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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 -
Surgery Nov 2020Most severe pain occurs within the first 72 hours after an operation, and current local anesthetics have a limited duration of action. HTX-011 is a dual-acting, local...
BACKGROUND
Most severe pain occurs within the first 72 hours after an operation, and current local anesthetics have a limited duration of action. HTX-011 is a dual-acting, local anesthetic containing bupivacaine, and low-dose meloxicam in an extended-release polymer. In a prior phase 3 inguinal herniorrhaphy study, HTX-011 alone provided superior pain relief for 72 hours and significantly decreased opioid use compared with saline placebo and bupivacaine hydrochloride. This open-label study assessed the safety, efficacy, and opioid-sparing properties of HTX-011 as the foundation of a scheduled, nonopioid, multimodal analgesia regimen in patients undergoing open inguinal herniorrhaphy.
METHODS
This study was conducted in 2 sequential cohorts. All patients received a single, intraoperative dose of HTX-011 prior to wound closure, followed by a scheduled postoperative regimen of oral ibuprofen and acetaminophen for 72 hours. Patients in cohort 2 also received a single intraoperative dose of ketorolac. Opioid analgesics were available by request only.
RESULTS
More than 90% of patients remained opioid-free through 72 hours postoperatively, and 83% of patients remained opioid-free through day 28 (last study visit). Pain was well controlled, and mean intensity of the pain never increased higher than the mild range during the first 72 hours. Ketorolac did not demonstrate any additional benefit. HTX-011 with this multimodal analgesia regimen was well tolerated.
CONCLUSION
HTX-011 when used as the foundation of a nonopioid, multimodal analgesia regimen, provided effective and well-tolerated analgesia without the need for opioids in the majority of patients recovering from an open inguinal herniorrhaphy.
Topics: Adult; Aged; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Female; Hernia, Inguinal; Herniorrhaphy; Humans; Male; Meloxicam; Middle Aged; Pain, Postoperative
PubMed: 32943200
DOI: 10.1016/j.surg.2020.06.036 -
Scientific Reports Jan 2021A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the... (Randomized Controlled Trial)
Randomized Controlled Trial
A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the trocar sites and intraperitoneal anesthetics administration at the end of the surgery. However, the evidence regarding their efficacy are conflicting. In addition, the combination of both aforementioned methods has been rarely studied. Our aim was to evaluate whether subcutaneous trocar site and/or intraperitoneal analgesia reduce pain after gynecologic operative laparoscopy. This was a single-centered, randomized, controlled, double-blinded trial. The patients were randomly assigned to one of four equally sized groups: group 1-subcutaneous and intraperitoneal analgesia; group 2-subcutaneous analgesia and intraperitoneal placebo; group 3-subcutaneous placebo and intraperitoneal analgesia; Group 4-subcutaneous and intraperitoneal placebo. The patients, the surgeons, and the pain evaluators were all blinded to the patient's allocation. Included were patients who underwent elective operative laparoscopy. Exclusion criteria were: active infection, pregnancy, known sensitivity to Bupivacaine-Hydrochloride, chronic pelvic pain, surgeries with additional vaginal procedures, conversion to laparotomy, and malignancy. A total of 9 ml of Bupivacaine-Hydrochloride (Marcaine) 0.5%, or Sodium-Chloride 0.9%, as a placebo, were injected subcutaneously to the trocar sites (3 ml to each trocar site), prior to skin incision. In addition, 10 ml of Bupivacaine-Hydrochloride 0.5%, diluted with 40 ml of Sodium-Chloride 0.9% (a total of 50 ml solution), or 50 ml of Sodium-Chloride 0.9%, as a placebo, were injected intraperitoneally at the end of the surgery. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. The study was approved by the local Institutional Review Board and has been registered at clinicaltrials.gov. We conformed to the CONSORT recommendations. Between December 2016 and July 2019, a total of 119 patients were included in the study. Demographic and interventional characteristics were similar among the groups. The level of postoperative pain, either at rest or with change of position, was not significantly different between the groups, at all-time points. Application of subcutaneous and/or intraperitoneal analgesia is not effective in reducing pain after gynecologic operative laparoscopy.Clinical trial identification number: NCT02976571. Date of trial registration 11/29/2016. URL of the registration site: https://clinicaltrials.gov .
Topics: Adult; Anesthesia, Local; Anesthetics; Anesthetics, Local; Bupivacaine; Double-Blind Method; Female; Gynecologic Surgical Procedures; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Laparoscopy; Middle Aged; Pain Measurement; Pain, Postoperative
PubMed: 33420214
DOI: 10.1038/s41598-020-80130-6 -
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 -
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 -
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 -
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 -
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 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 -
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