Towards a flexible and personalised development of veterinarians and veterinary nurses working in a companion animal referral care setting.

In the Netherlands, the demand for veterinarians and veterinary nurses (VNs) working within referral care is rapidly growing and currently exceeds the amount of available board-certified specialists. Simultaneously, a transparent structure to guide training and development and to assess quality of non-specialist veterinarians and VNs working in a referral setting is lacking. In response, we developed learning pathways guided by an entrustable professional activity (EPA) framework and programmatic assessment to support personalised development and competence of veterinarians and VNs working in referral settings. Between 4 and 35 EPAs varying per discipline (n = 11) were developed. To date, 20 trainees across five disciplines have been entrusted. Trainees from these learning pathways have proceeded to acquire new EPAs in addition to their already entrusted set of EPAs or progressed to specialist training during (n = 3) or after successfully completing (n = 1) the learning pathway. Due to their outcome-based approach, the learning pathways support flexible ways of development.

Evaluation of urine specific gravity as a predictor of hypotension during anaesthesia in healthy dogs premedicated with dexmedetomidine.

OBJECTIVE: To investigate the relationship between urine specific gravity (USG) and the risk of arterial hypotension during general anaesthesia (GA) in healthy dogs premedicated with dexmedetomidine and methadone. STUDY DESIGN: Prospective clinical cohort study. ANIMALS: A total of 75 healthy client-owned dogs undergoing GA for elective tibial plateau levelling osteotomy. METHODS: After placing an intravenous catheter, dogs were premedicated with dexmedetomidine (5 µg kg-1) and methadone (0.3 mg kg-1) intravenously. After induction of GA with alfaxalone to effect, the bladder was expressed and USG measured. An arterial catheter was placed, and residual blood was used to measure packed cell volume (PCV) and total protein (TP). GA was maintained with isoflurane vaporised in oxygen and a femoral and sciatic nerve block were performed. Arterial blood pressure < 60 mmHg was defined as hypotension and recorded by the anaesthetist. Treatment for hypotension was performed in a stepwise manner following a flow chart. Frequency of hypotension, treatment and response to treatment were recorded. Logistic regression modelling was used to assess the association between USG, TP and PCV and incidence of perioperative hypotension; p < 0.05. RESULTS: Data from 14 dogs were excluded. Of the 61 dogs, 16 (26%) were hypotensive during GA, 15 dogs needed treatment of which 12 were responsive to a decrease in inhalant vaporiser setting. The logistic regression model was not statistically significant (p = 0.8). There was no significant association between USG (p = 0.6), TP (p = 0.4), PCV (p = 0.8) and arterial hypotension during GA. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs premedicated with dexmedetomidine and methadone and maintained under GA with isoflurane and a femoral and sciatic nerve block, there was no relationship between the specific gravity of urine collected after premedication and intraoperative arterial hypotension.

Comparison of different methods to calculate venous admixture in anaesthetized horses.

OBJECTIVE: The aim of this study was to compare different methods to determine venous admixture (Q˙s/Q˙t) in anaesthetized horses. The first objective was to estimate Q˙s/Q˙t using jugular venous blood oxygen content (Q˙s/Q˙tjugular), and a fixed value for the oxygen extraction (F-shunt). The second objective was to assess the influence of blood pressure and positioning on oxygen extraction. The third objective was to perform regression analysis between jugular and mixed venous blood oxygen tensions. STUDY DESIGN: Prospective, experimental trial. ANIMALS: The study was performed with seven warmblood horses that were anaesthetized with detomidine, butorphanol, ketamine, diazepam and isoflurane in oxygen. METHODS: Multiple simultaneous arterial, jugular venous and pulmonary arterial blood samples were taken under normotensive and hypotensive conditions in lateral and dorsal recumbency. Arterial, mixed venous, and end-capillary oxygen content were calculated. RESULTS: A significant correlation between Q˙s/Q˙t and Q˙s/Q˙tjugular was found [intraclass correlation coefficient (ICC) = 0.68, p < 0.001], and Bland-Altman analysis showed a bias of -11.5% and wide limits of agreement (-27.7% to 4.6%). F-shunt significantly correlated with Q˙s/Q˙t (ICC = 0.88, p < 0.001), and Bland-Altman analysis showed a lower bias (-1.97) and narrower limits of agreement (-13.8% to 9.9%). Positioning and blood pressure significantly influenced oxygen extraction. The regression formula was Y = 0.80X + 2.61 (where Y is the calculated mixed venous oxygen tension and X is the jugular venous oxygen tension) when outliers were excluded (ICC=0.82, p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that F-shunt provides reasonable estimates of Q˙s/Q˙t but can possibly be improved by using simple algorithms without the need for pulmonary arterial catheterization. These algorithms use blood pressure- and positioning-dependent oxygen extraction and regression analysis between jugular venous and pulmonary arterial oxygen tension. Although promising, the validity of these algorithms needs to be determined in future studies.

The clinical efficacy of EMLA cream for intravenous catheter placement in client-owned dogs.

OBJECTIVE: To assess the reaction of client-owned dogs to intravenous (IV) catheter placement after applying a local anaesthetic (EMLA) or placebo cream for either 30 or 60 minutes. STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled, clinical trial. ANIMALS: A total of 202 client-owned dogs of various breeds. METHODS: With owner consent, dogs were randomly allocated to one of four treatment groups: EMLA 60 minutes, EMLA 30 minutes, Placebo 60 minutes and Placebo 30 minutes. After the cream was applied for the allocated time, an IV catheter was placed and the behavioural reaction of the dog was scored. The reaction score was analysed using a Kruskal-Wallis test followed by Mann-Whitney U tests of the multiple pairwise comparisons, with Bonferroni correction. RESULTS: A large number of dogs, even in the placebo groups, did not react to IV catheter placement. However, the Kruskal-Wallis test showed an overall difference between treatment groups (χ2 = 11.029, df = 3, p = 0.012). The pairwise comparisons showed a lower overall reaction score in the EMLA 60 group than in the EMLA 30 and Placebo 60 groups (adjusted p = 0.018 and adjusted p = 0.044, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that EMLA cream applied for 60 minutes reduces the behavioural reaction of dogs to IV catheter placement; therefore, this intervention can be advocated for routine use in veterinary medicine to enhance the welfare of dogs undergoing IV catheter placement.

Effect of premedication with butorphanol or methadone on ease of endoscopic duodenal intubation in dogs.

OBJECTIVE: The effect of premedication with butorphanol or methadone on ease of endoscopic duodenal intubation. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: A group of 20 client-owned dogs. METHODS: Dogs were assigned randomly to be administered intravenous (IV) premedication with either butorphanol (0.4 mg kg-1) or methadone (0.3 mg kg-1). General anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen. Sedation score 20 minutes after premedication administration and induction dose of propofol were recorded. Heart rate, mean arterial pressure, haemoglobin oxygen saturation, respiratory rate and end-tidal isoflurane concentration were recorded every 5 minutes. Spontaneous lower oesophageal and pyloric sphincter opening, presence of gastro-oesophageal and duodeno-gastric reflux, antral peristaltic contractions and response to endoscopy were recorded as yes or no. Ease of duodenal intubation (EDI) was graded on a scale ranging from 1 (immediate entry with minimal manoeuvring required) to 4 (no entry after 2 minutes). Time (seconds) from the start of pyloric intubation to successfully entering the duodenum was recorded. RESULTS: Median EDI score [3 ± 1 (butorphanol), 4 ± 1 (methadone), p = 0.035], time [65 ± 36 seconds (butorphanol), 120 ± 38 seconds (methadone), p = 0.028] and number of dogs with spontaneous pyloric sphincter opening [7/10 (butorphanol), 2/10 (methadone), p = 0.035] differed between groups. No other significant differences were found. CONCLUSIONS AND CLINICAL RELEVANCE: In these clinical cases, duodenal intubation was performed with greater ease, shorter time and more frequent spontaneous opening of the pyloric sphincter after premedication with butorphanol in comparison to methadone. The use of butorphanol facilitated the passage of the endoscope and is therefore recommended for premedication prior to upper gastrointestinal tract endoscopy.

Bleeding Diathesis in Fawn Hooded Rats-Possible Implications for Invasive Procedures and Refinement Strategies.

The Fawn hooded (FH) rat is commonly used in biomedical research. It is widely acknowledged that the FH rat has a bleeding disorder; leading to abundant bleedings. Although this bleeding disorder is investigated to model the storage pool defect; its impact on commonly performed invasive laboratory procedures has not yet been described. Our research group experienced clinically significant consequences of this bleeding disorder following invasive procedures (including intraperitoneal injections and neurocranial surgery) in the Rjlbm: FH stock. The clinical consequences of the surgical and anesthetic protocols applied; are described including the subsequent procedural refinements applied to minimize the impact of this disorder. It is strongly recommended to take the bleeding diathesis into account when performing invasive procedures in FH rats and to apply the suggested refinement of procedures.

Nociception and conditioned fear in rats: strains matter.

When using rats in pain research, strain-related differences in outcomes of tests for pain and nociception are acknowledged. However, very little is known about the specific characteristics of these strain differences. In this study four phylogenetically distant inbred rat strains, i.e. Wistar Kyoto (WKY), Fawn Hooded (FH), Brown Norway (BN) and Lewis (LE), were investigated in different tests related to pain and nociception. During Pavlovian fear conditioning, the LE and WKY showed a significantly longer duration of freezing behaviour than the FH and BN. Additionally, differences in c-Fos expression in subregions of the prefrontal cortex and amygdala between rat strains during retrieval and expression of conditioned fear were found. For example, the BN did not show recruitment of the basolateral amygdala, whereas the WKY, FH and LE did. During the hot plate test, the WKY and LE showed a lower thermal threshold compared to the BN and FH. In a follow-up experiment, the two most contrasting strains regarding behaviour during the hot plate test and Pavlovian fear conditioning (i.e. FH and WKY) were selected and the hot plate test, Von Frey test and somatosensory-evoked potential (SEP) were investigated. During the Von Frey test, the WKY showed a lower mechanical threshold compared to the FH. When measuring the SEP, the FH appeared to be less reactive to increasing stimulus intensities when considering both peak amplitudes and latencies. Altogether, the combined results indicate various differences between rat strains in Pavlovian fear conditioning, nociception related behaviours and nociceptive processing. These findings demonstrate the necessity of using multiple rat strains when using tests including noxious stimuli and suggest that the choice of rat strains should be considered. When selecting a strain for a particular study it should be considered how this strain behaves during the tests used in that study.

Predictability of painful stimulation modulates the somatosensory-evoked potential in the rat.

Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the effect of predictability on the SEP in animals, classical fear conditioning was applied to compare SEPs between rats receiving SEP-evoking electrical stimuli either predictably or unpredictably. As in humans, the rat's SEP increased when SEP-evoking stimuli were administered unpredictably. These data support the hypothesis that the predictability of noxious stimuli plays a distinctive role in the processing of these stimuli in animals. The influence of predictability should be considered when studying nociception and pain in animals. Additionally, this finding suggests that animals confronted with (un)predictable noxious stimuli can be used to investigate the mechanisms underlying the influence of predictability on central processing of noxious stimuli.

A comparison between the v-gel supraglottic airway device and the cuffed endotracheal tube for airway management in spontaneously breathing cats during isoflurane anaesthesia.

OBJECTIVE: To compare airway management using the v-gel supraglottic airway device (v-gel SGAD) to that using an endotracheal tube (ETT), with respect to practicability, leakage of volatile anaesthetics and upper airway discomfort in cats. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Twenty European Shorthair cats (9 males, 11 females), weighing 3.3 ± 0.7 kg. METHODS: Cats were randomly allocated to one of two groups, in which the airway was managed by either the v-gel SGAD or a cuffed ETT, and anaesthetized for neutering procedures. The dose of propofol necessary to insert the ETT or v-gel SGAD; time from the first injection of propofol to the first clinically acceptable reading on the capnograph; leakage of isoflurane around the airway device; and upper airway discomfort scores during recovery and during the first 24 hours after anaesthesia were recorded. Continuous and discrete variables were analyzed with the Mann-Whitney U-test and the Pearson chi-squared test, respectively. Results were considered statistically significant if p < 0.05. RESULTS: Time from the first injection of propofol to the first clinically acceptable reading on the capnograph was significantly shorter in the v-gel group. The ETT group showed significantly more stridor during recovery. No other significant differences were found. CONCLUSIONS AND CLINICAL RELEVANCE: Airway management with the v-gel SGAD is a sound and practicable alternative to endotracheal intubation with an ETT. However, larger prospective trials will be needed to draw firm conclusions on the benefits and/or drawbacks of the use of v-gel SGAD for airway management in cats.

Bispectral index and the clinically evaluated anaesthetic depth in dogs.

OBJECTIVE: This study investigated whether the bispectral index (BIS monitor) corresponded with the clinical assessment of anaesthetic depth in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Sixty-five dogs undergoing anaesthesia for surgery. METHODS: Dogs were assigned to one of three different anaesthetic techniques. A three point scale was devised to determine the clinical depth of anaesthesia (CDA); CDA 1 represented light, CDA 2 surgical and CDA 3 excessive depth of anaesthesia. BIS values were recorded and CDA assessed at specific times and points throughout surgery. Data were statistically analysed using mixed model regression. RESULTS: Clinical depth of anaesthesia was assessed as CDA 1 on 68, 2 on 748 and 3 on four occasions. The BIS recorded for CDA 1 differed significantly from that for CDA 2 (p<0.001). However, individual BIS values measured at light and surgical levels of anaesthesia overlapped considerably. The sensitivities and specificities calculated for BIS to diagnose CDA 1 compared to CDA 2 in the three anaesthetic protocols were 28-86% and 55-85%. The accompanying positive predictive value was 0.08-0.29 and the negative predictive value was 0.95-0.97. End-tidal isoflurane concentrations (anaesthetic techniques 1 and 3) and propofol infusion (technique 2) at CDA 1 was significantly lower than those at CDA 2 (p=0.001). CONCLUSIONS: Although BIS values overall distinguished between CDA scores, the calculated specificities, sensitivities and predictive values were low, and there were anomalous results in individual cases. CLINICAL RELEVANCE: The use of the BIS as the sole method to determine anaesthetic depth in dogs is imprudent.

Neurophysiological assessment of the sedative and analgesic effects of a constant rate infusion of dexmedetomidine in the dog.

The sedative and analgesic effects of continuous rate infusion (CRI) of dexmedetomidine (DEX) were investigated in Beagle dogs (n=8) using auditory and somatosensory evoked potentials (AEPs and SEPs) recorded before, during and after a CRI of saline or DEX (1.0, 3.0, 5.0 µg/kg bolus, followed by 1.0, 3.0, 5.0 µg/kg/h CRI, respectively). The results showed a significant reduction in AEP at doses of 1.0 µg/kg/h and above and a significant reduction of the SEP at doses of 3.0 and 5.0 µg/kg/h. Neither the AEP nor the SEP was further reduced at 5.0 µg/kg/h when compared to 3.0 µg/kg/h, although a slower return towards baseline values was observed at 5.0 µg/kg/h. The mean plasma levels (±SEM) of DEX during infusion were 0.533±0.053 ng/mL for the 1.0 µg/kg/h dose, 1.869±0.063 ng/mL for the 3.0 µg/kg/h dose and 4.017±0.385 for the 5.0 µg/kg/dose. It was concluded that in adult dogs, a CRI of DEX had a sedative and analgesic effect that could be described quantitatively using neurophysiological parameters. Sedation was achieved at lower plasma levels than required for analgesia, and DEX had a longer (but not larger) effect with infusion rates above 3.0 µg/kg/h.

Pain management in ferrets.

The growing popularity of ferrets as pets has created the demand for advanced veterinary care for these patients. Pain is associated with a broad range of conditions, including acute or chronic inflammatory disease, neoplasia, and trauma, as well as iatrogenic causes, such as surgery and diagnostic procedures. Effective pain management requires knowledge and skills to assess pain, good understanding of the pathophysiology of pain, and general knowledge of pharmacologic and pharmacodynamic principles. Unfortunately, scientific studies on efficacy, pharmacokinetics, pharmacodynamics, and safety of analgesic drugs in the ferret are limited. However, basic rules on the treatment of pain and mechanisms of action, safety, and efficacy of analgesic drugs in other species can be adapted and applied to pain management in ferrets. This article aims to make an inventory of what is known on the recognition of pain in ferrets, what analgesic drugs are currently used in ferrets, and how they can be adopted in a patient-orientated pain management plan to provide effective pain relief while reducing and monitoring for unwanted side effects.

The alpha(2)-adrenoceptor agonist dexmedetomidine suppresses memory formation only at doses attenuating the perception of sensory input.

It was investigated whether continuous rate infusion of the alpha(2)-adrenoceptor agonist dexmedetomidine can suppress memory formation by mechanisms other than reducing perception of sensory input in a fear-conditioning paradigm. Different groups of rats infused with either saline or dexmedetomidine (2.0, 4.0 or 10.0microg/kg bolus, followed by 2.0, 4.0 or 10.0microg/kg/h continuous rate infusion respectively), were subjected to a somatosensory-evoked potential (SEP) fear-conditioning paradigm. This paradigm combined the pairing of an innoxious conditioned stimulus (CS) and a noxious unconditioned stimulus (US), of which the latter was used to generate the SEPs (training phase).The following day, the perception of the US during the training phase was assessed by presenting the CS only and subsequently scoring the resulting duration of freezing behaviour (testing phase). Freezing behaviour was reduced only in those groups which demonstrated reduced SEPs. Based on these findings, it is concluded that dexmedetomidine suppresses memory formation only at doses reducing central nervous system activity in response to sensory input.

Nociception-related somatosensory evoked potentials in awake dogs recorded after intra epidermal electrical stimulation.

At present, the specific neurophysiologic methodology of recording pain-related evoked potentials is considered a most promising approach to objectively quantify pain in man. This study was designed to characterise and evaluate the use of somatosensory evoked potentials to study nociception in a canine model. To this aim, somatosensory evoked potentials were evoked by intra-epidermal electrical stimulation and recorded from the scalp in 8 beagle dogs. Characteristics determined were: (1) the conduction velocities of the peripheral nerve fibres involved, (2) the stimulus intensity response characteristics and (3) the evaluation of possible disturbance of the signals by muscular activity from the hind paw withdrawal reflex (EMG artefact). The results showed (1) the conduction velocities to be in the A-delta fibre range (i.e. fibres involved in nociception), (2) an increase in amplitude and a decrease in latency of the evoked potential following increasing stimulus intensities and (3) the absence of EMG artefact in the signals. These data indicate that the evoked potentials recorded, are related to nociception and thus are suited to quantitatively characterise the perception of noxious stimuli making this model useful for pain- and analgesia-related research.

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 microg 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.

Somatosensory-evoked potentials indicate increased unpleasantness of noxious stimuli in response to increasing stimulus intensities in the rat.

Recently, it has been shown in rats that specific characteristics of somatosensory-evoked potentials (SEPs) recorded from different sites on the scalp correlate differently to the amount of unpleasantness experienced by the animal following noxious stimulation. It was shown that the SEP recorded from vertex (Vx-SEP) did correlate with the unpleasantness, whereas the SEP recorded from the primary somatosensory cortex (SI-SEP) did not. In the present study, we further investigated the relationship between the Vx-SEP, SI-SEP and the unpleasantness of noxious stimuli. Therefore, different groups of rats were subjected to a SEP fear-conditioning paradigm in which the unconditioned stimulus (US), represented by noxious stimuli applied to evoke SEPs, was paired to a conditioned stimulus (CS) represented by a tone. Different stimulus intensities of the US were applied in the different groups. After CS-US presentation, CS-induced fear-conditioned behaviour was analysed in relation to the characteristics of the Vx- and SI-SEP during CS-US presentation. Results showed that increasing stimulus intensities led to increased SEP amplitudes, which were paralleled by an increased amount of CS-induced fear-conditioned behaviour. No differences between Vx-SEP and SI-SEP were found. The increase in the SEPs in parallel with the increased amount of fear-induced behaviour further supports the SEP to be a potentially valuable tool for studying acute pain and analgesia in animals.

Vertex-recorded, rather than primary somatosensory cortex-recorded, somatosensory-evoked potentials signal unpleasantness of noxious stimuli in the rat.

In the present study, we investigated in the rat whether vertex- or primary somatosensory cortex-recorded somatosensory-evoked potentials (Vx-SEP/SI-SEP, respectively) signal unpleasantness of noxious stimuli. Therefore, initially we characterised fentanyl effects (0, 20, 40 or 50 microg/kg/h) on somatosensory and auditory processing by recording Vx-/SI-SEPs and vertex- and primary auditory cortex-recorded auditory-evoked potentials (Vx-/AI-AEPs, respectively). Subsequently, in a separate experiment, the animals were subjected to a Pavlovian fear-conditioning paradigm. The noxious stimuli applied to evoke Vx-/SI-SEPs (unconditioned stimulus (US)) were paired to a tone (conditioned stimulus (CS)) under 'steady state' conditions of 0, 20, 40 or 50 microg/kg/h fentanyl. Vx-/SI-SEPs were recorded simultaneously during these trials. After CS-US presentation, CS-induced fear-conditioned behaviour was analysed in relation to the SEPs recorded during CS-US presentation and the AEPs recorded in the first experiment. While the SI-SEP and AI-AEP were minimally but significantly affected, fentanyl dose-dependently decreased the Vx-SEP and Vx-AEP. The decrease of the Vx-SEP and Vx-AEP was parallelled by the dose-dependent decrease of the amount of CS-induced fear-conditioned behaviour. These results suggest that the dose-dependent decrease of the Vx-SEP amplitude, rather than of the SI-SEP, indicates that the US was experienced as less unpleasant. Next to an altered US processing, altered CS processing contributed to the decrease of the amount of CS-induced fear-conditioned behaviour as indicated by the dose-dependent decrease of the Vx-AEP.