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BMC Anesthesiology Jul 2021Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However,...
BACKGROUND
Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However, pharmacokinetic (PK) parameters and safety of LB in the Chinese population have not been assessed.
METHODS
In this single-arm, single center, phase 1, open-label study, PK and safety of local infiltration with LB 266 mg were assessed in healthy Chinese adults. Eligible participants were aged 18 to 55 years with biologic parents and grandparents of Chinese ethnicity, in generally good health (i.e., no clinically significant abnormalities), and with a body mass index (BMI) 19.0 to 24.0 kg/m (inclusive) and body weight ≥ 50 kg.
RESULTS
Participants (N = 20) were predominantly men (80 %); mean age was 32 years; and mean BMI was 21.8 kg/m. After LB administration, mean plasma levels of bupivacaine rapidly increased during the first hour and continued to increase through 24 h; plasma levels then gradually decreased through 108 h followed by a monoexponential decrease through 312 h. Geometric mean maximum plasma concentration was 170.9 ng/mL; the highest plasma bupivacaine concentration detected in any participant was 374.0 ng/mL. Twenty-two treatment-emergent adverse events were reported (mild, n = 21; moderate, n = 1).
CONCLUSIONS
After single-dose administration of LB, PK measures were similar to a previously reported profile in US adults. The highest observed peak plasma concentration of bupivacaine was several-fold below the plasma concentration threshold accepted as being associated with neurotoxicity or cardiotoxicity (2000-4000 ng/mL). These data support that LB is well tolerated and safe in individuals of Chinese descent.
TRIAL REGISTRATION
NCT04158102 (ClinicalTrials.gov identifier), Date of registration: November 5, 2019.
Topics: Adult; Anesthetics, Local; Asian People; Bupivacaine; Female; Humans; Liposomes; Male; Young Adult
PubMed: 34315419
DOI: 10.1186/s12871-021-01407-5 -
Anaesthesia Apr 2001Regional anaesthesia has seen the development of a new local anaesthetic: levobupivacaine. This review aims to outline the rationale underlying the development of... (Review)
Review
Regional anaesthesia has seen the development of a new local anaesthetic: levobupivacaine. This review aims to outline the rationale underlying the development of levobupivacaine and to consider its place in modern regional anaesthesia.
Topics: Anesthesia, Conduction; Anesthetics, Local; Animals; Bupivacaine; Humans; Stereoisomerism
PubMed: 11284819
DOI: 10.1046/j.1365-2044.2001.01964.x -
Minerva Anestesiologica Jun 2005Regional anesthesia has become a routine practice in paediatric anesthesia and local anaesthetics are now widely used in infants and children. Although local... (Review)
Review
Regional anesthesia has become a routine practice in paediatric anesthesia and local anaesthetics are now widely used in infants and children. Although local anaesthetics are generally quite safe and effective, they may produce systemic toxic reactions affecting the heart and brain. Because postoperative analgesia is often the primary justification for regional anesthesia in infants and children, bupivacaine, a long-acting local anaesthetic, is the most commonly used local anaesthetic for paediatric regional anesthesia. Levobupiva-caine has been used in children by caudal injection, by lumbar epidural route for anesthesia during operation, by continuous epidural infusion for pain control after operation and for spinal anesthesia. Levobupivacaine had shown comparable clinical profiles to that of bupivacaine but produced lower incidence of residual motor blockade. Efforts to minimize the risk of complications during caudal anesthesia must be directed towards measures that reduce accidental intravenous and intraosseous injections, reduce the total amount of local anaesthetic used and use drugs with lower toxic potential. In patients under general anesthesia, when using a large amount of local anaesthetic, in case of accidental intravenous infusion, patients receiving levobupivacaine may tolerate larger doses before manifestation of toxicity compared with those receiving bupivacaine. There are clinical situations including prolonged local anaesthetic infusions, use in neonates or small babies, and caudal block, where replacement of bupivacaine with levobupivacaine appears to be safer.
Topics: Anesthesia, Caudal; Anesthesia, Epidural; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Child; Humans; Levobupivacaine; Nerve Block
PubMed: 15886598
DOI: No ID Found -
Anaesthesia Jan 1998We studied the influence of the timing of injection of bupivacaine into the vas deferens on the intensity and duration of scrotal pain following vasectomy. Forty-two... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
We studied the influence of the timing of injection of bupivacaine into the vas deferens on the intensity and duration of scrotal pain following vasectomy. Forty-two patients undergoing vasectomy under general anaesthesia were randomly allocated to have the operation performed on either the left or the right side first. On the first side to be operated upon, 5 ml bupivacaine 0.5% was infiltrated along the line of the scrotal incision. The vas deferens was identified and 1 ml bupivacaine 0.5% was injected into its lumen, with 0.5 ml directed proximally and 0.5 ml directed distally. After completion of the procedure on that side, the operation continued on the other side. On this occasion, the same dose of bupivacaine was injected into the vas deferens after division and ligation, and subcutaneously along the scrotal incision after skin closure. Median [interquartile range] visual analogue pain scores on the first side to be operated upon were significantly lower than on the second side on day 1 (7 [1.5-19] vs. 11 [2.5-47]) (p < 0.01) and day 7 (0 [0-8.5] vs. 0 [0-18.8]) (p < 0.05) postoperatively. The median [interquartile range] duration of postoperative discomfort was less on the first side operated upon than on the second (3 [1-7] vs. 6 [2-7]) (p < 0.01). Although statistically significant differences occurred between the treatment groups, the actual differences were small and may not be clinically significant.
Topics: Adult; Anesthesia, General; Anesthetics, Local; Bupivacaine; Drug Administration Schedule; Follow-Up Studies; Humans; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Vasectomy
PubMed: 9505749
DOI: 10.1111/j.1365-2044.1998.00239.x -
Iranian Journal of Medical Sciences Jul 2023Several adjuvants, added to local anesthetics, were suggested to induce an ideal regional block with high-quality analgesia. The purpose of this study was to evaluate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Several adjuvants, added to local anesthetics, were suggested to induce an ideal regional block with high-quality analgesia. The purpose of this study was to evaluate the particular blocking properties of low-dose bupivacaine in combination with meperidine and fentanyl in spinal anesthesia during Cesarean sections.
METHODS
A randomized, double-blind clinical trial was conducted at Hafez Hospital affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from February 2015 to February 2016. A total of 120 pregnant women, who underwent spinal anesthesia during elective Cesarean section were enrolled in the study. Based on block-wise randomization, the patients were randomly assigned to three groups, namely "B" group received 2 mL bupivacaine 0.5% (10 mg), "BM" group received 8 mg bupivacaine and 10 mg meperidine, and "BF" group received 8 mg bupivacaine and 15 µg fentanyl intrathecally. The block onset, the duration of analgesia, and the time of discharge from the post-anesthesia care unit (PACU) were all assessed. Data were analyzed using SPSS software version 21, and P<0.05 were considered statistically significant.
RESULTS
The mean duration of motor blocks in the B group (150 min) were significantly higher than the BM (102 min) and BF (105 min) groups (P<0.0001). In both the BM and BF groups, the duration of sensory and motor blocks was the same. The length of stay in the PACU was significantly longer in the B group (P<0.001) than the BM and BF groups. When meperidine or fentanyl was added to bupivacaine, the duration of the analgesia lengthened (P<0.001).
CONCLUSION
Intrathecal low-dose spinal anesthesia induced by bupivacaine (8 mg) in combination with meperidine and/or fentanyl for Cesarean section increased maternal hemodynamic stability, while ensuring effective anesthetic conditions, extending effective analgesia, and reducing the length of stay in PACU. IRCT2015013119470N14.
Topics: Humans; Female; Pregnancy; Bupivacaine; Cesarean Section; Fentanyl; Anesthesia, Spinal; Analgesia; Meperidine
PubMed: 37456203
DOI: 10.30476/IJMS.2022.95205.2653 -
Brazilian Journal of Anesthesiology... 2013In our study we aimed to investigate the effect of bupivacaine and levobupivacaine on QT, corrected QT (QTc), and P wave dispersion durations during spinal anesthesia in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
In our study we aimed to investigate the effect of bupivacaine and levobupivacaine on QT, corrected QT (QTc), and P wave dispersion durations during spinal anesthesia in cesarean section.
METHODS
Sixty parturients scheduled for elective cesarean section in ASA I-II risk groups were included in the study. Baseline electrocardiographic (ECG) records of the patients were obtained in the operation room. Heart rate (HR), non-invasive blood pressure (NIBP), peripheral oxygen saturation (SpO2) and respiration rates (RR) were recorded. Venous cannulation was performed with 18G cannula and fluid preload made with 10 mL.kg(-1). Lactated Ringer solution. After fluid preload, second ECG recordings were taken and the patients were randomly separated into two groups. Group B (n = 30) received 10mg of bupivacaine and Group L (n = 30) received 10mg of levobupivacaine for spinal anesthesia. ECG recordings were repeated at 1, 5 and 10 minutes after spinal block. HR, NIBP, SpO2, RR and sensory block levels were also recorded at the same time intervals. At predetermined time intervals of spinal anesthesia, P wave dispersion (Pwd), QT dispersion (QTd), and QTc dispersion (QTcd) durations were measured from ECG records. QT and QTc durations are calculated with Bazzett formula.
RESULTS
There was no difference between two groups according to block levels, hemodynamic parameters, Pwd, QTd, QTc and QTcd durations.
CONCLUSION
Bupivacaine and levobupivacaine may be preferred in spinal anesthesia in pregnant patients who have extended Pwd and QTcd preoperatively.
Topics: Adult; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Cesarean Section; Electrocardiography; Female; Humans; Levobupivacaine; Middle Aged; Pregnancy; Young Adult
PubMed: 24565127
DOI: 10.1016/j.bjane.2012.04.005 -
Brazilian Journal of Anesthesiology... 2018A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study...
BACKGROUND
A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study was to investigate the chondrotoxic and apoptotic effects of single-dose intra-articular injection of levobupivacaine and bupivacaine on rabbit knee joint tissues.
MATERIALS AND METHODS
The animals were allocated into two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5% bupivacaine (Group B) were applied intra-articularly to the left posterior joints of rabbits. At the same time, normal saline was applied to the right posterior leg knee joints of rabbits in both groups and used as a control (Group S). At the end of the 7th and 28th days after the intraarticular injections, ten randomly chosen rabbits in each group were killed by applying intraperitoneal thiopental. Sections of cartilage tissue samples were stained for light microscopic examinations and the TUNEL method was used to investigate apoptotic cells.
RESULTS
As a result of immunofluorescence microscopic examination, the number of apoptotic cells in Group B at day 7 and day 28 were both significantly higher than Group L and S ( < 0.05). Also, the number of apoptotic cells in Group L at day 7 and day 28 were both significantly higher than Group S ( < 0.05).
CONCLUSIONS
We found that bupivacaine is more chondrotoxic than other anesthetic agent and increases the number of apoptotic cells. These results indicated that bupivacaine caused high chondrotoxic damage and it led to more apoptotic activation than levobupivacaine.
Topics: Anesthetics, Local; Animals; Apoptosis; Bupivacaine; Cartilage, Articular; Female; Injections, Intra-Articular; Knee Joint; Levobupivacaine; Rabbits; Random Allocation
PubMed: 30201323
DOI: 10.1016/j.bjan.2018.06.013 -
Journal of Pharmacy & Pharmaceutical... 2002To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac-bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral impacted third... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
PURPOSE
To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac-bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral impacted third molar extractions.
METHOD
A randomised, double blind, two period cross-over design was employed. Six subjects (2 males, 4 females; age 19-25 years; weight 69.2+/-9.4 kg) received bupivacaine hydrochloride injection (6.6 ml) as rac-bupivacaine (0.5% as salt) or S-bupivacaine (0.5% as base) prior to extraction of impacted third molars on one side and three weeks later on the other side. Anesthesia, blood loss associated with surgery and post-operative pain experience were evaluated. Plasma samples were analysed for bupivacaine enantiomers by chiral HPLC.
RESULTS
In 7/12 operations, anesthesia adequate for surgery was delayed (>10 min) or unsatisfactory requiring lidocaine rescue medication. Despite this, there were no significant differences in onset and duration of anesthesia, blood loss or post-operative pain experience between the two arms of the study. Pharmacokinetic parameters were not significantly different and there was no evidence of chiral inversion after dosing with S-bupivacaine.
CONCLUSIONS
Both study drugs were inadequate as single anesthetic agent for third molar surgery. Any decision to use S-bupivacaine for oral surgery must rest on evidence that it is less toxic than the racemic drug.
Topics: Adult; Anesthesia, Local; Anesthetics, Local; Area Under Curve; Bupivacaine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Molar, Third; Stereoisomerism; Tooth Extraction
PubMed: 12207874
DOI: No ID Found -
PloS One 2015The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery.
METHODS
Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software.
RESULTS
Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone.
CONCLUSION
The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone.
LEVEL OF EVIDENCE
Level I, meta-analysis of Level I studies.
Topics: Arthroscopy; Bupivacaine; Humans; Knee; Knee Joint; Morphine; Pain Management
PubMed: 26474401
DOI: 10.1371/journal.pone.0140512 -
British Journal of Pharmacology Jan 2014Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient...
BACKGROUND AND PURPOSE
Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314.
EXPERIMENTAL APPROACH
We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed.
KEY RESULTS
Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314.
CONCLUSIONS AND IMPLICATIONS
Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful.
Topics: Anesthetics, Local; Animals; Behavior, Animal; Bupivacaine; Calcium; Cell Line; Foot Injuries; Ganglia, Spinal; Injections; Lidocaine; Male; Mice, Knockout; Nerve Block; Patch-Clamp Techniques; Peripheral Nerves; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Sodium Channel Blockers; TRPA1 Cation Channel; Transient Receptor Potential Channels
PubMed: 24117225
DOI: 10.1111/bph.12466