Pharmacokinetics of intra‐articular morphine in horses with lipopolysaccharide‐induced synovitis

ObjectiveTo describe the pharmacokinetics of intra-articularly (IA) administered morphine.Study designExperimental randomized, cross-over study.AnimalsEight adult healthy mixed breed horses aged 6.5 ± 2.3 (mean ± SD) years and weighing 535 ± 86 kg.MethodsUnilateral radiocarpal synovitis was induced by IA injection of 3 μg 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.ResultsInjection 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 relevanceIntra-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.     

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

ObjectiveTo compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis.AnimalsEight adult horses.Study designRandomized, observer blinded, double dummy trial with sequential crossover design.MethodsRadiocarpal 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 ≤ 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland–Altman method.ResultsIntra-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 relevanceAn 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.     

Analgesic and anti-hyperalgesic effects of epidural morphine in an equine LPS-induced acute synovitis model

Epidural morphine is widely used in veterinary medicine, but there is no information about the anti-hyperalgesic and anti-inflammatory effects in acute inflammatory joint disease in horses. The analgesic, anti-hyperalgesic and anti-inflammatory effects of epidural morphine (100mg/animal or 0.17±0.02mg/kg) were therefore investigated in horses with acute synovitis. In a cross-over study, synovitis was induced in the talocrural joint by intra-articular lipopolysaccharide (LPS). The effect of epidural morphine was evaluated using physiological, kinematic and behavioural variables. Ranges of motion (ROM) of the metatarsophalangeal and talocrural joints were measured, clinical lameness scores and mechanical nociceptive thresholds (MNTs) were assessed and synovial fluid inflammatory markers were measured. The injection of LPS induced transient synovitis, resulting in clinical lameness, decreased ranges of motion in the talocrural and metatarsophalangeal joints, decreased limb loading at rest and increased composite pain scores. Epidural morphine resulted in a significant improvement in clinical lameness, increased ROM and improved loading of the LPS-injected limb at rest, with no effects on synovial fluid inflammatory markers. Morphine prevented a decrease in MNT and, hence, inhibited the development of hyperalgesia close to the dorsal aspect of inflamed talocrural joints. This study showed that epidural morphine provides analgesic and anti-hyperalgesic effects in horses with acute synovitis, without exerting peripheral anti-inflammatory effects.     

Epidural administration of combinations of ropivacaine,morphine and xylazine in bitches undergoing total unilateral mastectomy: a randomized clinical trial

ObjectiveTo investigate the epidural administration of combinations of ropivacaine, morphine and xylazine in bitches undergoing unilateral mastectomy.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 22 bitches scheduled to undergo unilateral mastectomy for mammary tumor excision.MethodsDogs were anesthetized with acepromazine (0.02 mg kg^–1) and morphine (0.3 mg kg^–1) intramuscularly, propofol intravenously (IV) and isoflurane. Prior to the beginning of surgery, dogs were randomly administered one of three epidural treatments: ropivacaine (0.75 mg kg^–1) with morphine (0.1 mg kg^–1) (group RM, n = 7); ropivacaine with xylazine (0.1 mg kg^–1) (group RX, n = 8); or ropivacaine with morphine and xylazine (group RMX, n = 7). Cardiopulmonary variables and the expired concentration of isoflurane (Fe′Iso) were recorded intraoperatively. Meloxicam (0.1 mg kg^–1) was administered IV during skin closure. Postoperative pain scores were evaluated with the Glasgow composite measure pain scale short form for 24 hours, and rescue analgesia with morphine (0.5 mg kg^–1) was administered intramuscularly when pain scores were ≥ 6/24.ResultsFe′Iso was significantly higher in group RM than in groups RX and RMX. Heart rate decreased significantly in groups RX and RMX, but blood pressure remained within acceptable values. The number of dogs administered rescue analgesia within 24 hours was significantly higher in group RX (seven dogs, 87.5%) than in groups RM (one dog, 14.3%; p = 0.01) and RMX (two dogs, 28.6%; p = 0.04). Time to standing was significantly longer in group RX than in group RM.Conclusions and clinical relevanceAll epidural treatments provided adequate antinociception with minimal cardiovascular adverse effects during mastectomy. The inclusion of morphine (groups RM and RMX) provided the best postoperative analgesia. Owing to the undesirable effect of xylazine on ambulation, the combination ropivacaine–morphine appeared to provide greater benefits in bitches undergoing unilateral mastectomy.     

Bone gentamicin concentration after intra-articular injection or regional intravenous perfusion in the horse

Objective— To compare intra-articular (IA) and bone gentamicin concentrations achieved after intra-articular administration or regional intravenous perfusion (RIP).
Study Design— Experimental study.
Animals— Twelve healthy adult horses.
Methods— Horses were assigned to 2 treatment groups (  n = 6/group  ): Group 1, 1 g gentamicin administered simultaneously in both left and right metacarpophalangeal joints and group 2, 1 g gentamicin administered simultaneously in both left and right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were collected. Gentamicin concentrations were determined by fluorescence polarization immunoassay. Bone, synovial fluid, and serum gentamicin concentrations were compared over time and between groups using 2-way ANOVA. Significance of all tests were evaluated at   P < .05  .
Results— IA metacarpophalangeal joint administration resulted in higher concentration of gentamicin in synovial fluid than RIP administration. Synovial fluid concentration remained above minimum inhibitory concentration (MIC) for common pathogens for over 24 hours with IA and RIP administration. Bone gentamicin concentration remained above MIC for 8 hours with both methods; there was no significant difference in gentamicin concentration in bone with either method. Neither IA nor RIP administration had a significant effect on serum concentration of gentamicin.
Conclusions— In normal horses, there is no difference in bone gentamicin concentration obtained with IA or RIP administration.
Clinical Relevance— Based on MIC for common equine pathogens, administration of gentamicin intra-articularly or by regional intravenous perfusion should be useful for treatment of osteomyelitis.     

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 E₂, 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 E₂ 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.     

Sequential Plasma Lactate Concentrations as Prognostic Indicators in Adult Equine Emergencies

Background: Sequential lactate concentration ([LAC]) measurements have prognostic value in that hospitalized humans and neonatal foals that have a delayed return to normolactatemia have greater morbidity and case fatality rate.
Hypothesis: Prognosis for survival is decreased in horses with a delayed return to normal [LAC].
Animals: Two hundred and fifty adult horses presented for emergency evaluation excepting horses evaluated because of only ophthalmologic conditions, superficial wounds, and septic synovitis without systemic involvement.
Methods: Prospective observational study. [LAC] was measured at admission and then at 6, 12, 24, 48, and 72 hours after admission. The change in [LAC] over time ([LAC]Δ T ) was calculated from changes in [LAC] between sampling points.
Results: Median [LAC] was significantly ( P < .001) higher at admission in nonsurvivors (4.10 mmol/L [range, 0.60–18.20 mmol/L]) when compared with survivors (1.30 mmol/L [range, 0.30–13.90 mmol/L]) and this difference remained at all subsequent time points. The odds ratio for nonsurvival increased from 1.29 (95% confidence interval 1.17–1.43) at admission to 49.90 (6.47–384) at 72 hours after admission for every 1 mmol/L increase in [LAC]. [LAC]Δ T was initially positive in all horses but became negative and significantly lower in nonsurvivors for the time periods between 24–72 hours (− 0.47, P = .001) and 48–72 hours (− 0.07, P = .032) when compared with survivors (0.00 at both time periods) consistent with lactate accumulation in nonsurvivors.
Conclusions and Clinical Importance: These results indicate that lactate metabolism is impaired in critically ill horses and [LAC]Δ T can be a useful prognostic indicator in horses.     

Evaluation of Continuous Infusion of Lidocaine on Gastrointestinal Tract Function in Normal Horses

Objective— To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses.
Study Design— Experimental randomized cross-over study.
Animals— Healthy horses (n=6).
Methods— Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (number of microspheres observed on radiographs), fecal moisture content, borborygmus score, heart and respiratory rate, and signs of lidocaine toxicity (e.g., ataxia, CNS depression).
Results— During the first 24 hours of lidocaine administration, mean (±SD) fecal output (10.8±6.9 kg) was decreased compared with controls (15±4.9 kg). Mean (±SEM) time for passing 50% of the barium-filled microspheres was shorter in controls (42±1.13 hours) compared with the lidocaine group (50±1.32 hours).
Conclusions— Continuous infusion of lidocaine increases the transit time of feces in normal horses.
Clinical Relevance— Clinicians need to be aware of the effects of using a continuous infusion of lidocaine on the transit time of feces in normal horses, with a potential for exacerbating those effects when combined with drugs that decrease motility and in horses with medical colic (e.g., impaction) or where a diagnosis has not been made.     

Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs

Objective  To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Six adult mixed-breed male dogs weighing 12.0 ± 4.3 kg.
Methods  Dogs received intravenous administration (IV) of acepromazine (0.05 mg kg⁻¹) and 15 minutes later, one of four opioids was randomly administered IV in a cross-over design, with at least 1-week intervals. Dogs then received MOR 0.5 mg kg⁻¹; MET 0.5 mg kg⁻¹; BUT 0.15 mg kg⁻¹; or TRA 2.0 mg kg⁻¹. Indirect systolic arterial pressure (SAP), heart rate (HR), respiratory rate ( f _R), rectal temperature, pedal withdrawal reflex and sedation were evaluated at regular intervals for 90 minutes.
Results  Acepromazine administration decreased SAP, HR and temperature and produced mild sedation. All opioids further decreased temperature and MOR, BUT and TRA were associated with further decreases in HR. Tramadol decreased SAP whereas BUT decreased f _R compared with values before opioid administration. Retching was observed in five of six dogs and vomiting occurred in one dog in MOR, but not in any dog in the remaining treatments. Sedation scores were greater in MET followed by MOR and BUT. Tramadol was associated with minor changes in sedation produced by acepromazine alone.
Conclusions and clinical relevance  When used with acepromazine, MET appears to provide better sedation than MOR, BUT and TRA. If vomiting is to be avoided, MET, BUT and TRA may be better options than MOR.     

Efficacy of an Epidural Combination of Morphine and Detomidine in Alleviating Experimentally Induced Hindlimb Lameness in Horses

Amphotericin B-induced synovitis of the left tarsocrural joint was used to create a grade 3 of 4 lameness in 11 horses. Caudal epidural catheters were placed and advanced to the lumbosacral region. Baseline heart and respiratory rates were recorded and horses were videotaped at a walk and trot. Morphine sulphate (0.2 mg/kg) and detomidine hydrochloride (30 μg/kg) were administered to treated horses (n = 8) through the epidural catheter; an equivalent volume of physiologic saline solution was administered to control horses (n = 3) through the catheter. At hourly intervals after epidural injection for a total of 6 hours, heart and respiratory rates were recorded, and horses were videotaped walking and trotting. At the end of the observation period, video recordings were scrambled onto a master videotape. Lamenesses were scored by three investigators unaware of group assignment or treatment time. Lameness scores, heart rates, and respiratory rates were compared between groups using repeated measures analysis of variance. There was a significant decrease in lameness score after treatment with epidural morphine and detomidine ( P =.0003); average lameness scores of treated horses were less than grade 1 at each hourly observation for 6 hours after drug administration. Early in the observation period, heart rates significantly increased in control horses and decreased in treated horses ( P =.03). A similar trend occurred for respiratory rates ( P =.07). Results of this study demonstrate that epidural administration of a combination of morphine and detomidine is capable of providing profound hindlimb analgesia in horses.     

Fluticasone Propionate Aerosol is More Effective for Prevention than Treatment of Recurrent Airway Obstruction

Background: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment.
Objectives: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations.
Animals: Nine RAO affected horses.
Methods: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (ΔPpl_max), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness.
Results: In treatment trial, DEX and FP (6 mg) significantly decreased ΔPpl_max by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in ΔPpl_max that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis.
Conclusions and Clinical Importance: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.     

Pharmacokinetics and protein binding of morphine in horses

Morphine could be detected in horses dosed with 0.1 mg of drug/kg of body weight for up to 48 hours in blood and 144 hours in urine. This dose of morphine elicited no observable effects and is a suggested analgesic dose. Computer analysis revealed that a 3-compartment open system was the best fitting model with a serum half life (t1/2(beta)) of 87.9 minutes and a urine t1/2(beta) of 101.1 minutes. Binding to equine serum proteins was linear over a drug concentration range of 3.88 X 10(-5)M to 3.50 X 10(-8)M and averaged 31.6%. In RBC-partitioning experiments, 78.1% of the drug was found in the plasma fraction. The data indicated that a horse should not be given morphine closer than 1 week before a race.     

Effects of intramuscular administration of acepromazine on palmar digital blood flow, palmar digital arterial pressure, transverse facial arterial pressure, and packed cell volume in clinically healthy, conscious horses

Objective— To determine the magnitude and duration of effects of acepromazine administered intramuscularly (IM) on digital and systemic hemodynamic variables in clinically healthy horses.
Study Design— Experimental study.
Animals— Healthy adult horses (n=12).
Methods— An ultrasonic Doppler flow probe was surgically implanted around the medial palmar digital artery before the study. Catheters were inserted in the transverse facial artery, lateral palmar digital artery, and jugular vein. A treatment group (n=6) was administered 0.04 mg/kg body weight of acepromazine IM; control horses (n=6) were administered an equivalent volume of saline IM. Palmar digital blood flow, and digital and facial arterial pressures were measured at baseline and for 6 hours after administration. Venous blood was collected for measurement of packed cell volume (PCV).
Results— Horses administered acepromazine had significantly lower facial arterial pressure compared with control horses administered saline. Palmar digital arterial blood flow in acepromazine-treated horses was not significantly different from that in control horses but increased significantly post-administration, compared with the respective baseline values for acepromazine-treated horses. PCV significantly decreased in horses administered acepromazine compared with their respective baseline value.
Conclusion— IM acepromazine causes hypotension and increases palmar digital blood flow over time but the magnitude of the effect on digital blood flow was not sufficient to yield differences compared with saline-treated horses.
Clinical Relevance— IM acepromazine has a modest effect on palmar digital blood flow, facial arterial pressures and PCV in healthy horses with minimal sedation.     

Prevalence of and Risk Factors for Postoperative Ileus after Small Intestinal Surgery in Two Hundred and Thirty-Three Horses

Objectives— To determine the incidence of postoperative ileus (POI) in a population of horses after small intestinal surgery and the effect of multiple variables on development of POI.
Study Design— Case series.
Animals— Horses (n=233) aged ≥1 year that had exploratory celiotomy for small intestinal disease that recovered from surgery from 1995 to 2005.
Methods— Sixty-eight variables were collected from medical records (1995–2005) for each horse. POI was defined as nasogastric reflux volume >20 L over 24 hours or >8 L at any single time after surgery.
Results— Twenty-seven percent (64/233) of horses developed POI; 29 of 64 (46%) horses with POI had duodenitis proximal jejunitis (DPJ). When no intestinal resection was required at surgery, excluding horses with DPJ, 15% of horses had POI; 30% horses had POI after intestinal resection. Ten percent of horses had POI for >24 hours. When horses with DPJ were excluded, factors associated with increased risk of POI included high packed cell volume at hospital admission ( P =.024), increasing age ( P =.0004), and length of intestinal resection ( P =.05).
Conclusions— Risk factors for POI in this study were nonspecific although horses with intestinal resection are at higher risk compared with horses without intestinal resection.
Clinical Relevance— Predicting with certainty which cases will develop POI remains elusive.     

Use of force plate analysis to assess the analgesic effects of etodolac in horses with navicular syndrome

OBJECTIVE: To evaluate the musculoskeletal analgesic effect of etodolac administered PO every 12 or 24 hours in chronically lame horses by use of force plate analysis. ANIMALS: 22 horses with navicular syndrome. PROCEDURE: Horses received etodolac (23 mg/kg, PO, q 12 h; n = 7), etodolac (23 mg/kg, PO, q 24 h; 8), or corn syrup (20 mL, PO, q 24 h; control treatment; 7) for 3 days. Combined forelimb peak vertical ground reaction force (PVF) was measured via force plate analysis before the first treatment (baseline) and at 6, 12, 24, and 36 hours after the last treatment. Differences in mean PVF (mPVF) between baseline and subsequent measurements were analyzed (repeated-measures ANOVA) and evaluated for treatment and time effects and treatment-time interaction. RESULTS: Once- or twice-daily administration of etodolac resulted in significant increases in mPVF from baseline at 6, 12, and 24 hours after the last treatment, compared with the control treatment. There were no significant differences in mPVF between the etodolac treatment groups at any time point. In both etodolac treatment groups, there was a significant increase in mPVF from baseline at 6, 12, and 24 hours, compared with that at 36 hours. Etodolac-associated adverse effects were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome, once-daily oral administration of 23 mg of etodolac/kg appears to provide effective analgesia for as long as 24 hours. Twice-daily administration of etodolac at this same dose does not appear to provide any additional analgesic efficacy or duration of effect.     

Use of force plate analysis to compare the analgesic effects of intravenous administration of phenylbutazone and flunixin meglumine in horses with navicular syndrome

OBJECTIVE: To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered i.v. at typical clinical doses in horses with navicular syndrome. ANIMALS: 12 horses with navicular syndrome that were otherwise clinically normal. PROCEDURE: Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCI; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. RESULTS: At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome.     

Blood glucose concentrations in critically ill neonatal foals

Reasons for Performing Study: Critical illness is associated with hyperglycemia in humans, and a greater degree and duration of hyperglycemia is associated with nonsurvival. Hypoglycemia is also seen in critically ill humans, and is associated with nonsurvival. This might also be true in the critically ill foal.
Objectives: To investigate the association of blood glucose concentrations with survival, sepsis, and the systemic inflammatory response syndrome (SIRS).
Methods: Blood glucose concentrations at admission (515 foals) and 24 hours (159 foals), 36 hours (95), 48 hours (82), and 60 hours (45) after admission were analyzed. Logistic regression analyses were performed to investigate the association of glucose concentrations with survival, sepsis, a positive blood culture, or SIRS.
Results: 29.1% of foals had blood glucose concentrations within the reference range (76–131 mg/dL) at admission, 36.5% were hyperglycemic, and 34.4% were hypoglycaemic. Foals that did not survive to hospital discharge had lower mean blood glucose concentrations at admission, as well as higher maximum and lower minimum blood glucose concentrations in the 1st 24 hours of hospitalization, and higher blood glucose at 24 and 36 hours. Foals with blood glucose concentrations <2.8 mmol/L (50 mg/dL) or >10 mmol/L (180 mg/dL) at admission were less likely to survive. Hypoglycemia at admission was associated with sepsis, a positive blood culture, and SIRS.
Conclusions and Potential Relevance: Derangements of blood glucose concentration are common in critically ill foals. Controlling blood glucose concentrations may therefore be beneficial in the critically ill neonatal foal, and this warrants further investigation.     

Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses

OBJECTIVE: To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses. ANIMALS: 5 horses. PROCEDURES: Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radiographic detection in feces), fecal moisture content, borborygmus score, and signs of CNS excitement and colic. RESULTS: Administration of morphine resulted in gastrointestinal tract dysfunction for 6 hours after each injection. During those 6 hours, mean +/- SD defecation frequency decreased from 3.1 +/- 1 bowel movements in control horses to 0.9 +/- 0.5 bowel movements in treated horses, weight of feces decreased from 4.1 +/- 0.7 kg to 1.1 +/- 0.7 kg, fecal moisture content decreased from 76 +/- 2.7% to 73.5 +/- 2.9%, and borborygmus score decreased from 13.2 +/- 2.9 to 6.3 +/- 3.9. Mean gastrointestinal transit time was also increased, compared with transit times in control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered at 0.5 mg/kg twice daily decreased propulsive motility and moisture content in the gastrointestinal tract lumen. These effects may predispose treated horses to development of ileus and constipation.     

Analgesic and motor-blocking action of epidurally administered levobupivacaine or bupivacaine in the conscious dog

Objective  To compare the analgesic and motor-blocking effects of epidurally administered levobupivacaine and bupivacaine in the conscious dog.
Study design  Prospective, randomized, cross-over study.
Animals  Six adult female Beagle dogs.
Methods  Each animal received three doses of levobupivacaine or bupivacaine (0.5, 1.0 and 1.5 mg kg⁻¹; concentrations 0.25%, 0.50%, and 0.75%, respectively) in a total volume of 0.2 mL kg⁻¹ by means of a chronically implanted epidural catheter. Onset, duration (through pinch response in the sacral, lumbar and toe areas) and degree of analgesia and motor-blocking status was determined with a scoring system and at regular intervals over 8.5 hours before (baseline) and after drug administration.
Results  Epidurally administered levobupivacaine and bupivacaine had a similar dose-dependent analgesic action with no significant differences in onset (range: 5–8 minutes), duration (bupivacaine: 42 ± 28, 135 ± 68 and 265 ± 68 minutes, and levobupivacaine: 28 ± 33, 79 ± 55 and 292 ± 133 minutes; 0.25%, 0.50%, and 0.75%, respectively) or maximum degree of analgesia. However, levobupivacaine tended to produce a shorter duration of motor block than bupivacaine and the difference in the motor to nociceptive blockade times was significant at the highest dose.
Conclusion  Epidural levobupivacaine produced an analgesic action similar to that of bupivacaine.
Clinical relevance  Epidural levobupivacaine is suitable for clinical use in dogs, mostly at the highest dose if a high degree of analgesia is required.     

Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses

OBJECTIVE: To evaluate and compare effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H on avoidance threshold to noxious electrical stimulation over the dermatomes of the perineal, sacral, lumbar, and thoracic regions in horses. ANIMALS: 5 healthy adult horses. PROCEDURE: Using a Latin square complete repeated-measures design, horses were randomly assigned to receive 1 of 6 treatments (morphine, alfentanil, butorphanol, tramadol, U50488H, or sterile water) at intervals of at least 7 days. Agents were injected epidurally at the first intercoccygeal epidural space, and electrical stimulation was applied at repeated intervals for 24 hours to the dermatomes of the perineal, sacral, lumbar, and thoracic regions. Avoidance threshold to electrical stimulation was recorded. RESULTS: Administration of butorphanol, U50488H, and sterile water did not induce change in avoidance threshold. Alfentanil increased avoidance threshold during the first 4 hours, but not significantly. Tramadol and morphine significantly increased threshold and analgesic effects. Complete analgesia (avoidance threshold, >40 V) in the perineal and sacral areas was achieved 30 minutes after tramadol injection, compared with 6 hours after morphine injection. Duration of complete analgesia was 4 hours and 5 hours after tramadol and morphine injections, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of tramadol and morphine induces long-lasting analgesia in healthy adult horses. Epidural administration of opioids may provide long-lasting analgesia in horses without excitation of the CNS.