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Indian Journal of Pharmacology 2014The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and...
OBJECTIVES
The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patient's characteristics including age, body weight and sex on pharmacokinetic parameters.
MATERIALS AND METHODS
A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine.
RESULTS
One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population.
CONCLUSION
The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites.
Topics: Anesthetics, Local; Bupivacaine; Humans; Lumbosacral Plexus; Models, Biological; Nerve Block; Sciatic Nerve; Tissue Distribution
PubMed: 24741194
DOI: 10.4103/0253-7613.129318 -
Drug Design, Development and Therapy 2019Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has...
BACKGROUND
Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has a therapeutic effect on bupivacaine-induced neurotoxicity. The aim of this study was to determine the underlying mechanisms of bupivacaine-induced neurotoxicity and the potential neuroprotective role of GM1.
MATERIALS AND METHODS
A rat spinal cord neurotoxicity model was established by injecting bupivacaine (5%, 0.12 μL/g) intrathecally. The protective effect of GM1 (30 mg/kg) was evaluated by pretreating the animals with it prior to the bupivacaine regimen. The neurological and locomotor functions were assessed using standard tests. The histomorphological changes, neuron degeneration and apoptosis, and endoplasmic reticulum stress (ERS) relevant markers were analyzed using immunofluorescence, quantitative real-time PCR, and Western blotting.
RESULTS
Bupivacaine resulted in significant neurotoxicity in the form of aberrant neurolocomoter functions and spinal cord histomorphology and neuronal apoptosis. Furthermore, the ERS specific markers were significantly upregulated during bupivacaine-induced neurotoxicity. These neurotoxic effects were ameliorated by GM1.
CONCLUSION
Pretreatment with GM1 protects against bupivacaine-induced neurotoxicity via the inhibition of the GRP78/PERK/eIF2α/ATF4-mediated ERS.
Topics: Animals; Bupivacaine; Endoplasmic Reticulum Stress; Gangliosides; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Rats; Rats, Sprague-Dawley
PubMed: 30858700
DOI: 10.2147/DDDT.S192225 -
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 -
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 -
British Journal of Anaesthesia Apr 2004Spread of intrathecal local anaesthetics is determined principally by baricity and position of the patient. Hypobaric solutions of bupivacaine are characterized by an...
BACKGROUND
Spread of intrathecal local anaesthetics is determined principally by baricity and position of the patient. Hypobaric solutions of bupivacaine are characterized by an unpredictable spread of sensory block whereas addition of dextrose 80 g ml(-1) provides a predictable spread but to high thoracic levels. In contrast, dextrose concentrations between 8 and 30 g ml(-1) have shown reliable and consistent spread for surgery. Hence, the aim of this study was to determine the density of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose at both 23 and 37 degrees C before embarking on clinical studies.
METHODS
Density (g ml(-1)) was measured using the method of mechanical oscillation resonance, accurate to five decimal places on 1250 samples. 500 density measurements were performed in a randomized, blind fashion at 23 and 37 degrees C on 10 plain solutions of bupivacaine (2.5, 5, and 7.5 g ml(-1)) levobupivacaine (2.5, 5, and 7.5 g ml(-1)) and ropivacaine (2, 5, 7.5, and 10 g ml(-1)). Following this, 750 density measurements were taken at 23 and 37 degrees C on the 5 g ml(-1) solutions of bupivacaine, levobupivacaine, and ropivacaine with added dextrose (10, 20, 30, 50, and 80 g ml(-1)).
RESULTS
There was a linear relationship between density and dextrose concentration for all three local anaesthetics (R(2)=0.99) at 23 and 37 degrees C. The mean density of levobupivacaine 5 g ml(-1) was significantly greater than the densities of bupivacaine 5 g ml(-1) and ropivacaine 5 g ml(-1) after adjusting for dextrose concentration using analysis of covariance. This difference existed both at 23 and 37 degrees C. The mean (sd) density of levobupivacaine 7.5 g ml(-1) was 1.00056 (0.00003) g ml(-1), the lower 0.5% percentile (1.00047 g ml(-1)) lying above the upper limit of hypobaricity for all patient groups.
CONCLUSIONS
The density of local anaesthetics decreases with increasing temperature and increases in a linear fashion with the addition of dextrose. Levobupivacaine 5 g ml(-1) has a significantly higher density compared with bupivacaine 5 g ml(-1) and ropivacaine 5 g ml(-1) at 23 and 37 degrees C both with and without dextrose. Levobupivacaine 7.5 g ml(-1) is an isobaric solution within all patient groups at 37 degrees C [corrected]
Topics: Amides; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Electrolytes; Glucose; Levobupivacaine; Nerve Block; Ropivacaine; Solutions; Temperature
PubMed: 14766715
DOI: 10.1093/bja/aeh094 -
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 fl uid preload made with 10mL.kg(-1). Lactated Ringer solution. After fl uid 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 10minutes 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.
Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Cesarean Section; Double-Blind Method; Electrocardiography; Female; Humans; Levobupivacaine; Pregnancy; Prospective Studies
PubMed: 23601262
DOI: 10.1016/S0034-7094(13)70216-2 -
British Journal of Anaesthesia Sep 2011Spinal anaesthesia is the preferred anaesthetic technique for elective Caesarean deliveries. Hypotension is the most common side-effect and has both maternal and... (Meta-Analysis)
Meta-Analysis Review
Spinal anaesthesia is the preferred anaesthetic technique for elective Caesarean deliveries. Hypotension is the most common side-effect and has both maternal and neonatal consequences. Different strategies have been attempted to prevent spinal-induced hypotension, including the use of low-dose bupivacaine. We conducted a systematic search for randomized controlled trials comparing the efficacy of spinal bupivacaine in low dose (LD ≤8 mg) with conventional dose (CD >8 mg) for elective Caesarean delivery. Thirty-five trials were identified for eligibility assessment, 15 were selected for data extraction, and 12 were finally included in the meta-analysis. We investigated sources of heterogeneity, subgroup analysis, and meta-regression for confounding variables (baricity, intrathecal opioids, lateral vs sitting position, uterine exteriorization, and study population). Sensitivity analysis was performed to test the robustness of the results. In the LD group, the need for analgesic supplementation during surgery was significantly higher [risk ratio (RR)=3.76, 95% confidence interval (95% CI)=2.38-5.92] and the number needed to treat for an additional harmful outcome (NNTH) was 4 (95% CI=2-7). Furthermore, the LD group exhibited a lower risk of hypotension (RR=0.78, 95% CI=0.65-0.93) and nausea/vomiting (RR=0.71, 95% CI=0.55-0.93). Conversion to general anaesthesia occurred only in the LD group (two events). Neonatal outcomes (Apgar score, acid-base status) and clinical quality variables (patient satisfaction, surgical conditions) showed non-significant differences between LD and CD. This meta-analysis demonstrates that low-dose bupivacaine in spinal anaesthesia compromises anaesthetic efficacy (risk of analgesic supplementation: high grade of evidence), despite the benefit of lower maternal side-effects (hypotension, nausea/vomiting: moderate grade of evidence).
Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Cesarean Section; Female; Humans; Patient Satisfaction; Pregnancy
PubMed: 21764820
DOI: 10.1093/bja/aer200 -
Methods and Findings in Experimental... Jun 2007Unlike other drugs which act in the region of the synapse, local anesthetics are agents that reversibly block the generation and conduction of nerve impulses along a... (Comparative Study)
Comparative Study
Unlike other drugs which act in the region of the synapse, local anesthetics are agents that reversibly block the generation and conduction of nerve impulses along a nerve fiber. This study aims to investigate the comparative inhibitions of bupivacaine and ropivacaine on the frog sciatic nerve. Isolated nerves were transferred to the nerve chamber which includes Ringer's solution. The nerves were stimulated by standard square wave pulse protocols and the responses were recorded with conventional systems. Bupivacaine (n = 8) and ropivacaine (n = 8) were administered in the nerve chamber bath with cumulative concentrations (10(-9) to 10(-3) M) and the effects were monitored for variable time periods (5, 10 and 15 min). Both bupivacaine and ropivacaine significantly depressed the compound action potential (CAP) parameters in a dose-dependent (p < 0.05) and reversible manner. Difference in the effects of these two drugs was detectable only when the dose (> or =10(-5) M) and exposure time (15 min) were increased. Percent inhibitions in maximum derivatives and latency-period measurements have shown that ropivacaine is not only fast but also much more powerful in conduction block for longer and higher doses. Bupivacaine, on the other hand, is effective in the group of fibers with relatively slower conduction velocity for all the measured doses and time periods. In conclusion, ropivacaine has a sensory specific side of action, when compared with the bupivacaine.
Topics: Action Potentials; Amides; Anesthetics, Local; Animals; Bupivacaine; Dose-Response Relationship, Drug; Nerve Block; Ranidae; Ropivacaine; Sciatic Nerve
PubMed: 17805435
DOI: 10.1358/mf.2007.29.5.1117558 -
Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal spinal anaesthesia.British Journal of Anaesthesia Nov 2009Comparing the relative potency of new local anaesthetics such as levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic concentration model has... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Comparing the relative potency of new local anaesthetics such as levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic concentration model has not been described for neonatal spinal anaesthesia. This information is important to compare agents and to determine the most effective spinal dose.
METHODS
We performed a two-stage study to determine the ED50, the ED95, and the relative analgesic potency of isobaric spinal bupivacaine, levobupivacaine, and ropivacaine in infants. In phase 1, 81 infants were randomized in a Dixon-Massey study to describe the minimum local analgesic dose. In phase 2, a further 70 patients were randomly allocated to receive spinal anaesthesia with doses in the upper dose-response range to define the ED95.
RESULTS
The ED50 doses for bupivacaine, levobupivacaine, and ropivacaine were estimated by isotonic regression to be 0.30 mg kg(-1) [95% confidence interval (CI) 0.25-0.43], 0.55 mg kg(-1) (0.50-0.64), and 0.50 mg kg(-1) (0.43-0.64), respectively. The ED(95), respectively, of bupivacaine, levobupivacaine, and ropivacaine were 0.96 mg kg(-1) (95% CI 0.83-0.98), 1.18 mg kg(-1) (1.05-1.22), and 0.99 mg kg(-1) (0.73-1.50). The relative potency ratios at the ED(50) were bupivacaine:levobupivacaine 0.55 (95% CI 0.39-0.88), bupivacaine:ropivacaine 0.61 (0.41-1.00), and levobupivacaine:ropivacaine 1.09 (0.84-1.45).
CONCLUSIONS
Appropriate doses for infant spinal anaesthesia are 1 mg kg(-1) of isobaric 0.5% bupivacaine and ropivacaine and 1.2 mg kg(-1) of isobaric 0.5% levobupivacaine.
Topics: Amides; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Dose-Response Relationship, Drug; Hernia, Inguinal; Humans; Infant; Infant, Newborn; Levobupivacaine; Ropivacaine
PubMed: 19767606
DOI: 10.1093/bja/aep259 -
British Journal of Anaesthesia Feb 1985
Topics: Anesthesia, Epidural; Anesthesia, Obstetrical; Bupivacaine; Cesarean Section; Female; Humans; Pregnancy
PubMed: 3970807
DOI: No ID Found