Pain assessment in horses after orthopaedic surgery and with orthopaedic trauma.

Objective pain assessment is important to guide and tailor therapy in clinical practice. This study describes the clinical applicability and validity of two pain scales, the Composite Pain Scale (CPS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) in horses with orthopaedic trauma or after orthopaedic surgery. A cohort follow-up study was performed using 77 adult horses (n=43 with orthopaedic trauma or injury; n=34 controls). Composite and facial expression-based pain scores were assessed by direct observations of pairs of two independent observers. All horses were assessed at arrival, and on the first and second day after arrival or after surgery. Both CPS and EQUUS-FAP scores demonstrated high inter-observer reliability (Crohnbach's alpha=0.97 for CPS; Crohnbach's alpha=0.93 for EQUUS-FAP; P<0.001), with low bias (0.07 and -0.08 respectively) and limits of agreement of -1.9 to 1.9 for CPS and -1.9 to 1.9 for EQUUS-FAP. Both CPS and EQUUS-FAP scores showed significant differences between control horses and orthopaedic cases (P<0.001). Trauma cases had significantly higher pain scores compared to postoperative cases for both CPS (P<0.05) and for EQUUS-FAP (P<0.01) and both pain scores significantly decreased after nonsteroidal anti-inflammatory drug (NSAID) administration. In accordance with the findings in other types of equine pain, the CPS and FAP proved useful and valid for objective and repeatable assessment of pain in horses with orthopaedic trauma or after orthopaedic surgery. This can further aid treatment of horses in clinical practice and might improve equine welfare.

Objective pain assessment in horses (2014-2018).

In recent decades, much effort has been invested in scientific studies of objective and reliable assessment of pain in horses. Various types of pain assessment tools have been described and (partly) validated for different types of pain in horses. Currently, composite pain scales and facial expression-based pain scales seem to be the most promising tools for pain assessment in horses and numerous studies have recently been published on the use of these pain scales in horses. Therefore, this narrative review mainly focusses on these two types of pain scales and on the studies that have appeared describing these type of pain scales in horses. The extent to which these pain scales have been validated (sensitivity, specificity, inter-observer reliability etc.) and their potential use for clinical pain states is discussed. Possible future directions for new studies and their possible aid in assessing pain in hospitalised and ridden horses are presented. In this way, improved pain scoring could improve criteria used to evaluate the clinical efficacy of new analgesic drugs and techniques, potentially benefiting equine welfare.

Oxygen supplementation before induction of general anaesthesia in horses.

REASONS FOR PERFORMING STUDY: Hypoventilation or apnoea, caused by the induction of general anaesthesia, may cause hypoxaemia. Preoxygenation may lengthen the period before this happens. No scientific studies are published on preoxygenation in equine anaesthesia. OBJECTIVES: To determine whether supplementation of oxygen at a flow rate of 15 l/min for 3 min via a nasal cannula before induction of general anaesthesia is effective in elevating the arterial partial pressure of oxygen (PaO2 ) directly after induction. STUDY DESIGN: Randomised, prospective clinical trial. METHODS: A total of 18 American Society of Anesthesiologists physical status 1 or 2 adult horses undergoing elective anaesthesia were randomly allocated to one of 2 groups. The first group (control) received no oxygen supplementation before induction of general anaesthesia, whereas the second group (oxygen) did. All horses were anaesthetised with intravenous detomidine, butorphanol, ketamine, midazolam and isoflurane. Directly after induction (T = 0) and 30 min later (T = 30) an arterial blood sample was taken for blood gas analysis. At T = 30 an estimate of intrapulmonary shunt fraction (Qs/Qt) was calculated. RESULTS: At T = 0 arterial partial pressure of oxygen (PaO2 ) was significantly higher in the oxygen group compared with the control group (11.0 ± 2.6 kPa vs. 7.4 ± 1.6 kPa; mean ± s.d., P = 0.005) and at T = 30 differences were not statistically significant. Partial pressure of carbon dioxide (PaCO2 ) and Qs/Qt did not differ between groups. CONCLUSIONS: Supplementing oxygen by a nasal cannula before induction of general anaesthesia in horses is feasible and does effectively elevate the PaO2 immediately after induction. Future research is needed to determine whether supplementation of oxygen before induction of general anaesthesia in horses will affect outcomes.

Systematic pain assessment in horses.

Accurate recognition and quantification of pain in horses is imperative for adequate pain management. The past decade has seen a much needed surge in formal development of systematic pain assessment tools for the objective monitoring of pain in equine patients. This narrative review describes parameters that can be used to detect pain in horses, provides an overview of the various pain scales developed (visual analogue scales, simple descriptive scales, numerical rating scales, time budget analysis, composite pain scales and grimace scales), and highlights their strengths and weaknesses for potential clinical implementation. The available literature on the use of each pain assessment tool in specific equine pain states (laminitis, lameness, acute synovitis, post-castration, acute colic and post-abdominal surgery) is discussed, including any problems with sensitivity, reliability or scale validation as well as translation of results to other clinical pain states. The review considers future development and further refinement of currently available equine pain scoring systems.

In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis.

Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice, little is known about its in vivo effects on joint inflammation and cartilage turnover. This study investigates the effects of PBZ on inflammatory parameters, matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints with acute synovitis. In a two-period cross-over study, transient synovitis was induced at T = 0 h in the middle carpal joint of seven ponies by lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily) or placebo for 1 week, starting at T = 2 h. Arthroscopic assessment of the middle carpal joint was performed at T = -504, 48 and 672 h. Synovial fluid (SF) was sampled at T = -504, 0, 8, 24, 48, 168, 336 and 672 h and analysed for leukocytes and total protein, substance P, general MMP activity, glycosaminoglycans (GAG), collagen II cleavage marker C2C and synthesis marker CPII. Markers in PBZ- vs. placebo-treated joints were compared over time using a linear mixed model. LPS injection caused marked transient synovitis without visible cartilage changes. Substance P and general MMP activity were not significantly reduced by PBZ treatment, nor were SF GAG or C2C concentrations at any time point. Concentration of CPII was significantly lower at T = 24 and 168 h in PBZ treated joints compared to placebo. Although PBZ is clinically effective in treating acute synovitis, it does not limit inflammation-induced cartilage catabolism and may transiently reduce collagen anabolism as evidenced by SF markers.

Upregulation of articular synovial membrane µ-opioid-like receptors in an acute equine synovitis model.

Intra-articular injection of opioids provides analgesia in painful equine joints and µ-opioid receptors (MORs) have been demonstrated in equine synovial membranes. The aim of this study was to determine whether acute inflammatory conditions will lead to up-regulation of MOR in equine synovial membranes and whether anti-inflammatory treatment can prevent any such upregulation. In a two-period, blinded, placebo-controlled randomised cross-over design, lipopolysaccharide (LPS, 1.0 ng) was injected into the left or right middle carpal joint of seven healthy ponies. Arthroscopy and synovial membrane biopsy was performed under general anaesthesia at baseline, 48 h (T48) and 672 h (T672) after LPS injection, with ponies assigned to receive either phenylbutazone (PBZ 2.2mg/kg PO BID) or placebo from 2h post-LPS. Ponies were scored for pain and lameness. Repeated synovial fluid samples were obtained and the degree of synovitis scored both macroscopically and microscopically. The density and staining pattern of MOR-like protein in synovial membrane biopsies over the course of the synovitis with or without PBZ treatment was evaluated using immunohistochemical techniques. LPS injection consistently induced a severe transient synovitis. Pain and lameness were significantly attenuated by treatment with PBZ. Up-regulation of MOR-like protein in the inflamed equine synovial membrane could be demonstrated in the placebo treated animals, but not in the PBZ-treated animals overall, although there were no significant differences at any individual time-point between the two groups. It was concluded that acute inflammation will up-regulate MOR, while anti-inflammatory treatment will attenuate this response.

Pain recognition and treatment in the horse: a survey of equine veterinarians in The Netherlands and Belgium.

This survey investigated the attitudes of equine veterinarians in The Netherlands and the Flemish region of Belgium towards pain management in the horse. Questionnaires were sent out to 771 equine veterinarians, all members of the Dutch or Flemish equine practitioners society. The return rate of completed questionnaires was 16.6%. The survey provided information about the use of analgesic drugs, factors influencing their prescription, pain scoring, analgesic therapy for specific clinical conditions, use of epidural analgesia, and appraisal of personal knowledge of pain management. The pain scores attributed to specific clinical conditions showed considerable variation. Non-steroidal anti-inflammatory drugs (NSAIDS) were the most-often prescribed analgesic drugs, with older drugs still having an important role in pain management. Butorphanol was the main opioid used. A substantial proportion of the respondents considered their knowledge of pain recognition and analgesic therapy to be insufficient or moderate.

Intra-articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model.

REASONS FOR PERFORMING STUDY: Intra-articular administration of morphine as a local analgesic and anti-inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti-inflammatory efficacy. OBJECTIVES: To use an inflammatory orthopaedic pain model to investigate the analgesic and anti-inflammatory effects of intra-articularly administered morphine as a new treatment modality in horses with acute arthritis. METHODS: In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra-articular injection of 0.5 ng lipopolyssacharide (LPS). The effect of 120 mg morphine, intra-articularly administered at 1 h after induction of synovitis, was evaluated using both physiological and behavioural pain variables. Synovial fluid was sampled at 0, 4, 8, 28 and 52 h after induction of synovitis and analysed for total protein concentration, leucocyte count and for prostaglandin E(2), bradykinin and substance P concentrations by ELISA. Ranges of motion of metatarsophalangeal and talocrural joints were measured as kinematic variables with the horses walking and trotting on a treadmill under sound and lame conditions. Clinical lameness scores and several behavioural variables related to the perception of pain were obtained. RESULTS: LPS injection caused marked transient synovitis, resulting in increased concentrations of inflammatory synovial fluid markers, clinical lameness, joint effusion and several behavioural changes, such as increased time spent recumbent, decreased limb loading at rest and decreased time spent eating silage. Intra-articular morphine resulted in a significant decrease in synovial white blood cell count, prostaglandin E(2) and bradykinin levels and improvement in clinical lameness, kinematic and behavioural parameters, compared to placebo treatment. CONCLUSIONS: Intra-articular morphine offers potent analgesic and anti-inflammatory effects in horses suffering from acute synovitis. POTENTIAL RELEVANCE: Local administration of opioids may be useful for horses with acute inflammatory joint pain and offers possibilities for multimodal analgesic therapies without opioid-related systemic side effects.

Lumbosacral spinal cord somatosensory evoked potentials for quantification of nociception in horses.

REASONS FOR PERFORMING STUDY: There is a need for objective evaluation and quantification of the efficacy of analgesic drugs and analgesic techniques in horses. OBJECTIVES: To determine whether lumbosacral spinal cord somatosensory evoked potentials (SSEP) can be a useful and reliable tool to assess nociception in equines. METHODS: SSEPs and electromyograms (EMG) from the epaxial muscles were recorded simultaneously, following electrical stimulation applied to the distal hindlimb in lightly anaesthetised Shetland ponies (n=7). In order to validate the model, the effect of increasing stimulus intensity was documented and the conduction velocities (CV) of the stimulated nerves were calculated. The effect of epidurally applied methadone (0.4 mg/kg bwt) in a randomised, crossover design was investigated. RESULTS: Two distinct complexes (N1P1 and N2P2) were identified in the SSEP waveform. Based on their latency and conduction velocity and the depressant effect of epidurally applied methadone, the SSEP N2P2 was ascribed to nociceptive Adelta-afferent stimulation. The SSEP N1P1 originated from non-nociceptive Abeta-afferent stimulation and was not influenced by epidurally applied methadone. CONCLUSIONS AND POTENTIAL RELEVANCE: The nociceptive Adelta component of the SSEP, the N2P2 complex, is presented as a valid and quantitative parameter of spinal nociceptive processing in the horse. Validation of the equine SSEP model enables the analgesic effects of new analgesics/analgesic techniques to be quantified and analgesia protocols for caudal epidural analgesia in equidae improved.

Post-anaesthetic myelopathy in a 3-year-old Friesian gelding.

A 3-year-old Friesian stallion was referred to the Department of Equine Sciences at Utrecht University with signs of colic. Laparotomy was performed and the stallion was castrated bilaterally because of an incarcerated inguinal hernia. Intestinal resection was not performed. Eight days postoperatively, the horse showed signs of severe colic and was admitted for re-laparotomy. After resection of 1.5 m of strangulated jejunum and severe intraoperative hypotension, bradycardia, and electrolyte disorders, the horse showed problems during recovery with signs of hindquarter paralysis. There was no pain perception in the hind limbs and there were no patellar or anal reflexes. The muscles of the hindquarters and the long extensor muscles of the back were soft and not painful on palpation. No improvement was seen 60 minutes after intravenous injection of corticosteroids. Because of the tentative diagnosis of post-anaesthetic myelopathy and its poor prognosis, and the fact that the horse was restless and did not accept being lifted with a sling system, the horse was euthanized with the owner's consent. Post-anaesthetic myelopathy is a rare neuropathological condition in the horse. Because of its low incidence, knowledge about its aetiology and contributing factors is rather limited. This case report presents the clinical observations and the anaesthetic protocol and compares this case with previously reported cases in the literature.

Umbilical cord clamping in term piglets: a useful model to study perinatal asphyxia?

Perinatal asphyxia results in tissue and cellular changes during the reperfusion period and clinical signs like perinatal mortality and decreased vitality at birth in newborn piglets. This study aimed to develop and validate a model of birth asphyxia, mimicking the evolvement of birth asphyxia in natural farrowings by conducting umbilical cord clamping (UCC) in term piglets during caesarean sections under general anaesthesia. In total 23 piglets were subjected to 5-8min of UCC and 24 piglets served as controls. Acid-base balance values and heart rates measured before UCC remained fairly constant throughout the surgical procedure, indicating nearly identical starting conditions of piglets within and between litters. UCC resulted in a significant, mild, mixed respiratory-metabolic acidosis (pH 7.22, pCO(2) 9.8kPa, BE(ecf) 2mmol/L, lactate 6.5mmol/L; controls: pH 7.31, pCO(2) 8.5kPa, BE(ecf) 5mmol/L, lactate 4mmol/L) at 10min after birth (defined as simultaneous cutting of the umbilical cord and removal of a plastic bag that had been placed over the head to avoid air intake). Heart rates were significantly decreased during UCC (range: 83-107beats/min versus 128-134beats/min in controls). Rectal temperatures and changes in body weight until 72h of life were not affected by UCC. Interestingly, four control and seven clamped piglets did not survive as no independent respiration could be attained. Birth weights and duration of UCC of these piglets did not differ significantly from those in surviving control and clamped piglets. In conclusion the mixed respiratory-metabolic acidosis arising in the surviving clamped piglets is not as severe as can be expected in highly asphyxiated, vaginally delivered newborn piglets. Repeatability of the model is compromised by considerable variation in the individual response to UCC.

Animal models for tracheal research.

Tracheal research covers two main areas of interest: tracheal reconstruction and tracheal fixation. Tracheal reconstructions are aimed at rearranging or replacing parts of the tracheal tissue using implantation and transplantation techniques. The indications for tracheal reconstruction are numerous: obstructing tracheal tumors, trauma, post-intubation tissue reactions, etc. Although in the past years much progress has been made, none of the new developed techniques have resulted in clinical application at large scale. Tissue engineering is believed to be the technique to provide a solution for reconstruction of tracheal defects. Although developing functional tracheal tissue from different cultured cell types is still a challenge. Tracheal fixation research is relatively new in the field and concentrates on solving fixation-related problems for laryngectomized patients. In prosthetic voice rehabilitation tracheo-esophageal silicon rubber speech valves and tracheostoma valves are used. This is often accompanied by many complications. The animal models used for tracheal research vary widely and in most publications proper scientific arguments for animal selection are never mentioned. It showed that the choice on animal models is a multi-factorial process in which non-scientific arguments tend to play a key role. The aim of this study is to provide biomaterials scientists with information about tracheal research and the animal models used.

In vitro evaluation of the PUCA II intra-arterial LVAD.

The "pulsatile catheter" (PUCA) pump is a minimally invasive intra-arterial left ventricular assist device intended for acute support of critically ill heart failure patients. To assess the hydrodynamic performance of the PUCA II, driven by an Arrow AutoCat IABP driver, we used a (static) mock circulatory system in which the PUCA II was tested at different loading conditions. The PUCA II was subsequently introduced in a (dynamic) cardiovascular simulator (CVS) to mimic actual in vivo operating conditions, with different heart rates and 2 levels of left ventricular (LV) contractility. Mock circulation data shows that PUCA II pump performance is sensitive to afterload, pump rate and preload. CVS data demonstrate that PUCA II provides effective LV unloading and augments diastolic aortic pressure. The contribution of PUCA II to total flow is inversely related to LV contractility and is higher at high heart rates. We conclude that, with the current IABP driver, the PUCA II is most effective in 1:1 mode in left ventricles with low contractility.

Groningen temporomandibular joint prosthesis. Development and first clinical application.

Patients with a severely degenerated temporomandibular joint (TMJ) may benefit from an alloplastic TMJ replacement. The aim of the study was to develop a safe and properly functioning TMJ prosthesis. The design was based on imitation of anterior condylar translation by an inferiorly located centre of rotation, unrestricted mandibular movements by a double articulation, correct fit to the skull by a self-adjusting skull part consisting of two connected parts, and stable fixation by bone screws that are rigidly connected to the prosthesis parts. The prosthesis consists of a titanium skull part with ceramic inlay, a titanium mandibular part with a ceramic spherical head, and an intervening polyethylene disc. Titanium-alloy bone screws are used for fixation. All parts are available in a number of different shapes. In vitro laboratory and in vivo animal tests showed a low wear rate, the possibility of a close fit to the skull, a stable fixation, sufficient mechanical strength, appropriate choice of materials and proper functioning. Thereafter the step to first patient application was made. First patient application was carried out without adverse events. In conclusion, the presented TMJ prosthesis passed the pre-clinical tests and has progressed to clinical application. The fit to the skull, the expected lifetime of the device and the reliability of the implantation procedure require further evaluation in well-designed clinical trials.

A computer study of biodegradable plates for internal fixation of mandibular angle fractures.

PURPOSE: This computer-based study was performed to determine the suitability of small biodegradable plate systems for mandibular angle fractures. MATERIALS AND METHODS: In a 3-dimensional computer model of the mandible, fracture mobility and plate strain were calculated for bite forces applied on 13 bite points on the dental arch. The angle fracture was fixed with 2 polylactide (PLA) midiplates or with 2 PLA maxiplates. The first plate was positioned buccally on the external oblique ridge. Two positions of the second plate were studied: halfway up the height of the mandible or on the lower border. Maximum fracture mobility was set at a limit of 150 microm to enable undisturbed fracture healing. Maximum plate strain was set at the yield strain of PLA. RESULTS: Fixation with the PLA maxiplates, with the second plate positioned halfway up the height of the mandible, resulted in fracture mobility below the set limit for all bite points. For the other PLA fixation strategies, fracture mobility exceeded the set limit. Fixation with the second plate positioned halfway up the height of the mandible generally resulted in less fracture mobility than with the plate positioned on the lower border. The yield strain of PLA was not exceeded in any of the fixation strategies. CONCLUSIONS: Based on the computer model, 2 PLA maxiplates are suitable for fixation of mandibular angle fractures. One plate should be positioned buccally on the external oblique ridge, and the other should be positioned halfway up the height of the mandible.

A short-term study in sheep with the Groningen temporomandibular joint prosthesis.

As part of the pre-clinical testing process of a newly developed temporomandibular joint (TMJ) prosthesis, animal experiments were performed. In 14 sheep, the right TMJ was replaced by the developed TMJ prosthesis. The prosthesis consisted of a skull part, a mandibular part and an intervening polyethylene disc. In the first series (6 sheep), three designs were tested, differing in the applied metal (stainless steel or titanium) and in the fitting method of the skull part (a fitting member or bone cement). The sheep were sacrificed after 8-16 weeks. In the second series (8 sheep), the preferred titanium fitting member design was applied, and the sheep were sacrificed after 2-10 weeks. One sheep was excluded because no correct position of the prosthesis parts could be achieved. At sacrifice, the removal torque of the screws was measured, and the surrounding tissues were harvested for histologic examination. The sheep recovered well and functioned until the end of the scheduled sacrifice date. Encountered problems were two disc dislocations, one fistula formation, and one screw failure. All mandibular parts were clinically stable, as were most skull parts with a fitting member, and one of both skull parts fitted with bone cement. The clinically observed stability was confirmed by the removal torque values, which indicated well-integrated screws. It is concluded that the TMJ prosthesis could remain stable and functional over the initial healing period. The main restriction of the sheep model is the much larger translatory capacity compared with patients, which adversely influences tissue healing.

Fitting a temporomandibular joint prosthesis to the skull.

Fitting a temporomandibular joint (TMJ) prosthesis to the skull by using stock prostheses seems to be an appropriate method. However, fitting the skull with one stock part requires many differently shaped parts. Therefore, we fitted the skull with two connected stock parts. The aim of the study was to test whether it is possible to achieve a close fit to the skull with this design, with a maximum of 10 different parts. The articular eminence was fitted with a gully-shaped fitting member, which was rotationally connected to a basic part that fitted to the lateral side of the TMJ. The relevant dimensions of 20 dry skulls were measured and the results were used to derive the optimal dimensions of the prosthesis parts. Prototypes were subsequently fabricated. The fit of the prototypes was tested by measuring the maximum gap between fitting member and skull. All skulls could be fit with a set of four different basic parts and three different fitting members. The average maximum gap between fitting member and skull was 0.20 mm (range 0.11-0.43 mm). It was concluded that a close fit to the skull can be achieved with two connected stock parts and with a total number of seven parts.

Design and wear testing of a temporomandibular joint prosthesis articulation.

As part of the development of a total temporomandibular joint prosthesis, a prosthesis articulation was designed. The articulation consists of a spherical head (ball) of the mandibular part, rotating against an enveloping ultra-high-molecular-weight polyethylene (UHMWPE) disc with a flat cranial side, which slides along the opposing skull part. The aim of this study was to determine the in vitro wear rate of the articulation, and to predict the in vivo wear rate from the results. Based on a disc thickness of 5 mm and a ball diameter of 8 mm, the stresses within the disc were calculated by means of a finite element computer model. The wear rate of the ball-disc articulation was determined by in vitro wear tests, with a stainless-steel ball rotating against a UHMWPE disc in a serum-based lubricant. Eight discs were tested for seven million cycles each. The in vitro wear rate of the disc-skull part articulation was calculated from the test results of the ball-disc articulation. The maximum Von Mises' stress was less than the yield strength of UHMWPE and, therefore, was sufficiently low. The in vitro wear rate of the ball-disc articulation was 0.47 mm3 per million cycles. The in vivo expected total wear rate is 0.65 mm3 per year, corresponding with a yearly decrease of disc thickness of 0.0094 mm. Although it is difficult to judge whether this wear rate is sufficiently low, because the influence of UHMWPE wear particles in the TMJ region is unknown, both the expected wear rate and the decrease of thickness appear to be acceptable.