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British Journal of Anaesthesia May 1990We found a similar time (about 0.4 h) to maximum serum concentration after extradural administration of bupivacaine 1.78 (SD 0.27) mg kg-1 to six pregnant patients at... (Comparative Study)
Comparative Study
We found a similar time (about 0.4 h) to maximum serum concentration after extradural administration of bupivacaine 1.78 (SD 0.27) mg kg-1 to six pregnant patients at term, 1.58 (0.13) mg kg-1 to six women younger than 65 yr and 1.50 mg kg-1 to six women older than 65 yr. There were no significant differences in terminal half-life. No unconjugated 4'-hydroxy-bupivacaine was detected in the serum and urine of pregnant patients, in contrast with the other groups. The pregnant patients had significantly greater serum concentrations of the N-dealkylated metabolite, N-desbutyl-bupivacaine (DBB), than the non-pregnant groups. In contrast with 4'-hydroxy-bupivacaine, no conjugated forms of bupivacaine and desbutyl-bupivacaine were detected in urine. The mean total urinary excretion of bupivacaine and its metabolites and their conjugates varied between 2.46 and 3.22% of the total dose administered in the three patient groups, indicating that both 4'-hydroxylation and N-dealkylation are minor metabolic pathways in man.
Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Epidural; Anesthesia, Obstetrical; Bupivacaine; Cesarean Section; Female; Humans; Middle Aged; Pregnancy
PubMed: 2354094
DOI: 10.1093/bja/64.5.556 -
Anesthesiology Jun 2006The current study investigated whether racemic bupivacaine and its S(-)- and R(+)-enantiomers, levobupivacaine and dextrobupivacaine, differ in somatic and visceral... (Comparative Study)
Comparative Study
BACKGROUND
The current study investigated whether racemic bupivacaine and its S(-)- and R(+)-enantiomers, levobupivacaine and dextrobupivacaine, differ in somatic and visceral antinociception and neurotoxicity when administered intrathecally in rats.
METHODS
In experiment 1, rats intrathecally received 15 microl saline or 0.125, 0.25, 0.5, or 1% bupivacaine, levobupivacaine, or dextrobupivacaine. The tail-flick and colorectal distension tests were performed to assess somatic and visceral antinociceptive effects, respectively, for 180 min after injection. In experiment 2, rats given 0.25% anesthetic solutions were evaluated with colorectal distension-induced response in blood pressure and heart rate. In experiment 3, four groups of rats received a 1-h infusion of saline or 2.5% bupivacaine, levobupivacaine, or dextrobupivacaine. Additional rats received either 1.25% bupivacaine or levobupivacaine for 1 h. Four days after infusion, animals were assessed for persistent sensory impairment using the tail-flick test. Spinal cords and nerve roots were obtained for histologic analysis.
RESULTS
In experiment 1, the three drugs produced similar time course effects and dose-effect relations in tail-flick latency. Colorectal distension thresholds and motor paralysis were slightly lower and less apparent, respectively, at some concentrations in rats given levobupivacaine than in those given the other agents. In experiment 2, colorectal distension-induced response in heart rate was less depressed in rats given levobupivacaine than in those given the other anesthetics. In experiment 3, three groups of rats given 2.5% anesthetic solutions developed similar significant increases in tail-flick latency and incurred similar morphologic damage. Two groups of rats receiving 1.25% anesthetic solutions were similar in functional impairment and nerve injury scores.
CONCLUSIONS
The results suggest that, when administered intrathecally in rats, bupivacaine and its R(+)- and S(-)-enantiomers are similar for somatic antinociception and neurotoxicity but slightly different in visceral antinociception and motor paralysis, in which levobupivacaine is less potent than the others.
Topics: Anesthesia, Spinal; Anesthetics, Local; Animals; Blood Pressure; Bupivacaine; Heart Rate; Injections, Spinal; Levobupivacaine; Male; Nervous System; Pain Measurement; Rats; Rats, Sprague-Dawley; Reaction Time; Stereoisomerism; Tail
PubMed: 16732097
DOI: 10.1097/00000542-200606000-00021 -
Medical Science Monitor : International... Oct 2017BACKGROUND The median effective dose (ED50) of a drug gives the amount or dose of drug needed to produce effective therapeutic response or desired effect in at least 50%... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND The median effective dose (ED50) of a drug gives the amount or dose of drug needed to produce effective therapeutic response or desired effect in at least 50% of the population taking it. Our study focused on determining the ED50 required for effective motor block using hyperbaric and plain bupivacaine, and evaluated the influence of baricity on the ED50 required for motor block. MATERIAL AND METHODS A total of 38 patients were randomly assigned into 2 groups according to the baricity of bupivacaine: group P received plain bupivacaine and group H received hyperbaric bupivacaine. The patients were administered 0.5% plain or hyperbaric bupivacaine intrathecally. The dosage of anesthetics in each patient was calculated according to the standard up-down sequential allocation method of Dixon. The first patient in each group received a dose of 7.5 mg bupivacaine, and a dose of 1.0 mg was used as the testing interval. The dose was increased or decreased by 1.0 mg for each patient according to the estimated score of motor block. RESULTS The ED50 required for effective motor block in spinal anesthesia was 7.20 and 10.05 mg in groups H and P, respectively. Their relative motor blocking potency ratio was found to be 0.72. CONCLUSIONS The ED50 for motor block was significantly decreased using hyperbaric bupivacaine intrathecally compared with plain bupivacaine, and the baricity of bupivacaine obviously affected the ED50 for the motor block.
Topics: Adult; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Demography; Dose-Response Relationship, Drug; Humans; Middle Aged; Nerve Block
PubMed: 28965122
DOI: 10.12659/msm.904033 -
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 -
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 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 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 -
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 -
British Journal of Anaesthesia Mar 2019An injectable liposomal bupivacaine suspension (EXPAREL™) is approved by the US Food and Drug Administration for analgesia by tissue infiltration and interscalene...
BACKGROUND
An injectable liposomal bupivacaine suspension (EXPAREL™) is approved by the US Food and Drug Administration for analgesia by tissue infiltration and interscalene brachial plexus, but not for use in the neuraxial space. This pilot study describes neurological and histological outcomes of escalating doses of this extended-release formulation of bupivacaine after subarachnoid administration.
METHODS
Twenty-five pigs (Sus scrofa domesticus) weighing 36.2 (4.4) kg were randomly assigned to one of five groups to receive a subarachnoid injection of sodium chloride 0.9%, 3 ml (negative control), preservative-free bupivacaine hydrochloride 0.5%, 3 ml (positive control), or one of three doses of liposomal bupivacaine suspension 1.33%: 1.5, 3, or 5 ml. After recovering from general anaesthesia, neurological outcomes were assessed by blinded observers. Three weeks later, the animals were sacrificed for histological evaluations of neurotoxicity.
RESULTS
Animals that received sodium chloride 0.9%, bupivacaine hydrochloride, or liposomal bupivacaine 1.5 ml recovered within 2, 5, or 4 h, respectively. Animals that received liposomal bupivacaine 3 or 5 ml exhibited signs of neuraxial block (decreased nociception and proprioception) up to 32 h after injection. No histological evidence of neurotoxicity was found in any of the groups.
CONCLUSIONS
Subarachnoid administration of liposomal bupivacaine in pigs exhibited a dose-response effect, and resulted in longer duration of neuraxial block than bupivacaine hydrochloride without histological evidence of neurotoxicity. Our study contributes preliminary data to inform further toxicological assessments and regulatory approval before subarachnoid administration in humans.
Topics: Anesthetics, Local; Animals; Bupivacaine; Delayed-Action Preparations; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Spinal; Neurotoxicity Syndromes; Pilot Projects; Subarachnoid Space; Swine
PubMed: 30770056
DOI: 10.1016/j.bja.2018.10.025 -
Anaesthesia Sep 2009The objective of this study was to compare the block durations and haemodynamic effects associated with intrathecal levobupivacaine or bupivacaine in elderly patients... (Comparative Study)
Comparative Study Randomized Controlled Trial
The objective of this study was to compare the block durations and haemodynamic effects associated with intrathecal levobupivacaine or bupivacaine in elderly patients undergoing transurethral prostate surgery. Eighty patients were prospectively randomised to receive plain 1.5 ml levobupivacaine 0.5% (group levobupivacaine) or 1.5 ml plain bupivacaine 0.5% (group bupivacaine) in combination with fentanyl 0.3 ml (15 microg) for spinal anaesthesia. The time to reach T10 and peak sensory block level, and to maximum motor block were significantly shorter in group bupivacaine compared to group levobupivacaine (p < 0.05). Peak sensory block level was also significantly higher in group bupivacaine. In group bupivacaine, mean arterial pressure was significantly lower than group levobupivacaine, starting from 10 min until 30 min after injection (p < 0.05). Hypotension and nausea were less common in group levobupivacaine than group bupivacaine (p < 0.05). Because of the better haemodynamic stability and fewer side-effects associated with levobupivacaine, it may be preferred for spinal anaesthesia in elderly patients.
Topics: Aged; Anesthesia, Spinal; Anesthetics, Local; Blood Pressure; Bupivacaine; Fentanyl; Heart Rate; Humans; Hypotension; Levobupivacaine; Male; Middle Aged; Movement; Postoperative Nausea and Vomiting; Prospective Studies; Sensation; Transurethral Resection of Prostate
PubMed: 19686477
DOI: 10.1111/j.1365-2044.2009.05995.x