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.

Monitoring equine visceral pain with a composite pain scale score and correlation with survival after emergency gastrointestinal surgery.

Recognition and management of equine pain have been studied extensively in recent decades and this has led to significant advances. However, there is still room for improvement in the ability to identify and treat pain in horses that have undergone emergency gastrointestinal surgery. This study assessed the validity and clinical application of the composite pain scale (CPS) in horses after emergency gastrointestinal surgery. Composite pain scores were determined every 4h over 3 days following emergency gastrointestinal surgery in 48 horses. Inter-observer reliability was determined and another composite visceral pain score (numerical rating scale, NRS) was determined simultaneously with CPS scores. CPS scores had higher inter-observer reliability (r=0.87, K=0.84, P<0.001), compared to NRS scores (r=0.68, K=0.72, P<0.001). Horses that survived without complications had significantly lower CPS and NRS scores compared to horses that were euthanased or had to undergo re-laparotomy (P<0.001). Breed and the location in the intestinal tract (small or large intestine) did not influence pain scores. In conclusion, the use of the CPS improved objectivity of pain scoring in horses following emergency gastrointestinal surgery. High inter-observer reliability allows for comparisons between different observers. This will be of great benefit in larger veterinary hospitals where several attending clinicians are often involved in the care of each case.

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.

Optimizing the dosing interval of buprenorphine in a multimodal postoperative analgesic strategy in the rat: minimizing side-effects without affecting weight gain and food intake.

Buprenorphine is commonly used as (part of) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6-12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.

Antinociceptive effects of low dose lumbosacral epidural ropivacaine in healthy ponies.

The objective of this study was to evaluate the safety and efficacy of low dose lumbosacral epidural ropivacaine in ponies. Antinociceptive effects of epidural ropivacaine were evaluated by means of mechanical nociceptive thresholds (MNTs) at several spinal levels in conscious ponies. The effects of ropivacaine on nociceptive afferent transmission to the spinal cord were also assessed by measuring spinal cord somatosensory evoked potentials (SSEPs) in anaesthetised ponies. Ataxia scores were determined in conscious ponies to assess the effects on motor function. A randomised, placebo controlled, double blind cross-over design was used. Low dose lumbosacral epidural ropivacaine led to increases in MNTs at various anatomical locations with a maximum effect at the lumbosacral and sacrococcygeal regions, both with respect to increase in threshold and duration of effect. Analysis of SSEPs showed that epidural ropivacaine influenced both Aß- and Aδ-mediated afferent transmission to the spinal cord at the level of the lumbosacral junction. Ponies showed mild ataxia after low dose lumbosacral epidural ropivacaine, but all ponies remained standing. Application of low dose lumbosacral epidural ropivacaine provided safe and efficacious antinociceptive effects in conscious and anaesthetised ponies, and could therefore be a valuable addition to multimodal analgesic protocols in Equidae.

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.

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

OBJECTIVE: To evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats. STUDY DESIGN: Prospective, randomized, crossover experimental study. ANIMALS: Six goats, three does and three wethers. METHODS: General 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). RESULTS: Isoflurane 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 RELEVANCE: In goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.

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.

[Antibiotics in animal husbandry: a thorny problem]. / Antibiotica in de veehouderij: netelig probleem.

The widespread use of antibiotics in animal husbandry in the Netherlands poses a problem to human health, due to the development of antibiotic resistance. However, agricultural managers have to adjust to an economic reality in which antibiotic use is profitable. In the long term, there has to be far more attention to prevention of infection and biosecurity in animal husbandry so that fewer antibiotics are required and the risks of passing on resistant organisms to the population are limited. An important stimulus would be for the meat-processing industry, the supermarkets and the consumers to impose demands concerning food-safety and to be prepared to pay for them. Alternatively, making antibiotics more expensive is a negative stimulus which could work well.

Total intravenous anaesthesia (TIVA) with propofol-fentanyl and propofol-midazolam combinations in spontaneously-breathing goats.

OBJECTIVE: To compare the efficacy and cardiopulmonary effects of propofol and fentanyl, with propofol and midazolam for total intravenous anaesthesia. STUDY DESIGN: Prospective, randomized, crossover experimental study. ANIMALS: Six goats; three does and three wethers. METHODS: Goats received either fentanyl 0.02 mg kg(-1) (treatment FP) or midazolam 0.3 mg kg(-1) (treatment MP) intravenously. One minute later anaesthesia was induced with propofol, then maintained by constant rate infusion of propofol 12.0 mg kg(-1) hour(-1) and fentanyl 0.02 mg kg(-1) hour(-1) (treatment FP) or propofol 12.0 mg kg(-1) hour(-1) and midazolam 0.3 mg kg(-1) hour(-1) (treatment MP) for 90 minutes. Response to noxious stimulus was tested every 10 minutes and propofol dose adjusted to prevent purposeful movement. Cardiopulmonary parameters were measured continuously, and arterial blood-gas analysis performed intermittently. Recovery was timed and quality scored. Results are presented as median (IQR). RESULTS: Differences in the propofol induction dose [4.00 (3.96-4.01) and 3.97 (3.91-4.00) mg kg(-1) for treatments FP and MP, respectively] were not significant. Quality of induction in both groups was smooth. The median propofol dose for maintenance was less (p = 0.004) with treatment FP (12.0 mg kg(-1) hour(-1) than MP (18.0 mg kg(-1) hour(-1). Cardiopulmonary function was well maintained with both treatments. Recovery times in minutes from the end of anaesthetic infusion for treatments FP and MP respectively were; to extubation 3.0 (3.0-3.0) and 4.5 (3.3-5.0); to sternal position, 4.5 (3.3-5.0) and 5.0 (5.0-6.5) and to standing 13.0 (10.3-15.0) and 15.0 (11.3-17.3). Quality of recovery was acceptable in both groups, but abnormal behavioural signs were observed after treatment FP. CONCLUSIONS AND CLINICAL RELEVANCE: Total intravenous anaesthesia with propofol and fentanyl or propofol and midazolam, at the doses studied, in spontaneously-breathing, oxygen-supplemented goats is practicable. Recovery from the fentanyl-propofol combination is not always smooth.

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.

Use of epidurally derived evoked potentials for quantification of caudal nociception in ponies.

OBJECTIVE: To determine whether epidurally derived evoked potentials (EPs) can be used to reliably assess nociception and antinociception in ponies. ANIMALS: 7 ponies. PROCEDURES: EPs and electromyograms (EMGs) from the quadriceps femoris muscles were recorded simultaneously, following electrical stimulation applied to the distal portion of the hind limb. The effect of increasing stimulus intensity, conduction velocities of the stimulated nerves, effect of epidurally applied methadone, and effect of systemically administered propofol were evaluated. RESULTS: In the EP and EMG waveforms, 2 distinct complexes, the EP N25 and P50 and the EMG P27 and N62, respectively, were identified. On the basis of their latency and calculated conduction velocities, the EP P50 and EMG N62 were considered to be related to nociception (AD-mediated). All complexes increased significantly in amplitude with increasing stimulus intensity and decreased significantly following epidural administration of methadone or systemic administration of propofol. CONCLUSIONS AND CLINICAL RELEVANCE: Although the experimental setup allowed successful discrimination between tactile- and nociceptive-associated responses, the identified EPs, considered to reflect activity in the spinal cord, could not be definitively differentiated from activity in the lumbosacral epaxial musculature. Further research is required to refine measurement techniques to allow for discrimination between these 2 signals. Similar to other species, neurophysiologic variables such as EPs could potentially become a useful additional tool in quantifying nociception in equidae.

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

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

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.

The cardiorespiratory effects of a fentanyl infusion following acepromazine and glycopyrrolate in dogs.

We investigated whether the analgesic mu-opioid fentanyl can be used safely in dogs in everyday clinical veterinary practice, with limited and non-invasive monitoring. To this end, the cardiorespiratory effects of fentanyl, administered in doses reported to be adequate for inducing opiate analgesia in spontaneously breathing canine patients, were evaluated by measuring the respiration rate, oxygen saturation (SpO2), heart rate, respiratory sinus arrhythmia (RSA), and rectal body temperature. Ten Beagle dogs, all spontaneously breathing room air, underwent three separate sessions in which they received in random order either saline, fentanyl 5 microg/kg/h or fentanyl 10 microg/kg/h. Each session started with a non-medication period, followed by acepromazine with glycopyrrolate, followed by a loading dose and infusion of saline or fentanyl, and ended with the administration of the antagonist naloxone. At the doses studied, fentanyl did not significantly change the respiration rate or have a clinically relevant effect on SpO2 or RSA, whereas it significantly decreased the heart rate and core body temperature. In the dose range tested and under the conditions described in this protocol, we conclude that fentanyl can be safely administered to healthy dogs spontaneously breathing room air.

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.

Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs.

OBJECTIVE: To evaluate cardiovascular and respiratory effects and pharmacokinetics of a 24-hour intravenous constant rate infusion (CRI) of dexmedetomidine (DMED) during and after propofol (PRO) or isoflurane (ISO) anaesthesia in dogs. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Ten healthy adult Beagles. METHODS: Instrumented dogs received a DMED-loading bolus (25 microg m(-2)) at time 0 followed by a 24-hour CRI (25 microg m(-2) hour(-1)), with PRO or ISO induction/maintenance of anaesthesia during the first 2 hours (PRO and ISO treatment groups, respectively). Cardiovascular, respiratory, blood gas, airway gas, serum chemistry variables and DMED plasma concentration data were collected at -15, 5, 15, 30, 45, 60, 90 and 120 minutes. A number of cardiorespiratory and tissue oxygenation variables were calculated from the above data. After the 2-hours of anaesthesia, heart and respiratory rates and electrocardiograms were recorded and DMED plasma concentrations were determined for up to 26 hours. RESULTS: Vasopressor effects and the decrease in heart rate (HR) and cardiac index induced by DMED were greater for PRO than ISO, but were within clinically acceptable ranges. Adequate oxygenation was maintained above the critical O(2) delivery level. The overall incidence of unfavourable arrhythmias was low and tended to vary inversely with HR. Mean DMED plasma concentration ranged from 0.23 to 0.47 ng mL(-1) for both groups during the 24-hour CRI with a mean elimination half-life of approximately 0.46 hour. CONCLUSION AND/CLINICAL RELEVANCE: DMED CRI resulted in typical alpha(2)-agonist induced haemodynamic changes with minimal respiratory effects, and appeared to be an efficacious adjunct during and after PRO or ISO anaesthesia in healthy dogs.

Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients.

OBJECTIVE: To determine the effects of three rates of dexmedetomidine (DMED) constant rate infusion (CRI) on overall tissue perfusion, isoflurane (ISO) requirements, haemodynamics and quality of recovery in canine surgical patients. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Client-owned dogs presented for soft tissue or orthopaedic surgery. METHODS: Following intravenous (IV) pre-medication with DMED (5 microg kg(-1)) and buprenorphine (10 microg kg(-1)) and propofol induction, anaesthesia was maintained with ISO in oxygen/air supplemented with a DMED CRI (1, 2 or 3 microg kg(-1) hour(-1); groups 1, 2 and 3, respectively). Ventilation was controlled in all animals using intermittent positive pressure ventilation (IPPV). Monitoring included end-tidal (ET) gases, ECG, arterial blood pressure, body temperature and sequential arterial blood gas and lactate measurements. Quality of recovery was scored after intramuscular (IM) administration of atipamezole (ATI) (12.5 microg kg(-1)). Immediate post-operative analgesia was provided with carprofen and/or buprenorphine. An analysis of variance was conducted for repeated measurements obtained during 80 minutes after first incision. Categorical data were evaluated with Chi-square analyses. RESULTS: Arterial blood pressure remained stable and within clinically acceptable limits. Mean heart rate in group 2 was significantly lower than in group 1. The incidence of 2nd degree AV block type II was significantly higher in group 3. Mean arterial lactate concentrations remained below 2 mmol/L in all groups during the study, with a significant increase occurring during recovery compared with surgery for group 3. Mean e'ISO% was similar and <1% in all groups. Complete recovery from anaesthesia was achieved after ATI administration and was of good quality in all but three animals. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine CRI is a reliable and valuable adjunct to ISO anaesthesia in maintaining surgical anaesthesia in ASA I-II dogs. Data reported indicate adequate overall tissue perfusion and a low ISO requirement while enabling a smooth and rapid recovery following ATI. The DMED CRI of 1 microg kg(-1) hour(-1) following a loading dose of 5 microg kg(-1) produced the most favourable results.