Prolongation of Nerve and Epidural Anesthetic Blockade by Bupivacaine in a Lipid Emulsion (original) (raw)
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A dose–response study of epidural liposomal bupivacaine in rabbits
Journal of Controlled Release, 1999
Liposomes are drug delivery systems used to prolong local effects of bupivacaine. We studied the relationships between motor and hemodynamic changes and epidural doses of plain bupivacaine (P) and liposomal bupivacaine (L) in rabbits equipped with chronical lumbar epidural and femoral arterial catheters. Liposomal (phosphatidylcholine-cholesterol) 21 suspensions contained 20 mg ml of lipid, and different doses of bupivacaine (Lipo 7.557.5-; Lipo 3.753.75-; Lipo 2.552.5-; Lipo 1.251.25-; and Lipo 0.750.65-mg of bupivacaine per ml). Forty rabbits were randomly assigned to five groups to receive epidural anesthesia (1 ml) as follows: Groups I to V received 0.65 to 7.5 mg of bupivacaine as P then as L. Release rate of bupivacaine from liposome was significantly slower using Lipo 3.7 than after Lipo 2.5 (T was 3.9 h and 1.7 d h respectively). Increasing the doses of L and P resulted in faster onset time for complete motor blockade and in a prolonged duration of motor effects. Liposomal formulation appears to be a powerful delivery system to prolong the motor effects of bupivacaine since E was lower and E higher than after the use of plain solution (E 4.4961.81 mg and E 152640 50 max 50 max min for P; and E 2.6160.23 mg and E 20269 min for L). Hemodynamic changes were linearly related to doses of 50 max bupivacaine injected. The best bupivacaine-to-lipid ratio to prolong motor effects using our model was 3.75 mg and 20.0 mg respectively (Lipo 3.7).
Anesthetic activity of the lipospheres bupivacaine delivery system in the rat
Anesthesia progress, 1992
The Lipospheres Bupivacaine Delivery System (bupivacaine-lipospheres) is a novel sustained-release local anesthetic preparation that has recently been made available for research purposes. This investigation compared the local anesthetic efficacy and safety of 2% bupivacaine-lipospheres, 0.5% bupivacaine plus 1:200,000 epinephrine, lipospheres plain, and physiologic saline following subcutaneous tail injection in the rat. A modified tail-flick paradigm was used to assess local anesthetic efficacy. Animals treated with 2% bupivacaine-lipospheres or 0.5% bupivacaine with epinephrine displayed significant antinociception (P < 0.05) compared to saline or lipospheres plain with 5 min of injection. Bupivacaine with epinephrine had an anesthetic duration of 30 min, whereas 2% bupivacaine-lipospheres had a duration of 3 hr. The local anesthetic blockade produced by both active solutions was completely reversible. All animals gained weight normally during the 1-wk course of the study, and...
innovative publication
Background: Bupivacaine is a long-acting local anesthetic. Addition of epinephrine is thus rarely required. It blocks initiation and transmission of nerve impulses at the site of application by stabilizing the neuronal membrane. Objectives: To study effectiveness of 0.5% Bupivacaine for sensory blockade as local anesthesia in epidural and spinal Phase. Methodology: After obtaining local ethical committee approval and informed consent a total number of 60 patient posted for orthopedic lower limb surgery, under combined spinal epidural were included in the study. They were divided into three groups of twenty patients each randomly. All cases were of the ASA I and ASA II in the age group of 18 to 60 years and randomly grouped in to A, B and C each including 20 cases. Group A: Epidural top up with 10 ml bupivacaine 0.5%, Group B: Epidural top up with 10 ml saline. Group C: served as a control and received no injection epidurally, but epidural injection was simulated by manipulating the epidural catheter. ANOVA test used for statistical analysis. Results: The physical characteristics such as age, height, weight were found to be comparable in all the three groups. Statistically significant rise in sensory blockade was noticed, following administration of epidural drugs [in Group A and Group B] significant higher in group A as compared to those in group. Also it was found that time taken to achieve maximum level of sensory blockade after epidural top-up in group A was greater than that of group B which was found to be statistically significant. Conclusion: The extension of sensory blockaded induced by an epidural top-up with a local anesthetic in CSF appears to be effected by a dual mechanism. The initial rapid increase was caused by a combination of volume effect and local anesthetic itself. The local anesthetic acts over a longer period of time which explains the prolonged but less rapid increase in level of sensory blockade in the later stages.
Sciatic nerve blockade with lipid-protein-sugar particles containing bupivacaine
Pharmaceutical research, 2000
To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs. Sensory and motor nerve blockade were measured in the hindpaw, as were contralateral functional deficits (a measure of systemic drug distribution). Poly(lactic-co-glycolic) acid (PLGA) microspheres were used as a reference. 10% (w/w) bupivacaine LPSPs (60% dipalmitoylphosphatidylcholine) were 4.4+/-0.39 microm in diameter, with a tap density of 0.11 +/-0.04 g/ml. These LPSPs and 50% (w/w) PLGA microspheres had comparable durations of sensory blockade (468+/-210 min vs. 706+/-344 min, p = 0.08), although the LPSPs produced a much lesser duration of motor blockade (508+/-258 min vs. 1062+/-456 min, p = 0.005). Systemic toxicity was minimal in both groups. LPSPs provide sensory blockade ...
Journal of Evidence Based Medicine and Healthcare, 2014
BACKGROUND: Hyperbaric bupivacaine has been the gold standard drug for the safe conduct of spinal anaesthesia. It offers duration of 1.5 to 2.5 hours of anaesthesia and analgesia, various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. clonidine, an α 2 adrenergic agonist is new neuraxial adjuvant gaining popularity. AIM: The purpose of this study was to compare the efficacy of sensory and motor block, degree of postoperative analgesia, and adverse effects of clonidine and fentanyl used intrathecally with hyperbaric bupivacaine for spinal anaesthesia. SETTINGS AND DESIGN: the study was conducted in prospective, double blind manner, included 60 ASA class I and II patients undergoing lower limb, lower abdominal, gynaecological and urological surgeries under spinal anaesthesia after approval from hospital ethics committee with written and informed consent of patients. MATERIALS AND METHODS: the patients were randomly allocated into two groups (30 patients each), group C received hyperbaric bupivacaine 15mg with clonidine 1µg. kg-1 and group F received hyperbaric bupivacaine15mg with fentanyl 25µg. This randomized study was conducted to compare the effects with regards to, Onset and duration of block, degree of post-operative analgesia (evaluated by VAS scale) and side effects associated with the drugs were recorded. RESULTS: Patients in group C had significantly longer sensory and motor block times than group F. The mean onset of sensory block in group C was 136.67sec and in group F was 138.33 sec. The mean onset of motor block in group C was 200.00sec and in group F was 206.67 sec. There were no differences with respect to the onset of block .The mean duration of sensory block in group C was 343.67min and in group F was 250.83min. CONCLUSIONS: There were no differences in the onset of sensory and motor blockade. The duration of analgesia, two segment regressions, and recovery of motor blockade were prolonged when clonidine 1µg.kg-1 was used as an additive to intrathecal hyperbaric bupivacaine compared to fentanyl 25µg for spinal anaesthesia, with side effects like bradycardia, hypotension and pruritus which did not require any treatment. Mild sedation was associated with intrathecal administration of clonidine 1µg.kg-1 which did not require any treatment. KEYWORDS: α 2 adrenorecepor agonist, bupivacaine, clonidine, fentanyl, spinal anaesthesia. INTRODUCTION: Hyperbaric bupivacaine has been the gold standard drug for the safe conduct of spinal anaesthesia. 1 It offers duration of 1.5 to 2.5 hours of anaesthesia and analgesia. Discovery of various spinal receptors like α 2-adrenergic, cholinergic, opioid, NMDA, GABA,
TURKISH JOURNAL OF MEDICAL SCIENCES, 2019
2.1. Preparation of liposome formulations Structurally multilamellar liposomes were prepared from dipalmitoyl phosphatidyl choline (DPPC)-cholesterol in 50% ratio using the dry-film hydration by vortex mixer Background/aim: Based on our previous in vitro study with multilamellar liposomal bupivacaine (MLB) versus bupivacaine alone in artificial cerebrospinal fluid, we aimed to investigate in vivo antinociceptive effect of intrathecal MLB by determining tail flick latency (TFL) time after thermal stimulation in rats. Materials and methods: After preparing MLB and high-yield drug entrapment in liposome (HYDEL) bupivacaine, 18 female Wistar rats were assigned to 3 groups as control (bupivacaine) and study groups (MLB and HYDEL bupivacaine) including 6 rats in each group to administer these drugs intrathecally. Antinociceptive activity was determined in terms of TFL time after thermal stimulation. Maximum possible effect (MPE) calculated from TFL times and rats with motor block were documented. Results: TFL times after intrathecal injection of HYDEL bupivacaine were significantly longer than that of the control and MLB groups (P < 0.05) and returned to baseline 180 min after intrathecal injection. MPE (100%) with intrathecal HYDEL bupivacaine occurred between 10 to 45 min. Afterwards, MPEs were 70% and 50% for the control and MLB groups, respectively. Motor block disappeared after 20 min in the study groups while it lasted 75 min in the control. Conclusion: Intrathecal administration of MLB and HYDEL bupivacaine in rats resulted in longer duration of antinociceptive activity with shorter motor block duration.
Anesthesiology and Pain Medicine, 2011
Background: Tricyclic antidepressants (TCAs) are commonly used orally for treating chronic pain states, such as neuropathic pain. TCAs produce analgesia by various mechanisms, including sodium channels, N-methyl-d-aspartate receptors, biogenic amines, opioids, inflammatory mediators, and substance P. Studies have shown that intrathecal tricyclic administration effectively attenuates pain and thermal hyperalgesia in inflammatory and neuropathic pain in rats. Objectives: The aim of this study was to evaluate the effect of two tertiary TCAs in sensory and motor block. We also used bupivacaine as a strong local anesthetic for the control group. Materials and Methods: In a double-blind randomized controlled trial in an animal lab, intrathecal injection of drugs was performed in 30 Wistar male rats. We divided the subjects into 3 groups: group 1: 90 µL Doxepine (50 mM), group 2: 90 µl amitriptyline (60 mM). and group 3: 90 µL bupivacaine (23 mM). Then sensory, motor, and proprioceptive changes were measured at 1, 2, 3, 4, 6, and 12 hours by one examiner. Results: In Groups 1 and 2, a total of 3 rats died. After adjusting the concentrations, amitriptyline had a similar potency but a longer duration of spinal blockade of motor, proprioception, and nociception than did bupivacaine (p < 0.05), whereas doxepin had a reasonable but lower efficacy and shorter duration of spinal blockade than did bupivacaine (p < 0.05). The full recovery time for Group 2 was significantly longer. Conclusions: It seems that tertiary amine drugs such as amitriptyline and doxepin had reasonable potencies of spinal blockade when compared to bupivacaine. However, amitriptyline had a more potent and long-acting spinal anesthetic effect. Amitriptyline may turn out to be a clinically valuable local anesthetic.
Prolongation of epidural bupivacaine effects with hyaluronic acid in rabbits
International journal of pharmaceutics, 2004
To assess the prolongation of epidural bupivacaine by hyaluronic acid viscous formulations we designed a cross-over study in rabbits. Different doses of bupivacaine (3 or 6 mg) either as a solution (bupivacaine hydrochloride), or as viscous formulations with hyaluronic acid (bupivacaine base and bupivacaine hydrochloride) were administered in a rabbit model of epidural anesthesia. In the first part of the study, in vitro release characteristics were determined. Then pharmacodynamic effects and pharmacokinetic profiles of each bupivacaine formulation were studied. The rank order release rate of bupivacaine in vitro was always hydrochloride solution > viscous physical mixture of bupivacaine with hyaluronic acid > viscous ionic complex of bupivacaine base with hyaluronic acid. Onset time of epidural anesthesia was similar whatever the formulation of bupivacaine used. We did not find any blockade prolongation when 3mg bupivacaine was administered, but significant blockade prolonga...
Annals of Medical Research, 2020
The aim of this study was to investigate the effect of combining sodium bicarbonate with bupivacaine on prolonging peripheral nerve block time. Material and Method: Following the approval of the required Ethics Committee, 24 male New Zealand rabbit (4250-5350 g) were randomized and divided into three groups. Group 1 sham n:8; Group 2 (bupivacaine): 0.5 mL of 0.5% bupivacaine (0.5 mg / kg) injected into the perineural area. n:8; and Group 3 (bupivacaine + sodium bicarbonate): 0.5 ml of 0.5% bupivacaine + sodium bicarbonate (125 ml of 8.4% injected into the perineural area. n: 8. After the skin was closed in all groups, the paw pull response was monitored and recorded every 30 minutes until the sensory block of the experimental animal returned back. Hot-plate test was used for analgesia evaluation. In addition, tissue histopathology was examined for histopathological evaluation of the injection site. Sensory block was evaluated with claw tightening test and claw pull test (hot-plate) response. The measurements were carried out every 30 minutes for 120 minutes or until the block was completely resolved. Results: 30., 60. and 90.min paw pull response in Group 2 and Group 3 showed statistically significant elongation when compared to Group 1, this difference disappeared in 120 minutes. Compared to the sham group, the 30 min hot plate and claw pull response was significantly longer in group 3 (sodium bicarbonate and bupivacaine), this difference disappeared in 60 minutes (p = 0.018). Conclusion: When sodium bicarbonate and bupivacaine are combined, it was seen in this study that the sensory block was prolonged. We believe that the current results can be used as a guide for future studies