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Research suggests biological sex differences may affect pain perception, however the difference in analgesic tolerance between male and females not been extensively studied. Therefore, here we studied the response of male and female Sprague-Dawley rats to prolonged duration local anesthetics; including conventional amino-amide anesthetics (bupivacaine), site 1 sodium channel blockers (tetrodotoxin) and a prolonged duration liposomal formulation (Exparel). This study examined the incidence and duration of sensory and motor blockade; systemic side effects, as well as local neurotoxicity and myotoxicity in both male and female rodents in an in vivo model of sciatic nerve blockade. The data collected does not indicate a sexual dimorphism among the agents studied. / 2019-07-03T00:00:00Z

Intra-articular bupivacaine is a common analgesic used in dogs with orthopedic disease. Bupivacaine has been linked to chondrotoxicity. The mechanism for bupivacaine's chondrotoxicity is unknown, but may involve inflammation. Prostaglandin E2 (PGE2) is an inflammatory mediator and a marker of joint inflammation. The aim of this study was to compare synovial fluid PGE2 concentrations after a single intra-articular injection of bupivacaine with a saline control in normal canine stifles. We hypothesized that bupivacaine stifles would have a significantly elevated PGE2 concentration compared to controls. Stifles from eight healthy, adult Beagles were randomly selected as the treated stifle and infused with bupivacaine. The contralateral stifle was injected with saline. Synovial fluid was collected before and after injection. PGE2 was quantified using a commercial ELISA. Data were transformed and mixed model ANOVA was performed with significance set at p<0.05. There were no significant differences in PGE2 concentration between treatment groups or times. Samples acquired with one or two aspiration attempts had significantly lower PGE2 concentrations than samples with =3 aspiration attempts (p=0.001). When adjusted for number of attempts, PGE2 concentrations were significantly higher 24 (p=0.003) and 48 (p=0.041) hours after injection compared to baseline in the bupivacaine group, but not in the saline group. Intra-articular bupivacaine injection did not result in increased synovial fluid PGE2 concentrations compared to controls; however, multiple aspiration attempts did, suggesting that synovial fluid PGE2 concentration is sensitive to multiple fluid collection attempts. Future studies investigating synovial fluid inflammatory mediators should consider methods to minimize aspiration attempts. / M. S. / Intra-articular bupivacaine is a popular pain relief medication commonly used in joint surgery. Despite its historically wide use, bupivacaine has been scrutinized due to its potentially toxic effects on joint cartilage. Currently, the mechanism of this toxicity has not been identified, though it may be associated with inflammation. Prostaglandin E₂ (PGE₂) is considered an indicator of joint inflammation. The purpose of this study was to quantify the concentration of PGE₂ within the joint fluid following a single injection of bupivacaine in normal canine stifles as compared to a saline control. Eight healthy, adult Beagles were used for this study. Stifles were randomized into treatment (bupivacaine) or control (saline) groups such that each dog had one stifle infused with bupivacaine and the opposite stifle with saline. Joint fluid was collected at the following time points: before injection (T0), 30 minutes, 60 minutes, 24 hours and 48 hours. Samples were analyzed in duplicate for PGE₂ concentration. There was no significant effect of treatment group (bupivacaine vs. saline) or time on joint fluid PGE₂ concentration. The number of sampling attempts did have an effect. Samples acquired with only one or two attempts had significantly lower PGE₂ concentrations than samples that required 3 or more sampling attempts. When adjusted for number of attempts, PGE₂ concentrations were significantly higher 24 and 48 hours after injection compared to baseline within the bupivacaine group, but not the saline group. Intra-articular bupivacaine injection did not result in increased joint fluid PGE₂ concentration compared to saline control. The data indicates that joint fluid PGE₂ concentration is highly sensitive to fluid collection attempts.

The effect of inducing agents of cytochrome P-450 on the binding and metabolism of three local anaesthetic agents: lidocaine, mepivacaine and bupivacaine has been investigated. All three local anaesthetic agents bound to the type I binding site of cytochrome P-450, which is characteristic of substrate binding to cytochrome P-450, and stimulated the CO-inhibitable oxidation of NADPH. Lidocaine is shown to be metabolized by cytochrome P-450 to the products MEGX and acetaldehyde. The forms of cytochrome P-450 elevated with phenobarbital and/or pregnenolone-16α-carbonitrile were shown to play an important role in the binding of lidocaine to cytochrome P-450. Cytochrome P-448 did not appear to be involved in the binding of lidocaine to cytochrome P-450. These findings are supported by the ability of the inhibitors of cytochrome P-450 viz. metyrapone, SKF 525-A and CO:O₂ to inhibit binding of lidocaine to cytochrome P-450. No single form of cytochrome P-450 appears to preferentially metabolize lidocaine, but rather multiple forms of the enzyme appear to be involved in the metabolism of lidocaine. The phenobarbital inducible form of cytochrome P-450 appears to play a major role in the binding of mepivacaine to cytochrome P-450. Cytochrome P-450 in microsomes from rats pretreated with β-naphthoflavone and pregnenolone-16α-carbonitrile does not appear to have a significant role in the binding of mepivacaine to cytochrome P-450. All forms of cytochrome P-450 are involved in the metabolism of mepivacaine· to metabolic products as assessed by the oxidation of NADPH. However, the form of cytochrome P-450 induced by pretreatment of rats with phenobarbital may play a predominant role in the total metabolism of mepivacaine. Multiple forms of cytochrome P-450 appear to be involved in the binding and total metabolism of bupivacaine. As in the case of mepivacaine, the total metabolism of bupivacaine, as assessed by the oxidation of NADPH, may be predominantly catalyzed by the form of cytochrome P-450 found in microsomes from rats pretreated with phenobarbital. Partially purified cytochrome P-450 was found to bind lidocaine in a type I manner and, in the presence of the artificial electron donor H₂O₂, produce MEGX. This further supports the role of cytochrome P-450 in the in vitro metabolism of lidocaine. Hepatocytes were found to metabolize lidocaine to MEGX, indicating that lidocaine metabolism in vivo might well be mediated by cytochrome P-450.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Epidurals used for labor are common regional anesthesia techniques that are easily placed and controlled, while providing the most reliable method of pain relief in obstetrics for parturient women. Local anesthetics, narcotics, and/or combinations of the two are administered through epidurals to treat labor pain. Hence, the choice of medication is important, as it can highly influence outcomes of pain relief. The purpose of this DNP project was to evaluate the effectiveness of a new service line medication, bupivacaine 0.1% with fentanyl 2mcg/ml, to treat labor pain in parturient women at a rural community hospital in southern California guided by the Johns Hopkins Nursing Evidence Based Practice Model. A quantitative, time-series, retrospective, and prospective design was used to analyze data from a convenience sampling of participants who received ropivacaine and bupivacaine with fentanyl. Paired samples t-tests compared differences in verbal pain scores before and after epidural insertion with initial boluses alongside frequencies of top-off boluses required to achieve adequate pain relief. Findings showed that both medications were equally effective in the treatment of labor pain within the first hour after the intervention. However, the ropivacaine group had higher rebolus demands, while the bupivacaine with fentanyl group had only a minimal amount. The complexity of healthcare today demands inter and intraprofessional collaboration to improve and sustain best outcomes for high quality care. The bupivacaine with fentanyl project impacts social change by improving the quality of care for parturient women, addressing the fear and anxiety of childbirth pain, and highlighting the importance of collaboration with other clinical providers to change practice using the evidence.

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