Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog

Alpha(2)-adrenoreceptor agonists (alpha(2)-agonists) are commonly used in small animal anaesthesia for their potent sedative and analgesic properties, although concerns about their cardiovascular effects have prevented their full adoption into veterinary practice. Research into alpha(2) adrenoreceptor agonists and their clinical use is extensive, therefore this review focuses on the use of dexmedetomidine and medetomidine in dogs. Emphasis is given to the cardiovascular effects and antinociceptive action of these agents.     

Phosphorus use efficiency of improved faba bean (Vicia faba) varieties in low‐input agro‐ecosystems

The use of phosphorus (P)‐efficient legumes is a prerequisite for sustainable intensification of low‐input agro‐ecosystems. A study was undertaken in a farmer's field in the tropical highlands of Ethiopia to assess the agronomic performance, P acquisition efficiency (PAE), and P utilization efficiency (PUE) of six improved faba bean varieties (Vicia faba L. var. CS‐20DK, Degaga, Gebelcho, Moti, Obse, Walki) without and with P application. Varieties showed significant variations in PUE, but P application had no significant effect on PUE. Variety Moti demonstrated highest PUE of 272 kg grain kg^?1 P, which was 1.6‐fold higher than the lowest PUE (164 kg grain kg^?1 P) of Gebelcho. PUE was significantly and positively correlated with grain yield (r = 0.542) and negatively correlated with shoot PAE (r = –0.541), indicating that PUE is important for grain yield. The results demonstrate that variations in grain and biomass yield of faba beans were largely due to differences in PUE and not due to PAE. Therefore, we argue that genetic resources of faba bean varieties showing optimal agronomic performance and high PUE in low‐input agro‐ecosystems should be better explored. Introduction of such varieties in low‐input cereal‐based cropping systems could improve and enhance P use efficiency at the system level.     

Investigation of the interaction between buprenorphine and sufentanil during anaesthesia for ovariectomy in dogs

OBJECTIVE: To investigate the effect of buprenorphine pre-treatment on sufentanil requirements in female dogs undergoing ovariectomy. STUDY DESIGN: Randomized, 'blinded', prospective clinical study. ANIMALS: Thirty healthy female dogs referred for ovariectomy. MATERIALS AND METHODS: Dogs were randomly assigned to one of two pre-anaesthetic treatment groups. Those in the buprenorphine group (B) received buprenorphine 20 microg kg(-1) and acepromazine 0.03 mg kg(-1) IM. Control group (C) animals received an equal volume of NaCl 0.9% and acepromazine 0.03 mg kg(-1) IM. The anaesthetic technique was identical in both groups. Pre-anaesthetic medication consisted of intravenous (IV) sufentanil (1.0 microg kg(-1)) and midazolam (0.05 mg kg(-1)) and intramuscular atropine (0.03 mg kg(-1)). Anaesthesia was induced with propofol and maintained with a constant rate infusion of sufentanil (1.0 microg kg(-1) hour(-1)) and with oxygen-isoflurane. Ventilation was controlled mechanically. Ovariectomy was performed using a standard technique. Baseline heart rate (HR) and direct mean arterial blood pressure (MAP) were recorded before the first incision. Increases in HR and MAP of > or =20% over baseline and, or spontaneous ventilation were controlled using IV sufentanil (1.0 microg kg(-1)) repeated after 5 minutes if haemodynamic variables remained elevated or attempts at spontaneous ventilation persisted. Analysis of variance was used to determine group differences in mean and median HR and MAP and to compare the maximum HR and MAP attained during surgery. Poisson regression was used to compare the number of sufentanil injections required in both groups. RESULTS: Group B required 2.46 times more sufentanil injections (p = 0.00487) than dogs in group C to maintain haemodynamic stability and prevent spontaneous ventilation during surgery. Group B dogs also had a significantly higher (p = 0.034) marginal mean of the log maximum MAP (4.756 +/- 0.036) compared with group C (4.642 +/- 0.036). CONCLUSIONS: Pre-treatment with buprenorphine appears to negatively influence the antinociceptive efficacy of intra-operative sufentanil. CLINICAL RELEVANCE: Withholding buprenorphine therapy 6-8 hours before anaesthesia incorporating pure mu receptor agonists is probably advisable. Alternative methods of analgesia should be provided in this period.     

Application of a Composite Pain Scale to Objectively Monitor Horses with Somatic and Visceral Pain under Hospital Conditions

Pain recognition and management in animals has advanced considerably in the last decade and currently animal welfare is receiving increasing public interest. However, the comprehensive assessment of pain has been inadequately addressed in horses and till recently composite pain scales (CPSs) have hardly been validated for use in patients. We investigated the reliability and clinical applicability of a CPS, originally developed under experimental conditions for assessing pain in horses with various acute soft-tissue and orthopedic conditions before and after general anesthesia and/or (non)elective surgery. These clinical cases (n = 94) were scored by means of the CPS twice daily. Horses without painful conditions and horses admitted for nonpainful diagnostic procedures under general anesthesia were compared with those that were admitted with either acute or chronic surgical and nonsurgical painful conditions of both visceral and somatic origin. Scores of observer 1 were compared with observer 2 to study inter-observer reliability. Composite pain scores showed low baseline values in healthy animals with nonpainful conditions and were not affected when general anesthesia was the only intervention. Inter-observer reliability was very high (n = 23 horses; weighted kappa correlation coefficient, κ = 0.81). Horses with painful conditions responding well to analgesic treatment could be discriminated from horses that had to be euthanized on humane grounds because of painful nonresponsive conditions. We found the CPS to be a promising tool that has the potential to provide a good basis for direct day-to-day assessment of pain status in equine patients with various painful conditions in the future.     

Clinical and Electrophysiological Characterization of Myokymia and Neuromyotonia in Jack Russell Terriers

Background: Generalized myokymia and neuromyotonia (M/NM) in Jack Russell Terriers (JRTs) is related to peripheral nerve hyperexcitability syndrome in humans, a symptom complex resulting from diverse etiologies. Objective: Clinical and electrodiagnostic evaluation is used to narrow the list of possible etiological diagnoses in JRTs with M/NM. Animals: Nine healthy JRTs and 8 affected JRTs. Methods: A prospective study was conducted comparing clinical and electrophysiological characteristics in 8 JRTs affected by M/NM with 9 healthy JRT controls. Results: All affected dogs except 1 had clinical signs typical of hereditary ataxia (HA). In 6 dogs, neuromyotonic discharges were recorded during electromyogram. Motor nerve conduction studies showed an axonal neuropathy in only 1 affected dog. Compared with controls, brainstem auditory‐evoked potentials (BAEP) showed prolonged latencies (P < .05) accompanied by the disappearance of wave components in 3 dogs. Onset latencies of tibial sensory‐evoked potentials (SEP) recorded at the lumbar intervertebral level were delayed in the affected group (P < .001). The BAEP and SEP results of the only neuromyotonic dog without ataxia were normal. Conclusions and Clinical Importance: The BAEP and spinal SEP abnormalities observed in JRTs with M/NM were associated with the presence of HA. Therefore, these electrophysiological findings presumably arise from the neurodegenerative changes characterizing HA and do not directly elucidate the pathogenesis of M/NM. An underlying neuronal ion channel dysfunction is thought to be the cause of M/NM in JRTs.     

Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line

Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and analgesic properties, ketamine possesses a cytokine-modulating activity. However, to date, no data are available regarding the inhibitory effect of ketamine on the cytokine response in horses. In horses, cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play a pivotal role in the pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence, the objective of this study was to assess the influence of ketamine on LPS-induced TNF-alpha and IL-6 formation in an equine macrophage cell line (eCAS cells). The results demonstrate a cytokine-modulating activity of ketamine in an equine cell line, suggesting a beneficial role for ketamine in the treatment of equine endotoxaemia.     

Evaluation of analgesic and sedative effects of continuous infusion of dexmedetomidine by measuring somatosensory- and auditory-evoked potentials in the rat

Objective  To study, the analgesic and sedative effects of different constant rate infusions (CRI) of dexmedetomidine, in the rat, by measurement of specific electroencephalographic parameters. The recorded parameters were somatosensory-evoked potentials (SEPs) and auditory-evoked potentials (AEPs), which have been shown to be related to analgesia and sedation respectively.
Animals  Nine male Wistar rats (HsdCpb:Wu, Harlan Netherlands BV, body weight 300–350 g).
Methods  Somatosensory-evoked potentials were recorded from the primary somatosensory cortex and the vertex location (SI/Vx-SEPs). Auditory-evoked potentials were recorded from the primary auditory cortex and vertex location (AI/Vx-AEPs). Primary somatosensory cortex and vertex location recorded SEPs and AI/Vx-AEPs were recorded alternately, during CRI of dexmedetomidine (4.0, 10.0, 20.0 μg kg⁻¹ hour⁻¹) and a control (saline).
Results  The primary somatosensory cortex-evoked potentials were not affected by the dexmedetomidine CRI, but the other three parameters were significantly affected; although the AI-SEP to a lesser extent than the Vx-SEP and Vx-AEP. A maximum effect on the Vx-AEP was reached at lower doses than on the Vx-SEP.
Conclusions  Based on the present findings, it is suggested that CRI of dexmedetomidine provided profound sedation at low doses, whereas higher doses are needed to provide concurrent analgesia.
Clinical relevance  A constant rate infusion of dexmedetomidine can be a valuable adjunct in the provision of sedation and/or analgesia. However, analgesia cannot be produced without sedation, and sedation is not necessarily accompanied by comparative degrees of analgesia.     

The use of visible and near-infrared reflectance measurements for identifying the source of suspended sediment in rivers and comparison with geochemical fingerprinting

Purpose

Visible and near-infrared (Vis-NIR) reflectance measurements may be an alternative technique to identify suspended sediment sources in streams of headwater catchments. In this study, we examined if Vis-NIR reflectance measurements are capable of estimating sediment source contributions to sediment yield and compared this technique with a more conventional (i.e. geochemical) technique.

Materials and methods

Two headwater catchments in Ethiopia, Unta (2,052 ha) and Desera (1,657 ha), were analysed with the same techniques in order to find similarities and differences in the results obtained. The first technique used Vis-NIR spectral analysis as a fingerprint, using a partial least squares regression model. The second technique was a quantitative composite fingerprinting technique using geochemical analysis of source materials and suspended sediment samples. As a comparison, the partial least squares model was also used on the geochemical data. In August and September 2009, 30 soil samples of three different land uses (landslides, croplands, and grazing lands) and 21 suspended sediment samples at the catchment outlet were collected. Source samples were sieved to <63 μm. Geochemical analyses consisted of total element concentrations, percentage carbon, percentage nitrogen, and atom percentage ¹⁵N and δ¹³C. Reflectance measurements were taken on dried source samples with a spectrometer.

Results and discussion

Neither technique was able to predict the contributions of the three land use types; they could only distinguish between landslide and topsoil material. The agreement between the results of both techniques was significant for the Unta catchment (R ²?=?0.80) but not for the Desera catchment (R ²?=?0.39). The uncertainty of the technique using Vis-NIR reflectance measurements was slightly higher than with the geochemical approach. Both techniques revealed that topsoil erosion played an important role during storm runoff discharges. Using the partial least squares model for the geochemical data revealed that uncertainty can differ greatly when using other statistical techniques.

Conclusions

The quantitative composite fingerprinting technique using spectral signatures from both source and suspended sediment samples was able to quantify the contribution of two source materials (landslides and topsoil). It provided a faster and more cost effective alternative to the conventional geochemical procedure.     

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

ObjectiveTo 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 designProspective, randomised, blinded, positive-controlled parallel-group clinical study.AnimalsForty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery.MethodsAfter surgery, a loading dose of either DMED (25 μg m^?2) or MOR (2500 μg m^?2) followed by a 24-hour CRI of DMED (25 μg m^?2 hour^?1) or MOR (2500 μg 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.ResultsForty 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 RelevanceDexmedetomidine 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.     

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats.Study designProspective, randomized, crossover experimental study.AnimalsSix goats, three does and three wethers.MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg^?1 followed by a constant rate infusion (CRI) of 0.05 mg kg^?1 minute^?1 (treatment LPROP); bolus of 1.0 mg kg^?1 followed by a CRI of 0.1 mg kg^?1 minute^?1 (treatment MPROP), bolus of 2.0 mg kg^?1 followed by a CRI of 0.2 mg kg^?1 minute^?1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance).ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory.Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.