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Anesthesiology Jun 1995Ropivacaine is a new amide local anesthetic structurally similar to bupivacaine and mepivacaine. Previous studies showed that ropivacaine has a similar clinical effect... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Ropivacaine is a new amide local anesthetic structurally similar to bupivacaine and mepivacaine. Previous studies showed that ropivacaine has a similar clinical effect as bupivacaine with regard to sensory anesthesia and slightly less motor blockade than bupivacaine. Ropivacaine appears to be less cardiotoxic and arrhythmogenic than bupivacaine. The clinical and pharmacokinetic effects of 0.5% ropivacaine (5 mg/ml) versus 0.5% bupivacaine (5 mg/ml) when used epidurally for elective cesarean section were investigated.
METHODS
Using a randomized, double-blind study design, 60 ASA physical status 1 or 2 term parturients presenting for elective cesarean section received either 0.5% bupivacaine (150 mg) or 0.5% ropivacaine (150 mg) epidurally in appropriate fractionated doses over a 10-min period. Onset, duration, and regression of sensory and motor blockade were noted until complete resolution was observed. Quality of intraoperative anesthesia and abdominal wall muscle relaxation were noted. Maternal plasma concentrations of local anesthetic were determined before anesthetic administration and 5, 10, 20, 30, and 60 min and 2, 3, 6, 8, 12, and 24 h after drug injection in 20 subjects. Umbilical cord blood was obtained at time of delivery for acid-base values and determination of the free and total plasma concentration of local anesthetic. Neonates also were examined for neurobehavioral assessments by Scanlon's and Neurologic and Adaptive Capacity Scores at 2 and 24 h after delivery.
RESULTS
All patients received satisfactory anesthesia for operation. The onset, duration, and regression of sensory blockade were similar for both groups. Onset of degree 1 and 2 motor blockade was faster, and duration of degree 1 motor block was longer in the group receiving bupivacaine. Hemodynamic sequelae were similar between groups. All neonates had 5-min Apgar scores of 7 or greater and normal acid-base values and neurobehavioral assessments. Pharmacokinetic analysis showed that the Cmax was similar for both drugs (1.3 +/- 0.09 for ropivacaine and 1.1 +/- 0.09 micrograms/ml for bupivacaine). The T1/2 of the terminal decline in plasma concentration was shorter for ropivacaine versus bupivacaine (5.2 +/- 0.60 versus 10.9 +/- 1.08 h, respectively; P < 0.01). The free (i.e., unbound) concentrations of ropivacaine were approximately twice those of bupivacaine in both maternal and neonatal blood at the time of delivery. The ratio of umbilical vein to maternal vein concentration of unbound drug was 0.72 for ropivacaine and 0.69 for bupivacaine.
CONCLUSIONS
Ropivacaine, 0.5%, epidurally provided satisfactory and similar sensory anesthesia compared to 0.5% bupivacaine for elective cesarean section. The Cmax was similar for both drugs, although the terminal half-life of ropivacaine was significantly shorter, and the blood concentrations of free ropivacaine were significantly greater than that for bupivacaine. These values were less than concentrations shown to be toxic in animals.
Topics: Adolescent; Adult; Amides; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetics, Local; Bupivacaine; Cesarean Section; Double-Blind Method; Female; Fetal Blood; Humans; Pregnancy; Ropivacaine
PubMed: 7793647
DOI: 10.1097/00000542-199506000-00004 -
Journal of Clinical Anesthesia Dec 2021To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY).
STUDY OBJECTIVE
To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.
DESIGN
Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).
SETTING
Operating room.
PATIENTS
Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).
INTERVENTION
Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).
MEASUREMENTS
The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [C], time to C) and safety of liposomal bupivacaine, respectively.
MAIN RESULTS
Baseline characteristics were comparable across groups. Mean C after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to C of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.
CONCLUSIONS
Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.
Topics: Adolescent; Adult; Analgesia; Anesthetics, Local; Bupivacaine; Child; Humans; Liposomes; Pain, Postoperative
PubMed: 34534923
DOI: 10.1016/j.jclinane.2021.110503 -
Anesthesiology Jun 2002Ropivacaine is believed to have a lower incidence of clinical cardiac side effects than bupivacaine. The aim of this study was to compare the direct cardiac effects of...
BACKGROUND
Ropivacaine is believed to have a lower incidence of clinical cardiac side effects than bupivacaine. The aim of this study was to compare the direct cardiac effects of the optically pure S(-)-ropivacaine isomer and its nonclinically used R(+)-isomer with both optically pure bupivacaine isomers in isolated hearts. The hypothesis was that differences in direct cardiac effects are distinguished not only by stereoselective actions of local anesthetic molecules to specific receptors, but also by physicochemical differences triggered by replacing the butyl- by a propyl-residual on pipecoloxylide.
METHODS
Guinea pig hearts (n = 31) were excised and perfused by the Langendorff method. Atrial and ventricular bipolar electrodes were placed to measure heart rate and atrioventricular conduction time. Left ventricular pressure, coronary flow, and oxygen tensions were measured. Twelve hearts were perfused with increasing concentrations (0.5, 1.0, 5.0, and 10 microm) of both isomers of bupivacaine, and 13 hearts were perfused with the same concentrations of ropivacaine isomers. Six hearts were perfused with higher concentrations (20, 30, 40, and 50 microm) of both isomers of ropivacaine. The order of isomers and anesthetic chosen were randomized.
RESULTS
Both anesthetics had negative inotropic and chronotropic effects without evidence of stereoselectivity. Equal concentrations of both isomers of bupivacaine had negative inotropic effects greater than that of ropivacaine isomers. Atrioventricular conduction time was prolonged by both anesthetics in a concentration-dependent manner, but bupivacaine isomers increased atrioventricular conduction time more than ropivacaine isomers. In contrast to other variables, atrioventricular conduction time showed evident stereoselectivity for bupivacaine at the lowest concentration (0.5 microm) but only at higher concentrations for ropivacaine (> 30 microm). The R(+)-isomer was more potent than the S(-)-isomer on increasing atrioventricular conduction time for both bupivacaine and ropivacaine.
CONCLUSIONS
The results confirm that stereoselectivity can be demonstrated by a lengthening of atrioventricular conduction time for the more fat-soluble bupivacaine. However, for the less fat-soluble ropivacaine, the S(-)-isomer has no advantage over the R(+)-isomer for preventing slowing of atrioventricular conduction in clinical concentrations. Neither anesthetic showed stereoselective inotropic effects, but ropicavaine isomers had lesser cardiodepressant effects than bupivacaine isomers because of the replacement of the butyl- by a propyl-terminal group.
Topics: Amides; Anesthetics, Local; Animals; Bupivacaine; Coronary Circulation; Dose-Response Relationship, Drug; Guinea Pigs; Heart; In Vitro Techniques; Oxygen Consumption; Ropivacaine; Solubility; Stereoisomerism; Structure-Activity Relationship
PubMed: 12170056
DOI: 10.1097/00000542-200206000-00023 -
The Journal of Arthroplasty Oct 2020HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free application during surgery. The active ingredients are released from the polymer by controlled diffusion over 72 hours.
METHODS
This phase 2b, double-blind, placebo-controlled and active-controlled trial enrolled patients undergoing primary unilateral total knee arthroplasty under general anesthesia. Two hundred thirty-two patients were randomized into 4 groups: HTX-011 400 mg bupivacaine/12 mg meloxicam, applied without a needle into the surgical site, the same dose of HTX-011 with a separate 50 mg ropivacaine injection into the posterior capsule, bupivacaine hydrochloride (HCl) 125 mg injection, and saline placebo injection. Only opioids were permitted for postoperative pain rescue. Primary and key secondary endpoints were mean area under the curve of pain intensity scores over 48 hours and 72 hours, respectively, for HTX-011 groups vs placebo.
RESULTS
Both HTX-011 groups had significantly reduced mean pain intensity vs placebo through 48 and 72 hours (both P < .001). Ropivacaine added a small initial benefit in the first 12 hours. Both HTX-011 groups also had decreased mean pain intensity vs bupivacaine HCl alone through 48 and 72 hours (P < .05). The HTX-011 groups had significantly earlier discharge readiness along with lower opioid consumption through 72 hours. HTX-011 alone or with ropivacaine was well-tolerated with a safety profile similar to controls.
CONCLUSION
Needle-free application of HTX-011 400 mg bupivacaine/12 mg meloxicam provided superior pain reduction through 72 hours after total knee arthroplasty compared with placebo and bupivacaine HCl alone.
Topics: Analgesics, Opioid; Anesthetics, Local; Arthroplasty, Replacement, Knee; Bupivacaine; Double-Blind Method; Humans; Pain Measurement; Pain, Postoperative
PubMed: 32561266
DOI: 10.1016/j.arth.2020.05.044 -
Anesthesiology Oct 2000This study was designed to determine the disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments, using multiple sampling time...
BACKGROUND
This study was designed to determine the disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments, using multiple sampling time points in chronically prepared awake pregnant rats.
METHODS
All animals received an intravenous infusion of bupivacaine at a rate of 0.33 mg. kg-1. min-1 over a period of 15 min. The fetuses were delivered either at the end of infusion or at 2 or 4 h after dosing. Maternal and fetal blood and tissue samples were obtained for the assays of bupivacaine and its metabolites using capillary gas chromatography-mass spectrometry.
RESULTS
The elimination half-life of bupivacaine was 37.7 min. The major metabolite was 3'-hydroxybupivacaine. Bupivacaine and 3'-hydroxybupivacaine were present in all samples at the end of administration. The fetal to maternal concentration ratio of bupivacaine in plasma was 0.29, and in the placenta was 0.63. The amnion contained the highest bupivacaine concentration: threefold higher in the maternal and 11-fold higher than in the fetal plasma. At 4 h after dosing, bupivacaine was no longer detectable in any maternal and fetal samples, whereas 3'-hydroxybupivacaine was still present in all tissues except the fetal plasma and heart.
CONCLUSIONS
These data indicate that a considerable amount of bupivacaine is taken up by both sides of the placenta, as well as the amnion and myometrium. 3'-Hydroxybupivacaine was present in all tissues except the fetal plasma and heart samples, even after the parent compound became no longer detectable. Whether this slow elimination of 3'-hydroxybupivacaine causes any adverse effects on the fetus-newborn needs to be explored.
Topics: Amnion; Anesthetics, Local; Animals; Blood Pressure; Bupivacaine; Female; Fetus; Heart Rate; Maternal-Fetal Exchange; Myometrium; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 11020763
DOI: 10.1097/00000542-200010000-00031 -
Pain Research & Management 2021The optimal dose and concentration of analgesic efficacy of ropivacaine (RPV) and bupivacaine (BPV) for postoperative pain relief in paediatric abdominal surgery... (Meta-Analysis)
Meta-Analysis
Comparative Analgesic Efficacies of Ropivacaine and Bupivacaine for Postoperative Rectus Sheath Block in Paediatric Abdominal Surgery: A Meta-Analysis of Randomized Controlled Trial and Retrospective Cohort Studies.
BACKGROUND
The optimal dose and concentration of analgesic efficacy of ropivacaine (RPV) and bupivacaine (BPV) for postoperative pain relief in paediatric abdominal surgery patients is still unclear. Therefore, this meta-analysis compared the efficacy of these analgesics, their administered modes (ultrasound-guided RSB versus LAI) for postoperative pain relief, and side effects.
METHODS
Three databases, PubMed, Embase, and Cochrane Database of Systematic Reviews, were exhaustively searched with predefined keywords. Eight randomized clinical trials and retrospective studies were selected. Analgesic effect, postoperative pain score, level of side effect, applied dose, and concentration of drug were analysed.
RESULTS
Drug dose ranged from 0.5-2.5 mL/kg of 0.2 to 0.5% concentrations. Male participant for RSB and LAI treatment groups varied from 40-62% and 25-83%, respectively. Mean age of RSB and LAI groups ranged from 3.8-11.65 years and 4.3-11.27 years, respectively. Our meta-analysis revealed that RSB could reduce total opioid use postoperatively (WMD = -0.02, 95% CI: -0.02, -0.02), with value of 15%. We found that the RPV (0.25%, 2.5 ml/kg) was optimal in suppressing the pain. Its lower concentration (0.2%) was ineffective, whereas higher one (0.375%) seems to increase risk of systemic toxicity. Similarly, BPV (0.25%, 2.5 mg/kg) efficaciously reduced the pain score, while its lower concentration was ineffective. The combined postoperative pain score in the RPV-treated group was found to be significantly reduced ( < 0.01) with value of 85% indicating high heterogeneity.
CONCLUSION
Both RPV and BPV were significantly effective in reducing postoperative pain score. It appears that RSB could be a preferred choice to deliver analgesia, due to reduced opiate dose requirement and improved clinical safety without significant postoperative adverse events.
Topics: Anesthetics, Local; Bupivacaine; Child; Child, Preschool; Female; Humans; Male; Nerve Block; Postoperative Period; Randomized Controlled Trials as Topic; Rectus Abdominis; Retrospective Studies; Ropivacaine
PubMed: 33815632
DOI: 10.1155/2021/5535730 -
Journal of Zhejiang University.... Sep 2006To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats.
OBJECTIVE
To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats.
METHODS
Full-thick myometrial strips were prepared from 18- to 21-day pregnant (n=8) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was recorded.
RESULTS
Two local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency.
CONCLUSION
These results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility. The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.
Topics: Anesthetics, Local; Animals; Bupivacaine; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Levobupivacaine; Pregnancy; Rats; Rats, Sprague-Dawley; Uterine Contraction
PubMed: 16909479
DOI: 10.1631/jzus.2006.B0757 -
Brazilian Journal of Anesthesiology... 2014Success rate of catheter applications is low in supraclavicular block. Thus, bupivacaine and levobupivacaine become important with their long effect time in single... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Success rate of catheter applications is low in supraclavicular block. Thus, bupivacaine and levobupivacaine become important with their long effect time in single injection practices. In this study, we aimed to compare the effectiveness, side effects and complications of bupivacaine and levobupivacaine in supraclavicular block.
METHODS
Sixty patients aged between 20 and 65, with body weight between 50 and 100 kg, in the ASA I-II-III group who were scheduled for hand, forearm and arm surgery using supraclavicular block were randomized into two groups of 30. The patients received 30 ml 0.5% bupivacaine (Group B) or 30 ml 0.5% levobupivacaine (Group L). Motor and sensory blocks were evaluated. Motor and sensory block onset times, total block durations, postoperative pain, amount of postoperative analgesic used and patient satisfaction were recorded.
RESULTS
Demographic data, distribution of surgical area and hemodynamic data were similar between the two groups. Surgery, motor and sensory block durations of Group B and L patients did not vary statistically significantly. However, motor and sensory block onset times in Group B were significantly shorter than Group L (p<0.05). The mean time for first postoperative analgesic demand were 16.6 ± 8.0 h in Group B and 14.4 ± 7.3h in Group L (p>0.05).
CONCLUSION
30 ml 0.5% bupivacaine and levobupivacaine provide similar block characteristics for supraclavicular block. Bupivacaine leads to faster motor and sensory block onset compared to levobupivacaine however similar duration of postoperative analgesia.
Topics: Adult; Aged; Analgesics; Anesthetics, Local; Bupivacaine; Double-Blind Method; Female; Humans; Levobupivacaine; Male; Middle Aged; Nerve Block; Pain, Postoperative; Patient Satisfaction; Time Factors; Young Adult
PubMed: 24907877
DOI: 10.1016/j.bjane.2013.03.015 -
Anesthesiology Jan 2007Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia.
METHODS
Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal-epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 microg sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose-response curves were constructed using a probit regression model.
RESULTS
The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P=0.0027) and levobupivacaine (P=0.0006). Ropivacaine and levobupivacaine were of similar potency (P=0.91).
CONCLUSIONS
This full dose-response study suggests that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine is more potent than both other drugs.
Topics: Adolescent; Adult; Amides; Analgesia, Epidural; Analgesia, Obstetrical; Anesthetics, Local; Bupivacaine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Spinal; Levobupivacaine; Middle Aged; Pregnancy; Ropivacaine; Sufentanil
PubMed: 17197857
DOI: 10.1097/00000542-200701000-00024 -
Anesthesiology Jun 1999Bupivacaine exists as a mixture of two enantiomers, levobupivacaine and dexbupivacaine. Data suggest that levobupivacaine has equal local anesthetic potency, with... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Bupivacaine exists as a mixture of two enantiomers, levobupivacaine and dexbupivacaine. Data suggest that levobupivacaine has equal local anesthetic potency, with reduced potential for central nervous system and cardiovascular toxicity. The present study compares the efficacy of 0.5% levobupivacaine with 0.5% bupivacaine for epidural anesthesia in parturients undergoing elective cesarean delivery.
METHODS
Sixty healthy obstetric patients undergoing elective cesarean delivery with epidural anesthesia completed the study. Patients were randomized to receive 30 ml of either 0.5% levobupivacaine or 0.5% bupivacaine in a double-blind fashion. The efficacy endpoint measures included onset, offset, and quality of anesthesia. Neonatal blood gas analyses, Apgar score determinations, and neurobehavioral examinations were performed. Venous samples for pharmacokinetic studies and serial electrocardiograms were obtained in 10 patients in each group.
RESULTS
Levels of sensory block, motor block, muscle relaxation, and overall quality of anesthesia did not differ between groups. The frequency of hypotension was 84.4% in the levobupivacaine group and 100% for the bupivacaine group (P < or = 0.053). No significant difference in observed maximum concentration of drug after dosing or area under the plasma drug concentration versus time curve were seen. The maximum concentrations were 1.017 and 1.053 microg/ml, and the areas were 4.082 and 3.765 h(microg/ml) for the levobupivacaine and bupivacaine groups, respectively. Umbilical vein-to-maternal vein ratios were 0.303 for the levobupivacaine group and 0.254 for the bupivacaine group.
CONCLUSIONS
The use of epidural 0.5% levobupivacaine for cesarean delivery results in equally efficacious anesthesia compared with 0.5% bupivacaine. Pharmacokinetic parameters were similar in the two groups.
Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetics, Local; Blood Pressure; Bupivacaine; Cesarean Section; Electrocardiography; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Stereoisomerism
PubMed: 10360857
DOI: 10.1097/00000542-199906000-00015