NEW & NOTEWORTHY Electrical impedance tomography measurements of regional ventilation and perfusion applied to etorphine-immobilized white rhinoceroses in lateral recumbency revealed a pronounced disproportional shift of the measured ventilation and perfusion toward the nondependent lung. The dependent lung was minimally ventilated and perfused, but still aerated. Perfusion was found primarily around the hilum of the nondependent lung. These shifts can explain the gas exchange impairments found in this study. Breath holding can redistribute ventilation. [ABSTRACT FROM AUTHOR]

Twenty free-ranging warthogs (Phacochoerus africanus) in the Kruger National Park, South Africa, were immobilized with a combination of etorphine (0.039 ± 0.005 mg/kg) and azaperone (0.44 ± 0.06 mg/kg) administered intramuscularly by dart. Butorphanol (1 mg per mg etorphine) was administered intravenously at t = 5 min. A standardized scoring system was used to record induction, immobilization and recovery characteristics. Physiological parameters were recorded at 5 min intervals and an arterial sample collected for blood gas analyses every 15 min. At 45 min after butorphanol administration, immobilization was partially reversed by administering naltrexone (40x etorphine dose in mg) intravenously. Overall, induction quality was good, with the mean time to safe handling 5.9 ± 1.4 min. The majority of immobilization scores (54%) over the entire monitoring period (40 min) were at level 3, consistent with a light plane in which palpebral and laryngeal reflexes were still present but the animal could be safely handled. Overall mean heart rate was 94.7 ± 15.3 beats per min, mean respiratory rate was 14.7 ± 9.8 breaths per min, and the mean rectal temperature was 38.5 ± 1.0°C. Significant hypoxia (overall mean oxygen arterial partial pressure 38.8 ± 8.4 mmHg), hypercapnia (mean carbon dioxide arterial partial pressure 63.3 ± 7.8 mmHg), and acidosis (mean pH 7.28 ± 0.04) were observed in immobilized warthogs. Following antagonist administration, warthogs were standing within 1.0 ± 0.4 min, with the majority of recoveries scored as excellent. The drug combination proved to be effective in the immobilization of free-ranging warthogs with rapid induction and recovery, but with significant cardio-respiratory changes. Therefore, this drug combination may be useful when rapid immobilization and recovery are indicated, but should be used cautiously in compromised warthogs.

To evaluate the immobilization quality and cardiopulmonary effects of etorphine alone compared with etorphine–azaperone in blesbok (Damaliscus pygargus phillipsi). Blinded, randomized, crossover design. A total of 12 boma-habituated female blesbok weighing [mean ± standard deviation (SD)] 57.5 ± 2.5 kg. Each animal was administered etorphine (0.09 mg kg–1) or etorphine–azaperone (0.09 mg kg–1; 0.35 mg kg–1) intramuscularly with 1-week intertreatment washout period. Time to first sign of altered state of consciousness and immobilization time were recorded. Physiological variables were recorded, arterial blood samples were taken during a 40-minute immobilization period, and naltrexone (mean ± SD: 1.83 ± 0.06 mg kg–1) was intravenously administered. Recovery times were documented, and induction, immobilization and recovery were subjectively scored. Statistical analyses were performed; p < 0.05 was significant. No difference was observed in time to first sign, immobilization time and recovery times between treatments. Time to head up was longer with etorphine–azaperone (0.5 ± 0.2 versus 0.4 ± 0.2 minutes; p = 0.015). Etorphine caused higher arterial blood pressures (mean: 131 ± 17 versus 110 ± 11 mmHg, p < 0.0001), pH, rectal temperature and arterial oxygen partial pressure (59.2 ± 7.7 versus 42.2 ± 9.8 mmHg), but lower heart (p = 0.002) and respiratory rates (p = 0.01). Etorphine–azaperone combination led to greater impairment of ventilatory function, with higher end-tidal carbon dioxide (p < 0.0001) and arterial partial pressure of carbon dioxide (58.0 ± 4.5 versus 48.1 ± 5.1 mmHg). Immobilization quality was greater with etorphine-azaperone than with etorphine alone (median scores: 4 versus 3; p < 0.0001). Both treatments provided satisfactory immobilization of blesbok; however, in addition to a deeper level of immobilization, etorphine–azaperone caused greater ventilatory impairment. Oxygen supplementation is recommended with both treatments. [ABSTRACT FROM AUTHOR]

Potent opioids are known to cause negative alterations to the physiology of immobilised antelope. How these effects differ between species has not been studied. This study aimed to compare time to recumbence and effects of opioid-based immobilisation on the physiology of impala (Aepyceros melampus) and blesbok (Damaliscus pygargus phillipsi). Eight animals of each species were immobilised, with 0.09 mg/kg etorphine and 0.09 mg/kg thiafentanil respectively, in a randomised two-way cross-over study. Variables measured and analysed by means of a linear mixed model included time to recumbence, heart rate, respiratory rate, arterial blood pressure, blood gases, lactate and glucose. In blesbok, mean time to recumbence was not significantly different with either drug (2.5 minutes and 2.2 min, respectively), but in impala thiafentanil achieved a shorter time to recumbence (2.0 min) than etorphine (3.9 min). Mean heart rates of immobilised impala were within reported physiological limits, but lower in immobilised blesbok when both opioids were used (35 beats/min to 44 beats/min vs. 104 ± 1.4 beats/min resting heart rate). Impala developed severe respiratory compromise and hypoxaemia from both opioids (overall mean PaO2 values ranged from 38 mmHg to 59 mmHg over 30 min). In contrast, blesbok developed only moderate compromise. Therefore, significantly different species-specific physiological responses to potent opioid drugs exist in blesbok and impala. Given that these different responses are clinically relevant, extrapolation of immobilising drug effects from one species of African ungulate to another is not recommended. [ABSTRACT FROM AUTHOR]

Five free-ranging male (subadults, n = 3; adults, n = 2) plains zebras (Equus quagga) were immobilized using a combination of etorphine (0.017 mg/kg), medetomidine (0.017 mg/kg), and azaperone (0.24 mg/kg) by means of a blank cartridge-fired projector. Time to recumbency was recorded and a descriptive score used to assess the quality of immobilization, manipulation, maintenance, and recovery. Physiological parameters were recorded at 5-min intervals for 20 min. At the end of the procedure, naltrexone (0.23 mg/kg) was administered intramuscularly and time to standing documented. The combination evaluated in this study allowed for successful immobilization and safe recovery of all animals, including during the subsequent 15 days. Despite the good outcome in this pilot study, as a result of the periodic apneic events and hypercapnia documented in the zebras, the authors suggest that physiological parameters be thoroughly monitored when using this protocol. Further studies are needed to improve upon chemical immobilization protocols in free-ranging plains zebras. [ABSTRACT FROM AUTHOR]

To determine whether the R-enantiomer of 8-hydroxy-2-(di-n-propylamino) tetralin (R-8-OH-DPAT) alleviates respiratory depression in antelope species immobilized with etorphine. The experiment also aimed to establish the most clinically effective dose of this serotonin 5- HT 1A receptor agonist. A group of six female blesbok and six female impala. Each animal was subjected to four immobilization treatments in a prospective four-way crossover design—control treatment consisting of only etorphine at 0.09 mg kg–1 and three treatments consisting of etorphine at 0.09 mg kg–1 combined with 0.005, 0.02 and 0.07 mg kg–1 of R-8-OH-DPAT, respectively. Induction, quality of immobilization and recovery were monitored in each treatment. Physiological variables including heart rate, respiratory rate, arterial blood pressure and blood gases were measured for 35 minutes during immobilization. A linear mixed model was used to assess the effects of treatments over the recumbency period. R-8-OH-DPAT did not influence induction, immobilization or recovery scores. Respiratory rate in blesbok was increased in the medium- and high-dosage R-8-OH-DPAT treatment group. However, this increased respiratory rate did not translate into improvements of arterial partial pressure of oxygen (PaO 2) values in the blesbok. The medium and higher dosages of R-8-OH-DPAT in impala led to an improved PaO 2 as well as to decreased opioid-induced tachycardia during the first 10 minutes of immobilization. Previous reports indicated that the racemic mixture of 8-OH-DPAT injected intravenously had a positive effect on blood-gas values in etorphine-treated hypoxemic goats. In this experiment, similar effects could be seen in impala at the higher dosage rates of R-8-OH-DPAT. However, failure to achieve an improvement of blood-gas values in blesbok was an unexpected result. It could be speculated that the dosage, species-specific differences of serotonin receptors or the use of the R-enantiomer of 8-OH-DPAT might play a role. [ABSTRACT FROM AUTHOR]

We recently demonstrated that prolonged treatment with morphine increases the antinociceptive potency of the delta-opioid receptor (deltaOR) agonist deltorphin and promotes cell surface targeting of deltaORs in neurons of the dorsal horn of the rat spinal cord (Cahill et al., 2001b). In the present study we examined whether these effects were mediated selectively via muOR. Using the same intermittent treatment regimen as for morphine, we found that methadone and etorphine, but not fentanyl, enhanced [D-Ala2]-deltorphin-mediated antinociception. However, continuous delivery of fentanyl for 48 hr resulted in augmented deltaOR-mediated antinociception when compared with saline-infused animals. Time course studies confirmed that a 48 hr treatment with morphine was necessary for the establishment of enhanced deltaOR-mediated antinociception. The observed increases in deltaOR agonist potency and deltaOR plasma membrane density were reversed fully 48 hr after discontinuation of morphine injections. Wild-type C57BL/6 mice pretreated with morphine for 48 hr similarly displayed enhanced deltaOR-mediated antinociception in a tonic pain paradigm. Accordingly, the percentage of plasma membrane-associated deltaOR in the dorsal horn of the spinal cord, as assessed by immunogold electron microscopy, increased from 6.6% in naive to 12.4% in morphine-treated mice. In contrast, morphine treatment of muOR gene knock-out (KO) mice did not produce any change in deltaOR plasma membrane density. These results demonstrate that selective activation of muOR is critical for morphine-induced targeting of deltaOR to neuronal membranes, but not for basal targeting of this receptor to the cell surface.

We recently demonstrated that prolonged treatment with morphine increases the antinociceptive potency of the delta-opioid receptor (deltaOR) agonist deltorphin and promotes cell surface targeting of deltaORs in neurons of the dorsal horn of the rat spinal cord (Cahill et al., 2001b). In the present study we examined whether these effects were mediated selectively via muOR. Using the same intermittent treatment regimen as for morphine, we found that methadone and etorphine, but not fentanyl, enhanced [D-Ala2]-deltorphin-mediated antinociception. However, continuous delivery of fentanyl for 48 hr resulted in augmented deltaOR-mediated antinociception when compared with saline-infused animals. Time course studies confirmed that a 48 hr treatment with morphine was necessary for the establishment of enhanced deltaOR-mediated antinociception. The observed increases in deltaOR agonist potency and deltaOR plasma membrane density were reversed fully 48 hr after discontinuation of morphine injections. Wild-type C57BL/6 mice pretreated with morphine for 48 hr similarly displayed enhanced deltaOR-mediated antinociception in a tonic pain paradigm. Accordingly, the percentage of plasma membrane-associated deltaOR in the dorsal horn of the spinal cord, as assessed by immunogold electron microscopy, increased from 6.6% in naive to 12.4% in morphine-treated mice. In contrast, morphine treatment of muOR gene knock-out (KO) mice did not produce any change in deltaOR plasma membrane density. These results demonstrate that selective activation of muOR is critical for morphine-induced targeting of deltaOR to neuronal membranes, but not for basal targeting of this receptor to the cell surface.

Grevy's zebra (Equus grevyi) is an endangered species often found in zoological collections. Veterinary care for this species often requires immobilization. This study retrospectively evaluated behavioral and physiological parameters from Grevy's zebra records after three immobilization protocols: etorphine and alpha-2 agonist (EA2; n = 11); etorphine, alpha-2 agonist, and ketamine (EA2K; n = 16); and thiafentanil, alpha-2 agonist, and ketamine (TA2K; n = 6). Median time to working depth was statistically different (P = 0.03; EA2 = 6.5 min, EA2K = 6.3 min, TA2K = 14.5 min) by the Kruskal–Wallis test. When EA2 + EA2K were combined and compared with TA2K (Wilcoxon rank sum test), median recumbency time (P = 0.02) was also significantly longer (15 min compared with 6 min) for TA2K. There were no significant differences between the groups for physiological parameters or recovery time after reversal. Although all protocols produced anesthesia in Grevy's zebra, increased time to achieve working depth was observed with the alpha-2 and thiafentanil combinations. [ABSTRACT FROM AUTHOR]

Background: Studying wild animals in situ is fundamental to collecting baseline information, but generally they need to be immobilised for examination, sampling, marking and/or equipping with tracking apparatus. Capturing wild animals is inherently risky and there is a need for immobilisation methods that are safe for both the animals and researchers. Methods: A total of 16 free‐ranging swamp buffalo (Bubalus bubalis) were chemically captured by dart for the application of satellite tracking collars in tropical northern Australia; 7 animals were anesthetised with a thiafentanil–etorphine–azaperone (TEA) combination and 9 animals with a thiafentanil–azaperone (TA) combination. Anaesthesia was reversed with intravenous naltrexone. Mean dosages of etorphine and thiafentanil for animals in the TEA group were 0.01 mg/kg of each drug and mean dosage of thiafentanil for animals in the TA group was 0.02 mg/kg. Total dose per animal of azaperone and naltrexone was 80 mg and 150 mg, respectively. Anaesthetic monitoring was by physical observation of physiological variables, pulse oximetry and capnography. Blood laboratory parameters including creatine kinase (CK), aspartate transaminase (AST), serum bicarbonate and anion gap were measured. Results: All subject animals recovered well from anaesthesia despite the occurrence of subclinical acidosis in some patients. There was no significant difference between the treatment groups. Conversely, chase time had an adverse effect on body temperature, irrespective of the anaesthetic combination used. Conclusions: Thiafentanil and azaperone, with or without etorphine, delivered rapid safe, effective, reversible field anaesthesia in healthy swamp buffalo. [ABSTRACT FROM AUTHOR]

This report describes weekly repeated anesthesia in a 7-yr-old, 1,030 kg, female Eastern black rhinoceros (Diceros bicornis michaeli), that was immobilized six times using a combination of 2 mg etorphine (0.002 mg/kg), 5 mg medetomidine (0.005 mg/kg), 25 mg midazolam (0.024 mg/kg), and 300 mg ketamine (0.29 mg/kg) delivered intramuscularly (IM) via remote dart to facilitate long-term medical care of a bilateral, obstructive Actinomyces sp. rhinitis. The drug combination described in this study resulted in reliable, rapid recumbency of the animal within 2–8 min after initial administration via dart and produced deep anesthesia for 34–78 min without supplemental anesthetic administration. Antagonist drugs (100 mg naltrexone [0.1 mg/kg] and 25 mg atipamezole [0.024 mg/kg] IM) produced reliable and uneventful recoveries in all the procedures. During each anesthetic procedure, the animal was intubated and provided intermittent positive pressure ventilation with a megavertebrate demand ventilator. Tachycardia and hypoxia noted after induction resolved after positive pressure ventilation with oxygen. This report provides useful information on a novel anesthetic protocol used repeatedly for intensive medical management in a black rhinoceros. [ABSTRACT FROM AUTHOR]

The effects of etorphine on the pulmonary vascular system of white rhinoceros (Ceratotherium simum) have not been described and could play a role in the severe hypoxemia that develops after immobilization with etorphine-based drug combinations. Characterization of these effects requires measurement of pulmonary vascular pressures and cardiac output (CO). To refine a technique for pulmonary arterial catheterization, five boma-habituated white rhinoceros (three females and two males weighing 1,012–1,572 kg) were immobilized by remote injection with etorphine plus azaperone followed by butorphanol. This afforded the opportunity to perform a pilot study and acquire preliminary measurements of pulmonary arterial pressure (PAP) and CO before and after supplemental etorphine given intravenously. Ultrasonographic guidance was used to insert a sheath introducer into a linguofacial branch of a jugular vein. A 160-cm-long pulmonary artery catheter with a balloon and thermistor was then passed through the introducer and positioned with its tip in the pulmonary artery. It was not long enough to permit wedging for measurement of pulmonary artery occlusion pressure. Mean PAP was 35 mm Hg (minimum, maximum 32, 47 mm Hg) and increased (P = 0.031) by 83% (28, 106%) after supplemental etorphine. Thermodilution CO was 120 L/min (92, 145 L/min) and increased 27% (3, 43%) (P = 0.031). Heart rate was 100 (88, 112) beats/min and increased 20% (4, 45%) (P = 0.031), whereas arterial partial pressure of oxygen was 35 mm Hg (30, 94 mm Hg) and decreased 47% (20, 72%) (P = 0.031). The cardiovascular observations could result from etorphine-induced generalized sympathetic outflow, as has been reported in horses. Further studies of etorphine in isolation are needed to test this suggestion and to discern how the changes in pulmonary vascular pressures and blood flow might relate to hypoxemia in etorphine-immobilized white rhinoceros. [ABSTRACT FROM AUTHOR]

Immobilizing and handling large, free-ranging animals without proper facilities in harsh environmental conditions poses significant challenges. During two field expeditions, a total of 29 female muskoxen (Ovibos moschatus) were immobilized in Northeast Greenland (74°N, 20°E). Fixed doses of immobilizing drugs were used regardless of animal size: 2 mg etorphine, 30 mg xylazine, 0.3 mg medetomidine, and 40 mg ketamine. Physiologic and behavioral monitoring was performed during the second expedition on 15 female muskoxen. The observed heart rates were 35–58 beats/min and respiratory rates were 25–30 breaths/min. Mean arterial pressures measured using oscillometry ranged between 117–142 mmHg. Pulse oximeter readings ranged from 91–98% with oxygen supplementation, nasal end-tidal carbon dioxide values were 24–42 mmHg, and rectal temperature ranged from 38.9–39.6°C. Induction time was 6–8 min, recovery time 2–6 min after reversal, and duration of anesthesia was 50–100 min. This anesthetic regime thus provided reliable immobilization with minimal pathophysiologic alterations. [ABSTRACT FROM AUTHOR]

Chemical immobilization is necessary for the physiological study of large wild animals. However, the immobilizing drugs can adversely affect the cardiovascular and respiratory systems, yielding data that do not accurately represent the normal, resting state. We hypothesize that these adverse effects can be ameliorated by reversing the immobilizing agent while holding the animal under general anaesthesia. We used habituated sheep Ovis aries (N = 5, 46.9 ± 5.3 kg body mass, mean ± SEM) and goats Capra hircus (N = 4, 27.7 ± 2.8 kg) as ungulate models for large wild animals, and measured their cardiorespiratory function under three conditions: (1) mild sedation (midazolam), as a proxy for the normal resting state, (2) immobilization (etorphine and azaperone), and (3) general anaesthesia (propofol) followed by etorphine antagonism (naltrexone). Cardiac output for both sheep and goats remained unchanged across the three conditions (overall means of 6.2 ± 0.9 and 3.3 ± 0.3 L min−1, respectively). For both sheep and goats, systemic and pulmonary mean arterial pressures were significantly altered from initial midazolam levels when administered etorphine + azaperone, but those arterial pressures were restored upon transition to propofol anaesthesia and antagonism of the etorphine. Under etorphine + azaperone, minute ventilation decreased in the sheep, though this decrease was corrected under propofol, while the minute ventilation in the goats remained unchanged throughout. Under etorphine + azaperone, both sheep and goats displayed arterial blood hypoxia and hypercapnia (relative to midazolam levels), which failed to completely recover under propofol, indicating that more time might be needed for the blood gases to be adequately restored. Nonetheless, many of the confounding cardiorespiratory effects of etorphine were ameliorated when it was antagonized with naltrexone while the animal was held under propofol, indicating that this procedure can largely restore the cardiovascular and respiratory systems closer to a normal, resting state. [ABSTRACT FROM AUTHOR]

Etorphine–azaperone is the most commonly used drug combination for chemical immobilisation of free-ranging white rhinoceroses, but causes several profound physiological disturbances, including muscle tremors. The addition of benzodiazepine sedatives, such as midazolam, has been proposed to reduce the muscular rigidity and tremors in immobilised rhinoceroses. Twenty-three free-ranging, sub-adult white rhinoceros bulls were darted and captured using a combination of etorphine plus either azaperone or midazolam. Skeletal muscle tremors were visually evaluated and scored by an experienced veterinarian, and tremor scores and distance run were compared between groups using the Wilcoxon rank sum test. No statistical differences were observed in tremor scores (p = 0.435) or distance run (p = 0.711) between the two groups, and no correlation between these variables was detected (r = –0.628; p = 0.807). Etorphine–midazolam was as effective as etorphine–azaperone at immobilising rhinoceroses, with animals running similar distances. Although the addition of midazolam to the etorphine did not reduce tremor scores compared to azaperone, it might have other beneficial immobilising effects in rhinoceroses, and further investigation is necessary to elucidate possible methods of reducing muscle tremoring during chemical immobilisation of rhinoceroses. [ABSTRACT FROM AUTHOR]

Etorphine-azaperone immobilisation was evaluated for translocation of Masai giraffes. Nine giraffes were darted with 0.012 ± 0.001 mg/kg etorphine and 0.07 ± 0.01 mg/kg azaperone. Once ataxic, giraffes were roped for recumbency and restrained manually. Naltrexone (3 mg/mg etorphine) was immediately given intravenously to reverse etorphine-related side effects. Protocol evaluation included physiological monitoring, blood-gas analyses, anaesthetic times, and quality scores (1 = excellent, 4 = poor). Sedation onset and recumbency were achieved in 2.6 ± 0.8 and 5.6 ± 1.4 min. Cardio-respiratory function (HR = 70 ± 16, RR = 32 ± 8, MAP = 132 ± 16) and temperature (37.8 ± 0.5) were stable. Arterial gas analysis showed hypoxaemia in some individuals (PaO2 = 67 ± 8 mmHg) and metabolic acidosis (pH = 7.23 ± 0.05, PaCO2 = 34 ± 4 mmHg, HCO3− = 12.9 ± 1.2 mmol/l). Minor startle response occurred, while higher induction-induced excitement correlated to longer inductions, worse restraint, and decreased HCO3−. After 19 ± 3.5 min of restraint, giraffes were allowed to stand and were loaded onto a chariot. Immobilisations were good and scored 2 (1−3). Inductions and recoveries were smooth and scored 1 (1−2). Translocations were uneventful and no complications occurred in 14-days boma follow-up.

Sable antelope ( Hippotragus niger ), a large, dominant species, often require chemical immobilization for captive management. Despite several recorded protocols, limited objective or subjective data are available to guide chemical immobilization of this species. This study retrospectively compared immobilization drug combinations of carfentanil-xylazine (CX), thiafentanil-xylazine (TX), etorphine-xylazine (EX), carfentanil-acepromazine (CA), and butorphanol-azaperone-medetomidine (BAM) for healthy sable antelope at one institution. Clinically applicable physiologic measures, subjective ratings, and timing of anesthetic milestones of 161 events for 107 individuals revealed the following statistically significant findings ( P < 0.05). Induction ratings were best for TX, highest degree of muscle relaxation occurred with BAM and TX, and anesthetic ratings were best for TX and EX. Time to recovery was longest and complications 2.56 times more likely with CX. Time to recumbency was shortest in TX. Heart rate was highest in CA and lowest in BAM. For immobilization procedures, this study suggests TX would be the preferred combination for H. niger . However, all drug combinations evaluated can be used successfully to immobilize H. niger, and certain combinations may be situationally preferred based on desired muscle relaxation, expected induction or recovery times, or anticipated procedure length.

Physiological studies involving the use of isotopic water required chemical restraint of free-ranging walruses (Odobenus rosmarus) for several hours. In August 2000, six male walrus (total body mass: 1050–1550 kg) were immobilized in East Greenland by remote delivery of 8.0–9.8 mg of etorphine and subsequently restrained for up to 6.75 h by administration of medetomidine. The effects of etorphine were reversed with 10–24 mg diprenorphine. After termination of the etorphine-induced apnoea, lasting an average of 15.8 min (SD = 9.7, range = 9.5–35.2 min, n = 6), the animals were initially given 10–20 mg medetomidine intramuscularly. The initial dose was further augmented by 5 mg at intervals of 5 min. In two cases, when medetomidine was administered through a catheter inserted in the extradural vein, the animal became instantly apnoeic and regained respiratory function only after intravenous injection of the prescribed dose of the antagonist atipamezole and of the respiratory stimulant doxapram. After an average of 3.5 hours of immobilisation, rectal temperature began to increase and it is conceivable that this is the factor that will ultimately limit the duration of immobilisation. The animals became conscious and fully mobile shortly after an intravenous injection of a dose of atipamezole approximately twice the mass of the total dose of medetomidine given during the procedure followed by 400 mg of doxapram. It is concluded that medetomidine appears to be a suitable drug for chemical restraint of walruses for time-consuming procedures following initial immobilisation by etorphine. With animals of total body mass around 1,000–1,500 kg, the drug should be given intramuscularly in 10–20 mg increments (total mass 10–60 mg) until the breathing rate falls to approximately 1 min-1. At this level, breathing is maintained and animals do not respond to touch or injection.

Objective To investigate the effects of postinduction butorphanol administration in etorphine-immobilized white rhinoceros on respiration and blood gases. Study design Randomized crossover study. Animals A group of - sub-adult male white rhinoceros. Methods Etorphine, or etorphine followed by butorphanol 12 minutes after recumbency, was administered intramuscularly [2.5 mg etorphine, 25 mg butorphanol (1000e1250 kg), or 3.0 mg etorphine, 30 mg butorphanol (1250e1500 kg)]. Sampling started at 10 minutes after initial recumbency, and was repeated at 5 minute intervals for 25 minutes. Arterial blood gases, limb muscle tremors, expired minute ventilation and respiratory frequency were measured at each sampling point. Calculated values included alveolarearterial oxygen gradient [P(A-a) O2 ], expected respiratory minute volume (V- E), tidal volume (VT), oxygen consumption (̇O2 ) and carbon dioxide production (̇ CO2 ). Results Etorphine administration resulted in an initial median (range) hypoxaemia [arterial partial pressure of oxygen 25.0 (23.0e28.0) mmHg], hypercapnia [arterial partial pressure of carbon dioxide 76.2 (67.2e81.2) mmHg], increased P(A-a) O2 [41.7 (36.6e45.1) mmHg,̇O2 [11.1 (10.0e12.0) L minute-1] and muscle tremors. Butorphanol administration was followed by rapid, although moderate, improvements in arterial partial pressure of oxygen [48.5 (42.0e51.0) mmHg] and arterial partial pressure of carbon dioxide [62.8 (57.9e75.2) mmHg]. In rhinoceros administered butorphanol,̇O2 [4.4 (36e5.1) L minute-1] anḋCO2 [4.2 (3.8e4.4) L minute-1] were lower than in those not administered butorphanol. Increased arterial oxygen tension was associated with lower oxygen consumption (p= 0.002) which was positively associated with lower muscle tremor scores (p < 0.0001). Conclusions and clinical relevance Hypoxaemia and hypercapnia in etorphine-immobilized rhinoceros resulted from an increased [P(A-a) O2 ] and increaseḋO2 anḋCO2 associated with muscle tremors. Rather than being associated with changes iṅE, it appears that improved blood gases following butorphanol administration were a consequence of decreaseḋO2 associated with reduced muscle tremoring. [ABSTRACT FROM AUTHOR]

To date no problem-free method exists for the immobilisation of free‑ranging walruses (Odobenus rosmarus). In the period 1989-2001, 69 immobilisations with etorphine HCl were performed by remote darting of 41 individual free-ranging adult Atlantic walruses (O. r. rosmarus), with body masses 633 ‑ 1883 kg, as a rerequisite for the attachment of radio tracking and dive recording instruments, and for studies of metabolism. Ten individuals were immobilised several times. We present data on these 69 immobilisations and evaluate the method. Full immobilisation was achieved in 58 cases (84 %). The animals were insufficiently restrained in 6 cases (9 %) and 5 animals died (7 %) following the immobilisation. The animals were fully immobilised and approachable after 5 min (n = 38, range = 1.9 ‑ 12.4 min, SD = 2.2) with a dose of etorphine of 6.1 μg/kg (range 2.4 ‑ 12.6 μg /kg, SD = 2.4). Induction time was negatively correlated with the dosage of etorphine. Etorphine-induced apnoea lasted 13.7 min (n = 36, range 17.0 ‑ 26.7 min, SD = 5.1) and was reversed by multiple doses of the antagonist diprenorphine HCl. The first dose of antagonist of 12.2 mg (n = 39, range 6.0 ‑ 21.0 mg, SD = 3.5) was administered 8.4 min (n = 38, range 4.7 ‑ 18.0 min, SD = 2.8) after injection of the agonist. The total dose of diprenorphine per animal ranged between 7.7 and 41.7 μg/kg (n = 31, mean = 17.2 μg/kg, SD = 7.5). For some animals blood pH values were measured following the apnoea and reached low levels (min pH 6.8). For animals that were immobilised several times there were no indications of changed sensitivity to etorphine as reflected in unchanged induction times. Mortalities could neither be related to the doses of agonist and antagonist, nor to the times of administration of the drugs. From this (n = 69) and other (n = 103) studies involving etorphine immobilisation of walruses (both Atlantic and Pacific) the overall success rate is 83 % (8 % casualty rate). We conclude that the combination etorphine‑ diprenorphine is suitable for both single and multiple immobilisations of walruses provided that (a) a casualty rate of 7-8% is acceptable (b) the antagonist diprenorphine is administered fast and well into a tissue with good blood irrigation, and (c) the animal is promptly intubated endotracheally to facilitate the restoration of breathing after drug-induced apnoea.

Records of 56 Persian fallow deer ( Dama dama mesopotamica) immobilized for translocation were reviewed. Twenty-three were administered 0.05 ± 0.01 (mean ± SD) mg/kg thiafentanil (THIA), 20 were administered 0.045 ± 0.008 mg/kg thiafentanil combined with 0.19 ± 0.03 mg/kg azaperone (THIA-AZP), and 13 were administered 0.032 ± 0.04 mg/kg etorphine-acepromazine (ETOR-ACP) by intramuscular remote injection. Parameters recorded and compared between groups included induction and recovery times, heart rate, respiratory rate, rectal temperature, oxygen saturation, blood pressure, reflexes, quality of immobilization, and blood concentrations of lactate and glucose. Naltrexone (THIA groups) or diprenorphine (ETOR-ACP) were administered for reversal. Mean induction time was significantly shorter in the THIA group versus the ETOR-ACP group (2.0 ± 1.3 and 4.8 ± 2.8 min, respectively), but not significantly shorter than the THIA-AZP group (2.8 ± 3.1 min). Respiratory rate was significantly higher in the THIA group in comparison to the two other groups. None of the protocols provided excellent immobilization quality, which was significantly poorer in the THIA group. Following antagonist administration, all deer from the THIA and ETOR-ACP groups recovered quickly, while there were five perianesthetic morbidity and mortality cases in the THIA-AZP group. Mean recovery time was significantly shorter in the THIA group versus the THIA-AZP and ETOR-ACP groups (0.5 ± 0.3, 1.1 ± 0.8, and 2.3 ± 1.1 min, respectively). In conclusion, the use of THIA provided faster induction and recovery, with less respiratory depression, but poorer immobilization. The THIA-AZP combination should be used with caution in Persian fallow deer until further investigation. [ABSTRACT FROM AUTHOR]

Objective To study the effect of heterothermia on anaesthetic drug requirements in semi-free ranging Arabian oryx and to assess the temperature quotient (Q10) of oxygen consumption. Study design Prospective observational study and controlled metabolic experiment. Animals Sixty-eight anaesthetic events in 59 Arabian oryx fromMahazat As-Sayd protected area, Saudi Arabia. Methods Anaesthesia was induced by remote injection of 25 mg ketamine, 10 mg midazolam and 0.5 mg medetomidine with a variable amount of etorphine based on a target dosage of 20 µg kg-1 and subjective assessment of body mass. Animals not recumbent within 15minutes or insufficiently anaesthetized were physically restrained and administered supplementary etorphine intravenously depending on the anaesthetic depth. Body temperature (Tb) was measured rectally immediately upon handling of each animal. Fromsix anaesthetized oryx, expiratory gasses for oxygen analysis and metabolic rate calculation were collected at twoTbs; before and after submersion in icewater for approximately 30 minutes. Results: Forty-two animals (62%) became recumbent with the initial dose, with a mean induction time (± standard deviation) of 9 ± 2 minutes. The remaining animals could be handled but needed 0.3 ± 0.1 mg etorphine intravenously to reach the desired level of anaesthesia. There was a significant positive correlation between Tb and effective etorphine dosage (R² = 0.48, p < 0.0001). Average Tb of the six animals in which metabolic rate was measured decreased from 40.0 ± 0.5°C immediately after induction to 35.5 ± 0.5°C after cooling. This reduction was associated with a reduction in oxygen uptake from 3.11 ± 0.33 to 2.22 ± 0.29 mL O2 minute-1 kg-1, reflected in Q10 of 2.17 ± 0.14. Conclusions and clinical relevance: Tb significantly affects anaesthetic requirements in Arabian oryx and should be considered when selecting dosages for anaesthetic induction for species showing diurnal heterothermy. [ABSTRACT FROM AUTHOR]

Little is known about the mechanisms causing tremors during immobilisation of rhinoceros and whether cardiorespiratory supportive interventions alter their intensity. Therefore, we set out to determine the possible mechanisms that lead to muscle tremors and ascertain whether cardiorespiratory supportive interventions affect tremor intensity. We studied tremors and physiological responses during etorphine-azaperone immobilisation in eight boma-held and 14 free-living white rhinoceroses. Repeated measures analysis of variance and a Friedman test were used to determine differences in variables over time and between interventions. Spearman and Pearson correlations were used to test for associations between variables. Tremor intensity measured objectively by activity loggers correlated well (p < 0.0001; r² = 0.9) with visual observations. Tremor intensity was greatest when animals were severely hypoxaemic and acidaemic. Tremor intensity correlated strongly and negatively with partial pressure of oxygen (PaO2) (p = 0.0003; r² = 0.9995) and potential of hydrogen (pH) (p = 0.02, r² = 0.97). It correlated strongly and positively with adrenaline concentrations (p = 0.003; r² = 0.96), and adrenaline correlated strongly and negatively with PaO2 (p = 0.03; r² = 0.95) and pH (p = 0.03; r² = 0.94). Therefore, hypoxaemia and acidaemia were likely associated with the intensity of tremors through their activation of the release of tremorgenic levels of adrenaline. Tremors can be reduced if circulating adrenaline is reduced, and this can be achieved by the administration of butorphanol plus oxygen insufflation. Furthermore, to assist with reducing the risks associated with rhinoceros immobilisation, tremor intensity could be used as a clinical indicator of respiratory and metabolic compromise. [ABSTRACT FROM AUTHOR]

Objectives To evaluate and compare the efficacy of two opioid agonist-antagonists, nalbuphine and butorphanol, in reversing etorphine-induced respiratory depression in immobilized goats. Study design Prospective, crossover, experimental trial conducted at 1753 m.a.s.l. Animals Eight adult female Boer goats ( Capra hircus). Methods Eight minutes following immobilization with an intramuscular injection of 0.1 mg kg−1 etorphine, goats were given one of nalbuphine (0.8 mg kg−1), butorphanol (0.1 mg kg−1) or sterile water intravenously, in random order in three trials. Respiratory rate ( fR), ventilation, tidal volume, oxygen consumption ( [ABSTRACT FROM AUTHOR]

Objectives To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. Study design A prospective, crossover experimental trial conducted at 1753 m.a.s.l. Animals Eight adult female Boer goats ( Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. Methods Following immobilization with 0.1 mg kg−1 etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2, Pa CO2, pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes. Results Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low Pa CO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute−1 above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial. Conclusions CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats. Clinical relevance Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals. [ABSTRACT FROM AUTHOR]

Nineteen white rhinoceroses ( Ceratotherium simum) were anesthetized with 4 mg of etorphine hydrochloride; 35-40 mg of midazolam; and 7,500 international units of hyaluronidase for dehorning purposes at a game ranch in South Africa, to investigate this anesthetic combination. Median time to recumbency was 548 sec (range 361-787 sec). Good muscle relaxation and no muscle rigidity or tremors were observed in 18 animals, and only 1 individual showed slight tremors. In addition, all animals received butorphanol i.v. 5 min after recumbency at the ratio of 10 mg of butorphanol per 1 mg of etorphine. Blood gas and selected physiologic parameters were measured in the recumbent animal, immediately before and 10 min after the administration of butorphanol. Statistically significant improvements were observed in blood gas physiologic and cardiopulmonary parameters 10 min after the administration of butorphanol, with a reduction in arterial partial pressure of carbon dioxide, systolic blood pressure, and heart rate and an increase in pH, arterial partial pressure of oxygen, oxygen saturation, and respiratory rate (all P < 0.005). After i.v. naltrexone reversal, recovery was uneventful, and median time to walking or running was 110 sec (range 71-247 sec). The results indicate etorphine and midazolam combination is an effective alternative anesthetic protocol and produces good muscle relaxation. Furthermore, i.v. butorphanol was associated with improved blood gas values and cardiopulmonary function for at least 10 min postinjection. [ABSTRACT FROM AUTHOR]

A 30-year-old female domestic Asian elephant (Elephas maximus) was referred to Kasetsart University Veterinary Teaching Hospital for investigation of an esophageal obstruction. “Vomiting” had been noted for several days before admission. Initial sedation was achieved by azaperone (80 mg), delivered intramuscularly (IM). Once sedated supporting straps and a sling were fitted, and weight-bearing support was provided by a crane. General anesthesia was induced using 2 mg etorphine hydrochloride (0.00066 mg/kg) by intravenous (IV) injection. Using the crane, she was lowered onto a thickly bedded area on the floor and placed in right lateral recumbency. Oxygen was initially provided via the trunk. Blind endotracheal intubation was unsuccessful until further two incremental doses of etorphine hydrochloride (0.5 and 1.5 mg) had been administered. Even though subsequently maintained on 5% isoflurane, a third increment of etorphine hydrochloride (1 mg) was required to fully abolish jaw tone. Following successful endoscopy for gastro-esophageal evaluation anesthesia was reversed through cessation of isoflurane and administration of naltrexone (500 mg by IM injection). Some reflexes including ear twitching and leg moving were noticed within 1 min and endotracheal extubation was carried out after 2 min, when jaw tone returned. First attempts at standing took place after 3 min, the elephant could stand with support after 8 min and was ambulatory at 11 min after reversal. The total time from sedation to independent walking was 1.16 hr. [ABSTRACT FROM AUTHOR]

Impala ( Aepyceros melampus) are a notoriously difficult species to manage in captivity, and anesthesia is associated with a high risk of complications including mortality. The aim of this study was to compare an opioid-based protocol with an α-2 agonist-based protocol. Nine female impala were studied in a random cross-over design. Subjects received either an etorphine-acepromazine (EA) protocol: 15 μg/kg etorphine and 0.15 mg/kg acepromazine, or a medetomidine-ketamine (MK) protocol: 109 μg/kg medetomidine and 4.4 mg/kg ketamine on day 1. Anaesthesia was repeated 3 days later with the alternative protocol. Subjective assessments of the quality of induction, muscle relaxation, and recovery were made by a blinded observer. Objective monitoring included blood pressure, end-tidal CO2, regional tissue oxygenation, and blood gas analysis. EA provided a significantly quicker (mean EA, 7.17 mins; MK, 17.6 mins) and more-reliable (score range EA, 3-5; MK, 1-5) induction. Respiratory rates were lower for EA with higher end-tidal CO2, but no apnoea was observed. As expected, blood pressures with EA were lower, with higher heart rates; however, arterial oxygenation and tissue oxygenation were equal or higher than with the MK protocol. In conclusion, at these doses, EA provided superior induction and equivalent muscle relaxation and recovery with apparent improved oxygen tissue delivery when compared to MK. [ABSTRACT FROM AUTHOR]

There is a growing necessity to perform long-term anesthesia in wildlife, especially antelope. The costs and logistics of transporting wildlife to veterinary practices make surgical intervention a high-stakes operation. Thus there is a need for a field-ready total intravenous anesthesia (TIVA) infusion to maintain anesthesia in antelope. This study explored the feasibility of an etorphine-ketamine-medetomidine TIVA for field anesthesia. Ten wild-caught, adult impala ( Aepyceros melampus) were enrolled in the study. Impala were immobilized with a standardized combination of etorphine (2 mg) and medetomidine (2.2 mg), which equated to a median (interquartile range [IQR]) etorphine and medetomidine dose of 50.1 (46.2-50.3) and 55.1 (50.8-55.4) μg/kg, respectively. Recumbency was attained in a median (IQR) time of 13.9 (12.0-16.5) min. Respiratory gas tensions, spirometry, and arterial blood gas were analyzed over a 120-min infusion. Once instrumented, the TIVA was infused as follows: etorphine at a variable rate initiated at 40 μg/kg per hour (adjusted according to intermittent deep-pain testing); ketamine and medetomidine at a fixed rate of 1.5 mg/kg per hour and 5 μg/kg per hour, respectively. The etorphine had an erratic titration to clinical effect in four impala. Arterial blood pressure and respiratory and heart rates were all within normal physiological ranges. However, arterial blood gas analysis revealed severe hypoxemia, hypercapnia, and acidosis. Oxygenation and ventilation indices were calculated and highlighted possible co-etiologies to the suspected etorphine-induced respiratory depression as the cause of the blood gas derangements. Impala recovered in the boma post atipamezole (13 mg) and naltrexone (42 mg) antagonism of medetomidine and etorphine, respectively. The etorphine-ketamine-medetomidine TIVA protocol for impala may be sufficient for field procedures of up to 120-min duration. However, hypoxemia and hypercapnia are of paramount concern and thus oxygen supplementation should be considered mandatory. Other TIVA combinations may be superior and warrant further investigation. [ABSTRACT FROM AUTHOR]