Joost J Uilenreef

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.

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.

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.

Ultrasound-guided serial transabdominal cardiac biopsies in cats.

A percutaneous/transdiaphragmatic core needle biopsy technique was developed in cats to obtain serial biopsies from different locations of the left ventricle, through which morphological and molecular changes within the same individual can be studied to unravel the mechanisms of feline cardiomyopathies. Transmural left ventricular myocardial samples were obtained from 29 anesthetized, healthy, adult cats with ultrasound guidance. An 18G automatic biopsy needle was inserted between the last left rib and the sternum through the diaphragm into the thorax. Biopsies were obtained from the left ventricular wall. In five cats, three single biopsies were taken with 4-week intervals. Autopsy was performed on six cats, of which three cats had serial biopsies. In total, 87 biopsies were obtained without long-term effects on cardiac function or structure. The biopsies caused transient single ventricular premature complexes and mild pericardial effusion without tamponade. Necropsy revealed a minimal amount of fibrous connective tissue in the diaphragm and the heart without any significant microscopic lesions in the adjacent muscle tissue. The high quality biopsy material was suitable for morphological and molecular studies. This minimally invasive, ultrasound-guided cardiac biopsy technique thus allows for the safe collection of serial biopsies to study feline cardiomyopathies in an experimental setting.

Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long-term use of meloxicam in young, growing piglets.

Non-invasive blood pressure measurement in ferrets (Mustela putorius furo) using high definition oscillometry

This study was conducted to validate the use of high definition oscillometry (HDO) for non-invasive blood pressure (NIBP) measurements in ferrets and to establish reference ranges for NIBP in minimally sedated, healthy, young adult ferrets (<4years of age). The bias, limits of agreement and correlation for HDO compared to direct arterial blood pressure (DABP) measurement were established in 14 anaesthetised ferrets. Measurements were performed at the forelimb, hind limb and tail under hypo- (<110mmHg), normo- (110-170mmHg) and hypertensive (>170mmHg) conditions. Although HDO correlated well with DABP (r>0.90), it showed significant proportional bias, whereby HDO generally underestimated DABP with hyper- and normotensive conditions, and overestimated DABP with hypotensive conditions. Measurements obtained from the hind limb showed higher bias than those obtained from the tail or forelimb (P<0.001). Based on the above, and for practical reasons, the tail was selected as the preferred site of cuff placement in ferrets. Subsequently, a cross-over study was performed in 10 ferrets to establish the minimum dose of butorphanol and midazolam needed to successfully obtain NIBP in 100% of cases. Using this dose (0.2mg/kg IM, each), reference intervals for NIBP from 63 healthy, young adult ferrets were established at 95-155mmHg (systolic), 69-109mmHg (mean) and 51-87mmHg (diastolic) arterial pressures.