Maj Halling Thomsen

Analgesic efficacy of intra-articular morphine in experimentally induced radiocarpal synovitis in horses.

OBJECTIVE To compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis. ANIMALS Eight adult horses. STUDY DESIGN Randomized, observer blinded, double dummy trial with sequential crossover design. METHODS Radiocarpal synovitis was induced by IA injection of lipopolysaccharide on two occasions separated by a 3-week washout period. In one study period horses received treatment IA; morphine IA (0.05 mg kg(-1)) plus saline IV and in the other study period they received treatment IV; saline IA plus morphine IV (0.05 mg kg(-1)). Lameness and pain were evaluated repeatedly by two observers throughout each of the two 168-hour study periods. Pain was evaluated by use of a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS). Comparison of treatments was performed by analysis of variance with repeated measurements. Significance level was set to p < or = 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland-Altman method. RESULTS Intra-articular injection of LPS elicited a marked synovitis resulting in lameness and pain. IA morphine resulted in significantly less lameness than IV morphine (p = 0.03). CMPS (p = 0.09) and VAS (p = 0.10) pain scores did not differ significantly between treatments. Inter-observer agreement of the CMPS was classified as good, but only fair for the VAS. Agreement between the two pain scales was considered fair. CONCLUSIONS AND CLINICAL RELEVANCE An analgesic effect of IA morphine was demonstrated by significantly reduced lameness scores. The results support the common practice of including IA morphine in a multimodal analgesic protocol after arthroscopic surgery, although further studies in clinical cases are needed. The employed CMPS had good reproducibility, and was easy to use, but may have limited sensitivity at mild intensity pain.

Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis

OBJECTIVE To compare the effects of intra-articular (IA) versus IV administration of morphine on local and systemic inflammatory responses in horses with experimentally induced acute synovitis. ANIMALS 8 horses. PROCEDURES Each horse received the following 2 treatments 4 hours after synovitis was induced: IA administration of morphine (0.05 mg/kg) with IV administration of 1 mL of saline (0.9% NaCl) solution/100 kg, and IA administration of 1 mL of saline solution/100 kg with IV administration of morphine (0.05 mg/kg). Treatments were administered in randomized order with a washout period of 3 weeks between treatments. Before each treatment, aseptic synovitis was induced by injection of lipopolysaccharide into a radiocarpal joint. For the second treatment, the contralateral radiocarpal joint was selected. Joint swelling and skin temperature over the treated joints were recorded. Clinical examinations were performed, and blood WBC count, serum amyloid A (SAA) concentration, serum cortisol concentration, synovial fluid WBC count, synovial fluid total protein (TP) concentration, and synovial fluid SAA concentration were measured before and repeatedly during each of the two 168-hour study periods. Data were analyzed by use of ANOVA with repeated measures. RESULTS IA administration of morphine resulted in significantly less joint swelling and lower synovial fluid TP and serum and synovial fluid SAA concentrations, and blood WBC count than did IV administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE IA administration of morphine exerted anti-inflammatory properties in horses with experimentally induced acute synovitis, supporting its use as a part of a balanced analgesic protocol.

Agreement between accelerometric symmetry scores and clinical lameness scores during experimentally induced transient distension of the metacarpophalangeal joint in horses.

REASONS FOR PERFORMING STUDY Equine lameness examination is based on subjective visual scoring of lameness. Instrumented objective methods for lameness examinations may be complicated to perform and the equipment is often stationary. Accelerometry has a potential clinical use; however, the reduction and interpretation of equine accelerometric data are not yet routine and the value of accelerometry in equine lameness examination is unclear. OBJECTIVES To use accelerometric data to calculate 2 different accelerometric symmetry scores and to evaluate the agreement of these with traditional lameness scores done by experienced equine practitioners. METHODS Six sound horses were equipped with a 3 axis 10G piezoresistant accelerometer at the lowest point of the back. Horses were trotted and video recorded at 0, 3, 15, 30, 45 and 60 min after injection of saline into one metacarpophalangeal joint. Video recordings were scored in a blind manner according to the AAEP scale by 2 experienced practitioners. Interobserver agreements and 2 symmetry scores S and A, developed on the basis of Fourier transformation of the obtained accelerometric data, were calculated and regression analysis between AAEP scores and symmetry scores was performed. RESULTS Interobserver agreements were 70%. There was a statistically significant relationship between AAEP lameness scores and both symmetry scores. CONCLUSIONS Both symmetry scores showed a significant relationship with the AAEP scores and can be a valuable tool in the detection and quantification of lameness. While the S score was able to detect changes in degree of lameness, the A score was capable of detecting the lame diagonal. However, more research is needed for the development of a combined accelerometric score to take advantage of the strengths of each of the symmetry scores.

Symmetry indices based on accelerometric data in trotting horses

Detection and quantification of lameness in horses consists primarily of a subjective assessment, whereby both intra- and inter-observer disagreements exist, especially with low grade lameness. Therefore, clinically applicable methods are needed for reliable, objective assessments. The aim of this study was to describe three symmetry indices derived from a simple accelerometric method and investigate these in sound trotting horses. The indices describe the overall symmetry of the gait, the symmetry of loads placed on the limbs and the symmetry in timing between left and right steps. These symmetry indices were able to quantify the high degree of symmetry of the trot in sound horses that has been described in earlier studies using other gait analysis methods. Also, we have analysed the variances and have found high repeatability for all three indices. This provides a basis for future investigations of the symmetry indices and their potential for objective detection and quantification of lameness in horses.

Accuracy and precision of gait events derived from motion capture in horses during walk and trot

This study aimed to create an evidence base for detection of stance-phase timings from motion capture in horses. The objective was to compare the accuracy (bias) and precision (SD) for five published algorithms for the detection of hoof-on and hoof-off using force plates as the reference standard. Six horses were walked and trotted over eight force plates surrounded by a synchronised 12-camera infrared motion capture system. The five algorithms (A-E) were based on: (A) horizontal velocity of the hoof; (B) Fetlock angle and horizontal hoof velocity; (C) horizontal displacement of the hoof relative to the centre of mass; (D) horizontal velocity of the hoof relative to the Centre of Mass and; (E) vertical acceleration of the hoof. A total of 240 stance phases in walk and 240 stance phases in trot were included in the assessment. Method D provided the most accurate and precise results in walk for stance phase duration with a bias of 4.1% for front limbs and 4.8% for hind limbs. For trot we derived a combination of method A for hoof-on and method E for hoof-off resulting in a bias of -6.2% of stance in the front limbs and method B for the hind limbs with a bias of 3.8% of stance phase duration. We conclude that motion capture yields accurate and precise detection of gait events for horses walking and trotting over ground and the results emphasise a need for different algorithms for front limbs versus hind limbs in trot.

Pharmacokinetics of intra-articular morphine in horses with lipopolysaccharide-induced synovitis.

OBJECTIVE To describe the pharmacokinetics of intra-articularly (IA) administered morphine. STUDY DESIGN Experimental randomized, cross-over study. ANIMALS Eight adult healthy mixed breed horses aged 6.5 +/- 2.3 (mean +/- SD) years and weighing 535 +/- 86 kg. METHODS Unilateral radiocarpal synovitis was induced by IA injection of 3 microg lipopolysaccharide (LPS) on two occasions (right and left radiocarpal joint, respectively) separated by a 3-week wash-out period. Treatments were administered 4 hours post-LPS-injection: Treatment IA; preservative free morphine IA (0.05 mg kg(-1)) plus saline intravenous (IV) and treatment IV; saline IA plus preservative free morphine IV (0.05 mg kg(-1)). Concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide (M6G) were determined repeatedly in serum and synovial fluid (SF) by high-performance liquid chromatography mass spectrometry, at 2 and 4 hours and then at 4 hours intervals until 28 hours post-treatment. RESULTS Injection of LPS elicited a marked and comparable synovitis in all LPS-injected radiocarpal joints. IA administered morphine was detectable in SF of all eight joints 24 hours post-treatment and in 6/8 joints 28 hours post-treatment. The terminal half-life of morphine in SF was estimated to be 2.6 hours. IA administration of morphine resulted in mean serum concentrations of morphine below 5 ng mL(-1) from 2 to 28 hours after treatment. CONCLUSIONS AND CLINICAL RELEVANCE Intra-articularly administered morphine remained within the joint for at least 24 hours. At the same time only very low serum concentrations of morphine and M6G were detected. The present results suggest that IA morphine at 0.05 mg kg(-1) may be used for IA analgesia lasting at least 24 hours and give strong support to the theory that previously observed analgesic and anti-inflammatory effects of IA morphine in horses are most likely to be mediated peripherally.

In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration

The objective of the present study was to explore the potential of using an in situ suspension forming drug delivery system of celecoxib to provide sustained drug exposure in the joint cavity following intra-articular administration. In vitro, precipitates were formed upon addition of a 400 mg/mL solution of celecoxib in polyethylene glycol 400 (PEG 400) to phosphate buffer, pH 7.4, or synovial fluid. The in vitro release profiles of the in situ formed suspensions were characterized by an initial fast release followed by a slower constant flux. In buffer solutions, these fluxes were comparable to those determined for a preformed suspension containing celecoxib in its most stable crystal form despite the in situ formed precipitates contained a mixture of two crystal forms of celecoxib as determined by X-ray powder diffraction. In situ suspension formation in synovial fluid was subject to considerable variation. A relatively high dose of celecoxib, corresponding to 1.25 mg/kg, in the form of PEG 400 solution (400 mg/mL) was injected into the radiocarpal joint in four horses. Celecoxib was present in serum samples taken over 10 days and in the joint tissue (post mortem), strongly indicating that joint sustained celecoxib exposure can be achieved using in situ suspension formation.

Quantification of symmetry for functional data with application to equine lameness classification

This paper presents a study on symmetry of repeated bi-phased data signals, in particular, on quantification of the deviation between the two parts of the signal. Three symmetry scores are defined using functional data techniques such as smoothing and registration. One score is related to the L 2-distance between the two parts of the signal, whereas the other two are constructed to specifically measure differences in amplitude and phase. Moreover, symmetry scores based on functional principal component analysis (PCA) are examined. The scores are applied to acceleration signals from a study on equine gait. The scores turn out to be highly associated with lameness, and their applicability for lameness quantification and detection is investigated. Four classification approaches turn out to give similar results. The scores describing amplitude and phase variation turn out to outperform the PCA scores when it comes to the classification of lameness.

The effect of a compression bandage on the distribution of radiodense contrast medium after palmar digital nerve blocks

BACKGROUND Studies have shown proximal diffusion of injected drugs in perineural blocks; such diffusion may affect specificity of the nerve block. OBJECTIVES To investigate the effect of a compression bandage applied to the pastern region on proximal diffusion of contrast medium injected over the palmar digital nerves. STUDY DESIGN Experimental study, randomised cross-over design. METHODS Radiodense contrast medium was injected over the lateral and medial palmar digital nerves of the left front limb of nine mature horses. Each horse was injected on two separate occasions, once with a 5 cm wide compression bandage applied proximal to the injection site and once without. The order of the two treatments was randomised with a wash-out period between treatments of at least 7 days. Radiographs were obtained at 5, 10, 20 and 30 min and distribution of the contrast column assessed. RESULTS Proximal distribution of the contrast medium was significantly reduced (P<0.01) with compression bandage. Furthermore, the compression bandage inhibited lymphatic drainage of the injected contrast medium. MAIN LIMITATIONS Clinical effect of the differences in diffusion length was not assessed. CONCLUSIONS The compression bandage reduced proximal diffusion and lymphatic drainage of contrast material causing it to stay localised around the injection site. Use of compression bandages could thus result in increased specificity of the nerve block and potentially prolong its effect.