• The Korean Journal of Pharmacology
• /
• v.28 no.1
• /
• pp.41-48
• /
• 1992

A concentration of 0.01 mM bupivacaine was necessary to maintain approximately 50% depression of contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4 at $30^{\circ}C$. Sodium pyruvate, sodium acetate, and fructose partially restored the contractility of the bupivacaine-depressed atria. However, 20 mM glucose had no effect on the bupivacaine-depressed atria, although this concentration of glucose markedly increased the contractility of normal atria not to be exposed to bupivacaine. Contractility of normal atria was not significantly influenced by sodium pyruvate, sodium acetate, and fructose. The results suggested that at least part of the negative inotropic action of bupivacaine is the result of inhibition of glucose uptake or utilization in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phosphofructokinase step.

• Journal of Dental Anesthesia and Pain Medicine
• /
• v.19 no.4
• /
• pp.209-215
• /
• 2019

Background: Pain is an unpleasant sensation ranging from mild localized discomfort to agony and is one of the most commonly experienced symptoms in oral surgery. Usually, local anesthetic agents and analgesics are used for pain control in oral surgical procedures. Local anesthetic agents including lignocaine and bupivacaine are routinely used in varying concentrations. The present study was designed to evaluate and compare the efficacy of 0.25% and 0.5% bupivacaine for postoperative analgesia in infraorbital nerve block. Methods: Forty-one patients undergoing bilateral maxillary orthodontic extraction received 0.5% bupivacaine (n = 41) on one side and 0.25% bupivacaine (n = 41) on the other side at an interval of 7 d. The parameters evaluated for both the bupivacaine concentrations were onset of action, pain during procedure (visual analog scale score [VAS]), and duration of action. The results were noted, tabulated, and analyzed using the Wilcoxon signed rank test. Results: The onset of action of 0.5% bupivacaine was quicker than that of 0.25% bupivacaine, but the difference was not statistically significant (P = 0.306). No significant difference was found between the solutions for VAS scores (P = 0.221) scores and duration of action (P = 0.662). Conclusion: There was no significant difference between 0.25% bupivacaine and 0.5% bupivacaine in terms of onset of action, pain during procedure, and duration of action. The use of 0.25% bupivacaine is recommended.

• The Korean Journal of Pain
• /
• v.18 no.2
• /
• pp.181-186
• /
• 2005

Background: Hydromorphone has an intermediate lipid solubility range that falls between morphine and fentanyl. Lipophilic activity during opioid epidural administration is important in relation to both the side effects and analgesic efficacy. The purpose of this study was to compare epidural hydromorphone and fentanyl when concomitantly infused with bupivacaine in patients undergoing a thoracotomy. Methods: Seventy-seven thoracotomy patients, with patient-controlled epidural analgesia (PCEA), were blindly allocated into two groups [group F (n = 34); 0.1% bupivacaine and fentanyl $5{\mu}g/ml$, group H (n = 34); 0.1% bupivacaine and hydromorphone $16{\mu}g/ml$)]. The basal PCEA rate and demand dose were 4 ml/hr and 3 ml, respectively. The visual analogue scale (VAS) for pain, and pruritus, sedation and nausea were measured at 6, 12 and 24 hours after the operation. Results: There were no significant differences in the VAS pain scores and the incidences of pruritus, nausea and sedation between the two groups. The total infused volume after 24 hours was lower in H compared to that of F group (P < 0.05). Conclusions: We conclude that epidural hydromorphone or fentanyl administration has a similar analgesic efficacy and shows similar incidences of side effects, when concomitantly infused with bupivacaine, in the management of acute pain following a thoracotomy.

• The Korean Journal of Pain
• /
• v.27 no.3
• /
• pp.229-238
• /
• 2014

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

• International Journal of Oral Biology
• /
• v.32 no.2
• /
• pp.45-49
• /
• 2007

In this study, the cytotoxicity of commonly used local anesthetics was evaluated on odontoblasts which are essential for pulpal homeostasis in vitro. Local anesthetics, such as articaine, bupivacaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, and procaine, were tested on the odontoblast cell line, MDPC-23. The concentration-and time-dependent cytotoxic effects of local anesthetics on odontoblasts were measured by MTT assay. Among local anesthetics treated for 18 h, only bupivacaine significantly showed cell death in a concentration-($LC_{50}=1.2mM$) and time-dependent manner. To confirm cell death induced by bupivacaine, the observation of cell morphology and FACS using Annexin V and propidium iodide (PI) staining were performed. As a result of Annexin V and PI staining, as well as the morphological change, only bupivacaine induced apoptotic cell death on odontoblasts when compared with levobupivacaine and lidocaine. These results suggest that bupivacaine might affect normal pulpal integrity even after uneventful local anesthesia.

• Journal of Chest Surgery
• /
• v.26 no.7
• /
• pp.538-542
• /
• 1993

An approach to the treatment of post-operative pain by the injection of bupivacaine into the pleural space through an intrapleural cathter has been studied. Among 24 thoracotomy patients, bupivacaine was injected only to experimental group[ 12 patients ] when the patient was able to head up for oneself during recovery from anesthesia. The pain and ROM[ range of motion ] scores, respiration rate, PaCO2 level of both experimental and control group were measured at the time of head-up and 30 and 120 minutes thereafter.The scores of pain and ROM of experimental group were significantly[ P value < 0.05 ] decreased in 30 minutes and 120 minutes after bupivacaine injection compared with those of control group but respiration rate and PaCO2 level were not changed significantly. With this result, we can suggest that intrapleural injection of bupivacaine is useful for pain relief following thoracotomy.

• The Korean Journal of Pain
• /
• v.29 no.4
• /
• pp.229-238
• /
• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• YAKHAK HOEJI
• /
• v.45 no.6
• /
• pp.623-633
• /
• 2001

Various bupivacaine-loaded microspheres were prepared using poly(d,1-lactide) (PLA) and poly(d,1-lactic-co-glycolide) (PLGA) by a solvent evaporation method for the sustained release of drug. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their drug loading, size distribution, surface morphology and release kinetics. Drug loading efficiency and yield of PLGA micro- spheres were higher than those of PLA microspheres. The prepared microspheres had an average particle size below 5${\mu}{\textrm}{m}$. The particle size range of microspheres was 1.65~2.24${\mu}{\textrm}{m}$. As a result of SEM, the particle size of PLA microspheres was smaller than that of PLGA microspheres. In morphology studies, microspheres showed a spherical shape and smooth surface in all process conditions. In thermal analysis, bupivacaine-loaded microspheres showed no peaks originating from bupivacaine. This suggested that bupivacaine base was molecular-dispersed in the polymer matrix of microspheres. The release pattern of the drug from microspheres was evaluated for 96 hours. The initial burst release of bupivacaine base decreased with increasing the molecular weight of PLGA, and the drug from microspheres released slowly. In conclusion, bupivacaine-loaded microspheres were successfully prepared from poly(d,1-lactide) and poly (d,1- lactic-co-glycolide) polymers with different molecular weights allowing control of the release rate.

• The Korean Journal of Pain
• /
• v.12 no.1
• /
• pp.48-53
• /
• 1999

Background: Despite the popularity of epidural bupivacaine-morphine infusions for postoperative pain management, the optimum concentrations and dosages of bupivacaine have not been determined. At present, due to the disadvantages conferred by intense motor block and the increased risk of toxicity, many trials focus on reducing bupivacaine concentration and thus the evaluation of concentrations less than 0.1% may be warranted. Methods: Forty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of two study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly 1 hr before the end of surgery and continuous epidural infusion was started using a two-day Infusor containing 4 mg of morphine in 100 ml of 0.125% bupivacaine (Group 0.125B, n=20) or 100 ml of 0.0625% bupivacaine (Group 0.0625B, n=20). Study endpoints included visual analog scales (VAS) for pain during rest and movement, sensory change and motor blockade. They were assessed at 2, 4, 8, 16, 24, 32, 40 and 48 hrs postoperatively. Results: For VAS during rest, no significance could be found between two groups over the course of study. But for VAS during movement, the 0.125B group showed more satisfactory results especially during early postoperative periods. For the incidence of complications, the 0.125B group revealed greater frequency of sensory change (25.0%) and motor blockade (10.0%) compared with the 0.0625B group. Conclusion: This study suggests that 0.0625% bupivacaine with morphine via epidural route was sufficient for pain control during rest but it was not satisfactory during movement especially in early postoperative periods. We also recommend that careful attention to motor blockade should be paid when using 0.125% bupivacaine.

• Journal of Yeungnam Medical Science
• /
• v.7 no.2
• /
• pp.121-130
• /
• 1990

Plain 0.5% bupivacaine and hyperbaric 0.5% tetracaine were compared for spinal anesthesia in 40 patients undergoing operation of lower extremities. Lumbar puncture was performed with a 22 gauge spinal needle with the patient in the lateral recumbent position. The third lumbar interspace was chosen for the puncture, when a free flow of clear CSF was obtained, the local anesthetic solution (2.5ml of 0.5% bupivacaine or 2.0ml of hyperbaric 0.5% tetracaine) was injected at a rate of 0.1ml/sec without barbotage. After injection of anesthetics, clinical features were observed and compared between the two groups. The results were as follows : 1. The two groups were well matched for age, sex, height and weight. 2. In both groups, sensory block to $T_{12}$ dermatome was obtained within 4 minutes, mean maximal level of analgesia was $T_{6-7}$, and the mean time for maximal level was around 20 minutes. 3. The onset times of motor block were similar in both groups and complete motor block was obtained in all cases within 20 minutes. 4. The duration of analgesia above the $T_{12}$ dermatome was 3 hours, postoperative analgesia was 7 hours. These values were significantly prolonged than those of the tetracaine group(p<0.05). 5. The changes in systolic pressure in the bupivacaine group were significantly less than those of the tetracaine group(p<0.05). 6. The complications after spinal anesthesia were headache, numbness, urinary retention and backpain, and were no significant difference in both groups. From the obtained results, we concluded that plain 0.5% bupivacaine was a relatively satisfactory agent for spinal anesthesia for operation of lower extremities. The time of onset, height of block and the complications of postoperative period were similar in both groups. The advantages of plain 0.5% bupivacaine were less hypotension and long duration of analgesia.