Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles

Intra‐articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra‐articular injection. Eight healthy beagles with normal stifles and 22 large and giant‐breed dogs with stifle osteoarthritis (OA) were treated with a single intra‐articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra‐articular injection.     

Caudal epidural anti‐nociception using lidocaine,bupivacaine or their combination in cows undergoing reproductive procedures

ObjectiveTo evaluate the anti-nociceptive effects of lidocaine, lidocaine-bupivacaine combination or bupivacaine following caudal epidural administration in cows undergoing reproductive procedures.Study designBlinded, randomized experimental study.AnimalsThirty seven healthy Holstein cows (mean weight ± SD, 633 ± 41 kg).MethodsAnimals were allocated randomly to receive one of four treatments: group LID, 0.2 mg kg^?1 lidocaine 2%; group LID-BUP, lidocaine-bupivacaine mixture in a 1:1 volume ratio (0.1 mg kg^?1 and 0.025 mg kg^?1, respectively); group BUP-LD, 0.05 mg kg^?1 bupivacaine 0.5%; and group BUP-HD, 0.06 mg kg^?1 bupivacaine 0.5%. The onset and duration of perineal anti-nociception were determined using superficial and deep pin pricks and the number of cows with complete perineal anti-nociception was recorded. Parameters were compared using anova followed by Duncan's test where relevant.ResultsMean ± SD time to onset of anti-nociception following epidural administration of BUP-LD was significantly longer than for LID-BUP (p < 0.05). The duration (in minutes) of perineal anti-nociception was significantly longer following epidural administration of BUP-HD (247 ± 31) versus LID-BUP (181 ± 33) and LID (127 ± 25) minutes respectively. The % of cows with complete anti-nociception was increased in the group treated with BUP-HD compared to BUP-LD. Severe ataxia or recumbency did not occur in any groups.Conclusions and clinical relevanceEpidurally administered bupivacaine, at a dose of 0.06 mg kg^?1, may provide satisfactory caudal epidural anti-nociception for longer-duration obstetric and surgical procedures.     

Epidural anesthesia with bupivacaine, bupivacaine and fentanyl, or bupivacaine and sufentanil during intravenous administration of propofol for ovariohysterectomy in dogs

OBJECTIVE: To compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol. STUDY DESIGN: Prospective randomized masked clinical trial. ANIMALS: 30 female dogs of various breeds. PROCEDURES: Dogs were allocated into 3 groups of 10 each. One group received fentanyl (2 microg/kg [0.91 microg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1 group received sufentanil (1 microg/kg) and bupivacaine (1 mg/kg), and 1 group received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) and continuous infusion of propofol for sedation. The agents were administered into the lumbosacral space and diluted in saline (0.9% NaCl) solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia, sedation level, serum cortisol concentrations, and plasma catecholamine concentrations were measured regularly for 6 hours. RESULTS: No important changes in cardiovascular, respiratory, or sedation variables were observed. Degree of analgesia in the postoperative period was higher in the sufentanil group, although use of fentanyl and bupivacaine also resulted in a sufficient level of analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the 3 anesthetic techniques permitted ovariohysterectomy with sufficient analgesia and acceptable neuroendocrine modulation of pain with minimal adverse effects.     

Epidural anaesthesia using lignocaine, bupivacaine or a mixture of lignocaine and bupivacaine in dogs

The time to loss of interdigital reflex, duration of action, duration of muscle relaxation and cardiorespiratory effects were compared after epidural block using lignocaine, bupivacaine or a combination of lignocaine and bupivacaine in dogs. Dogs were pre-medicated with methotrimeprazine, anaesthesia was induced with thiopentone, in order to facilitate epidural puncture, and a lumbosacral epidural block was performed. Body temperature fell after pre-medication, thiopentone and epidural anaesthesia. Minimal changes were observed in arterial O₂ saturation, end tidal CO₂, respiratory rate, heart rate and mean arterial blood pressure. The combination of bupivacaine with lignocaine produced a shorter time to loss of interdigital reflex than bupivacaine alone, longer analgesia than lignocaine alone and longer muscle relaxation than either lignocaine or bupivacaine. The combination appeared to be the best choice when surgical time is prolonged.     

Neurotoxicity of intraneural injection of bupivacaine liposome injectable suspension versus bupivacaine hydrochloride in a porcine model

Objective

To test whether neurotoxic effects of a bupivacaine liposome injectable suspension differ from those of a standard formulation of bupivacaine hydrochloride (HCl) after intraneural injection into the sciatic nerves in pigs.

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs

Objective— To estimate maximum plasma concentration (C_max) and time to maximum plasma (t_max) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate C_max, T_max and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C_max, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean C_max (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C_max below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.     

Comparison of bupivacaine femoral and sciatic nerve block versus bupivacaine and morphine epidural for stifle surgery in dogs

ObjectiveTo evaluate the efficacy of combined femoral and sciatic nerve blocks as an alternative to epidural anesthesia and analgesia in dogs undergoing stifle surgery under general anesthesia.Study designProspective, blinded, randomized, clinical comparison.AnimalsTwenty dogs weighing 37 ± 11 (mean ± SD) kg, aged 3 (1–8) [median (minimum–maximum)] years undergoing elective unilateral tibial-plateau leveling osteotomy.MethodsDogs were assigned randomly to receive either epidural anesthesia (bupivacaine 0.5%, 0.5 mg kg^?1 + morphine 0.1%, 0.1 mg kg^?1, in 0.2 mL kg^?1; EPID) or femoral and sciatic nerve blocks (Bupivacaine 0.5%, 0.1 mL kg^?1, was administered at each site; F + S) guided by electrolocation. All patients received a standard general anesthesia technique. Pain and sedation were scored (on scales of 0–10 and 0–3, respectively) pre-operatively, at extubation, and at 1, 4 and then every 4 hours thereafter up to 24 hours. Postoperatively, hydromorphone was administered to any patient with a pain score of >5 or whenever the blinded caregiver determined that more hydromorphone was necessary. Intraoperative heart rate (HR), mean arterial pressure (MAP), end tidal isoflurane (FE′ISO), body temperature, post-operative pain scores, time to first hydromorphone dose after surgery, time to first feeding, time to first drinking, time to first urination, time to first ambulation (walk on a lead) and cumulative dose of hydromorphone were recorded.ResultsIntra-operatively, FE′ISO and MAP were significantly lower in the EPID group (p = 0.05 and p = 0.04, respectively). Postoperatively, the cumulative hydromorphone consumption (p = 0.04) and the incidence of urinary retention (p = 0.03) were higher in the EPID group.Conclusion and clinical relevance F + S is a practical alternative to EPID that produces less urine retention and reduces opioid consumption in the 24 hours after surgery. EPID might be associated with a lower isoflurane requirement and lower systemic blood pressure.     

Plasma bupivacaine concentrations following orbital injections in cats

Objective

To determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats.

Alterations in lycopene concentration and Z‐isomer content in egg yolk of hens fed all‐E‐isomer‐rich and Z‐isomer‐rich lycopene

Effects of feeding lycopene isomers to laying hens on egg qualities such as lycopene concentration and color of the yolk were investigated. Firstly, to evaluate the dietary transfer of lycopene to egg yolk, (all‐E)‐lycopene–rich diets (lycopene content, 100, 200, or 300 mg/kg diet) were fed to hens for 21 days. Lycopene in egg yolk could be detected after 4 days or more from the start of feeding, and the lycopene concentration increased according to the feed amount and period. Even though most of the dietary lycopene was the all‐E‐isomer, more than 65% of lycopene in egg yolk was present as Z‐isomers. Thus, the effect of lycopene Z‐isomer content in the diet (lycopene content, 200 mg/kg diet; lycopene Z‐isomer content, 35.1% or 61.3%) on egg qualities was investigated. As the Z‐isomer content increased, the lycopene concentration in the egg yolk increased, for example, when fed a diet rich in Z‐isomers (61.3%), the lycopene concentration in the egg yolk was approximately three times higher than when fed the (all‐E)‐lycopene–rich diet for 21 days. The results indicated that Z‐isomers of lycopene had higher bioavailability and/or higher transfer efficiency to the egg yolk than the all‐E‐isomer.     

Insulin‐independent actions of glucagon‐like peptide‐1 in wethers

Insulin‐independent actions of glucagon‐like peptide‐1 (GLP‐1) are not yet clear in ruminants. Four Suffolk mature wethers (60.0 ± 6.7 kg body weight (BW)) were intravenously infused with insulin (0.5 mU/kg BW/min; from 0 to 90 min) and GLP‐1 (0.5 μg/kg BW/min; from 60 to 150 min) with both hormones co‐administered from 60 to 90 min, in a repeated‐measure design under euglycemic clamp for 150 min, to investigate whether GLP‐1 has insulin‐independent actions. Jugular blood samples were taken at 15‐min intervals for plasma hormones and metabolites analysis. Compared to baseline concentrations (at 0 min), insulin infusion decreased (P < 0.05) plasma concentrations of glucagon, non‐esterified fatty acids (NEFA), lactate, nonessential amino acids (NEAA), branched‐chain amino acids (BCAA), total amino acids (TAA) and urea nitrogen (UN). Insulin plus GLP‐1 infusion induced a greater increase (P < 0.05) in plasma concentrations of insulin and triglyceride (TG), but decreased (P < 0.05) glucagon, total cholesterol (T‐Cho), NEAA and UN plasma concentrations. GLP‐1 infusion increased (P < 0.05) NEFA, β‐hydroxybutyrate and TG, but decreased (P < 0.05) glucagon, T‐Cho, NEAA, BCAA and UN plasma concentrations. In conclusion, GLP‐1 exerts extrapancreatic roles in ruminants not only insulin‐independent but probably, in contrast to non‐ruminants, antagonistic to insulin effects.