Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia.

PubMed

Berde, Charles B; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina

2011-12-01

Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

Use of 0.5% bupivacaine with buprenorphine in minor oral surgical procedures.

PubMed

Nagpal, Varun; Kaur, Tejinder; Kapila, Sarika; Bhullar, Ramandeep Singh; Dhawan, Amit; Kaur, Yashmeet

2017-01-01

Minor oral surgical procedures are the most commonly performed procedures by oral and maxillofacial surgeons. Performance of painless surgical procedure is highly appreciated by the patients and is possible through the use of local anesthesia, conscious sedation or general anesthesia. Postoperative pain can also be controlled by the use of opioids, as opioid receptors exist in the peripheral nervous system and offers the possibility of providing postoperative analgesia in the surgical patient. The present study compares the efficacy of 0.5% bupivacaine versus 0.5% bupivacaine with 0.3 mg buprenorphine in minor oral surgical procedures. The present study was conducted in 50 patients who required minor oral surgical procedures under local anesthesia. Two types of local anesthetic solutions were used- 0.5% bupivacaine with 1:200000 epinephrine in group I and a mixture of 39 ml of 0.5% bupivacaine with epinephrine 1:200000 and 1 ml of 300 μg buprenorphine (3 μg/kg)in group II. Intraoperative and postoperative evaluation was carried out for both the anesthetic solutions. The mean duration of postoperative analgesia in bupivacaine group (508.92 ± 63.30 minutes) was quite less than the buprenorphine combination group (1840.84 ± 819.51 minutes). The mean dose of postoperative analgesic medication in bupivacaine group (1.64 ± 0.99 tablets) was higher than buprenorphine combination group (0.80 ± 1.08 tablets). There was no significant difference between the two groups regarding the onset of action of the anesthetic effect and duration of anesthesia. Buprenorphine can be used in combination with bupivacaine for patients undergoing minor oral surgical procedures to provide postoperative analgesia for a longer duration.

Binding of long-lasting local anesthetics to lipid emulsions.

PubMed

Mazoit, Jean-Xavier; Le Guen, Régine; Beloeil, Hélène; Benhamou, Dan

2009-02-01

Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics. The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity, racemic bupivacaine and levobupivacaine seem to clear more rapidly than ropivacaine.

Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.

PubMed

Santos, A C; Arthur, G R; Wlody, D; De Armas, P; Morishima, H O; Finster, M

1995-03-01

Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups. The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.

[Comparative study between 0.5% bupivacaine, 0.5% enantiomeric mixture of bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, for epidural cesarean section anesthesia.].

PubMed

Côrtes, Carlos Alberto Figueiredo; Oliveira, Amaury Sanchez; Castro, Luis Fernando Lima; Cavalcanti, Franz Schubert; Serafim, Maurício Marsaioli; Taia, César; Taia Filho, Siguero

2003-04-01

Clinical trials with local anesthetic levo-enantiomers have shown higher safety due to lower cardiotoxicity. This study aimed at evaluating quality of anesthesia and maternal/fetal repercussions of 0.5% bupivacaine, enantiomeric 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, in epidural cesarean section anesthesia. Participated in this study 90 full-term pregnant women, physical status ASA I, submitted to elective cesarean section under epidural anesthesia, who were divided into tree groups: group I - 23 ml racemic 0.5% bupivacaine with epinephrine; Group II -23 ml enantiomeric 0.5% bupivacaine (S75-R25) with epinephrine; Group III - 23 ml of 0.75% ropivacaine. Fentanyl (2 ml) was associated to local anesthetics in all groups. The following parameters were evaluated: onset, analgesia duration, sensory and motor block degree, time to hysterotomy and delivery, quality of muscle relaxation and anesthesia, maternal hemodynamic and respiratory changes, newborn vitality (evaluated through Apgar score and cord-blood gases analysis), and side-effects. There were no differences among groups, except for anesthesia quality. In groups with predominant levo-enantiomer fraction were clinically worse with the need for anesthetic complementation in three cases. Analgesia duration was longer in the ropivacaine group. Enantiomeric mixture 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine for epidural anesthesia have provided as good conditions as racemic 0.5% bupivacaine for the surgical act. Newborn repercussions have shown that all solutions were equally safe.

[The influence of local anesthetics on human leukocyte functions studied by micro whole blood collection and flowcytometry].

PubMed

Okuno, S; Noda, H; Kugimiya, T; Saionji, K

1996-03-01

The influence of local anesthetics (pure bupivacaine and lidocaine with no preservative) on human leukocyte functions was examined. (a) The effect of bupivacaine on the phagocytosis of granulocyte was studied by bioassay. (b) The effect of lidocaine on the appearance of iC3b receptor (CR3) of granulocyte and monocyte (which is an important cell-adhesion-factor) was examined using flowcytometry. (c) The influence of lidocaine on phagocytosis of granulocyte and monocyte and on respiratory burst of granulocyte was examined using flowcytometry. (d) The influence of lidocaine on phagocytosis and that on respiratory burst were compared. These studies revealed that both phagocytosis and respiratory burst were inhibited by lidocaine, and the inhibition of respiratory burst was stronger than the inhibition of phagocytosis by local anesthetics' immunosuppressive effects. It was concluded that the balance of immunosuppressive action due to antimicrobial action and bactericidal ability of local anesthetics determined the occurrence of local bacterial infection.

Development of bupivacaine decorated reduced graphene oxide and its local anesthetic effect-In vivo study.

PubMed

Zhang, Zhi; Zhang, Xin; Li, Aixiang; Ma, Chuangen

2018-03-01

The present works aims to develop bupivacaine modified reduced graphene oxide (BPV/RGO), and comparative evaluation of their anesthetic effect with free bupivacaine (BPV). The prepared BPV/RGO was studied by using various spectroscopic and microscopic characterization studies. In vitro drug release from BPV/RGO was studied using HPLC analysis. The cytotoxicity of BPV/RGO was studied against fibroblast (3T3) cells. In vivo evaluation of anesthetic effects was performed on animal models. BPV/RGO showed a prolonged in vitro release and lower cytotoxicity when compared to free BPV. Also, BPV/RGO showed a significantly prolonged analgesic effect when compared to free BPV. Further, the prepared BPV/RGO drug delivery system demonstrated to function as gifted to overcome the drawbacks of free BPV and other available drug delivery systems by prolonging the anesthetic effect with poor cytotoxicity. Copyright © 2018. Published by Elsevier B.V.

Comparison between analgesic effect of bupivacaine thoracic epidural and ketamine infusion plus wound infiltration with local anesthetics in open cholecystectomy.

PubMed

Megahed, Nagwa Ahmed Ebrahim; Ellakany, Mohamed; Elatter, Ahmed Mohammed Ibrahim; Moustafa Teima, Mohamed Ahmed Ali

2014-01-01

Neuraxial blocks result in sympathetic block, sensory analgesia and motor block. Continuous epidural anesthesia through a catheter offers several options for perioperative analgesia. Local anesthetic boluses or infusions can provide profound analgesia. Although the role of low-dose ketamine (<2 mg/kg intramuscular, <1 mg/kg intravenous [IV] or ≤ 20 μg/kg/min by IV infusion) in the treatment of post-operative pain is controversial, perioperative administration of a small dose of ketamine may be valuable to a multimodal analgesic regimen. A local anesthetic can be used for wound infiltration intra-operative to minimized the surgical pain. A prospective randomized study was performed in which 40 patients scheduled for elective open cholecystectomy under general anesthesia admitted to the Medical Research Institute were included and further subdivided into two groups, group A, received thoracic epidural catheter at T7-8, activation was done 20 min before induction of anesthesia with plain bupivacaine at a concentration of 0.25% at a volume of 1 ml/segment aiming to block sensory supply from T4-L2, then received continuous thoracic epidural infusion intra and postoperatively with plain bupivacaine at a concentration of 0.125% at a rate of 5 ml/h for 24 h, group B received 0.3 mg/kg bolus of ketamine at the time of induction then 0.1 mg/kg/h ketamine IV infusion during surgery followed by wound infiltration with 15 ml of plain bupivacaine 0.5% at the time of skin closure. Bupivacaine thoracic epidural analgesia had better control on heart rate and mean arterial blood pressure than ketamine infusion plus wound infiltration with local anesthetic in patients undergoing open cholecystectomy. Thoracic epidural analgesia had better control on hemodynamic changes intra-and postoperatively than ketamine infusion with local wound infiltration in open cholecystectomy.

Sufentanil in combination with low-dose hyperbaric bupivacaine in spinal anesthesia for cesarean section: a randomized clinical trial.

PubMed

Dourado, Alexandre Dubeux; Filho, Ruy Leite de Melo Lins; Fernandes, Raphaella Amanda Maria Leite; Gondim, Marcelo Cavalcanti de Sá; Nogueira, Emmanuel Victor Magalhães

A double blind randomized clinical trial of sufentanil as an adjunct in spinal anesthesia for cesarean section and, thereby, be able to reduce the dose of bupivacaine, a local anesthetic, with the same result of an anesthetic block with higher doses but with fewer perioperative side effects, such as hypotension. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Sufentanil in combination with low-dose hyperbaric bupivacaine in spinal anesthesia for cesarean section: a randomized clinical trial].

PubMed

Dourado, Alexandre Dubeux; Lins Filho, Ruy Leite de Melo; Fernandes, Raphaella Amanda Maria Leite; de Sá Gondim, Marcelo Cavalcanti; Nogueira, Emmanuel Victor Magalhães

A double blind randomized clinical trial of sufentanil as an adjunct in spinal anesthesia for cesarean section and, thereby, be able to reduce the dose of bupivacaine, a local anesthetic, with the same result of an anesthetic block with higher doses but with fewer perioperative side effects, such as hypotension. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain.

PubMed

Bergese, Sergio D; Onel, Erol; Portillo, Juan

2011-11-01

SUMMARY An extended-release, multivesicular liposome-encapsulated form of the local anesthetic bupivacaine, DepoFoam(®) bupivacaine (proposed proprietary name EXPAREL™), is in development for use as part of a multimodal regimen for the treatment of postsurgical pain. Placebo- and active-controlled clinical trials in patients who have undergone either orthopedic or soft-tissue procedures indicate that a single local administration into the surgical site results in analgesic activity for up to 3-4 days and decreases the use of opioid rescue medication. The safety profile of DepoFoam bupivacaine appears to be similar to that of bupivacaine HCl, and adverse events are dose-related.

Liposomal bupivacaine for regional anesthesia.

PubMed

Uskova, Anna; O'Connor, Jessica E

2015-10-01

Using a regional block in a multimodal approach to postoperative analgesia management involves addressing, which local anesthetic and how much should be used to ensure adequate pain relief to reduce related morbidity and mortality. This article will review literature surrounding the recently approved formulation of slow release liposomal bupivacaine, define its proven benefits, and identify ongoing studies to further examine the utility of this novel formulation by various routes. Recent Phase II and III clinical trials have demonstrated the ability of liposomal bupivacaine to provide prolonged analgesia, maintain a high safety profile in therapeutic doses, and decrease opioid requirements when compared with placebo in local infiltration applications for up to 24 h. Between 24 and 72 h after study drug administration, there was minimal to no difference between EXPAREL and placebo treatments on mean pain intensity. Conventional bupivacaine or ropivacaine groups (current standard practice in many hospitals in the USA) were not compared. In addition, the analgesic efficacy, cost-effectiveness, and safety profile of liposomal bupivacaine has not thoroughly been studied in various standard clinical settings such as perineural, intrathecal, and epidural administration. Current published data do not provide superior clinical results for EXPAREL over conventional bupivacaine based upon the lack of adequately powered multicentered clinical trials with comparison groups. Further investigation is necessary to identify the analgesic efficacy and safety profile of liposomal bupivacaine versus standard local anesthetics and to define the optimal clinical indication for liposomal bupivacaine administration in regional anesthesia.

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

PubMed

Kamphuis, E T; Ionescu, T I; Kuipers, P W; de Gier, J; van Venrooij, G E; Boon, T A

1998-02-01

The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics for spinal anesthesia seems to be preferable.

Local anesthetic effects of bupivacaine loaded lipid-polymer hybrid nanoparticles: In vitro and in vivo evaluation.

PubMed

Ma, Pengju; Li, Ting; Xing, Huaixin; Wang, Suzhen; Sun, Yingui; Sheng, Xiugui; Wang, Kaiguo

2017-05-01

There is a compelling need for prolonged local anesthetic that would be used for analgesia with a single administration. However, due to the low molecular weight of local anesthetics (LA) (lidocaine, bupivacaine, procaine, dibucaine, etc), they present fast systemic absorption. The aim of the present study was to develop and evaluate bupivacaine lipid-polymer hybrid nanoparticles (BVC LPNs), and compared with BVC loaded PLGA nanoparticles (BVC NPs). Their morphology, particle size, zeta potential and drug loading capacity were evaluated. In vitro release study, stability and cytotoxicity were studied. In vivo evaluation of anesthetic effects was performed on animal models. A facile nanoprecipitation and self-assembly method was optimized to obtain BVC LPNs, composed of PLGA, lecithin and DSPE-PEG 2000 , of ∼175nm particle size. Compared to BVC NPs, BVC LPNs exhibited prolonged in vitro release in phosphate-buffered saline (pH=7.4). Further, BVC LPNs displayed enhanced in vitro stability in 10% FBS and lower cytotoxicity (the concentration of BVC ranging from 1.0μM to 20μM). In addition, BVC LPNs exhibited significantly prolonged analgesic duration. These results demonstrate that the LPNs could function as promising drug delivery system for overcoming the drawbacks of poor stability and rapid drug leakage, and prolonging the anesthetic effect with slight toxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

PubMed

Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

2017-01-01

This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

Chondrotoxicity of Liposomal Bupivacaine in Articular Chondrocytes: Preliminary Findings.

PubMed

Shaw, K Aaron; Johnson, Peter C; Zumbrun, Steve; Chuang, Augustine H; Cameron, Craig D

2017-03-01

The chondrotoxicity of local anesthetics has been previously recognized. Recent introduction of a liposomal formulation of bupivacaine has been found to significantly improve postoperative pain control but its effect on chondrocyte viability has yet to be investigated with this new formulation. We sought to assess the in vitro chondrotoxicity of liposomal bupivacaine. Chondrocytes were isolated from articular cartilage from fresh stifle joints and grown in culture medium. Cultured chondrocyte-derived cells (CDCs) were treated with 0.9% normal saline solution, 0.5%, 0.25%, and 0.13% bupivacaine and ropivacaine, 1.3% liposomal bupivacaine for 1 hour. Following treatment, cells were washed and incubated in media for 23 hours. The CDCs were then harvested and viability was assessed by flow cytometry using SYTOX green dead cell stain. Treated CDCs demonstrated a dose-response effect for chondrocyte viability when treated with bupivacaine, ropivacaine, and liposomal bupivacaine. Liposomal bupivacaine demonstrated the highest chondrocyte viability following treatment. Ropivacaine demonstrated higher chondrocyte viability than bupivacaine. Following 1 hour of treatment, liposomal bupivacaine demonstrated the highest chondrocyte viability. Chondrocyte viability was inversely proportional to anesthetic concentration. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Raman and Infrared spectroscopies and X-ray diffraction data on bupivacaine and ropivacaine complexed with 2-hydroxypropyl-β-cyclodextrin.

PubMed

Martins, Murillo L; Eckert, Juergen; Jacobsen, Henrik; Dos Santos, Everton C; Ignazzi, Rosanna; de Araujo, Daniele Ribeiro; Bellissent-Funel, Marie-Claire; Natali, Francesca; Marek Koza, Michael; Matic, Aleksander; de Paula, Eneida; Bordallo, Heloisa N

2017-12-01

The data presented in this article are related to the research article entitled "Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations (http://dx.doi.org/10.1016/j.ijpharm.2017.03.051)" (Martins et al., 2017) [1]. This work shows the molecular and structural behavior of the local anesthetics (LAs) bupivacaine (BVC, C 18 H 28 N 2 O) and ropivacaine (RVC, C 17 H 26 N 2 O) before and after complexation with the water-soluble oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HP-β-CD).

Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

PubMed Central

Iwasaki, Koji; Sudo, Hideki; Yamada, Katsuhisa; Ito, Manabu; Iwasaki, Norimasa

2014-01-01

Background Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell–alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time- and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death. PMID:24642945

Effect of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on intraocular pressure in dogs.

PubMed

Sarchahi, Ali Asghar; Eskandari, Mehdi

2018-06-23

To measure IOP in animals, it is often necessary to use topical anesthetics. The use of these drugs may cause changes in IOP and interfere with the final results. To address this issue, the effects of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on IOP were investigated in ten adult dogs. One drop of tetracaine was instilled in the right eye of half of the dogs and in the left eye of the other dogs; normal saline was instilled in the fellow eyes. The IOP in each dog was measured before and at 0, 5, 10, 15, 20, 25, 30, and 35 min after drug instillation using an electronic rebound tonometer. The effects of the other anesthetics were studied in the same way at intervals of at least 1 week. After instillation of tetracaine, the IOP decreased gradually, such that after 15 min, the IOP was significantly lower than the baseline (p = 0.022) and control values (p = 0.048). Proparacaine also reduced IOP after 10 min compared to baseline values (p = 0.046), but the two other drugs, bupivacaine and lidocaine, had no significant effect on IOP. The duration of eye anesthesia was 16, 20, 22, and 34 min for tetracaine, lidocaine, bupivacaine, and proparacaine, respectively. We recommend using drugs that combine inducing longer anesthesia with producing the smallest change in IOP, such as bupivacaine and, subsequently, lidocaine. Tetracaine and proparacaine have a significant effect on IOP, and if these drugs are used, this effect should be considered.

Liposomal bupivacaine and clinical outcomes.

PubMed

Tong, Yi Cai Isaac; Kaye, Alan David; Urman, Richard D

2014-03-01

In the multimodal approach to the management of postoperative pain, local infiltration and regional blocks have been increasingly utilized for pain control. One of the limitations of local anesthetics in the postoperative setting is its relatively short duration of action. Multivesicular liposomes containing bupivacaine have been increasingly utilized for their increased duration of action. Compared with bupivacaine HCl, local infiltration of liposomal bupivacaine has shown to have an increase in duration of action and causes delay in peak plasma concentration. In this article, we attempt to review the clinical literature surrounding liposomal bupivacaine and its evolving role in perioperative analgesia. This new bupivacaine formation may have promising implications in postoperative pain control, resulting in increased patient satisfaction and a decrease in both hospital stay and opioid-induced adverse events (AEs). Although more studies are needed, the preliminary clinical trials suggest that liposomal bupivacaine has predictable pharmacokinetics, a similar side effect profile compared with bupivacaine HCl, and is effective in providing increased postoperative pain control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.

PubMed

Bräu, M E; Vogel, W; Hempelmann, G

1998-10-01

Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae.

PubMed

Ok, Seong-Ho; Lee, Soo Hee; Kwon, Seong-Chun; Choi, Mun Hwan; Shin, Il-Woo; Kang, Sebin; Park, Miyeong; Hong, Jeong-Min; Sohn, Ju-Tae

2017-02-13

The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH₂-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization.

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae

PubMed Central

Ok, Seong-Ho; Lee, Soo Hee; Kwon, Seong-Chun; Choi, Mun Hwan; Shin, Il-Woo; Kang, Sebin; Park, Miyeong; Hong, Jeong-Min; Sohn, Ju-Tae

2017-01-01

The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH2-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization. PMID:28208809

Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia.

PubMed

Golembiewski, Julie; Dasta, Joseph

2015-06-01

Opioid analgesics, the cornerstone of effective postsurgical pain management, may be associated with risk of opioid-related adverse drug events (ADEs) that may complicate the postsurgical experience. Perioperative multimodal analgesic regimens have the potential to improve postsurgical pain control and may permit use of lower analgesic doses and reduce the incidence of opioid-related ADEs. Utility of traditional local anesthetic formulations to provide analgesia over the entire postsurgical period is limited by their short duration of action. Liposome bupivacaine, a liposomal formulation of bupivacaine indicated for single-dose administration into the surgical site to produce postsurgical analgesia, was evaluated in multiple surgical models as part of multimodal analgesic regimens and was found in clinical trials to provide postsurgical analgesia for up to 72 hours. Here, we provide an overview of the available multimodal analgesic options and recent recommendations for optimal postsurgical pain management. A review of the literature was conducted, and results from recent clinical trials are included. The use of a multimodal analgesic regimen, including liposome bupivacaine, can extend the time to first postsurgical opioid use, may reduce postsurgical opioid consumption, and reduce hospital length of stay and costs compared with an opioid-only analgesic regimen. Use of multimodal analgesic regimens is a practical way to achieve good postsurgical analgesia while minimizing reliance on opioids and associated adverse events. Taken as a whole, evidence from the clinical studies of liposome bupivacaine suggests this local anesthetic formulation may be a useful component of multimodal analgesic regimens for managing postsurgical pain in select patients, with the potential to reduce opioid use and opioid-related ADEs in the postsurgical setting. As with bupivacaine, appropriate use of liposome bupivacaine to optimize clinical effects, economic implications, and patient tolerability will depend on appropriate patient selection, practitioner training, and institutional protocols. As a component of a multimodal analgesic regimen, liposome bupivacaine represents a new approach to extending the duration of postsurgical analgesia. Further studies across a range of surgical settings should help clarify the most appropriate roles for this prolonged-release formulation of bupivacaine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

PubMed

Ohri, Rachit; Wang, Jeffrey Chi-Fei; Blaskovich, Phillip D; Pham, Lan N; Costa, Daniel S; Nichols, Gary A; Hildebrand, William P; Scarborough, Nelson L; Herman, Clifford J; Strichartz, Gary R

2013-09-01

Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the incision. Significant suppression of postoperative pain by the slow-release bupivacaine preparation outlasts its anesthetic action on intact skin. These findings demonstrate preventive analgesia and indicate the importance of acute processes in the development of chronic postoperative pain.

Effect of intrathecal hyperbaric bupivacaine with small dose clonidine versus hyperbaric bupivacaine alone in lower abdominal surgeries: A comparative study

PubMed Central

Tyagi, Amit; Rastogi, Shivani; Tripathi, Manoj; Bhandari, Rajlaxmi; Bais, Prateek Singh; Singh, Mahendra

2016-01-01

Context: The continued success of regional anesthetic techniques can be credited due to improved local anesthetic drugs, with lower toxicities and longer duration of action, but still many efforts are being done to increase the duration of the block and postoperative analgesia. Therefore, use of adjuvant drugs for anesthesia is intended to prolong analgesia and preventing deleterious clinical effects of local anesthetics. Aims: The present study is designed to evaluate effects of intrathecal hyperbaric bupivacaine versus hyperbaric bupivacaine with low dose clonidine on the onset and level of sensory and motor block, the intensity of motor blockade, and time of analgesia required in the postoperative period. Settings and Design: Study area were our operation theater and postanesthesia care unit of Department of Anesthesiology, this was a prospective, randomized, placebo-controlled, and double-blind study for a period of 1 year comprising of 60 patients. Materials and Methods: Patients were randomly allocated into two groups: Group 1 (S) (n = 30): Patients received intrathecal hyperbaric bupivacaine 12.5 mg with normal saline 0.5 ml and Group 2 (C) (n = 30): Patients received intrathecal hyperbaric bupivacaine 12.5 mg with 1 μg/kg clonidine (approximated to 0.5 ml with normal saline). Statistical Analysis: Two groups were compared by Student's t-test, Chi-square test; ANOVA and significance of mean difference bet were done by Newman–Keuls test. Results and Conclusion: Duration of analgesia was prolonged in Group C (363.07 ± 166.30 min) patients compared to Group S patients (226.95 ± 119 min) and they also required less top up analgesic in the postoperative period. PMID:27212746

The systemic toxicity of equipotent proxymetacaine, oxybuprocaine, and bupivacaine during continuous intravenous infusion in rats.

PubMed

Hung, Ching-Hsia; Liu, Kuo-Sheng; Shao, Dong-Zi; Cheng, Kuang-I; Chen, Yu-Chung; Chen, Yu-Wen

2010-01-01

Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity. After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After i.v. infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate. Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses. Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity.

Technique for Periarticular Local Infiltrative Anesthesia Delivery Using Liposomal Bupivacaine in Total Knee Arthroplasty.

PubMed

Connelly, Jacob O; Edwards, Paul K; Mears, Simon C; Barnes, C Lowry

2015-01-01

Postoperative pain control after total knee arthroplasty is a major contributing factor to patient satisfaction, rehabilitation, and length of stay. Current clinical practice guidelines recommend a multimodal pain management protocol, including the use of regional anesthesia. Periarticular injection (PAI) has been shown to provide excellent pain relief after total knee arthroplasty. Recently, liposomal bupivacaine has been introduced as a long-acting alternative to traditional local anesthetics, such as bupivacaine or ropivacaine. Liposomal bupivacaine is a sustained-release preparation designed to provide local analgesia up to 72 hours after initial application. The efficacy of PAI relies significantly on a meticulous, systematic injection technique. This article details recommendations for solution preparation and injection during total knee arthroplasty on the basis of the experience of a high-volume orthopaedic reconstruction service.

Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses

PubMed Central

Paganelli, Meaghan A.

2015-01-01

NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775

Ultra-long-duration local anesthesia produced by injection of lecithin-coated methoxyflurane microdroplets.

PubMed

Haynes, D H; Kirkpatrick, A F

1985-11-01

This study was designed to evaluate a new drug delivery system. The authors undertook to determine if microdroplets prepared by encapsulating volatile anesthetics with a membrane of lecithin could be used for local anesthesia. Local anesthesia was determined by monitoring the response of the rat to tail clamping and electrical stimulation of the skin following the intradermal injection of the microdroplets. Microdroplets were prepared from isoflurane, enflurane, halothane, methoxyflurane, diethyl ether, chloroform, and heptane. Although all microdroplet preparations produced local anesthesia, only methoxyflurane microdroplets produced an ultra-long duration of local anesthesia (approximately 24 h). Further characterization of the methoxyflurane microdroplets revealed two important differences from conventional local anesthetics. First, the local anesthetic effect of methoxyflurane reached a plateau that did not change significantly for 20 h while the injection of lidocaine and bupivacaine resulted in a peak effect that returned to baseline within 1 and 3 h, respectively. Second, the anesthetic effect of methoxyflurane remained essentially localized to the site of injection, while the anesthetic effect of lidocaine and bupivacaine migrated 15 cm in less than 1 h. The toxicity and safety of methoxyflurane were evaluated. When administered over the dosage range 1-16% (v/v) intradermally, or by injections into muscle, or by repeat injections every 4 days for 16 days, all animals regained their pretreatment response to painful stimulations, and there was no evidence of gross injury to tissue. Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect. The present study demonstrates that methoxyflurane microdroplets produce an anesthetic effect that is highly localized, stable in intensity, ultra-long in duration, and reversible.

Analgesic effect of bupivacaine on extraperitoneal laparoscopic hernia repair.

PubMed

Saff, G N; Marks, R A; Kuroda, M; Rozan, J P; Hertz, R

1998-08-01

Local anesthetics decrease postoperative pain when placed at the surgical site. Patients benefit from laparoscopic extraperitoneal hernia repair because this allows earlier mobilization than the more classical open surgical approach. The purpose of this study was to determine the pain-sparing efficacy of local anesthetics placed in the preperitoneal fascial plane during extraperitoneal laparoscopic inguinal hernia surgery. Forty-two outpatients were included in a double-blind, randomized, placebo-controlled, institutional review board-approved study. At the conclusion of a standardized general anesthetic, 21 patients received 60 mL of 0.125% bupivacaine into the preperitoneal fascial plane before incisional closure, whereas the other 21 patients received 60 mL of the isotonic sodium chloride solution placebo. Postoperative pain was assessed 1, 4, 8, 24, and 72 h postoperatively. In addition, postoperative fentanyl and outpatient acetaminophen 500 mg/hydrocodone 5 mg requirements were recorded. All hernia repairs were performed by the same surgeon. Appropriate statistical analyses were used. There were no significant differences between the bupivacaine and isotonic sodium chloride solution groups with regard to postoperative pain scores, length of postanesthesia care unit stay, or analgesic requirements. Furthermore, neither unilateral versus bilateral repair nor operative time affected the measured parameters. The addition of 60 mL of 0.125% bupivacaine into the preperitoneal fascial plane during extraperitoneal laparoscopic hernia repair did not significantly alter pain scores, supplementary analgesic requirements, or recovery room length of stay. The placement of 60 mL of 0.125% bupivacaine into the preperitoneal fascial plane during extraperitoneal laparoscopic hernia repair did not significantly alter pain scores, supplementary analgesic requirements, or recovery room length of stay.

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.

PubMed

Heinonen, J A; Schramko, A A; Skrifvars, M B; Litonius, E; Backman, J T; Mervaala, E; Rosenberg, P H

2017-04-01

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid ® ( n = 7) with Ringer's acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer's acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.

Bupivacaine (Marcaine): an evaluation of its tissue and systemic toxicity in humans.

PubMed

Moore, D C; Mather, L E; Bridenbaugh, L D; Thompson, G E; Balfour, R I; Lysons, D F; Horton, W G

1977-01-01

In countries other than the U.S.A., dosages of bupivacaine have been limited to 100 mg without epinephrine and 150 mg with epinephrine. A review of 7,688 regional block procedures employing bupivacaine in concentrations of 0.25, 0.5, and 0.75%, and in dosages as high as 600 mg, indicated that such stringent restrictions: (1) are unwarranted, (2) make comparisons with other local anesthetic agents difficult, and (3) are in need of revision.

Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

PubMed Central

Martín, Pedro; Enrique, Nicolás; Palomo, Ana R. Roldán; Rebolledo, Alejandro; Milesi, Veronica

2012-01-01

Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 µM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 µM) can also block whole-cell K+ currents (~45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account. PMID:22688134

Potential Side Effect of Inadvertent Intravascular Administration of Liposomal Bupivacaine

DTIC Science & Technology

2017-06-01

treat and is potentially fatal. LAST can impair function of the central nervous system and cause cardiovascular collapse, with potentially...in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. ILE is gaining...to the sites of toxic action in the central nervous system and the heart. However, liposomal formulations of local anesthetics (EXPAREL in

Liposomal Bupivacaine for Pain Control After Anterior Cruciate Ligament Reconstruction: A Prospective, Double-Blinded, Randomized, Positive-Controlled Trial.

PubMed

Premkumar, Ajay; Samady, Heather; Slone, Harris; Hash, Regina; Karas, Spero; Xerogeanes, John

2016-07-01

Local anesthetics are commonly administered into surgical sites as a part of multimodal pain control regimens. Liposomal bupivacaine is a novel formulation of bupivacaine designed for slow diffusion of a single dose of local anesthetic over a 72-hour period. While early results are promising in various settings, no studies have compared pain management regimens containing liposomal bupivacaine to traditional regimens in patients undergoing anterior cruciate ligament (ACL) reconstruction. To evaluate liposomal bupivacaine in comparison with 0.25% bupivacaine hydrochloride (HCl) for pain control after ACL reconstruction. Randomized controlled trial; Level of evidence, 1. A total of 32 adult patients undergoing primary ACL reconstruction with a soft tissue quadriceps tendon autograft between July 2014 and March 2015 were enrolled. All patients received a femoral nerve block immediately before surgery. Patients then received either a 40-mL suspension of 20 mL Exparel (1 vial of bupivacaine liposome injectable suspension) and 20 mL 0.9% injectable saline or 20 mL 0.5% bupivacaine HCl and 20 mL 0.9% injectable saline, which was administered into the graft harvest site and portal sites during surgery. Patients were given either a postoperative smartphone application or paper-based journal to record data for 1 week after ACL reconstruction. Of the 32 patients recruited, 29 patients were analyzed (90.6%). Two patients were lost to follow-up, and 1 was excluded because of a postoperative hematoma. There were no statistically significant differences in postoperative pain, medication use, pain location, recovery room time, or mobility between the 2 study groups. There were comparable outcomes with 0.25% bupivacaine HCl at a 200-fold lower cost than liposomal bupivacaine. This study does not support the widespread use of liposomal bupivacaine for pain control after ACL reconstruction in the setting of a femoral nerve block. ClinicalTrials.gov NCT02189317. © 2016 The Author(s).

Addition of dexmedetomidine to bupivacaine in supraclavicular brachial plexus block.

PubMed

Aksu, Recep; Bicer, Cihangir

2017-06-26

Research is ongoing to determine the lowest dose of local anesthetics in brachial plexus block that provides adequate anesthesia and postoperative analgesia and reduces complications related to local anesthetics. Patients 18-65 years of age who underwent upper limb surgery and who received ultrasound-guided supraclavicular brachial plexus block at the Erciyes University Faculty of Medicine Hospital between February 2014 and January 2015 were included in the study (n=50). Supraclavicular brachial plexus blocks were performed on Group B cases by adding 30 ml 0.33% bupivacaine and on Group BD cases by adding 15 ml 0.33% bupivacaine and 1 µg / kg dexmedetomidine. Block success was evaluated by the onset and block duration of motor and sensory block and the duration of analgesia. The block success of Group B and Group BD was 92.6% and 89.3%, respectively (P = 1.000). Onset time of sensory block, degree of sensory block, duration of sensory block, onset time of motor block, degree of motor block and duration of motor block were similar in both groups in the intergroup comparison (P > 0.05). Duration of analgesia and the operative conditions of groups were similar (P > 0.05). In the implementation of ultrasound-guided supraclavicular brachial plexus block, block success, sensory and motor block and analgesia duration were similar for patients anaesthetized with 30 ml of bupivacaine in comparison with dexmedetomidine+bupivacaine (when the bupivacaine dose was reduced by 50% by the addition of the adjuvant).

Comparison of spinal block after intrathecal clonidine-bupivacaine, buprenorphine-bupivacaine and bupivacaine alone in lower limb surgeries.

PubMed

Arora, Major Vishal; Khan, Mohammad Zafeer; Choubey, Major Sanjay; Rasheed, Mohammad Asim; Sarkar, Arindam

2016-01-01

Various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. The α2-adrenergic agonist clonidine and potent opioid buprenorphine have the ability to potentiate the effects of local anesthetics. The purpose of this prospective, double-blind study was to compare onset, duration of sensory and motor block, effect on hemodynamics, level of sedation, duration of postoperative analgesia, and any adverse effects of clonidine and buprenorphine. Seventy-five American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into three Groups A, B, and C. Control Group A received injection bupivacaine 0.5% (heavy) 2.5 ml + saline 0.5 ml whereas Group B received injection bupivacaine 0.5% (heavy) 2.5 ml + injection buprenorphine 50 μg and Group C received injection bupivacaine 0.5% (heavy) 2.5 ml + preservative free injection clonidine 50 μg intrathecally. Unpaired Student's t -test and Z-test were used for comparing data. Statistically highly significant differences in mean time of sensory regression to L1, mean time to attain the Bromage Score of 1, and mean time of first rescue analgesic request were observed between the three groups. The patients did not suffer any serious side effects. Administration of buprenorphine and clonidine intrathecally does potentiate the duration of analgesia, sensory and motor block, with buprenorphine having a long-lasting effect.

In vitro characterization and in vivo analgesic and anti-allodynic activity of PLGA-bupivacaine nanoparticles

NASA Astrophysics Data System (ADS)

Garcia, Xavier; Escribano, Elvira; Domenech, Josep; Queralt, Josep; Freixes, Joan

2011-05-01

An injectable controlled release system containing local anesthetics able to provide long-lasting analgesia in nociceptive and neuropathic pain could have a marked impact in pain management. In order to address this issue, bupivacaine, a widely used local anesthetic, has been nanoencapsulated using poly(lactic-co-glycolic acid) from an oil-in-water emulsion by the solvent evaporation technique. Nanoparticles were evaluated in vitro studying their drug release mechanism by fitting different model equations, and in vivo by testing its analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury in rats, respectively. The particle size of the PLGA nanoparticles obtained was of 453 ± 29 nm, the encapsulation efficiency, drug loading, and burst effect at 30 min were 82.10 ± 0.001, 45.06 ± 0.001, and 4.6 ± 0.6%, respectively. A prolonged release of the drug in comparison to bupivacaine solution was seen. The mean dissolution time (MDT) obtained for nanoparticles was relatively long (9.44 ± 0.56 h) proving the sustained release process, while the dissolution efficiency (DE) (84.10 ± 1.01%) was similar to the maximum percentage of drug released. Korsmeyer-Peppas was the best model that fitted our release data. A non-Fickian mechanism was concluded to be involved in the release of bupivacaine from the nanoparticles, taking into account the value of the diffusional exponent obtained ( n = 0.95). After local infiltration in the rat, the antinociceptive and anti-allodynic activity of the nanoencapsulated bupivacaine was longer lasting than that of bupivacaine solution. An increase in the values of the area under the curve (AUC) of the antinociceptive and anti-allodynic effect versus time of 67 and 36%, respectively, was observed when the drug was encapsulated.

Modifying the baricity of local anesthetics for spinal anesthesia by temperature adjustment: model calculations.

PubMed

Heller, Axel R; Zimmermann, Katrin; Seele, Kristin; Rössel, Thomas; Koch, Thea; Litz, Rainer J

2006-08-01

Although local anesthetics (LAs) are hyperbaric at room temperature, density drops within minutes after administration into the subarachnoid space. LAs become hypobaric and therefore may cranially ascend during spinal anesthesia in an uncontrolled manner. The authors hypothesized that temperature and density of LA solutions have a nonlinear relation that may be described by a polynomial equation, and that conversion of this equation may provide the temperature at which individual LAs are isobaric. Density of cerebrospinal fluid was measured using a vibrating tube densitometer. Temperature-dependent density data were obtained from all LAs commonly used for spinal anesthesia, at least in triplicate at 5 degrees, 20 degrees, 30 degrees, and 37 degrees C. The hypothesis was tested by fitting the obtained data into polynomial mathematical models allowing calculations of substance-specific isobaric temperatures. Cerebrospinal fluid at 37 degrees C had a density of 1.000646 +/- 0.000086 g/ml. Three groups of local anesthetics with similar temperature (T, degrees C)-dependent density (rho) characteristics were identified: articaine and mepivacaine, rho1(T) = 1.008-5.36 E-06 T2 (heavy LAs, isobaric at body temperature); L-bupivacaine, rho2(T) = 1.007-5.46 E-06 T2 (intermediate LA, less hypobaric than saline); bupivacaine, ropivacaine, prilocaine, and lidocaine, rho3(T) = 1.0063-5.0 E-06 T (light LAs, more hypobaric than saline). Isobaric temperatures (degrees C) were as follows: 5 mg/ml bupivacaine, 35.1; 5 mg/ml L-bupivacaine, 37.0; 5 mg/ml ropivacaine, 35.1; 20 mg/ml articaine, 39.4. Sophisticated measurements and mathematic models now allow calculation of the ideal injection temperature of LAs and, thus, even better control of LA distribution within the cerebrospinal fluid. The given formulae allow the adaptation on subpopulations with varying cerebrospinal fluid density.

Serum Ropivacaine Concentrations and Systemic Local Anesthetic Toxicity in Trauma Patients Receiving Long-Term Continuous Peripheral Nerve Block Catheters

DTIC Science & Technology

2010-02-01

concentrations were calculated from the following 2 methods: 1. Using peak area ratio of ropivacaine/ bupivacaine of samples versus peak area ratio of...ropivacaine/ bupivacaine of standards (0–3000 ng/mL) using the following formula: RopS (PA of Rop)/(PA of Bup)S /(PA of Rop)/(PA of Bup)STD Bup...1/mL serum used) where Rop ropivacaine, Bup bupivacaine , PA peak area, S sample, and STD standard. 2. Samples of ropivacaine concentrations

Duration of Action of Bupivacaine Hydrochloride Used for Palatal Sensory Nerve Block in Infant Pigs

PubMed Central

Holman, Shaina Devi; Gierbolini-Norat, Estela M.; Lukasik, Stacey L.; Campbell-Malone, Regina; Ding, Peng; German, Rebecca Z.

2015-01-01

Summary Bupivacaine hydrochloride is frequently used in veterinary dental procedures to reduce the amount of general anesthesia needed and to reduce post-procedural pain. The aim of this study was to develop a novel method to test local anesthetic duration in mammals. Six infant pigs were placed under deep/surgical anesthesia with 3 % isoflurane and oxygen while 0.5 ml of 0.5 % bupivacaine hydrochloride was injected to block the two greater palatine and the nasopalatine nerves. They were then maintained under light anesthesia with 0.5–1.0 % isoflurane. Beginning 15-minutes after the injection, 7 sites in the oral cavity were stimulated using a pointed dental waxing instrument, including 3 sites on the hard palate. The response, or lack of response, to the stimulus was recorded on video and in written record. The bupivacaine hydrochloride injections lasted 1 to 3-hours before the animals responded to the sensory stimulation with a reflexive movement. This study provides evidence that bupivacaine used to anesthetize the hard palate has a relatively short and variable duration of action far below what is expected based on its pharmacokinetic properties. PMID:25185333

Pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration in surgical patients: simultaneous investigation of absorption and disposition kinetics using stable isotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burm, A.G.; Van Kleef, J.W.; Vermeulen, N.P.

1988-10-01

The pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration were studied in 12 surgical patients using a stable isotope method. After subarachnoid administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of the unlabelled and the deuterium-labelled local anesthetics were determined using a combination of capillary gas chromatography and mass fragmentography. Bi-exponential functions were fitted to the plasma concentration-time data of the deuterium-labelled local anesthetics. The progression of the absorption was evaluated using deconvolution. Mono- and bi-exponential functions were then fitted to the fraction absorbed versus timemore » data. The distribution and elimination half-lives of the deuterium-labelled analogues were 25 +/- 13 min (mean +/- SD) and 121 +/- 31 min for lidocaine and 19 +/- 10 min and 131 +/- 33 min for bupivacaine. The volumes of the central compartment and steady-state volumes of distribution were: lidocaine 57 +/- 10 l and 105 +/- 25 l, bupivacaine 25 +/- 6 l and 63 +/- 22 l. Total plasma clearance values averaged 0.97 +/- 0.21 l/min for lidocaine and 0.56 +/- 0.14 l/min for bupivacaine. The absorption of lidocaine could be described by a single first order absorption process, characterized by a half-life of 71 +/- 17 min in five out of six patients. The absorption of bupivacaine could be described adequately assuming two parallel first order absorption processes in all six patients. The half-lives, characterizing the fast and slow absorption processes of bupivacaine, were 50 +/- 27 min and 408 +/- 275 min, respectively. The fractions of the dose, absorbed in the fast and slow processes, were 0.35 +/- 0.17 and 0.61 +/- 0.16, respectively.« less

Ultrasound-guided rectus sheath block or wound infiltration in children: A randomized blinded study of analgesia and bupivacaine absorption

PubMed Central

Flack, Sean H.; Martin, Lizabeth D.; Walker, Benjamin J.; Bosenberg, Adrian T.; Helmers, Laurilyn D.; Goldin, Adam B.; Haberkern, Charles M.

2014-01-01

Background Rectus sheath block can provide analgesia following umbilical hernia repair. However, conflicting reports on its analgesic effectiveness exist. No study has investigated plasma local anesthetic concentration following ultrasound-guided rectus sheath block (USGRSB) in children. Objectives Compare the effectiveness and bupivacaine absorption following USGRSB or wound infiltration (WI) for umbilical hernia repair in children. Methods A randomized blinded study comparing WI to USGRSB in 40 children undergoing umbilical hernia repair was performed. Group WI (n=20) received wound infiltration 1mg/kg 0.25% bupivacaine. Group RS (n=20) received USGRSB 0.5mg/kg 0.25% bupivacaine per side in the posterior rectus sheath compartment. Pain scores and rescue analgesia were recorded. Blood samples were drawn at 0, 10, 20, 30, 45 and 60 minutes. Results Patients in the WI group had a 2-fold increased risk of requiring morphine (Hazard ratio 2.06, 95% CI 1.01, 4.20, p=0.05). When required, median time to first morphine dose was longer in the USGRSB group (65.5 min vs 47.5 min, p=0.049). Peak plasma bupivacaine concentration was higher following USGRSB than WI (median: 631.9 ng/ml IQR: 553.9 – 784.1 vs 389.7 ng/ml IQR: 250.5-502.7, p= 0.002). Tmax was longer in the USGRSB group (median 45 min IQR: 30 - 60 vs 20 min IQR: 20 – 45, p= 0.006). Conclusions USGRSB provides more effective analgesia than WI for umbilical hernia repair. USGRSB with 1mg/kg 0.25% bupivacaine is associated with safe plasma bupivacaine concentration that peaks higher and later than WI. Caution against using larger volumes of higher concentration local anesthetic for USGRSB is advised. PMID:24853314

Development of Ultra Long Duration Local Anesthetic Agents in a Rat Model

DTIC Science & Technology

1994-02-24

this formulation is not toxic to the spinal cord. Initial trials with lecithin-coated bupivacaine microcrystals indic,-.. that this preparation also has...an ultra long duration local anesthetic effect, producing a 43 hour block in the rat tail. Clinical trials of this preparation in a human model are...l f _ _ _ Memorandum for LTC Dean E. Calcagni, M.D. Director, Combat Casualty Research Program USAMRDC Subject: Annual Report for Clinical

Dexmedetomidine decreases the required amount of bupivacaine for ultrasound-guided transversus abdominis plane block in pediatrics patients: a randomized study.

PubMed

Raof, Rehab Abdel; El Metainy, Shahira Ahmed; Alia, Doaa Abou; Wahab, Moataza Abdel

2017-02-01

The effect of dexmedetomidine on the potency of bupivacaine for transversus abdominis plane (TAP) block in pediatric patients has not been investigated. The primary objective of this study was to assess the effectiveness of dexmedetomidine to decrease the concentration of bupivacaine needed for analgesia for ultrasound-guided TAP block in a pediatric patient undergoing hernia repair or hydrocelectomy. This is a randomized, double-blind, up-down, dose-finding study. Operating room. Sixty American Society of Anesthesiologists I and II patients aged 1-4 years scheduled for elective unilateral herniorrhaphy or hydrocelectomy. Patients were randomly assigned to 1 of the 2 groups: group B (0.125% bupivacaine, 1mL/kg) TAP block or group BD (0.125% bupivacaine plus 2μg/kg dexmedetomidine, 1mL/kg) TAP block. The response of each child was observed for 60 seconds after skin incision and evaluated as 'unsuccessful' when skin incision caused a change in hemodynamic parameters (heart rate and mean blood pressure) 20% more than the preincision values. If the response was determined to be unsuccessful, the concentration of bupivacaine administrated to the next patient was increased by 0.02%. If it was successful, the concentration of bupivacaine administrated to the next patient was decreased by 0.02%. The minimum local anesthetic concentration of bupivacaine was 0.0839% (0.0137) in the B group and 0.0550% (0.0169) in the BD group. The difference was statistically significant (t=7.165, P=.0001). The total postoperative analgesic dosage of morphine was significantly higher in the B group (0.17±0.04 mg/kg) than the BD group (0.11±0.02 mg/kg, P=.001). The addition of 2μg/kg of dexmedetomidine reduced the minimum local anesthetic concentration of bupivacaine used for a TAP block and improved postoperative analgesia in children undergoing surgery for inguinal hernia repair or hydrocelectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Local Anesthetic Microcapsulation.

DTIC Science & Technology

1982-06-14

viscosities as disparate as R. S. V. 4.~O~6dl/g. ’ Microencapsulation of lidocaine (base) yielded 212-300 micron microcapsules with 50% in vitro drug...release in 6 hours; 150-212 micron microcapsules released 3-0% i7n-2 hours. Etidocaing and bupivacaine vo> 41’. were microencapsulated in a more...Etidocaine Microencapsulation 9 c. Bupivacaine Microencapsulation 12 3. In Vitro Drug Release from Microcapsules 15 a. Lidocaine (base) Release Studies

Spinal anesthesia: an evergreen technique.

PubMed

Di Cianni, Simone; Rossi, Maria; Casati, Andrea; Cocco, Caterina; Fanelli, Guido

2008-04-01

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

Synergistic interaction between fentanyl and bupivacaine given intrathecally for labor analgesia.

PubMed

Ngan Kee, Warwick D; Khaw, Kim S; Ng, Floria F; Ng, Karman K L; So, Rita; Lee, Anna

2014-05-01

Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans. Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity. The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction. The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

Local anesthetic infusion pump for pain management following open inguinal hernia repair: a meta-analysis.

PubMed

Wu, Chien-Chih; Bai, Chyi-Huey; Huang, Ming-Te; Wu, Chih-Hsiung; Tam, Ka-Wai

2014-01-01

Open inguinal hernia repair is one of the most painful procedures in day surgery. A continuous ambulatory analgesic is thought to reduce postoperative pain when it is applied to the surgical site. The aim of this study is to evaluate the efficacy of local anesthetic infusion pump following open inguinal hernia repair for the reduction of postoperative pain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that have investigated the outcomes of using an infusion pump for delivering a local anesthetic contrasted to a control group for open inguinal hernia repair. Pain was assessed from Day 1 to Day 5 following the surgery. The secondary outcomes included analgesia use and postoperative complications. We reviewed 5 trials that totaled 288 patients. The analgesic effects of bupivacaine (4 trials) and ropivacaine (one trial) were compared with a placebo group. The pooled mean difference in the score measuring the degree of pain diminished significantly at Day 1 to Day 4 in the experimental group. Two studies have reported that the number of analgesics required also decreased in the experimental group. No bupivacaine-related complication was reported. Our results revealed that applying a local anesthetic infusion pump following inguinal hernia repairs was more efficacious for reducing postoperative pain than a placebo. However, the findings were based on a small body of evidence in which methodological quality was not high. The potential benefits of applying a local anesthetic infusion pump to hernia repair must still be adequately investigated using further RCTs. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Liposomal bupivacaine: an innovative nonopioid local analgesic for the management of postsurgical pain.

PubMed

Candiotti, Keith

2012-09-01

Local anesthetics are a cornerstone of multimodal pain control strategies in the surgical setting as they have a long history of use and an established safety profile. Although effective, their duration of action is relatively short, which usually leads to the use of other agents, such as opioids, for effective postsurgical pain control in most patients. A medical need exists to extend the duration of analgesia with local anesthetics to help reduce the reliance on opioids in the postsurgical setting. Liposomal bupivacaine uses a product delivery platform to release bupivacaine slowly over 96 hours after infiltration at the surgical site. Liposomal bupivacaine was compared with placebo in two pivotal, multicenter, randomized, double-blind, parallel-group trials in 189 adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults undergoing orthopedic surgery (bunionectomy). Among patients undergoing hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain scores for up to 72 hours (primary end point) as measured by the area under the curve of pain scores on the numeric rating scale (p<0.0001), reduced overall opioid consumption (p ≤ 0.0006), increased the proportion of patients who did not receive opioids (p<0.0008), delayed time to first opioid by more than 13 hours (p<0.0001), and was associated with significantly higher rates of patient satisfaction (p=0.0007) compared with placebo. Similarly, in patients undergoing bunionectomy, liposomal bupivacaine significantly reduced total consumption of rescue opioids (p=0.0077) and cumulative pain scores as measured by the area under the curve of pain scores on the numeric rating scale (p=0.0005) during the first 24 postsurgical hours (primary end point) relative to placebo. Furthermore, liposomal bupivacaine also significantly delayed the time to first use of opioid rescue (p<0.0001) and increased the proportion of patients requiring no rescue opioid treatment (p ≤ 0.0404) compared with placebo. The most common adverse events with liposomal bupivacaine were nausea, vomiting, and constipation. No adverse effects on the QTc interval or cardiac safety signal have been detected in the clinical trial development program (823 patients) when liposomal bupivacaine was infiltrated into the surgical site. The beneficial effects of liposomal bupivacaine on postsurgical pain management and opioid use, significantly reducing both, are likely to translate into improved clinical and economic outcomes. © 2012 Pharmacotherapy Publications, Inc.

Neurotoxicity Induced by Bupivacaine via T-Type Calcium Channels in SH-SY5Y Cells

PubMed Central

Wen, Xianjie; Xu, Shiyuan; Liu, Hongzhen; Zhang, Quinguo; Liang, Hua; Yang, Chenxiang; Wang, Hanbing

2013-01-01

There is concern regarding neurotoxicity induced by the use of local anesthetics. A previous study showed that an overload of intracellular calcium is involved in the neurotoxic effect of some anesthetics. T-type calcium channels, which lower the threshold of action potentials, can regulate the influx of calcium ions. We hypothesized that T-type calcium channels are involved in bupivacaine-induced neurotoxicity. In this study, we first investigated the effects of different concentrations of bupivacaine on SH-SY5Y cell viability, and established a cell injury model with 1 mM bupivacaine. The cell viability of SH-SY5Y cells was measured following treatment with 1 mM bupivacaine and/or different dosages (10, 50, or 100 µM) of NNC 55-0396 dihydrochloride, an antagonist of T-type calcium channels for 24 h. In addition, we monitored the release of lactate dehydrogenase, cytosolic Ca2+ ([Ca2+]i), cell apoptosis and caspase-3 expression. SH-SY5Y cells pretreated with different dosages (10, 50, or 100 µM) of NNC 55-0396 dihydrochloride improved cell viability, reduced lactate dehydrogenase release, inhibited apoptosis, and reduced caspase-3 expression following bupivacaine exposure. However, the protective effect of NNC 55-0396 dihydrochloride plateaued. Overall, our results suggest that T-type calcium channels may be involved in bupivacaine neurotoxicity. However, identification of the specific subtype of T calcium channels involved requires further investigation. PMID:23658789

Does Reducing the Concentration of Bupivacaine When Performing Therapeutic Shoulder Joint Injections Impact the Clinical Outcome?

PubMed

Fox, Michael G; Patrie, James T

2016-04-01

Mixtures of local anesthetics and steroids are routinely injected intraarticularly to temporarily relieve joint pain, even though local anesthetics have been reported to cause chondrocyte death in a dose- and time-dependent manner. This study aimed to determine if intraarticular injections of bupivacaine 0.5% and bupivacaine 0.25% would provide similar pain relief. All fluoroscopically guided glenohumeral joint injections performed using 2.5 mL of bupivacaine and 0.5 mL (20 mg) of triamcinolone acetonide over a 42-month period were included if a pain score was recorded before, 5-10 minutes after, and 1 week after injection. Pain reduction of more than 2 points was considered much improved clinically with pain reduction of more than 1 point considered the minimum clinically important difference (MCID) threshold. Statistically significant and much improved pain reduction was achieved using both bupivacaine 0.5% and 0.25% 5-10 minutes (-3.7 points; 95% CI, -3.4 to -4.0 points; p ≤ 0.001; and -3.3 points; 95% CI, -3.0 to -3.5 points; p ≤ 0.001) and 1 week (-2.5 points; 95% CI, -2.2 to -2.9 points; p ≤ 0.001; and -2.1 points; 95% CI, -1.8 to -2.3 points; p ≤ 0.001) after injection, respectively. Adjusting for age, sex, pain score before injection, and indication, the mean decrease in pain was greater in the bupivacaine 0.5% group by 0.30 points 5-10 minutes after injection (95% CI, -0.03 to 0.63 points; p = 0.08) and 0.46 points 1 week after injection (95% CI, 0.13-0.77 points; p = 0.01). Both bupivacaine 0.5% and bupivacaine 0.25% provide statistically significant and much improved pain relief 5-10 minutes and 1 week after intraarticular glenohumeral injections. Bupivacaine 0.5% provided greater pain relief than bupivacaine 0.25%, but the difference was less than 0.5 points and therefore did not meet the MCID threshold.

Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus)

PubMed Central

Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

2017-01-01

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days –1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain. PMID:28905717

Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

PubMed

Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

2017-01-01

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels.

PubMed

Nakahira, Kei; Oshita, Kensuke; Itoh, Masayuki; Takano, Makoto; Sakaguchi, Yoshiro; Ishihara, Keiko

2016-04-01

Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8-10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5-2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side.

Periarticular Liposomal Bupivacaine Injection Versus Intra-Articular Bupivacaine Infusion Catheter for Analgesia After Total Knee Arthroplasty: A Double-Blinded, Randomized Controlled Trial.

PubMed

Smith, Eric B; Kazarian, Gregory S; Maltenfort, Mitchell G; Lonner, Jess H; Sharkey, Peter F; Good, Robert P

2017-08-16

Intra-articular bupivacaine hydrochloride (HCl) infusion catheters and periarticular injections of liposomal bupivacaine are often used as postoperative local anesthetics. The purpose of this study was to compare the efficacies of these local anesthetics following total knee arthroplasty. This study was a superiority trial with a randomized, controlled, double-blinded design. Patients were randomly assigned to either delivery of bupivacaine HCl by the ON-Q* Pain Relief System pump (n = 96) or by an injection of Exparel (liposomal bupivacaine) (n = 104). The primary outcome of this study was cumulative narcotic consumption on postoperative days 0 through 3. Narcotic consumption data were collected retrospectively from in-hospital records while patients were in the hospital. Following discharge, narcotic consumption data were gathered from patient surveys, as were secondary outcomes measures. We did not identify greater narcotic use in the ON-Q* group compared with the Exparel group (p = 0.641). The mean difference between the groups was 0.5 morphine equivalent (95% confidence interval [CI] = -1.7 to +2.8), with the ON-Q* group consuming an average 10.4 morphine equivalents (95% CI = 8.7 to 12.0) compared with 10.9 (95% CI = 9.3 to 12.5) in the Exparel group. There were no significant differences between groups with regard to any of the secondary measures of pain with the exception of pain while walking and pain with physical therapy (p = 0.019 and p = 0.010, respectively), both of which showed an approximately 1-point difference in favor of the ON-Q* group on a visual analog scale (VAS). There were also no differences in the postoperative side effects, including nausea, constipation, or vomiting, or in the rates of study-related complications, patient satisfaction, or length of hospital stay. Exparel did not have superior efficacy compared with the ON-Q* Pain Relief System as reflected by narcotic consumption, our primary outcome. There were small significant differences, in favor of the ON-Q* group, in 2 secondary measures of pain during activity, but these approximately 1-point VAS differences are unlikely to be clinically relevant. The choice of a local anesthetic modality should be based on a combination of safety, convenience, and cost considerations. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Buffered lidocaine and bupivacaine mixture - the ideal local anesthetic solution?

PubMed

Best, Corliss A; Best, Alyssa A; Best, Timothy J; Hamilton, Danielle A

2015-01-01

The use of injectable local anesthetic solutions to facilitate pain-free surgery is an integral component of many procedures performed by the plastic surgeon. In many instances, a solution that has both rapid onset and prolonged duration of analgesia is optimal. A combination of lidocaine and bupivacaine, plain or with epinephrine, is readily available in most Canadian health care settings where such procedures are performed, and fulfills these criteria. However, commercially available solutions of both medications are acidic and cause a burning sensation on injection. Buffering to neutral pH with sodium bicarbonate is a practical method to mitigate the burning sensation, and has the added benefit of increasing the fraction of nonionized lipid soluble drug available. The authors report on the proportions of the three drugs to yield a neutral pH, and the results of an initial survey regarding the use of the combined solution with epinephrine in hand surgery.

Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.

1986-03-01

It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree thanmore » does lidocaine, 40 mg/L.« less

Pluronic Microemulsions as Nanoreservoirs for Extraction of Bupivacaine from Normal Saline

PubMed Central

Varshney, Manoj; Morey, Timothy E.; Shah, Dinesh O.; Flint, Jason A.; Moudgil, Brij M.; Seubert, Christoph N.

2013-01-01

We hypothesized that custom-designed microemulsions would effectively scavenge compounds from bulk media. Pluronic-based oil-in-water microemulsions were synthesized that efficiently reduced the free concentration of the local anesthetic bupivacaine in 0.9% NaCl. Both the molecular nature and concentration of the constituents in the microemulsions significantly affected extraction efficiencies. Pluronic F127-based microemulsions extracted bupivacaine more efficiently than microemulsions synthesized using other Pluronic surfactants (L44, L62, L64, F77, F87, F88, P104). Extraction was markedly increased by addition of fatty acid sodium salts due to greater oil/water interface area, increased columbic interaction between bupivacaine and fatty acids sodium salt, and greater surface activity. These data suggest that oil-in-water microemulsions may be an effective agent to treat cardiotoxicity caused by bupivacaine or other lipophilic drugs. PMID:15099093

Local anesthesia for treatment of hernia in elder patients: Levobupicavaine or Bupivacaine?

PubMed Central

2013-01-01

Background Inguinal hernia is one of the most common diseases in the elderly. Treatment of this pathology is exclusively surgical and relies almost always on the use of local anesthesia. While in the past hernia surgery was carried out mainly by general anesthesia, in recent years there has been growing emphasis on the role of local anesthesia. Methods The aim of our study was to compare intra-and postoperative analgesia obtained by the use of levobupivacaine to the same obtained by bupivacaine. Bupivacaine is one of the main local anesthetics used in the intervention of inguinal hernioplasty. Levobupivacaine is an enantiomer of racemic bupivacaine with less cardiotoxicity and neurotoxicity. The study was conducted from March 2011 to March 2013. We collected data of eighty patients, male and female, aged between 65 and 86 years, who underwent inguinal hernioplasty with local anesthesia. Results Evaluation of intra-operatively pain shows that minimal pain is the same in both groups. Mild pain was more frequent in the group who used levobupivacaine. Moderate pain was slightly more frequent in the group who used bupivacaine. Only one reported intense pain. Two drugs seem to have the same effect at a distance of six, twelve, eighteen and twentyfour hours. Bupivacaine shows a significantly higher number of complications, as already demonstrated by previous studies. Degree of satisfaction expressed by patients has been the same in the two groups. Levobupivacaine group has shown a greater request for paracetamol while patients who experienced bupivacaine have showed a higher request of other analgesics. Conclusions Clinical efficacy of levobupivacaine and racemic bupivacaine are actually similar, when used under local intervention of inguinal hernioplasty. In the field of ambulatorial surgery our working group prefers levobupivacaine for its fewer side effects and for its easy handling. PMID:24267484

Neurotoxicity of subarachnoid hyperbaric bupivacaine in dogs.

PubMed

Ganem, E M; Vianna, P T; Marques, M; Castiglia, Y M; Vane, L A

1996-01-01

The study investigated possible neurotoxic effects of increasing concentrations and doses of bupivacaine administered into the subarachnoid space in dogs. Fifty animals were allocated to five experimental groups: G1, control; G2, 5 mg 0.5 bupivacaine in 10% glucose solution; G3, 10 mg of 1% bupivacaine in 10% glucose solution; G4, 20 mg 2% bupivacaine in 10% glucose solution, and G5, 20 mg 2% bupivacaine in water. After 72 hours of observation, the animals were killed and the spinal cords removed for histologic examination by light microscopy. None of the animals showed any neurologic clinical disturbance following recovery from spinal anesthesia. One case of necrosis of nerve tissue was observed in G3 and four in G4. Increasing concentrations and doses of hyperbaric bupivacaine solutions increased the incidence of nerve tissue damage, which did not occur with hypobaric solutions. These results should contribute to the further understanding of neurologic complications following spinal anesthesia when large doses of local anesthetics in hyperbaric solutions are used.

Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.

PubMed

Ohri, Rachit; Wang, Jeffery Chi-Fei; Pham, Lan; Blaskovich, Phillip D; Costa, Daniel; Nichols, Gary; Hildebrand, William; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary R

2014-01-01

Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery. Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days. Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated before the incision (group VI) reduced hypersensitivity for only approximately 2 hours, an overall insignificant effect. Bupivacaine slowly released for 72 hours from microspheres adsorbed to the hernia mesh significantly suppresses evoked postoperative hypersensitivity for at least 1 week and is more effective than a suspension of these microspheres or preoperative single-shot infiltration of bupivacaine.

Effects of Lidocaine, Bupivacaine, and Ropivacaine on Calcitonin Gene-Related Peptide and Substance P Levels in the Incised Rat Skin.

PubMed

Lapin, Guilherme A F; Hochman, Bernardo; Maximino, Jessica R; Chadi, Gerson; Ferreira, Lydia M

2016-04-01

To evaluate the effect of 2% lidocaine, 0.5% bupivacaine, and 0.75% ropivacaine on the release of substance P (SP) and calcitonin gene-related peptide (CGRP) in skin wounds. A primary, experimental, analytical, prospective, self-controlled, blinded study. The study is set in a university research center. Twenty-eight Wistar rats were randomly divided into 4 groups: lidocaine, bupivacaine, ropivacaine, and the control. After general anesthesia, a local anesthetic or 0.9% saline (control) was injected subdermally along a 2-cm line on the dorsal midline of each rat; 30 minutes later, an incision (nociceptive stimulus) was made along this line. The animals were euthanized, and skin samples were collected from the center of the incision line and sent for CGRP and SP quantification. Quantification of CGRP and SP by Western blotting. Substance P levels were similar in the lidocaine and ropivacaine groups but were significantly lower than those of the control group (P = .002); no significant difference in SP levels was found between the bupivacaine and control groups. Procalcitonin gene-related peptide levels were significantly lower in the experimental groups than those in control subjects (P = .009), with no significant differences among the experimental groups. No significant differences in CGRP levels were found among all groups. Lidocaine and ropivacaine inhibited SP release. All 3 local anesthetics inhibited the release of procalcitonin gene-related peptide, but not the release of CGRP in rat skin. Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.

Different anesthetic agents-soaked sinus packings on pain management after functional endoscopic sinus surgery: which is the most effective?

PubMed

Haytoğlu, Süheyl; Kuran, Gökhan; Muluk, Nuray Bayar; Arıkan, Osman Kürşat

2016-07-01

In the present study, we investigated the efficacy of local anesthetics soaked non-absorbable sinus packs on pain management after functional endoscopic surgery (FESS). One hundred and fifty patients with the diagnosis of bilateral chronic sinusitis with or without nasal polyps who underwent FESS were included into the study. Their pre-operative Lund-Mackay computerized tomography (CT) Scores were similar. We applied anesthetic agents of 2 % lidocaine HCl, 0.25 % Bupivacaine HCl, 0.2 % Ropivacaine, 2 % Prilocaine and 0.9 % NaCl (Saline) in groups 1-5 onto the sinus packs after FESS. At postoperative period, acetaminophen (250 mg/5 ml) was used in 10-15 mg/kg per dose (4 times a day). Bleeding grade, operation duration, postoperative number of gauze/24 h, additional painkiller need, pain values at 1, 2, 4, 8, 12 and 24 h were noted. Lund-Kennedy endoscopic scores were also evaluated at 1st, 2nd and 4th weeks postoperatively. In saline group, 93.3 % of the patients needed additional painkiller. Whereas, in Bupivacaine group, additional painkiller use (20.0 %) is less than the other groups. In Bupivacaine group, number of gauze/24 h use was lower than lidocaine, ropivacaine and prilocaine groups. In our study, except 1st and 24th hours, pain values of groups can be written in ascending order (from less to higher) as Bupivacaine, Lidocaine, Prilocaine, Ropivacaine and Saline. In the first hour, pain values of groups can be written in ascending order (from less to higher) as Lidocaine, Prilocaine, Bupivacaine, Ropivacaine and Saline. In the 2nd week, in the Bupivacaine and Lidocaine Groups separately, postoperative Lund-Kennedy scores were lower than the Prilocaine and Saline Groups. In the 1st month, Lidocaine Group's Lund-Kennedy scores were significantly lower than the Saline Group. Synechia values were not different between groups. Bupivacaine help the lower pain values and less additional painkiller need after FESS. Therefore, we recommend to use Bupivacaine soaked sinus packs after FESS for achieve less pain values and to improve patient satisfaction.

Comparative analysis of tissue reactions to anesthetic solutions: histological analysis in subcutaneous tissue of rats.

PubMed Central

Ribeiro, Paulo Domingos; Sanches, Marcio Giampietro; Okamoto, Tetuo

2003-01-01

Postanesthetic pain is a relatively common complication after local anesthesia. This complication may be caused by the anesthetic technique or by the anesthetic solution used. Tissue reactions induced by the anesthetic solutions may be one of the factors resulting in pain after anesthesia. The objective of this study was to comparatively analyze tissue reactions induced by different anesthetic solutions in the subcutaneous tissue of rats. The following solutions were utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with 1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with 1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control. Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in the solutions and implanted in the subcutaneous region. The sacrifice periods were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained with hematoxylin and eosin for histological analysis. The results showed that there is a difference in tissue irritability produced by the local anesthetic solutions. The results also showed that there is no relation between the concentration of the drug and the inflammatory intensity, that the mepivacaine and articaine solutions promoted less inflammatory reaction than the bupivacaine, and that the lidocaine solution produced the least intense inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:14959905

Transient left ventricular dysfunction due to coronary spasm after spinal anesthesia with bupivacaine - a case report.

PubMed

Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Słomczyński, Marek; Horbacka, Karolina; Bartkowski, Jarosław; Kalawski, Bartosz

2017-10-23

Bupivacaine is a long-acting local anesthetic (LA) used for cutaneous infiltration, peripheral nerve blocks, epidural and spinal anesthesia. However, its application may result in cardiovascular complications such as: hypotension, bradycardia, cardiac arrest and toxic myocardial injury. The authors describe a 53-year-old male with a history of cigarette smoking, admitted for an elective inguinal hernia surgery. Before surgery, the patient received subarachnoid injection of bupivacaine (20 mg). After the operation, he developed transient hypotension. Blood pressure returned to normal after gelofusine infusion; no sympathomimetics were administered. The male denied chest pain; however, ECG showed ST segment elevation coexisting with left ventricular anterolateral hypokinesia and decreased longitudinal strain in echocardiography. A significant increase in troponin I level was suggestive rather of myocardial infarction than of takotsubo cardiomyopathy. Urgent coronary angiography revealed left anterior descending artery spasm, which remitted after intracoronary nitroglycerin injection. Normalization of ECG and echocardiography was observed within a few days. The authors indicate that the presented atypical adverse effect of bupivacaine manifested itself with delay and that coronary spasm proceeded without angina. A close observation of the patient after anesthetic procedure with LA should be extended over the postoperative period.

Insulin Signaling in Bupivacaine-induced Cardiac Toxicity: Sensitization during Recovery and Potentiation by Lipid Emulsion

PubMed Central

Fettiplace, Michael R.; Kowal, Katarzyna; Ripper, Richard; Young, Alexandria; Lis, Kinga; Rubinstein, Israel; Bonini, Marcelo; Minshall, Richard; Weinberg, Guy

2015-01-01

Background The impact of local anesthetics on regulation of glucose homeostasis by protein kinase B (Akt) and 5’-Adenosine monophosphate activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by intravenous lipid emulsion (ILE). Methods Sprague-Dawley rats received 10mg/kg bupivacaine over 20 seconds followed by nothing or 10mL/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70s6k, s6, IRS1, GSK-3β, AMPK, ACC, TSC2 were quantified. Three animals received Wortmannin to irreversibily inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002—a reversible Pi3K inhibitor. Results Bupivacaine cardiotoxicity rapidly de-phosphorylated Akt at S473 to 63 ± 5% of baseline and phosphorylated AMPK to 151 ± 19%. AMPK activation inhibited targets downstream of mTORC1 via TSC2. Feedback dephosphorylation of IRS1 to 31 ± 8% of baseline sensitized Akt signaling in hearts resulting in hyper-phosphorylation of Akt at T308 and GSK-3β to 390 ± 64% and 293 ± 50% of baseline respectively. Glycogen accumulated to 142 ± 7% of baseline. Irreversible inhibition of Pi3k upstream of Akt exacerbated bupivacaine cardiotoxicity, while pretreating with a reversible inhibitor delayed onset of toxicity. ILE rapidly phosphorylated Akt at S473 and T308 to 150 ± 23% and 167 ± 10% of baseline, respectively but did not interfere with AMPK or targets of mTORC1. Conclusion Glucose handling by Akt and AMPK is integral to recovery from bupivacaine cardiotoxicity and modulation of these pathways by ILE contributes to lipid resuscitation. PMID:26646023

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles

NASA Astrophysics Data System (ADS)

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-06-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles.

PubMed

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-12-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

Impact of local administration of liposome bupivacaine for postsurgical analgesia on wound healing: a review of data from ten prospective, controlled clinical studies.

PubMed

Baxter, Richard; Bramlett, Kenneth; Onel, Erol; Daniels, Stephen

2013-03-01

Liposome bupivacaine is a liposomal formulation that allows delivery of bupivacaine for 96 hours with a single local administration. It is indicated for the management of postsurgical pain. This retrospective review of 10 clinical trials assessed the potential impact of local anesthetics on wound healing and chondrolysis. Various doses of liposome bupivacaine and bupivacaine hydrochloride (HCl) were evaluated. Primary inclusion criteria across the 10 Phase 2 and Phase 3 randomized, double-blind studies required that patients be ≥18 years of age at the screening visit and scheduled to undergo the specified surgical procedure in each study (inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Key exclusion criteria were: a history of clinically significant medical conditions (including cardiovascular, hepatic, renal, neurologic, psychiatric, or metabolic disease) or laboratory results that indicated an increased vulnerability to the study drugs and/or procedures; medical condition(s) or concurrent surgery that may have required analgesic treatment in the postoperative period for pain that was not strictly related to the study surgery; and/or any clinically significant event or condition discovered during surgery that could have complicated the patient's postsurgical course. Assessments included the clinician's overall satisfaction with the patient's wound healing, wound status (erythema, drainage, edema, and induration), and wound scarring. Adverse events (AEs) potentially manifesting as wound complications and local AEs were also assessed. In total, 823 patients received liposome bupivacaine at doses ranging from 66 to 532 mg across the 5 different surgical settings; 446 patients received bupivacaine HCl (75-200 mg), and 190 patients received placebo. Few studies showed statistically significant differences between liposome bupivacaine and the comparator (bupivacaine HCl or placebo) with regard to the clinician's overall satisfaction with patient wound healing; the incidence of erythema, drainage, edema, and induration; and wound scarring. The incidences of local AEs were similar between treatments, ranging from 9% to 20% with liposome bupivacaine across the studies compared with 8% to 19% with bupivacaine HCl. Liposome bupivacaine given locally at the surgical wound site appeared to have no clinically evident impact on wound or bone healing at doses up to 532 mg across different surgical models. The wound-healing profile of liposome bupivacaine was similar to that of bupivacaine HCl. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Bupivacaine drug-induced liver injury: a case series and brief review of the literature.

PubMed

Chintamaneni, Preethi; Stevenson, Heather L; Malik, Shahid M

2016-08-01

Bupivacaine is an established and efficacious anesthetic that has become increasingly popular in postoperative pain management. However, there is limited literature regarding the potential for bupivacaine-induced delayed liver toxicity. Describe cholestasis as a potential adverse reaction of bupivacaine infusion into a surgical wound. Retrospective review of patients' medical records. We report the cases of 3 patients with new onset of cholestatic injury after receiving bupivacaine infusion for postoperative herniorrhaphy pain management. All patients had negative serologic workups for other causes of liver injury. All patients achieved eventual resolution of their liver injury. Bupivacaine-induced liver injury should be on the differential of individuals presenting with jaundice and cholestasis within a month of infusion via a surgically placed catheter of this commonly used anesthetic. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of local anesthetics on postoperative pain.

PubMed

Roberge, C W; McEwen, M

1998-12-01

This study was performed to determine if intraoperative local anesthesia improved control of postoperative pain after inguinal herniorrhaphy and to compare the effects of two commonly used local anesthetics on pain management. The Gate Control Theory of Pain formed the theoretical basis for this study. A retrospective nonexperimental study in an ex post facto design was used. Data were collected from 1990 through 1997 on 120 patient charts. The use of local anesthetic intraoperatively significantly decreased patients' lengths of stay postoperatively (P = 0.00) and need for postoperative narcotics (P = 0.00). Bupivacaine was found to be superior to lidocaine in decreasing the need for postoperative narcotic analgesia. Researchers concluded that many patients would benefit from intraoperative injection of local anesthesia. This information can affect patient care outcomes through decreasing recovery time, reducing postoperative pain, and reducing health care costs.

The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses.

PubMed

Jinks, Maggie R; Fontenot, Robin L; Wills, Robert W; Betbeze, Caroline M

2017-12-12

To compare the efficacy and duration of effect of three local anesthetics on corneal sensitivity when administered subconjunctivally in horses. Eight healthy adult horses. A randomized, masked, crossover study design was used, with a two-week washout period between trials. The subconjunctival space of the randomly selected eye was injected with 0.2 mLs of bupivacaine (0.5%), lidocaine (2%), mepivacaine (2%), or saline. All horses received each medication once. The contralateral eye served as a control. The corneal touch threshold (CTT) was measured in both eyes with a Cochet-Bonnet esthesiometer prior to sedation with xylazine, after sedation, and at 10-min intervals after subconjunctival injection until corneal sensitivity returned to baseline. The total time of decreased CTT and the maximum decrease in CTT were compared for each medication using a general linear mixed model (P < 0.05). Total time of decreased CTT was 105.0 min for bupivacaine, 103.8 min for lidocaine, 138.8 min for mepivacaine, and 7.5 min for saline. All local anesthetics decreased CTT longer than saline (P < 0.001) and mepivacaine decreased CTT longer than lidocaine (P = 0.04). The mean minimum CTT was 1.67 cm for bupivacaine, 1.42 cm for lidocaine, and 0.73 cm for mepivacaine, which were all significantly less (P < 0.001) than saline (4.73 cm). No evidence of corneal toxicity was noted with any treatment. Subconjunctival injections of lidocaine, bupivacaine, and mepivacaine effectively and safely reduce corneal sensitivity in eyes of healthy horses for 1.5-2 h, and may be useful for providing perioperative analgesia for equine corneal procedures. © 2017 American College of Veterinary Ophthalmologists.

Systemic toxicity of ropivacaine during ovine pregnancy.

PubMed

Santos, A C; Arthur, G R; Pedersen, H; Morishima, H O; Finster, M; Covino, B G

1991-07-01

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

Dose-Response Curves for Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine Given for Labor Analgesia in Nulliparous Women.

PubMed

Ngan Kee, Warwick D; Ng, Floria F; Khaw, Kim S; Tang, Shannon P Y; Koo, Alison G P

Bupivacaine, levobupivacaine, and ropivacaine are often given intrathecally for labor analgesia, but limited data are available for their dose-response properties in this context. The objective of this study was to describe the dose-response curves of these local anesthetics when given intrathecally for labor analgesia, to determine values for D50 (dose producing a 50% response) and to compare the calculated values of D50 for levobupivacaine and ropivacaine with those for bupivacaine. With ethics approval and written consent, we randomized 270 nulliparous laboring patients requesting neuraxial analgesia at 5-cm cervical dilation or less to receive a single dose of intrathecal local anesthetic without opioid as part of a combined spinal-epidural technique. Patients received either bupivacaine, levobupivacaine, or ropivacaine at a dose of 0.625, 1.0, 1.5, 2.5, 4.0, or 6.25 mg (n = 15 per group). Visual analog scale pain scores were measured for 15 minutes, after which further analgesia and management were at the clinician's discretion. The primary end point was percentage reduction of pain score at 15 minutes. Logistic sigmoidal dose-response curves were fitted to the data using nonlinear regression, and D50 values were calculated for each drug. Data were analyzed from 270 patients. Patient characteristics were similar between groups. The calculated D50 and 95% confidence interval values were as follows: bupivacaine, 1.56 mg (1.25-1.94 mg); ropivacaine, 1.95 mg (1.57-2.43 mg); and levobupivacaine, 2.20 mg (1.76-2.73 mg). The results of this study support previous work showing that intrathecal levobupivacaine and ropivacaine are less potent than bupivacaine. Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-09000773) and Centre of Clinical Trials Clinical Registry of the Chinese University of Hong Kong (identifier: CUHK_CCT00245).

Effects of levobupivacaine and bupivacaine on rat myometrium*

PubMed Central

Li, Zi-gang; Zhou, Liang; Tang, Hui-fang

2006-01-01

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. PMID:16909479

Delayed hypersensitivity reaction of the knee after injection of arthroscopy portals with bupivacaine (marcaine)

PubMed

Craft, D V; Good, R P

1994-06-01

The number of arthroscopic procedures performed annually for the management of intraarticular injuries has grown at an exponential rate. Whether done with the patient under general anesthesia or local anesthesia supplemented with intravenous sedation, it is common practice to postoperatively inject each portal as well as the joint with a local anesthetic to provide pain relief in the transition to the recovery room and discharge after outpatient surgery. To our knowledge, no previous reports of localized urticaria and delayed hypersensitivity reaction have been reported in the postarthroscopy setting. We are reporting a case of delayed hypersensitivity reaction and urticaria of the knee that presented after bupivacaine (Marcaine) injection of arthroscopic portals after routine meniscectomy.

Does the baricity of bupivacaine influence intrathecal spread in the prolonged sitting position before elective cesarean delivery? A prospective randomized controlled study.

PubMed

Loubert, Christian; Hallworth, Stephen; Fernando, Roshan; Columb, Malachy; Patel, Nisa; Sarang, Kavita; Sodhi, Vinnie

2011-10-01

Difficulties in inserting an epidural catheter while performing combined spinal-epidural anesthesia for cesarean delivery may lead to undue delays between the spinal injection of the local anesthetic mixture and the adoption of the supine position with lateral tilt. We hypothesized that this delay may affect the intrathecal distribution of local anesthetic of different baricities such that hypobaric local anesthetic would lead to a higher sensory block level. Healthy parturients with uncomplicated pregnancies undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this prospective double-blind randomized controlled trial. The subjects were allocated to receive hyperbaric (hyperbaric group), isobaric (isobaric group), or hypobaric (hypobaric group) spinal bupivacaine 10 mg. After the spinal injection, the subjects remained in the sitting position for 5 minutes (to simulate difficulty in inserting the epidural catheter) before being helped into the supine lateral tilt position. The primary outcome was the sensory block level during the 25 minutes after the spinal injection. Other end points included motor block score, maternal hypotension, and vasopressor requirements. Data from 89 patients were analyzed. Patient characteristics were similar in all groups. The median [interquartile range] (95% confidence interval) sensory levels after spinal injection were significantly higher with decreasing baricity: hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8-4] (T8-5) (P < 0.001, Cuzick trend). All patients in the hypobaric group reached a sensory block level of T4 at 25 minutes after spinal injection compared with 80% of the patients in both the isobaric and hyperbaric groups (P = 0.04; difference 20%, 95% confidence interval of difference 4%-33%). Significantly more patients in the hypobaric group had complete lower limb motor block (Bromage score = 4) (hyperbaric 43%, isobaric 63%, and hypobaric 90%; P < 0.001). The incidences of maternal hypotension and nausea and vomiting were similar among groups, although the ephedrine requirements were significantly increased in the isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared with the hyperbaric group (P < 0.001, Cuzick trend). We demonstrated that when parturients undergoing cesarean delivery were maintained in the sitting position for 5 minutes after spinal injection of the local anesthetic, hypobaric bupivacaine resulted in sensory block levels that were higher compared with isobaric and hyperbaric bupivacaine, respectively, during the study period.

Comparative clinical trial of topical anesthetic agents in cataract surgery: lidocaine 2% gel, bupivacaine 0.5% drops, and benoxinate 0.4% drops.

PubMed

Soliman, Mahmoud M; Macky, Tamer A; Samir, M Khaled

2004-08-01

To assess the efficacy of lidocaine gel, bupivacaine drops, and benoxinate drops as topical anesthetic agents in cataract surgery. Kasr El-Aini Hospital, Cairo University, Cairo, Egypt. This prospective randomized study comprised 90 patients scheduled for routine cataract extraction. Patients were randomized into 3 groups of 30 each based on which anesthetic agent they received: lidocaine 2% gel, bupivacaine 0.5% drops, or benoxinate 0.4% drops. Subjective pain at application of the agent and intraoperatively was quantified by the patients using a verbal pain score (VPS) scale from 0 to 10. The duration of discomfort at application, duration of surgery, rate of supplemental sub-Tenon's anesthesia, and complications were recorded. The mean VPS at application was 2.97, 1.53, and 1.03 in the lidocaine, bupivacaine, and benoxinate groups, respectively; the VPS in the lidocaine group was statistically significantly higher than in the other 2 groups (P<.001). The mean duration of pain at application was 25 seconds, 14 seconds, and 6 seconds in the lidocaine, bupivacaine, and benoxinate groups, respectively, and was statistically significantly higher in the lidocaine group (P<.001). The mean VPS during surgery was 1.6, 4.1, and 7.1 in the lidocaine, bupivacaine, and benoxinate groups; the lidocaine group had a statistically significantly lower mean VPS than the other 2 groups (P<.001). The incidence of supplemental sub-Tenon's injection was 3.3%, 10.0%, and 73.3%, respectively, and was statistically significantly lower in the lidocaine and bupivacaine groups than in the benoxinate group (P<.001). The patients' overall satisfaction was statistically significantly higher in the lidocaine and bupivacaine groups than in the benoxinate group (93.3%, 83.3%, and 33.3%, respectively) (P<.001). Three patients in the lidocaine group had corneal haze at the time of surgery, which was not statistically significant (P>.1). Lidocaine gel was a better topical anesthetic agent than bupivacaine and benoxinate drops. Bupivacaine drops were effective in providing deep topical anesthesia.

Dual effect of local anesthetics on the function of excitable rod outer segment disk membrane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashimo, T.; Abe, K.; Yoshiya, I.

1986-04-01

The effects of local anesthetics and a divalent cation, Ca2+, on the function of rhodopsin were estimated from the measurements of light-induced proton uptake. The light-induced proton uptake by rhodopsin in the rod outer segment disk membrane was enhanced at lower pH (4) but depressed at higher pHs (6 to 8) by the tertiary amine local anesthetics lidocaine, bupivacaine, tetracaine, and dibucaine. The order of local anesthetic-induced depression of the proton uptake followed that of their clinical anesthetic potencies. The depression of the proton uptake versus the concentration of the uncharged form of local anesthetic nearly describes the same curvemore » for small and large dose of added anesthetic. Furthermore, a neutral local anesthetic, benzocaine, depressed the proton uptake at all pHs between 4 and 7. These results indicate that the depression of the proton uptake is due to the effect of only the uncharged form. It is hypothesized that the uncharged form of local anesthetics interacts hydrophobically with the rhodopsin in the disk membrane. The dual effect of local anesthetics on the proton uptake, on the other hand, suggests that the activation of the function of rhodopsin may be caused by the charged form. There was no significant change in the light-induced proton uptake by rhodopsin when 1 mM of Ca2+ was introduced into the disk membrane at varying pHs in the absence or presence of local anesthetics. This fact indicates that Ca2+ ion does not influence the diprotonating process of metarhodopsin; neither does it interfere with the local anesthetic-induced changes in the rhodopsin molecule.« less

Cell Toxicity in Fibroblasts, Tenocytes, and Human Mesenchymal Stem Cells-A Comparison of Necrosis and Apoptosis-Inducing Ability in Ropivacaine, Bupivacaine, and Triamcinolone.

PubMed

Zhang, Anja Z; Ficklscherer, Andreas; Gülecyüz, Mehmet F; Paulus, Alexander C; Niethammer, Thomas R; Jansson, Volkmar; Müller, Peter E

2017-04-01

To analyze the ability of ropivacaine, bupivacaine, and triamcinolone to induce apoptosis and necrosis in fibroblasts, tenocytes, and human mesenchymal stem cells. Human dermal fibroblasts, adipose-derived human mesenchymal stem cells (hMSCs), and tenocytes gained from the rotator cuff tendon were seeded with a cell density of 0.5 × 10 4 /cm 2 . One specimen of ropivacaine, bupivacaine, and triamcinolone was tested separately on the cells with separate concentrations of 0.5%, 0.25%, and 0.125% for each specimen. The negative control received no agent, only a change of medium. The incubation period for each agent was 30 minutes. After a change of medium and 1 hour, 24 hours, and 7 days of incubation, 10 4  cells were harvested and analyzed via fluorescence-activated cell sorting with double-staining with annexin V and propidium iodide. Statistical analysis to determine significant difference (P < .05) between the groups with SPSS statistics 23 through one-way analysis of variance with a univariate general linear model was performed. Bupivacaine showed necrosis-inducing effects on fibroblasts and tenocytes, with the necrotic effect peaking at 0.5% and 0.25%. Ropivacaine and triamcinolone caused no significant necrosis. Compared with fibroblasts and tenocytes, hMSCs did not show significant necrotic or apoptotic effects after exposure to bupivacaine. Overall, no significant differences in apoptosis were detected between different cell lines, varying concentrations, or time measurements. Bupivacaine 0.5% and 0.25% have the most necrosis-inducing effects on fibroblasts and tenocytes. Ropivacaine caused less necrosis than bupivaine. Compared with fibroblasts and tenocytes, hMSCs were not affected by necrosis using any of the tested agents. A significant apoptosis-inducing effect could not be detected for the different cell lines. Possible cell toxicity raises questions of concern for intra-articular injections using local anesthetics and corticosteroids. The present study demonstrates the necrotic and apoptotic effects of ropivacaine, bupivacaine, and triamcinolone and may give recommendations for intra-articular use of local anesthetics and corticosteroids. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonar-guided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery.

PubMed

Alzeftawy, Ashraf Elsayed; El-Daba, Ahmad Ali

2016-01-01

Cooling of local anesthetic potentiates its action and increases its duration. Magnesium sulfate (MgSo 4 ) added to local anesthetic prolongs the duration of anesthesia and postoperative analgesia with minimal side effects. The aim of this prospective, randomized, double-blind study was to compare the effect of cold to 4°C bupivacaine 0.5% and Mg added to normal temperature (20-25°C) bupivacaine 0.5% during sonar-guided combined femoral and sciatic nerve blocks on the onset of sensory and motor block, intraoperative anesthesia, duration of sensory and motor block, and postoperative analgesia in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery. A total of 90 American Society of Anesthesiologists classes I and II patients who were scheduled to undergo elective ACL reconstruction were enrolled in the study. The patients were randomly allocated to 3 equal groups to receive sonar-guided femoral and sciatic nerve blocks. In Group I, 17 ml of room temperature (20-25°C) 0.5% bupivacaine and 3 ml of room temperature saline were injected for each nerve block whereas in Group II, 17 ml of cold (4°C) 0.5% bupivacaine and 3 ml of cold saline were injected for each nerve block. In Group III, 17 ml of room temperature 0.5% bupivacaine and 3 ml of MgSo 4 5% were injected for each nerve block. The onset of sensory and motor block was evaluated every 3 min for 30 min. Surgery was started after complete sensory and motor block were achieved. Intraoperatively, the patients were evaluated for heart rate and mean arterial pressure, rescue analgesic and sedative requirements plus patient and surgeon satisfaction. Postoperatively, hemodynamics, duration of analgesia, resolution of motor block, time to first analgesic, total analgesic consumption, and the incidence of side effects were recorded. There was no statistically significant difference in demographic data, mean arterial pressure, heart rate, and duration of surgery. Onset of both sensory and motor block was significantly shorter in both Groups II and III compared to Group I. Intraoperative anesthetic quality was comparable between groups with good patient and surgeon satisfaction. The time to first analgesia was significantly longer in Groups II and III compared to Group I with nonsignificant difference between each other. Moreover, the total opioid consumption was significantly lower in Groups II and III and duration of analgesia and motor block were significantly longer in Groups II and III compared to Group I. There was no difference in the incidence of side effects. The use of cold 0.5% bupivacaine or the addition of Mg to normal temperature 0.5% bupivacaine prolongs the sensory and motor block duration without increasing side effects and enhances the quality of intra- and post-operative analgesia with better patient satisfaction in sonar-guided femoral and sciatic nerve block for arthroscopic ACL reconstruction surgery.

Evidence-based clinical update: Which local anesthetic drug for pediatric caudal block provides optimal efficacy with the fewest side effects?

PubMed

Dobereiner, Elisabeth F A; Cox, Robin G; Ewen, Alastair; Lardner, David R

2010-12-01

The purpose of this evidence-based clinical update is to identify the best evidence when selecting a long-acting local anesthetic agent for single-shot pediatric caudal anesthesia in children. A structured literature search was conducted using PubMed and Medline (OVID) using the terms "caudal" and combinations of at least two of "bupivacaine", "ropivacaine", and "levobupivacaine". The search limits included "randomized controlled trials" (RCTs), "meta-analysis", "evidence-based reviews" or "reviews", "human", and "all child: 0-18 yr". Seventeen RCTs were identified that concerned single-shot pediatric caudal anesthesia with at least two of the three drugs in question. Data were extracted for the areas of clinical efficacy and side effects. Study findings were assigned levels of evidence, and grades of recommendation were made according to Centre for Evidence-Based Medicine criteria. The three drugs investigated were found to be equivalent in terms of efficacy. Evidence showed bupivacaine with the highest incidence of motor block and ropivacaine with the lowest. Adverse effects were rare and unrelated to the choice of drug. There were no serious adverse events. None of the three agents was shown to be superior in terms of efficacy. Bupivacaine is preferred if motor block is desired, ropivacaine is preferred if motor block is to be minimized. Adverse effects in human studies are rare, mild, and unrelated to the choice of drug. Despite encountering the absence of serious adverse events in each of the studies reviewed, it is noted that animal studies suggest a safer profile with ropivacaine or levobupivacaine than with bupivacaine.

Intraperitoneal lignocaine (lidocaine) versus bupivacaine after laparoscopic cholecystectomy: results of a randomized controlled trial.

PubMed

Khan, Muhammad Rizwan; Raza, Rushna; Zafar, Syed Nabeel; Shamim, Faisal; Raza, Syed Ahsan; Pal, Khawaja Muhammad Inam; Zafar, Hasnain; Alvi, Rehman; Chawla, Tabish; Azmi, Rizwan

2012-12-01

Intraperitoneal local anesthetics have been shown to improve postoperative pain after laparoscopic cholecystectomy (LC). However, the choice of local anesthetic agent is debatable. We compared the analgesic efficacy of intraperitoneal lignocaine (lidocaine) versus bupivacaine after elective LC. We conducted a double-blind, randomized, controlled trial. We randomized consecutive patients undergoing LC into two groups. Group L received 10 mL 2% lignocaine (lidocaine), whereas Group B received 10 mL 0.5% bupivacaine, each diluted in 10 mL normal saline. All patients underwent standard perioperative anesthesia and analgesia protocol. We assessed patients at 0, 4, 8, 12, and 24 h postoperatively for pain using the visual analogue scale and verbal rating scale, and the need for additional analgesic medications. We analyzed a total of 206 patients: 106 in Group L and 100 in Group B. Demographic details were similar between groups (P > 0.05). Abdominal pain decreased significantly with time in both groups, with a similar mean response profile (P < 0.001). There was no statistically significant difference between groups with regard to abdominal or shoulder pain by both visual analogue scale and verbal rating scale at all five time intervals (P > 0.05). There was also no significant difference in the side effect profile of both drugs (P > 0.05). A lower proportion of patients in Group B required additional narcotic analgesia (87%) compared with Group L (94%). This difference was marginally significant (P = 0.057). Bupivacaine and lignocaine (lidocaine) are both safe and equally effective at decreasing postoperative pain after LC. Copyright © 2012 Elsevier Inc. All rights reserved.

Bupivacaine Lozenge Compared with Lidocaine Spray as Topical Pharyngeal Anesthetic before Unsedated Upper Gastrointestinal Endoscopy: A Randomized, Controlled Trial

PubMed Central

Salale, Nesrin; Treldal, Charlotte; Mogensen, Stine; Rasmussen, Mette; Petersen, Janne; Andersen, Ove; Jacobsen, Jette

2014-01-01

Unsedated upper gastrointestinal endoscopy (UGE) can induce patient discomfort, mainly due to a strong gag reflex. The aim was to assess the effect of a bupivacaine lozenge as topical pharyngeal anesthetic compared with standard treatment with a lidocaine spray before UGE. Ninety-nine adult outpatients undergoing unsedated diagnostic UGE were randomized to receive either a bupivacaine lozenge (L-group, n = 51) or lidocaine spray (S-group, n = 42). Primary objective was assessment of patient discomfort including acceptance of the gag reflex during UGE. The L-group assessed the discomfort significantly lower on a visual analog scale compared with the S-group (P = 0.02). There was also a significant difference in the four-point scale assessment of the gag reflex (P = 0.03). It was evaluated as acceptable by 49% in the L-group compared with 31% in the S-group. A bupivacaine lozenge compared with a lidocaine spray proved to be a superior option as topical pharyngeal anesthetic before an UGE. PMID:25374463

Levobupivacaine vs racemic bupivacaine in spinal anesthesia for sequential bilateral total knee arthroplasty: a retrospective cohort study.

PubMed

Chen, Chee Kean; Lau, Francis C S; Lee, Woo Guan; Phui, Vui Eng

2016-09-01

To compare the anesthetic potency and safety of spinal anesthesia with higher dosages of levobupivacaine and bupivacaine in patients for bilateral sequential for total knee arthroplasty (TKA). Retrospective cohort study. Operation theater with postoperative inpatient follow-up. The medical records of 315 patients who underwent sequential bilateral TKA were reviewed. Patients who received intrathecal levobupicavaine 0.5% were compared with patients who received hyperbaric bupivacaine 0.5% with fentanyl 25 μg for spinal anesthesia. The primary outcome was the use of rescue analgesia (systemic opioids, conversion to general anesthesia) during surgery for both groups. Secondary outcomes included adverse effects of local anesthetics (hypotension and bradycardia) during surgery and morbidity related to spinal anesthesia (postoperative nausea, vomiting, and bleeding) during hospital stay. One hundred fifty patients who received intrathecal levobupivacaine 0.5% (group L) were compared with 90 patients given hyperbaric bupivacaine 0.5% with fentanyl 25 μg (group B). The mean volume of levobupivacaine administered was 5.8 mL (range, 5.0-6.0 mL), and that of bupivacaine was 3.8 mL (range, 3.5-4.0 mL). Both groups achieved similar maximal sensory level of block (T6). The time to maximal height of sensory block was significantly shorter in group B than group L, 18.2 ± 4.5 vs 23.9 ± 3.8 minutes (P< .001). The time to motor block of Bromage 3 was also shorter in group B (8.7 ± 4.1 minutes) than group L (16.0 ± 4.5 minutes) (P< .001). Patients in group B required more anesthetic supplement than group L (P< .001). Hypotension and postoperative bleeding were significantly less common in group L than group B. Levobupivacaine at a higher dosage provided longer duration of spinal anesthesia with better safety profile in sequential bilateral TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

Lipid resuscitation in acute poisoning: after a decade of publications, what have we really learned?

PubMed

Hoegberg, Lotte C G; Gosselin, Sophie

2017-08-01

The decision to provide intravenous lipid emulsion (ILE) therapy as a treatment modality for the reversal of various drug toxicity was discovered in the last decade. Numerous publications, in both humans and animals attest to its clinical use, but current supporting evidence is inconsistent. A recent systematic review reported evidence for benefit of ILE in bupivacaine toxicity. Human randomized trials, large observational studies as well as animal models of orogastric poisoning failed to report a clear benefit of ILE for nonlocal anesthetics poisoning. ILE can be used to resuscitate local anesthetics especially bupivacaine. The impact of ILE on oral overdoses is controversial and clear evidence on benefit is lacking. A thorough risk benefit assessment with consideration of alternative options is warranted to minimize the risk of adverse effects. Evidence supports using bolus doses of ILE, while infusion rates are still debatable.

A prospective randomized double-blinded controlled study of ropivacaine 0.75% versus bupivacaine 0.5%-mepivacaine 2% for peribulbar anesthesia.

PubMed

Luchetti, M; Magni, G; Marraro, G

2000-01-01

Ropivacaine 1% has recently been used in clinical trials for peribulbar anesthesia. This study aims to compare the safety and the efficacy of ropivacaine 0.75% with that of a 1:1 mixture of bupivacaine 0.5% and mepivacaine 2% for peribulbar anesthesia. Two thousand patients undergoing peribulbar anesthesia for elective cataract phacoemulsification were prospectively studied over a 1-year period and randomly assigned to 1 of 2 groups according to the local anesthetic used. One thousand patients were administered peribulbar anesthesia with 9 mL of ropivacaine 0.75% plus 1 mL of hyaluronidase (group R), and 1,000 patients received peribulbar anesthesia with 4 mL of bupivacaine 0.5% plus 4 mL of mepivacaine 2% plus 1 mL of hyaluronidase plus 1 mL of sodium bicarbonate (group BM). Peribulbar anesthesia was always accomplished by the same physician by 2 injections of 5 mL each, with a 25-gauge 25-mm needle. Evaluation was performed by another physician blinded to the technique used and included assessment of pain on local anesthetic injection, ocular and eyelid akinesia, need for top-up injections, onset time and duration of anesthesia, intraoperative analgesia, duration of surgery, hemodynamic parameters, and incidence of perioperative complications. A greater incidence of pain on injection was found in group BM (P<.001). No difference between the groups was found regarding the onset time and the duration of anesthesia. Perioperative analgesia was satisfactory in both groups with no significant difference. Patients in group R showed a reduced need for top-up injection and a better ocular akinesia at 8 and 10 minutes (P<.01). The akinesia of the eyelid was comparable in the 2 groups and complete in all cases at 8 minutes. Cardiac arrhythmias were more frequent in group BM (P<.01). Local complications did not differ between the groups. An increase in mean artierial blood pressure and heart rate was observed in both groups 1 minute after injection of local anesthetic. Peribulbar anesthesia with ropivacaine provided better ocular akinesia 8 to 10 minutes after block insertion than a bupivacaine-mepivacaine mixture, which reduced the need for top-up injections. Ropivacaine also caused less pain on injection.

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

PubMed Central

Sancho-Puchades, Manuel; Vílchez-Pérez, Miguel A.; Paredes-García, Jordi; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

2012-01-01

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability. Key words:Bupivacaine, articaine, third molar, anesthesia, postoperative pain. PMID:22143739

Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1

PubMed Central

Beigh, Mushtaq Ahmad; Showkat, Mehvish; Bashir, Basharat; Bashir, Asma; Hussain, Mahboob ul; Andrabi, Khurshid Iqbal

2014-01-01

Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation. PMID:24605337

History of T-cain: a local anesthetic developed and manufactured in Japan.

PubMed

Tobe, Masaru; Saito, Shigeru

2015-10-01

In many anesthesia textbooks written in English, lidocaine, tetracaine, bupivacaine, ropivacaine, and chloroprocaine are listed as useful local anesthetics for spinal anesthesia. In contrast, T-cain is not included in these lists, even though it has been reported to be suitable for spinal anesthesia in Japan. T-cain was developed as a local anesthetic in the early 1940s by Teikoku Kagaku Sangyo Inc. in Itami, Japan, by replacing a methyl group on tetracaine (Pantocaine(®)) with an ethyl group. T-cain was clinically approved for topical use in Japan in November 1949, and a mixture of dibucaine and T-cain (Neo-Percamin S(®)) was approved for spinal use in May 1950. Simply because of a lack of foreign marketing strategy, T-cain has never attracted global attention as a local anesthetic. However, in Japan, T-cain has been used topically or intrathecally (as Neo-Percamin S(®)) for more than 60 years. Other than the side effects generally known for all local anesthetics, serious side effects have not been reported for T-cain. In fact, several articles have reported that T-cain decreases the neurotoxicity of dibucaine. In this historical review, the characteristics of T-cain and its rise to become a major spinal anesthetic in Japan are discussed.

Comparative Evaluation of Anesthetic Efficacy of 2% Lidocaine, 4% Articaine, and 0.5% Bupivacaine on Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double-blind Clinical Trial.

PubMed

Aggarwal, Vivek; Singla, Mamta; Miglani, Sanjay

2017-01-01

To compare the anesthetic efficacy of 1.8 mL of 2% lidocaine with 1:200,000 epinephrine, 4% articaine with 1:100,000 epinephrine, and 0.5% bupivacaine with 1:200,000 epinephrine on producing inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. A total of 91 adult patients who were actively experiencing mandibular molar pain were involved in this study. The patients were randomly divided into three groups on the basis of the anesthetic solution used. The first group received IANB with 1.8 mL of 2% lidocaine with 1:200,000 epinephrine, the second group received IANB with 4% articaine with 1:100,000 epinephrine, and the third group received IANB with 0.5% bupivacaine with 1:200,000 epinephrine. After 15 minutes of IANB, conventional endodontic access preparation was started. The pain during the treatment was noted on a Heft-Parker visual analog scale (HP VAS). The primary outcome measure was anesthetic success, and anesthesia was considered successful if the patient reported no pain or weak/mild pain (HP VAS score < 55 mm) during endodontic treatment (pulp access and canal preparation procedures). The data were analyzed with one-way analysis of variance and chi-square test. The anesthetic success rates of 2% lidocaine, 4% articaine, and 0.5% bupivacaine were 23%, 33%, and 17%, respectively. The differences were statistically insignificant (P > .05). The 2% lidocaine solution used for IANB had similar success rates when compared with 4% articaine and 0.5% bupivacaine.

Anesthetic Efficacy of Bupivacaine Solutions in Inferior Alveolar Nerve Block

PubMed Central

Volpato, Maria Cristina; Ranali, José; Ramacciato, Juliana Cama; de Oliveira, Patrícia Cristine; Ambrosano, Glaúcia Maria Bovi; Groppo, Francisco Carlos

2005-01-01

The purpose of this study was to compare the anesthetic efficacy of 2 bupivacaine solutions. Twenty-two volunteers randomly received in a crossover, double-blinded manner 2 inferior alveolar nerve blocks with 1.8 mL of racemic bupivacaine and a mixture of 75% levobupivacaine and 25% dextrobupivacaine, both 0.5% and with 1 : 200,000 epinephrine. Before and after the injection, the first mandibular pre-molar was evaluated every 2 minutes until no response to the maximal output (80 reading) of the pulp tester and then again every 20 minutes. Data were analyzed using the Wilcoxon paired test and the paired t test. No differences were found between the solutions for onset and duration of pulpal anesthesia and duration of soft tissue anesthesia (P > .05). It was concluded that the solutions have similar anesthetic efficacy. PMID:16596912

Epidural Analgesia with Amide Local Anesthetics, Bupivacaine, and Ropivacaine in Combination with Fentanyl for Labor Pain Relief: A Meta-Analysis

PubMed Central

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-01-01

Background The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Material/Methods Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I2 index. Results Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of −6.87 (−10.98, −2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. Conclusions In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block. PMID:25816849

Epidural analgesia with amide local anesthetics, bupivacaine, and ropivacaine in combination with fentanyl for labor pain relief: a meta-analysis.

PubMed

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-03-29

The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I^2 index. Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of -6.87 (-10.98, -2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block.

Effectiveness for pain after laparoscopic cholecystectomy of 0.5% bupivacaine-soaked Tabotamp placed in the gallbladder bed: a prospective, randomized, clinical trial.

PubMed

Feroci, Francesco; Kröning, Katrin Christel; Scatizzi, Marco

2009-10-01

Some scientific studies, with controversial results, have evaluated the efficacy in reducing pain of some different local anesthetic molecules, which were administered at different dosages and in different ways. The primary goal of this randomized, controlled, prospective study (Clinical Trials.gov ID NCT00599144) was to assess the effectiveness of 0.5% bupivacaine for pain control after video-laparoscopic cholecystectomy at its optimal dosage of 2 mg/kg infiltrated in the muscular fasciae of the trocars, or positioned in the gallbladder soaking a sheet of regenerated oxidized cellulose (Tabotamp). A total of 45 patients underwent elective video-laparoscopic cholecystectomy. They were randomized in three groups each made of 15 patients: group A (bupivacaine-soaked Tabotamp positioned in the gallbladder bed), group B (bupivacaine infiltrated in the muscular fasciae of the trocars' seat), group C (control group, not using local anesthetic). Six and twenty-four hours after the intervention, the nature of the pain and its intensity were recorded with the use of a Visual Analogue Scale (VAS). Six hours after the intervention, VAS average was 29.6 +/- 10.92 for group A, 25.86 +/- 16.06 for group B, and 36.13 +/- 16.62 for group C. At 24 h, we recorded 19.26 +/- 15.81, 18.53 +/- 12.3, and 20.46 +/- 20.08 for groups A, B, and C, respectively (p > 0.05). Comparing groups A and B between them and with the control group at 6 and 24 h, we deduced how only the first group showed a statistically significant advantage (p < 0.05) in reducing visceral and shoulder pain compared with the two other groups. Wound infiltration resulted in being statistically favorable in reducing parietal pain only when compared with Group A. For groups A and B, bupivacaine significantly reduced the use of postoperative pain killers. Bupivacaine, either infiltrated in trocars' wounds or kept soaked in a regenerated oxidized cellulose sheet positioned in the gallbladder bed, although safe and not economically demanding, can increase postoperative comfort.

[Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia].

PubMed

Kozlov, S P; Svetlov, V A; Luk'ianov, M V

1998-01-01

Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p < 0.05) but was no shorter (124.1 +/- 3.37 min) than operative analgesia with 0.75% hyperbaric bupivacaine (120.0 +/- 5.10 min). Isobaric bupivacaine provided the longest effective analgesia (215.0 +/- 45.0 min, p < 0.05). Microcatheter technique improved the safety and control of subarachnoidal anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.

Cardiovascular tolerance of intravenous bupivacaine in broiler chickens (Gallus gallus domesticus) anesthetized with isoflurane.

PubMed

DiGeronimo, Peter M; da Cunha, Anderson F; Pypendop, Bruno; Brandão, João; Stout, Rhett; Rinaldi, Max; Tully, Thomas N

2017-03-01

To determine the median effective dose (ED 50 ) of intravenous (IV) bupivacaine associated with a 50% probability of causing clinically relevant cardiovascular effects [defined as 30% change in heart rate (HR) or mean arterial pressure (MAP)] in chickens anesthetized with isoflurane. Randomized up-and-down study. A total of 14 Ross-708 broiler chickens (Gallus gallus domesticus) weighing 1.70-2.75 kg. Anesthesia was induced and maintained with isoflurane. Monitoring included the electrocardiogram and invasive arterial pressures. Chickens were administered bupivacaine IV over 2 minutes using a dose based on the response of the previous animal. Dose was decreased when HR and/or MAP in the previous animal increased or decreased ≥30% after bupivacaine administration, or increased when HR or MAP changed <30%. The ED 50 was defined as the dose resulting in ≥30% variation in HR or MAP in 50% of the population studied. The IV ED 50 of bupivacaine was 1.94 mg kg -1 using Dixon's up-and-down method and 1.96 mg kg -1 by logistic regression. These results suggest that 1.33 and 1.96 mg kg -1 of IV bupivacaine are associated with a respective 1 or 50% probability of a clinically significant change in MAP in isoflurane-anesthetized chickens. Identification of the cardiovascular changes associated with different doses of bupivacaine can be used as the basis for studies of therapeutic applications in the domestic chicken. Further studies are required to determine interspecies variation. Published by Elsevier Ltd.

Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes

PubMed Central

Block, Linda; Jörneberg, Per; Björklund, Ulrika; Westerlund, Anna; Biber, Björn; Hansson, Elisabeth

2013-01-01

Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na+ channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, < 10−8 m, evoked Ca2+ transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca2+ signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, < 10−8 m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca2+ signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist. PMID:24083665

Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.

PubMed

Duncan, Michael A; McNicholas, Walter; O'Keeffe, Declan; O'Reilly, Maeve

2002-01-01

Sternal fracture pain is severe and is difficult to alleviate due to the forces acting on the chest wall during respiration. We describe a continuous infusion regional analgesic technique for pain due to sternal fracture. A 47-year-old woman presented with a spontaneous sternal fracture, precluding effective coughing. Diclofenac and increasing doses of opioids did not give adequate pain relief and led to opioid toxicity. Two brief periods of analgesia were achieved with deep subcutaneous infiltration of bupivacaine. An epidural catheter was positioned periosteally, and an infusion of bupivacaine was commenced at 5 mL/h, achieving long-lasting analgesia. The bupivacaine concentration was reduced in a stepwise fashion from 0.5% to 0.25% and was changed to levobupivacaine after 3 days. Adding morphine (5 mg/60 mL levobupivicaine) permitted a reduction in infusion rate. The catheter was removed after 14 days because a local infection developed that resolved uneventfully with antibiotic therapy. Continuous infusion of local anesthetic and opioid to a sternal fracture site using a periosteally positioned catheter led to successful analgesia and hence improved respiratory function. Clinicians should consider placing a periosteal catheter when pain associated with sternal fracture cannot be adequately controlled with conventional methods.

Dynamic Changes in Acetylcholine Output in the Medial Striatum during Place Reversal Learning

ERIC Educational Resources Information Center

Ragozzino, Michael E.; Choi, Daniel

2004-01-01

The present studies explored the role of the medial striatum in learning when task contingencies change. Experiment 1 examined whether the medial striatum is involved in place reversal learning. Testing occurred in a modified cross-maze across two consecutive sessions. Injections of the local anesthetic, bupivacaine, into the medial striatum, did…

Hyperbaric versus plain bupivacaine for spinal anesthesia for cesarean delivery.

PubMed

Heng Sia, Alex Tiong; Tan, Kok Hian; Sng, Ban Leong; Lim, Yvonne; Chan, Edwin S Y; Siddiqui, Fahad Javaid

2015-01-01

Bupivacaine is an amide local anesthetic used in hyperbaric and plain forms administered as spinal anesthesia for cesarean delivery. In this systematic review, we summarized the effectiveness and safety of hyperbaric versus plain bupivacaine in providing anesthesia for cesarean delivery. We considered the adequacy of anesthesia for completion of cesarean delivery and the need for interventions to treat complications. We searched the CENTRAL, MEDLINE, and EMBASE databases. We imposed no language restriction. We included all randomized controlled trials involving patients undergoing spinal anesthesia for elective cesarean delivery that compared the use of hyperbaric bupivacaine with plain bupivacaine. We included 6 studies with a total of 394 patients in this review. These studies have small sample size, few observed events, differences in methodology, and insufficient information pertaining to assessment of risk of bias. This prevented us from calculating pooled estimates. Results show that there is no compelling evidence in favor of the use of intrathecal plain or hyperbaric bupivacaine for spinal anesthesia for cesarean delivery. There is a lack of clear evidence regarding the superiority of hyperbaric compared with plain bupivacaine for spinal anesthesia for cesarean delivery. The need for conversion to general anesthesia because of failed spinal anesthesia is an important clinical outcome, but current data are insufficient to compare spinal anesthesia induced with hyperbaric compared with plain bupivacaine for this outcome. Further research is required.

Local anesthetic use in tumescent liposuction: an American Society of Plastic Surgeons survey.

PubMed

Paik, Angie M; Daniali, Lily N; Lee, Edward S; Hsia, Henry C

2015-02-01

Current guidelines favor the use of lidocaine in liposuction wetting solutions. The use of bupivacaine as an alternative remains controversial despite reports of its use with safe and favorable outcomes suggesting faster postoperative recovery time secondary to improved pain control. The goals of this study were to determine the prevalence of bupivacaine use, examine liposuction practices of bupivacaine users, and elucidate opinions regarding bupivacaine use. An online survey was distributed to 2500 randomly selected members of the American Society of Plastic Surgeons. Data were collected and analyzed with special attention toward the practice and opinions of bupivacaine use. The response rate of the survey met the average American Society of Plastic Surgeons online survey response rate at 12.8% (n=320). Respondents (7.2%; n=22) reported using bupivacaine in their wetting solutions (bupivacaine group) and provided a dosage range of 62.5 to 150 mg. Respondents (83.5%; n=254) reported using either lidocaine or prilocaine (no-bupivacaine group). There were no reports of bupivacaine toxicity in 2011. The demographic profile and liposuction practices of both groups were comparable. Although 36% of the no-bupivacaine group did not know or had no opinion on when it is appropriate to use bupivacaine in liposuction wetting solutions, 85% of this group has used bupivacaine for other clinical purposes. A review of 320 plastic surgeons' experiences revealed that 7% of respondents are using bupivacaine in their tumescent solutions with no reported cases of toxicity. Bupivacaine users differed dramatically only in their opinion regarding the safety of bupivacaine in tumescent liposuction. The recent studies suggesting better postoperative pain control with bupivacaine along with the proportion of respondents reporting bupivacaine use call for distinct guidelines on bupivacaine use in liposuction. Further studies, including a rigorous clinical trial documenting the safety and efficacy of bupivacaine when compared with lidocaine, would be warranted.

Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

PubMed Central

Ok, Seong-Ho; Byon, Hyo-Jin; Kwon, Seong-Chun; Park, Jungchul; Lee, Youngju; Hwang, Yeran; Baik, Jiseok; Choi, Mun-Jeoung; Sohn, Ju-Tae

2015-01-01

Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca2+]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca2+]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF. PMID:26664257

Does Preincisional Infiltration with Bupivacaine Reduce Postoperative Pain in Laparoscopic Bariatric Surgery?

PubMed

Moncada, Rafael; Martinaitis, Linas; Landecho, Manuel; Rotellar, Fernando; Sanchez-Justicia, Carlos; Bellver, Manuel; de la Higuera, Magdalena; Silva, Camilo; Osés, Beatriz; Martín, Elena; Pérez, Susana; Hernandez-Lizoain, Jose Luis; Frühbeck, Gema; Valentí, Victor

2016-02-01

Current evidence suggests that local anesthetic wound infiltration should be employed as part of multimodal postoperative pain management. There is scarce data concerning the benefits of this anesthetic modality in laparoscopic weight loss surgery. Therefore, we analyzed the influence of trocar site infiltration with bupivacaine on the management of postoperative pain in laparoscopic bariatric surgery. This retrospective randomized study included 47 patients undergoing primary obesity surgery between January and September 2014. Laparoscopic gastric bypass was performed in 39 cases and sleeve gastrectomy in 8 cases. Patients were stratified into two groups depending on whether preincisional infiltration with bupivacaine and epinephrine was performed (study group, 27 patients) or not (control group, 20 patients). Visual analogue scale (VAS), International Pain Outcomes questionnaire, and rescue medication records were reviewed to assess postoperative pain. VAS scores in the study group and sleeve gastrectomy group were lower than those in the control and gastric bypass groups in the first 4 h postoperatively without reaching statistical significance (p > 0.05). VAS scores did not differ in any other period of time. No statistically significant differences in pain perception were registered according to the patient's pain outcomes questionnaire or the need for rescue medication. The present study did not conclusively prove the efficacy of bupivacaine infiltration by any of the three evaluation methods analyzed. Nevertheless, preincisional infiltration provides good level of comfort in the immediate postoperative period when analgesia is most urgent.

Continuous spinal labor analgesia for two deliveries in a parturient with severe subvalvular aortic stenosis.

PubMed

Hyuga, Shunsuke; Okutomi, Toshiyuki; Kato, Rie; Hosokawa, Yuki

2016-12-01

Various degrees of left ventricular outflow tract (LVOT) obstruction have been seen in patients with subvalvular aortic stenosis (SAS). Regional analgesia during labor for parturients with SAS is relatively contraindicated because it has a potential risk for hemodynamic instability due to sympathetic blockade as a result of vasodilation by local anesthetics. We thought continuous spinal analgesia (CSA) using an opioid and minimal doses of local anesthetic could provide more stable hemodynamic status. We demonstrate the management of a 28-year-old pregnant patient with SAS who received CSA for her two deliveries. For her first delivery (peak pressure gradient (∆P) between LV and aorta was approximately 55 mmHg), intrathecal fentanyl was used as a basal infusion, but we needed a small amount of bupivacaine to provide supplemental intrathecal analgesia as labor progressed. Although there were mild fluctuations in hemodynamics, she was asymptomatic. For her second delivery (∆P between LV and aorta was approximately 90 mmHg), minimal doses of continuous bupivacaine were used as a basal infusion. For her additional analgesic requests, bolus co-administration of fentanyl was effective. There were no fluctuations in her hemodynamics. Although her SAS in her second pregnancy was more severe than in the first, her hemodynamics exhibited less fluctuation during the second delivery with this method. In conclusion, CSA using fentanyl combined with minimal doses of bupivacaine provided satisfactory analgesia and stable hemodynamics in parturient with severe SAS.

iTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways.

PubMed

Zhao, Wei; Liu, Zhongjie; Yu, Xujiao; Lai, Luying; Li, Haobo; Liu, Zipeng; Li, Le; Jiang, Shan; Xia, Zhengyuan; Xu, Shi-yuan

2016-02-01

Bupivacaine, a commonly used local anesthetic, has potential neurotoxicity through diverse signaling pathways. However, the key mechanism of bupivacaine-induced neurotoxicity remains unclear. Cultured human SH-SY5Y neuroblastoma cells were treated (bupivacaine) or untreated (control) with bupivacaine for 24 h. Compared to the control group, bupivacaine significantly increased cyto-inhibition, cellular reactive oxygen species, DNA damage, mitochondrial injury, apoptosis (increased TUNEL-positive cells, cleaved caspase 3, and Bcl-2/Bax), and activated autophagy (enhanced LC3II/LC3I ratio). To explore changes in protein expression and intercommunication among the pathways involved in bupivacaine-induced neurotoxicity, an 8-plex iTRAQ proteomic technique and bioinformatics analysis were performed. Compared to the control group, 241 differentially expressed proteins were identified, of which, 145 were up-regulated and 96 were down-regulated. Bioinformatics analysis of the cross-talk between the significant proteins with altered expression in bupivacaine-induced neurotoxicity indicated that phosphatidyl-3-kinase (PI3K) was the most frequently targeted protein in each of the interactions. We further confirmed these results by determining the downstream targets of the identified signaling pathways (PI3K, Akt, FoxO1, Erk, and JNK). In conclusion, our study demonstrated that PI3K may play a central role in contacting and regulating the signaling pathways that contribute to bupivacaine-induced neurotoxicity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The acute toxicity of local anesthetics.

PubMed

Mather, Laurence E

2010-11-01

Systemic toxicity, usually from overdose or intravascular dose, is feared because it mainly affects the heart and brain, and may be acutely life-threatening. Pharmacological studies of local anesthetic toxicity have largely been reviewed primarily relating to the evaluation of ropivacaine and levobupivacaine during the past decade. This review/opinion focuses more on the principles and concepts underlying the main models used, from chemical pharmacological and pharmacokinetic perspectives. Research models required to produce pivotal toxicity data are discussed. The potencies for neural blockade and systemic toxicity are associated across virtually all models, with some deviations through molecular stereochemistry. These models show that all local anesthetics can produce direct cardiovascular system toxicity and CNS excitotoxicity that may further affect the cardiovascular system response. Whereas the longer-acting local anesthetics are more likely to cause cardiac death by malignant arrhythmias, the shorter-acting agents are more likely to cause cardiac contraction failure. In most models, equi-anesthetic doses of ropivacaine and levobupivacaine are less likely to produce serious toxicity than bupivacaine. Of the various models, this reviewer favors a whole-body large animal preparation because of the comprehensive data collection possible. The conscious sheep preparation has contributed more than any other, and may be regarded as the de facto 'standard' experimental model for concurrent study of local anesthetic toxicity ± pharmacokinetics, using experimental designs that can reproduce the toxicity seen in clinical accidents.

Comparison of Bupivacaine and Lidocaine Use for Postoperative Pain Control in Endodontics

PubMed Central

Moradi, Saeed; Naghavi, Neda

2010-01-01

INTRODUCTION: Many patients suffer from mild, moderate or severe pain during or after root canal therapy. Theoretically, post-operative pain control can be achieved by using long-acting local anesthetics. The aim of this study was to evaluate the efficacy of a long acting anesthesia, bupivacaine, on preventing post-operative pain associated with endodontic treatment, and to compare it with lidocaine. MATERIALS AND METHODS: This study was a double blind and randomized clinical trial on 30 patients' anterior maxillary teeth. The patients were divided into two groups of fifteen. One group was administered lidocanine (2% with 1:100000 epinephrine) local anesthesia and the other group was given bupivacaine (0.5% without epinephrine). The pain in patients were compared using the visual analogue scale (VAS) at definite times i.e. before treatment, during treatment and 2,4,6,8,10,12,24,36 and 48 hours after operation. Data were analyzed using One-way ANOVA tests. RESULTS: Bupivacaine significantly decreased postoperative pain compared to lidocaine. Postoperative pain was directly related to preoperative pain. Women reported more pain, though significant difference in postoperative pain report was not found between different ages. CONCLUSION: In conclusion, a single dose of bupivacaine 0.5% used in infiltration anesthesia could be more effective in reduction or prevention of post-operative endodontic pain compared with lidocaine. PMID:24778680

The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis.

PubMed

Sultan, Pervez; Murphy, Caitriona; Halpern, Stephen; Carvalho, Brendan

2013-09-01

The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs). We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs. Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD -14.03; 95% CI -27.52 to -0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05). When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.

Intrathecal magnesium sulfate does not reduce the ED50 of intrathecal hyperbaric bupivacaine for cesarean delivery in healthy parturients: a prospective, double blinded, randomized dose-response trial using the sequential allocation method.

PubMed

Xiao, Fei; Xu, Wenping; Feng, Ying; Fu, Feng; Zhang, Xiaomin; Zhang, Yinfa; Wang, Lizhong; Chen, Xinzhong

2017-01-17

Addition of intrathecal magnesium sulfate to local anesthetics has been reported to potentiate spinal anesthesia and prolong analgesia in parturients. The current study was to determine whether intrathecal magnesium sulfate would reduce the dose of hyperbaric bupivacaine in spinal anesthesia with bupivacaine and sufentanil for cesarean delivery. Sixty healthy parturients undergoing scheduled cesarean delivery were randomly assigned to receive spinal anesthesia with 0.5% hyperbaric bupivacaine and 5 μg sufentanil with either 0.9% sodium chloride (Control group) or 50% magnesium sulfate (50 mg) (Magnesium group). Effective anesthesia was defined as a bilateral T 5 sensory block level achieved within 10 min of intrathecal drug administration and no additional epidural anesthetic was required during surgery. Characteristic of spinal anesthesia and the incidence of side effects were observed. The ED 50 for both groups was calculated using the Dixon and Massey formula. There was no significant difference in the ED 50 of bupivacaine between the Magnesium group and the Control group (4.9 mg vs 4.7 mg) (P = 0.53). The duration of spinal anesthesia (183 min vs 148 min, P < 0.001) was longer, the consumption of fentanyl during the first 24 h postoperatively (343 μg vs 550 μg, P < 0.001) was lower in the Magnesium group than that in the Control group. Intrathecal magnesium sulfate (50 mg) did not reduce the dose requirement of intrathecal bupivacaine, but can extend the duration of spinal anesthesia with no obvious additional side effects. This study was registered with Chinese Clinical Trial Registry (ChiCTR) on 15 Jul. 2014 and was given a trial ID number ChiCTR-TRC- 14004954 .

Effect of lipid emulsion on the central nervous system and cardiac toxicity of bupivacaine and levobupivacaine in awake rats.

PubMed

Oda, Yutaka; Ikeda, Yuko

2013-08-01

Despite numerous studies examining the effect of lipid emulsion on bupivacaine-induced cardiac toxicity, few studies have examined its effect on central nervous system (CNS) toxicity of local anesthetics. We investigated the effect of lipid emulsion on the CNS and cardiac toxicity of bupivacaine and levobupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly allocated to control-bupivacaine (CB), control-levobupivacaine (CL), lipid-bupivacaine (LB), and lipid-levobupivacaine (LL) groups (n = 8 in each group). After infusion of saline (CB and CL groups) or 20 % lipid emulsion (LB and LL groups) for 5 min, bupivacaine (CB and LB groups) or levobupivacaine (CL and LL groups) was administered IV at 1 mg/kg/min. Cumulative dose of anesthetics and their plasma concentrations at the onset of convulsions and cardiac arrest were measured. The doses of bupivacaine for inducing convulsions and cardiac arrest in the LB group (8.8 ± 1.7 and 10.2 ± 1.5 mg/kg, respectively) were significantly larger than those in the CB group (5.9 ± 1.1 and 7.1 ± 1.3 mg/kg, respectively, p < 0.001 for both). The doses of levobupivacaine for inducing convulsions and cardiac arrest in the LL group (10.0 ± 2.0 and 13.7 ± 3.6 mg/kg, respectively) were significantly larger than those in the CL group (7.7 ± 1.6 and 9.4 ± 2.4 mg/kg, p = 0.03 and p = 0.02, respectively). Plasma concentrations of bupivacaine at the onset of convulsions and cardiac arrest in the LB group (12.9 ± 2.9 and 41.4 ± 5.2 μg/ml, respectively) were significantly higher than those in the CB group (7.9 ± 1.2 and 21.6 ± 3.3 μg/ml, respectively, p < 0.001 for both). Plasma concentrations of levobupivacaine at the onset of convulsions and cardiac arrest in the LL group (17.5 ± 1.5 and 47.6 ± 6.1 μg/ml, respectively) were significantly higher than in the CL group (10.9 ± 2.2 and 29.2 ± 3.5 μg/ml, respectively, p < 0.001 for both). Lipid emulsion decreased CNS and cardiac toxicity of both bupivacaine and levobupivacaine.

Effects of the addition of subarachnoid clonidine to the anesthetic solution of sufentanil and hyperbaric or hypobaric bupivacaine for labor analgesia.

PubMed

Tebaldi, Thaís Cristina; Malbouisson, Luíz Marcelo Sá; Kondo, Mario M; Cardoso, Mônica M S C

2008-01-01

The addition of subarachnoid clonidine (alpha-agonist) prolongs the analgesia produced by the combination of sufentanil and isobaric bupivacaine in combined labor analgesia(1). The objective of this study was to compare the quality of analgesia and the prevalence of side effects after the addition of subarachnoid clonidine to the anesthetic solution in labor analgesia. After approval by the Ethics Commission, 22 pregnant women in labor were randomly assigned to the subarachnoid administration of either 2.5 mg of 0.5% hyperbaric bupivacaine (CLON/HYPER Group; n = 11) or 2.5 mg of 0.5% isobaric bupivacaine (CLON/ISO Group; n = 11) associated with 2.5 microg of sufentanil and 30 microg of clonidine. Pain, evaluated by the Visual Analogue Scale, heart rate, and mean arterial pressure were assessed every 5 minutes during the first 15 minutes, and then every 15 minutes afterwards until delivery. The prevalence of side effects (nausea, vomiting, pruritus, and sedation) was evaluated. The study was terminated whenever the patient needed supplemental epidural analgesia (pain > 3) or upon delivery of the fetus. The Student t test, Chi-square test, Fisher exact test, and two-way ANOVA for repeated measurements were used in the statistical analysis and a p < 0.05 was considered significant. Anthropometric data, duration of analgesia (70.9 +/- 32.9 vs. 85.4 +/- 39.5), heart rate, and the incidence of pruritus, sedation, nausea, and vomiting were similar in both groups. Mean arterial pressure was significantly lower in the CLON/ISO Group than in the CLON/HYPER Group at 15, 30, and 45 minutes (p < 0.05). Under the conditions of the present study, the association of a small dose of clonidine (30 microg) with sufentanil caused a higher incidence of hypotension when the isobaric solution of the local anesthetic was used. For all other side effects, both hyperbaric and isobaric solutions showed similar behavior.

The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.

PubMed

Suresh, Santhanam; Ecoffey, Claude; Bosenberg, Adrian; Lonnqvist, Per-Anne; de Oliveira, Gildasio S; de Leon Casasola, Oscar; de Andrés, José; Ivani, Giorgio

2018-02-01

Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.

Which one is more effective for analgesia in infratentorial craniotomy? The scalp block or local anesthetic infiltration.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Vehid, Hayriye; Ibısoglu, Lutfiye Serap; Tunali, Yusuf

2017-03-01

The most painful stages of craniotomy are the placement of the pin head holder and the skin incision. The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5% on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies. The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h. This prospective, randomized and placebo controlled study included forty seven patients (ASA I, II and III). The scalp block was performed in the Group S, the local anesthetic infiltration was performed in the Group I and the control group (Group C) only received remifentanil as an analgesic during the intraoperative period. The hemodynamic response to the pin head holder application and the skin incision, as well as postoperative pain intensity, cumulative morphine consumption and opioid related side effects were compared. The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies. The local anesthetic infiltration reduced the hemodynamic response to the skin incision. As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h. Moreover, the pain intensity was lower after scalp block in the early postoperative period. The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential mortality of male spectacled eiders (Somateria fischeri) and king eiders (Somateria spectabilis) subsequent to anesthesia with propofol, bupivacaine, and ketoprofen

USGS Publications Warehouse

Mulcahy, Daniel M.; Tuomi, Pamela A.; Larsen, R.S.

2003-01-01

Twenty free-ranging spectacled eiders (Somateria fischeri; 10 male, 10 female), 11 free-ranging king eiders (Somateria spectabilis; 6 male, 5 female), and 20 female common eiders (Somateria mollissima) were anesthetized with propofol, bupivacaine, and ketoprofen for the surgical implantation of satellite transmitters. Propofol was given to induce and maintain anesthesia (mean total dose, 26.2-45.6 mg/kg IV), bupivacaine (2-10 mg/kg SC) was infused into the incision site for local analgesia, and ketoprofen (2-5 mg/kg IM) was given at the time of surgery for postoperative analgesia. Four of 10 male spectacled eiders and 5 of 6 male king eiders died within 1-4 days after surgery. None of the female spectacled or common eiders and only 1 of the 5 female king eiders died during the same postoperative period. Histopathologic findings in 2 dead male king eiders were severe renal tubular necrosis, acute rhabdomyolysis, and mild visceral gout. Necropsy findings in 3 other dead male king eiders were consistent with visceral gout. We suspect that the perioperative use of ketoprofen caused lethal renal damage in the male eiders. Male eiders may be more susceptible to renal damage than females because of behavioral differences during their short stay on land in mating season. The combination of propofol, bupivacaine, and ketoprofen should not be used to anesthetize free-ranging male eiders, and nonsteroidal anti-inflammatory drugs should not be used perioperatively in any bird that may be predisposed to renal insufficiency.

Effect of wound infiltration with ropivacaine or bupivacaine analgesia in breast cancer surgery: A meta-analysis of randomized controlled trials.

PubMed

Tam, Ka-Wai; Chen, Shin-Yan; Huang, Tsai-Wei; Lin, Chao-Chun; Su, Chih-Ming; Li, Ching-Li; Ho, Yuan-Soon; Wang, Wan-Yu; Wu, Chih-Hsiung

2015-10-01

Although not completely painless, breast-conserving surgery is considerably less painful than modified radical mastectomy. Local anesthetics are speculated to reduce postoperative pain when placed at the surgical site. Thus, we conducted a systematic review of randomized controlled trials to evaluate the efficacy of bupivacaine or ropivacaine analgesia for pain relief in breast cancer surgery. PubMed, Embase, the Cochrane Library, Scopus, and the ClinicalTrials.gov registry were searched for studies published up to July 2015. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size by using random effects models. Pain was assessed using a visual analog scale at 1, 2, 12, and 24 h postoperatively. The secondary outcomes included complications and analgesic consumption. We reviewed 13 trials with 1150 patients. We found no difference in postoperative pain reduction at 1, 12, and 24 h after breast cancer surgery between the experimental and control groups. The severity of pain was significantly reduced in the experimental group (weighted mean difference -0.19; 95% confidence interval: -0.39-0.00) at 2 h postoperatively. Moreover, postoperative analgesic consumption did not differ significantly between the groups. No major drug-related complication was observed in any study. Administration of the local anesthetics bupivacaine or ropivacaine during breast cancer surgery decreased pain significantly at only 2 h but did not reduce pain at 12, and 24 h postoperatively. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

TASK channel deletion reduces sensitivity to local anesthetic-induced seizures

PubMed Central

Du, Guizhi; Chen, Xiangdong; Todorovic, Marko S.; Shu, Shaofang; Kapur, Jaideep; Bayliss, Douglas A.

2011-01-01

Background Local anesthetics (LAs) are typically used for regional anesthesia but can be given systemically to mitigate postoperative pain, supplement general anesthesia or prevent cardiac arrhythmias. However, systemic application or inadvertent intravenous injection can be associated with substantial toxicity, including seizure induction. The molecular basis for this toxic action remains unclear. Methods We characterized effects of different LAs on homomeric and heteromeric K+ channels containing TASK-1 (K2P3.1, KCNK3) and TASK-3 (K2P9.1, KCNK9) subunits in a mammalian expression system. In addition, we used TASK-1/TASK-3 knockout mice to test the possibility that TASK channels contribute to LA-evoked seizures. Results LAs inhibited homomeric and heteromeric TASK channels in a range relevant for seizure induction; channels containing TASK-1 subunits were most sensitive and IC50 values indicated a rank order potency of bupivacaine > ropivacaine ⟫ lidocaine. LAs induced tonic-clonic seizures in mice with the same rank order potency, but higher LA doses were required to evoke seizures in TASK knockout mice. For bupivacaine, which produced the longest seizure times, seizure duration was significantly shorter in TASK knockout mice; bupivacaine-induced seizures were associated with an increase in electroencephalogram power at frequencies <5 Hz in both wild type and TASK knockout mice. Conclusions These data suggest that increased neuronal excitability associated with TASK channel inhibition by LAs contributes to seizure induction. Since all LAs were capable of evoking seizures in TASK channel deleted mice, albeit at higher doses, the results imply that other molecular targets must also be involved in this toxic action. PMID:21946151

The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain.

PubMed

Parirokh, Masoud; Yosefi, Mohammad Hosein; Nakhaee, Nouzar; Abbott, Paul V; Manochehrifar, Hamed

2015-05-01

Achieving adequate anesthesia with inferior alveolar nerve blocks (IANB) is of great importance during dental procedures. The aim of the present study was to assess the success rate of two anesthetic agents (bupivacaine and lidocaine) for IANB when treating teeth with irreversible pulpitis. Sixty volunteer male and female patients who required root canal treatment of a mandibular molar due to caries participated in the present study. The inclusion criteria included prolonged pain to thermal stimulus but no spontaneous pain. The patients were randomly allocated to receive either 2% lidocaine with 1:80,000 epinephrine or 0.5% bupivacaine with 1:200,000 epinephrine as an IANB injection. The sensitivity of the teeth to a cold test as well as the amount of pain during access cavity preparation and root canal instrumentation were recorded. Results were statistically analyzed with the Chi-Square and Fischer's exact tests. At the final step, fifty-nine patients were included in the study. The success rate for bupivacaine and lidocaine groups were 20.0% and 24.1%, respectively. There was no significant difference between the two groups at any stage of the treatment procedure. There was no difference in success rates of anesthesia when bupivacaine and lidocaine were used for IANB injections to treat mandibular molar teeth with irreversible pulpitis. Neither agent was able to completely anesthetize the teeth effectively. Therefore, practitioners should be prepared to administer supplemental anesthesia to overcome pain during root canal treatment.

Efficacy of Liposomal Bupivacaine Infiltration on the Management of Total Knee Arthroplasty.

PubMed

Sakamoto, Bryan; Keiser, Shelly; Meldrum, Russell; Harker, Gene; Freese, Andrew

2017-01-01

Liposomal bupivacaine is a novel extended-duration anesthetic that has recently been used for local infiltration in total knee arthroplasty (TKA). Athough liposomal bupivacaine is widely used, it is unknown if the benefits justify the cost in the veteran population at our institution. To evaluate a change in practice: the effect of local infiltration of liposomal bupivacaine on perioperative outcomes in patients undergoing primary TKA. A retrospective cohort study was conducted among patients who underwent primary TKA at a Veterans Affairs Medical Center before (March 3, 2013-March 2, 2014) and after (March 3, 2014-March 2, 2015) the implementation of liposomal bupivacaine for local infiltration in TKA. Drug utilization evaluation of liposomal bupivacaine for local infiltration in TKA. Use of opioids after discharge from the postanesthesia care unit. Among 199 patients, those who received liposomal bupivacaine after primary TKA (mean [SD] age, 65.3 [6.9] years; 93 males and 5 females) had a reduced median opioid use in the first 24 hours after surgery compared with those who did not receive liposomal bupivacaine (mean [SD] age, 64.9 [8.4] years; 95 males and 6 females; [intravenous morphine equivalents, 12.50 vs 22.50 mg; P = .001]). The use of patient-controlled analgesia was also reduced among patients who received liposomal bupivacaine vs those who did not (49 vs 91; P < .001). A reduction in the use of antiemetics was observed in the first 24 hours after surgery (13 vs 34; P = .001) and in the postanesthesia care unit among those who received liposomal bupivacaine vs those who did not (4 vs 20; P = .001). The number of patients in the postanesthesia care unit with no pain was improved among those who received liposomal bupivacaine vs those who did not (44 vs 19; P < .001). Although median (interquartile range) pain scores in the postanesthesia care unit were improved among patients who received liposomal bupivacaine vs those who did not (4.0 [0.0-6.6] vs 5.5 [3.0-7.5]; P = .001), patients who received liposomal bupivacaine had greater median (interquartile range) pain scores 48 hours (5.5 [4.0-7.0] vs 5.0 [3.0-6.0]; P = .01), 72 hours (5.0 [4.0-6.0] vs 4.0 [2.0-6.0]; P = .002), and 96 hours (5.0 [3.0-6.5] vs 4.0 [1.0-5.0]; P = .003) after surgery than those who did not receive liposomal bupivacaine. There was no difference in the median length of stay between the 2 groups. Institutional cost savings was estimated at $27 000 per year. Local infiltration of liposomal bupivacaine reduces use of opioids in the first 24 hours after primary TKA. Similarly, reduction in antiemetic use and improved postoperative pain are also seen in the first 24 hours after surgery but are limited to this time frame. Furthermore, a positive institutional cost savings was observed.

OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells

PubMed Central

Liu, Zhong-Jie; Zhao, Wei; Zhang, Qing-Guo; Li, Le; Lai, Lu-Ying; Jiang, Shan; Xu, Shi-Yuan

2015-01-01

Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use. PMID:26161242

Bupivacaine application reduces post thyroidectomy pain: Cerrahpasa experience

PubMed Central

Teksoz, Serkan; Soylu, Selen; Erbabacan, Safak Emre; Ozcan, Murat; Bukey, Yusuf

2016-01-01

Background We aimed to evaluate the impact of bupivacaine administration into the surgical field after total thyroidectomy on post-operative pain and analgesic requirement with a double-blind, prospective, clinical and randomized study. Methods The study was performed between 2010 and 2011. Pain assessment was performed with the visual analog score (VAS). Patients were pre-operatively, randomly divided into two groups to receive either bupivacaine or saline. One group received a 10-mL of bupivacaine solution while the other group was treated with the same volume of 0.9% NaCl through the drain after completion of total thyroidectomy procedure. All patients were anesthetized and operated with the same anesthesia and surgical team. Results Ninety-one patients (20 males) were included in the study. No patient dropped out of the study during the procedures. No mortality was seen. The VAS scores were significantly lower in the bupivacaine administered group at post-operative minute 30 (3.7±3.2 vs. 5±2.9; P=0.03), hour one (3.04±2.4 vs. 4.2±2.8; P=0.04), and hour eight (1.8±2.04 vs. 3.2±2.1; P=0.005). Thirteen patients required analgesia during their hospital stay in the bupivacaine group while this number was twenty-two in the saline group (P=0.005). Conclusions Local bupivacaine administration into the surgical field after total thyroidectomy reduces pain and analgesic requirement during the hospital stay. PMID:28149801

Double-blind, randomized controlled clinical trial on analgesic efficacy of local anesthetics articaine and bupivacaine after impacted third molar extraction.

PubMed

Olmedo-Gaya, Maria Victoria; Manzano-Moreno, Francisco Javier; Muñoz-López, Jose Luis; Vallecillo-Capilla, Manuel Francisco; Reyes-Botella, Candela

2018-02-15

The objective of this randomized controlled clinical trial (RCT) was to compare the effect of bupivacaine and articaine at habitual doses on pain intensity and the need for analgesics after lower third molar extraction. The final study sample comprised 50 Caucasian volunteers (26 males and 24 females; age range, 18-30 years) undergoing scheduled surgical extraction of impacted lower third molar. A computer-generated random sequence was used to allocate participants to the articaine (4%) or bupivacaine (0.5%) group. Surgeons and patients were blinded by labeling the articaine and bupivacaine carpules with numbers (1 and 2, respectively). Postoperative pain intensity (primary outcome) was evaluated with a visual analogue scale (VAS), while the requirement for and timing of rescue medication and the quality of intraoperative anesthesia were also measured (secondary outcomes). VAS-measured pain intensity was significantly higher (p < 0.05) in the articaine group than in the bupivacaine group at all time points except for 8 h post-surgery (p = 0.052). Rescue medication was required by 13 (52%) patients in the articaine group and 8 (32%) patients in the bupivacaine group, although the difference did not reach statistical significance (p = 0.252). The groups did not significantly differ (p = 0.391) in the quality of the intraoperative anesthesia. Bupivacaine is a valid alternative to articaine in third molar surgery and may offer residual anesthesia as a means of reducing postoperative pain. However, further well-designed RCTs are required in larger study populations to verify the effectiveness of bupivacaine to achieve residual analgesia after oral surgery. These findings suggest that bupivacaine may be useful as a coadjuvant to control acute postoperative pain. ACTRN12617001138370.

The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain

PubMed Central

Yosefi, Mohammad Hosein; Nakhaee, Nouzar

2015-01-01

Objectives Achieving adequate anesthesia with inferior alveolar nerve blocks (IANB) is of great importance during dental procedures. The aim of the present study was to assess the success rate of two anesthetic agents (bupivacaine and lidocaine) for IANB when treating teeth with irreversible pulpitis. Materials and Methods Sixty volunteer male and female patients who required root canal treatment of a mandibular molar due to caries participated in the present study. The inclusion criteria included prolonged pain to thermal stimulus but no spontaneous pain. The patients were randomly allocated to receive either 2% lidocaine with 1:80,000 epinephrine or 0.5% bupivacaine with 1:200,000 epinephrine as an IANB injection. The sensitivity of the teeth to a cold test as well as the amount of pain during access cavity preparation and root canal instrumentation were recorded. Results were statistically analyzed with the Chi-Square and Fischer's exact tests. Results At the final step, fifty-nine patients were included in the study. The success rate for bupivacaine and lidocaine groups were 20.0% and 24.1%, respectively. There was no significant difference between the two groups at any stage of the treatment procedure. Conclusions There was no difference in success rates of anesthesia when bupivacaine and lidocaine were used for IANB injections to treat mandibular molar teeth with irreversible pulpitis. Neither agent was able to completely anesthetize the teeth effectively. Therefore, practitioners should be prepared to administer supplemental anesthesia to overcome pain during root canal treatment. PMID:25984478

The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017.

PubMed

Neal, Joseph M; Barrington, Michael J; Fettiplace, Michael R; Gitman, Marina; Memtsoudis, Stavros G; Mörwald, Eva E; Rubin, Daniel S; Weinberg, Guy

2018-02-01

The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

In vivo potency of different ligands on voltage-gated sodium channels.

PubMed

Safrany-Fark, Arpad; Petrovszki, Zita; Kekesi, Gabriella; Liszli, Peter; Benedek, Gyorgy; Keresztes, Csilla; Horvath, Gyongyi

2015-09-05

The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of a local anesthetic lozenge in relief of symptoms in burning mouth syndrome.

PubMed

Treldal, C; Jacobsen, C B; Mogensen, S; Rasmussen, M; Jacobsen, J; Petersen, J; Lynge Pedersen, A M; Andersen, O

2016-03-01

Patients with burning mouth syndrome (BMS) often represent a clinical challenge as available agents for symptomatic treatment are few and often ineffective. The aim was to evaluate the effect of a bupivacaine lozenge on oral mucosal pain, xerostomia, and taste alterations in patients with BMS. Eighteen patients (4 men and 14 women) aged 39-71 years with BMS were included in this randomized, double-blinded, placebo-controlled, crossover trial. Lozenges (containing bupivacaine or placebo) were administrated three times a day for 2 weeks for two separate treatment periods. Assessment of oral mucosal pain, xerostomia, and taste alterations was performed in a patient diary on a visual analog scale (ranging from 0 to 100 mm) before and after the lozenge was dissolved. The bupivacaine lozenge significantly reduced the burning oral pain (P < 0.001), increased the sense of taste disturbances (P < 0.001), and had no impact on xerostomia, when adjusted for the treatment period. Our results indicate that the bupivacaine lozenge offers a novel therapeutic modality to patients with BMS, although without alleviating effect on the associated symptoms, taste alterations, and xerostomia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Three Newly Approved Analgesics: An Update

PubMed Central

Saraghi, Mana; Hersh, Elliot V.

2013-01-01

Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain. PMID:24423420

The effect of morphine added to bupivacaine in ultrasound guided transversus abdominis plane (TAP) block for postoperative analgesia following lower abdominal cancer surgery, a randomized controlled study.

PubMed

El Sherif, Fatma Adel; Mohamed, Sahar Abdel-Baky; Kamal, Shereen Mamdouh

2017-06-01

Transversus abdominis plane (TAP) block used for management of surgical abdominal pain by injecting local anesthetics into the plane between the internal oblique and transversus abdominis muscles. We aimed to explore the effect of adding morphine to bupivacaine in ultrasound guided TAP-block in patients undergoing lower abdominal cancer surgery. Randomized, double-blind, prospective study. Clinical trial identifier: NCT02566096. Academic medical center. Sixty patients were enrolled in this study after ethical committee approval. Patients divided into 2 groups (30 each): Bupivacaine group (GB): given ultrasound guided TAP-block 20ml 0.5% bupivacaine diluted in 20ml saline; Morphine group (GM): given ultrasound guided TAP-block with 20ml 0.5% bupivacaine+10mg morphine sulphate diluted in 20ml saline. Patients were observed for total morphine consumption, time for first request of rescue analgesia, sedation scores, hemodynamics and side effects for 24h postoperatively. Morphine added to bupivacaine in TAP block compared to bupivacaine alone reduced total morphine consumption (5.33±1.28mg) (10.70±3.09mg) respectively (p<0.001), prolonged the time to first request of analgesia (10.40±4.96h) (6.97±3.26h) respectively (p<0.008), with a statistically significant decrease in (VAS-M) in GM compared with GB at 12h postoperatively (p<0.002). No significant differences in hemodynamics, respiratory rate, oxygen saturation, sedation score, and side effects except for nausea were observed (p>0.05). Addition of morphine to bupivacaine in TAP block is effective method for pain management in patients undergoing major abdominal cancer surgery without serious side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Pain Reduction in Untreated Symptomatic Irreversible Pulpitis Using Liposomal Bupivacaine (Exparel): A Prospective, Randomized, Double-blind Trial.

PubMed

Bultema, Kristy; Fowler, Sara; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2016-12-01

In the treatment of patients with symptomatic irreversible pulpitis, endodontic debridement is a predictable method to relieve pain. However, there are clinical situations in which emergency care cannot be provided immediately. An unexplored treatment option in these cases may be the use of a long-acting anesthetic to reduce pain in untreated irreversible pulpitis. Some medical studies have shown potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA) to prolong pain relief and reduce opioid use postoperatively. The Food and Drug Administration has approved Exparel only for infiltrations; therefore, the purpose of this study was to compare an infiltration of liposomal bupivacaine versus bupivacaine for pain control in untreated, symptomatic irreversible pulpitis. Ninety-five emergency patients received 2% lidocaine with 1:100,000 epinephrine via infiltration or an inferior alveolar nerve block to relieve their initial presenting pain. Patients then randomly received either 4 mL liposomal bupivacaine (13.3 mg/mL) or 4 mL 0.5% bupivacaine with 1:200,000 epinephrine by infiltration. Patients received a diary for the day of the appointment and 3 days postinjection to record soft tissue numbness, pain levels, and analgesic (non-narcotic and narcotic) use. No significant differences (P < .05) were found between the 2 anesthetic formulations for pain or the use of pain medications. A statistically higher level of soft tissue numbness was found on days 1 to 3 for the liposomal bupivacaine group. Although liposomal bupivacaine had some effect on soft tissue anesthesia, it did not reduce pain to manageable clinical levels in patients presenting with untreated, symptomatic irreversible pulpitis. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Local anesthesia for abdominoplasty, liposuction, and combined operations.

PubMed

Mottura, A A

1993-01-01

This article describes a procedure to perform abdominoplasty, liposuction, and combined operations under local anesthesia. With an anesthetic solution composed of 25 cc of 2% lidocaine, 25 cc of 0.5% bupivacaine, 1 cc of epinephrine or ornipresine, and 350 cc of saline solution, a satisfactory dilution with low concentration and lasting effects was obtained. After infiltration a large amount was lost in the incision, the dissection, and the resected dermofatty tissue. A small amount of anesthetic remained in the operated area to be metabolized by the liver. Low lidocaine levels were found in venous blood samples during surgery. This type of anesthesia is advised in minor, limited, and normal abdominoplasties in normal-sized patients, or major abdominoplasties in small patients. In liposuction procedures, it is possible to anesthetize the patient using the same procedure and operate in an equivalent area. As a high proportion of the infiltrated anesthesia was lost during the operation, a similar amount could be used to infiltrate and operate other areas so that an abdominoplasty might be combined with liposuction or mastoplasty. We have experience with 25 abdominoplasties and 21 liposuctions performed under local anesthesia. There were no complications related to local anesthesia and no one had unpleasant memories of intraoperative events.

The Minimum Effective Dose of Lidocaine Needed to Block Evoked Potentials in the Sciatic Nerve of the Rat

DTIC Science & Technology

1998-10-01

which include the sciatic nerve, will be described. Gilman and Newman (1996) describe the PNS in their book, Manter and Gatz’s Essentials of Clinical ...Neural Blockade in Clinical Anesthesia and Management of Pain. He wrote that sensory and motor messages are transported along a nerve in the form of an...different groups of local anesthetics, the esters (procaine, chloroprocaine, tetracaine) and the amides (lidocaine, mepivacaine, bupivacaine , etidocaine

Ultrasound-guided rectus sheath and transversus abdominis plane blocks for perioperative analgesia in upper abdominal surgery: A randomized controlled study.

PubMed

Abdelsalam, Khaled; Mohamdin, O W

2016-01-01

Regional anesthetic techniques can be used to alleviate postoperative pain in patients undergoing major upper abdominal surgery. Our aim was to evaluate the efficacy of bilateral ultrasound (US)-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks for better perioperative analgesia. It is a prospective, observer-blinded, randomized clinical study. 40 eligible patients undergoing elective liver resection or Whipple procedure were included. All patients received a standardized anesthetic technique. Group 1 (n = 20) received preincisional US-guided bilateral RS and TAP blocks using 20 ml volume of bupivacaine 0.25% for each, and group 2 (n = 20) received local wound infiltration at end of surgery with 40 ml of bupivacaine 0.25%. A standardized postoperative analgesic regimen composed of intravenous paracetamol and a morphine patient-controlled analgesia (PCA). The use of intraoperative fentanyl and recovery room morphine boluses, PCA-administered morphine, pain scores as well as number of patients' experienced postoperative nausea and vomiting in the ward at 6 and 24 h were recorded. Group 1 patients received a significantly lower cumulative intraoperative fentanyl, significantly lesser boluses of morphine in postanesthesia care unit, as well, significantly lower cumulative 24 h postoperative morphine dosage than the group 2 patients. Pain visual analog scale scores were significantly lower at both 6 and 24 h postoperatively in TAP group when compared with the no-TAP group. There were no complications related to the TAP block procedures. No signs or symptoms of local anesthetic systemic toxicity were detected. The combination of bilateral US-guided RS and TAP blocks provides excellent perioperative analgesia for major upper abdominal surgery.

The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

PubMed

Tang, Wan; Wang, Quanguang; Shi, Kejian; Dong, Jiaojiao; Lin, Shengxian; Zhao, Shishi; Wu, Cong; Xia, Yun; Papadimos, Thomas J; Xu, Xuzhong

2016-11-01

Lipid infusions have been proposed to treat local anesthetic-induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. After administration of intravenous infusion of bupivacaine at 2 mg·kg·min for 5 minutes in Sprague-Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg·min for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group. LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

Concepts for Injectable Nanoparticles for In Vivo Removal of Overdose Toxins from Blood

DTIC Science & Technology

2002-01-01

Amitriptyline Bupivacaine Antiarrhythmic Antidepressant Anesthetic where X = aminoalkyl (similar to VX) o X II X CH3H3C NH C=O X • Initially, the research...basic due to an aminoalkyl group pendant to a benzene ring. It will be demonstrated that the pi electron density in at least bupivacaine is high...Science & Technology Attenuation of The Cardiotoxic Effects of Bupivacaine in Guinea Pig Isolated Heart by Macroemulsion 1 2 3 4 5 6 Q R S In te rv al

GaAs laser therapy reestablishes the morphology of the NMJ and nAChRs after injury due to bupivacaine.

PubMed

Pissulin, Cristiane Neves Alessi; de Souza Castro, Paula Aiello Tomé; Codina, Flávio; Pinto, Carina Guidi; Vechetti-Junior, Ivan Jose; Matheus, Selma Maria Michelin

2017-02-01

Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle. Thirty-two adult male Wistar rats received injections of bupivacaine 0.5% (Bupi: right antimere) and 0.9% sodium chloride (Cl: left antimere). Next, the animals were divided into a Control group (C) and a Laser group (LLLT). The laser group received LLLT (GaAs 904nm, 50mW, 4,8J) in both antimeres for five consecutive days. After seven days, the animals were euthanized and the surface portion of the sternomastoid muscle was removed, frozen, and subjected to morphological and morphometric analyses of the NMJs (nonspecific esterase reaction), confocal laser scanning, and an ultrastructural analysis. The nAChRs were quantified by Western blotting. In the chloride group, the morphology and morphometry of the NMJs remained stable. The maximum diameters of the NMJs were lower in the Bupi (15.048±1.985) and LLLT/Bupi subgroups (15.456±1.983) compared to the Cl (18.502±2.058) and LLLT/Cl subgroups (19.356±2.522) (p<0.05). Ultrastructurally, LLLT reduced myonecrosis observed after application of bupivacaine, with recovery in the junctional folds and active zone. There was an increase in the perimeter of the LLLT/Bupi subgroup (150.33) compared to the Bupi subgroup (74.69) (p<0.01) observed by confocal microscopy. There was also an increase in the relative planar area of the NMJ after LBI (8.75) compared to CBupi (4.80) (p<0.01). An analysis of the protein expression of nAChRα1 showed no major differences in the groups studied. There was an increase in protein expression of the ε subunit after application of LLLT (13.055) compared to Bupi (0.251) (p<0.01). Taken together, the present experiments indicate that there was a positive association of the α and γ subunits (p<0.05). These results demonstrate that LLLT at the dose used in this study reduced structural alterations in the NMJ and molecular changes in nAChRs triggered by bupivacaine, providing important data supporting the use of LLLT in therapeutic protocols for injuries triggered by local anesthetics. Copyright © 2016 Elsevier B.V. All rights reserved.

[Preemptive local anesthetic infiltration in hallux valgus one-day surgery].

PubMed

Gądek, Artur; Liszka, Henryk

2015-01-01

The surgical treatment of hallux valgus deformity is connected with significant postoperative pain. Spinal and general anesthesia as well as peripheral blocks are successfully used in foot surgery. The purpose of this study was to evaluate the influence of local anesthetic infiltration before hallux valgus one-day surgery on postoperative pain and the need for analgesics. 134 patients underwent chevron or miniinvasive Mitchell-Kramer osteotomy of the first distal metatarsal. After general anesthesia each patient randomly received an infiltration of 7ml of local anesthetic (4 ml of 0.25% bupivacaine and 3 ml of 2% lidocaine) or the same amount of normal saline 15 minutes before the skin incision. Both the patient and the surgeon were blinded. The patient was discharged after approximately 2 hours of observation. 2, 4, 8, 12, 16, 24 and 72 hours after the release of the tourniquet the level of pain was assessed by the visual analogue scale (VAS). Rescue analgesia, side effects and the use of painkillers were noted. Preemptive local anesthetic infiltration significantly decreased pain during the first 24 hours after the surgery. None of the patients from the injected group and 38 from the placebo group received 100 mg of ketoprofen intravenously for rescue analgesia in the first 2 hours after the release of the tourniquet. During the first 24 hours we noted significantly decreased use of 1000 mg of paracetamol and 100 mg mg of ketoprofen orally in the injected group. No systemic adverse effects were noted. One patient from placebo group had allergic rush after use of 100 mg ketoprofen. Preemptive local anesthetic infiltration in one-day hallux valgus surgery significantly decreases postoperative pain. It is safe, efficient and allows fast discharge.

Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats.

PubMed

Iwasaki, Koji; Sudo, Hideki; Kasahara, Yasuhiko; Yamada, Katsuhisa; Ohnishi, Takashi; Tsujimoto, Takeru; Iwasaki, Norimasa

2016-10-01

To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints. There is no strong evidence that intra-articular bupivacaine injection induces degenerative changes in articular cartilage. Therefore, these results may apply to normal and osteoarthritic joints. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials

PubMed Central

Yan, Jianqin; Wang, Ruike; Wang, Ying; Xu, Mu

2016-01-01

Objective The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. Methods A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias. Results This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). Conclusion Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus. PMID:27032092

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials.

PubMed

Hu, Jiajia; Zhang, Chengliang; Yan, Jianqin; Wang, Ruike; Wang, Ying; Xu, Mu

2016-01-01

The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg's funnel plots and Egger's linear regression test were used to detect any publication bias. This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = -1.0 min, 95% CI -1.5 to -0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.

Ropivacaine and Bupivacaine prevent increased pain sensitivity without altering neuroimmune activation following repeated social defeat stress.

PubMed

Sawicki, Caroline M; Kim, January K; Weber, Michael D; Jarrett, Brant L; Godbout, Jonathan P; Sheridan, John F; Humeidan, Michelle

2018-03-01

Mounting evidence indicates that stress influences the experience of pain. Exposure to psychosocial stress disrupts bi-directional communication pathways between the central nervous system and peripheral immune system, and can exacerbate the frequency and severity of pain experienced by stressed subjects. Repeated social defeat (RSD) is a murine model of psychosocial stress that recapitulates the immune and behavioral responses to stress observed in humans, including activation of stress-reactive neurocircuitry and increased pro-inflammatory cytokine production. It is unclear, however, how these stress-induced neuroimmune responses contribute to increased pain sensitivity in mice exposed to RSD. Here we used a technique of regional analgesia with local anesthetics in mice to block the development of mechanical allodynia during RSD. We next investigated the degree to which pain blockade altered stress-induced neuroimmune activation and depressive-like behavior. Following development of a mouse model of regional analgesia with discrete sensory blockade over the dorsal-caudal aspect of the spine, C57BL/6 mice were divided into experimental groups and treated with Ropivacaine (0.08%), Liposomal Bupivacaine (0.08%), or Vehicle (0.9% NaCl) prior to exposure to stress. This specific region was selected for analgesia because it is the most frequent location for aggression-associated pain due to biting during RSD. Mechanical allodynia was assessed 12 h after the first, third, and sixth day of RSD after resolution of the sensory blockade. In a separate experiment, social avoidance behavior was determined after the sixth day of RSD. Blood, bone marrow, brain, and spinal cord were collected for immunological analyses after the last day of RSD in both experiments following behavioral assessments. RSD increased mechanical allodynia in an exposure-dependent manner that persisted for at least one week following cessation of the stressor. Mice treated with either Ropivacaine or Liposomal Bupivacaine did not develop mechanical allodynia following exposure to stress, but did develop social avoidance behavior. Neither drug affected stress-induced activation of monocytes in the bone marrow, blood, or brain. Neuroinflammatory responses developed in all treatment groups, as evidenced by elevated IL-1β mRNA levels in the brain and spinal cord after RSD. In this study, psychosocial stress was associated with increased pain sensitivity in mice. Development of mechanical allodynia with RSD was blocked by regional analgesia with local anesthetics, Ropivacaine or Liposomal Bupivacaine. Despite blocking mechanical allodynia, these anesthetic interventions did not prevent neuroimmune activation or social avoidance associated with RSD. These data suggest that stress-induced neuroinflammatory changes are not associated with increased sensitivity to pain following RSD. Thus, blocking peripheral nociception was effective in inhibiting enhanced pain signaling without altering stress-induced immune or behavioral responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Lumbar paravertebral blockade as intractable pain management method in palliative care.

PubMed

Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Główka, Franciszek; Luczak, Jacek

2013-01-01

Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine's side effects were absent. Coadministered drugs could mask LA's toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine's elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours(-1)) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours(-1)) had an acceptable risk-benefits ratio, but was ineffective.

In vitro myotoxic effects of bupivacaine on rhabdomyosarcoma cells, immortalized and primary muscle cells.

PubMed

Metterlein, Thomas; Hoffmann, Petra; Späth, Ruth; Gruber, Michael; Graf, Bernhard M; Zink, Wolfgang

2015-01-01

Rhabdomyosarcoma is a rare malignant skeletal muscle tumor. It mainly occurs in children and young adults and has an unsatisfactory prognosis. Prior studies showed a direct myotoxic effect of bupivacaine on differentiated muscle cells in vitro and in vivo. Exact mechanisms of this myotoxicity are still not fully understood, but a myotoxic effect on malignant muscle tumor cells has not been examined so far. Thus, the aim of this study was to examine if bupivacaine has cytotoxic effects on rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells. Cell lines of rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells were established. After microscopic identification, cells were exposed to various concentrations of bupivacaine (500, 1,000, 1,750, 2,500 and 5,000 ppm) for 1 and 2 h, respectively. 24 and 28 h after incubation the cultures were stained with propidium iodid and analyzed by flow cytometry. The fraction of dead cells was calculated for each experiment and the concentration with 50% cell survival (IC50) was computed. Cell groups as well as incubation and recovery time were compared (ANOVA/Bonferroni p < 0.01). The total number of cultured cells was similar for the different local anesthetics and examined concentrations. Increasing concentrations of bupivacaine led to a decrease in survival of muscle cells. IC50 was highest for immortalized cells, followed by rhabdomyosarcoma cells and differentiated cells. Exposure time, but not recovery time, had an influence on survival. Bupivacaine has clear but different cytotoxic effects on various muscle cell types in vitro. Differentiated primary cells seem to be more vulnerable than tumor cells possibly because of more differentiated intracellular structures.

Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthetic Agent in Scalp Block and Scalp Infiltration to Control Postcraniotomy Pain: A Double-Blind Randomized Trial.

PubMed

Vallapu, Shankar; Panda, Nidhi Bidyut; Samagh, Navneh; Bharti, Neerja

2018-01-01

Scalp infiltration and scalp block are being used to manage postcraniotomy pain. Dexmedetomidine has been successfully used as an adjuvant in regional anesthesia. The study was intended to compare whether addition of dexmedetomidine prolonged the duration of analgesia as well as to compare the two techniques. The primary objective was to assess whether addition of dexmedetomidine to bupivacaine prolonged the duration of analgesia. The secondary objective was to compare between scalp nerve block and scalp infiltration as techniques for pain relief. The randomized control study was conducted in a tertiary care center from November 2013 to October 2014. A total of 150 American Society of Anesthesiologists Physical Status I-II patients, aged 18-70 years undergoing elective craniotomy were included. Patients were randomized into three groups of 50 patients, i.e., Group BI (bupivacaine infiltration), Group BDI (bupivacaine and dexmedetomidine infiltration), and Group BDNB (bupivacaine and dexmedetomidine scalp nerve block). Patient's pain score, pain-free interval, rescue analgesic requirement, and hemodynamic and respiratory parameters were noted for 48 h. Patients were followed up at 1 and 3 months to assess postcraniotomy pain. Pain-free period was significantly longer in Group BDNB than Groups BDI and BI ( P < 0.0001) and pain control was better in dexmedetomidine containing groups than in bupivacaine group (BI) ( P < 0.0001). The rescue analgesic requirement was significantly lower in Group BDNB and Group BDI compared to Group BI. The addition of dexmedetomidine (1 μg/kg) to bupivacaine prolonged the pain-free period. Scalp nerve block is a superior technique than scalp infiltration.

Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

PubMed Central

An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

2015-01-01

Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone, but not systemic dexamethasone, could prevent axon degeneration and demyelination. There was no significant caspase-dependent apoptosis process in the mouse sciatic nerve among all study groups during our study period. Conclusions Perineural, not systemic, dexamethasone added to a clinical concentration of bupivacaine may not only prolong the duration of sensory and motor blockade of sciatic nerve, but also prevent the bupivacaine-induced reversible neurotoxicity and short-term “rebound hyperalgesia” after the resolution of nerve block. PMID:25856078

Unilateral spinal anesthesia using low-flow injection through a 29-gauge Quincke needle.

PubMed

Meyer, J; Enk, D; Penner, M

1996-06-01

Restriction of sympathetic denervation during spinal anesthesia may minimize hemodynamic alterations. Theoretically, the use of nonisobaric anesthetics may allow unilateral anesthesia and thus restrict sympathetic denervation to one side of the body. The present prospective study investigates the incidence of unilateral spinal anesthesia using hyperbaric bupivacaine 0.5% (1.4 mL, 1.6 mL, 1.8 mL, or 2.0 mL) injected via a 29-gauge Quincke needle with a pump-controlled injection flow of 1 mL/min. In 96 consecutive patients undergoing unilateral surgery of the lower extremities, spinal anesthesia was performed in the lateral decubitus position, which was maintained for 20 min postinjection. Increases in foot temperature of at least 0.5 degrees C were defined as sympathetic blockade. The incidence of unilateral block was not significantly influenced by the amount of bupivacaine. For all 96 patients, the incidence of unilateral sympathetic and complete motor block was 69% and 77%, respectively. Frequency of unilateral sensory block (assessed by pinprick and temperature discrimination) was significantly lower (28%). Strict unilateral spinal anesthesia was achieved in 24 cases (25%). Twenty minutes after injection of the local anesthetic, mean arterial blood pressure decreased significantly in patients with bilateral sympathetic blockade from 87 +/- 8 to 83 +/- 8 mm Hg (P < 0.01) but not in patients with unilateral sympathetic blockade (from 87 +/- 11 to 85 +/- 10 mm Hg). In conclusion, low-flow injection (1 mL/min) of hyperbaric bupivacaine 0.5% via a 29-gauge Quincke needle prevented bilateral sympathetic blockade in more than 69% of the patients. The data further suggest that loss of temperature discrimination alone is not a reliable estimation of sympathetic block.

Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

PubMed

Fettiplace, Michael R; McCabe, Daniel J

2017-08-01

The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I 2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

Intrathecal oxybuprocaine and proxymetacaine produced potent and long-lasting spinal anesthesia in rats.

PubMed

Hung, Ching-Hsia; Wang, Jhi-Joung; Chen, Yu-Chung; Chu, Chin-Chen; Chen, Yu-Wen

2009-05-01

Proxymetacaine and oxybuprocaine were clinically used for topical ocular anesthesia but never for spinal anesthesia, and therefore spinal anesthetic effects of proxymetacaine and oxybuprocaine were performed and compared with bupivacaine and lidocaine. After rats were injected intrathecally with proxymetacaine, oxybuprocaine, bupivacaine, and lidocane, dose-response curves were constructed. We evaluated the potencies (ED(50)) and durations (time to full recovery) of proxymetacaine and oxybuprocaine on spinal blockades of motor function, proprioception, and nociception and compared with bupivacaine and lidocaine in rats. We found that proxymetacaine and oxybuprocaine acted like bupivacaine or lidocaine and produced dose-related spinal blockades of motor function, proprioception and nociception. On the ED(50) basis, the ranks of potencies in motor, proprioception, and nociception were proxymetacaine>oxybuprocaine>bupivacaine>lidocaine (P<0.01 for the differences). On an equipotent basis (ED(20), ED(50), ED(80)), oxybuprocaine and bupivacaine produced similarly longer spinal blockades than did proxymetacaine or lidocaine (P<0.05 for the differences). Intrathecal proxymetacaine, oxybuprocaine, and bupivacaine also produced longer sensory blockade than motor blockade. These data demonstrated that oxybuprocaine and proxymetacaine produced more potent spinal blockades, when compared with bupivacaine or lidocaine. Oxybuprocaine and bupivacaine with a more sensory-selective action over motor blockade produced longer spinal blockade than did proxymetacaine or lidocaine.

Effect of Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

PubMed

Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

2018-01-01

Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD < 0.001} and bupivacaine (1205.17 ± 34.32 vs. 364.67 ± 16.50 min) {p B, BD < 0.001}. 24-h requirement for rescue analgesics was more in Groups B and R when compared to Groups BD and RD. The increase in duration of analgesia was more when Groups R and RD (928.66 min) were compared than Groups B and BD (840.5 min). Similar results were seen with onset times and duration of sensory and motor block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

Efficacy and Safety of Ketamine Added to Local Anesthetic in Modified Pectoral Block for Management of Postoperative Pain in Patients Undergoing Modified Radical Mastectomy.

PubMed

Othman, Ahmed H; El-Rahman, Ahmad M Abd; El Sherif, Fatma

2016-01-01

Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain. Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries. This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery. A randomized, double-blind, prospective study. Academic medical center. This study is registered at www.clinicaltrials.gov under number: (NCT02620371) after approval by the ethics committee of South Egypt Cancer Institute, Assuit University, Assuit, Egypt. Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and randomly assigned into 2 groups (30 patients each): Control group patients were given ultrasound-guided, Pecs block with 30 mL of 0.25% bupivacaine only. Ketamine group patients were given ultrasound-guided, Pecs block with 30 mL of 0.25% bupivacaine plus ketamine hydrochloride (1 mg/kg). Patients were followed up for 48 hours postoperatively for vital signs, VAS score, first request of rescue analgesia and total morphine consumption, sedation score, and side effects. Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia (18.25 ± 1.98), (12.56 ± 2.64), respectively (P < 0.001), reduced total morphine consumption (12.50 ± 4.63), (18.86 ± 6.28), respectively (P = 0.016). With no significant difference in hemodynamics, respiratory rate, oxygen saturation, VAS and sedation scores, and side effects observed between the 2 groups (P > 0.05). This study is limited by its sample size. The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy. Ketamine, bupivacaine, pecs block, postoperative, pain, breast cancer.

[Local anesthesia of the knee for arthroscopic surgery. Our experience in 1,000 cases].

PubMed

Monzó, E; Manzanos, A; Cruz, A; Ruiz-Uchupi, P; Mansilla, T

1992-01-01

We performed local anesthesia of the knee for arthroscopic surgery in 1,000 patients who were diagnosed of meniscopathy, chondropathy, or block of the knee. We established two anesthetic times. The first consisted of an intraarticular administration of 40 ml of a mixture containing bupivacaine 0.5%, lidocaine 0.5% or prilocaine 1%, and adrenaline 1:200,000. The second was extraarticular and consisted of a local infiltration at the sites of entrance of the arthroscope or instrumental material with lidocaine 0.5% or prilocaine 1%, with adrenaline 1:100,000. We kept a latency period of 10 to 15 min, time required for setting up the arthroscopic procedure. Ischemia was systematically avoided. With this technique the following surgical treatments were performed: meniscectomy, curettage of articular cartilage, synovectomy, plica sections, and extraction of free bodies. Tolerance to surgery was excellent in 32.3% cases, good in 46.5%, regular in 16%, and bad in 5.2%. In no cases more complex anesthetic techniques were undertaken. We conclude that the anesthetic technique used in this study is appropriate for arthroscopic surgery of the knee and allows to perform ambulatory surgery. The procedure is not useful in cases of ligament reconstruction, regional infection, and rupture of the articular capsula. Although the anesthetic technique is easy some factors should be considered before indication of the procedure such as a careful selection of the patient, skillfulness of the surgeon in performing the arthroscopy, and the accuracy of the preoperative diagnosis.

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

PubMed

Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

2002-07-01

Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

Local Infiltration of Analgesics at Surgical Wound to Reduce Postoperative Pain After Laparotomy in Rats.

PubMed

Kroin, Jeffrey S; Li, Jinyuan; Moric, Mario; Birmingham, Brian W; Tuman, Kenneth J; Buvanendran, Asokumar

There is an increasing use of local infiltration analgesia (LIA) to reduce postoperative pain. Despite widespread use of LIA, wide variations in drug combinations and concomitant use of systemic analgesics have made it difficult to determine the optimal drug combinations for LIA. Using a previously validated rat laparotomy model, the optimal LIA combination of medications to reduce postoperative pain was determined. Laparotomy was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, and dexamethasone were injected over the sutured muscle wound before skin closing, and compared to saline (placebo). The same medications were injected systemically as controls. Postoperative pain was assessed by measuring spontaneous rearing activity. A high-dose 3-drug LIA combination (50 μL of bupivacaine 0.75%, ketorolac 6.0 mg/mL, and dexamethasone 2.0 mg/mL) increased rearing (decreased pain) at 2 hours (P = 0.0032) postsurgery compared to saline. However, the same 3 drugs injected systemically had a similar analgesic effect (P = 0.0002). Bupivacaine 0.75% alone was not effective for LIA. When low-dose (9-fold reduction) 3-drug LIA combination was used, LIA increased rearing (P = 0.0034) whereas the same 3 drugs injected systemically had no effect. Low-dose LIA ketorolac/dexamethasone (2-drug combination) also increased rearing (P = 0.0393). Our animal study suggests that clinical trials with low-dose LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid may be useful for reducing postoperative pain after laparotomy.

Neurostimulation in ultrasound-guided infraclavicular block: a prospective randomized trial.

PubMed

Dingemans, Emmanuel; Williams, Stephan R; Arcand, Geneviève; Chouinard, Philippe; Harris, Patrick; Ruel, Monique; Girard, François

2007-05-01

Ultrasound guidance (USG) for infraclavicular blocks provides real time visualization of the advancing needle and local anesthetic distribution. Whether visualization of local anesthetic spread can supplant neurostimulation as the end point for local anesthetic injection during USG block has never been formally evaluated. Therefore, for this prospective randomized study, we recruited 72 patients scheduled for hand or forearm surgery and compared the speed of execution and quality of USG infraclavicular block with either USG alone (Group U) or USG combined with neurostimulation (Group S). In Group U, local anesthetic was deposited in a U-shaped distribution posterior and to each side of the axillary artery using as few injections as possible (1, 2, and 3 injections in 29, 6, and 3 patients, respectively). In Group S, a single injection was made after obtaining a distal motor response with a stimulating current between 0.3 and 0.6 mA. The anesthetic solution consisted of 0.5 mL/kg of lidocaine 1.5%, bupivacaine 0.125%, and epinephrine 1:200 000 (final concentrations). Procedure times were significantly shorter in Group U compared with Group S (3.1 +/- 1.6 min and 5.2 +/- 4.7 min, respectively; P = 0.006). In Group S, anesthetic spread was mainly anterior to the axillary artery in 37% of patients and mainly posterior in 63% of patients. Thirty minutes after the injection, 86% of patients in Group U had complete sensory block in the musculocutaneous, median, radial, and ulnar nerve territories compared with 57% in Group S (P = 0.007). Patients blocked in Group U with a single injection had the same rate of complete block (86%) as those blocked with more than one injection (86%). Block supplementation rates were 8% in Group U versus 26% in Group S (P = 0.049). Block failure occurred in one patient in Group S because of an inability to obtain a distal stimulation after 20 min. We conclude that USG infraclavicular block is more rapidly performed and yields a higher success rate when visualization of local anesthetic spread is used as the end point for injection. Posterolateral spread of local anesthetic around the axillary artery predicts successful block, circumventing the need for direct nerve visualization.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

PubMed

Protic, Mladjan; Veljkovic, Radovan; Bilchik, Anton J; Popovic, Ana; Kresoja, Milana; Nissan, Aviram; Avital, Itzhak; Stojadinovic, Alexander

2017-02-01

Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. This study was designed as single-blinded PRCT. This study was conducted in an academic medical center. Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

The antioxidant N-acetyl cysteine suppresses lidocaine-induced intracellular reactive oxygen species production and cell death in neuronal SH-SY5Y cells.

PubMed

Okamoto, Akihisa; Tanaka, Masahiro; Sumi, Chisato; Oku, Kanako; Kusunoki, Munenori; Nishi, Kenichiro; Matsuo, Yoshiyuki; Takenaga, Keizo; Shingu, Koh; Hirota, Kiichi

2016-10-24

The local anesthetic lidocaine can affect intra- and extra-cellular signaling pathways in both neuronal and non-neuronal cells, resulting in long-term modulation of biological functions, including cell growth and death. Indeed, lidocaine was shown to induce necrosis and apoptosis in vitro. While several studies have suggested that lidocaine-induced apoptosis is mitochondrial pathway-dependent, it remains unclear whether reactive oxygen species (ROS) are involved in this process and whether the observed cell death can be prevented by antioxidant treatment. The effects of lidocaine and antioxidants on cell viability and death were evaluated using SH-SY5Y cells, HeLa cells, and HeLa cell derivatives. Cell viability was examined via MTS/PES ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt]/phenazine ethosulfate) assay. Meanwhile, cell apoptosis and necrosis were evaluated using a cell death detection assay with Annexin V-FITC and PI staining, as well as by assaying for caspase-3/7 and caspase-9 activity, and by measuring the release of lactate dehydrogenase, respectively. Mitochondrial transmembrane potential (ΔΨm) was assessed using the fluorescent probe tetramethylrhodamine ethyl ester. Lidocaine treatment resulted in suppression of the mitochondrial electron transport chain and subsequent attenuation of mitochondrial membrane potential, as well as enhanced ROS production, activation of caspase-3/7 and caspase-9, and induction of apoptosis and necrosis in SH-SY5Y cells in a dose- and time-dependent manner. Likewise, the anesthetics mepivacaine and bupivacaine also induced apoptosis in SH-SY5Y cells. Notably, the antioxidants N-acetyl cysteine (NAC) and Trolox successfully scavenged the mitochondria-derived ROS and suppressed local lidocaine-induced cell death. Our findings demonstrate that the local anesthetics lidocaine, mepivacaine, and bupivacaine inhibited the activity of mitochondria and induced apoptosis and necrosis in a dose-dependent manner. Furthermore, they demonstrate that treatment with the antioxidants NAC, Trolox, and GGA resulted in preservation of mitochondrial voltage and inhibition of apoptosis via suppression of caspase activation.

The myotoxic effect of bupivacaine and ropivacaine on myotubes in primary mouse cell culture and an immortalized cell line.

PubMed

Hofmann, Petra; Metterlein, Thomas; Bollwein, Gabriele; Gruber, Michael; Plank, Christoph; Graf, Bernhard M; Zink, Wolfgang

2013-09-01

The 2 local anesthetics (LAs) bupivacaine and ropivacaine have acute cytotoxic effects on different tissues. In this respect, LA-induced myotoxicity has been subject to various studies; however, the exact mechanisms are still not fully understood. Most in vitro studies use immortalized cell lines because of feasibility. Thus, establishing a primary cell line might result in more accurate results. In this study, we examined the effects of immortalization on bupivacaine- and ropivacaine-induced myotoxicity in vitro. An immortalized (N = 6) and a primary cell line (N = 8) of the same tissue and species were established, and differentiation in myotubes was induced. Cells were exposed to increasing concentrations of bupivacaine and ropivacaine for 1 or 2 hours, respectively. Twenty-four and 48 hours after treatment, the fractions of dead and vital cells were measured using flow cytometry. Significance was tested through 1-way analysis of variance with post hoc Dunnett T3 test. Medians of dataset pairs were compared by T test. In both cell lines, increasing concentrations of both LAs resulted in decreased cell survival (e.g., P < 0.001 for 5000 ppm bupivacaine, 1 or 2 hours of incubation, and 24 hours recovery in both cell lines). For the same LA concentrations, survival was significantly higher in the immortalized cell culture (e.g., P < 0.001 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). In addition, equal concentrations of bupivacaine resulted in significantly fewer vital cells compared with ropivacaine (e.g., P = 0.032 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). Two hours of incubation resulted in a significantly higher rate of dead cells compared with 1 hour of incubation (e.g., P = 0.004 for C2C12 cells, 2500 ppm bupivacaine, and 24 hours recovery). Primary skeletal muscle cells are more vulnerable to LAs than immortalized cells. The higher myotoxic potential of bupivacaine compared with ropivacaine in vivo can be reproduced in vitro. Incubation time has an influence on cell survival.

A low-dose bupivacaine: a comparison of hyperbaric and hypobaric solutions for unilateral spinal anesthesia.

PubMed

Kaya, Menşure; Oğuz, Selma; Aslan, Kemal; Kadioğullari, Nihal

2004-01-01

The injection of small doses of local anesthetic solutions through pencil-point directional needles and maintaining the lateral decubitus position for 15 to 30 minutes after the injection have been suggested to facilitate the unilateral distribution of spinal anesthesia. We evaluated the effects of hypobaric and hyperbaric bupivacaine in attempting to achieve unilateral spinal anesthesia for patients undergoing lower limb orthopedic surgery. Fifty patients were randomly allocated into 2 groups to receive either 1.5 mL hyperbaric bupivacaine 0.5% (7.5 mg; n = 25) or 4.2 mL hypobaric bupivacaine 0.18% (7.5 mg; n = 25). Drugs were administered at the L3-4 interspace with the patient in the lateral position. Patients remained in this position for 15 minutes before turning supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale on both sides. Unilateral spinal block was observed in 20 patients in the hyperbaric group (80%) and in 19 patients in the hypobaric group (76%) while in the lateral position. However, 15 minutes after patients were turned supine, unilateral spinal anesthesia decreased to 68% of cases in the hyperbaric group and 24% of cases in the hypobaric group (P <.05). The motor block was more intense during the first 5 and 10 minutes (P <.05), but at the end of operation there was no difference between the groups. The hemodynamic changes were similar between the groups. As a result, unilateral spinal anesthesia with hyperbaric and hypobaric bupivacaine provided a rapid motor and sensory recovery and good hemodynamic stability, but more unilateral spinal block was achieved in patients in the hyperbaric group when compared with patients in the hypobaric group.

Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial

PubMed Central

Ammar, Amany S.; Mahmoud, Khaled M.

2012-01-01

Purpose: Different adjuvants have been used to improve the quality and increase the duration of local anesthetics during various nerve block techniques. The current study was aimed to evaluate the effect of adding dexamethasone to bupivacaine on the quality and duration of transversus abdominis plane (TAP) block. Methods: Sixty adult patients undergoing elective open abdominal hysterectomy were randomly allocated to receive TAP block using 20 mL of bupivacaine hydrochloride 0.25% + 2 mL saline 0.9% (control group, n=30) or 20 mL of bupivacaine hydrochloride 0.25% + 2 mL dexamethasone “8 mg” (dexamethasone group, n=30). The primary outcome was postoperative pain, as evaluated by visual analog scale (VAS) for pain scoring at 1, 2, 4, 12, 24 and 48 h postoperatively, whereas the secondary outcomes were time to first analgesia (TFA), morphine consumption and the occurrence of nausea, vomiting or somnolence. Results: The pain VAS score was significantly lower at the postoperative 2 h (4.9 vs. 28.1, P=0.01), 4 h (12.2 vs. 31.1, P=0.01) and 12 h (15.7 vs. 25.4, P=0.02). Furthermore, TFA was significantly longer in the dexamethasone group (459.8 vs. 325.4 min, P=0.002), with lesser morphine requirements in the postoperative 48 h (4.9 vs. 21.2 mg, P=0.003) and lower incidence of nausea and vomiting (6 vs. 14, P=0.03). No complications attributed to the block were recorded. Conclusion: Addition of dexamethasone to bupivacaine in TAP block prolonged the duration of the block and decreased the incidence of nausea and vomiting. PMID:23162395

Low-level laser therapy (LLLT) accelerates the sternomastoid muscle regeneration process after myonecrosis due to bupivacaine.

PubMed

Alessi Pissulin, Cristiane Neves; Henrique Fernandes, Ana Angélica; Sanchez Orellana, Alejandro Manuel; Rossi E Silva, Renata Calciolari; Michelin Matheus, Selma Maria

2017-03-01

Because of its long-lasting analgesic action, bupivacaine is an anesthetic used for peripheral nerve block and relief of postoperative pain. Muscle degeneration and neurotoxicity are its main limitations. There is strong evidence that low-level laser therapy (LLLT) assists in muscle and nerve repair. The authors evaluated the effects of a Gallium Arsenide laser (GaAs), on the regeneration of muscle fibers of the sternomastoid muscle and accessory nerve after injection of bupivacaine. In total, 30 Wistar adult rats were divided into 2 groups: control group (C: n=15) and laser group (L: n=15). The groups were subdivided by antimere, with 0.5% bupivacaine injected on the right and 0.9% sodium chloride on the left. LLLT (GaAs 904nm, 0,05W, 2.8J per point) was administered for 5 consecutive days, starting 24h after injection of the solutions. Seven days after the trial period, blood samples were collected for determination of creatine kinase (CK). The sternomastoid nerve was removed for morphological and morphometric analyses; the surface portion of the sternomastoid muscle was used for histopathological and ultrastructural analyses. Muscle CK and TNFα protein levels were measured. The anesthetic promoted myonecrosis and increased muscle CK without neurotoxic effects. The LLLT reduced myonecrosis, characterized by a decrease in muscle CK levels, inflammation, necrosis, and atrophy, as well as the number of central nuclei in the muscle fibers and the percentage of collagen. TNFα values remained constant. LLLT, at the dose used, reduced fibrosis and myonecrosis in the sternomastoid muscle triggered by bupivacaine, accelerating the muscle regeneration process. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating.

PubMed

Alejo, Teresa; Andreu, Vanesa; Mendoza, Gracia; Sebastian, Victor; Arruebo, Manuel

2018-08-01

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Periarticular Liposomal Bupivacaine Infiltration in Patients Undergoing Total Knee Arthroplasty-A Meta-analysis of Comparative Trials.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Trikha, Anjan; Michos, Lia; Sinha, Ashish; Goudra, Basavana

2017-02-01

Over last 2 years, many trials have evaluated newly approved liposomal bupivacaine for periarticular infiltration in total knee arthroplasty (TKA) with mixed results. Our meta-analysis attempts to consolidate the results and make evidence-based conclusions. Trails comparing periarticular infiltration of liposomal bupivacaine to conventional analgesic regimens for total knee arthroplasty published till June 2016 were searched in medical database. Comparisons were made for length of stay (LOS), postoperative pain scores, range of motion, and opioid consumption. Meta-regression was performed for LOS to evaluate various analgesic control subgroups. Sixteen trials were included in the final analysis. Liposomal bupivacaine group showed a shorter LOS (reported in 13 subgroups) than control group by 0.17 ± 0.04 days (random effects, P < .001, I 2  = 84.66%). Meta-regression for various types of control showed a predictability (R 2 ) of 73%, τ 2  = 0.013 (random effects, P < .001, I 2  = 45.16). Only femoral block subgroup attained statistically significant shorter LOS on splitting the control group. Numeric pain scores were lower for pooled control group and local anesthetic infiltration subgroup in immediate postoperative phase. Second postoperative day analgesia was statistically superior to overall clubbed controls and femoral block subgroup. Superiority and/or inferiority of liposomal bupivacaine could not be proven for opioid consumption and range of motion because of a small pooled sample size. Publication bias is likely for LOS (Egger test, X intercept = 2.42, P < .001). Liposomal bupivacaine infiltration has questionable clinical advantage, as it marginally shortens patient's hospital stay especially in comparison with patients receiving analgesic femoral nerve block. Compared with conventional regimens, it can provide slightly superior yet sustained (till second postoperative day) perioperative analgesia. High heterogeneity suggests need for standardization of infiltration techniques for better predictability of results. Copyright © 2016 Elsevier Inc. All rights reserved.

Peripheral nerve catheters and local anesthetic infiltration in perioperative analgesia.

PubMed

Merritt, Christopher K; Mariano, Edward R; Kaye, Alan David; Lissauer, Jonathan; Mancuso, Kenneth; Prabhakar, Amit; Urman, Richard D

2014-03-01

Peripheral nerve catheters (PNCs) and local infiltration analgesia (LIA) represent valuable options for controlling perioperative pain. PNCs have been increasingly utilized to provide both surgical anesthesia and prolonged postoperative analgesia for a wide variety of procedures. PNCs can be more technically challenging to place than typical single-injection nerve blocks (SINB), and familiarity with the indications, contraindications, relevant anatomy, and appropriate technical skills is a prerequisite for the placement of any PNC. PNCs include risks of peripheral nerve injury, damage to adjacent anatomic structures, local anesthetic toxicity, intravascular injection, risks associated with motor block, risks of unnoticed injury to the insensate limb, and risks of sedation associated with PNC placement. In addition to these common risks, there are specific risks unique to each PNC insertion site. LIA strategies have emerged that seek to provide the benefit of targeted local anesthesia while minimizing collateral motor block and increasing the applicability of durable local anesthesia beyond the extremities. LIA involves the injection and/or infusion of a local anesthetic near the site of surgical incision to provide targeted analgesia. A wide variety of techniques have been described, including single-injection intraoperative wound infiltration, indwelling wound infusion catheters, and the recent high-volume LIA technique associated with joint replacement surgery. The efficacy of these techniques varies depending on specific procedures and anatomic locations. The recent incorporation of ultra-long-acting liposomal bupivacaine preparations has the potential to dramatically increase the utility of single-injection LIA. LIA represents a promising yet under-investigated method of postoperative pain control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty.

PubMed

Lombardi, Adolph V; Berend, Keith R; Mallory, Thomas H; Dodds, Kathleen L; Adams, Joanne B

2004-11-01

The purpose of this study was to determine if an intraoperative intraarticular and soft-tissue injection of local anaesthetic, epinephrine, and morphine has a beneficial effect for total knee arthroplasty. A control group of 138 patients (181 knees) received no intraoperative injection. The study group of 171 patients (197 knees) received intraoperative injection of 0.25% bupivacaine with epinephrine and morphine with 2/3 injected into the soft tissues and 1/3 injected into the joint. Patients having bilateral simultaneous procedures received a divided dose. The pain treatment protocol otherwise was identical. Pain, sedation, rescue narcotic usage, narcotic reversal and blood loss were examined. Pain levels during the immediate postoperative period, blood loss, and bleeding indices were reduced with injection. Considerably more control patients required rescue doses of narcotics. Preemptive analgesia with soft tissue and intra-articular injection of long-acting local anesthetic with epinephrine and morphine provides better pain control in the immediate postoperative period, decreases blood loss, and decreases the need for rescue narcotics and reversal agents. This simple, inexpensive method provides an effective adjunct to a multimodal approach in improving the postoperative course of primary total knee arthroplasty.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

PubMed

Dinh, Van Vuong; Suh, Yun-Suhk; Yang, Han-Kwang; Lim, Yong Taik

2016-12-01

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

Bupivacaine Versus Liposomal Bupivacaine For Pain Control.

PubMed

Beiranvand, Siavash; Moradkhani, Mahmoud Reza

2017-11-06

Local infiltrations and regional blocks have been some of the effective ways employed to manage and control post-operative pain. One of the limitations of administration of local anesthesia drugs in post-operative conditions is its inability to act for a longer period of time. Multi-vesicular liposomes made up of bupivacaine have been progressively used for their increased duration of action. Compared to bupivacaine HCL, local infiltration of liposomal bupivacaine have shown to have a significantly increase the duration and delay in peak plasma concentration. In this article, we attempt to compare liposomal bupivacaine and bupivacaine based on available clinical literatures. Liposomal bupivacaine has been demonstrated to have promising implications in post- operative pain control resulting in increased patient satisfaction; reduced hospital admission and opioid induced adverse events. Clinical studies have identified liposomal bupivacaine to be effective in delivering increased post-operative pain control. The purpose of this review is to give a comprehensive comparison between bupivacaine liposomal and conventional bupivacaine based on reported clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

Neosaxitoxin in Rat Sciatic Block: Improved Therapeutic Index Using Combinations with Bupivacaine, with and without Epinephrine.

PubMed

Templin, Jay S; Wylie, Matthew C; Kim, Joseph D; Kurgansky, Katherine E; Gorski, Grzegorz; Kheir, John; Zurakowski, David; Corfas, Gabriel; Berde, Charles

2015-10-01

Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker undergoing clinical trials as a prolonged-duration local anesthetic. Rat sciatic block and intravenous infusion models were used to assess efficacy and local and systemic toxicities for NeoSTX in saline (NeoSTX-Saline), bupivacaine (Bup), and their combination (NeoSTX-Bup). Exploratory studies evaluated the effects of addition of epinephrine to NeoSTX-Bup (NeoSTX-Bup-Epi). Rats received percutaneous sciatic blocks with escalating doses of NeoSTX-Saline or NeoSTX-Bup. Sensory-nocifensive block was assessed using modified hotplate and Von Frey filaments. Motor-proprioceptive function was assessed by extensor postural thrust. Nerves were examined histologically after 7 days and scored on the Estebe-Myers scale. Median lethal dose was estimated for NeoSTX-Saline and in combinations. Accidental intravenous overdose was simulated in isoflurane-anesthetized, spontaneously breathing rats receiving NeoSTX-Saline (n = 6), Bup (n = 7), or NeoSTX-Bup (n = 13), with respiratory, hemodynamic, and electrocardiographic endpoints. Additional groups received blocks with NeoSTX-Bup-Epi (n = 80). Investigators were blinded for behavioral and histologic studies. NeoSTX-Bup produced more prolonged sensory and motor block compared with NeoSTX-Saline or Bup. NeoSTX-Bup-Epi further prolonged median time to near-complete recovery for 3 μg/kg NeoSTX-Bup (hotplate: 48 vs. 6 h, P < 0.001). With sciatic injections, addition of Bup did not worsen the systemic toxicity (median lethal dose) compared with NeoSTX-Saline. Intravenous NeoSTX-Saline infusion had significantly longer times to apnea, first arrhythmia, and asystole compared with Bup (P < 0.001 for each). Histologic injury scores overall were low for all groups, with median scores of 0 (interquartile range, 0 to 0) on a 5-point scale. NeoSTX-Bup and NeoSTX-Bup-Epi hold promise for prolonged-duration local anesthesia.

The efficiency and safety of local liposomal bupivacaine infiltration for pain control in total hip arthroplasty: A systematic review and meta-analysis.

PubMed

Zhang, Xin; Yang, Qing; Zhang, Zhi

2017-12-01

This meta-analysis aimed to compare the efficiency and safety of local liposomal bupivacaine infiltration and traditional cocktail analgesia for pain management in total hip arthroplasty (THA). PubMed, Embase, Web of science, Medline, and Cochrane library databases were systematically searched. Participants: patients planned for a THA with a diagnosis of hip osteoarthritis. liposomal bupivacaine was administrated in the experimental groups for pain control. Comparisons: the control groups received local infiltration of traditional analgesics. pain scores, opioids consumption, and postoperative complications among the patients. randomized control trials (RCTs) and non-RCTs. Methodological Index for Non-Randomized Studies scale was used to assess the methodological quality of the included studies. Meta-analysis was conducted by Stata 11.0 software. Systematic review registration number is CRD42017120981. Four articles involving 308 participants were included. Current meta-analysis revealed that there were significant differences regarding postoperative pain score at 12 hours (standard mean difference [SMD] = -0.496, 95% CI: -0.717 to -0.275, P = .000), 24 hours (SMD = -0.537, 95% CI: -0.760 to -0.313, P = .000), and 48 hours (SMD = -0.802, 95% CI: -1.029 to -0.576, P = .000). Liposomal bupivacaine intervention was found to significantly decrease opioid consumption at 12 hours (SMD = -0.544, 95% CI: -0.766 to -0.323, P = .000), 24 hours (SMD = -0.357, 95% CI: -0.577 to -0.138, P = .001), and 48 hours (SMD = -0.370, 95% CI: -0.589 to -0.151, P = .001). Local liposomal bupivacaine infiltration could significantly reduce visual analogue scale (VAS) scores and opioid consumption within the first 48 hours following THA surgery. In addition, there was a decreased risk of nausea and vomiting in liposomal bupivacaine groups. The overall evidence level was low, which means that further research is likely to significantly alter confidence levels in the effect, as well as potentially changing the estimates. In any subsequent research, further studies should focus on the optimal dose of local anesthetics and the potential adverse side effects. In addition, surgeries that can improve pain relief and enable faster rehabilitation and earlier discharges should also be explored. Several potential limitations of this study should be noted. Four articles are included and the sample size in each trial is small. Some important outcome parameters such as range of motion were not fully described and could not be included in the meta-analysis. All included studies were retrospectives which may decrease evidence levels for the meta-analysis. The evidence quality for each outcome was low which may influence the results of the meta-analysis. Short-term follow-ups may lead to the underestimation of complications, such as neurotoxicity and cardiotoxicity. Publication bias is an inherent weakness that exists in all meta-analyses.

Intrafascicular injection of ammonium sulfate and bupivacaine in peripheral nerves of neonatal and juvenile rats.

PubMed

Hertl, M C; Hagberg, P K; Hunter, D A; Mackinnon, S E; Langer, J C

1998-01-01

Regional nerve blocks are often used for the treatment of postoperative pain in children. Ammonium sulfate is a non-narcotic anesthetic agent, which has been reported to provide pain relief lasting days to weeks, with few reported side effects in adult studies. Prior to considering clinical use in children, the neurotoxicity of ammonium sulfate in 4-day and 3-week old rats was assessed and compared with that of bupivacaine. Each rat received a posterior tibial nerve intrafascicular injection (0.01 mL in 4-day-old and 0.02 mL in 3-week-old rats) using either 10% ammonium sulfate (n = 24 per age group), 0.5% bupivacaine (n = 18 per age group), 0.9% saline (n = 18 per age group), or 5% phenol (n = 18 per age group). A functional assessment by serial walking track analysis and a morphologic assessment by neurohistology were made. No abnormalities in serial walking track analysis and no structural nerve damage were detected after ammonium sulfate, bupivacaine, or saline injection. Bupivacaine caused mild focal changes in both age groups, which recovered by 8 weeks. Intrafascicular injection of ammonium sulfate was as safe as bupivacaine in this animal model. Further animal studies must be made before human trials are initiated.

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain.

PubMed

Victory, R A; Gajraj, N M; Van Elstraete, A; Pace, N A; Johnson, E R; White, P F

1995-05-01

To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. A prospective, randomized, double-blind study. University medical center. 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg i.v., droperidol 50 micrograms/kg i.v., and sufentanil 0.5 microgram/kg i.v. and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 microgram/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.

PubMed

Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin

2015-10-01

Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.

Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats.

PubMed

Buvanendran, Asokumar; Kroin, Jeffrey S; Della Valle, Craig J; Moric, Mario; Tuman, Kenneth J

2016-01-01

There is increasing interest in local infiltration analgesia (LIA) to reduce postoperative pain with knee surgery. Despite widespread use of LIA, wide variations in drug combinations, infiltration techniques, and the concomitant use of systemic analgesics have made it difficult to determine the optimal drug combination for LIA.Using a previously validated animal knee surgery model, we aimed to determine the optimal combination of medications to reduce postoperative pain, and the best anatomical location and timing for local drug injection during surgery. Knee surgery was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, dexamethasone, and morphine were injected around the knee and compared to saline placebo. Similar medications were injected systemically as a comparator group. Postoperative pain was assessed by measuring spontaneous rearing activity. Injections were given after bone drilling and/or just before wound closure. The 3-drug LIA combination of bupivacaine, ketorolac, and dexamethasone increased rearing (decreased pain) at 2 hours (P = 0.0198) and 24 hours (P = 0.0384) postsurgery compared to saline. The same drugs injected systemically had no effect. The ketorolac/dexamethasone combination for LIA was also effective at 2 hours (P = 0.0006) and 24 hours (P = 0.0279), and ketorolac alone reduced pain at 2 hours (P = 0.0045). Bupivacaine alone was less effective, and the addition of morphine had no effect. The 3-drug combination infiltrated just after creating holes in bone was more effective than when given into the wound just before wound closure. Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect.Perioperative physicians should consider delivering LIA earlier during the procedure as opposed to solely at the time of wound closure.

Effect of warming bupivacaine 0.5% on ultrasound-guided axillary plexus block. Randomized prospective double-blind study.

PubMed

Trabelsi, W; Ben Gabsia, A; Lebbi, A; Sammoud, W; Labbène, I; Kchelfi, S; Ferjani, M

2017-02-01

To evaluate the effect of warming bupivacaine 0.5% on ultrasound-guided axillary brachial plexus block. Prospective, randomized, double-blind. Eighty patients undergoing elective or emergency surgery beyond the distal third of the upper limb were divided into two groups of 40 patients: the warm group received 15mL bupivacaine 0.5% heated to 37°C; the cold group received 15mL 0.5% bupivacaine stored for at least 24hours in the lower compartment of a refrigerator at 13-15°C. Onset and duration of sensory and motor blocks were evaluated every 5minutes for 40minutes. Postoperative pain was evaluated at 1, 3, 6, 12 and 24hours. Effective analgesia time was recorded as the interval between anesthetic injection and the first analgesia requirement (VAS>30mm). Time to onset of sensory and motor block was significantly shorter in the warm group, and mean duration of sensory and motor block and of postoperative analgesia significantly longer. Warming bupivacaine 0.5% to 37°C accelerated onset of sensory and motor block and extended action duration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

THE EFFECTS OF INTRATHECAL NEOSTIGMINE ADDED TO BUPIVACAINE ON POSTOPERATIVE ANALGESIC REQUIREMENT IN PATIENTS UNDERGOING LOWER LIMB ORTHOPEDIC SURGERY.

PubMed

Kayalha, Hamid; Mousavi, Zinat; Sadat Barikani, Ameneh; Yaghoobi, Siamak; Khezri, Marzieh Beigom

2015-06-01

Several additives have been suggested to enhance analgesic effect of local anesthetic agents to decrease the adverse effects of them and increase the degree of satisfaction. We designed this randomized double-blind controlled study to evaluate the analgesic efficacy of the neostigmine added to bupivacaine using spinal anesthesia in patients undergoing lower limb orthopedic surgery. Sixty patients 18-80 yr old American Society of Anesthesiologists (ASA) physical status I or II, scheduled for femur surgery under spinal anesthesia, were recruited in a prospective, double-blinded, randomized way. The patients were randomly allocated to one of two groups of 30 each. The neostigmine group (group N) received bupivacaine 20 mg combined with 25 µg neostigmine, and the placebo group (group C) received bupivacaine 20 mg combined with 0.5ml distilled water (intrathecally) 5 minutes prior to surgery. The time to the first analgesic request, analgesic requirement in the first 12 hours after surgery, the duration of sensory and motor blockade, the incidence of adverse effects such as nausea,vomiting,hypotension, ephedrine requirements, bradycardia, and hypoxemia were recorded. Patients receiving neostigmine had a significantly prolonged duration of motor block (C95% CI 30.27 to 87.65; P < 0.001) and sensory block (C95% CI 101.04 to 224.64; P < 0.001) compared to the control group. The difference of the mean time to the first analgesic request was also significantly longer in neostigmine group (C95% CI 83.139 to 208.526; P < 0.001). The total analgesic consumption during the first 12 hours after surgery was devoid of any significant difference between groups N and C (p = 0.41).The two groups were not significantly different in terms of intraoperative and postoperative side effects. Intrathecal neostigmine 25 µg with bupivacaine caused a prolonged time to the first analgesic request and its use was not associated with any side effects.

A comparative study of clonidine and dexmedetomidine as an adjunct to bupivacaine in supraclavicular brachial plexus block.

PubMed

Tripathi, Archana; Sharma, Khushboo; Somvanshi, Mukesh; Samal, Rajib Lochan

2016-01-01

Various additives are mixed with local anesthetic agents to increase the quality of block in regional anesthesia. We compared clonidine and dexmedetomidine as an adjunct to bupivacaine in supraclavicular brachial plexus block with respect to the onset and duration of sensory and motor block and duration of analgesia. Sixty American Society of Anesthesiologists Grades I and II patients scheduled for various orthopedic surgeries of the upper limb under supraclavicular brachial plexus block were divided into two equal groups in a randomized, double-blind manner. Patients were assigned randomly to one of the two groups. In Group C (n = 30), 39 ml of 0.25% bupivacaine plus 1 ml (1 μg/kg) clonidine and in Group D (n = 30), 39 ml of 0.25% bupivacaine plus 1 ml (1 μg/kg) dexmedetomidine were given. The onset and duration of sensory and motor block, duration of analgesia, and quality of anesthesia were studied in both the groups. There was no statistically significant difference in the onset of sensory and motor block in both the groups. The durations of sensory and motor block were 316.67 ± 45.21 and 372.67 ± 44.48 min, respectively, in Group C, whereas they were 502.67 ± 43.78 and 557.67 ± 38.83 min, respectively, in Group D. The duration of analgesia was 349.33 ± 42.91 min, significantly less in Group C compared to 525.33 ± 42.89 min in Group D (P < 0.001). The quality of anesthesia was significantly better in dexmedetomidine group compared to clonidine group (P < 0.001). The addition of dexmedetomidine prolongs the durations of sensory and motor block and duration of analgesia and improves the quality of anesthesia as compared with clonidine when injected with bupivacaine in supraclavicular brachial plexus block.

Comparison of Postoperative Pain After Epidural Anesthesia Using 0.5%, 0.75% Ropivacaine and 0.5% Bupivacaine in Patients Undergoing Lower Limb Surgery: A Double-Blind Study.

PubMed

Bindra, Tripat Kaur; Singh, Rajvinder; Gupta, Ruchi

2017-01-01

Ropivacaine (S (-)-1-propyl-2", 6"; pipecoloxylidide hydrochloride) a newer long-acting amide local anesthetic has various clinical and pharmacokinetic advantages over bupivacaine. The aim of this study is to compare the onset as well as the duration of sensory block, hemodynamic variables, and postoperative analgesia with 0.5%, 0.75% ropivacaine and 0.5% bupivacaine after epidural anesthesia for lower limb orthopedic surgery. Sixty American Society of Anesthesiologists I and II patients scheduled for lower limb orthopedic surgery were enrolled into this randomized, double-blind study. Epidural block was obtained with 15 ml of 0.5% ropivacaine (Group I), 15 ml of 0.75% ropivacaine (Group II), and 15 ml of 0.5% bupivacaine (Group III). The onset time, duration, and maximum level of sensory blockade achieved, as well as hemodynamic parameters and any side effects, were noted and treated accordingly. Postoperative monitoring for pain by visual analog scale (VAS) was done every 2 hourly for 24 h and transient neurological symptoms for 72 h. Chi-square test for nonparametric data and ANOVA for parametric data. Demographic characteristics were similar among groups. The onset of sensory block varied from 22.35 ± 2.74 min (mean ± standard deviation [SD]) in Group I, 16.95 ± 2.96 min (mean ± SD) in Group II, and 19.70 ± 2.25 min (mean ± SD) in Group III. The mean duration of analgesia in Group III (157 ± 14.90 min)was comparable to Group II (149 ± 16.51 min) but it was significantly more than Group I (141.5 ± 17.55 min). Postoperatively, VAS scores were higher in Group I patients who required more number of postoperative epidural top-ups with tramadol. Adverse effects were noted and treated accordingly. There was no incidence of transient neurological symptoms postoperatively. Both ropivacaine and bupivacaine provided effective epidural anesthesia for lower limb surgery. Postoperative pain was less with 0.5% bupivacaine and 0.75% ropivacaine as compared to 0.5% ropivacaine.

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg

PubMed Central

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Introduction Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. Methods In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients’ socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Results Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. Conclusion The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability. PMID:29515726

Lumbar paravertebral blockade as intractable pain management method in palliative care

PubMed Central

Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Główka, Franciszek; Łuczak, Jacek

2013-01-01

Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour−1) or in boluses (10 mL of 0.125%–0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine’s side effects were absent. Coadministered drugs could mask LA’s toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine’s elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9–927.4 ng mL−1). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours−1) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours−1) had an acceptable risk-benefits ratio, but was ineffective. PMID:24043944

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg.

PubMed

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients' socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability.

Pethidine efficacy in achieving the ultrasound-guided oblique subcostal transversus abdominis plane block in laparoscopic cholecystectomy: A prospective study.

PubMed

Breazu, Caius Mihai; Ciobanu, Lidia; Bartos, Adrian; Bodea, Raluca; Mircea, Petru Adrian; Ionescu, Daniela

2017-02-21

Pethidine is a synthetic opioid with local anesthetic properties. Our goal was to evaluate the analgesic efficacy of pethidine for achieving the ultrasound-guided oblique subcostal transversus abdominis plane (OSTAP) block in laparoscopic cholecystectomy. This prospective, double-blind study included 79 patients of physical status I and II according to American Society of Anesthesiologists, scheduled for elective laparoscopic cholecystectomy. The patients were randomly allocated into three groups, depending on the drug used to achieve preoperative bilateral OSTAP block: 1) OSTAP-Placebo (treated with normal saline); 2) OSTAP-Bupivacaine (treated with 0.25% bupivacaine); and 3) OSTAP-Pethidine (treated with 1% pethidine). The efficacy of pethidine in achieving the OSTAP block was analyzed using visual analog scale (VAS), intraoperative opioid dose, opioid consumption in post anesthesia care unit, and opioid consumption in the first 24 postoperative hours. The pain scores assessed by VAS at 0, 2, 4, 6, 12, and 24 hours were significantly lower in OSTAP-Pethidine than in OSTAP-Placebo group (p < 0.001). The mean intraoperative opioid consumption was significantly lower in OSTAP-Pethidine compared to OSTAP-Placebo group (150 versus 400 mg, p < 0.001), as well as the mean opioid consumption in the first 24 hours (20.4 versus 78 mg, p < 0.001). Comparing VAS assessment between OSTAP-Bupivacaine and OSTAP-Pethidine groups, statistically significant differences were observed only for the immediate postoperative pain assessment (0 hours), where lower values were observed in OSTAP-Pethidine group (p = 0.004). There were no statistically significant differences in the incidence of postoperative nausea and vomiting (p = 0.131) between the groups. The use of 1% pethidine can be an alternative to 0.25% bupivacaine in achieving OSTAP block for laparoscopic cholecystectomy.

Mepivacaine Spinal Anesthesia Facilitates Rapid Recovery in Total Knee Arthroplasty Compared to Bupivacaine.

PubMed

Mahan, M Chad; Jildeh, Toufic R; Tenbrunsel, Troy N; Davis, Jason J

2018-06-01

Mepivacaine as a spinal anesthetic for rapid recovery in total knee arthroplasty (TKA) has not been assessed. The purpose of this study is to compare spinal mepivacaine vs bupivacaine for postoperative measures in patients undergoing primary TKA. Retrospective review of a prospectively collected single-institution database was performed on 156 consecutive patients who underwent primary TKA. Fifty-three patients were administered mepivacaine and 103 patients were administered bupivacaine. Primary outcomes were urinary retention, length of stay, pain control, opioid consumption, and distance associated with physical therapy. Statistical analysis with univariate logistic regression was performed to evaluate the effect of anesthetic with primary outcomes. Patients undergoing TKA with mepivacaine had a shorter length of stay (28.1 ± 11.2 vs 33.6 ± 14.4 hours, P = .002) and fewer episodes of straight catheterization (3.8% vs 16.5%, P = .021) compared to bupivacaine. Patients administered mepivacaine exhibited slightly higher VAS pain scores and morphine consumption in the postanesthesia care unit (1.3 ± 1.9 vs 0.5 ± 1.3, P = .002; 2.2 ± 3.3 vs 0.8 ± 2.1 equivalents/h, P = .002), but otherwise exhibited no difference in VAS scores or morphine consumption afterwards. There was no need to convert to general anesthesia or transient neurologic symptom complication in either group. Mepivacaine for spinal anesthesia with TKA had adequate duration to complete the surgery and facilitated a more rapid recovery with less urinary complications and a shorter length of stay. Patients administered mepivacaine did not display worse pain control or transient neurologic symptoms afterwards. Copyright © 2018 Elsevier Inc. All rights reserved.

Regenerative capability of skeletal muscle in chicken muscular dystrophy.

PubMed

Nonaka, I; Fujita, T; Sugita, H

1984-06-01

To examine the morphological sequence of regenerating fibers after myonecrosis in dystrophic muscles, 0.5 ml of 0.5% bupivacaine hydrochloride (BPVC) (Marcaine) solution, a local anesthetic with a cytotoxic effect on the muscle fibers, was injected directly into the dystrophic (line 413) and nondystrophic (line 412) posterior latissimus dorsi (PLD) muscles of young and adult chickens. Although the dystrophic muscles after BPVC injection showed a rapid recovery with a similar tempo to that of nondystrophic ones, they showed different morphological behavior in the early phase of regeneration, including marked variability in the size of fibers and in the intracytoplasmic enzyme activities of nicotinamide adenine dinucleotide, reduced-tetrazolium reductase (NADH-TR), acetylcholinesterase (AChE), and nonspecific esterase (NSE).

Intrathecal hypobaric versus hyperbaric bupivacaine with morphine for cesarean section.

PubMed

Richardson, M G; Collins, H V; Wissler, R N

1998-08-01

Both hyper- and hypobaric solutions of bupivacaine are often combined with morphine to provide subarachnoid anesthesia for cesarean section. Differences in the baricity of subarachnoid solutions influence the intrathecal distribution of anesthetic drugs and would be expected to influence measurable clinical variables. We compared the effects of hyper- and hypobaric subarachnoid bupivacaine with morphine to determine whether one has significant advantages with regard to intraoperative anesthesia and postoperative analgesia in term parturients undergoing elective cesarean section. Thirty parturients were randomized to receive either hyper- or hypobaric bupivacaine (15 mg) with morphine sulfate (0.2 mg). Intraoperative outcomes compared included extent of sensory block, quality of anesthesia, and side effects. Postoperative outcomes, including pain visual analog scale scores, systemic analgesic requirements, and side effects, were monitored for 48 h. Sedation effects were quantified and compared using Trieger and digit-symbol substitution tests. We detected no differences in sensory or motor block, quality of anesthesia, quality of postoperative analgesia, incidence of side effects, or psychometric scores. Both preparations provide highly satisfactory anesthesia for cesarean section and effective postoperative analgesia. Dextrose alters the density of intrathecal bupivacaine solutions and is thought to influence subarachnoid distribution of the drug. We randomized parturients undergoing cesarean section to one of two often used spinal bupivacaine preparations, hypobaric and hyperbaric. We detected no differences in clinical outcomes between groups.

Minimum Effective Concentration of Bupivacaine in Ultrasound-Guided Femoral Nerve Block after Arthroscopic Knee Meniscectomy: A Randomized, Double-Blind, Controlled Trial.

PubMed

Moura, Ed Carlos Rey; de Oliveira Honda, Claudio A; Bringel, Roberto Cesar Teixeira; Leal, Plinio da Cunha; Filho, Gasper de Jesus Lopes; Sakata, Rioko Kinmiko

2016-01-01

Adequate analgesia is important for early hospital discharge after meniscectomy. A femoral nerve block may reduce the need for systemic analgesics, with fewer side effects; however, motor block can occur. Ultrasound-guided femoral nerve block may reduce the required local anesthetic concentration, preventing motor block. The primary objective of this study was to determine the lowest effective analgesic concentration of bupivacaine in 50% (EC50) and in 90% (EC90) of patients for a successful ultrasound-guided femoral nerve block in arthroscopic knee meniscectomy. This was a prospective, randomized, double-blind, controlled trial. This study was conducted at Hospital São Domingos. A total of 52 patients undergoing arthroscopic knee meniscectomy were submitted to ultrasound-guided femoral nerve block using 22 mL bupivacaine. The bupivacaine concentration given to a study patient was determined by the response of the previous patient (a biased-coin design up-down sequential method). If the previous patient had a negative response, the bupivacaine concentration was increased by 0.05% for the next case. If the previous patient had a positive response, the next patient was randomized to receive the same bupivacaine concentration (with a probability of 0.89) or to have a decrease by 0.05% (with a probability of 0.11). A successful block was defined by a numerical pain intensity scale score < 4 (0 = no pain; 10 = worst imaginable pain) in 3 different evaluations. If the pain intensity score was = 4 (moderate or severe pain) at any time, the block was considered failed. General anesthesia was induced with 30 µg/kg alfentanil and 2 mg/kg propofol, followed by propofol maintanance, plus remifentanil if needed. Postoperative analgesia supplementation was performed with dipyrone; ketoprofen and tramadol were given if needed. The following parameters were evaluated: numerical pain intensity score, duration of analgesia, supplementary analgesic dose in 24 hours, and need for intraoperative remifentanil. The EC50 was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300). There was no difference in numerical pain intensity score for the different concentrations of bupivacaine. A successful block was achieved in 45 patients, with no difference according to bupivacaine concentration. Time to first analgesic supplementation dose was longer for bupivacaine concentrations = 0.3% (543.8 ± 283.8 min.), compared to 0.25% (391.3 ± 177.8 min.) and < 0.25% (302.3 ± 210.1 min.). There were no differences in supplementary analgesic dose in 24 hours nor in the use of intraoperative remifentanil according to bupivacaine concentration. The analgesic effect was measured only during the first 2 hours. Bupivacaine EC50 for ultrasound-guided femoral nerve block was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300).

The efficiency and safety of local liposomal bupivacaine infiltration for pain control in total hip arthroplasty

PubMed Central

Zhang, Xin; Yang, Qing; Zhang, Zhi

2017-01-01

Abstract Objective: This meta-analysis aimed to compare the efficiency and safety of local liposomal bupivacaine infiltration and traditional cocktail analgesia for pain management in total hip arthroplasty (THA). Methods: PubMed, Embase, Web of science, Medline, and Cochrane library databases were systematically searched. Inclusion criteria: Participants: patients planned for a THA with a diagnosis of hip osteoarthritis. Interventions: liposomal bupivacaine was administrated in the experimental groups for pain control. Comparisons: the control groups received local infiltration of traditional analgesics. Outcomes: pain scores, opioids consumption, and postoperative complications among the patients. Study design: randomized control trials (RCTs) and non-RCTs. Methodological Index for Non-Randomized Studies scale was used to assess the methodological quality of the included studies. Meta-analysis was conducted by Stata 11.0 software. Systematic review registration number is CRD42017120981. Results: Four articles involving 308 participants were included. Current meta-analysis revealed that there were significant differences regarding postoperative pain score at 12 hours (standard mean difference [SMD] = −0.496, 95% CI: −0.717 to −0.275, P = .000), 24 hours (SMD = −0.537, 95% CI: −0.760 to −0.313, P = .000), and 48 hours (SMD = −0.802, 95% CI: −1.029 to −0.576, P = .000). Liposomal bupivacaine intervention was found to significantly decrease opioid consumption at 12 hours (SMD = −0.544, 95% CI: −0.766 to −0.323, P = .000), 24 hours (SMD = −0.357, 95% CI: −0.577 to −0.138, P = .001), and 48 hours (SMD = −0.370, 95% CI: −0.589 to −0.151, P = .001). Conclusion: Local liposomal bupivacaine infiltration could significantly reduce visual analogue scale (VAS) scores and opioid consumption within the first 48 hours following THA surgery. In addition, there was a decreased risk of nausea and vomiting in liposomal bupivacaine groups. The overall evidence level was low, which means that further research is likely to significantly alter confidence levels in the effect, as well as potentially changing the estimates. In any subsequent research, further studies should focus on the optimal dose of local anesthetics and the potential adverse side effects. In addition, surgeries that can improve pain relief and enable faster rehabilitation and earlier discharges should also be explored. Several potential limitations of this study should be noted. Four articles are included and the sample size in each trial is small. Some important outcome parameters such as range of motion were not fully described and could not be included in the meta-analysis. All included studies were retrospectives which may decrease evidence levels for the meta-analysis. The evidence quality for each outcome was low which may influence the results of the meta-analysis. Short-term follow-ups may lead to the underestimation of complications, such as neurotoxicity and cardiotoxicity. Publication bias is an inherent weakness that exists in all meta-analyses. PMID:29245214

Effect of Locally Administered Dexmedetomidine as Adjuvant to Levobupivacaine in Supraclavicular Brachial Plexus Block: Double-blind Controlled Study.

PubMed

Bisui, Bikash; Samanta, Swastika; Ghoshmaulik, Sumanta; Banerjee, Amit; Ghosh, Tirtha R; Sarkar, Suman

2017-01-01

Brachial plexus block is effective with good postoperative analgesia in upper limb surgery has gained importance as it safe, low cost, and maintains stable hemodynamics intraoperatively. To decrease the onset time and prolong the duration of nerve block bicarbonate, opioids (morphine, fentanyl, etc.), sympathomimetic agents (epinephrine, phenylephrine, etc.), α-2 agonists (clonidine and dexmedetomidine), calcium channel blocker (verapamil), magnesium sulfate, etc., were studied with local anesthetics and their isomers. For their sedative, analgesic, perioperative sympatholytic, and cardiovascular stabilizing effects with reduced anesthetic requirements, α-2 adrenergic receptor agonists, such as more potent and highly selective dexmedetomidine, have been the focus of interest for regional anesthesia. Intravenous dexmedetomidine infusion resulted in significant opioid-sparing effects as well as a decrease in inhalational anesthetic requirements. Animal studies proved that dexmedetomidine enhances sensory and motor blockade along with increased duration of analgesia. In humans, dexmedetomidine has also shown to prolong the duration of block and postoperative analgesia when added to local anesthetic in various regional blocks. Bupivacaine, the widely used local anesthetic in regional anesthesia, is available in a commercial preparation as a racemic mixture (50:50) of its two enantiomers: levobupivacaine, S (-) isomer and dextrobupivacaine, R (+) isomer. Severe central nervous system and cardiovascular adverse reactions reported in the literature after inadvertent intravascular injection or intravenous regional anesthesia have been linked to the R (+) isomer of bupivacaine. The levorotatory isomers were shown to have a safer pharmacological profile with less cardiac and neurotoxic adverse effects. The decreased toxicity of levobupivacaine is attributed to its faster protein binding rate. The pure S (-) enantiomers of bupivacaine, i.e., ropivacaine and levobupivacaine were thus introduced into the clinical anesthesia practice. Such an increased usage mandates the documentation of evidence-based literature with regard to risk and safety concerns as well as clinical issues related to levobupivacaine. This study is designed to assess the efficacy of adding dexmedetomidine to levobupivacaine during placement of supraclavicular brachial plexus blockade. This prospective observational double-blinded study was conducted over a 1-year period among randomly selected seventy ( n = 35) American Society of Anesthesiologists Classes I and II patients of ages between 18 and 60 years of both sexes scheduled to undergo upper limb surgery. With nerve locator, levobupivacaine (0.5%) 28 ml and 2 ml normal saline for Group L and levobupivacaine (0.5%) 28 ml and 0.75 μg/kg dexmedetomidine made up a solution of 2 ml, for Group D, a total 30 ml will be injected locally, in both the groups. Onset and duration of sensory and motor block will be assessed. One patient in Group L and two patients in Group D failed to achieve block within 30 min. Those three patients were then excluded from the analysis. Hence, the analysis was done by taking 34 patients in Group L and 33 patients in Group D. Onset of sensory and motor block was earlier in Group D (12.03 ± 0.85 and 13.58 ± 0.97) than Group L (14.32 ± 1.15 and 15 ± 0.98), and the difference is statistically significant ( P < 0.0001). Duration of sensory and motor block was longer in Group D (563.94 ± 15.60 and 495.15 ± 10.34) than Group L (368.53 ± 9.89 and 321.47 ± 7.84), and the difference is also statistically significant ( P < 0.0001). Duration of analgesia was longer in Group D (672.12 ± 11.39) than Group L (506.47 ± 9.497), and the difference is statistically significant ( P < 0.0001). Heart rate and mean arterial pressure were well maintained within the presumed range of significant variation, i.e., 20% from baseline, though at some point of time, intergroup comparison was statistically significant. Visual analog scale score compared at the time for administration of rescue analgesic between the groups come out to be statistically significant. Addition of 0.75 μg/kg dexmedetomidine to 0.5% levobupivacaine for supraclavicular plexus block shortens sensory and motor block onset time and extends sensory block, motor block, and analgesia duration.

Liposomal Bupivacaine Use in Transversus Abdominis Plane Blocks Reduces Pain and Postoperative Intravenous Opioid Requirement After Colorectal Surgery.

PubMed

Stokes, Audrey L; Adhikary, Sanjib D; Quintili, Ashley; Puleo, Frances J; Choi, Christine S; Hollenbeak, Christopher S; Messaris, Evangelos

2017-02-01

Enhanced recovery protocols frequently use multimodal postoperative analgesia to improve postoperative outcomes in patients undergoing colorectal surgery. The purpose of this study was to evaluate liposomal bupivacaine use in transversus abdominis plane blocks on postoperative pain scores and opioid use after colorectal surgery. This was a retrospective cohort study comparing outcomes between patients receiving nonliposomal anesthetic (n = 104) and liposomal bupivacaine (n = 303) blocks. The study was conducted at a single tertiary care center. Patients included those identified within an institutional database as inpatients undergoing colorectal procedures between 2013 and 2015 who underwent transversus abdominis plane block for perioperative analgesia. The study measured postoperative pain scores and opioid requirements. Patients receiving liposomal bupivacaine had significantly lower pain scores for the first 24 to 36 postoperative hours. Pain scores were similar after 36 hours. The use of intravenous opioids among the liposomal bupivacaine group decreased by more than one third during the hospitalization (99.1 vs 64.5 mg; p = 0.040). The use of ketorolac was also decreased (49.0 vs 18.3 mg; p < 0.001). In subgroup analysis, the decrease in opioid use was observed between laparoscopic and robotic procedures but not with laparotomies. No significant differences were noted in the use of oral opioids, acetaminophen, or ibuprofen. Postoperative length of stay and total cost were decreased in the liposomal bupivacaine group but did not achieve statistical significance. The study was limited by its retrospective, single-center design and heterogeneity of block administration. Attenuated pain scores observed with liposomal bupivacaine use were associated with significantly lower intravenous opioid and ketorolac use, suggesting that liposomal bupivacaine-containing transversus abdominis plane blocks are well aligned with the opioid-reducing goals of many enhanced recovery protocols.

Distribution of bupivacaine hydrochloride after sciatic and femoral nerve blocks in cats: A magnetic resonance imaging study.

PubMed

Evangelista, Marina C; de Lassalle, Julie; Chevrier, Christine; Carmel, Eric N; Fantoni, Denise T; Steagall, Paulo V M

2017-12-01

The objective of this study was to evaluate the distribution of bupivacaine hydrochloride using magnetic resonance imaging (MRI) after electrical nerve stimulator (ENS)-guided sciatic (ScN) and femoral (FN) nerve blocks in cats. Six adult cats (body weight 4.8±0.6kg) were anesthetized with acepromazine-buprenorphine-propofol-isoflurane. Transverse and sagittal plan sequences of pelvic limbs were obtained using a high-field magnet (1.5T). Afterwards, the ScN and FN blocks (one block per limb) were performed using 0.1mL/kg of bupivacaine 0.5% per site and the MRI sequence was repeated after each block. The injection was considered successful when bupivacaine was in contact with the nerve. Injectate location and complications were recorded. The length (mm) of contact (spread) between bupivacaine and nerves was measured and classified as fair (<15mm) or adequate (≥15mm). Five out of six ScN injections were successful; of these, four had adequate spread over the nerve [26 (13-39) mm]. All FN injections were successful, but in one case bupivacaine was administered over the motor branch of FN, distally to the bifurcation between the femoral and saphenous nerve. It was not possible to measure neither the length of contact between bupivacaine and FN nor to identify iatrogenic trauma caused by the injections. MRI can be used for the evaluation of bupivacaine distribution, but not complications, following ENS-guided ScN and FN blocks in cats. Despite most of the injections were considered successful, individual variability regarding the injectate location may explain differences in efficacy in the clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

7, 8, 3′-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons

PubMed Central

Shi, Haohong; Luo, Xingjing

2016-01-01

Background 7, 8, 3′-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro. Material/Methods Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively. Results THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine-induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons. Conclusions THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation. PMID:27371503

PDPH in obstetric anesthesia: comparison of 24-gauge Sprotte and 25-gauge Quincke needles and effect of subarachnoid administration of fentanyl.

PubMed

Devcic, A; Sprung, J; Patel, S; Kettler, R; Maitra-D'Cruze, A

1993-01-01

Postdural puncture headache (PDPH) is a frequent complication of spinal anesthesia. Some investigators have recommended the use of the Sprotte needle to reduce the incidence of this serious complication. This study prospectively compared the incidence of PDPH with two spinal needles of different size and design: the 24-gauge Sprotte (noncutting point) versus the 25-gauge Quincke (diamond, cutting point). The hypothesis that subarachnoid fentanyl will reduce the incidence of PDPH, as suggested in the literature, was also studied. Only patients for emergency or elective cesarean delivery were studied. One hundred ninety four patients were randomly assigned to receive spinal anesthesia with one of the two needles (Sprotte, n = 96; Quincke, n = 98). Simultaneously, each patient was assigned to receive hyperbaric 0.75% bupivacaine local anesthetic or a combination of the same concentration of local anesthetic with 20 micrograms of fentanyl (Sprotte with fentanyl, n = 47; Sprotte without fentanyl, n = 49; Quincke with fentanyl, n = 49; Quincke without fentanyl, n = 49). All patients were evaluated during the first 4 postoperative days, and follow-up telephone interviews were conducted 3 weeks after discharge. Four patients (4.2%) in the Sprotte group and seven (7.1%) in the Quincke group developed PDPH. Three out of four patients with headache in the Sprotte and four out of seven in the Quincke group received fentanyl as an adjunct for spinal anesthesia. Two patients in the Sprotte group required an epidural blood patch as a therapy for PDPH. Two patients in the Quincke group had severe headache and required an epidural blood patch. In the current study, the use of the 24-gauge Sprotte spinal needle resulted in a low incidence of severe PDPH, but was not significantly different when compared with the use of a 25-gauge Quincke needle (oriented parallel to the longitudinal dural fibers). The addition of fentanyl to hyperbaric bupivacaine spinal anesthesia did not reduce the risk of PDPH.

Macrophage apoptosis in rat skeletal muscle treated with bupivacaine hydrochloride: possible role of MCP-1.

PubMed

Horiguchi, Taisuke; Shibata, Masa-Aki; Ito, Yuko; Eid, Nabil A S; Abe, Muneaki; Otsuki, Yoshinori

2002-07-01

The fate of macrophages infiltrating damaged rat skeletal muscle fibers after intramuscular injection of the anesthetic bupivacaine hydrochloride (BPVC) and the possible roles of monocyte chemoattractant protein-1 (MCP-1) were investigated. The number of macrophages reached a maximum level at 2 days after the injection and then gradually decreased. The number of apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was elevated at 2-4 days and decreased thereafter. In serial sections, TUNEL-positive cells were also immunopositive for RM-4, an antibody specific for identification of macrophages. Electron microscopy further confirmed that it was the macrophages themselves that were undergoing apoptosis. As assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), high levels of MCP-1 mRNA in BPVC-treated muscles were observed and positively correlated with maximum macrophage infiltration. However, the levels of MCP-1 mRNA returned to normal low values coincident with decrease of inflammation and healing of damaged muscle fiber. Local apoptosis of macrophages, under the control of MCP-1, may be involved in healing of BPVC-treated muscles. Copyright 2002 Wiley Periodicals, Inc.

Treating pain on skin graft donor sites: Review and clinical recommendations.

PubMed

Sinha, Sarthak; Schreiner, Amanda J; Biernaskie, Jeff; Nickerson, Duncan; Gabriel, Vincent A

2017-11-01

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

Pain control following impacted third molar surgery with bupivacaine irrigation of tooth socket: a prospective study.

PubMed

Khorshidi Khiavi, Reza; Pourallahverdi, Maghsood; Pourallahverdi, Ayda; Ghorani Khiavi, Saadat; Ghertasi Oskouei, Sina; Mokhtari, Hadi

2010-01-01

The surgical removal of the lower third molars is a procedure generally followed by side effects such as postoperative pain. The aim of this study was to evaluate the efficacy of socket irrigation with an anesthetic solution in relieving pain following impacted third molar surgery. Thirty-four patients (17 males and 17 females), aged 18-24 years, with bilateral impacted lower third molars were selected. Both third molars were extracted in one surgical session. Tooth sockets in each patient were rinsed randomly either with 4 mL of 0.5% bupivacaine hydrochloride plain (without vasoconstrictor) anesthetic solu-tion or 4 mL of normal saline, used as control. The patients were instructed not to use analgesics as long as possible, and if not, they were instructed to use an analgesic, and record the time. Pain severity was assessed using a visual analogue pain scale (VAPS) at 1-, 6-, 12-, and 24-hour intervals post-operatively. Data were analyzed using Pearson's chi-square test and P <0.05 was considered statistically significant. Post-operative pain difference between the two groups was statistically significant at 1-, 6-, 12- and 24-hour post-operative intervals (P <0.05). Post-operative pain increased in both groups to a maximum 12 hours after surgery with signif-icant improvements after that. Based on the results, the irrigation of surgery site with bupivacaine after third molar surgery significantly reduces post-operative pain.

Pain Control Following Impacted Third Molar Surgery with Bupivacaine Irrigation of Tooth Socket: A Prospective Study

PubMed Central

Khorshidi Khiavi, Reza; Pourallahverdi, Maghsood; Pourallahverdi, Ayda; Ghorani Khiavi, Saadat; Ghertasi Oskouei, Sina; Mokhtari, Hadi

2010-01-01

Background and aims The surgical removal of the lower third molars is a procedure generally followed by side effects such as postoperative pain. The aim of this study was to evaluate the efficacy of socket irrigation with an anesthetic solution in relieving pain following impacted third molar surgery. Materials and methods Thirty-four patients (17 males and 17 females), aged 18-24 years, with bilateral impacted lower third molars were selected. Both third molars were extracted in one surgical session. Tooth sockets in each patient were rinsed randomly either with 4 mL of 0.5% bupivacaine hydrochloride plain (without vasoconstrictor) anesthetic solu-tion or 4 mL of normal saline, used as control. The patients were instructed not to use analgesics as long as possible, and if not, they were instructed to use an analgesic, and record the time. Pain severity was assessed using a visual analogue pain scale (VAPS) at 1-, 6-, 12-, and 24-hour intervals post-operatively. Data were analyzed using Pearson’s chi-square test and P <0.05 was considered statistically significant. Results Post-operative pain difference between the two groups was statistically significant at 1-, 6-, 12- and 24-hour post-operative intervals (P <0.05). Post-operative pain increased in both groups to a maximum 12 hours after surgery with signif-icant improvements after that. Conclusion Based on the results, the irrigation of surgery site with bupivacaine after third molar surgery significantly reduces post-operative pain. PMID:23346335

Coelomic implantation of satellite transmitters in the bar-tailed godwit (Limosa lapponica) and the bristle-thighed curlew (Numenius tahitiensis) using propofol, bupivacaine, and lidocaine

USGS Publications Warehouse

Mulcahy, Daniel M.; Gartrell, Brett D.; Gill, Robert E.; Tibbitts, T. Lee; Ruthrauff, Daniel R.

2011-01-01

Intravenous propofol was used as a general anesthetic with a 2∶1 (mg∶mg) adjunctive mixture of lidocaine and bupivacaine as local anesthetics infiltrated into the surgical sites for implantation of satellite transmitters into the right abdominal air sac of 39 female and 4 male bar-tailed godwits (Limosa lapponica baueri and Limosa lapponica menzbeiri) and 11 female and 12 male bristle-thighed curlews (Numenius tahitiensis). The birds were captured on nesting grounds in Alaska, USA, and on overwintering areas in New Zealand and Australia from 2005 through 2008. As it was developed, the mass of the transmitter used changed yearly from a low of 22.4 ± 0.2 g to a high of 27.1 ± 0.2 g and weighed 25.1 ± 0.2 g in the final year. The mean load ratios ranged from 5.2% to 7.7% for godwits and from 5.7% to 7.5% for curlews and exceeded 5% for all years, locations, and genders of both species. The maximum load ratio was 8.3% for a female bar-tailed godwit implanted in Australia in 2008. Three godwits and no curlews died during surgery. Most birds were hyperthermic upon induction but improved during surgery. Two godwits (one in New Zealand and one in Australia) could not stand upon release, likely due to capture myopathy. These birds failed to respond to treatment and were euthanized. The implanted transmitters were used to follow godwits through their southern and northern migrations, and curlews were followed on their southern migration.

Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.

PubMed

Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J

2013-11-01

Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of <24 hours. A liposomal bupivacaine formulation (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration but not peripheral nerve blocks. Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n = 14). For each block, liposomal bupivacaine (0-80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received 2 different doses, 1 on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI, 43%-93%), block duration usually lasted much longer: for bupivacaine doses >40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.

Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study

PubMed Central

Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.

2013-01-01

Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with bupivacaine dose (0.06 h/mg, SE = 0.14, 95% CI −0.27 to 0.39, p = 0.707). Conclusions The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of more than 24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a Phase 3 study with a far larger sample size, and these results should be viewed as suggestive, requiring confirmation in a future trial. PMID:24108252

Intravenous dexamethasone and perineural dexamethasone similarly prolong the duration of analgesia after supraclavicular brachial plexus block: a randomized, triple-arm, double-blind, placebo-controlled trial.

PubMed

Abdallah, Faraj W; Johnson, James; Chan, Vincent; Murgatroyd, Harry; Ghafari, Mohammad; Ami, Noam; Jin, Rongyu; Brull, Richard

2015-01-01

Perineural dexamethasone prolongs the duration of single-injection peripheral nerve block when added to the local anesthetic solution. Postulated systemic mechanisms of action along with theoretical safety concerns have prompted the investigation of intravenous dexamethasone as an alternative, with decidedly mixed results. We aimed to confirm that addition of intravenous dexamethasone will prolong the duration of analgesia after single-injection supraclavicular block compared with conventional long-acting local anesthetic alone or in combination with perineural dexamethasone for ambulatory upper extremity surgery. Seventy-five patients were randomized to receive supraclavicular block using 30-mL bupivacaine 0.5% alone (Control), with concomitant intravenous dexamethasone 8 mg (DexIV), or with perineural dexamethasone 8 mg (DexP). Duration of analgesia was designated as the primary outcome. To test our hypothesis, the superiority of DexIV was first compared with Control and then with DexP. Motor block duration, pain scores, opioid consumption, opioid-related side effects, patient satisfaction, and block-related complications were also analyzed. Twenty-five patients per group were analyzed. The duration of analgesia (mean [95% confidence interval]) was prolonged in the DexIV group(25 hours [17.6–32.4]) compared with Control (13.2 hours [11.5–15.0]; P < 0.001) but similar to the DexP group (25 hours[19.5–30.5]; P = 1). [corrected] Both DexIV and DexP had reduced pain scores, reduced postoperative opioid consumption, and improved satisfaction compared with Control. In a single-injection supraclavicular block with long-acting local anesthetic, the effectiveness of intravenous dexamethasone in prolonging the duration of analgesia seems similar to perineural dexamethasone.

[Analgesic effect of intra-artcular fentanyl in knee arthroscopy to treat patellofemoral lateral hyperpressure syndrome].

PubMed

Gutiérrez-Mendoza, Israel; Pérez-Correa, José J; Serna-Vela, Francisco; Góngora-Ortega, Javier; Vilchis-Huerta, Ventura; Pérez-Guzmán, Carlos; Hernández-Garduño, Eduardo; Vidal-Rodríguez, Francisco Alberto

2009-01-01

During arthroscopy for the treatment of patellofemoral lateral hyper-pressure syndrome (LHS), intra-articular morphine or its derivatives (fentanyl) may reduce postoperative pain when combined with anesthetics. We therefore decided to determine whether adding fentanyl to epinephrine and bupivacaine produced an increased analgesia. We randomly distributed 40 patients into two groups. The experimental group (n=20) was given 0.5% bupivacaine (2 mg/kg), epinephrine (100 microg) and fentanyl (2.5 microg/kg). The control group (n=20) received 0.5% bupivacaine (2 mg/kg) and epinephrine (100 microg). Patients underwent chondroplasty and retinacular release, and we assessed pain, time of analgesia and postoperative range of motion at postoperative hours 6 and 24. The age and the grade of patellofemoral chondromalacia (PFC) were similar in both groups (p > 0.05). No differences were found in pain and ranges of motion intraoperatively and at postoperative hours 6 and 24 (p > 0.05) between both groups. The postoperative analgesia time was similar (p > 0.05). Adding intra-articular fentanyl to the combination of epinephrine plus bupivacaine did not decrease pain, and did not increase neither the analgesia time nor the range of motion in patients with LHS undergoing knee arthroscopy.

Comparing the Effect of Adding Fentanyl, Sufentanil, and Placebo with Intrathecal Bupivacaine on Duration of Analgesia and Complications of Spinal Anesthesia in Patients Undergoing Cesarean Section

PubMed Central

Farzi, Farnoush; Mirmansouri, Ali; Naderi Nabi, Bahram; Atrkar Roushan, Zahra; Ghazanfar Tehran, Samaneh; Nematollahi Sani, Mona; Makhlooghi Azad, Soodabe; Nemati, Maryam

2017-01-01

Background Spinal anesthesia is the method of choice for most elective and emergency Cesarean sections. To increase the duration of anesthesia and improve the quality of analgesia during and after surgery, intrathecal opioids, as adjuvant drugs, are used in combination with local anesthetics. Methods This was a double-blind clinical trial performed on 99 patients. Women were divided into 3 groups of fentanyl, sufentanil, and placebo. For fentanyl group, 12.5 mg of bupivacaine and 25 micrograms of fentanyl; for sufentanil group, 12.5 mg of bupivacaine and 2.5 micrograms of sufentanil; and for placebo group, 12.5 mg of bupivacaine and a half mL of normal saline were injected in subarachnoid space. The sensory and motor block, hemodynamic status (mean blood pressure and heart rate), and probable complications were assessed. Results There was no significant difference between the groups in demographic characteristics. Durations of analgesia were, respectively, 314 ± 42.95, 312.5 ± 34.44, and 116.1 ± 42.24 minutes in the fentanyl, sufentanil, and placebo groups (P = 0.0001). Duration of sensory and motor block was higher in fentanyl and sufentanil groups compared with the placebo group. The highest duration of sensory and motor block was noted in sufentanil group (P = 0.0001). No significant difference was found between the groups in the hemodynamic parameters (P > 0.05). The frequency of itching in the fentanyl group was higher than sufentanil and placebo groups (P = 0.003). Also, shivering was higher in the placebo group compared with other groups (P = 0.036). Conclusions According to the results, adding 25 microgram fentanyl or 2.5 microgram sufentanil to intrathecal bupivacaine increased the duration of analgesia and provided hemodynamic stability with no major complication. As administering intrathecal fentanyl had a similar duration of analgesia like sufentanil with faster return of motor block and ambulation, it seems that it is a preferred additive for Cesarean section surgery. PMID:29696107

Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site.

PubMed

Hu, DeeDee; Onel, Erol; Singla, Neil; Kramer, William G; Hadzic, Admir

2013-02-01

Local anaesthetics are often used as part of multimodal pain management techniques to manage postsurgical pain and lessen the need for opioid analgesics; however, the duration of action of traditional formulations of local anaesthetics is short. Liposome bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound. This article provides a summary of the pharmacokinetic profile of liposome bupivacaine compared with bupivacaine HCl based on data compiled from four randomized, active- and placebo-controlled trials that included pharmacokinetic assessments following single administrations of study drug. Each study evaluated the safety, efficacy and pharmacokinetic profile of liposome bupivacaine in separate surgical populations (patients undergoing inguinal hernia repair, total knee arthroplasty, haemorrhoidectomy or bunionectomy). Pharmacokinetic parameters included maximum plasma drug concentration (C(max)), area under the curve (AUC) for plasma bupivacaine concentration over time extrapolated to infinity (AUC(∞)), time to observed C(max) (t(max)) and terminal elimination half-life of bupivacaine (t(½)). The studies assessed single administrations of liposome bupivacaine at dose levels ranging from 106 to 532 mg or bupivacaine HCl 100 to 150 mg or placebo (0.9 % sodium chloride) given locally via wound infiltration at the end of surgery prior to wound closure. Male and non-pregnant female patients (n = 253) aged ≥18 years, scheduled to undergo surgery as per the specific protocol for each study, were enrolled. Patient characteristics were stratified by liposome bupivacaine doses ≤266 mg and >266 mg, and bupivacaine HCl treatment arms. Pharmacokinetic parameters for liposome bupivacaine doses of 106, 266, 399 and 532 mg were compared. Plasma concentration versus time profiles were quantitatively similar across these four dose levels of liposome bupivacaine, with an initial peak occurring within 1 h after administration followed by a second peak about 12-36 h later. The overall incidence of adverse events was lower in the liposome bupivacaine ≤266-mg group than the liposome bupivacaine >266-mg and bupivacaine HCl groups (100- or 150-mg doses). In summary, liposome bupivacaine was well tolerated across the four studies and varied surgical models, and exhibited bimodal kinetics with rapid uptake observed during the first few hours and prolonged release through 96 h after administration.

Progress in analgesia for labor: focus on neuraxial blocks

PubMed Central

Ranasinghe, J Sudharma; Birnbach, David J

2010-01-01

Neuraxial analgesia is widely accepted as the most effective and the least depressant method of providing pain relief in labor. Over the last several decades neuraxial labor analgesia techniques and medications have progressed to the point now where they provide high quality pain relief with minimal side effects to both the mother and the fetus while maximizing the maternal autonomy possible for the parturient receiving neuraxial analgesia. The introduction of the combined spinal epidural technique for labor has allowed for the rapid onset of analgesia with minimal motor blockade, therefore allowing the comfortable parturient to ambulate. Patient-controlled epidural analgesia techniques have evolved to allow for more flexible analgesia that is tailored to the individual needs of the parturient and effective throughout the different phases of labor. Computer integrated systems have been studied to provide seamless analgesia from induction of neuraxial block to delivery. New adjuvant drugs that improve the effectiveness of neuraxial labor analgesia while decreasing the side effects that may occur due to high dose of a single drug are likely to be added to future labor analgesia practice. Bupivacaine still remains a popular choice of local anesthetic for labor analgesia. New local anesthetics with less cardiotoxicity have been introduced, but their cost effectiveness in the current labor analgesia practice has been questioned. PMID:21072273

Prevention of hypotension and prolongation of postoperative analgesia in emergency cesarean sections: A randomized study with intrathecal clonidine

PubMed Central

Bajwa, Sukhminder Jit Singh; Bajwa, Sukhwinder Kaur; Kaur, Jasbir; Singh, Amarjit; Singh, Anita; Parmar, Surjit Singh

2012-01-01

Background and Context: Different adjuvants been tried out for neuraxial anesthesia in emergency caesarean section so that the dose of the local anesthetic can be reduced and hypotension thereby prevented. Aims and Objectives: The present study was carried out in patients presenting for emergency lower segment caesarean section (LSCS) to establish the dose of intrathecal clonidine that would allow reduction of the dose of local anesthetic (thereby reducing the incidence and magnitude of hypotension) while at the same time providing clinically relevant prolongation of spinal anesthesia without significant side effects. Materials and Methods: This randomized clinical study was carried out in our institution among 100 pregnant females who underwent emergency caesarean section. The participants were divided randomly into four groups: A, B, C, and D, each comprising 25 parturients. Subarachnoid block was performed using a 26G Quincke needle, with 12 mg of hyperbaric bupivacaine (LA) in group A, 9 mg of LA + 30 μg of clonidine in group B, LA + 37.5 μg of clonidine in group C, and LA + 45 μg of clonidine in group D. The solution was uniformly made up to 2.2 mL with normal saline in all the groups. Onset of analgesia at T10 level, sensory and motor blockade levels, maternal heart rate and blood pressure, neonatal Apgar scores, postoperative block characteristics, and adverse events were looked for and recorded. Statistical analysis was carried out with SPSS® version 10.0 for Windows®, using the ANOVA test with post hoc significance, the Chi-square test, and the Mann-Whitney U test. P<.05 was considered significant and P<.0001 as highly significant. Results: One hundred patients were enrolled for this study. The four groups were comparable with regard to demographic data and neonatal Apgar scores. Onset and establishment of sensory and motor analgesia was significantly shorter in groups C and D, while hypotension (and the use of vasopressors) was significantly higher in groups A and D. Perioperative shivering, nausea, and vomiting were significantly higher in groups A and D, while incidence of dry mouth was significantly higher in group D. Conclusions: The addition of 45 μg, 37.5 μg, and 30 μg of clonidine to hyperbaric bupivacaine results in more prolonged complete and effective analgesia, allowing reduction of up to 18% of the total dose of hyperbaric bupivacaine. From the results of this study, 37.5 μg of clonidine seems to be the optimal dose. PMID:22837893

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

PubMed

Gosselin, Sophie; Hoegberg, Lotte C G; Hoffman, Robert S; Graudins, Andis; Stork, Christine M; Thomas, Simon H L; Stellpflug, Samuel J; Hayes, Bryan D; Levine, Michael; Morris, Martin; Nesbitt-Miller, Andrea; Turgeon, Alexis F; Bailey, Benoit; Calello, Diane P; Chuang, Ryan; Bania, Theodore C; Mégarbane, Bruno; Bhalla, Ashish; Lavergne, Valéry

2016-12-01

Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid ® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats

PubMed Central

Zheng, Qingshan; Yang, Xiaolin; Lv, Rong; Ma, Longxiang; Liu, Jin; Zhu, Tao; Zhang, Wensheng

2017-01-01

Objective The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination. Methods QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine. Results 0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks. Conclusion The combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment. PMID:28334014

The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats.

PubMed

Yin, Qinqin; Li, Jun; Zheng, Qingshan; Yang, Xiaolin; Lv, Rong; Ma, Longxiang; Liu, Jin; Zhu, Tao; Zhang, Wensheng

2017-01-01

The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination. QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine. 0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks. The combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment.

Prospective study of lidocaine, bupivacaine, and epinephrine levels and blood loss in patients undergoing liposuction and abdominoplasty.

PubMed

Swanson, Eric

2012-09-01

Bupivacaine levels have not been measured in cosmetic surgery patients to establish safety. Blood loss has been underestimated using the small volumes present in the aspirate. The proportion of wetting solution removed by liposuction has not been reliably ascertained. To remedy these deficiencies, a prospective study was undertaken among 322 consecutive patients presenting for superwet ultrasonic liposuction and/or abdominoplasty, and other combined procedures, using infusions containing 0.05% lidocaine (liposuction) and/or 0.025% bupivacaine (abdominoplasty) with 1:500,000 epinephrine. Plasma levels of lidocaine, bupivacaine, and epinephrine were studied in a subset of 76 consecutive patients, including hourly intraoperative samples in 39 consecutive patients. Anesthetic levels were also measured in 12 consecutive patients during the 24-hour period after infusion. The maximum lidocaine dose was 3243 mg and the maximum level was 2.10 μg/ml. The maximum bupivacaine dose was 550 mg and the maximum level was 0.81 μg/ml. No clinical toxicity was encountered. Estimated blood loss from liposuction was 217.5 cc + 187 cc/liter of aspirate (r = 0.65). Abdominoplasty added 290 cc of blood loss, on average. The mean proportion of wetting solution removed by liposuction was 9.8 percent. Bupivacaine may be safely used in cosmetic surgery. A concentration of 1:500,000 epinephrine is safe and effective when administered as part of a wetting solution that is limited to less than 5 liters. Estimated blood loss is higher than previous estimates based on lipocrits. Combination procedures are safe.

Baricity of Bupivacaine on Maternal Hemodynamics after Spinal Anesthesia for Cesarean Section: A Randomized Controlled Trial

PubMed Central

Atashkhoei, Simin; Abedini, Naghi; Pourfathi, Hojjat; Znoz, Ali Bahrami; Marandi, Pouya Hatami

2017-01-01

Background: After spinal anesthesia, patients undergoing cesarean section are more likely to develop hemodynamic changes. The baricity of local anesthetic has an important role on spinal blockade effects. The aim of this study was to compare the isobar and hyperbaric bupivacaine 0.5% plus fentanyl on maternal hemodynamics after spinal anesthesia for C/S. Methods: In this double-blind study, 84 healthy pregnant women undergoing C/S using bupivacaine 0.5% isobar (study group, n=42) or hyperbaric (control group, n=42) for spinal anesthesia were scheduled. The study was conducted from 21 April 2014 to 21 November 2014 at Al-Zahra Hospital, Tabriz, Iran. Parameters such as maternal hemodynamics, block characteristics, side effects, and neonatal Apgar scores were recorded. Data were analyzed using the SPSS software by performing chi-square test, Fisher’s exact test, one-way ANOVA, Mann-Whitney U-test, and student’s t test. Results: The incidence of hypotension in the isobar group was lower than the hyperbaric group, although it was not statistically significant (40.47% vs. 61.9%, P=0.08). The duration of hypotension was shorter in the study group (1.6±7.8 min vs. 7.4±12.5 min, P=0.004). The dose of ephedrine was lower in the study group (2.4±6.6 mg vs. 5.3±10.7 mg, P=0.006). The main maternal side effect is sustained hypotension that was seen in 0 patients of the isobar and 7 (16.66%) of hyperbaric groups (P=0.006). None of the neonates had Apgar score≤7 at 5 min of delivery (P=1.0). Sensory and motor block duration was shorter in the study group (P=0.01). Conclusion: Isobaric bupivacaine is associated with more hemodynamic stability and shorter sensory and motor blockade in mothers under spinal anesthesia for C/S. Trial Registration Number: IRCT201401287013N7 PMID:28360439

Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: A randomized double-blind study

PubMed Central

Reddy, Velayudha Sidda; Shaik, Nawaz Ahmed; Donthu, Balaji; Reddy Sannala, Venkata Krishna; Jangam, Venkatsiva

2013-01-01

Background: Alpha2-adrenergic agonists have synergistic action with local anesthetics and may prolong the duration of sensory, motor blockade and postoperative analgesia obtained with spinal anesthesia. Aim: The objectives of this study are to compare and evaluate the efficacy of intravenous dexmedetomidine premedication with clonidine and placebo on spinal blockade duration, postoperative analgesia and sedation in patients undergoing surgery under bupivacaine intrathecal block. Materials and Methods: In this prospective, randomized, double-blind placebo-controlled study, 75 patients of the American Society of Anesthesiologists status I or II, scheduled for orthopedic lower limb surgery under spinal anesthesia, were randomly allocated into three groups of 25 each. Group DE received dexmedetomidine 0.5 μgkg−1, group CL received clonidine 1.0 μgkg−1 and placebo group PL received 10 ml of normal saline intravenously before subarachnoid anesthesia with 15 mg of 0.5% hyperbaric bupivacaine. Onset time and regression times of sensory and motor blockade, the maximum upper level of sensory blockade were recorded. Duration of postoperative analgesia and sedation scores along with side effects were also recorded. Data was analyzed using analysis of variance or Chi-square test, and the value of P < 0.05 was considered statistically significant. Results: The sensory block level was higher with dexmedetomidine (T4 ± 1) than clonidine (T6 ± 1) or placebo (T6 ± 2). Dexmedetomidine also increased the time (243.35 ± 56.82 min) to first postoperative analgesic request compared with clonidine (190.93 ± 42.38 min, P < 0.0001) and placebo (140.75 ± 28.52 min, P < 0.0001). The maximum Ramsay sedation score was greater in the dexmedetomidine group than other two groups (P < 0.0001). Conclusion: Premedication with intravenous dexmedetomidine is better than intravenous clonidine to provide intraoperative sedation and postoperative analgesia during bupivacaine spinal anesthesia. PMID:24106359

L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats.

PubMed

Wong, Gail K; Pehora, Carolyne; Crawford, Mark W

2017-03-01

The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg -1 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. In the first of two experiments, L-carnitine 100 mg·kg -1 iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg -1 ·min -1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg -1 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg -1 , L-carnitine 100 mg·kg -1 , 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. In the first study, L-carnitine 100 mg·kg -1 increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). These findings suggest that acute administration of L-carnitine 100 mg·kg -1 decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.

Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts.

PubMed

Bentov, Itay; Damodarasamy, Mamatha; Spiekerman, Charles; Reed, May J

2016-09-01

The aged are at increased risk of postoperative wound healing complications. Because local anesthetics are infiltrated commonly into the dermis of surgical wounds, we sought to determine whether local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1), growth factors that are important regulators of wound healing. Human dermal fibroblasts (HFB) from aged and young donors were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine on proliferation of HFB. Lidocaine was most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-β1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-β1 was evaluated for their effects on proliferation and expression of dermal collagens, respectively. Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95% confidence interval [CI], 80%-98%, P = .009 and for mepivacaine 90% of control, 95% CI, 81%-99%, P = .032) but not in young HFB. Ropivacaine and bupivacaine did not inhibit proliferation. Because of the clinical utility of lidocaine relative to mepivacaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and insulin-like growth factor-1 receptor (IGF1R) in fibroblasts from aged donors (IGF-1, log2 fold-change -1.25 [42% of control, 95% CI, 19%-92%, P = .035] and IGF1R, log2 fold-change -1.00 [50% of control, 95% CI, 31%-81%, P = .014]). In contrast, lidocaine did not affect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change -1.28 [41% of control, 95% CI, 20%-83%, P = .022] in aged HFB and log2 fold-change -1.60 [33% of control, 95% CI, 15%-73%, P = .019] in young HFB). Transcripts for collagen I were decreased in aged HFB (log2 fold-change -1.82 [28% of control, 95% CI, 14%-58%, P = .006]) but not in the young HFB. Similar to the transcripts, lidocaine also inhibited the protein expression of collagen III in young and aged HFB (log2 fold-change -1.79 [29% of control, 95% CI, 18%-47%, P = .003] in young HFB and log2 fold-change -1.76 [30% of control, 95% CI, 9%-93%, P = .043] in aged HFB). The effect of lidocaine on the expression of collagen III protein was obviated by TGF-β1 in both young and aged HFB. Our results show that lidocaine inhibits processes relevant to dermal repair in aged HFB. The detrimental responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-β1.

Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.

PubMed

Chen, Yu-Wen; Chu, Chin-Chen; Chen, Yu-Chung; Hung, Ching-Hsia; Hsueh, Meng-I; Wang, Jhi-Joung

2011-06-08

The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. On an ED(50) basis, the rank of drug potency was oxybuprocaine>bupivacaine>dextrorphan (P<0.01). Mixtures of clonidine (0.12μmol) with oxybuprocaine, bupivacaine or dextrorphan (ED(50) or ED(95)) extended the duration of action and increased the potency on infiltrative cutaneous analgesia. Among these drugs, the addition of clonidine to bupivacaine (amide type) elicits the most effective cutaneous analgesia. Clonidine at the dose of 0.12 and 0.24μmol did not produce cutaneous analgesia. Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model.

PubMed

Zaballos, M; Sevilla, R; González, J; Callejo, D; de Diego, C; Almendral, J; Quintela, O; Anadón, M J

2016-01-01

The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. Twelve pigs were anesthetized with intravenous sodium thiopental 5mg kg(-1) and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg(-1) was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg(-1)of IL over one minute, followed by an infusion of 0.25 mL kg min(-1). Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration. Bupivacaine (4.33±0.81 mg/kg in IL group and 4.66±1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Ganglion blocks as a treatment of pain: current perspectives

PubMed Central

Gunduz, Osman Hakan; Kenis-Coskun, Ozge

2017-01-01

The inputs from sympathetic ganglia have been known to be involved in the pathophysiology of various painful conditions such as complex regional pain syndrome, cancer pain of different origin, and coccygodynia. Sympathetic ganglia blocks are used to relieve patients who suffer from these conditions for over a century. Many numbers of local anesthetics such as bupivacaine or neurolytic agents such as alcohol can be chosen for a successful block. The agent is selected according to its duration of effect and the purpose of the injection. Most commonly used sympathetic blocks are stellate ganglion block, lumbar sympathetic block, celiac plexus block, superior hypogastric block, and ganglion Impar block. In this review, indications, methods, effectiveness, and complications of these blocks are discussed based on the data from the current literature. PMID:29276402

Trial of Injected Liposomal Bupivacaine vs Bupivacaine Infusion After Surgical Stabilization of Rib Fractures

ClinicalTrials.gov

2017-10-06

Drug Effect; Rib Fractures; Rib Trauma; Surgical Procedure, Unspecified; Pain; Catheter (Other); Nerve Pain; Local Infiltration; Anesthesia, Local; Intercostal Rib; Opioid Dependence; Chest Injury Trauma; Pneumonia

Liposomal bupivacaine versus traditional bupivacaine for pain control after total hip arthroplasty

PubMed Central

Ma, Ting-Ting; Wang, Yu-Hui; Jiang, Yun-Feng; Peng, Cong-Bin; Yan, Chao; Liu, Zi-Gui; Xu, Wei-Xing

2017-01-01

Abstract Background: In the past, the efficacy of local infiltration of liposomal bupivacaine for total hip arthroplasty (THA) patients was in debate. Therefore, this meta-analysis was conducted to determine whether local infiltration of liposomal bupivacaine provides better pain relief after THA. Methods: We searched Web of Science, PubMed, Embase, and the Cochrane Library databases to the April 2017. Any studies comparing liposomal bupivacaine and traditional bupivacaine were included in our meta-analysis. The outcomes included visual analog scale (VAS) at 24, 48, and 72 hours, total morphine consumption at 24 hours, and the length of hospital stay. We assessed the pooled data using a random-effect model. Results: Six studies were finally included in this meta-analysis. Our pooled data analysis demonstrated that liposomal bupivacaine was more effective than the traditional bupivacaine in terms of VAS at 24 hours (P  =  .018) and the length of hospital stay (P  =  .000). There was no significant difference in terms of the VAS at 48 and 72 hours and total morphine consumption at 24 hours (P >.05). Conclusion: Compared with the traditional bupivacaine, liposomal bupivacaine shows better pain control at 24 hours and reduces the length of hospital stay after THA. Its economic costs must be assessed in multimodal center randomized controlled trials when being recommended as a long-acting alternative analgesic agent for a THA patient. PMID:28640101

Liposomal bupivacaine versus traditional bupivacaine for pain control after total hip arthroplasty: A meta-analysis.

PubMed

Ma, Ting-Ting; Wang, Yu-Hui; Jiang, Yun-Feng; Peng, Cong-Bin; Yan, Chao; Liu, Zi-Gui; Xu, Wei-Xing

2017-06-01

In the past, the efficacy of local infiltration of liposomal bupivacaine for total hip arthroplasty (THA) patients was in debate. Therefore, this meta-analysis was conducted to determine whether local infiltration of liposomal bupivacaine provides better pain relief after THA. We searched Web of Science, PubMed, Embase, and the Cochrane Library databases to the April 2017. Any studies comparing liposomal bupivacaine and traditional bupivacaine were included in our meta-analysis. The outcomes included visual analog scale (VAS) at 24, 48, and 72 hours, total morphine consumption at 24 hours, and the length of hospital stay. We assessed the pooled data using a random-effect model. Six studies were finally included in this meta-analysis. Our pooled data analysis demonstrated that liposomal bupivacaine was more effective than the traditional bupivacaine in terms of VAS at 24 hours (P  =  .018) and the length of hospital stay (P  =  .000). There was no significant difference in terms of the VAS at 48 and 72 hours and total morphine consumption at 24 hours (P >.05). Compared with the traditional bupivacaine, liposomal bupivacaine shows better pain control at 24 hours and reduces the length of hospital stay after THA. Its economic costs must be assessed in multimodal center randomized controlled trials when being recommended as a long-acting alternative analgesic agent for a THA patient.

Use of Nonopioid Analgesics and the Impact on Patient Outcomes.

PubMed

Sanzone, Anthony G

2016-05-01

Although opioids are widely used for the management of pain in patients with hip fracture, these medications are known to have a wide range of adverse effects that can result in suboptimal outcomes or serious life-threatening complications. Common opioid-related adverse events include gastrointestinal effects, central nervous system effects, and respiratory depression. Hip fractures occur most frequently among the elderly-the very population that is most susceptible to the adverse effects of opioids and the risks of serious physiological complications. There has been much interest during recent years in identifying alternative analgesic approaches that are less opioid-dependent. There is good evidence to show that nerve blocks can be effective in managing the acute pain associated with hip fracture. However, sciatic and femoral nerve blocks seem to increase the risk of several clinically significant adverse events. A retrospective cohort study that examined the effectiveness of scheduled intravenous acetaminophen as part of the pain management protocol for hip fracture patients revealed significant improvement in pain scores, narcotic use, length of stay, and missed physical therapy sessions. Limited data exist in patients with hip fracture on the effects of infiltration of the surgical site with the local anesthetic agent, bupivacaine. However, extensive use of bupivacaine in hip arthroplasty surgery suggests that it may be highly beneficial in the patient with hip fracture.

The effects of bupivacaine, L-nitro-L-arginine-methyl ester, and phenylephrine on cardiovascular adaptations to asphyxia in the preterm fetal lamb.

PubMed

Santos, A C; Yun, E M; Bobby, P D; Noble, G; Arthur, G R; Finster, M

1997-12-01

The preterm fetal lamb that is exposed to clinically relevant plasma concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received an intravenous injection of L-nitro-L-arginine-methyl ester (L-NAME) (25 mg/kg), and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in mean arterial blood pressure above the level noted at 90 min of cord occlusion, and an increase in fetal PaO2 toward control levels. This was accompanied by a reduction in organ blood flows to preasphyxia levels. In asphyxiated Group III fetuses, titration of the phenylephrine infusion to achieve blood pressure increases similar to those noted with L-NAME were also associated with an increase in fetal PaO2. These data indicate that bupivacaine abolishes some of the circulatory adaptations to mild to moderate asphyxia induced by partial cord occlusion in the preterm fetal lamb. It is not clear whether these effects of bupivacaine are due to inhibition of NO. In the preterm fetal lamb, clinically relevant plasma concentrations of bupivacaine achieved by intravenous infusion to the pregnant ewe (80% gestation) abolished some of the fetal cardiovascular adaptations to asphyxia induced by partial umbilical cord occlusion.

Efficacy and pharmacokinetics of bupivacaine with epinephrine or dexmedetomidine after intraperitoneal administration in cats undergoing ovariohysterectomy.

PubMed

Benito, Javier; Monteiro, Beatriz; Beaudry, Francis; Steagall, Paulo

2018-04-01

The aim of this study was to determine the efficacy and pharmacokinetics of bupivacaine in combination with epinephrine or dexmedetomidine after intraperitoneal administration in cats undergoing ovariohysterectomy. Sixteen healthy adult cats (3.3 ± 0.6 kg) were included in a prospective, randomized, masked clinical trial after obtaining owners' consent. Anesthetic protocol included buprenorphine-propofol-isoflurane. Meloxicam [0.2 mg/kg body weight (BW)] was administered subcutaneously before surgery. Cats were randomly divided into 2 groups to receive 1 of 2 treatments. Intraperitoneal bupivacaine 0.25% (2 mg/kg BW) was administered with epinephrine (BE group; 2 μg/kg BW) or dexmedetomidine (BD group; 1 μg/kg BW) before ovariohysterectomy ( n = 8/group). A catheter was placed in the jugular vein for blood sampling. Blood samples were collected for up to 8 h after bupivacaine was administered. Plasma concentrations and pharmacokinetics of bupivacaine were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS) and non-compartmental model, respectively. Pain was evaluated using the UNESP-Botucatu multidimensional composite pain scale (MCPS), the Glasgow composite feline pain scale (GPS), and a dynamic visual analog scale up to 8 h after extubation. Rescue analgesia was provided with buprenorphine if MCPS was ≥ 6. Repeated measures linear models were used for analysis of pain and sedation scores ( P < 0.05). Maximum bupivacaine plasma concentrations (Cmax) for BE and BD were 1155 ± 168 ng/mL and 1678 ± 364 ng/mL ( P = 0.29) at 67 ± 13 min (Tmax) and 123 ± 59 min ( P = 0.17), respectively. Pharmacokinetic parameters and pain scores were not different between treatments ( P > 0.05). One cat in the BE group received rescue analgesia ( P = 0.30). Intraperitoneal bupivacaine with epinephrine or dexmedetomidine produced concentrations below toxic levels and similar analgesic effects. It is therefore safe to administer these drug combinations in cats undergoing ovariohysterectomy.

Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

PubMed

Wijayasinghe, Nelun; Andersen, Kenneth G; Kehlet, Henrik

2017-02-01

Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block proposes to block these nerves and has provided pain relief for patients undergoing breast cancer surgery, but has yet to be evaluated in patients with PPBCS. The aim of this pilot study was to examine the effects of the Pecs block on summed pain intensity (SPI) and sensory function (through quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. Patients experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. This pilot study suggests that the pectoral nerves play a role in the maintenance of pain in the breast area in PPBCS and begs for further research. © 2016 World Institute of Pain.

Comparison of hypobaric, hyperbaric, and isobaric solutions of bupivacaine during continuous spinal anesthesia.

PubMed

Van Gessel, E F; Forster, A; Schweizer, A; Gamulin, Z

1991-06-01

This study was designed to compare the anesthetic properties of hypobaric bupivacaine with those of isobaric and hyperbaric solutions when administered in the supine position in an elderly population undergoing hip surgery using continuous spinal anesthesia. Plain bupivacaine (0.5%) was mixed with equal volumes of 10% dextrose (hyperbaric), 0.9% NaCl (isobaric), or distilled water (hypobaric) to obtain 0.25% solutions. In a double-blind fashion, all patients received 3 mL (7.5 mg) of their particular solution injected through the spinal catheter in the horizontal supine position. The sensory level obtained in the hyperbaric group (median, T4; range, T3-L3) was significantly higher than in both the isobaric (median, T11; range, T6-L1) and hypobaric (median, L1; range, T4-L3) groups. A motor blockade of grade 2 or 3 was obtained in 14 of 15 and 12 of 15 patients in, respectively, the hyperbaric and isobaric groups, but only in 8 of 15 patients in the hypobaric group. After the initial injection of 3 mL (7.5 mg), a sensory level of T10 and a motor blockade of grade 2 or 3 was obtained in 14 of 15, 5 of 15, and 3 of 15 patients in the hyperbaric, isobaric, and hypobaric groups, respectively. All remaining patients received 1 or 2 additional milliliters (2.5-5 mg) and achieved these required anesthetic conditions, except for one patient in the hyperbaric group and eight patients in the hypobaric group in whom anesthesia was achieved with hyperbaric tetracaine. The decrease in mean arterial pressure was significantly more severe in the hyperbaric (30%) than in either the isobaric (18%) or hypobaric (14%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphine Spinal Block Anesthesia in Patients Who Undergo an Open Hemorrhoidectomy: A Prospective Analysis of Pain Control and Postoperative Complications

PubMed Central

Moreira, José PT; Isaac, Raniere R; Alves-Neto, Onofre; Moreira, Thiago AC; Vieira, Tiago HM; Brasil, Andressa MS

2014-01-01

Purpose This study evaluated the use of adding morphine to bupivacaine in spinal anesthesia for pain control in patients who underwent an open hemorrhoidectomy. Methods Forty patients were prospectively selected for an open hemorrhoidectomy at the same institution and were randomized into two groups of 20 patients each: group 1 had a spinal with 7 mg of heavy bupivacaine associated with 80 µg of morphine (0.2 mg/mL). Group 2 had a spinal with 7 mg of heavy bupivacaine associated with distilled water, achieving the same volume of spinal infusion as that of group 1. Both groups were prescribed the same pain control medicine during the postoperative period. Pain scores were evaluated at the anesthetic recovery room and at 3, 6, 12, and 24 hours after surgery. Postoperative complications, including pruritus, nausea, headaches, and urinary retention, were also recorded. Results There were no anthropometric statistical differences between the two groups. Pain in the anesthetic recovery room and 3 hours after surgery was similar for both groups. However, pain was better controlled in group 1 at 6 and 12 hours after surgery. Although pain was better controlled for group 1 after 24 hours of surgery, the difference between the groups didn't achieved statistical significance. Complications were more common in group 1. Six patients (6/20) presented coetaneous pruritus and 3 with (3/20) urinary retention. Conclusion A hemorrhoidectomy under a spinal with morphine provides better pain control between 6 and 12 hours after surgery. However, postoperative complications, including cutaneous pruritus (30%) and urinary retention (15%), should be considered as a negative side of this procedure. PMID:24999465

Possible delayed respiratory depression following intrathecal injection of morphine and bupivacaine in an alpaca.

PubMed

Martínez, Miguel; Murison, Pamela J; Murrell, Jo

2014-01-01

To describe general anesthesia and successful treatment of an alpaca, which developed respiratory arrest 2 hours after intrathecal injection of morphine and bupivacaine. A 10-day-old female alpaca weighing 7.3 kg was presented to our hospital with a fractured right tibia. The cria was anesthetized to repair the fracture with a dynamic compression plate. Anesthesia was induced with IV propofol and maintained with sevoflurane in 100% oxygen. Prior to the start of surgery the alpaca received an unintended intrathecal injection of 0.6 mL of a solution of 0.5 mg morphine (0.068 mg/kg) and 1.5 mg bupivacaine (0.2 mg/kg), after an attempted lumbo-sacral epidural. The alpaca developed respiratory arrest 120 minutes after the intrathecal injection was administered. Adequate hemoglobin-oxygen saturation was maintained despite minimal intermittent manual ventilation, but marked hypercapnia developed (PaCO2 of 17.3 KPa [130 mm Hg]). Delayed respiratory depression resulting from cephalad migration of intrathecal morphine was suspected. Ventilation was supported until the end of surgery when sevoflurane was discontinued. The trachea remained intubated, 100% oxygen was supplied, and ventilation was supported at 2-4 breaths/min for the next 60 minutes, but no attempts to breathe spontaneously were detected. Intravenous naloxone (0.3 mg [0.04 mg/kg]) was administered slowly to effect until adequate spontaneous ventilation and full consciousness returned. The anesthetic recovery of the alpaca was rapid and uneventful after the opioid antagonist was given. Delayed respiratory depression is a potential complication after intrathecal administration of morphine. Careful dose-adjustment may reduce the risk, and close monitoring will result in early detection and treatment of this complication. © Veterinary Emergency and Critical Care Society 2014.

Problems of long-term spinal opioid treatment in advanced cancer patients.

PubMed

Mercadante, S

1999-01-01

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.

Preemptive Analgesia in Thumb Basal Joint Arthroplasty: Immediate Postoperative Pain with Preincision versus Postincision Local Anesthesia.

PubMed

Labrum, Joseph T; Ilyas, Asif M

2017-08-01

Purpose  Currently no guidelines exist for the timing of the injection of anesthetics in surgeries performed under general anesthesia to minimize postoperative pain. To better understand the role of timing of the injection of local anesthesia in hand surgery performed under general anesthesia, we evaluated the effect of pre- versus postincisional local analgesic injection on immediate postoperative pain experience. We hypothesize that the preincisional (preemptive) injection will result in decreased immediate postoperative pain experience and analgesic use when compared with postincisional injection. Methods  Consecutive cases of thumb basal joint arthroplasty performed over a 4-year period were retrospectively reviewed. During the first half of the study period, the surgical site was infiltrated with 0.5% bupivacaine at the completion of surgery following closure. During the second half of the study period, the surgical site was infiltrated with 0.5% bupivacaine prior to skin incision. Data collected included patient demographics, immediate postoperative recovery room (PACU) pain scores, and postoperative opioid consumption in morphine equivalents. Results  Two-tailed t -test identified no significant difference between the pre- and postincision cohorts relative to PACU entrance pain scores and time spent in the PACU. PACU exit pain scores were significantly lower in the preincision cohort. The mean PACU pain score was also significantly lower in the preincision cohort. PACU opioid consumption, converted into morphine equivalents, was found to be 211 mg in the preincision versus 299 mg in the postincision cohort. Conclusion  The preincisional (preemptive) injection of local anesthesia was found to result in lower pain scores during and upon exit of the PACU as compared with the postclosure group. In addition, the preincision cohort also trended toward lower opioid consumption while in the PACU. Consideration should be given to the routine use of preincision injection of local anesthesia to maximize pain relief in a multimodal pain strategy in hand surgical patients. Level of Evidence  Therapeutic level III.

Local infiltration for postsurgical analgesia following total hip arthroplasty: a comparison of liposomal bupivacaine to traditional bupivacaine.

PubMed

Asche, Carl V; Ren, Jinma; Kim, Minchul; Gordon, Kate; McWhirter, Marie; Kirkness, Carmen S; Maurer, Brian T

2017-07-01

To assess postsurgical clinical and economic outcomes of patients who received local infiltration containing liposomal bupivacaine versus traditional bupivacaine for pain management following total hip arthroplasty (THA). This retrospective study included two groups of consecutive patients undergoing THA. The experimental group received local infiltration with a combination of liposomal bupivacaine, bupivacaine HCl 0.25% with epinephrine 1:200,000, and ketorolac for postsurgical analgesia. The historical control group received the previous standard of care: local infiltration with a combination of bupivacaine HCl 0.25% with epinephrine 1:200,000 and ketorolac. Key outcomes included distance walked, length of stay (LOS), opioid medication use, numeric pain scores, hospital charges, hospital costs, all-cause 30 day readmission rate, and adverse events (AEs). Both unadjusted and adjusted (i.e. age, sex, insurance type, living situation, body mass index, procedure side, and comorbidity) outcomes were compared between the two groups. The experimental group (n = 64) demonstrated statistically significant improvement versus the historical control group (n = 66) in mean distance walked on discharge day (249.2 vs. 180.0 feet; unadjusted p = .025, adjusted p = .070), mean LOS (2.0 vs. 2.7 days; p < .001, p = .002), proportion of patients who used opioid rescue medication on postoperative day (POD) 1 (29.7% vs. 56.1%; p = .002, p = .003) and POD 2 (7.8% vs. 30.3%; p = .001, p = .003), mean cumulative area under the curve for pain score on POD 0 (127.6 vs. 292.5; p < .001, both), POD 1 (92.9 vs. 185.0; p < .001, both), and POD 2 (93.8 vs. 213.8; p = .006, both). Among a subgroup of patients with available financial information, mean hospital charges were lower in the experimental group ($43,794 [n = 24] vs. $48,010 [n = 66]; p < .001, both). Rates of all-cause 30 day readmission and AEs were not significantly different between groups. No falls occurred. Infiltration at the surgical site with liposomal bupivacaine was associated with improved postsurgical outcomes when compared with traditional bupivacaine in patients undergoing THA.

Time to Analgesia Onset and Pharmacokinetics After Separate and Combined Administration of Liposome Bupivacaine and Bupivacaine HCl: Considerations for Clinicians

PubMed Central

Gadsden, Jeffrey; Long, William J.

2016-01-01

Background: Liposome bupivacaine is a prolonged-release bupivacaine formulation indicated for single-dose administration into the surgical site to produce postsurgical analgesia. Methods: An overview of time to onset of analgesia observed with liposome bupivacaine in human studies is provided, as well as a summary of data from pharmacokinetic studies including those that assessed pharmacokinetics after separate versus coadministration of liposome bupivacaine and bupivacaine HCl. Results: Data from multiple studies show that local administration of liposome bupivacaine is associated with rapid onset and effective analgesia after surgery. However, the efficacy profile observed in controlled settings may not replicate the profile observed in clinical practice; time to onset may be impacted by nonpharmacologic factors, such as amount of drug given, location and relative vascularity, and variances in surgical techniques. Some clinicians coadminister or admix bupivacaine HCl and liposome bupivacaine based on the supposition that adjuvant use will result in more rapid onset of efficacy. To date, no clinical studies have been conducted comparing pain-related outcomes following coadministration versus liposome bupivacaine alone. Preclinical pharmacokinetic studies have assessed the potential impact of combined use, which resulted in predictable, additive systemic exposure without compromising the prolonged-release profile of liposome bupivacaine, and without signs of toxicity. Conclusion: Based on available data and approved package insert, in the setting of wound infiltration, clinicians have the flexibility to administer liposome bupivacaine alone, coadminister separately with bupivacaine HCl, or admix with bupivacaine HCl prior to injection, providing the bupivacaine HCl dose does not exceed 50% of the liposome bupivacaine dose. PMID:27347237

Liposomal bupivacaine decreases pain following retropubic sling placement: a randomized placebo-controlled trial.

PubMed

Mazloomdoost, Donna; Pauls, Rachel N; Hennen, Erin N; Yeung, Jennifer Y; Smith, Benjamin C; Kleeman, Steven D; Crisp, Catrina C

2017-11-01

Midurethral slings are commonly used to treat stress urinary incontinence. Pain control, however, may be a concern. Liposomal bupivacaine is a local anesthetic with slow release over 72 hours, demonstrated to lower pain scores and decrease narcotic use postoperatively. The purpose of this study was to examine the impact of liposomal bupivacaine on pain scores and narcotic consumption following retropubic midurethral sling placement. This randomized, placebo-controlled trial enrolled women undergoing retropubic midurethral sling procedures with or without concomitant anterior or urethrocele repair. Subjects were allocated to receive liposomal bupivacaine (intervention) or normal saline placebo injected into the trocar paths and vaginal incision at the conclusion of the procedure. At the time of drug administration, surgeons became unblinded, but did not collect outcome data. Participants remained blinded to treatment. Surgical procedures and perioperative care were standardized. The primary outcome was the visual analog scale pain score 4 hours after discharge home. Secondary outcomes included narcotic consumption, time to first bowel movement, and pain scores collected in the mornings and evenings until postoperative day 6. The morning pain item assessed "current level of pain"; the evening items queried "current level of pain," "most intense pain today," "average pain today with activity," and "average pain today with rest." Likert scales were used to measure satisfaction with pain control at 1- and 2-week postoperative intervals. Sample size calculation deemed 52 subjects per arm necessary to detect a mean difference of 10 mm on a 100-mm visual analog scale. To account for 10% drop out, 114 participants were needed. One hundred fourteen women were enrolled. After 5 exclusions, 109 cases were analyzed: 54 women received intervention, and 55 women received placebo. Mean participant age was 52 years, and mean body mass index was 30.4 kg/m 2 . Surgical and demographic characteristics were similar, except for a slightly higher body mass index in the placebo group (31.6 vs 29.2 kg/m 2 ; P=.050), and fewer placebo arm subjects received midazolam during anesthesia induction (44 vs 52; P=.015). For the primary outcome, pain score (millimeter) 4 hours after discharge home was lower in the intervention group (3.5 vs 13.0 millimeters; P=.014). Pain scores were also lower for subjects receiving liposomal bupivacaine at other time points collected during the first three postoperative days. Furthermore, fewer subjects in the intervention group consumed narcotic medication on postoperative day 2 (12 vs 27; P=.006). There was no difference in satisfaction with pain control between groups. Side-effects experienced, rate of postoperative urinary retention, and time to first bowel movement were similar between groups. Finally, no serious adverse events were noted. Liposomal bupivacaine decreased postoperative pain scores following retropubic midurethral sling placement, though pain was low in both the intervention and placebo groups. Participants who received liposomal bupivacaine were less likely to use narcotics on postoperative day 2. For this common outpatient surgery, liposomal bupivacaine may be a beneficial addition. Given the cost of this intervention, however, future cost-effective analyses may be useful. Published by Elsevier Inc.

The efficacy of adding dexamethasone, midazolam, or epinephrine to 0.5% bupivacaine in supraclavicular brachial plexus block.

PubMed

El-Baradey, Ghada F; Elshmaa, Nagat S

2014-11-01

The aim was to assess the effectiveness of adding either dexamethasone or midazolam in comparison with epinephrine addition to 0.5% bupivacaine in supraclavicular brachial plexus block. This is a prospective randomized controlled observer-blinded study. This study was carried out in Tanta University Hospital on 60 patients of both sexes; American Society of Anesthesiologists physical Status I and II, age range from 18 to 45 years undergo elective surgery to upper limb. All patients were anesthetized with ultrasound guided supraclavicular brachial plexus block and randomly divided into three groups (each group 20 patients) Group E (epinephrine): 30 mL bupivacaine 0.5%with 1:200,000 epinephrine (5 μg/mL). Group D (dexamethasone): 30 mL bupivacaine 0.5% and dexamethasone 8 mg. Group M (midazolam): 30 ml bupivacaine 0.5% and midazolam 50 μg/kg. The primary outcome measures were onset and duration of sensory and motor block and time to first analgesic request. The windows version of SPSS 11.0.1 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented in form of mean ± standard deviation multiple analysis of variance (ANOVA) was used to compare the three groups and Scheffe test was used after ANOVA. Power of significance P < 0.05 was considered to be statistically significant. Onset of sensory and motor block was significantly rapid (P < 0.05) in Groups D and M in comparison with Group E. Time of administration of rescue analgesic, duration of sensory and motor block showed significant increase (P < 0.05) in Group D in comparison with Group M which showed significant increase (P < 0.05) in comparison with Group E. In comparison with epinephrine and midazolam addition of dexamethasone to bupivacaine had rapid onset of block and longer time to first analgesic request with fewer side-effects.

Update on ropivacaine.

PubMed

Wang, R D; Dangler, L A; Greengrass, R A

2001-12-01

Long-acting local anaesthetics are primarily used in the practice of anaesthesia, particularly in regional anaesthesia and analgesia. Ropivacaine is a new long-acting local anaesthetic that has been the focus of interest because of its increased cardiovascular safety compared with bupivacaine. Other advantages of ropivacaine over bupivacaine include a greater sensorimotor differential block and shorter elimination half-life (t(1/2)), with a lower potential for accumulation. The most important attribute of ropivacaine, however, is its increased margin of safety compared with bupivacaine when given in equal doses. Many post-marketing studies have focused on the comparisons of efficacy in blocks and toxicity profiles of bupivacaine versus ropivacaine. Recent animal toxicity studies confirm the results of original studies showing that ropivacaine has less cardiovascular toxicity than bupivacaine with respect to direct myocardial depression, success of resuscitation and arrhythmogenic potential when given in equal doses. Reduced cardiotoxicity may be a distinct characteristic of ropivacaine. A review of current literature suggests that, at clinically relevant doses, ropivacaine provides the lowest potential risk of cardiotoxicity for inadvertent intravascular injection. Studies are currently under way comparing ropivacaine with levobupivacaine, the latest addition to the group of long-acting local anaesthetics.

Circumvertical reduction mastoplasty: new considerations.

PubMed

Mottura, A Aldo

2003-01-01

The circumvertical technique is a mixture of the periareolar and the vertical techniques in which the skin resection is performed around the areola and is continued in an inverted cone that starts at the infraareolar area and ends 2-4 cm above the submammary crease. Some advantages of this technique are: The glands are removed from the inferior glandular quadrant and from the inferior borders of the lateral and medial quadrants. The areola is moved upward and attached to the gland, preserving the nursing function. There is a harmonious distribution of the pleats around the areola and at the vertical wound. The vertical suture never crosses the submammary crease. The postoperative result is acceptable. Local anesthesia with vasoconstrictor is used minimizing bleeding. Bupivacaine is also included, prolonging the anesthetic effect hours after surgery. This paper describes this simple and rapid surgery and discusses some new, previously unpublished considerations and tricks.

Analgesic efficacy of intraperitoneal administration of bupivacaine in cats.

PubMed

Benito, Javier; Monteiro, Beatriz; Lavoie, Anne-Marie; Beauchamp, Guy; Lascelles, B Duncan X; Steagall, Paulo V

2016-11-01

Objectives The aim of this study was to evaluate the analgesic efficacy of intraperitoneal (IP) bupivacaine in cats undergoing ovariohysterectomy (OVH). Methods Forty-five cats were included in a randomized, prospective, blinded study after owners' written consent was obtained. The anesthetic protocol included acepromazine-buprenorphine-propofol-isoflurane. A ventral midline incision was made and cats (n = 15/group) were administered either IP saline 0.9% (negative and positive control groups; NG and PG, respectively) or IP bupivacaine (2 mg/kg; bupivacaine group; BG). Cats in the PG received meloxicam (0.2 mg/kg SC). An OVH was performed and postoperative pain was evaluated using a dynamic interactive visual analog scale (DIVAS), the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT) for up to 8 h after the end of surgery. Postoperative sedation was evaluated using DIVAS. Rescue analgesia was provided with buprenorphine and/or meloxicam. Repeated measures linear models and a Cochran-Mantel-Haenszel test were used for statistical analysis ( P <0.05). Results There was a significant effect of treatment on the number of times rescue analgesia was administered ( P = 0.002) (PG, n = 2, 13%; NG, n = 12, 80%; BG, n = 4, 27%) with the number of rescues being higher in the NG group than in the PG ( P = 0.0004) and BG ( P = 0.02) groups. The DIVAS, MCPS and MNT were significantly different when compared with baseline values at different time points; however, data were not significantly different among groups. Conclusions and relevance Treatments PG and BG produced similar analgesia in terms of pain scores, number of times rescue analgesia was administered and MNT. Based on rescue analgesia, IP administration of bupivacaine provides analgesia in cats after OVH.

Anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin for dental anaesthesia after inferior alveolar nerve block in rats.

PubMed

Serpe, L; Franz-Montan, M; Santos, C P dos; Silva, C B da; Nolasco, F P; Caldas, C S; Volpato, M C; Paula, E de; Groppo, F C

2014-05-01

Bupivacaine is a long-acting local anaesthetic that is widely used in medicine and dentistry. The duration and intensity of its sensory blockade in animal models is increased by its inclusion in complexes with cyclodextrins. The aim of the present study was to evaluate the anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex for dental anaesthesia after inferior alveolar nerve block in rats. Thirty rats were each given an injection close to the mandibular foramen of 0.2ml of one of the following formulations: 0.5% bupivacaine alone; 0.5% bupivacaine with 1:200,000 epinephrine; and 0.5% bupivacaine-HPβCD inclusion complex (bupivacaine-HPβCD). The other sides were used as controls, with either 0.9% saline or anaesthetic-free HPβCD solution being injected. The onset, success, and duration of pulpal anaesthesia were assessed by electrical stimulation ("pulp tester") on inferior molars. Results were analysed using ANOVA (Tukey), log rank, and chi square tests (α=5%). There were no differences among the formulations in onset of anaesthesia (p=0.59) or between the bupivacaine plus epinephrine and bupivacaine plus HPβCD in duration of anaesthesia, but bupivacaine plus epinephrine gave significantly higher values than bupivacaine alone (p=0.007). Bupivacaine plus epinephrine was a better anaesthetic than bupivacaine alone (p=0.02), while Bupi-HPβCD gave intermediate results, and therefore did not differ significantly from the other 2 groups (p=0.18 with bupivacaine alone; and p=0.44 with bupivacaine plus epinephrine). The bupivacaine-HPβCD complex showed similar anaesthetic properties to those of bupivacaine with epinephrine. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Effects of surgical wound infiltration with bupivacaine on postoperative analgesia in cats undergoing bilateral mastectomy.

PubMed

Yilmaz, Özge Turna; Toydemir, T Seval Fatma; Kirşan, İsmail; Dokuzeylul, Banu; Gunay, Zeynep; Karacam, Esra

2014-12-01

The analgesic effect of wound infiltration with bupivacaine was evaluated in cats undergoing bilateral mastectomy. Twenty-one female cats with mammary gland tumors were anesthetized with propofol and oxygen-isoflurane anesthesia following premedication with atropine. In the trial group (Group I; n=11), 30 ml of saline containing 2 mg/kg of bupivacaine was infiltrated topically into the surgical wound right after removal of the mammary glands, whereas only saline solution was infiltrated in the control group (Group II; n=10). At the same time, carprofen (4 mg/kg) was also administered subcutaneously in both groups. Behavioral signs of pain were monitored during the recovery period after general anesthesia. In order to examine the behavioral changes associated with acute pain, a questionnaire was prepared and given to the owners to be completed 4 hr and then 10 hr after the operation. According to the owners' anwers to the questionnaire, a pain score was specified using a "numerical rating scale" for each cat. Although some cats showed mild to moderate pain, the pain score recorded at 4 hr after the operation was significantly lower in Group I (P<0.001). No significant difference was found at 10 hr after the operation between the groups. The incidence of vocalization, aggression and convulsion within 2 hr after the operation was also lower in Group I. In conclusion, wound infiltration with bupivacaine before incisional closure provided reliable analgesia at least 4 hr after bilateral radical mastectomy in cats.

Effects of Topical Anesthetics on Behavior, Plasma Corticosterone, and Blood Glucose Levels after Tail Biopsy of C57BL/6NHSD Mice (Mus musculus)

PubMed Central

Dudley, Emily S; Johnson, Robert A; French, DeAnne C; Boivin, Gregory P

2016-01-01

Tail biopsy is a common procedure that is performed to obtain genetic material for determining genotype of transgenic mice. The use of anesthetics or analgesics is recommended, although identifying safe and effective drugs for this purpose has been challenging. We evaluated the effects of topical 2.5% lidocaine–2.5% prilocaine cream applied to the distal tail tip at 5 or 60 min before biopsy, immersion of the tail tip for 10 seconds in ice-cold 70% ethanol just prior to biopsy, and immersion of the tail tip in 0.5% bupivacaine for 30 s after biopsy. Mice were 7, 11, or 15 d old at the time of tail biopsy. Acute behavioral responses, plasma corticosterone, and blood glucose were measured after biopsy, and body weight and performance in elevated plus maze and open-field tests after weaning. Ice-cold ethanol prior to biopsy prevented acute behavioral responses to biopsy, and both ice-cold ethanol and bupivacaine prevented elevations in corticosterone and blood glucose after biopsy. Tail biopsy with or without anesthesia did not affect body weight or performance on elevated plus maze or open-field tests. We recommend the use of ice-cold ethanol for topical anesthesia prior to tail biopsy in mice 7 to 15 d old. PMID:27423152

Effects of Topical Anesthetics on Behavior, Plasma Corticosterone, and Blood Glucose Levels after Tail Biopsy of C57BL/6NHSD Mice (Mus musculus).

PubMed

Dudley, Emily S; Johnson, Robert A; French, DeAnne C; Boivin, Gregory P

2016-01-01

Tail biopsy is a common procedure that is performed to obtain genetic material for determining genotype of transgenic mice. The use of anesthetics or analgesics is recommended, although identifying safe and effective drugs for this purpose has been challenging. We evaluated the effects of topical 2.5% lidocaine-2.5% prilocaine cream applied to the distal tail tip at 5 or 60 min before biopsy, immersion of the tail tip for 10 seconds in ice-cold 70% ethanol just prior to biopsy, and immersion of the tail tip in 0.5% bupivacaine for 30 s after biopsy. Mice were 7, 11, or 15 d old at the time of tail biopsy. Acute behavioral responses, plasma corticosterone, and blood glucose were measured after biopsy, and body weight and performance in elevated plus maze and open-field tests after weaning. Ice-cold ethanol prior to biopsy prevented acute behavioral responses to biopsy, and both ice-cold ethanol and bupivacaine prevented elevations in corticosterone and blood glucose after biopsy. Tail biopsy with or without anesthesia did not affect body weight or performance on elevated plus maze or open-field tests. We recommend the use of ice-cold ethanol for topical anesthesia prior to tail biopsy in mice 7 to 15 d old.

Intrathecal Hydromorphone and Bupivacaine Combination Therapy for Post-Laminectomy Syndrome Optimized with Patient-Activated Bolus Device.

PubMed

Hayek, Salim M; Veizi, Elias; Hanes, Michael

2016-03-01

Intrathecal (IT) pumps have become a valuable tool in managing intractable non-cancer pain. The purpose of this study was to evaluate the efficacy of using a rigorous treatment algorithm for trialing and implanting IT pumps with hydromorphone and bupivacaine in managing a more homogeneous population of post-laminectomy syndrome or failed back surgery syndrome (FBSS) patients. This is a retrospective analysis of FBSS patients with chronic intractable back pain implanted with IT pumps delivering hydromorphone and bupivacaine. A cohort of 57 (26 males, 31 females) consecutively implanted FBSS patients was analyzed. The average age at implant was 65.4 years. Average pain scores were 8.4 ± 0.2 (pre-implant), 4.9 ± 0.4 (6 months), 5.2 ± 0.5 (12 months), and 4.3 ± 0.5 (24 months). Average oral opioid doses in morphine equivalents were 56 ± 10 mg/day (pre-implant), 12.0 ± 3.5 mg/day (12 months), 15 ± 6 mg/day (24 months). Average IT hydromorphone doses were 79 ± 6.8 mcg/day (at implant), 184 ± 22 mcg/day (6 months), 329 ± 48 mcg/day (12 months), and 487 ± 80 mcg (24 months). IT hydromorphone dose escalation from baseline was 133% (6 months vs baseline), 78% (12 months vs 6 months), and 48% from 12 months to 24 months. Average IT bupivacaine doses were 5.8 ± 0.3 mg/day (implant), 9.5 ± 0.6 mg/day (6 months), 12.2 ± 0.7 mg/day (12 months), and 12.6 ± 0.9 mg/day (24 months). IT hydromorphone and bupivacaine are effective in treating chronic pain of FBSS, as demonstrated by the reduction of pain intensity and oral opioid consumption. However, an IT dose escalation phenomenon was observed, although at a reduced rate compared with what had been previously reported in the literature. It is possible that the local anesthetic combination delivered via a patient-activaed bolus device is an important factor. Despite demonstrating effectiveness, the clinical utility of myPTM-optimized IT therapy remains limited by a lack of prospective, placebo-controlled trials and comparative effectiveness research. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of epidural butorphanol and fentanyl as adjuvants in the lower abdominal surgery: A randomized clinical study

PubMed Central

Kaur, Jasleen; Bajwa, Sukhminder Jit Singh

2014-01-01

Background: Epidural opioids acting through the spinal cord receptors improve the quality and duration of analgesia along with dose-sparing effect with the local anesthetics. The present study compared the efficacy and safety profile of epidurally administered butorphanol and fentanyl combined with bupivacaine (B). Materials and Methods: A total of 75 adult patients of either sex of American Society of Anesthesiologist physical status I and II, aged 20-60 years, undergoing lower abdominal under epidural anesthesia were enrolled into the study. Patients were randomly divided into three groups of 25 each: B, bupivacaine and butorphanol (BB) and bupivacaine + fentanyl (BF). B (0.5%) 20 ml was administered epidurally in all the three groups with the addition of 1 mg butorphanol in BB group and 100 μg fentanyl in the BF group. The hemodynamic parameters as well as various block characteristics including onset, completion, level and duration of sensory analgesia as well as onset, completion and regression of motor block were observed and compared. Adverse events and post-operative visual analgesia scale scores were also noted and compared. Data was analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher's exact test. Value of P < 0.05 was considered significant and P < 0.001 as highly significant. Results: The demographic profile of patients was comparable in all the three groups. Onset and completion of sensory analgesia was earliest in BF group, followed by BB and B group. The duration of analgesia was significantly prolonged in BB group followed by BF as compared with group B. Addition of butorphanol and fentanyl to B had no effect on the time of onset, completion and regression of motor block. No serious cardio-respiratory side effects were observed in any group. Conclusions: Butorphanol and fentanyl as epidural adjuvants are equally safe and provide comparable stable hemodynamics, early onset and establishment of sensory anesthesia. Butorphanol provides a significantly prolonged post-operative analgesia. PMID:24843326

Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

PubMed Central

Yu, Xu-jiao; Zhao, Wei; Li, Yu-jie; Li, Feng-xian; Liu, Zhong-jie; Xu, Hua-li; Lai, Lu-ying; Xu, Rui; Xu, Shi-yuan

2017-01-01

Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2′,7′-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P < 0.05). There were no significant differences in mitochondrial injury and apoptosis between the bupivacaine and procaine subgroups (P > 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity. PMID:28338089

Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine).

PubMed

Nonaka, I; Takagi, A; Ishiura, S; Nakase, H; Sugita, H

1983-01-01

A single direct injection of a local anesthetic, 0.5% bupivacaine hydrochloride (BPVC) (Marcaine), into rat soleus and extensor digitorum longus (EDL) muscles produced massive fiber necrosis with extensive phagocytosis followed by rapid regeneration, predominantly in the soleus. Since the sarcoplasmic reticulum (SR) was functionally disturbed by BPVC administration as confirmed by an in vitro study, the sarcolemmal lysis seen in the early phase of degeneration was not assumed to simply result from direct damage to the plasma membrane caused by BPVC. The extracellular fluid containing a high concentration of calcium (Ca) ions then permeated into the sarcoplasm through the defective membrane resulting in hyper-contracted myofibrils. Selective damage to the Z-line, an early sign of muscle degeneration, was shown by electron microscopy and SDS gel electrophoresis (preferential loss of alpha-actinin). Administration of leupeptin, a thiol protease inhibitor, proved to be ineffective in inhibiting the necrotic process, because the BPVC induced muscle fiber breakdown was probably too acute and fulminant to demonstrate the inhibitory effect upon the degenerative process. Well preserved satellite cells, peripheral nerves, and acetylcholinesterase activity, and the absence of fibrous tissue proliferation in this system may be responsible for the extremely rapid regeneration with complete muscle fiber type differentiation. Since the sequence of fiber breakdown induced by BPVC administration was similar to that of progressive muscular dystrophy, this chemical will be one of the most useful tools for studying the pathophysiology of fiber necrosis and regeneration in diseased muscle.

Neurologic Outcomes After Low-Volume, Ultrasound-Guided Interscalene Block and Ambulatory Shoulder Surgery.

PubMed

Rajpal, Gaurav; Winger, Daniel G; Cortazzo, Megan; Kentor, Michael L; Orebaugh, Steven L

2016-01-01

Postoperative neurologic symptoms after interscalene block and shoulder surgery have been reported to be relatively frequent. Reports of such symptoms after ultrasound-guided block have been variable. We evaluated 300 patients for neurologic symptoms after low-volume, ultrasound-guided interscalene block and arthroscopic shoulder surgery. Patients underwent ultrasound-guided interscalene block with 16 to 20 mL of 0.5% bupivacaine or a mix of 0.2% bupivacaine/1.2% mepivacaine solution, followed by propofol/ketamine sedation for ambulatory arthroscopic shoulder surgery. Patients were called at 10 days for evaluation of neurologic symptoms, and those with persistent symptoms were called again at 30 days, at which point neurologic evaluation was initiated. Details of patient demographics and block characteristics were collected to assess any association with persistent neurologic symptoms. Six of 300 patients reported symptoms at 10 days (2%), with one of these patients having persistent symptoms at 30 days (0.3%). This was significantly lower than rates of neurologic symptoms reported in preultrasound investigations with focused neurologic follow-up and similar to other studies performed in the ultrasound era. There was a modest correlation between the number of needle redirections during the block procedure and the presence of postoperative neurologic symptoms. Ultrasound guidance of interscalene block with 16- to 20-mL volumes of local anesthetic solution results in a lower frequency of postoperative neurologic symptoms at 10 and 30 days as compared with investigations in the preultrasound period.

Patterns of Use of Peripheral Nerve Blocks and Trigger Point Injections for Pediatric Headache: Results of a survey of the American Headache Society Pediatric & Adolescent Section

PubMed Central

Szperka, Christina L.; Gelfand, Amy A.; Hershey, Andrew D.

2016-01-01

Objective To describe current patterns of use of nerve blocks and trigger point injections for treatment of pediatric headache. Background Peripheral nerve blocks are often used to treat headaches in adults and children, but the available studies and practice data from adult headache specialists have shown wide variability in diagnostic indications, sites injected, and medication(s) used. The purpose of this study was to describe current practice patterns in the use of nerve blocks and trigger point injections for pediatric headache disorders. Methods A survey was created in REDCap, and sent via email to the 82 members of the Pediatric & Adolescent Section of the American Headache Society in June 2015. The survey queried about current practice and use of nerve blocks, as well as respondents’ opinions regarding gaps in the evidence for use of nerve blocks in this patient population. Results Forty-one complete, 5 incomplete, and 3 duplicate responses were submitted (response rate complete 50%). Seventy-eight percent of the respondents identified their primary specialty as Child Neurology, and 51% were certified in headache medicine. Twenty-six (63%) respondents perform nerve blocks themselves, and 7 (17%) refer patients to another provider for nerve blocks. Chronic migraine with status migrainosus was the most common indication for nerve blocks (82%), though occipital neuralgia (79%), status migrainosus (73%), chronic migraine without flare (70%), post-traumatic headache (70%), and new daily persistent headache (67%) were also common indications. The most commonly selected clinically meaningful response for status migrainosus was ≥50% reduction in severity, while for chronic migraine this was a ≥50% decrease in frequency at 4 weeks. Respondents inject the following locations: 100% inject the greater occipital nerve, 69% lesser occipital nerve, 50% supraorbital, 46% trigger point injections, 42% auriculotemporal, and 34% supratrochlear. All respondents used local anesthetic, while 12 (46%) also use corticosteroid (8 bupivacaine only, 4 each lidocaine + bupivacaine, lidocaine + corticosteroid, bupivacaine + corticosteroid, lidocaine + bupivacaine + corticosteroid, and 2 lidocaine only). Conclusion Despite limited evidence, nerve blocks are commonly used by pediatric headache specialists. There is considerable variability among clinicians as to injection site(s) and medication selection, indicating a substantial gap in the literature to guide practice, and supporting the need for further research in this area. PMID:27731894

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ultrasound guided transversus abdominis plane vs surgeon administered intraoperative regional field infiltration with bupivacaine for early postoperative pain control in children undergoing open pyeloplasty.

PubMed

Lorenzo, Armando J; Lynch, Johanne; Matava, Clyde; El-Beheiry, Hossam; Hayes, Jason

2014-07-01

Regional analgesic techniques are commonly used in pediatric urology. Ultrasound guided transversus abdominis plane block has recently gained popularity. However, there is a paucity of information supporting a benefit over regional field infiltration. We present a parallel group, randomized, controlled trial evaluating ultrasound guided transversus abdominis plane block superiority over surgeon delivered regional field infiltration for children undergoing open pyeloplasty at a tertiary referral center. Following ethics board approval and registration, children 0 to 6 years old were recruited and randomized to undergo perioperative transversus abdominis plane block or regional field infiltration for early post-pyeloplasty pain control. General anesthetic delivery, surgical technique and postoperative analgesics were standardized. A blinded assessor regularly captured pain scores in the recovery room using the FLACC (Face, Legs, Activity, Cry, Consolability) scale. The primary outcome was the need for rescue morphine administration based on a FLACC score of 3 or higher. Two pediatric urologists performed 57 pyeloplasties during a 2.5-year period, enrolling 32 children (16 in each group, balanced for age and weight). There were statistically significant differences in the number of children requiring rescue morphine administration (13 of 16 receiving transversus abdominis plane block and 6 of 16 receiving regional field infiltration, p = 0.011), mean ± SD total morphine consumption (0.066 ± 0.051 vs 0.028 ± 0.040 mg/kg, p = 0.021) and mean ± SD pain scores (5 ± 5 vs 2 ± 3, p = 0.043) in the recovery room, in favor of surgeon administered regional field infiltration. No local anesthetic specific adverse events were noted. Ultrasound guided transversus abdominis plane block is not superior to regional field infiltration with bupivacaine as a strategy to minimize early opioid requirements following open pyeloplasty in children. Instead, our data suggest that surgeon delivered regional field infiltration provides better pain control. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity.

PubMed

Li, Yu-Jie; Zhao, Wei; Yu, Xu-Jiao; Li, Feng-Xian; Liu, Zi-Ting; Li, Le; Xu, Shi-Yuan

2017-01-01

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury.

Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity

PubMed Central

Zhao, Wei; Yu, Xu-jiao; Li, Feng-xian; Liu, Zi-ting

2017-01-01

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury. PMID:28751934

Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine.

PubMed

Rodrigues da Silva, Gustavo H; Ribeiro, Lígia N M; Mitsutake, Hery; Guilherme, Viviane A; Castro, Simone R; Poppi, Ronei J; Breitkreitz, Márcia C; de Paula, Eneida

2017-08-30

The short time of action and systemic toxicity of local anaesthetics limit their clinical application. Bupivacaine is the most frequently used local anaesthetic in surgical procedures worldwide. The discovery that its S(-) enantiomeric form is less toxic than the R(+) form led to the introduction of products with enantiomeric excess (S75:R25 bupivacaine) in the market. Nevertheless, the time of action of bupivacaine is still short; to overcome that, bupivacaine S75:R25 (BVC S75 ) was encapsulated in nanostructured lipid carriers (NLC). In this work, we present the development of the formulation using chemometric tools of experimental design to study the formulation factors and Raman mapping associated with Classical Least Squares (CLS) to study the miscibility of the solid and the liquid lipids. The selected formulation of the nanostructured lipid carrier containing bupivacaine S75:R25 (NLC BVC ) was observed to be stable for 12 months under room conditions regarding particle size, polydispersion, Zeta potential and encapsulation efficiency. The characterisation by DSC, XDR and TEM confirmed the encapsulation of BVC S75 in the lipid matrix, with no changes in the structure of the nanoparticles. The in vivo analgesic effect elicited by NLC BVC was twice that of free BVC S75 . Besides improving the time of action , no statistical difference in the blockage of the sciatic nerve of rats was found between 0.125% NLC BVC and 0.5% free BVC S75 . Therefore, the formulation allows a reduction in the required anaesthesia dose, decreasing the systemic toxicity of bupivacaine, and opening up new possibilities for different clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Post-operative analgesic effect of dexmedetomidine administration in wound infiltration for abdominal hysterectomy: A randomised control study

PubMed Central

Singh, Swati; Prasad, Chandrakant

2017-01-01

Background and Aims: Local infiltration of the surgical wound is one of the important components of multimodal analgesia for post-operative pain relief. This study determines the post-operative analgesic effect of addition of dexmedetomidine to bupivacaine for local infiltration of the surgical wound. Methods: Sixty women belonging to American Society of Anesthesiologists’ Grade 1 or 2 posted for abdominal hysterectomy were randomly allocated to Group I (control group) where patients received wound infiltration with 30 mL 0.25% bupivacaine at the end of surgery, or Group II, where patients received wound infiltration with 1.0 μg/kg dexmedetomidine diluted in 30 mL 0.25% bupivacaine. The primary objective of the study was to assess post-operative pain scores. Number of patients requiring rescue analgesia and total morphine consumption during 24 h after surgery were also recorded. Statistical significance for analgesic requirement was determined by one-way analysis of variance. Results: Pain scores were lower at rest for 12 h and on cough for 6 h in Group II (<0.01). All patients in Group I required supplemental morphine compared to only 3 patients in Group II (P < 0.003). Post-operative analgesia requirement was significantly less in patients receiving dexmedetomidine in wound infiltration compared to patients receiving bupivacaine alone (P < 0.001). Conclusions: Wound infiltration of dexmedetomidine with bupivacaine provides superior pain relief compared to bupivacaine alone. PMID:28655956

A physiologically based pharmacokinetic (PBPK) model for predicting the efficacy of drug overdose treatment with liposomes in man.

PubMed

Howell, Brett A; Chauhan, Anuj

2010-08-01

Physiologically based pharmacokinetic (PBPK) models were developed for design and optimization of liposome therapy for treatment of overdoses of tricyclic antidepressants and local anesthetics. In vitro drug-binding data for pegylated, anionic liposomes and published mechanistic equations for partition coefficients were used to develop the models. The models were proven reliable through comparisons to intravenous data. The liposomes were predicted to be highly effective at treating amitriptyline overdoses, with reductions in the area under the concentration versus time curves (AUC) of 64% for the heart and brain. Peak heart and brain drug concentrations were predicted to drop by 20%. Bupivacaine AUC and peak concentration reductions were lower at 15.4% and 17.3%, respectively, for the heart and brain. The predicted pharmacokinetic profiles following liposome administration agreed well with data from clinical studies where protein fragments were administered to patients for overdose treatment. Published data on local cardiac function were used to relate the predicted concentrations in the body to local pharmacodynamic effects in the heart. While the results offer encouragement for future liposome therapies geared toward overdose, it is imperative to point out that animal experiments and phase I clinical trials are the next steps to ensuring the efficacy of the treatment. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Comparison thoracic epidural and intercostal block to improve ventilation parameters and reduce pain in patients with multiple rib fractures.

PubMed

Hashemzadeh, Shahryar; Hashemzadeh, Khosrov; Hosseinzadeh, Hamzeh; Aligholipour Maleki, Raheleh; Golzari, Samad E J; Golzari, Samad

2011-01-01

Chest wall blunt trauma causes multiple rib fractures and will often be associated with significant pain and may compromise ventilator mechanics. Analgesia has great roll in rib fracture therapies, opioid are useful, but when used as sole agent may require such high dose that they produce respiratory depression, especially in elderly .the best analgesia for a severe chest wall injury is a continuous epidural infusion of local anesthetic. This provides complete analgesia allowing inspiration and coughing without of the risk of respiratory depression. sixty adult patients who with multiple rib fractures were enrolled in this study. They were divided into Group A or thoracic epidural with bupivacaine 0.125 % +1mg/5ml morphine and group B or intercostal block with 0.25% bupivacaine. The patients were assessed through ICU and hospital stay length, ventilation function tests. Pain score among the patients was measured with verbal rating scale, before and after administration of the analgesia. We found a significant improvement in ventilatory function tests during the 1st, 2nd, and 3rd days after epidural analgesia compared with the intercostal block (P < 0.004). Changes in the visual Analogue Scale were associated with marked improvement regarding pain at rest and pain caused by coughing and deep breathing in group A compared group B... ICU and hospital stay markedly reduced in Group A. thoracic epidural analgesia is superior to intercostals block regarding pain relief of rib fractures. Patients who received epidural analgesia had significantly lower pain scores at all studied times.

Efficacy of Periarticular Injection With a Long-Acting Local Analgesic in Joint Arthroplasty.

PubMed

Barrington, John W

2015-10-01

Attention to patient satisfaction is critical in today's health care environment-satisfaction surveys inform the development of hospital performance standards and can influence an institution's rankings and reimbursement. The effectiveness of postoperative pain management can affect clinical outcomes and also influence the patient's perception of the overall surgical experience. Ample clinical- trial data now exist that demonstrate the benefits of periarticular injections as part of a multimodal regimen in patients undergoing joint arthroplasty. One option that surgeons now use widely is bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc), a long-acting local analgesic that the orthopedic surgeon can administer intraoperatively. The US Food and Drug Administration has approved liposomal bupivacaine for injection into the surgical site to produce postsurgical analgesia. The safety and efficacy of liposomal bupivacaine has been demonstrated in clinical studies in multiple types of surgical procedure, including double-blind, randomized, controlled clinical trials that involved over 1300 patients. In a case-control study comparing clinical and economic parameters before and after the introduction of liposomal bupivacaine as a component of the multimodal perioperative pain regimen for total joint arthroplasty, liposomal bupivacaine provided improved overall pain scores, an increase in patients reporting a pain score of 0, increased patient satisfaction, decreased length of stay, and a decrease in overall costs.

Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?

PubMed

Casati, Andrea; Putzu, Marta

2005-06-01

Two new, long-acting local anaesthetics have been developed after the evidence of bupivacaine-related severe toxicity: levobupivacaine and ropivacaine. Both these agents are pure left-isomers and, based on their three-dimensional structure, they have less toxic potential both on the central nervous system and on the heart. Several clinical studies have evaluated their toxicology and clinical profiles: theoretically and experimentally, some differences can be seen, but the reflections of these characteristics into clinical practice have not been evident. Evaluating randomised, controlled trials that have compared these three local anaesthetics, this chapter supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences observed between the three agents are mainly related to the slightly different anaesthetic potency, with racemic bupivacaine>levobupivacaine>ropivacaine. However, the reduced toxic potential of the two pure left-isomers supports their use in those clinical situations in which the risk of systemic toxicity related to either overdosing or unwanted intravascular injection is high, such as during epidural or peripheral nerve blocks.

Enhanced Expression of WD Repeat-Containing Protein 35 via Nuclear Factor-Kappa B Activation in Bupivacaine-Treated Neuro2a Cells

PubMed Central

Huang, Lei; Kondo, Fumio; Harato, Misako; Feng, Guo-Gang; Ishikawa, Naoshisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression. PMID:24466034

Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

PubMed Central

Sung, Hui-Jin; Ok, Seong-Ho; Sohn, Jin-Young; Son, Yong Hyeok; Kim, Jun Kyu; Lee, Soo Hee; Han, Jeong Yeol; Lim, Dong Hoon; Shin, Il-Woo; Lee, Heon-Keun; Chung, Young-Kyun; Choi, Mun-Jeoung; Sohn, Ju-Tae

2012-01-01

Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2 = 0.9563; P < 0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa. PMID:22778542

Treatment of local-anesthetic toxicity with lipid emulsion therapy.

PubMed

Burch, Melissa S; McAllister, Russell K; Meyer, Tricia A

2011-01-15

The use of lipid emulsion to treat local-anesthetic toxicity is discussed. Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia. There is increasing evidence that lipid emulsion may be an effective treatment to reverse the cardiac and neurologic effects of local-anesthetic toxicity. A literature search identified seven case reports of local-anesthetic toxicity in which lipid emulsion was used. Lipid emulsion was found to be successful in the treatment of local-anesthetic toxicity associated with various regional anesthetic techniques and multiple local anesthetics. The majority of patients in the case reports reviewed were unresponsive to initial management of local-anesthetic toxicity with standard resuscitative measures, but all recovered completely after receiving lipid emulsion therapy. The initial dose of lipid emulsion administered varied among the case reports, as well as whether a lipid emulsion infusion was started and at what point during resuscitation. Based on the case reports reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min as soon as local-anesthetic toxicity is suspected seems most beneficial. The pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic toxicity has not been fully elucidated but likely involves increasing metabolism, distribution, or partitioning of the local anesthetic away from receptors into lipid within tissues. Lipid emulsion has been reported useful in the treatment of systemic toxicity caused by local anesthetics. The mechanism of effect is unclear, and evidence for the benefit of lipid therapy in humans is from case reports only.

Lipid Emulsion for Local Anesthetic Systemic Toxicity

PubMed Central

Ciechanowicz, Sarah; Patil, Vinod

2012-01-01

The accidental overdose of local anesthetics may prove fatal. The commonly used amide local anesthetics have varying adverse effects on the myocardium, and beyond a certain dose all are capable of causing death. Local anesthetics are the most frequently used drugs amongst anesthetists and although uncommon, local anaesthetic systemic toxicity accounts for a high proportion of mortality, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade, there has been convincing evidence of intravenous lipid emulsions as a rescue in local anesthetic-cardiotoxicity, and anesthetic organisations, over the globe have developed guidelines on the use of this drug. Despite this, awareness amongst practitioners appears to be lacking. All who use local anesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using local anesthetics, and the initial management of systemic toxicity with intravenous lipid emulsion. In this paper we intend to discuss the pharmacology and pathophysiology of local anesthetics and toxicity, and the rationale for lipid emulsion therapy. PMID:21969824

Inadvertent intrathecal injection of labetalol in a patient undergoing post-partum tubal ligation.

PubMed

Balestrieri, P J; Hamza, M S; Ting, P H; Blank, R S; Grubb, C T

2005-10-01

After receiving a continuous spinal anesthetic for labor following an inadvertent dural puncture with a 17-gauge epidural needle, a morbidly obese parturient underwent post-partum tubal ligation 12 h after vaginal delivery. The patient received a total of 2 mL of 0.75% hyperbaric bupivacaine for the surgery. In response to moderate hypertension the patient received intravenous labetalol hydrochloride 20 mg. She subsequently was inadvertently administered approximately 15 mg of labetalol through the spinal catheter. The spinal catheter was removed immediately after the procedure. She suffered no apparent adverse neurologic effects.

Combined spinal epidural anesthesia during colon surgery in a high-risk patient: case report.

PubMed

Imbelloni, Luiz Eduardo; Fornasari, Marcos; Fialho, José Carlos

2009-01-01

Combined spinal epidural anesthesia (CSEA) has advantages over single injection epidural or subarachnoid blockades. The objective of this report was to present a case in which segmental subarachnoid block can be an effective technique for gastrointestinal surgery with spontaneous respiration. Patient with physical status ASA III, with diabetes mellitus type II, hypertension, and chronic obstructive pulmonary disease was scheduled for resection of a right colon tumor. Combined spinal epidural block was performed in the T5-T6 space and 8 mg of 0.5% isobaric bupivacaine with 50 microg of morphine were injected in the subarachnoid space. The epidural catheter (20G) was introduced four centimeters in the cephalad direction. Sedation was achieved with fractionated doses of 1 mg of midazolam (total of 6 mg). A bolus of 25 mg of 0.5% bupivacaine was administered through the catheter two hours after the subarachnoid block. Vasopressors and atropine were not used. This case provides evidence that segmental spinal block can be the anesthetic technique used in gastrointestinal surgeries with spontaneous respiration.

Pitfalls in chronobiology: a suggested analysis using intrathecal bupivacaine analgesia as an example.

PubMed

Shafer, Steven L; Lemmer, Bjoern; Boselli, Emmanuel; Boiste, Fabienne; Bouvet, Lionel; Allaouchiche, Bernard; Chassard, Dominique

2010-10-01

The duration of analgesia from epidural administration of local anesthetics to parturients has been shown to follow a rhythmic pattern according to the time of drug administration. We studied whether there was a similar pattern after intrathecal administration of bupivacaine in parturients. In the course of the analysis, we came to believe that some data points coincident with provider shift changes were influenced by nonbiological, health care system factors, thus incorrectly suggesting a periodic signal in duration of labor analgesia. We developed graphical and analytical tools to help assess the influence of individual points on the chronobiological analysis. Women with singleton term pregnancies in vertex presentation, cervical dilation 3 to 5 cm, pain score >50 mm (of 100 mm), and requesting labor analgesia were enrolled in this study. Patients received 2.5 mg of intrathecal bupivacaine in 2 mL using a combined spinal-epidural technique. Analgesia duration was the time from intrathecal injection until the first request for additional analgesia. The duration of analgesia was analyzed by visual inspection of the data, application of smoothing functions (Supersmoother; LOWESS and LOESS [locally weighted scatterplot smoothing functions]), analysis of variance, Cosinor (Chronos-Fit), Excel, and NONMEM (nonlinear mixed effect modeling). Confidence intervals (CIs) were determined by bootstrap analysis (1000 replications with replacement) using PLT Tools. Eighty-two women were included in the study. Examination of the raw data using 3 smoothing functions revealed a bimodal pattern, with a peak at approximately 0630 and a subsequent peak in the afternoon or evening, depending on the smoother. Analysis of variance did not identify any statistically significant difference between the duration of analgesia when intrathecal injection was given from midnight to 0600 compared with the duration of analgesia after intrathecal injection at other times. Chronos-Fit, Excel, and NONMEM produced identical results, with a mean duration of analgesia of 38.4 minutes (95% CI: 35.4-41.6 minutes), an 8-hour periodic waveform with an amplitude of 5.8 minutes (95% CI: 2.1-10.7 minutes), and a phase offset of 6.5 hours (95% CI: 5.4-8.0 hours) relative to midnight. The 8-hour periodic model did not reach statistical significance in 40% of bootstrap analyses, implying that statistical significance of the 8-hour periodic model was dependent on a subset of the data. Two data points before the change of shift at 0700 contributed most strongly to the statistical significance of the periodic waveform. Without these data points, there was no evidence of an 8-hour periodic waveform for intrathecal bupivacaine analgesia. Chronobiology includes the influence of external daily rhythms in the environment (e.g., nursing shifts) as well as human biological rhythms. We were able to distinguish the influence of an external rhythm by combining several novel analyses: (1) graphical presentation superimposing the raw data, external rhythms (e.g., nursing and anesthesia provider shifts), and smoothing functions; (2) graphical display of the contribution of each data point to the statistical significance; and (3) bootstrap analysis to identify whether the statistical significance was highly dependent on a data subset. These approaches suggested that 2 data points were likely artifacts of the change in nursing and anesthesia shifts. When these points were removed, there was no suggestion of biological rhythm in the duration of intrathecal bupivacaine analgesia.

Quality of labour neuraxial analgesia and maternal satisfaction at a tertiary care teaching hospital: a prospective observational study.

PubMed

Clivatti, Jefferson; Siddiqui, Naveed; Goel, Akash; Shaw, Melissa; Crisan, Ioana; Carvalho, Jose C A

2013-08-01

Current labour analgesia practices are evidence-based; however, such evidence often originates in controlled trials, the results of which may not be readily applicable in the context of day-to-day clinical practice. The objective of this study was to evaluate the effectiveness of and maternal satisfaction with the neuraxial labour analgesia regimen provided at a tertiary care teaching hospital. All women with a viable pregnancy who requested neuraxial analgesia for labour during November 2011 at our institution were approached to participate in this prospective study. Patients were managed as per departmental routine based on a patient-controlled epidural analgesia regimen with a maintenance solution of 0.0625% bupivacaine and fentanyl 2 μg·mL(-1). Demographic and obstetric data, characteristics of the neuraxial analgesia, pain scores, side effects, and complications were recorded. After delivery, patients completed a satisfaction questionnaire. All 332 eligible women were approached, and 294 completed the study. Most women received epidural analgesia and considered its placement comfortable. A large number of women reported having experienced pain during the first or second stages of labour (38% and 26%, respectively). Although 24.4% of women required top-ups both by nurses and physicians, adjustment in the local anesthetic maintenance concentration was made in only 7.8% of the cases. Most women (92%) were satisfied with the quality of analgesia. Unintentional dural puncture occurred in three (1%) cases, and there were no cases of intravascular catheter insertion or systemic local anesthetic toxicity. Overweight women (body mass index 25-30 kg·m(-2)) (adjusted odds ratio [AOR] = 2.56; 95% confidence interval [CI]: 1.1 to 5.97), those undergoing induced labour (AOR = 2.4; 95% CI: 1.2 to 5.2), and those requiring top-ups by the anesthesiologist (AOR = 5.08; 95% CI: 2.31 to 11.11) were associated with more dissatisfaction with pain control during the first stage of labour. Although our technique with dilute local anesthetic-opioid infusion was considered effective in previous randomized clinical trials, it did not provide sufficient labour analgesia for a large proportion of women. Nevertheless, most women were satisfied with their pain management and childbirth experience. Strategies to individualize care for labour and delivery should be readily available while providing labour analgesia.

Efficacy of 0.5% Hyperbaric Bupivacaine with Dexamethasone versus 0.5% Hyperbaric Bupivacaine alone in Spinal Anaesthesia for Patient Undergoing Lower Abdominal Urological and Lower Limb Orthopedic Surgeries.

PubMed

Haque, M M; Aleem, M A; Haque, F H; Siddique, A B; Afrose, R

2018-04-01

Spinal anaesthesia with local anaesthetics has limited duration. Different additives have been used to prolong spinal anaesthesia. The aim of this study was to determine the efficacy of adding dexamethasone to bupivacaine in spinal anaesthesia specially whether it would prolong the duration of sensory block/ surgical analgesia and post-operative analgesia/pain free period or not. This randomized, prospective, double-blind, clinical study was conducted in the Department of Anaesthesia, Analgesia and Critical Care of Combined Military Hospital, Chittagong from October 2016 to August 2017. Seventy two (72) adult patients scheduled for lower abdominal urological and lower limb orthopedic surgery under spinal anaesthesia were included. They were divided in two groups; each group comprised 36 patients to receive 20mg 0.5% hyperbaric bupivacaine (Bupivacaine group) or 15mg 0.5% hyperbaric bupivacaine plus 5mg dexamethasone (Bupivacaine-Dexamethasone/case group) intrathecally. The patients were evaluated for quality, quantity and duration of sensory block/surgical analgesia, post-operative analgesia/pain free period, blood pressure, heart rate, nausea, and vomiting or other complications. There were no significant differences in demographic data, sensory level and onset time of the sensory block between two groups. Duration of sensory block/Surgical analgesia in the bupivacaine group was 92.32±8.34 minutes and in the bupivacaine- dexamethasone/case group was 122.11±10.59 minutes which was statistically highly significant (p<0.001). The duration of post-operative analgesia/pain free period was 208.78±41.57 minutes in the bupivacaine group; whereas it was 412.82±71.51 minutes in the bupivacaine-dexamethasone/case group which was also statistically highly significant (p<0.001). The frequency of complications was not different between two groups. This study has shown that the addition of dexamethasone to bupivacaine in spinal anaesthesia significantly improved the duration of sensory block/surgical analgesia as well as post-operative analgesia/pain free period without any complications.

Cost-benefit evaluation of liposomal bupivacaine in the management of patients undergoing total knee arthroplasty.

PubMed

Kirkness, Carmen S; Asche, Carl V; Ren, Jinma; Kim, Minchul; Rainville, Edward C

2016-05-01

Results of a cost-benefit analysis of intraoperative use of liposomal bupivacaine for postsurgical pain management in patients undergoing total knee arthroplasty (TKA) are presented. In a retrospective single-site study, clinical and cost outcomes were compared in a group of 134 consecutive patients who received liposomal bupivacaine (by local infiltration) during TKA and a propensity score-matched historical cohort of 134 patients undergoing TKA who received usual care (continuous femoral nerve blockade with conventional bupivacaine delivered via elastomeric pump). Postsurgical pain scores and opioid use were similar in the two study groups; the mean total amount of nonsteroidal antiinflammatory drugs administered was lower in the liposomal bupivacaine group. Patients who received liposomal bupivacaine typically ambulated earlier than those who received usual care (22% and 3%, respectively, walked on the day of surgery; p < 0.05) and were more likely to be discharged within two days (50% versus 19%, p < 0.001); on average, liposomal bupivacaine- treated patients walked farther on the day of surgery (6.0 m versus 3.1 m, p < 0.001) and the day after surgery (63.7 m versus 25.5 m, p < 0.001) and had a shorter length of stay (LOS) (3.1 days versus 3.6 days, p < 0.03). The mean adjusted total direct hospital cost per patient was significantly lower with liposomal bupivacaine use versus usual care ($8758 versus $9213, p = 0.033). In patients undergoing TKA, intraoperative administration of liposomal bupivacaine for management of postsurgical pain was found to offer advantages over usual care, including decreased time to ambulation and reduced hospital LOS. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Intrathecal Bupivacaine Monotherapy with a Retrograde Catheter for the Management of Complex Regional Pain Syndrome of the Lower Extremity.

PubMed

McRoberts, W Porter; Apostol, Catalina; Haleem, Abdul

2016-01-01

Complex regional pain syndrome (CRPS) presents a therapeutic challenge due to its many presentations and multifaceted pathophysiology. There is no approved treatment algorithm and clinical interventions are often applied empirically. In cases of CRPS where symptoms are localized to an extremity, a targeted treatment is indicated. We describe the use of intrathecal bupivacaine monotherapy, delivered through a retrograde catheter, in the treatment of CRPS affecting the lower extremity. The patient, a 57-year-old woman with a history of failed foot surgery, was seen in our office after 2 years of ineffective treatments with local blocks and neurolytic procedures. We advanced therapy to moderately invasive procedures with an emphasis on neuromodulation. A combined central and peripheral stimulation technique that initially provided 75% pain relief, failed to provide lasting analgesia. We proceeded with an intrathecal pump implant. Based on the results of dorsal root ganglion (DRG) mapping, L5-S1 was identified as the optimal target for therapy and a retrograde catheter was placed at this level. Various intrathecal medications were tested individually. An intrathecal morphine trial was ineffective (visual analog scale [VAS] 7), while intrathecal clonidine provided excellent pain relief (VAS 0) that was limited by severe side effects. Bupivacaine provided 100% analgesia with tolerable side effects (lower extremity weakness and minor bladder incontinence) and was selected for intrathecal infusion. After 14 months, bupivacaine treatment continued to control pain exacerbations. We conclude that CRPS patients benefit from early identification of the predominant underlying symptoms and a targeted treatment with moderately invasive techniques when less invasive techniques fail. Intrathecal bupivacaine, bupivacaine monotherapy, retrograde catheter, complex regional pain syndrome (CRPS), dual stimulation, dosal root ganglion (DRG) testing.

Levobupivacaine: a review of its use in regional anaesthesia and pain management.

PubMed

Sanford, Mark; Keating, Gillian M

2010-04-16

Levobupivacaine (Chirocaine) is a long-acting amide local anaesthetic that is effective when administered as an epidural, spinal, peripheral nerve or ocular block, or by topical application or local infiltration. In comparative trials, its clinical effects were not generally significantly different from those of bupivacaine or ropivacaine, although there was some variability in efficacy findings in different clinical populations. Levobupivacaine was generally well tolerated. Levobupivacaine provides effective anaesthesia and analgesia for a wide range of clinical populations and is a useful alternative to bupivacaine.

Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials

PubMed Central

Manchikanti, Laxmaiah; Nampiaparampil, Devi E.; Manchikanti, Kavita N.; Falco, Frank J.E.; Singh, Vijay; Benyamin, Ramsin M.; Kaye, Alan D.; Sehgal, Nalini; Soin, Amol; Simopoulos, Thomas T.; Bakshi, Sanjay; Gharibo, Christopher G.; Gilligan, Christopher J.; Hirsch, Joshua A.

2015-01-01

Background: The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups. Methods: Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV). Results: A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone. Conclusion: This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone. PMID:26005584

Efficacy of premixed versus sequential administration of clonidine as an adjuvant to hyperbaric bupivacaine intrathecally in cesarean section

PubMed Central

Sachan, Prachee; Kumar, Nidhi; Sharma, Jagdish Prasad

2014-01-01

Background: Density of the drugs injected intrathecally is an important factor that influences spread in the cerebrospinal fluid. Mixing adjuvants with local anesthetics (LA) alters their density and hence their spread compared to when given sequentially in seperate syringes. Aims: To evaluate the efficacy of intrathecal administration of hyperbaric bupivacaine (HB) and clonidine as a mixture and sequentially in terms of block characteristics, hemodynamics, neonatal outcome, and postoperative pain. Setting and Design: Prospective randomized single blind study at a tertiary center from 2010 to 2012. Materials and Methods: Ninety full-term parturient scheduled for elective cesarean sections were divided into three groups on the basis of technique of intrathecal drug administration. Group M received mixture of 75 μg clonidine and 10 mg HB 0.5%. Group A received 75 μg clonidine after administration of 10 mg HB 0.5% through separate syringe. Group B received 75 μg clonidine before HB 0.5% (10 mg) through separate syringe. Statistical analysis used: Observational descriptive statistics, analysis of variance with Bonferroni multiple comparison post hoc test, and Chi-square test. Results: Time to achieve complete sensory and motor block was less in group A and B in which drugs were given sequentially. Duration of analgesia lasted longer in group B (474.3 ± 20.79 min) and group A (472.50 ± 22.11 min) than in group M (337 ± 18.22 min) with clinically insignificant influence on hemodynamic parameters and sedation. Conclusion: Sequential technique reduces time to achieve complete sensory and motor block, delays block regression, and significantly prolongs the duration of analgesia. However, it did not matter much whether clonidine was administered before or after HB. PMID:25886098

Effects of opioid and nonopioid analgesics on canine wheal formation and cultured human mast cell degranulation.

PubMed

Schmidt-Rondon, Eric; Wang, Zhenping; Malkmus, Shelle A; Di Nardo, Anna; Hildebrand, Keith; Page, Linda; Yaksh, Tony L

2018-01-01

Mast cell (MC) degranulation has been implicated in the side effect profile of a variety of clinically useful agents. Thus, after intrathecal delivery, formation of space-occupying, meningeally-derived masses may be related to local MC degranulation. We systematically characterized degranulating effects of opioid and nonopioid analgesics on cutaneous flares in the dog and in primary human MC (hMC) cultures. Dogs were anesthetized with IV propofol and received intradermal (ID) injections (50μL). Flare diameters were measured at 30min. Drugs showing flare responses were tested after intramuscular (IM) cromolyn (10mg/kg), a MC stabilizer. Human primary MCs (human cord blood CD34 + /CD45 + cells) were employed and β-hexosaminidase in cell-free supernatants were measured to assess degranulation. A significant skin flare for several classes of agents was observed including opioids, ziconotide, ketamine, ST-91, neostigmine, adenosine, bupivacaine, lidocaine, MK-801 and 48/80. Tizanidine, fentanyl, alfentanil, gabapentin and baclofen produced no flare. Flare produced by all ID agents, except adenosine, bupivacaine and lidocaine, was reduced by cromolyn. Naloxone had no effect upon opiate or 48/80 evoked flares. In hMC studies, 48/80 resulted in a concentration-dependent release of β-hexosaminidase. The rank order of drug-induced hMC β-hexosaminidase release was similar to that for flares. A variety of therapeutically useful drugs degranulate MCs. This action may account for side effects such as the intrathecal granuloma resulting from spinally-delivered opioids. This degranulating effect may be useful in predicting potential intrathecal toxicity in the development of novel agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Looking at hydrogen motions in confinement. The uniqueness of Quasi-Elastic Neutron Scattering

NASA Astrophysics Data System (ADS)

Fischer, J.; Tsapatsaris, N.; de Paula, E.; Bordallo, H. N.

2014-09-01

Why in a barren and hot desert, clays can contain a significant fraction of water? Why does concrete crack? How can we demonstrate that complexation of a drug does not alter its conformation in a way that affects its functionality? In this paper we present results on various studies using Quasi-Elastic Neutron Scattering aimed at clarifying these questions. To allow for a better understanding of neutron scattering, a brief introduction to the basics of its theory is presented. Following the theoretical part, experimental results dealing with the effects of confinement on the water dynamics caused by the interfaces in clays and the nano- and micro-pores of concrete are reviewed in detail. At the end, recent Quasi-Elastic Neutron Scattering investigations on the complexation of the local anesthetics Bupivacaine (BVC.HCl, C18H28N20.HCl.H2O) and Ropivacaine (RVC.HCl, C17H26N20.HCl.H2O) into the cyclic β-cyclodextrin oligosaccharide are presented. To conclude, the perspectives that the European Spallation Source brings to this subject are discussed.

Survey of external cephalic version for breech presentation and neuraxial blockade use.

PubMed

Weiniger, Carolyn F; Sultan, Pervez; Dunn, Ashley; Carvalho, Brendan

2016-11-01

Neuraxial blockade may increase external cephalic version (ECV) success rates. This survey aimed to assess the frequency and characteristics of neuraxial blockade used to facilitate ECV. We surveyed Society for Obstetric Anesthesia and Perinatology members regarding ECV practice using a 15-item survey developed by 3 obstetric anesthesiologists and tested for face validity. The survey was e-mailed in January 2015 and again in February 2015 to the 1056 Society of Obstetric Anesthesiology and Perinatology members. We present descriptive statistics of responses. Our survey response rate was 322 of 1056 (30.5%). Neuraxial blockade was used for ECV always by 18 (5.6%), often by 52 (16.1%), sometimes by 98 (30.4%), rarely by 78 (24.2%), and never by 46 (14.3%) of respondents. An anesthetic sensory block target was selected by 141 (43.8%) respondents, and analgesic by 102 (31.7%) respondents. Epidural drug doses ranged widely, including sufentanil 5-25 μg; lidocaine 1% or 2% 10-20 mL, bupivacaine 0.0625% to 0.5% 6-15 mL, and ropivacaine 0.2% 20 mL. Intrathecal bupivacaine was used by 182 (56.5%) respondents; the most frequent doses were 2.5 mg used by 24 (7.5%), 7.5 mg used by 35 (10.9%), and 12 mg used by 30 (9.3%). Neuraxial blockade is not universally offered to facilitate ECV, and there is wide variability in neuraxial blockade techniques, in drugs and doses administered, and in the sensory blockade (anesthetic or analgesic) targeted. Future studies need to evaluate and remove barriers to allow for more widespread use of neuraxial blockade for pain relief and to optimize ECV success rates. Copyright © 2016 Elsevier Inc. All rights reserved.

A rapid recovery program: early home and pain free.

PubMed

Lombardi, Adolph V; Berend, Keith R; Adams, Joanne B

2010-09-07

Enhancement of our perioperative pain management protocols has resulted in accelerated rehabilitation. At our facility, the majority of patients undergoing total and partial knee arthroplasty are treated with a single-shot spinal anesthetic consisting of a combination of bupivacaine and duramorph. The bupivacaine affords the immediate perioperative anesthetic while the duramorph results in sustained analgesia for a period of 12 to 24 hours. We use intra-articular injections delivered directly into the soft tissue of the knee. Our current intra-articular injection is 60 mL of 0.5% ropivacaine with 0.5 mg of epinephrine. In patients with a normal renal function, 30 mg of ketorolac is added. The injection is administered throughout all of the soft tissues in and around the knee. Prophylactic antiemetics are administered in the form of dexamethasone, ondansetron, and a scopolamine patch. The use of this perioperative anesthesia provides effective pain relief with no motor blockade. Patients are able to participate in physiotherapy within several hours of the operative procedure, performing active range of motion and ambulating with assistive devices. Patients with no significant cardiovascular history are given celecoxib preoperatively, which is continued for approximately 2 weeks postoperatively. Additionally, all patients are treated with oxycodone, either preoperatively or within 2 hours of arrival to the floor postoperatively. Patients younger than 70 years are given 20 mg of oxycodone while those older than 70 years are given 10 mg of oxycodone. The oxycodone is continued for the first 24 hours of the hospital stay. Patients are then managed with oxycodone and hydrocodone. Length of stay has decreased and currently averages <2 days. Copyright 2010, SLACK Incorporated.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

PubMed Central

Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

2002-01-01

Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

Local Anesthetic-Induced Neurotoxicity

PubMed Central

Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

2016-01-01

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor. PMID:26959012

Local Anesthetic-Induced Neurotoxicity.

PubMed

Verlinde, Mark; Hollmann, Markus W; Stevens, Markus F; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

2016-03-04

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor.

[Combined spinal epidural anesthesia during endoprosthetic surgeries for bone tumors in old-age children].

PubMed

Matinian, N V; Saltanov, A I

2005-01-01

Thirty-five patients (ASA II-III) aged 12 to 17 years, diagnosed as having osteogenic sarcoma and Ewing's sarcoma localizing in the femur and tibia, were examined. Surgery was performed as sectoral resection of the affected bone along with knee joint endoprosthesis. Surgical intervention was made under combined spinal and epidural anesthesia (CSEA) with sedation, by using the methods for exact dosing of propofol (6-4 mg/kg x h). During intervention, a child's respiration remains is kept spontaneous with oxygen insufflation through a nasal catheter. CSEA was performed in two-segmental fashion. The epidural space was first catheterized. After administration of a test dose, 0.5% marcaine spinal was injected into dermatomas below the subarachnoidal space, depending on body weight (3.0-4.0 ml). Sensory blockade developed following 3-5 min and lasted 90-120 min, thereafter a local anesthetic (bupivacaine) or its mixture plus promedole was epidurally administered. ??Anesthesia was effective in all cases, motor blockade. During surgery, there was a moderate arterial hypotension that did not require the use of vasopressors. The acid-alkali balance suggested the adequacy of spontaneous respiration. The only significant complication we observed was atony of the bladder that requires its catheterization till the following day. An epidural catheter makes it possible to effect adequate postoperative analgesia.

Minimum anesthetic volume in regional anesthesia by using ultrasound-guidance.

PubMed

Di Filippo, Alessandro; Falsini, Silvia; Adembri, Chiara

2016-01-01

The ultrasound guidance in regional anesthesia ensures the visualization of needle placement and the spread of Local Anesthetics. Over the past few years there was a substantial interest in determining the Minimum Effective Anesthetic Volume necessary to accomplish surgical anesthesia. The precise and real-time visualization of Local Anesthetics spread under ultrasound guidance block may represent the best requisite for reducing Local Anesthetics dose and Local Anesthetics-related effects. We will report a series of studies that have demonstrated the efficacy of ultrasound guidance blocks to reduce Local Anesthetics and obtain surgical anesthesia as compared to block performed under blind or electrical nerve stimulation technique. Unfortunately, the results of studies are widely divergent and not seem to indicate a dose considered effective, for each block, in a definitive way; but it is true that, through the use of ultrasound guidance, it is possible to reduce the dose of anesthetic in the performance of anesthetic blocks. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

PubMed Central

Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

2014-01-01

Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

Sensory blockade after thoracic paravertebral injection of ropivacaine or bupivacaine.

PubMed

Hura, G; Knapik, P; Misiołek, H; Krakus, A; Karpe, J

2006-08-01

No clinical trials comparing the characteristics of sensory blockade caused by various local anaesthetics in thoracic paravertebral blockade have been published. The aim of this prospective study was a clinical assessment of sensory blockade after paravertebral injection of ropivacaine or bupivacaine in patients undergoing modified radical mastectomy. Seventy ASA I-II patients were randomized to receive a single injection of ropivacaine 0.5% (n = 35) or bupivacaine 0.5% (n = 35) at the T4 level. General anaesthesia with propofol and fentanyl was provided during the procedure and patients were not intubated. The following parameters were analysed: duration and dynamics of the sensory blockade and the patient's and surgeon's assessment. Both ropivacaine and bupivacaine provided a similar level of analgesia. Ropivacaine was characterized by more rapid onset - after only 5 min 53% of patients in this group had the extent of sensory blockade wide enough to perform modified radical mastectomy in comparison to only 20% after bupivacaine (P 9 segments blocked) was noted more often in the ropivacaine group (88% vs. 65%, P < 0.05), lasted longer and appeared to be wider than sensory blockade produced by bupivacaine. Regression of sensory blockade was initially similar, but after 24 h sensory blockade in the ropivacaine group still had a potential to provide analgesia for modified radical mastectomy in 81% of patients in comparison to only 50% of such patients in the bupivacaine group (P < 0.05). Degree of postoperative pain, performance of the cardiovascular system, consumption of medications and complications were all similar between the study groups. Both agents provide satisfactory conditions for mastectomy, but ropivacaine seems to be superior to bupivacaine for thoracic paravertebral blockade during breast cancer surgery.

[A case of emergency surgery in a patient with bronchial asthma under continuous spinal anesthesia].

PubMed

Noda, Keiichi; Ryo, Kenshu; Nakamoto, Ai

2003-10-01

A 78-year-old male, observed for bronchial asthma, underwent two emergency operations within eight days. The first operation was performed under general anesthesia with tracheal intubation. Anesthesia was maintained by sevoflurane-oxygen and continuous infusion of propofol in combination with epidural injection of lidocaine. During the operation, respiratory sound was almost clear. But wheezing occurred as he awoke after discontinuation of the anesthetics. He needed ventilatory support for three days for status asthmatics. The second operation was performed under continuous spinal anesthesia using hypobaric tetracaine and hyperbaric bupivacaine. No ventilatory support was necessary after the operation and he was discharged uneventfully.

The Thermodynamics of General and Local Anesthesia

PubMed Central

Græsbøll, Kaare; Sasse-Middelhoff, Henrike; Heimburg, Thomas

2014-01-01

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates, and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. Using this analysis, we are able to describe experimentally observed calorimetric profiles and predict the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff effect of long-chain alcohols and the additivity of the effect of general and local anesthetics. PMID:24853743

The Thermodynamics of General and Local Anesthesia

NASA Astrophysics Data System (ADS)

Græsbøll, Kaare; Sasse-Middelhoff, Henrike; Heimburg, Thomas

2014-05-01

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. This analysis is able to describe experimentally observed calorimetric profiles and permits prediction of the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff-effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.

Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel.

PubMed

Muroi, Yukiko; Chanda, Baron

2009-01-01

Local anesthetics block sodium channels in a state-dependent fashion, binding with higher affinity to open and/or inactivated states. Gating current measurements show that local anesthetics immobilize a fraction of the gating charge, suggesting that the movement of voltage sensors is modified when a local anesthetic binds to the pore of the sodium channel. Here, using voltage clamp fluorescence measurements, we provide a quantitative description of the effect of local anesthetics on the steady-state behavior of the voltage-sensing segments of a sodium channel. Lidocaine and QX-314 shifted the midpoints of the fluorescence-voltage (F-V) curves of S4 domain III in the hyperpolarizing direction by 57 and 65 mV, respectively. A single mutation in the S6 of domain IV (F1579A), a site critical for local anesthetic block, abolished the effect of QX-314 on the voltage sensor of domain III. Both local anesthetics modestly shifted the F-V relationships of S4 domain IV toward hyperpolarized potentials. In contrast, the F-V curve of the S4 domain I was shifted by 11 mV in the depolarizing direction upon QX-314 binding. These antagonistic effects of the local anesthetic indicate that the drug modifies the coupling between the voltage-sensing domains of the sodium channel. Our findings suggest a novel role of local anesthetics in modulating the gating apparatus of the sodium channel.

Randomized clinical trial of local anesthetic versus a combination of local anesthetic with self-hypnosis in the management of pediatric procedure-related pain.

PubMed

Liossi, Christina; White, Paul; Hatira, Popi

2006-05-01

A prospective controlled trial was conducted to compare the efficacy of an analgesic cream (eutectic mixture of local anesthetics, or EMLA) with a combination of EMLA with hypnosis in the relief of lumbar puncture-induced pain and anxiety in 45 pediatric cancer patients (age 6-16 years). The study also explored whether young patients can be taught and can use hypnosis independently as well as whether the therapeutic benefit depends on hypnotizability. Patients were randomized to 1 of 3 groups: local anesthetic, local anesthetic plus hypnosis, and local anesthetic plus attention. Results confirmed that patients in the local anesthetic plus hypnosis group reported less anticipatory anxiety and less procedure-related pain and anxiety and that they were rated as demonstrating less behavioral distress during the procedure. The level of hypnotizability was significantly associated with the magnitude of treatment benefit, and this benefit was maintained when patients used hypnosis independently. 2006 APA, all rights reserved

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade: a prospective, randomised pragmatic trial.

PubMed

Yadeau, J T; Goytizolo, E A; Padgett, D E; Liu, S S; Mayman, D J; Ranawat, A S; Rade, M C; Westrich, G H

2013-05-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade. A prospective, randomised pragmatic trial

PubMed Central

Goytizolo, Enrique A.; Padgett, Douglas E.; Liu, Spencer S.; Mayman, David J.; Ranawat, Amar S.; Rade, Matthew C.; Westrich, Geoffrey H.

2014-01-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine, and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR. PMID:23632672

Anesthetic management of super-morbidly obese parturients for cesarean delivery with a double neuraxial catheter technique: a case series.

PubMed

Polin, C M; Hale, B; Mauritz, A A; Habib, A S; Jones, C A; Strouch, Z Y; Dominguez, J E

2015-08-01

Parturients with super-morbid obesity, defined as body mass index greater than 50kg/m(2), represent a growing segment of patients who require anesthetic care for labor and delivery. Severe obesity and its comorbid conditions place the parturient and fetus at greater risk for pregnancy complications and cesarean delivery, as well as surgical and anesthetic complications. The surgical approach for cesarean delivery in these patients may require a supra-umbilical vertical midline incision due to a large pannus. The dense T4-level of spinal anesthesia can cause difficulties with ventilation for the obese patient during the procedure, which can be prolonged. Patients also may have respiratory complications in the postoperative period due to pain from the incision. We describe the anesthetic management of three parturients with body mass index ranging from 73 to 95kg/m(2) who had a cesarean delivery via a supra-umbilical vertical midline incision. Continuous lumbar spinal and low thoracic epidural catheters were placed in each patient for intraoperative anesthesia and postoperative analgesia, respectively. Continuous spinal catheters were dosed with incremental bupivacaine boluses to achieve surgical anesthesia. In one case, the patient required respiratory support with non-invasive positive pressure ventilation. Two cases were complicated by intraoperative hemorrhage. All patients had satisfactory postoperative analgesia with a thoracic epidural infusion. None suffered postoperative respiratory complications or postdural puncture headache. The use of a continuous lumbar spinal catheter and a low thoracic epidural provides several advantages in the anesthetic management of super-morbidly obese parturients for cesarean delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

PubMed Central

2013-01-01

Despite a long history in medical and dental application, the molecular mechanism and precise site of action are still arguable for local anesthetics. Their effects are considered to be induced by acting on functional proteins, on membrane lipids, or on both. Local anesthetics primarily interact with sodium channels embedded in cell membranes to reduce the excitability of nerve cells and cardiomyocytes or produce a malfunction of the cardiovascular system. However, the membrane protein-interacting theory cannot explain all of the pharmacological and toxicological features of local anesthetics. The administered drug molecules must diffuse through the lipid barriers of nerve sheaths and penetrate into or across the lipid bilayers of cell membranes to reach the acting site on transmembrane proteins. Amphiphilic local anesthetics interact hydrophobically and electrostatically with lipid bilayers and modify their physicochemical property, with the direct inhibition of membrane functions, and with the resultant alteration of the membrane lipid environments surrounding transmembrane proteins and the subsequent protein conformational change, leading to the inhibition of channel functions. We review recent studies on the interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol. Understanding the membrane interactivity of local anesthetics would provide novel insights into their anesthetic and cardiotoxic effects. PMID:24174934

The Combination of IV and Perineural Dexamethasone Prolongs the Analgesic Duration of Intercostal Nerve Blocks Compared with IV Dexamethasone Alone.

PubMed

Maher, Dermot P; Serna-Gallegos, Derek; Mardirosian, Rodney; Thomas, Otto J; Zhang, Xiao; McKenna, Robert; Yumul, Roya; Zhang, Vida

2017-06-01

 The use of multiple-level, single-injection intercostal nerve blocks for pain control following video-assisted thorascopic surgery (VATS) is limited by the analgesic duration of local anesthetics. This study examines whether the combination of perineural and intravenous (IV) dexamethasone will prolong the duration of intraoperatively placed intercostal nerve blocks following VATS compared with IV dexamethasone and a perineural saline placebo.  Prospective, double-blind, randomized placebo-controlled trial.  Single level-1 academic trauma center.  Forty patients undergoing a unilateral VATS under the care of a single surgeon.  Patients were randomly assigned to two groups and received an intercostal nerve block containing 1) 0.5% bupivacaine with epinephrine and 1 ml of 0.9% saline or 2) 0.5% bupivacaine with epinephrine and 1 ml of a 4 mg/ml dexamethasone solution. All patients received 8 mg of IV dexamethasone.  Group 2 had lower NRS-11 scores at post-operative hours 8 (5.05, SD = 2.13 vs 3.50, SD = 2.50; p  = 0.04), 20 (4.30, SD = 2.96 vs 2.26, SD = 2.31; p  = 0.02), and 24 (4.53, SD = 1.95 vs 2.26, SD = 2.31; p  = 0.02). Equianalgesic opioid requirement was decreased in group 2 at 32 hours (5.78 mg, SD = 5.77 vs 1.67 mg, SD = 3.49; p  = 0.02). Group 2 also had greater FEV1 measured at 8, 12, 24, and 44 hours; greater FVC at 24 hours; greater PEF at 28 through 48 hours; and greater FEV1/FVC at 8 and 36 hours.  The combination of IV and perineural dexamethasone prolonged the duration of a single-injection bupivacaine intercostal nerve block as measured by NRS-11 compared with IV dexamethasone alone at 24 hours. Reduced NRS-11 at other times, reduced opioid requirements, and increased PFTs were observed in group 2. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Local anesthetic lidocaine delivery system: chitosan and hyaluronic acid-modified layer-by-layer lipid nanoparticles.

PubMed

Zhang, Laizhu; Wang, Jianguo; Chi, Huimin; Wang, Shilei

2016-11-01

Transdermal local anesthesia is one of the most applied strategies to avoid systemic adverse effects; there is an appealing need for a prolonged local anesthetic that would provide better bioavailability and longer pain relief with a single administration. Layer-by-layer (LBL) technique was used in this study to explore a nanosized drug delivery system for local anesthetic therapy. LBL-coated lidocaine-loaded nanostructured lipid nanoparticles (LBL-LA/NLCs) were prepared and characterized in terms of particle size (PS), zeta potential, drug encapsulation efficiency (EE), in vitro skin permeation and in vivo local anesthetic studies. Evaluation of the in vitro skin permeation and in vivo anesthesia effect illustrated that LBL-LA/NLCs can enhance and prolong the anesthetic effect of LA. LBL-LA/NLCs could function as a promising drug delivery strategy for overcoming the barrier function of the skin and could deliver anesthetic through the skin with sustained release behavior for local anesthetic therapy.

Stability of local anesthetics in the dental cartridge.

PubMed

Hondrum, S O; Seng, G F; Rebert, N W

1993-01-01

Recent manufacturer recalls of local anesthetics have emphasized the problems with storage stability. This article reviews the principles of drug stability, mechanisms of degradation of commonly used vasoconstrictors, research on the stability of commercially produced local anesthetic preparations, and possible effects of the container-closure system. The review concludes with a list of practical and clinical suggestions on how to minimize storage stability problems with dental local anesthetics.

A Guideline to Local Anesthetic Allergy Testing

PubMed Central

Canfield, David W.; Gage, Tommy W.

1987-01-01

Patients with a history of adverse reactions to a local anesthetic may often be incorrectly labeled as “allergic.” Determining if a patient is allergic to a local anesthetic is essential in the selection of appropriate pain control techniques. Local anesthetic allergy testing may be performed safely and with reasonable accuracy by a knowledgeable practitioner. This paper presents guidelines for an allergy testing method. ImagesFigure 1 PMID:3318567

Comparison of Nerve Stimulation-guided Axillary Brachial Plexus Block, Single Injection versus Four Injections: A Prospective Randomized Double-blind Study.

PubMed

Badiger, Santoshi V; Desai, Sameer N

2017-01-01

A variety of techniques have been described for the axillary block using nerve stimulator, either with single injection, two, three, or four separate injections. Identification of all the four nerves is more difficult and time-consuming than other methods. Aim of the present study is to compare success rate, onset, and duration of sensory and motor anesthesia of axillary block using nerve stimulator, either with single injection after identification of any one of the four nerves or four separate injections following identification of each of nerve. Prospective, randomized, double-blind study. Patients undergoing forearm and hand surgeries under axillary block. One hundred patients, aged 18-75 years, were randomly allocated into two groups of 50 each. Axillary block was performed under the guidance of nerve stimulator with a mixture of 18 ml of 1.5% lignocaine and 18 ml of 0.5% bupivacaine. In the first group ( n = 50), all 36 ml of local anesthetic was injected after the identification of motor response to any one of the nerves and in Group 2, all the four nerves were identified by the motor response, and 9 ml of local anesthetic was injected at each of the nerves. The success rate of the block, onset, and duration of sensory and motor block was assessed. Categorical variables were compared using the Chi-square test, and continuous variables were compared using independent t -test. The success rate of the block with four injection technique was higher compared to single-injection technique (84% vs. 56%, P = 0.02). Four injection groups had a faster onset of sensory and motor block and prolonged duration of analgesia compared to single-injection group ( P < 0.001). There were no significant differences in the incidence of accidental arterial puncture and hemodynamic parameter between the groups. Identification of all the four nerves produced higher success rate and better quality of the block when compared to single-injection technique.

Lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic doses.

PubMed

Lee, Soo Hee; Sung, Hui-Jin; Ok, Seong-Ho; Yu, Jongsun; Choi, Mun-Jeoung; Lim, Jin Soo; Sohn, Ju-Tae

2013-11-01

Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10(-4) M levobupivacaine, 2×10(-3) M ropivacaine, and 7×10(-3) M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10(-3) M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

Single-Dose Adductor Canal Block With Local Infiltrative Analgesia Compared With Local Infiltrate Analgesia After Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Nader, Antoun; Kendall, Mark C; Manning, David W; Beal, Matthew; Rahangdale, Rohit; Dekker, Robert; De Oliveira, Gildasio S; Kamenetsky, Eric; McCarthy, Robert J

A single-dose adductor canal block can provide postoperative analgesia for patients undergoing total knee arthroplasty (TKA). The purpose of this study was to assess postoperative opioid consumption after ultrasound-guided single-injection bupivacaine compared with saline adductor canal block for patients undergoing TKA. After institutional review board approval, written informed consent was obtained from patients (>18 years old) undergoing elective TKA. Subjects were randomized into 2 groups as follows: adductor canal blockade with 10 mL of bupivacaine 0.25% with epinephrine 1:300,000 or 10 mL of normal saline. All patients received a periarticular infiltration mixture intraoperatively with scheduled and patient requested oral and IV analgesics postoperatively for breakthrough pain. Personnel blinded to group allocation recorded pain scores and opioid consumption every 6 hours. Pain burden, area under the numeric rating score for pain, was calculated for 36 hours. The primary outcome was postoperative IV/IM morphine (mg morEq) consumption at 36 hours after surgery. Forty (28 women/12 men) subjects were studied. Postoperative opioid consumption was reduced in the bupivacaine 48 (39 to 61) mg morEq compared with saline 60 (49 to 85) mg morEq, difference -12 (-33 to -2) mg morEq (P = 0.03). Pain burden at rest was decreased in the bupivacaine 71 (37 to 120) score · hours compared with saline 131 (92 to 161) score · hours, difference -60 (-93 to -14) score · hours (P = 0.009). Adductor canal blockade with bupivacaine 0.25% with epinephrine 1:300,000 effectively reduces pain and opioid requirement in the postoperative period after TKA. Adductor canal blockade is an effective pain management adjunct for patients undergoing TKA.

Benefit-risk assessment of ropivacaine in the management of postoperative pain.

PubMed

Zink, Wolfgang; Graf, Bernhard M

2004-01-01

Ropivacaine is a long-acting amide-type local anaesthetic, released for clinical use in 1996. In comparison with bupivacaine, ropivacaine is equally effective for subcutaneous infiltration, epidural and peripheral nerve block for surgery, obstetric procedures and postoperative analgesia. Nevertheless, ropivacaine differs from bupivacaine in several aspects: firstly, it is marketed as a pure S(-)-enantiomer and not as a racemate, and secondly, its lipid solubility is markedly lower. These features have been suggested to significantly improve the safety profile of ropivacaine, and indeed, numerous studies have shown that ropivacaine has less cardiovascular and CNS toxicity than racemic bupivacaine in healthy volunteers. Extensive clinical data have demonstrated that epidural 0.2% ropivacaine is nearly identical to 0.2% bupivacaine with regard to onset, quality and duration of sensory blockade for initiation and maintenance of labour analgesia. Ropivacaine also provides effective pain relief after abdominal or orthopaedic surgery, especially when given in conjunction with opioids or other adjuvants. Nevertheless, epidurally administered ropivacaine causes significantly less motor blockade at low concentrations. Whether the greater degree of blockade of nerve fibres involved in pain transmission (Adelta- and C-fibres) than of those controlling motor function (Aalpha- and Abeta-fibres) is due to a lower relative potency compared with bupivacaine or whether other physicochemical properties or stereoselectivity are involved, is still a matter of intense debate. Recommended epidural doses for postoperative or labour pain are 20-40 mg as bolus with 20-30 mg as top-up dose, with an interval of >or=30 minutes. Alternatively, 0.2% ropivacaine can be given as continuous epidural infusion at a rate of 6-14 mL/h (lumbar route) or 4-10 mL/h (thoracic route). Preoperative or postoperative subcutaneous wound infiltration, during cholecystectomy or inguinal hernia repair, with ropivacaine 100-175 mg has been shown to be more effective than placebo and as effective as bupivacaine in reducing wound pain, whereby the vasoconstrictive potency of ropivacaine may be involved. Similar results were found in peripheral blockades on upper and lower limbs. Ropivacaine shows an identical efficacy and potency to that of bupivacaine, with similar analgesic duration over hours using single shot or continuous catheter techniques. In summary, ropivacaine, a newer long-acting local anaesthetic, has an efficacy generally similar to that of the same dose of bupivacaine with regard to postoperative pain relief, but causes less motor blockade and stronger vasoconstriction at low concentrations. Despite a significantly better safety profile of the pure S(-)-isomer of ropivacaine, the increased cost of ropivacaine may presently limit its clinical utility in postoperative pain therapy.

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

PubMed

Rice, David; Heil, Justin W; Biernat, Lukasz

2017-03-01

Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

Duration of motor block with intrathecal ropivacaine versus bupivacaine for caesarean section: a meta-analysis.

PubMed

Malhotra, R; Johnstone, C; Halpern, S; Hunter, J; Banerjee, A

2016-08-01

Bupivacaine is a commonly used local anaesthetic for spinal anaesthesia for caesarean section, but may produce prolonged motor block, delaying discharge from the post-anaesthesia care unit. Ropivacaine may have a shorter time to recovery of motor function compared with bupivacaine. We performed a meta-analysis to assess the time difference in duration of motor block with intrathecal ropivacaine compared with bupivacaine for caesarean section. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases for randomised controlled trials comparing ropivacaine with bupivacaine in parturients undergoing elective caesarean section under spinal anaesthesia. The primary outcome was the duration of motor block. Secondary outcomes included the time to onset of sensory block, need for conversion to general anaesthesia and the incidence of hypotension. Thirteen trials comprising 743 spinal anaesthetics were included. Intrathecal ropivacaine resulted in a reduced duration of motor block, regressing 35.7min earlier compared with intrathecal bupivacaine (P<0.00001). There was no difference in the time to onset of sensory block (P=0.25) or the incidence of hypotension (P=0.10). Limited data suggested no difference in the rate of conversion to general anaesthesia, but an earlier request for postoperative analgesia with ropivacaine. Compared with bupivacaine, intrathecal ropivacaine is associated with more rapid recovery of motor block despite similar sensory properties and no increased rate of conversion to general anaesthesia. This may be useful in centres in which recovery of motor block is a criterion for discharge from the post-anaesthesia care unit. However, small numbers of trials and significant heterogeneity limit the interpretation of our results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occurrence of paresthesia after dental local anesthetic administration in the United States.

PubMed

Garisto, Gabriella A; Gaffen, Andrew S; Lawrence, Herenia P; Tenenbaum, Howard C; Haas, Daniel A

2010-07-01

Several studies have suggested that the likelihood of paresthesia may depend on the local anesthetic used. The purpose of this study was to determine if the type of local anesthetic administered had any effect on reports of paresthesia in dentistry in the United States. The authors obtained reports of paresthesia involving dental local anesthetics during the period from November 1997 through August 2008 from the U.S. Food and Drug Administration Adverse Event Reporting System. They used chi(2) analysis to compare expected frequencies, on the basis of U.S. local anesthetic sales data, with observed reports of oral paresthesia. During the study period, 248 cases of paresthesia occurring after dental procedures were reported. Most cases (94.5 percent) involved mandibular nerve block. The lingual nerve was affected in 89.0 percent of cases. Reports involving 4 percent prilocaine and 4 percent articaine were 7.3 and 3.6 times, respectively, greater than expected (chi(2), P < .0001) on the basis of local anesthetic use by U.S. dentists. These data suggest that paresthesia occurs more commonly after use of 4 percent local anesthetic formulations. These findings are consistent with those reported in a number of studies from other countries. Until further research indicates otherwise, dentists should consider these results when assessing the risks and benefits of using 4 percent local anesthetics for mandibular block anesthesia.

Anesthetic approach to high-risk patients and prolonged awake craniotomy using dexmedetomidine and scalp block.

PubMed

Garavaglia, Marco M; Das, Sunit; Cusimano, Michael D; Crescini, Charmagne; Mazer, C David; Hare, Gregory M T; Rigamonti, Andrea

2014-07-01

Awake craniotomy with intraoperative speech or motor testing is relatively contraindicated in cases requiring prolonged operative times and in patients with severe medical comorbidities including anxiety, anticipated difficult airway, obesity, large tumors, and intracranial hypertension. The anesthetic management of neurosurgical patients who possess these contraindications but would be optimally treated by an awake procedure remains unclear. We describe a new anesthetic approach for awake craniotomy that did not require any airway manipulation, utilizing a bupivacaine-based scalp nerve block, and dexmedetomidine as the primary hypnotic-sedative agent. Using this technique, we provided optimal operative conditions to perform awake craniotomy facilitating safe tumor resection, while utilizing intraoperative electrocorticography for motor and speech mapping in a cohort of 10 patients at a high risk for airway compromise and complications associated with patient comorbidities. All patients underwent successful awake craniotomy, intraoperative mapping, and tumor resection with adequate sedation for up to 9 hours (median 3.5 h, range 3 to 9 h) without any loss of neurological function, airway competency, or the need to provide any active rescue airway management. We report 4 of these cases that highlight our experience: 1 case required prolonged surgery because of the complexity of tumor resection and 3 patients had important medical comorbidities and/or relative contraindication for an awake procedure. Dexmedetomidine, with concurrent scalp block, is an effective and safe anesthetic approach for awake craniotomy. Dexmedetomidine facilitates the extension procedure complexity and duration in patients who might traditionally not be considered to be candidates for this procedure.

A comparison of four methods of analgesia in cats following ovariohysterectomy.

PubMed

Tobias, Karen M; Harvey, Ralph C; Byarlay, Judy M

2006-11-01

To evaluate the effectiveness of preoperative administration of oral carprofen, subcutaneous ketoprofen, and local nerve block with bupivacaine in preventing postoperative pain-associated behavior in cats after ovariohysterectomy. Fifty-two female intact cats. Materials and methods Cats received butorphanol (0.44 mg kg(-1) IM), carprofen (2.2 mg kg(-1) PO), ketoprofen (2.2 mg kg(-1) SQ), or bupivacaine infiltration block (1.1 mg kg(-1) SQ) before surgery. Cortisol and drug concentrations and visual analog scale (VAS) and interactive visual analog scale (IVAS) pain-associated behavior scores were measured 2 hours before and 0, 1, 2, 4, 8, 12, and 24 hours after ovariohysterectomy. Cats receiving butorphanol had significantly increased IVAS scores 2 hours after surgery compared with baseline measurements. Cats receiving carprofen, ketoprofen, and bupivacaine had significant increases from baseline in VAS and IVAS scores 1 and 2 hours after surgery. VAS and IVAS scores for cats receiving bupivacaine were significantly greater 1 and 2 hours after surgery than for cats that received butorphanol. Cats receiving carprofen had significant increases in cortisol 1 hour after surgery and significant decreases 24 hours after surgery compared with baseline measurements. Preoperative carprofen and ketoprofen have effects on pain-associated behavior similar to butorphanol in cats undergoing ovariohysterectomy. Cats receiving bupivacaine blocks may require additional analgesics immediately after surgery.

Advances in labor analgesia

PubMed Central

Wong, Cynthia A

2010-01-01

The pain of childbirth is arguably the most severe pain most women will endure in their lifetimes. The pain of the early first stage of labor arises from dilation of the lower uterine segment and cervix. Pain from the late first stage and second stage of labor arises from descent of the fetus in the birth canal, resulting in distension and tearing of tissues in the vagina and perineum. An array of regional nerve blocks, systemic analgesic, and nonpharmacologic techniques are currently used for labor analgesia. Nonpharmacologic methods are commonly used, but the effectiveness of these techniques generally lacks rigorous scientific study. Continuous labor support has been shown to decrease the use of pharmacologic analgesia and shorten labor. Intradermal water injections decrease back labor pain. Neuraxial labor analgesia (most commonly epidural or combined spinal-epidural) is the most effective method of pain relief during childbirth, and the only method that provides complete analgesia without maternal or fetal sedation. Current techniques commonly combine a low dose of local anesthetic (bupivacaine or ropivacaine) with a lipid soluble opioid (fentanyl or sufentanil). Neuraxial analgesia does not increase the rate of cesarean delivery compared to systemic opioid analgesia; however, dense neuraxial analgesia may increase the risk of instrumental vaginal delivery. PMID:21072284

Vasoconstrictors in local anesthesia for dentistry.

PubMed Central

Sisk, A. L.

1992-01-01

Addition of a vasoconstrictor to a local anesthetic may have several beneficial effects: a decrease in the peak plasma concentration of the local anesthetic agent, increase in the duration and the quality of anesthesia, reduction of the minimum concentration of anesthetic needed for nerve block, and decrease of blood loss during surgical procedures. The addition of a vasoconstrictor to a local anesthetic may also have detrimental effects. A review of the literature indicates that vasoconstrictor concentrations in local anesthetics marketed for dental use in the United States are not always optimal to achieve the purposes for which they are added. In most cases, a reduced concentration of vasoconstrictor could achieve the same goal as the marketed higher concentration, with less side-effect liability. PMID:8250339

A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with tx360(®) as acute treatment for chronic migraine.

PubMed

Cady, Roger; Saper, Joel; Dexter, Kent; Manley, Heather R

2015-01-01

To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360(®) are superior in reducing pain associated with chronic migraine (CM) compared with saline. The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM. This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360(®) , which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure. The final dataset included 38 subjects, 26 in the bupivacaine group and 12 in the saline group. A repeated measures analysis of variance showed that subjects receiving treatment with bupivacaine experienced a significant reduction in the numeric rating scale scores compared with those receiving saline at baseline (M=3.78 vs M=3.18, P=.10), 15 minutes (M=3.51 vs M=2.53, P<.001), 30 minutes (M=3.45 vs M=2.41, P<.001), and 24 hours after treatment (M=4.20 vs M=2.85, P<.001), respectively. Headache Impact Test-6 scores were statistically significantly decreased in subjects receiving treatments with bupivacaine from before treatment to the final treatment (Mdiff  = -4.52, P=.005), whereas no significant change was seen in the saline group (Mdiff  = -1.50, P=.13). SPG blockade with bupivacaine delivered repetitively for 6 weeks with the Tx360(®) device demonstrates promise as an acute treatment of headache in some subjects with CM. Statistically significant headache relief is noted at 15 and 30 minutes and sustained at 24 hours for SPG blockade with bupivacaine vs saline. The Tx360(®) device was simple to use and not associated with any significant or lasting adverse events. Further research on sphenopalatine ganglion blockade is warranted. © 2014 The Authors. Headache published by Wiley Periodicals, Inc. on behalf of American Headache Society.

A Double-Blind, Placebo-Controlled Study of Repetitive Transnasal Sphenopalatine Ganglion Blockade With Tx360® as Acute Treatment for Chronic Migraine

PubMed Central

Cady, Roger; Saper, Joel; Dexter, Kent; Manley, Heather R

2015-01-01

Objective To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360® are superior in reducing pain associated with chronic migraine (CM) compared with saline. Background The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM. Method This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360®, which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure. Results The final dataset included 38 subjects, 26 in the bupivacaine group and 12 in the saline group. A repeated measures analysis of variance showed that subjects receiving treatment with bupivacaine experienced a significant reduction in the numeric rating scale scores compared with those receiving saline at baseline (M = 3.78 vs M = 3.18, P = .10), 15 minutes (M = 3.51 vs M = 2.53, P < .001), 30 minutes (M = 3.45 vs M = 2.41, P < .001), and 24 hours after treatment (M = 4.20 vs M = 2.85, P < .001), respectively. Headache Impact Test-6 scores were statistically significantly decreased in subjects receiving treatments with bupivacaine from before treatment to the final treatment (Mdiff = −4.52, P = .005), whereas no significant change was seen in the saline group (Mdiff = −1.50, P = .13). Conclusion SPG blockade with bupivacaine delivered repetitively for 6 weeks with the Tx360® device demonstrates promise as an acute treatment of headache in some subjects with CM. Statistically significant headache relief is noted at 15 and 30 minutes and sustained at 24 hours for SPG blockade with bupivacaine vs saline. The Tx360® device was simple to use and not associated with any significant or lasting adverse events. Further research on sphenopalatine ganglion blockade is warranted. PMID:25338927

Lidocaine impairs proliferative and biosynthetic functions of aged human dermal fibroblasts

PubMed Central

Bentov, Itay; Damodarasamy, Mamatha; Spiekerman, Charles; Reed, May J

2016-01-01

Background The aged are at increased risk of postoperative wound healing complications. Since local anesthetics are commonly infiltrated into the dermis of surgical wounds, we sought to determine if local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on IGF-1 and TGF-ß1, growth factors that are important regulators of wound healing. Methods Human dermal fibroblasts from aged and young donors (HFB) were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine and ropivacaine on proliferation of HFB. Lidocaine was the most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-ß1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-ß1 were evaluated for their effects on proliferation and expression of dermal collagens, respectively. Results Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95%CI 80%-98%, p=0.009 and for mepivacaine 90% of control, 95%CI 81%-99%, p=0.032), but not in young HFB. Ropivicaine and bupivicaine did not inhibit proliferation. Due to the clinical utility of lidocaine relative to mepivicaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and IGF1R in fibroblasts from aged donors (IGF-1, log2 fold-change −1.25 {42% of control, 95%CI 19%-92%, p=0.035} and IGF1R, log2 fold-change of −1.00 {50% of control, 95%CI 31%-81%, p=0.014}). In contrast, lidocaine did not effect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change −1.28 {41% of control, 95%CI 20%-83%, p=0.022} in aged HFB and log2 fold-change −1.60 {33% of control, 95%CI 15%-73%, p=0.019} in young HFB). Transcripts for collagen I were decreased in aged HFB (log2 fold-change −1.82 {28% of control 95%CI 14%-58%, p=0.006}), but were not in the young HFB. Similar to the transcripts, lidocaine also inhibited the protein expression of collagen III in young and aged HFB (log2 fold-change −1.79 {29% of control, 95%CI 18%-47%, p=0.003} in young HFB and log2 fold-change −1.76 {30% of control, 95%CI 9%-93%, p=0.043} in aged HFB). The effect of lidocaine on expression of collagen III protein was obviated by TGF-ß1 in both young and aged HFB. Conclusions Our results show that lidocaine inhibits processes relevant to dermal repair in aged HFB. The detrimental responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-ß1. PMID:27537755

The Effect of Needle Type, Duration of Surgery and Position of the Patient on the Risk of Transient Neurologic Symptoms

PubMed Central

Etezadi, Farhad; Karimi Yarandi, Kourosh; Ahangary, Aylar; Shokri, Hajar; Imani, Farsad; Safari, Saeid; Khajavi, Mohammad Reza

2013-01-01

Background The incidence of transient neurologic symptoms (TNS) after spinal anesthesia with lidocaine is reported as high as 40%. Objectives This prospective clinical trial was designed to determine the incidence of TNS in patients who underwent spinal anesthesia with two different needles, in two different surgical positions. Patients and Methods The present randomized clinical trial was conducted on 250 patients (ASA I-II), who were candidates for surgery in supine or lithotomy positions. According to the needle type (Sprotte or Quincke) and local anesthetics (lidocaine and bupivacaine) all patients were randomly divided into four groups. After performing spinal anesthesia in sitting position, the position was changed into supine or lithotomy, according to surgical procedure. The patients were observed for complications of spinal anesthesia during the first five post-operative days. The primary end-point for this trial was to recognize the incidence of TNS among the four groups. Our secondary objective was to evaluate the effect of patient's position, needle type, and duration of surgery on the development of TNS following spinal anesthesia. Results TNS was most commonly observed when lidocaine was used as anesthetic drug (P = 0.003). The impact of needle type, was not significant (P = 0.7). According to multivariate analysis, the duration of surgery was significantly lower in cases suffering from TNS (P = 0.04). Also, the risk of TNS increased following surgeries performed in lithotomy position (P = 0.00). Conclusions According to the results of this clinical study, spinal anesthesia with lidocaine, and the lithotomy position in surgery increased the risk of TNS. PMID:24223352

[Combined spinal-epidural anesthesia for cesarean section in a parturient with myotonic dystrophy].

PubMed

Mori, Kosuke; Mizuno, Ju; Nagaoka, Takehiko; Harashima, Toshiya; Morita, Sigeho

2010-08-01

Myotonic dystrophy (MD) is a muscle disorder characterized by progressive muscle wasting and weakness, and is the most common form of muscular dystrophy that begins in adulthood, often after pregnancy. MD might be related to occurrence of malignant hyperthermia. Therefore, the cesarean section is often performed for the parturient with MD. We had an experience of combined spinal-epidural anesthesia for cesarean section in a parturient complicated with MD. A 40-year-old woman had rhabdomyolysis caused by ritodrine at 15-week gestation and was diagnosed as MD by electromyography. Her first baby died due to respiratory failure fourth day after birth. She had hatchet face, slight weakness of her lower extremities, and easy fatigability. Her manual muscle test was 5/5 at upper extremities and 4/5 at lower extremities. She underwent emergency cesarean section for premature rupture of the membrane, weak pain during labor, and obstructed labor at 33-week gestation. We placed an epidural catheter from T12/L1 and punctured arachnoid with 25 G spinal needle. We performed spinal anesthesia using 0.5% hyperbaric bupivacaine 1.5 ml and epidural anesthesia using 2% lidocaine 6 ml. Her anesthetic level reached bilaterally to T7 and operation started 18 minutes after combined spinal-epidural anesthesia. Her baby was born 23 minutes after the anesthesia. As her baby was 1/5 at Apgar score, the baby was tracheally intubated and artificially ventilated. The cesarean section was finished in 33 minutes uneventfully. She had no adverse events and was discharged on the 8th postoperative day. Later her baby was diagnosed as congenital MD by gene analysis. Combined spinal-epidural anesthesia with the amide-typed local anesthetic agents could be useful and safe for cesarean section in the parturient with MD.

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

Transversus Abdominis Plane Block Versus Wound Infiltration for Analgesia After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Tawfik, Mohamed Mohamed; Mohamed, Yaser Mohamed; Elbadrawi, Rania Elmohamadi; Abdelkhalek, Mostafa; Mogahed, Maiseloon Mostafa; Ezz, Hanaa Mohamed

2017-04-01

Transversus abdominis plane (TAP) block and local anesthetic wound infiltration provide analgesia after cesarean delivery. Studies comparing the 2 techniques are scarce, with conflicting results. This double-blind, randomized controlled trial aimed to compare bilateral ultrasound-guided TAP block with single-shot local anesthetic wound infiltration for analgesia after cesarean delivery performed under spinal anesthesia. We hypothesized that the TAP block would decrease postoperative cumulative fentanyl consumption at 24 hours. Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia. Exclusion criteria were: <19 years of age or >40 years of age; height <150 cm, weight <60 kg, body mass index ≥40 kg/m; contraindications to spinal anesthesia; history of recent opioid exposure; hypersensitivity to any of the drugs used in the study; significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities. Eighty subjects were randomly allocated to 2 equal groups. In the infiltration group, participants received 15 mL of bupivacaine 0.25% in each side of the surgical wound (total 30 mL); and in the TAP group, participants received 20 mL of bupivacaine 0.25% bilaterally in the TAP block (total 40 mL). The TAP block and wound infiltration were performed by the primary investigator and the operating obstetrician, respectively. All participants received postoperative standard analgesia (ketorolac and paracetamol) and intravenous fentanyl via patient-controlled analgesia. Patients and outcome assessors were blinded to the study group. The primary outcome was the cumulative fentanyl consumption at 24 hours. Secondary outcomes were the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, the incidence of side effects (nausea and vomiting and pruritis), and patient satisfaction. Data from 78 patients (39 patients in each group) were analyzed. The mean ± SD of cumulative fentanyl consumption at 24 hours was 157.4 ± 63.4 μg in the infiltration group and 153.3 ± 68.3 μg in the TAP group (difference in means [95% confidence interval] is 4.1 [-25.6 to 33.8] μg; P = .8). There were no significant differences between the 2 groups in the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, and patient satisfaction. The incidence of side effects (nausea and vomiting and pruritis) was low in the 2 groups. TAP block and wound infiltration did not significantly differ regarding postoperative fentanyl consumption, pain scores, and patient satisfaction in parturients undergoing cesarean delivery under spinal anesthesia.

Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

PubMed

Ferrer, Leopoldo E; Romero, David J; Vásquez, Oscar I; Matute, Ednna C; Van de Velde, Marc

2017-11-01

Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

Selective spinal anesthesia versus intravenous propofol in transrectal ultrasound-guided prostate biopsy.

PubMed

Sundarathiti, Petchara; Sirinan, Chomchaba; Seangrung, Rattaphol; Watcharotayangul, Jittiya; Sithamwilai, Wannipa

2009-07-01

Selective spinal anesthesia (SSA) focuses on the use of minimal doses of intrathecal agents with greater precision and selectivity so that return of function occurs rapidly. The authors compared the efficacy of 1.25 mg of hyperbaric bupivacaine intrathecally with propofol anesthesia in terms of hemodynamic stability, surgical conditions and ability to bypass the post anesthetic care unit (PACU). Seventy male patients, 45-85 years old, ASA physical status I-III, were randomly allocated into two groups. Group 1 (n=35) received intrathecal 1.25 mg hyperbaric bupivacaine plus patients cerebrospinal fluid 0.75 ml. Group 2 (n=35) received propofol 1-1.5 mg/kg IV bolus dose and 6-10 mg/kg/hr infusion to maintain surgical anesthesia. The patients in group 1 had adequate anesthesia and were able to walk and bypass the PACU (100%). The need of supplemental oxygen and airway maneuver; the incidence of hypotension and bradycardia were found only in group 2. The surgical conditions were rated as excellent 100% in group 1 and 57.1% in group 2. SSA is superior to propofol anesthesia in terms of hemodynamic stability, surgical conditions and recovery profiles. Even elderly patients were able to walk out from the operating theatre immediately after the procedure.

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Palatoplasty.

PubMed

Day, Kristopher M; Nair, Narayanan M; Sargent, Larry A

2018-05-14

Liposomal bupivacaine (LB) is a long-acting local anesthetic reported to decrease postoperative pain in adults. The authors demonstrate the safe use of LB in pediatric patients with improved pain control following palatoplasty. Retrospective patient series of all single-surgeon palatoplasty patients treated at a tertiary craniofacial center from August 2014 to December 2015 were included. All patients received 1.3% LB intraoperatively as greater palatal nerve and surgical field blocks in 2-flap V-Y pushback palatoplasty. Postoperative oral intake, opioids administered, duration of hospitalization, and FLACC (face, legs, activity, cry, consolability) pain scores were measured. Twenty-seven patients (16 males and 11 females, average age of 10.8 months, weight 8.8 kg) received 2.9 ± 0.9 mL (2.6 ± 1.9 mg/kg) 1.3% LB. Average FLACC scores were 2.4 ± 2.2/10 in the postanesthesia care unit and 3.8 ± 1.8/10 while inpatients. Oral intake was first tolerated 10.3 ± 11.5 hours postoperatively and tolerated 496.4 ± 354.2 mL orally in the first 24 hours postoperatively. Patients received 8.5 ± 8.4 mg hydrocodone equivalents (0.46 ± 0.45 mg/kg per d hydrocodone equivalents) and were discharged 2.1 ± 1.3 days postoperatively. Opioid-related adverse events included emesis in 7.4% and pruritis in 3.7% of patients. The LB may be used safely in pediatric patients. Intraoperative injection of LB during palatoplasty can yield low postoperative opioid use and an early and adequate volume of oral intake over an average hospital stay. Further cost-efficacy studies of LB are needed to assess its value in pediatric plastic surgery.

Anesthetic diffusion through lipid membranes depends on the protonation rate.

PubMed

Pérez-Isidoro, Rosendo; Sierra-Valdez, F J; Ruiz-Suárez, J C

2014-12-18

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon.

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.

PubMed

Tsuchiya, Hironori

2017-08-18

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca ( Erythroxylum coca , Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme ( Thymus vulgaris , Lamiaceae) and clove ( Syzygium aromaticum , Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N -methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin.

Assessment of the densities of local anesthetics and their combination with adjuvants: an experimental study.

PubMed

Imbelloni, Luiz Eduardo; Moreira, Adriano Dias; Gaspar, Flávia Cunha; Gouveia, Marildo A; Cordeiro, José Antônio

2009-01-01

The relative density of a local anesthetic in relation to that of the cerebrospinal fluid (CSF) at 37 degrees C is one of the most important physical properties that affect the level of analgesia obtained after the subarachnoid administration of the drug. The objective of this study was to determine the density of local anesthetic solutions, with and without glucose, and the combination of the local anesthetic with adjuvants at 20 degrees C, 25 degrees C, and 37 degrees C. The density (g.mL(-1)) was determined by using a DMA 450 densimeter with a sensitivity of +/- 0.00001 g.mL(-1). The densities, and variations, according to the temperature were obtained for all local anesthetics and their combination with opioids at 20 degrees C, 25 degrees C, and 37 degrees C. The solution is hyperbaric if its density exceeds 1.00099, hypobaric when its density is lower than 1.00019, and isobaric when its density is greater than 1.00019 and lower than 1.00099. The densities of both local anesthetics and adjuvants decrease with the increase in temperature. At 37 degrees C, all glucose-containing solutions are hyperbaric. In the absence of glucose, all solutions are hypobaric. At 37 degrees C, morphine, fentanyl, sufentanil, and clonidine are hypobaric. The densities of local anesthetics and adjuvants decrease with the increase in temperature and increase when glucose is added. The knowledge of the relative density helps select the most adequate local anesthetic to be administered in the subarachnoid space.

21 CFR 346.22 - Permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) of this section. (c) Any single local anesthetic identified in § 346.10 may be combined with any single vasoconstrictor identified in § 346.12. (d) Any single local anesthetic identified in § 346.10 may be combined with any single astringent identified in § 346.18. (e) Any single local anesthetic...

21 CFR 346.22 - Permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) of this section. (c) Any single local anesthetic identified in § 346.10 may be combined with any single vasoconstrictor identified in § 346.12. (d) Any single local anesthetic identified in § 346.10 may be combined with any single astringent identified in § 346.18. (e) Any single local anesthetic...

Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro.

PubMed

Lirk, P; Hollmann, M W; Fleischer, M; Weber, N C; Fiegl, H

2014-07-01

Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of this study were to determine the effect of two amide local anaesthetics, ropivacaine and bupivacaine, on methylation in two breast cancer cell lines and to detect whether the combination of lidocaine with the chemotherapy agent 5-aza-2'-deoxycytidine (DAC) would result in additive demethylating effects. Breast cancer cell lines BT-20 [oestrogen receptor (ER)-negative] and MCF-7 (ER-positive) were incubated with lidocaine, bupivacaine, and ropivacaine to assess demethylating properties. Then, we tested varying concentrations of lidocaine and DAC to assess whether their demethylating effects were additive. Cell numbers and global methylation status were analysed. Lidocaine decreased methylation in BT-20 and MCF-7 cells, ropivacaine decreased methylation in BT-20 cells, and bupivacaine had no demethylating effect. When combined, lidocaine and DAC had additive demethylating effects. At clinically relevant doses, lidocaine and ropivacaine exert demethylating effects on specific breast cancer cell lines, but bupivacaine does not. The demethylating effects of lidocaine and DAC are indeed additive. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of fluoroscopic interlaminar epidural injections in managing chronic pain of lumbar disc herniation or radiculitis: a randomized, double-blind trial.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar; Falco, Frank J E

2013-09-01

There is continued debate on the effectiveness, indications, and medical necessity of epidural injections in managing pain and disability from lumbar disc herniation, despite extensive utilization. There is paucity of literature on interlaminar epidural injections in managing lumbar disc herniation or radiculitis in contemporary interventional pain management settings utilizing fluoroscopy. A randomized, double-blind, active-control trial was undertaken to assess the effectiveness of lumbar interlaminar epidural injections with or without steroids for disc herniation and radiculitis. The primary outcome was defined as pain relief and functional status improvement of ≥ 50%. One hundred twenty patients were randomly assigned to 1 of the 2 groups. Group I patients received lumbar interlaminar injections containing a local anesthetic (lidocaine 0.5%, 6 mL), whereas Group II patients received lumbar interlaminar epidural injections of 0.5% lidocaine, 5 mL, mixed with 1 mL of non-particulate betamethasone. In the patients who responded with initial 2 procedures with at least 3 weeks of relief, significant improvement was seen in 80% of the patients in the local anesthetic group and 86% of the patients in the local anesthetic and steroid group. The overall average procedures per year were 3.6 in the local anesthetic group and 4.1 in the local anesthetic and steroid group, with an average relief of 33.7 ± 18.1 weeks in the local anesthetic group and 39.1 ± 12.2 weeks in the local anesthetic and steroid group over a period of 52 weeks in the overall population. Lumbar interlaminar epidural injections of local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis, with potential superiority of steroids compared with local anesthetic alone at 1 year follow-up. © 2012 The Authors Pain Practice © 2012 World Institute of Pain.

An Uncommon Complication With Use of Topical Local Anesthetic Agents: Methemoglobinemia.

PubMed

Panikkath, Ragesh; Panikkath, Deepa; Wischmeyer, Jason

Although the use of topical local anesthetics is generally safe, several potentially fatal complications have been reported. Methemoglobinemia is a rare but potentially fatal complication. Methemoglobin is a naturally occurring oxidized metabolite of hemoglobin, and physiologic levels (<1%) are normal. Methemoglobinemia can be congenital or acquired. Several drugs including topical anesthetic agents like benzocaine can induce this condition. Sudden appearance of cyanosis, with a disproportionately better oxygen saturation of 85% after use of local anesthetics can be a helpful for diagnosis.

Comparison of ultrasound guided transversus abdominis plane block versus local wound infiltration for post operative analgesia in patients undergoing gynaecological surgery under general anaesthesia.

PubMed

Ranjit, S; Shrestha, S K

2014-01-01

Transversus abdominis plane block has been recently developed as a part of multimodal post operative analgesic techniques. We compared the analgesic efficacy of this technique with local bupivacaine infiltration in patients undergoing gynaecological surgeries with pfannenstiel incision and lower midline incision under general anaesthesia. To evaluate the efficacy of ultrasound guided transversus abdominis plane block for postoperative analgesia. Patients were randomly allocated to three groups: control group (n=15), transversus abdominis plane block group (n=15), who received bilateral transversus abdominis plane blockwith 0.25% bupivacaine, and local infiltration group (n=15), who received local wound infiltration with 0.25% bupivacaine at the end of surgery. All patients received intramuscular diclofenac 12 hourly and intravenous tramadol SOS in the postoperative period. Visual analogue scores for pain were assessed at 1,2,4,8,12 and 24 hours postoperatively and these were compared between the three groups. Average tramadol consumption in 24 hours were also compared among the three groups. Data were subjected to univariate ANOVA test and chi-square test. Level of significance was set at 0.05. Visual analogue scores were significantly less in transversus abdominis plane block group and effect lasted up to 12 hours at rest postoperatively and 8 hours during cough and movement. Bilateral Transversus abdominis plane block was effective in reducing postoperative pain scores for 8 to 12 hours postoperatively. This block was also successful in reducing postoperative opioid requirement.

Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia.

PubMed

Wahi, Ajay; Singh, Amanjot K; Syal, Kartik; Sood, Ajay; Pathania, Jyoti

2016-04-01

Clonidine is an α2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150μg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75μg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test). Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable.

Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia

PubMed Central

Singh, Amanjot K.; Syal, Kartik; Sood, Ajay; Pathania, Jyoti

2016-01-01

Introduction Clonidine is an α2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. Aim This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. Materials and Methods We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150μg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75μg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. Statistical Analysis The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test). Results Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. Conclusion Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable. PMID:27190921

Anesthetic Diffusion Through Lipid Membranes Depends on the Protonation Rate

PubMed Central

Pérez-Isidoro, Rosendo; Sierra-Valdez, F. J.; Ruiz-Suárez, J. C.

2014-01-01

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon. PMID:25520016

Local Anesthetic Microcapsules.

DTIC Science & Technology

1981-04-15

III Chemical Structure of Local Anesthetics 12 Table IV Processing Summary of Lidocaine Microencapsulation 15 Table V Lidocaine Microcapsule Size...Distribution 17 Table VI Processing Summary of Etidocaine Microencapsulation 18 Table VII Etidocaine Microcapsule Size Distribution 19 Table VIII Lidocaine...REPORT I PERIOD COVERED Annual Local Anesthetic Microcapsules 1 July 1980-30 March 1981 6. PERFORMING ORG. REPORT NUMBER 2106-1 7. AUTHOR() S

Intrathecal hyperbaric versus isobaric bupivacaine for adult non-caesarean-section surgery: systematic review protocol

PubMed Central

Uppal, Vishal; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

2016-01-01

Introduction Bupivacaine is the most commonly used local anaesthetic for spinal anaesthesia (SA). There are two forms of commercially available bupivacaine; isobaric bupivacaine (IB): a formulation with a specific gravity or density equal to cerebrospinal fluid, and hyperbaric bupivacaine (HB): a formulation with density heavier than cerebrospinal fluid. The difference in densities of the two available preparations is believed to affect the diffusion pattern that determines the effectiveness, spread and side-effect profile of bupivacaine. This systematic review will summarise the best available evidence regarding the effectiveness and safety on the use of HB compared with IB, when used to provide SA for surgery. Primarily, we will analyse the need for conversion to general anaesthesia. As secondary outcomes, we will compare the incidence of hypotension, incidence of nausea/vomiting, the onset time and duration of anaesthesia. Methods and analysis We will search key electronic databases using search strategy (1) injections, spinal OR intrathecal OR subarachnoid; (2) bupivacaine OR levobupivacaine; (3) hypobaric OR isobaric OR plain; (4) baricity. We will search MEDLINE, EMBASE and Cochrane databases, from their inception for randomised controlled trials, with no restrictions on language. Caesarean section surgery will be excluded. 2 reviewers will independently extract the data using a standardised form. Extracted items will include study characteristics, risk of bias domains, as per modified Cochrane risk of bias, participant disposition and study outcomes. We will conduct a meta-analysis for variables that can be compared across the studies. We will evaluate clinical heterogeneity by qualitatively appraising differences in study characteristics in participants, interventions and the outcomes assessed. We will report our findings as relative risks (dichotomous), and weighted mean differences (continuous) for individual outcomes, along with their 95% CIs. Ethics and dissemination We plan to submit, and will publish, our findings in a peer-reviewed scientific journal, and present our results at national and international meetings. Trial registration number CRD42015017672. PMID:27194318

Direct cardiac effects of intracoronary bupivacaine, levobupivacaine and ropivacaine in the sheep

PubMed Central

Chang, Dennis H-T; Ladd, Leigh A; Copeland, Susan; Iglesias, Miguel A; Plummer, John L; Mather, Laurence E

2001-01-01

The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. In previous preclinical studies of the safety of these drugs with intravenous administration in conscious ewes over a wide dose range, we found that central nervous system (CNS) excito-toxicity reversed the cardiac depressant effects when doses approached the convulsant threshold and thus precluded accurate comparison of their cardiovascular system (CVS) effects. To study CVS effects over a wide range of doses with minimal CNS and other influences, brief (3 min) infusions of bupivacaine, levobupivacaine or ropivacaine were administered into the left main coronary arteries of previously instrumented conscious ewes (∼50 Kg body weight). After dose-ranging studies, the drugs were compared in a randomized, blinded, parallel group design. Equimolar doses were increased from 8 μmol (≈amp;2.5 mg) in 8 μmol increments, to either a fatal outcome or a 40 μmol (≈amp;12.5 mg) maximum. All three drugs produced tachycardia, decreased myocardial contractility and stroke volume and widening of electrocardiographic QRS complexes. Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean±s.e.mean actual fatal dose: 21.8±6.4 μmol), five of seven with levobupivacaine (22.9±3.5 μmol), four of six with ropivacaine (22.9±5.9 μmol). No significant differences in survival or in fatal doses between these drugs were found. The findings suggest that ropivacaine, levobupivacaine and bupivacaine have similar intrinsic ability to cause direct fatal cardiac toxicity when administered by left intracoronary arterial infusion in conscious sheep and do not explain the differences between the drugs found with intravenous dosage. PMID:11159717

(/sup 3/H)Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNeal, E.T.; Lewandowski, G.A.; Daly, J.W.

1985-03-01

(/sup 3/H)Batrachotoxinin A benzoate ((/sup 3/H)BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of (/sup 3/H)BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of (/sup 3/H)BTX-B binding provides a rapid,more » quantitative, and facile method for the screening and investigation of local anesthetic activity.« less

Efficacy and safety of bupivacaine versus lidocaine in dental treatments: a meta-analysis of randomised controlled trials.

PubMed

Su, Naichuan; Wang, Hang; Zhang, Shu; Liao, Shuang; Yang, Shuying; Huang, Yi

2014-02-01

The objective of this study was to assess the efficacy and safety of bupivacaine compared with lidocaine in local anaesthesia in dental treatment. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organisation (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomised controlled trials comparing bupivacaine with lidocaine in terms of efficacy and safety. Sixteen studies were included, of which nine had low, six had moderate and one had high risk of bias. In comparison with 2% lidocaine plus 1:100,000 adrenaline, 0.5% bupivacaine plus 1:200,000 adrenaline showed a higher success rate in inflamed pulp (P = 0.03) but a lower success rate in vital pulp (P < 0.00001), a lower percentage of patients using postoperative analgesics (P < 0.00001), a longer onset times of pulpal anaesthesia and a longer duration of pulpal anaesthesia (P < 0.00001). In comparison with 2% lidocaine plus 1:80,000 adrenaline, 0.75% bupivacaine plus 1:200,000 adrenaline had same level of success rate (P = 0.29), and was better in postoperative pain control (P = 0.001) while 0.75% levobupivacaine had same level of postoperative pain control (P = 0.16); 0.5% levobupivacaine had higher success rate (P = 0.04) and was better in postoperative pain control (P = 0.001) than 2% lidocaine. There was no statistically significance in adverse events between two groups. Given the efficacy and safety, the bupivacaine group is better than the lidocaine group in dental operations that take a relatively long time, especially in endodontic treatments or where there is a need for postoperative pain management. © 2013 FDI World Dental Federation.

Comparison of the analgesic efficacy of ultrasound-guided rectus sheath block and local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children.

PubMed

Uchinami, Yuka; Sakuraya, Fumika; Tanaka, Nobuhiro; Hoshino, Koji; Mikami, Eri; Ishikawa, Taro; Fujii, Hitomi; Ishikawa, Takehiko; Morimoto, Yuji

2017-05-01

Ultrasound-guided rectus sheath block and local anesthetic infiltration are the standard options to improve postoperative pain for children undergoing surgery with a midline incision. However, there is no study comparing the effect of ultrasound-guided rectus sheath block with local anesthetic infiltration for children undergoing laparoscopic surgery. The aim of this trial was to compare the onset of ultrasound-guided rectus sheath block with that of local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children. We performed an observer-blinded, randomized, prospective trial. Enrolled patients were assigned to either an ultrasound-guided rectus sheath block group or a local anesthetic infiltration group. The ultrasound-guided rectus sheath block group (n = 17) received ultrasound-guided rectus sheath block with 0.2 ml·kg -1 of 0.375% ropivacaine per side in the posterior rectus sheath compartment. The local anesthetic infiltration group (n = 17) received local anesthetic infiltration with 0.2 ml·kg -1 of 0.75% ropivacaine. The Face, Legs, Activity, Cry, and Consolability (FLACC) pain scores were recorded at 0, 30, 60 min after arrival at the postanesthesia care unit. Of the 37 patients enrolled in this study, 34 completed the study protocol. A significant difference in the pain scale between the ultrasound-guided rectus sheath block group and local anesthetic infiltration group was found at 0 min (median: 0, interquartile range [IQR]: 0-1.5, vs median: 1, IQR 0-5, confidence interval of median [95% CI]: 0-3, P = 0.048), but no significant difference was found at 30 min (median: 1, IQR: 0-4 vs median: 6, IQR: 0-7, 95% CI: 0-5, P = 0.061), or 60 min (median: 0, IQR: 0-2 vs median: 1, IQR: 0-3, 95% CI: -1 to 1, P = 0.310). No significant difference was found in anesthesia time between the ultrasound-guided rectus sheath block and local anesthetic infiltration groups. No procedure-related complications were observed in either group. Ultrasound-guided rectus sheath block is a quicker way to control postoperative pain for pediatric patients undergoing laparoscopic extraperitoneal closure than local anesthetic infiltration, and thus may provide a clinical benefit. © 2017 John Wiley & Sons Ltd.

Synergism and antagonism in extracting local anesthetics from aqueous media with mixtures of solvents

NASA Astrophysics Data System (ADS)

Sukhanov, P. T.; Chibisova, T. V.; Korenman, Ya. I.

2014-12-01

The extraction of local anesthetics from aqueous media with mixtures of solvent is examined and its synergistic and antagonistic effects are determined. Synergism parameters, separation factors, constants for the formation of anesthetic complexes, and solvate numbers are calculated.

Opioids as an alternative to amide-type local anaesthetics for intra-articular application.

PubMed

Ickert, Irina; Herten, Monika; Vogl, Melanie; Ziskoven, Christoph; Zilkens, Christoph; Krauspe, Rüdiger; Kircher, Jörn

2015-09-01

Recently, the safety profile of local anaesthetics in intra-articular use became into focus of investigation. Opioid drugs have a different mode of action and may be a safe and potent alternative for intra-articular application. The purpose of this in vitro study is to provide evidence for significant chondrotoxicity of amide-type local anaesthetics even after short-term application on human chondrocytes and to demonstrate the absence of such negative effects for opioids [morphine, morphine-6-glucuronide (M6G)]. Visually intact cartilage explants of human, mainly osteoarthritic joints (n = 9), were harvested and cultivated in monolayer for expansion and transferred into alginate bead. The beads were incubated for increasing incubation times (15 min, 1 and 4 h) in decreasing concentrations (full, ½, ¼ for 15 min) of bupivacaine, ropivacaine, morphine, M6G or saline control. Adenosine triphosphate content of 798 beads was measured 3 days post-incubation to assess cell viability. A clear ranking of cytotoxic potency: bupivacaine > ropivacaine > morphine = M6G = saline was observed. Results reveal a dose- and time-dependent manner of cytotoxic effects on human chondrocytes for bupivacaine and ropivacaine but not for opioids. Cell viability after exposure to morphine and M6G was comparable to exposure to saline. The results confirm dose- and time-dependent cytotoxic effects on human chondrocytes for amide-type local anaesthetics. This study confirms the safety of morphine and M6G in terms of an absence of cytotoxic effects after intra-articular application, making them safe potential alternatives in clinical practice.

Polymer-xerogel composites for controlled release wound dressings.

PubMed

Costache, Marius C; Qu, Haibo; Ducheyne, Paul; Devore, David I

2010-08-01

Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol-gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer-xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings. 2010 Elsevier Ltd. All rights reserved.

Comparison between xCELLigence biosensor technology and conventional cell culture system for real-time monitoring human tenocytes proliferation and drugs cytotoxicity screening.

PubMed

Chiu, Chih-Hao; Lei, Kin Fong; Yeh, Wen-Ling; Chen, Poyu; Chan, Yi-Sheng; Hsu, Kuo-Yao; Chen, Alvin Chao-Yu

2017-10-16

Local injections of anesthetics, NSAIDs, and corticosteroids for tendinopathies are empirically used. They are believed to have some cytotoxicity toward tenocytes. The maximal efficacy dosages of local injections should be determined. A commercial 2D microfluidic xCELLigence system had been developed to detect real-time cellular proliferation and their responses to different stimuli and had been used in several biomedical applications. The purpose of this study is to determine if human tenocytes can successfully proliferate inside xCELLigence system and the result has high correlation with conventional cell culture methods in the same condition. First passage of human tenocytes was seeded in xCELLigence and conventional 24-well plates. Ketorolac tromethamine, bupivacaine, methylprednisolone, and betamethasone with different concentrations (100, 50, and 10% diluted of clinical usage) were exposed in both systems. Gene expression of type I collagen, type III collagen, tenascin-C, decorin, and scleraxis were compared between two systems. Human tenocytes could proliferate both in xCELLigence and conventional cell culture systems. Cytotoxicity of each drug revealed dose-dependency when exposed to tenocytes in both systems. Significance was found between groups. All the four drugs had comparable cytotoxicity in their 100% concentration. When 50% concentration was used, betamethasone had a relatively decreased cytotoxicity among them in xCELLigence but not in conventional culture. When 10% concentration was used, betamethasone had the least cytotoxicity. Strong and positive correlation was found between cell index of xCELLigence and result of WST-1 assay (Pearson's correlation [r] = 0.914). Positive correlation of gene expression between tenocytes in xCELLigence and conventional culture was also observed. Type I collagen: [r] = 0.823; type III collagen: [r] = 0.899; tenascin-C: [r] = 0.917; decorin: [r] = 0.874; and scleraxis: [r] = 0.965. Human tenocytes could proliferate inside xCELLigence system. These responses varied when tenocytes were exposed to different concentrations of ketorolac tromethamine, bupivacaine, methylprednisolone, and betamethasone. The result of cell proliferation and gene expression of tenocytes in both xCELLigence and conventional culture system is strongly correlated. xCELLigence culture system may replace conventional cell culture, which made real-time tenocyte proliferation monitoring possible.

Nocebo-induced hyperalgesia during local anesthetic injection.

PubMed

Varelmann, Dirk; Pancaro, Carlo; Cappiello, Eric C; Camann, William R

2010-03-01

Common practice during local anesthetic injection is to warn the patient using words such as: "You will feel a big bee sting; this is the worst part." Our hypothesis was that using gentler words for administration of the local anesthetic improves pain perception and patient comfort. One hundred forty healthy women at term gestation requesting neuraxial analgesia were randomized to either a "placebo" ("We are going to give you a local anesthetic that will numb the area and you will be comfortable during the procedure") or "nocebo" ("You are going to feel a big bee sting; this is the worst part of the procedure") group. Pain was assessed immediately after the local anesthetic skin injection using verbal analog scale scores of 0 to 10. Median verbal analog scale pain scores were lower when reassuring words were used compared with the harsher nocebo words (3 [2-4] vs 5 [3-6]; P < 0.001). Our data suggest that using gentler, more reassuring words improves the subjective experience during invasive procedures.

Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice.

PubMed

Grant, G J; Piskoun, B; Bansinath, M

2003-12-01

1. The objective of the present study was to assess the time-course profile of analgesia and bupivacaine concentrations at the site of injection after subcutaneous administration of a single dose of standard bupivacaine or a novel controlled-release liposomal bupivacaine formulation. 2. Groups of mice were injected subcutaneously with 0.2 mL of 0.5% standard bupivacaine or 0.5, 1 or 2% liposomal bupivacaine. 3. A prolonged duration of analgesia occurred in mice receiving liposomal bupivacaine. In the liposomal groups, the bupivacaine remained at the injection site for more than 96 h, compared with approximately 8 h in groups injected with standard bupivacaine. 4. These results confirm that the prolonged analgesia observed after injection of the liposomal formulation is associated with sustained higher levels of bupivacaine at the site of injection.

Local Anesthetics: Review of Pharmacological Considerations

PubMed Central

Becker, Daniel E; Reed, Kenneth L

2012-01-01

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article. PMID:22822998

Local anesthetic infusion pump for pain management following total knee arthroplasty: a meta-analysis.

PubMed

Zhang, Yeying; Lu, Ming; Chang, Cheng

2017-01-23

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) were to evaluate the effect and safety of local anesthetic infusion pump versus placebo for pain management following total knee arthroplasty (TKA). In September 2016, a systematic computer-based search was conducted in the Pubmed, ISI Web of Knowledge, Embase, Cochrane Database of Systematic Reviews. Randomized controlled trials of patients prepared for primary TKA that compared local anesthetic infusion pump versus placebo for pain management following TKA were retrieved. The primary endpoint was the visual analogue scale (VAS) with rest or mobilization at 24, 48 and 72 h and morphine consumption at 24 and 48 h. The second outcomes are range of motion, length of hospital stay (LOS) and complications (infection, deep venous thrombosis (DVT), prolonged drainage and postoperative nausea and vomiting (PONV)). Seven clinical studies with 587 patients were included and for meta-analysis. Local anesthetic infusion pump are associated with less pain scores with rest or mobilization at 24 and 48 h with significant difference. However, the difference was likely no clinical significance. There were no significant difference between the LOS, the occurrence of DVT, prolonged drainage and PONV. However, local anesthetic infusion pump may be associated with more infection. Based on the current meta-analysis, we found no evidence to support the routine use of local anesthetic infusion pump in the management of acute pain following TKA. More RCTs are still need to identify the pain control effects and optimal dose and speed of local anesthetic pain pump.

Preventive Analgesia by Local Anesthetics: The Reduction of Postoperative Pain by Peripheral Nerve Blocks and Intravenous Drugs

PubMed Central

Barreveld, Antje; Witte, Jürgen; Chahal, Harkirat; Durieux, Marcel E.; Strichartz, Gary

2012-01-01

The use of local anesthetics to reduce acute postoperative pain has a long history, but recent reports have not been systematically reviewed. In addition, the need to include only those clinical studies that meet minimum standards for randomization and blinding must be adhered to. In this review we have applied stringent clinical study design standards to identify publications on the use of perioperative local anesthetics. We first examined several types of peripheral nerve blocks, covering a variety of surgical procedures, and second, for effects of intentionally administered IV local anesthetic (lidocaine) for suppression of postoperative pain. Thirdly, we have examined publications in which vascular concentrations of local anesthetics were measured at different times after peripheral nerve block procedures, noting the incidence when those levels reached ones achieved during intentional IV administration. Importantly, the very large number of studies using neuraxial blockade techniques (epidural, spinal) has not been included in this review but will be dealt with separately in a later review. The overall results showed a strongly positive effect of local anesthetics, by either route, for suppressing postoperative pain scores and analgesic (opiate) consumption. In only a few situations were the effects equivocal. Enhanced effectiveness with the addition of adjuvants was not uniformly apparent. The differential benefits between drug delivery before, during, or immediately after a surgical procedure are not obvious, and a general conclusion is that the significant antihyperalgesic effects occur when the local anesthetic is present during the acute postoperative period, and its presence during surgery is not essential for this action. PMID:23408672

Anesthetic management of a 4-month-old red fox (Vulpes vulpes) for orthopedic surgery.

PubMed

Anagnostou, Tilemahos; Flouraki, Eugenia; Kostakis, Charalampos; Komnenou, Anastasia; Prassinos, Nikitas; Raptopoulos, Dimitrios

2015-03-01

A 4-mo-old red fox (Vulpes vulpes) was found recumbent after a vehicular accident. Radiology revealed several limb fractures and the fox underwent surgery after 24 hr of initial stabilization. Premedication consisted of dexmedetomidine and morphine. Anesthesia was induced with ketamine and midazolam and maintained with isoflurane. Lidocaine, bupivacaine, and morphine were administered epidurally and further analgesia was provided with meloxicam. The heart rate and respiratory rate of the fox remained stable during surgery and, except for a mild hypothermia, the recovery from anesthesia was uneventful. The postoperative pain scores were low and the animal was transported to a rehabilitation facility and eventually released to the wild. The low pain scores postoperatively should be attributed to the successful application of epidural anesthesia and analgesia.

Non-invasive continuous imaging of drug release from soy-based skin equivalent using wide-field interferometry

NASA Astrophysics Data System (ADS)

Gabai, Haniel; Baranes-Zeevi, Maya; Zilberman, Meital; Shaked, Natan T.

2013-04-01

We propose an off-axis interferometric imaging system as a simple and unique modality for continuous, non-contact and non-invasive wide-field imaging and characterization of drug release from its polymeric device used in biomedicine. In contrast to the current gold-standard methods in this field, usually based on chromatographic and spectroscopic techniques, our method requires no user intervention during the experiment, and only one test-tube is prepared. We experimentally demonstrate imaging and characterization of drug release from soy-based protein matrix, used as skin equivalent for wound dressing with controlled anesthetic, Bupivacaine drug release. Our preliminary results demonstrate the high potential of our method as a simple and low-cost modality for wide-field imaging and characterization of drug release from drug delivery devices.

Improved Chondrotoxic Profile of Liposomal Bupivacaine Compared With Standard Bupivacaine After Intra-articular Infiltration in a Porcine Model.

PubMed

Shaw, K Aaron; Moreland, Colleen; Jacobs, Jeremy; Hire, Justin M; Topolski, Richard; Hoyt, Nathan; Parada, Stephen A; Cameron, Craig D

2018-01-01

Increasingly, liposomal bupivacaine is being used with multimodal pain management strategies. In vitro investigations have shown decreased chondrotoxicity profiles for liposomal bupivacaine; however, there is no evidence regarding its in vivo effects. Hypothesis/Purpose: This study sought to investigate the in vivo chondrotoxicity of liposomal bupivacaine, hypothesizing that there would be increased chondrocyte viability after exposure to liposomal bupivacaine when compared with standard bupivacaine. Controlled laboratory study. Eight juvenile, female Yorkshire cross piglets underwent a lateral stifle joint injection with either 1.3% liposomal bupivacaine or 0.5% bupivacaine. Injections were performed on one joint per animal with no injection to the contralateral knee, which served as the control. Chondrocyte viability was assessed 1 week after injection with a live-dead staining protocol and histologic examination. Significant chondrocyte death was seen with the live-dead staining in the bupivacaine group (33% nonviable cells) in comparison with liposomal bupivacaine (6.2%) and control (5.8%) groups ( P < .01). However, histologic examination showed no differences in chondral surface integrity, fibrillation, and chondrocyte viability. Liposomal bupivacaine was found to be safe for intra-articular injection in this animal model. Although bupivacaine demonstrated decreased chondrocyte viability on a cellular level, histologically there were no changes. This study highlights the dichotomy between fluorescent staining and histologic appearance of articular chondrocytes in short-term analyses of viability. This study supports the peri-articular application of liposomal bupivacaine in the setting of preserved articular cartilage. A single injection of standard bupivacaine did not produce histologic changes in the articular cartilage.

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks.

PubMed

Ilfeld, Brian M; Viscusi, Eugene R; Hadzic, Admir; Minkowitz, Harold S; Morren, Michael D; Lookabaugh, Janice; Joshi, Girish P

2015-01-01

Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks. Data from 6 controlled (phases I-III) studies were compiled involving single-injection ankle, femoral nerve, and intercostal nerve blocks (2 each). Adverse events (AEs) were monitored for 1 to 30 days after study drug administration. Of 575 subjects, 335 received liposome bupivacaine (2-310 mg), 33 received bupivacaine HCl (75-125 mg), and 207 received normal saline (placebo). Overall, 76% of subjects receiving liposome bupivacaine experienced 1 or more AEs compared with 61% receiving bupivacaine HCl and 76% receiving placebo. The most frequently reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia, pruritus, constipation, and vomiting. The most common treatment-related AE was hypesthesia among subjects treated with liposome bupivacaine or bupivacaine HCl. Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs was 9%, 0%, and 12%, respectively. At least 1 serious AE occurred in 8% of subjects receiving liposome bupivacaine compared with 10% of those receiving placebo (none assessed by investigators as related to study medication). Liposome bupivacaine has a similar safety and side effect profile to bupivacaine HCl and normal saline, suggesting that most of the more common AEs are related to either opioid rescue or the surgical procedure itself.

Structural damage to periodontal tissues at varying rate of anesthetic injection.

PubMed

Sarapultseva, Maria; Sarapultsev, Alexey; Medvedeva, Svetlana; Danilova, Irina

2018-04-01

Incorrect administration of an anesthetic during local anesthesia is one of the most important causes of pain symptoms in patients scheduled for dental procedures. The current study assessed the severity of damage to periodontal tissue following different rates of anesthetic administration. The research was conducted on 50 outbred male rats with a body mass of 180-240 g. The anesthetic used was 1% articaine. The results showed that administration of the anesthetic at a rapid pace caused structural damage to the periodontal tissue. Further, signs of impaired microcirculation were noted at all rates of administration. Biochemical studies demonstrated changes in the level of glucose and enzymes with the rapid introduction of the anesthetic, indicating severe systemic stress response of the body. Injection of local anesthetic at any rate of introduction induces vascular congestion in the microcirculatory bloodstream and exudative reactions. Rapid introduction of an anesthetic causes progression of structural changes in the gingival tissue.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

PubMed

Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

2014-01-01

Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under ultrasound guidance after shoulder surgery, automated boluses of local anesthetic combined with PRN boluses did not provide any reduction in local anesthetic consumption or rescue analgesia, compared with continuous infusion combined with PRN boluses.

Densities of dextrose-free intrathecal local anesthetics, opioids, and combinations measured at 37 degrees C.

PubMed

Richardson, M G; Wissler, R N

1997-01-01

Dextrose-free anesthetic medications are commonly used to provide subarachnoid anesthesia and analgesia. Hypobaricity has been proposed as a mechanism to explain postural effects on the extent of sensory block produced by these drugs. Densities of dextrose-free solutions of local anesthetics and opioids, and commonly used anesthetic/opioid mixtures were determined at 37.00 degrees C for comparison with the density of human cerebrospinal fluid (CSF). Measurements accurate to 0.00001 g/mL were performed using a mechanical oscillation resonance frequency density meter. All undiluted solutions tested are hypobaric relative to human lumbar CSF with the exception of lidocaine 1.5% and 2.0% with epinephrine 1:200,000. All mixtures of local anesthetics and opioids tested are hypobaric. We observed good agreement between measured densities and calculated weighted average densities of anesthetic mixtures. While the influence of baricity on the clinical effects of dextrose-free intrathecal anesthetics remains controversial, attempts to attribute postural effects to the baricity of these drugs requires establishment of accurate density values. These density data may facilitate elucidation of the mechanisms underlying the behavior of dextrose-free intrathecal anesthetics.

The successful use of intralipid for treatment of local anesthetic-induced central nervous system toxicity: Some considerations for administration of intralipid in an emergency.

PubMed

Espinet, Anthony J; Emmerton, Mark T

2009-01-01

Intralipid has been proposed as a treatment option for local anesthetic (LA) toxicity, which does not respond to traditional resuscitation methods. This paper presents a case report of a patient who developed signs of local anesthetic toxicity and was subsequently treated with 20% Intralipid with a positive response. Some background and practical applications regarding this treatment are discussed.

Local Infiltration of Tramadol versus Bupivacaine for Post Cesarean Section Pain Control: A Double-Blind Randomized Study.

PubMed

Sahmeddini, Mohammad Ali; Azemati, Simin; Motlagh, Ehsan Masoudi

2017-05-01

Postoperative pain control after cesarean section (C/S) is important because inadequate postoperative pain control can result in a prolonged hospital stay. In this study, we compared postoperative somatic wound pain control between patients receiving tramadol and bupivacaine, infiltrated at the wound site. In this randomized clinical trial, 98 patients, eligible for elective C/S under general anesthesia, were randomly allocated to 2 groups. Before wound closure, 20 cc of 0.025% bupivacaine and 2 mg/kg of tramadol, diluted to 20 cc, were infiltrated at the wound site in groups A and B, respectively. After surgery, the pain score was measured using the visual analogue scale (VAS). Additionally, 24-hour total morphine consumption, nausea and vomiting, and respiratory depression were compared after 2, 4, 8, 16, and 24 hours between the 2 groups. The data were analyzed using SPSS with the Student independent t test, χ 2 test, Fisher exact test, and repeated measure test. Postoperatively, there was no significant difference between these 2 groups in their VAS scores until 16 hours (P>0.05). However, at the 16 th and 24 th hours, the mean VAS scores were 3.20±2.24 and 2.51±2.55 in the bupivacaine group and 2.51±0.99 and 1.40±0.88 in the tramadol group, respectively (P<0.05). There was no difference in nausea and vomiting during the 24-hour period between the 2 groups. Also, no respiratory depression was detected in the both groups. Local infiltration of tramadol (2 mg/kg) at the incision site of C/S was effective in somatic wound pain relief without significant complications. IRCT2013070111662N2.

Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial.

PubMed

Mont, Michael A; Beaver, Walter B; Dysart, Stanley H; Barrington, John W; Del Gaizo, Daniel J

2018-01-01

Local infiltration analgesia (LIA) with liposomal bupivacaine (LB) in patients undergoing total knee arthroplasty (TKA) has yielded mixed results. The PILLAR study, which was designed to minimize limitations associated with previous studies, compared the effects of LIA with or without LB on pain scores, opioid consumption, including proportion of opioid-free patients, time to first opioid rescue, and safety after primary unilateral TKA. Patients (N = 140) were randomized to LIA with LB 266 mg/20 mL (admixed with bupivacaine HCl 0.5%, 20 mL) or LIA with bupivacaine HCl 0.5%, 20 mL. Standardized infiltration techniques and a standardized multimodal pain management protocol were used. The coprimary efficacy endpoints were area under the curve (AUC) of visual analog scale pain intensity scores 12-48 hours (AUC 12-48 ) postsurgery and total opioid consumption 0-48 hours postsurgery. Mean AUC 12-48 of visual analog scale pain intensity score was 180.8 with LB and 209.3 without LB (least squares [LS] mean treatment difference -26.88, P = .0381). LS mean total opioid consumption 0-48 hours postsurgery was 18.7 mg with and 84.9 mg without LB (LS ratio 0.220, P = .0048). Significant differences in favor of LB were observed for the percentage of opioid-free patients (P < .01) and time to first opioid rescue (P = .0230). Treatments were similarly well tolerated. This study provides data on LIA with LB administered using optimal techniques specific to TKA. In this setting, LIA with LB significantly improved postsurgical pain, opioid consumption, and time to first opioid rescue, with more opioid-free patients and no unexpected safety concerns. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Intrathecal hyperbaric versus isobaric bupivacaine for adult non-caesarean-section surgery: systematic review protocol.

PubMed

Uppal, Vishal; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

2016-05-18

Bupivacaine is the most commonly used local anaesthetic for spinal anaesthesia (SA). There are two forms of commercially available bupivacaine; isobaric bupivacaine (IB): a formulation with a specific gravity or density equal to cerebrospinal fluid, and hyperbaric bupivacaine (HB): a formulation with density heavier than cerebrospinal fluid. The difference in densities of the two available preparations is believed to affect the diffusion pattern that determines the effectiveness, spread and side-effect profile of bupivacaine. This systematic review will summarise the best available evidence regarding the effectiveness and safety on the use of HB compared with IB, when used to provide SA for surgery. Primarily, we will analyse the need for conversion to general anaesthesia. As secondary outcomes, we will compare the incidence of hypotension, incidence of nausea/vomiting, the onset time and duration of anaesthesia. We will search key electronic databases using search strategy (1) injections, spinal OR intrathecal OR subarachnoid; (2) bupivacaine OR levobupivacaine; (3) hypobaric OR isobaric OR plain; (4) baricity. We will search MEDLINE, EMBASE and Cochrane databases, from their inception for randomised controlled trials, with no restrictions on language. Caesarean section surgery will be excluded. 2 reviewers will independently extract the data using a standardised form. Extracted items will include study characteristics, risk of bias domains, as per modified Cochrane risk of bias, participant disposition and study outcomes. We will conduct a meta-analysis for variables that can be compared across the studies. We will evaluate clinical heterogeneity by qualitatively appraising differences in study characteristics in participants, interventions and the outcomes assessed. We will report our findings as relative risks (dichotomous), and weighted mean differences (continuous) for individual outcomes, along with their 95% CIs. We plan to submit, and will publish, our findings in a peer-reviewed scientific journal, and present our results at national and international meetings. CRD42015017672. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The evidence for reducing the pain of administration of local anesthesia and cosmetic injectables.

PubMed

Babamiri, Kajal; Nassab, Reza

2010-09-01

Administration of injections, whether local anesthetic or cosmetic injectable, can result in significant distress and discomfort to patients. This review explores factors that can alleviate anxiety and pain associated with injections including cosmetic injectables. We highlight that many techniques used to reduce pain have only been reported based on anecdotal evidence and small series. The techniques that have been reported to reduce pain, by randomized controlled trials, include pretreatment with topical local anesthetic agents and combined cosmetic injectables with local anesthetics. © 2010 Wiley Periodicals, Inc.

Computer-controlled local anesthetic delivery for painless anesthesia: a literature review

PubMed Central

Kwak, Eun-Jung; Pang, Nan-Sim; Cho, Jin-Hyung; Jung, Bock-Young; Kim, Kee-Deog

2016-01-01

Local anesthesia is administered to reduce pain during dental treatments, but may itself cause pain and contribute to increased dental fear. Computer-controlled local anesthetic delivery (CCLAD) is one the method to reduce patient pain during local anesthesia; it is a device that slowly administers anesthetics by using a computerized device to control the injection speed. This literature review aims to provide an objective assessment of the usefulness of CCLAD for controlling pain by reviewing papers published to date that have used CCLAD. PMID:28879299

Pregnancy outcome after in utero exposure to local anesthetics as part of dental treatment: A prospective comparative cohort study.

PubMed

Hagai, Aharon; Diav-Citrin, Orna; Shechtman, Svetlana; Ornoy, Asher

2015-08-01

Dental treatment and use of local anesthetics during pregnancy generally are considered harmless because of lack of evidence of adverse pregnancy effects. Data on the safety of dental treatment and local anesthetics during pregnancy are scant. Dental care is often a reason for concern both among women and their health care providers. The primary objective of this study was to evaluate the rate of major anomalies after exposure to local anesthetics as part of dental care during pregnancy. The authors performed a prospective, comparative observational study at the Israeli Teratology Information Services between 1999 and 2005. The authors followed 210 pregnancies exposed to dental local anesthetics (112 [53%] in the first trimester) and compared them with 794 pregnancies not exposed to teratogens. The rate of major anomalies was not significantly different between the groups (4.8% versus 3.3%, P = .300). There was no difference in the rate of miscarriages, gestational age at delivery, or birth weight. The most common types of dental treatment were endodontic treatment (43%), tooth extraction (31%), and tooth restoration (21%). Most women (63%) were not exposed to additional medications. Approximately one-half (51%) of the women were not exposed to dental radiography, and 44% were exposed to radiation, mostly bite-wing radiography. This study's results suggest that use of dental local anesthetics, as well as dental treatment during pregnancy, do not represent a major teratogenic risk. There seems to be no reason to prevent pregnant women from receiving dental treatment and local anesthetics during pregnancy. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Relief of Injection Pain During Delivery of Local Anesthesia by Computer-Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial.

PubMed

Chang, Hyeyoon; Noh, Jiyoung; Lee, Jungwon; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul

2016-07-01

Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. Within the limitations of the present study, relief from injection pain is observed using CNR.

Corticosteroid Injection for the Treatment of Morton's Neuroma: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Trial.

PubMed

Lizano-Díez, Xavier; Ginés-Cespedosa, Alberto; Alentorn-Geli, Eduard; Pérez-Prieto, Daniel; González-Lucena, Gemma; Gamba, Carlo; de Zabala, Santiago; Solano-López, Alberto; Rigol-Ramón, Pau

2017-09-01

The effectiveness of corticosteroid injection for the treatment of Morton's neuroma is unclear. In addition, most of the studies related to it are case-control or retrospective case series. The purpose of this study was to compare the effectiveness between corticosteroid injection associated with local anesthetic and local anesthetic alone (placebo control group) for the treatment of Morton's neuroma. Forty-one patients with a diagnosis of Morton's neuroma were randomized to receive 3 injections of either a corticosteroid plus a local anesthetic or a local anesthetic alone. The patients and the researcher who collected data were blinded to the treatment groups. The visual analog scale for pain and the American Orthopaedic Foot & Ankle Score (metatarsophalangeal/interphalangeal score) were obtained at baseline, after each injection, and at 3 and 6 months after the last injection. There were no significant between-group differences in terms of pain and function improvement at 3 and 6 months after treatment completion in comparison with baseline values. At the end of the study, 17 (48.5%) patients requested surgical excision of the neuroma: 7 (44%) in the experimental group and 10 (53%) in the control group ( P = 1.0). The injection of a corticosteroid plus a local anesthetic was not superior to a local anesthetic alone in terms of pain and function improvement in patients with Morton's neuroma. Level I, randomized controlled trial.

The relationship between pH and concentrations of antioxidants and vasoconstrictors in local anesthetic solutions.

PubMed

Hondrum, S O; Ezell, J H

1996-01-01

pH affects the efficacy of local anesthetics by determining the percentage of the lipid-soluble base form of the anesthetic available for diffusion and penetration of the nerve sheath. The purpose of this study was to determine the relationship between pH and the concentrations of antioxidant and vasoconstrictor in dental local anesthetic solutions over real-time and after accelerated aging. Several batches of lidocaine and mepivacaine with vasoconstrictors were tested. Results showed that, immediately upon receipt from the manufacturers, three batches were below the USP pH limit (pH 3.3), and two batches contained less than the minimum limit of vasoconstrictors (90%). Real-time tests on batches that were within normal limits revealed that solutions were stable past 4 yr. Accelerated aging tests revealed a strong correlation between a decrease in pH and loss of antioxidants and vasoconstrictors. In conclusion, a quality batch of local anesthetic should remain efficacious long past the manufacturer's stated shelf life; a batch that is less than optimal, or one that is exposed to environmental stresses, will degrade rapidly, and efficacy may be affected by decreases in pH and loss of vasoconstrictor. pH may be an inexpensive, readily available screening test for efficacy of local anesthetics.

The relationship between pH and concentrations of antioxidants and vasoconstrictors in local anesthetic solutions.

PubMed Central

Hondrum, S. O.; Ezell, J. H.

1996-01-01

pH affects the efficacy of local anesthetics by determining the percentage of the lipid-soluble base form of the anesthetic available for diffusion and penetration of the nerve sheath. The purpose of this study was to determine the relationship between pH and the concentrations of antioxidant and vasoconstrictor in dental local anesthetic solutions over real-time and after accelerated aging. Several batches of lidocaine and mepivacaine with vasoconstrictors were tested. Results showed that, immediately upon receipt from the manufacturers, three batches were below the USP pH limit (pH 3.3), and two batches contained less than the minimum limit of vasoconstrictors (90%). Real-time tests on batches that were within normal limits revealed that solutions were stable past 4 yr. Accelerated aging tests revealed a strong correlation between a decrease in pH and loss of antioxidants and vasoconstrictors. In conclusion, a quality batch of local anesthetic should remain efficacious long past the manufacturer's stated shelf life; a batch that is less than optimal, or one that is exposed to environmental stresses, will degrade rapidly, and efficacy may be affected by decreases in pH and loss of vasoconstrictor. pH may be an inexpensive, readily available screening test for efficacy of local anesthetics. PMID:10323112

An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid-polymer hybrid nanoparticles for local anesthetic therapy.

PubMed

Wang, Jianguo; Zhang, Laizhu; Chi, Huimin; Wang, Shilei

2016-05-01

The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid-polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Their in vitro skin permeation was studied using a Franz diffusion cell mounted with depilated mouse skin in vitro. In vivo local anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Compared with LA-LPs, LA-LPNs showed significantly better in vitro skin permeation ability and in vivo local anesthetic effects. The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy.

General anesthesia versus segmental thoracic or conventional lumbar spinal anesthesia for patients undergoing laparoscopic cholecystectomy.

PubMed

Yousef, Gamal T; Lasheen, Ahmed E

2012-01-01

Laparoscopic cholecystectomy became the standard surgery for gallstone disease because of causing less postoperative pain, respiratory compromise and early ambulation. This study was designed to compare spinal anesthesia, (segmental thoracic or conventional lumbar) vs the gold standard general anesthesia as three anesthetic techniques for healthy patients scheduled for elective laparoscopic cholecystectomy, evaluating intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction. A total of 90 patients undergoing elective laparoscopic cholecystectomy, between January 2010 and May 2011, were randomized into three equal groups to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under segmental thoracic (TSA group) or conventional lumbar (LSA group) spinal anesthesia or general anesthesia (GA group). To achieve a T3 sensory level we used (hyperbaric bupivacaine 15 mg, and fentanyl 25 mg at L2/L3) for LSAgroup, and (hyperbaric bupivacaine 7.5 mg, and fentanyl 25 mg at T10/T11) for TSAgroup. Propofol, fentanyl, atracurium, sevoflurane, and tracheal intubation were used for GA group. Intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction were compared between the three groups. All procedures were completed laparoscopically by the allocated method of anesthesia with no anesthetic conversions. The time for the blockade to reach T3 level, intraoperative hypotensive and bradycardic events and vasopressor use were significantly lower in (TSA group) than in (LSA group). Postoperative pain scores as assessed throughout any time, postoperative right shoulder pain and hospital stay was lower for both (TSA group) and (LSA group) compared with (GA group). The higher degree of patients satisfaction scores were recorded in patients under segmental TSA. The present study not only confirmed that both segmental TSA and conventional lumber spinal anesthesia (LSA) are safe and good alternatives to general anesthesia (GA) in healthy patients undergoing laparoscopic cholecystectomy but also showed better postoperative pain control of both spinal techniques when compared with general anesthesia. Segmental TSA provides better hemodynamic stability, lesser vasopressor use and early ambulation and discharge with higher degree of patient satisfaction making it excellent for day case surgery compared with conventional lumbar spinal anesthesia.

Bupivacaine compared with etidocaine for vaginal delivery.

PubMed

Moore, D C; Bridenbaugh, P O; Bridenbaugh, L D; Thompson, G E; Balfour, R I; Lysons, D F

1975-01-01

A comparison of 0.5 percent etidocaine with 0.25 and 0.5 percent bupivacaine, using continuous (intermittent) caudal block in 60 vaginal deliveries, showed the latter two solutions to be the agents of choice. All solutions contained a final concentration of 1:2000,000 epihephrine. In 40 parturients given either 0.25 or 0.5 percent bupivacaine, all had pain relief after the initial dose, while 5 of 20 given etidocaine required a refill dose within 30 to 50 minutes for complete pain relief. The duration of action of the initial dose with both concentrations of bupivacaine was longer than that of etidocaine. The degree of motor blockade with 0.5 percent etidocaine was greater than with 0.5 percent bupivacaine, and with 0.5 percent concentrations of either etidocaine or bupivacaine was greater than with 0.25 percent bupivacaine. The duration of motor blockade of 0.5 percent etidocaine and bupivacaine was comparable. The duration of motor blockade of the 0.25 percent concentration of bupivacaine was shorter than with the 0.5 percent concentration of both etidocaine and bupivacaine; and with both bupivacaine concentrations the duration of sensory anesthesia in the extremities was longer than motor blockade; with etidocaine, the opposite occurred.

21 CFR 346.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... this part: (a) Analgesic, anesthetic drug. A topically (externally) applied drug that relieves pain by... cells of the epidermis. (h) Local anesthetic drug. A drug that produces local disappearance of pain...

21 CFR 346.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... this part: (a) Analgesic, anesthetic drug. A topically (externally) applied drug that relieves pain by... cells of the epidermis. (h) Local anesthetic drug. A drug that produces local disappearance of pain...

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review

PubMed Central

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures. PMID:27746520

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review.

PubMed

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures.

Updates of Topical and Local Anesthesia Agents.

PubMed

Boyce, Ricardo A; Kirpalani, Tarun; Mohan, Naveen

2016-04-01

As described in this article, there are many advances in topical and local anesthesia. Topical and local anesthetics have played a great role in dentistry in alleviating the fears of patients, eliminating pain, and providing pain control. Many invasive procedures would not be performed without the use and advances of topical/local anesthetics. The modern-day dentist has the responsibility of knowing the variety of products on the market and should have at least references to access before, during, and after treatment. This practice ensures proper care with topical and local anesthetics for the masses of patients entering dental offices worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block

PubMed Central

Sigirci, Aykut

2017-01-01

Background: Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1st day) pain control after total knee arthroplasty. Materials and Methods: 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Results: Group D patients experienced significantly better postoperative pain relief (P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) (P < 0.05). Group A got the best pain Vas score degrees in the 1st postoperative day which showed the success of combined periarticülar local anesthetic injection and femoral nerve block. Conclusion: The intraoperative periarticular application of local anesthetics in addition to one-shot femoral block is an efficient way of controlling postsurgical pain after TKA. PMID:28566779

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block.

PubMed

Sigirci, Aykut

2017-01-01

Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1 st day) pain control after total knee arthroplasty. 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Group D patients experienced significantly better postoperative pain relief ( P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1 st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) ( P < 0.05). Group A got the best pain Vas score degrees in the 1 st postoperative day which showed the success of combined periarticülar local anesthetic injection and femoral nerve block. The intraoperative periarticular application of local anesthetics in addition to one-shot femoral block is an efficient way of controlling postsurgical pain after TKA.

Steroid injections - tendon, bursa, joint

MedlinePlus

... a small amount of corticosteroid and a local anesthetic into the bursa. JOINT Any joint problem, such ... A small amount of corticosteroid and a local anesthetic will be injected into the joint. TENDON A ...

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

PubMed Central

Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

2015-01-01

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

Computer simulations of local anesthetic mechanisms: Quantum chemical investigation of procaine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Jeremy C; Bondar, A.N.; Suhai, Sandor

2007-02-01

A description at the atomic level of detail of the interaction between local anesthetics, lipid membranes and membrane proteins, is essential for understanding the mechanism of local anesthesia. The importance of performing computer simulations to decipher the mechanism of local anesthesia is discussed here in the context of the current status of understanding of the local anesthetics action. As a first step towards accurate simulations of the interaction between local anesthetics, proteins, lipid and water molecules, here we use quantum mechanical methods to assess the charge distribution and structural properties of procaine in the presence and in the absence ofmore » water molecules. The calculations indicate that, in the absence of hydrogen-bonding water molecules, protonated procaine strongly prefers a compact structure enabled by intramolecular hydrogen bonding. In the presence of water molecules the torsional energy pro?le of procaine is modified, and hydrogen bonding to water molecules is favored relative to intra-molecular hydrogen bonding.« less

The AAHKS Clinical Research Award: Liposomal Bupivacaine and Periarticular Injection Are Not Superior to Single-Shot Intra-articular Injection for Pain Control in Total Knee Arthroplasty.

PubMed

Jain, Rajesh K; Porat, Manny D; Klingenstein, Greg G; Reid, Jeremy J; Post, Robert E; Schoifet, Scott D

2016-09-01

Intraoperative injections can help reduce early postoperative pain in total knee arthroplasty. We proposed that liposomal bupivacaine would not be superior to more common and cheaper injections. A single-blinded prospective randomized study with 207 consecutive patients was completed. Patients were randomized to treatment with periarticular liposomal bupivacaine injection, periarticular injection of bupivacaine/morphine, or intra-articular injection of bupivacaine/morphine at the conclusion of the procedure. Postoperative visual analog pain scores and narcotic consumption were recorded and analyzed. There was no significant difference in postoperative visual analog pain scores or narcotic consumption among the 3 study groups. Intra-articular injection of bupivacaine and morphine is as effective for postoperative pain control in total knee arthroplasty as periarticular bupivacaine/morphine injection and liposomal bupivacaine. Use of liposomal bupivacaine in total knee arthroplasty is costly and not justified. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial.

PubMed

de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

2015-01-01

The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18-50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN.

Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial

PubMed Central

de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

2015-01-01

The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18–50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN. PMID:26061572

Comparison Between the Use of Ropivacaine Alone and Ropivacaine With Sufentanil in Epidural Labor Analgesia

PubMed Central

Wang, Xian; Xu, Shiqin; Qin, Xiang; Li, Xiaohong; Feng, Shan-Wu; Liu, Yusheng; Wang, Wei; Guo, Xirong; Shen, Rong; Shen, Xiaofeng; Wang, Fuzhou

2015-01-01

Abstract To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control. After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 μg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes. A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8–2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0–2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ± 2.06) than that in the combination group ($9.76 ± 3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes. The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids. PMID:26512604

Comparison Between the Use of Ropivacaine Alone and Ropivacaine With Sufentanil in Epidural Labor Analgesia.

PubMed

Wang, Xian; Xu, Shiqin; Qin, Xiang; Li, Xiaohong; Feng, Shan-Wu; Liu, Yusheng; Wang, Wei; Guo, Xirong; Shen, Rong; Shen, Xiaofeng; Wang, Fuzhou

2015-10-01

To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control.After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 μg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes.A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8-2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0-2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ± 2.06) than that in the combination group ($9.76 ± 3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes.The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids.

Effects of acepromazine and trazodone on anesthetic induction dose of propofol and cardiovascular variables in dogs undergoing general anesthesia for orthopedic surgery.

PubMed

Murphy, Lindsey A; Barletta, Michele; Graham, Lynelle F; Reichl, Lorna J; Duxbury, Margaret M; Quandt, Jane E

2017-02-15

OBJECTIVE To compare the doses of propofol required to induce general anesthesia in dogs premedicated with acepromazine maleate or trazodone hydrochloride and compare the effects of these premedicants on cardiovascular variables in dogs anesthetized for orthopedic surgery. DESIGN Prospective, randomized study. ANIMALS 30 systemically healthy client-owned dogs. PROCEDURES 15 dogs received acepromazine (0.01 to 0.03 mg/kg [0.005 to 0.014 mg/lb], IM) 30 minutes before anesthetic induction and 15 received trazodone (5 mg/kg [2.27 mg/lb] for patients > 10 kg or 7 mg/kg [3.18 mg/lb] for patients ≤ 10 kg, PO) 2 hours before induction. Both groups received morphine sulfate (1 mg/kg [0.45 mg/lb], IM) 30 minutes before induction. Anesthesia was induced with propofol (4 to 6 mg/kg [1.82 to 2.73 mg/lb], IV, to effect) and maintained with isoflurane or sevoflurane in oxygen. Bupivacaine (0.5 mg/kg [0.227 mg/lb]) and morphine (0.1 mg/kg [0.045 mg/lb]) were administered epidurally. Dogs underwent tibial plateau leveling osteotomy (n = 22) or tibial tuberosity advancement (8) and were monitored throughout anesthesia. Propofol induction doses and cardiovascular variables (heart rate and systemic, mean, and diastolic arterial blood pressures) were compared between groups. RESULTS The mean dose of propofol required for anesthetic induction and all cardiovascular variables evaluated did not differ between groups. Intraoperative hypotension developed in 6 and 5 dogs of the acepromazine and trazodone groups, respectively; bradycardia requiring intervention developed in 3 dogs/group. One dog that received trazodone had priapism 24 hours later and was treated successfully. No other adverse effects were reported. CONCLUSIONS AND CLINICAL RELEVANCE At the described dosages, cardiovascular effects of trazodone were similar to those of acepromazine in healthy dogs undergoing anesthesia for orthopedic surgery.

When pharmacologic anesthesia is precluded: the value of hypnosis as a sole anesthetic agent in dentistry.

PubMed

Kleinhauz, M; Eli, I

1993-01-01

Occasionally, a dental patient presents his/her dentist with a history of hypersensitivity to local anesthetic agents. The symptoms may include immediate reactions to the injection procedure (dizziness, shortness of breath, tachycardia, etc), or delayed reactions to the anesthetic (swelling, urticaria, etc). Although the true incidence of local anesthetic allergy is low, such a history often involves the patient's anxiety regarding the use of the drug in question, and the dentist's apprehension to treat the "problematic" patient. In such cases, hypnosis can play a major role in controlling pain and the associated distress. In the present article, the method concerning the implementation of hypnosis to induce local anesthesia is described and illustrated through case demonstrations.

Quantification of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using a simplified extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Cho, Sang-Hyun; Park, Jin-A; Zheng, Weijia; Abd El-Aty, A M; Kim, Seong-Kwan; Choi, Jeong-Min; Yi, Hee; Cho, Soo-Min; Afifi, Nehal A; Shim, Jae-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho-Chul

2017-10-15

In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC-MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Liposomal bupivacaine versus bupivacaine/epinephrine after video-assisted thoracoscopic wedge resection†.

PubMed

Parascandola, Salvatore A; Ibañez, Jessica; Keir, Graham; Anderson, Jacqueline; Plankey, Michael; Flynn, Deanna; Cody, Candice; De Marchi, Lorenzo; Margolis, Marc; Blair Marshall, M

2017-06-01

The purpose of this research is to compare liposomal bupivacaine and bupivacaine/epinephrine for intercostal blocks related to analgesic use and length of stay following video-assisted thoracoscopic wedge resection. A retrospective study of patients undergoing video-assisted thoracoscopic wedge resection from 2010 to 2015 was performed. We selected patients who stayed longer than 24 h in hospital. Primary outcomes were length of stay and postoperative analgesic use at 12-h intervals from 24 to 72 h. Intercostal blocks were performed with liposomal bupivacaine in 62 patients and bupivacaine/epinephrine in 51 patients. A Wilcoxon signed-rank test evaluated differences in median postoperative analgesic use and length of stay. Those who received liposomal bupivacaine consumed fewer analgesics than those who received bupivacaine/epinephrine, with a statistically significant difference from 24 to 36 h (20.25 vs 45.0 mg; P  = 0.0059) and from 60 to 72 h postoperatively (15.0 vs 33.75 mg; P  = 0.0350). In patients who stayed longer than 72 h, the median cumulative analgesic consumption in those who received liposomal bupivacaine was statistically significantly lower than those who received bupivacaine/epinephrine (120.0 vs 296.5 mg; P  = 0.0414). Median length of stay for the liposomal bupivacaine and bupivacaine/epinephrine groups were 45:05 h and 44:29 h, respectively. There were no adverse events related to blocks performed with liposomal bupivacaine. Thoracic surgery patients who have blocks performed with liposomal bupivacaine require fewer analgesics postoperatively. This may decrease complications related to poor pain control and decrease side effects related to narcotic use in our patient population. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain.

PubMed

Hamilton, Thomas W; Athanassoglou, Vassilis; Mellon, Stephen; Strickland, Louise H; Trivella, Marialena; Murray, David; Pandit, Hemant G

2017-02-01

Despite multi-modal analgesic techniques, acute postoperative pain remains an unmet health need, with up to three quarters of people undergoing surgery reporting significant pain. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained-release analgesia. To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. On 13 January 2016 we searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, ISI Web of Science and reference lists of retrieved articles. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. Randomised, double-blind, placebo- or active-controlled clinical trials in people aged 18 years or over undergoing elective surgery, at any surgical site, were included if they compared liposomal bupivacaine infiltration at the surgical site with placebo or other type of analgesia. Two review authors independently considered trials for inclusion, assessed risk of bias, and extracted data. We performed data analysis using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5.3. We planned to perform a meta-analysis and produce a 'Summary of findings' table for each comparison however there were insufficient data to ensure a clinically meaningful answer. As such we have produced two 'Summary of findings' tables in a narrative format. Where possible we assessed the quality of evidence using GRADE. We identified nine studies (10 reports, 1377 participants) that met inclusion criteria. Four Phase II dose-escalating/de-escalating trials, designed to evaluate and demonstrate efficacy and safety, presented pooled data that we could not use. Of the remaining five parallel-arm studies (965 participants), two were placebo controlled and three used bupivacaine hydrochloride local anaesthetic infiltration as a control. Using the Cochrane tool, we judged most studies to be at unclear risk of bias overall; however, two studies were at high risk of selective reporting bias and four studies were at high risk of bias due to size (fewer than 50 participants per treatment arm).Three studies (551 participants) reported the primary outcome cumulative pain intensity over 72 hours following surgery. Compared to placebo, liposomal bupivacaine was associated with a lower cumulative pain score between the end of the operation (0 hours) and 72 hours (one study, very low quality). Compared to bupivacaine hydrochloride, two studies showed no difference for this outcome (very low quality evidence), however due to differences in the surgical population and surgical procedure (breast augmentation versus knee arthroplasty) we did not perform a meta-analysis.No serious adverse events were reported to be associated with the use of liposomal bupivacaine and none of the five studies reported withdrawals due to drug-related adverse events (moderate quality evidence).One study reported a lower mean pain score at 12 hours associated with liposomal bupivacaine compared to bupivacaine hydrochloride, but not at 24, 48 or 72 hours postoperatively (very low quality evidence).Two studies (382 participants) reported a longer time to first postoperative opioid dose compared to placebo (low quality evidence).Two studies (325 participants) reported the total postoperative opioid consumption over the first 72 hours: one study reported a lower cumulative opioid consumption for liposomal bupivacaine compared to placebo (very low quality evidence); one study reported no difference compared to bupivacaine hydrochloride (very low quality evidence).Three studies (492 participants) reported the percentage of participants not requiring postoperative opioids over initial 72 hours following surgery. One of the two studies comparing liposomal bupivacaine to placebo demonstrated a higher number of participants receiving liposomal bupivacaine did not require postoperative opioids (very low quality evidence). The other two studies, one versus placebo and one versus bupivacaine hydrochloride, found no difference in opioid requirement (very low quality evidence). Due to significant heterogeneity between the studies (I 2 = 92%) we did not pool the results.All the included studies reported adverse events within 30 days of surgery, with nausea, constipation and vomiting being the most common. Of the five parallel-arm studies, none performed or reported health economic assessments or patient-reported outcomes other than pain.Using GRADE, the quality of evidence ranged from moderate to very low. The major limitation was the sparseness of data for outcomes of interest. In addition, a number of studies had a high risk of bias resulting in further downgrading. Liposomal bupivacaine at the surgical site does appear to reduce postoperative pain compared to placebo, however, at present the limited evidence does not demonstrate superiority to bupivacaine hydrochloride. There were no reported drug-related serious adverse events and no study withdrawals due to drug-related adverse events. Overall due to the low quality and volume of evidence our confidence in the effect estimate is limited and the true effect may be substantially different from our estimate.

Bupivacaine digital blocks: how long is the pain relief and temperature elevation?

PubMed

Calder, Kevin; Chung, Bryan; O'Brien, Cliona; Lalonde, Donald H

2013-05-01

The goals of this study are threefold: (1) to determine what effect epinephrine has on the duration of bupivacaine finger block anesthesia; (2) to see whether the duration of action of bupivacaine on digital pain relief is the same duration as numbness to touch/pressure; and (3) to assess the fingertip temperature changes that result from bupivacaine digital blocks. The ring fingers of both hands of 44 volunteers were randomized to injection of bupivacaine with or without 1:200,000 epinephrine. The durations of time for digits to return to normal pain, touch, pressure sensation, and fingertip temperature were measured and recorded. There were three main findings: (1) the pain block of bupivacaine lasts only half as long (15 hours) as the return to normal sensation (30 hours); (2) the effect of adding epinephrine to bupivacaine prolongs the duration of pain relief in a finger block for only an additional 1.5 hours; (3) in addition to pain relief, bupivacaine finger blocks cause fingertip hyperemia with consistent significant fingertip temperature elevation that lasts 15 hours. The duration of bupivacaine pain relief is the clinically important factor that needs to be reported in bupivacaine trials. Patients should be informed that the return of pain will occur much sooner than the return of normal sensation. Adding epinephrine to bupivacaine does not add a clinically significant length of time to pain relief. Bupivacaine finger blocks provide prolonged hyperemia and pain block to fingertips, which may be useful in the treatment of acute frostbite. Therapeutic, I.

Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

PubMed Central

Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

2014-01-01

Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was slower after rectal than after intrathecal administration (t½= 5.50 versus 2.02 hours, respectively). Limitations This study reports two cases only, and there could be inter-patient variation. Conclusion Bupivacaine in boluses administered intrathecally (0.25%, 2 mL) provided effective, safe analgesia in advanced cancer patients. Bupivacaine enema (100 mg·100 mL−1) was shown to be a valuable option for control of end-of-life tenesmoid cancer pain. PMID:25336967

Curcumin Attenuated Bupivacaine-Induced Neurotoxicity in SH-SY5Y Cells Via Activation of the Akt Signaling Pathway.

PubMed

Fan, You-Ling; Li, Heng-Chang; Zhao, Wei; Peng, Hui-Hua; Huang, Fang; Jiang, Wei-Hang; Xu, Shi-Yuan

2016-09-01

Bupivacaine is widely used for regional anesthesia, spinal anesthesia, and pain management. However, bupivacaine could cause neuronal injury. Curcumin, a low molecular weight polyphenol, has a variety of bioactivities and may exert neuroprotective effects against damage induced by some stimuli. In the present study, we tested whether curcumin could attenuate bupivacaine-induced neurotoxicity in SH-SY5Y cells. Cell injury was evaluated by examining cell viability, mitochondrial damage and apoptosis. We also investigated the levels of activation of the Akt signaling pathway and the effect of Akt inhibition by triciribine on cell injury following bupivacaine and curcumin treatment. Our findings showed that the bupivacaine treatment could induce neurotoxicity. Pretreatment of the SH-SY5Y cells with curcumin significantly attenuated bupivacaine-induced neurotoxicity. Interestingly, the curcumin treatment increased the levels of Akt phosphorylation. More significantly, the pharmacological inhibition of Akt abolished the cytoprotective effect of curcumin against bupivacaine-induced cell injury. Our data suggest that pretreating SH-SY5Y cells with curcumin provides a protective effect on bupivacaine-induced neuronal injury via activation of the Akt signaling pathway.

On Beyond Lidocaine: Reconsidering Local Anesthetics in Tumescent Liposuction-A Critical Review.

PubMed

Hsia, Henry C

2016-02-01

The use of tumescent solution in liposuction is now considered standard of care; however, much debate still exists regarding its ideal components, especially surrounding the inclusion of local anesthetics. This article reviews the discussion regarding the use of local anesthetics in tumescent liposuction and how it may evolve in the future. The need for local anesthetic additives in tumescent liposuction has been questioned, and the use of longer-acting agents discouraged; however, increasing number of reports in recent years have described the increasingly widespread use of tumescent anesthesia where a wetting solution is infiltrated to achieve anesthesia in an operative field for procedures other than liposuction. More high-level evidence, such as randomized controlled clinical trials, will be required; however, it should be possible to develop a useful standardized algorithm that can guide surgeons to optimize patient safety as well as patient experience.

Comparing the effects of single shot sciatic nerve block versus posterior capsule local anesthetic infiltration on analgesia and functional outcome after total knee arthroplasty: a prospective, randomized, double-blinded, controlled trial.

PubMed

Safa, Ben; Gollish, Jeffrey; Haslam, Lynn; McCartney, Colin J L

2014-06-01

Peripheral nerve blocks appear to provide effective analgesia for patients undergoing total knee arthroplasty. Although the literature supports the use of femoral nerve block, addition of sciatic nerve block is controversial. In this study we investigated the value of sciatic nerve block and an alternative technique of posterior capsule local anesthetic infiltration analgesia. 100 patients were prospectively randomized into three groups. Group 1: sciatic nerve block; Group 2: posterior local anesthetic infiltration; Group 3: control. All patients received a femoral nerve block and spinal anesthesia. There were no differences in pain scores between groups. Sciatic nerve block provided a brief clinically insignificant opioid sparing effect. We conclude that sciatic nerve block and posterior local anesthetic infiltration do not provide significant analgesic benefits. Copyright © 2014 Elsevier Inc. All rights reserved.

Percutaneous dermal drug delivery for local pain control

PubMed Central

Tadicherla, Sujatha; Berman, Brian

2006-01-01

Topical anesthetics have evolved from a simple solution of cocaine to creams, ointments, gels, liposomal preparations, and to the latest sophisticated patches and peels. Topical anesthetics are essential for performing diagnostic, therapeutic, and cosmetic dermatology procedures. These anesthetics noninvasively deliver anesthesia in locally required areas. In this review, we present an overview on the mechanism of precutaneous absorption of skin and address the composition, duration of onset of anesthetic effect, uses, and side effects that are applicable for the products. Also discussed are the novel advances of using heat to enhance penetration of the anesthetic as seen in Synera™ patch and delivery of anesthesia using a peel method as seen in the yet to be US Food and Drug Administration-approved S-Caine peel. PMID:18360585

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PubMed

Chen, Chuanyu; You, Peijun

2017-01-01

Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles.

PubMed

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-05-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles.

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles

PubMed Central

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-01-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles. PMID:28535859

Liposomal Bupivacaine Injection Technique in Total Knee Arthroplasty.

PubMed

Meneghini, R Michael; Bagsby, Deren; Ireland, Philip H; Ziemba-Davis, Mary; Lovro, Luke R

2017-01-01

Liposomal bupivacaine has gained popularity for pain control after total knee arthroplasty (TKA), yet its true efficacy remains unproven. We compared the efficacy of two different periarticular injection (PAI) techniques for liposomal bupivacaine with a conventional PAI control group. This retrospective cohort study compared consecutive patients undergoing TKA with a manufacturer-recommended, optimized injection technique for liposomal bupivacaine, a traditional injection technique for liposomal bupivacaine, and a conventional PAI of ropivacaine, morphine, and epinephrine. The optimized technique utilized a smaller gauge needle and more injection sites. Self-reported pain scores, rescue opioids, and side effects were compared. There were 41 patients in the liposomal bupivacaine optimized injection group, 60 in the liposomal bupivacaine traditional injection group, and 184 in the conventional PAI control group. PAI liposomal bupivacaine delivered via manufacturer-recommended technique offered no benefit over PAI ropivacaine, morphine, and epinephrine. Mean pain scores and the proportions reporting no or mild pain, time to first opioid, and amount of opioids consumed were not better with PAI liposomal bupivacaine compared with PAI ropivacaine, morphine, and epinephrine. The use of the manufacturer-recommended technique for PAI of liposomal bupivacaine does not offer benefit over a conventional, less expensive PAI during TKA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Synovial fluid bupivacaine concentrations following single intra-articular injection in normal and osteoarthritic canine stifles.

PubMed

Barry, S L; Martinez, S A; Davies, N M; Remsberg, C M; Sayre, C L; Bachelez, A

2015-02-01

Intra-articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra-articular injection. Eight healthy beagles with normal stifles and 22 large and giant-breed dogs with stifle osteoarthritis (OA) were treated with a single intra-articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra-articular injection. © 2014 John Wiley & Sons Ltd.

Recent advances in topical anesthesia

PubMed Central

2016-01-01

Topical anesthetics act on the peripheral nerves and reduce the sensation of pain at the site of application. In dentistry, they are used to control local pain caused by needling, placement of orthodontic bands, the vomiting reflex, oral mucositis, and rubber-dam clamp placement. Traditional topical anesthetics contain lidocaine or benzocaine as active ingredients and are used in the form of solutions, creams, gels, and sprays. Eutectic mixtures of local anesthesia cream, a mixture of various topical anesthetics, has been reported to be more potent than other anesthetics. Recently, new products with modified ingredients and application methods have been introduced into the market. These products may be used for mild pain during periodontal treatment, such as scaling. Dentists should be aware that topical anesthetics, although rare, might induce allergic reactions or side effects as a result of an overdose. Topical anesthetics are useful aids during dental treatment, as they reduce dental phobia, especially in children, by mitigating discomfort and pain. PMID:28879311

The efficacy of an intraosseous injection system of delivering local anesthetic.

PubMed

Leonard, M S

1995-01-01

This article describes the clinical testing of a new system for the intraosseous delivery of local anesthesia. The author concluded that the system delivered local anesthetic very effectively (in some situations more effectively than the traditional delivery method), thus offering a great potential advantage to both dentists and patients.

The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on uterine tone and fetal heart rate in labouring women: a randomised controlled study.

PubMed

Kuberan, A; Jain, K; Bagga, R; Makkar, J K

2018-07-01

The mechanism for fetal heart rate abnormalities following spinal opioids remains controversial. We evaluated uterine tone, using an intra-uterine pressure catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine plus 15 μg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was 13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group showed new onset fetal heart rate changes during the 30-min period after the spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however, these were transient and responded to intra-uterine resuscitation. Pain scores, sensory and motor block as well as neonatal outcomes were comparable between the groups. We found that raised baseline uterine tone was not more frequent when using bupivacaine-fentanyl rather than bupivacaine in the spinal component of combined spinal-epidural, although absolute values of baseline tone were higher, and fetal heart rate changes more frequent, in the former group. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

A randomized controlled study comparing intrathecal hyperbaric bupivacaine-fentanyl mixture and isobaric bupivacaine-fentanyl mixture in common urological procedures

PubMed Central

Upadya, Madhusudan; Neeta, S; Manissery, Jesni Joseph; Kuriakose, Nigel; Singh, Rakesh Raushan

2016-01-01

Background and Aims: Bupivacaine is available in isobaric and hyperbaric forms for intrathecal use and opioids are used as additives to modify their effects. The aim of this study was to compare the efficacy and haemodynamic effect of intrathecal isobaric bupivacaine-fentanyl mixture and hyperbaric bupivacaine-fentanyl mixture in common urological procedures. Methods: One hundred American Society of Anesthesiologists physical status 1 and 2 patients undergoing urological procedures were randomized into two groups. Group 1 received 3 ml of 0.5% isobaric bupivacaine with 25 μg fentanyl while Group 2 received 3 ml of 0.5% hyperbaric bupivacaine with 25 μg fentanyl. The parameters measured include heart rate, blood pressure, respiratory rate, onset and duration of motor and sensory blockade. Student's unpaired t-test and the χ2 test were used to analyse the results, using the SPSS version 11.5 software. Results: The haemodynamic stability was better with isobaric bupivacaine fentanyl mixture (Group 1) than with hyperbaric bupivacaine fentanyl mixture (Group 2). The mean onset time in Group 1 for both sensory block (4 min) and motor block (5 min) was longer compared with Group 2. The duration of sensory block (127.8 ± 38.64 min) and motor block (170.4 ± 27.8 min) was less with isobaric bupivacaine group compared with hyperbaric bupivacaine group (sensory blockade 185.4 ± 16.08 min and motor blockade 201.6 ± 14.28 min). Seventy percent of patients in Group 2 had maximum sensory block level of T6 whereas it was 53% in Group 1. More patients in Group 1 required sedation compared to Group 2. Conclusion: Isobaric bupivacaine fentanyl mixture was found to provide adequate anaesthesia with minimal incidence of haemodynamic instability. PMID:26962255

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

Intercostal nerve blockade with a mixture of bupivacaine and phenol enhance the efficacy of intravenous patient-controlled analgesia in the control of post-cholecystectomy pain.

PubMed

Maidatsi, P; Gorgias, N; Zaralidou, A; Ourailoglou, V; Giala, M

1998-09-01

Prolonged nerve conduction blockade has been proposed to result from the summed effects of charged and neutral local anaesthetics. Thirty-seven patients were randomly allocated to receive intravenous patient-controlled analgesia alone or combined with intercostal blockade (T7-T11) with a mixture of 0.45% bupivacaine and 0.6% phenol for post-cholecystectomy analgesia. Adequacy of pain relief was measured by patient scores on a 10-cm visual analogue scale and by dose-demand ratio, amounts of loading dose and total consumption of morphine and also the duration of patient-controlled analgesia in each group. No differences were found between groups in post-operative scores, dose-demand ratios and loading doses of morphine. However, in the combined treatment group, a significantly lower total consumption of morphine (P < 0.05), associated with a shorter duration of patient-controlled analgesia (P < 0.02) and a decreased mean number of unsuccessful demands (P < 0.001) were recorded. Intercostal blockade with bupivacaine-phenol supplements intravenous patient-controlled analgesia for post-cholecystectomy pain relief.

Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital.

PubMed

Knudson, Rachel A; Dunlavy, Paul W; Franko, Jan; Raman, Shankar R; Kraemer, Soren R

2016-09-01

Prior industry conducted studies have shown that long acting liposomal bupivacaine injection improves pain control postoperatively. To evaluate whether liposomal bupivacaine reduced the use of postoperative opioid (http://links.lww.com/DCR/A253) pain medication as compared to standard bupivacaine following colorectal surgery. A double blinded, prospective, randomized controlled trial comparing liposomal bupivacaine versus standard bupivacaine in patients undergoing elective colon resection. Community hospital with general surgery residency program with all cases performed by colorectal surgeons. Fifty-seven patients were randomized and reported as intention-to-treat analysis with 6 protocol violations. Sensitivity analysis excluding these 6 patients demonstrated no change in study results or conclusion. Mean age was 67 ± 2 years and 56% were male. There were 36 patients who underwent minimally invasive surgery, and 21 patients had an open colon resection. Experimental arm received liposomal bupivacaine while control arm received standard bupivacaine. Primary outcome measure was intravenous hydromorphone equivalent used via PCA during first 48 hours after operation. There was no significant difference between the two groups in the amount of opioid used orally or intravenously in the postoperative period. The primary outcome measure was PCA hydromorphone consumption during first two postoperative days after operation (hydromorphone equivalent use in standard bupivacaine group 11.3 ± 8.9 mg versus 13.3 ± 11.9 mg in liposomal bupivacaine group, p = 0.58 Mann-Whitney test). Small pragmatic trials typically remain underpowered for secondary analyses. A larger study could help to further delineate other outcomes that are impacted by postoperative pain. Liposomal bupivacaine did not change the amount of opioid used postoperatively. Based on our study, liposomal bupivacaine does not provide any added benefit over conventional bupivacaine after colon resection. (ClinicalTrials.gov: NCT02052557).

Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells

PubMed Central

2012-01-01

Background Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. Results Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H2O2) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H2O2. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H2O2-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H2O2-treated cells. Conclusions In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells. PMID:23227925

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

PubMed

Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

In Vivo Recording of Neural and Behavioral Correlates of Anesthesia Induction, Reversal, and Euthanasia in Cephalopod Molluscs.

PubMed

Butler-Struben, Hanna M; Brophy, Samantha M; Johnson, Nasira A; Crook, Robyn J

2018-01-01

Cephalopod molluscs are among the most behaviorally and neurologically complex invertebrates. As they are now included in research animal welfare regulations in many countries, humane and effective anesthesia is required during invasive procedures. However, currently there is no evidence that agents believed to act as anesthetics produce effects beyond immobility. In this study we demonstrate, for the first time, that two of the most commonly used agents in cephalopod general anesthesia, magnesium chloride and ethanol, are capable of producing strong and reversible blockade of afferent and efferent neural signal; thus they are genuine anesthetics, rather than simply sedating agents that render animals immobile but not insensible. Additionally, we demonstrate that injected magnesium chloride and lidocaine are effective local anesthetic agents. This represents a considerable advance for cephalopod welfare. Using a reversible, minimally invasive recording procedure, we measured activity in the pallial nerve of cuttlefish ( Sepia bandensis ) and octopus ( Abdopus aculeatus, Octopus bocki ), during induction and reversal for five putative general anesthetic and two local anesthetic agents. We describe the temporal relationship between loss of behavioral responses (immobility), loss of efferent neural signal (loss of "consciousness") and loss of afferent neural signal (anesthesia) for general anesthesia, and loss of afferent signal for local anesthesia. Both ethanol and magnesium chloride were effective as bath-applied general anesthetics, causing immobility, complete loss of behavioral responsiveness and complete loss of afferent and efferent neural signal. Cold seawater, diethyl ether, and MS-222 (tricaine) were ineffective. Subcutaneous injection of either lidocaine or magnesium chloride blocked behavioral and neural responses to pinch in the injected area, and we conclude that both are effective local anesthetic agents for cephalopods. Lastly, we demonstrate that a standard euthanasia protocol-immersion in isotonic magnesium chloride followed by surgical decerebration-produced no behavioral response and no neural activity during surgical euthanasia. Based on these data, we conclude that both magnesium chloride and ethanol can function as general anesthetic agents, and lidocaine and magnesium chloride can function as local anesthetic agents for cephalopod molluscs.

In Vivo Recording of Neural and Behavioral Correlates of Anesthesia Induction, Reversal, and Euthanasia in Cephalopod Molluscs

PubMed Central

Butler-Struben, Hanna M.; Brophy, Samantha M.; Johnson, Nasira A.; Crook, Robyn J.

2018-01-01

Cephalopod molluscs are among the most behaviorally and neurologically complex invertebrates. As they are now included in research animal welfare regulations in many countries, humane and effective anesthesia is required during invasive procedures. However, currently there is no evidence that agents believed to act as anesthetics produce effects beyond immobility. In this study we demonstrate, for the first time, that two of the most commonly used agents in cephalopod general anesthesia, magnesium chloride and ethanol, are capable of producing strong and reversible blockade of afferent and efferent neural signal; thus they are genuine anesthetics, rather than simply sedating agents that render animals immobile but not insensible. Additionally, we demonstrate that injected magnesium chloride and lidocaine are effective local anesthetic agents. This represents a considerable advance for cephalopod welfare. Using a reversible, minimally invasive recording procedure, we measured activity in the pallial nerve of cuttlefish (Sepia bandensis) and octopus (Abdopus aculeatus, Octopus bocki), during induction and reversal for five putative general anesthetic and two local anesthetic agents. We describe the temporal relationship between loss of behavioral responses (immobility), loss of efferent neural signal (loss of “consciousness”) and loss of afferent neural signal (anesthesia) for general anesthesia, and loss of afferent signal for local anesthesia. Both ethanol and magnesium chloride were effective as bath-applied general anesthetics, causing immobility, complete loss of behavioral responsiveness and complete loss of afferent and efferent neural signal. Cold seawater, diethyl ether, and MS-222 (tricaine) were ineffective. Subcutaneous injection of either lidocaine or magnesium chloride blocked behavioral and neural responses to pinch in the injected area, and we conclude that both are effective local anesthetic agents for cephalopods. Lastly, we demonstrate that a standard euthanasia protocol—immersion in isotonic magnesium chloride followed by surgical decerebration—produced no behavioral response and no neural activity during surgical euthanasia. Based on these data, we conclude that both magnesium chloride and ethanol can function as general anesthetic agents, and lidocaine and magnesium chloride can function as local anesthetic agents for cephalopod molluscs. PMID:29515454

No benefit of ultrasound-guided transversus abdominis plane blocks over wound infiltration with local anaesthetic in elective laparoscopic colonic surgery: results of a double-blind randomized controlled trial.

PubMed

Rashid, A; Gorissen, K J; Ris, F; Gosselink, M P; Shorthouse, J R; Smith, A D; Pandit, J J; Lindsey, I; Crabtree, N A

2017-07-01

Advances in laparoscopic techniques combined with enhanced recovery pathways have led to faster recuperation and discharge after colorectal surgery. Peripheral nerve blockade using transversus abdominis plane (TAP) blocks reduce opioid requirements and provide better analgesia for laparoscopic colectomies than do inactive controls. This double-blind randomized study was performed to compare TAP blocks using bupivacaine with standardized wound infiltration with local anaesthetic (LA). Seventy-one patients were randomized to receive either TAP block or wound infiltration. The TAP blocks were performed by experienced anaesthetists who used ultrasound guidance to deliver 40 ml of 0.25% bupivacaine post-induction into the transverse abdominis plane. In the control group, 40 ml of 0.25% bupivacaine was injected around the trocar and the extraction site by the surgeon. Both groups received patient-controlled analgesia (PCA) with intravenous morphine. Patients and nursing staff assessed pain scores 6, 12, 24 and 48 h after surgery. The primary outcome was overall morphine use in the first 48 h. Of the 71 patients, 20 underwent a right hemicolectomy and 51 a high anterior resection. The modified intention-to-treat analysis showed no significant differences in overall morphine use [47.3 (36.2-58.5) mg vs 46.7 (36.2-57.3) mg; mean (95% CI), P = 0.8663] in the first 48 h. Pain scores were similar at 6, 12, 24 and 48 h. No differences were found regarding time to mobilization, resumption of diet and length of hospital stay. In elective laparoscopic colectomies, standardized wound infiltration with LA has the same analgesic effect as TAP blocks post-induction using bupivacaine at 48 h. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Use of anesthetics associated to vasoconstrictors for dentistry in patients with cardiopathies. Review of the literature published in the last decade.

PubMed

Serrera Figallo, María A; Velázquez Cayón, Rocío T; Torres Lagares, Daniel; Corcuera Flores, Jose R; Machuca Portillo, Guillermo

2012-04-01

The use of local anesthetics associated to vasoconstrictor agents in dentistry is thoroughly justified and is widely extended, but we cannot ignore the fact that anesthetic infiltration poses risk of complications throughout the dental treatment period. The objective of the present review is to document the reported effects the use of the local anesthetics most widely employed in dentistry, with or without association to vasoconstrictor agents may have in patients with any sort of cardiopathy. We have searched for randomized clinical trials on the assessment of the cardiovascular effects of local anesthetics used in dentistry, without limits as regards age or sex, conducted in patients with any type of cardiopathy which were published during the last decade and were index-linked in Cochrane, Embase and Medline. We have found six randomized clinical trials index-linked in Medline and Cochrane in the past ten years. These trials compare different types of anesthetics: lidocaine 2%, mepivacaine 2%, prilocaine 2% , associated or not to different vasoconstrictor concentrations such as adrenaline or felypressin. The cardiopathies affecting the patients included in the different trials range from hypertension, ischemic heart disease, arrythmias, chronic coronary disease to heart transplantation. The use of anesthetics associated to vasoconstrictor agents is justified in the case of patients with cardiopathies (once we get over the period in which any type of dental manipulation is contraindicated) and in controlled hypertensive patients. In any case, we must be very careful with the choice and execution of the anesthetic technique, being it possible to use a dose between 1.8 and 3.6 ml, on a general basis. Further studies are necessary to establish the effects of these drugs on severe hypertensive patients or in patients with other more advanced cardiopathies. Key words:Vasoconstrictor agents, epinephrine/adverse effects, local anesthetics, dental restoration, oral surgery, cardiovascular diseases, coronary arteriosclerosis, heart disease, hypertension, arrhythmias, coronariopathy.

Use of anesthetics associated to vasoconstrictors for dentistry in patients with cardiopathies. Review of the literature published in the last decade

PubMed Central

Serrera Figallo, María A.; Velázquez Cayón, Rocío T.; Corcuera Flores, Jose R.; Machuca Portillo, Guillermo

2012-01-01

Objective: The use of local anesthetics associated to vasoconstrictor agents in dentistry is thoroughly justified and is widely extended, but we cannot ignore the fact that anesthetic infiltration poses risk of complications throughout the dental treatment period. The objective of the present review is to document the reported effects the use of the local anesthetics most widely employed in dentistry, with or without association to vasoconstrictor agents may have in patients with any sort of cardiopathy. Study Design: We have searched for randomized clinical trials on the assessment of the cardiovascular effects of local anesthetics used in dentistry, without limits as regards age or sex, conducted in patients with any type of cardiopathy which were published during the last decade and were index-linked in Cochrane, Embase and Medline. Results: We have found six randomized clinical trials index-linked in Medline and Cochrane in the past ten years. These trials compare different types of anesthetics: lidocaine 2%, mepivacaine 2%, prilocaine 2% , associated or not to different vasoconstrictor concentrations such as adrenaline or felypressin. The cardiopathies affecting the patients included in the different trials range from hypertension, ischemic heart disease, arrythmias, chronic coronary disease to heart transplantation. Conclusions: The use of anesthetics associated to vasoconstrictor agents is justified in the case of patients with cardiopathies (once we get over the period in which any type of dental manipulation is contraindicated) and in controlled hypertensive patients. In any case, we must be very careful with the choice and execution of the anesthetic technique, being it possible to use a dose between 1.8 and 3.6 ml, on a general basis. Further studies are necessary to establish the effects of these drugs on severe hypertensive patients or in patients with other more advanced cardiopathies. Key words:Vasoconstrictor agents, epinephrine/adverse effects, local anesthetics, dental restoration, oral surgery, cardiovascular diseases, coronary arteriosclerosis, heart disease, hypertension, arrhythmias, coronariopathy. PMID:24558534

Intrapleural bupivacaine analgesia after thoraco-abdominal incision for oesophagectomy.

PubMed

Tartiere, J; Samba, D; Lefrancois, C; Deshayes, J P; Samii, K; Bricard, H; Quesnel, J

1991-03-01

Intrapleural bupivacaine administration is said to produce good analgesia for the pain induced by a subcostal incision. However, reports of its efficacy after thoracotomy are conflicting. The goal of this study was to compare the analgesia produced by intrapleural administration of bupivacaine after oesophagectomy using a thoraco-abdominal incision with that obtained from intrapleural saline. After informed consent and institutional approval were obtained, 20 patients were randomly assigned to two groups of 10 patients each. Subjects received intrapleurally 10 ml of either 0.25% bupivacaine with 1:200,000 adrenaline or normal saline, every 8 h, beginning on the first post-operative day and lasting for 4 days. Pain was evaluated using a visual-analogue scale 2 h after the first daily treatment at rest and during physiotherapy. Pain scores were significantly lower in the bupivacaine group than in the saline group. Additionally, PaO2 was significantly higher in the bupivacaine group than in the saline group on Day 1 (P less than 0.05). The plasma bupivacaine concentration never reached the level of toxicity. Plasma bupivacaine concentrations on Day 1 after the first intrapleural bupivacaine injection were less than 350 ng ml-1; on Day 4 after the last injection they were less than 1300 ng ml-1. In conclusion, intrapleural administration of bupivacaine produces effective analgesia after oesophagectomy performed with a thoracoabdominal incision. The technique is easy to perform and is safe.

Pain control in augmentation mammaplasty using indwelling catheters in 687 consecutive patients: data analysis.

PubMed

Pacik, Peter T; Nelson, Craig E; Werner, Catherine

2008-01-01

Postoperative pain following augmentation mammaplasty can cause significant disability. In the authors' previously published prospective study of 644 consecutive augmentation mammaplasty patients, it was shown that the use of indwelling catheters for the postoperative instillation of bupivacaine is both safe and effective in postoperative pain management. This study analyzes a large population of augmentation mammaplasty patients to not only compare the effectiveness of catheter control with systemic analgesics but also to delineate sites of pain and determine if any of a variety of factors influence postoperative pain. Questionnaires were given to all patients to record the extent of pain reduction following the instillation of local anesthesia, patient preference for a variety of analgesics, and the locations of postoperative pain. Potential correlations to pain-including the number of children, age, handedness, preoperative fear, pain tolerance, and length of narcotic use-were investigated using statistical analysis. Operative aspects, such as the size of implants, use of asymmetrical implants, intraoperative expansion, duration of surgery, and sharp versus blunt dissection were also studied to determine if these factors influenced postoperative pain. Self-administration of bupivacaine the evening after surgery achieved pain reduction in 89% of patients. Patients gave high preference scores for the instillation of local anesthesia, comparable to rates achieved with the systemic narcotics Vicodin (Abbott Laboratories, Abbott Park, IL) and Percocet (Endo Pharmaceuticals, Chadds Ford, PA). Lower patient ratings were given to ibuprofen and methocarbamol. Patients identified multiple sites of postoperative pain, including the sternum, armpits, outer ribs, top of the breast (infraclavicular), interscapular region, and shoulders. Older patients experienced less pain. Patients who reported more pain, higher levels of fear, and sternal pain used narcotics for a longer period of time. Duration of surgery, blunt versus sharp dissection, and intraoperative expansion were not significantly related to pain. Combined implant size did not correlate with pain, though in the case of asymmetrical implants, greater pain (not statistically significant) on the larger side was reported. Postoperative pain following augmentation mammaplasty may be influenced by several factors, but these appear unrelated to implant size, specific operative techniques (blunt versus sharp dissection), or duration of surgery. Pain may involve not only the breasts, but also the sternum, sides of the chest, armpits, and infraclavicular and interscapular areas. The use of indwelling catheters for the instillation of a long-acting anesthetic is rated comparable in efficacy to the systemic narcotics Vicodin and Percocet. Sternal pain can be severe and may require narcotics for effective pain control.

Laparoscopic cholecystectomy under continuous spinal anesthesia in a patient with Steinert's disease.

PubMed

Correia, Mariana; dos Santos, Angela; Lages, Neusa; Correia, Carlos

2016-01-01

Steinert's disease is an intrinsic disorder of the muscle with multisystem manifestations. Myotonia may affect any muscle group, is elicited by several factors and drugs used in general anesthesia like hypnotics, sedatives and opioids. Although some authors recommend the use of regional anesthesia or combined anesthesia with low doses of opioids, the safest anesthetic technique still has to be established. We performed a continuous spinal anesthesia in a patient with Steinert's disease undergoing laparoscopic cholecystectomy using 10mg of bupivacaine 0.5% and provided ventilatory support in the perioperative period. Continuous spinal anesthesia was safely used in Steinert's disease patients but is not described for laparoscopic cholecystectomy. We reported a continuous spinal anesthesia as an appropriate technique for laparoscopic cholecystectomy and particularly valuable in Steinert's disease patients. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Extraction of mandibular premolars and molars: comparison between local infiltration via pressure syringe and inferior alveolar nerve block anesthesia.

PubMed

Thiem, Daniel G E; Schnaith, Florian; Van Aken, Caroline M E; Köntges, Anne; Kumar, Vinay V; Al-Nawas, Bilal; Kämmerer, Peer W

2018-04-01

The purpose of this study was to evaluate the anesthetic efficiency of local infiltration anesthesia administered with a pressure syringe (P-INF) via a special technique versus direct block anesthesia of the inferior alveolar nerve (IANB) for tooth extraction in the posterior mandible. In a prospective randomized study, 101 teeth in 101 patients were extracted in the posterior mandible under local anesthesia whereby two different administration techniques were used (P-INF n = 48; IANB n = 53). Primary objectives were comparisons of anesthetic success rate (yes/no) and efficacy (full/sufficient vs. insufficient). Secondary objectives were patients' pain perception during treatment, pain of injection (numerical rating scale), need for second injections (always IANB), time until onset of anesthetic action (min), and duration of local numbness (min). IANB was successful in all cases, whereas initial P-INF achieved 35% of success only. Furthermore, IANB reached significant higher values of anesthetic efficacy compared to P-INF (P < 0.001). Concerning pain of injection, patients rated IANB to be more painful (P = 0.039). Second injections were significantly more often necessary for P-INF (P = 0.006) whereas duration until onset of action as well as the duration of local numbness were found to be equal. For anesthetic efficacy as well as anesthetic success, block anesthesia of the inferior alveolar nerve (IANB) turned out to be more proficient to local infiltration via special delivering system with a special technique. Infiltration, even when performed with 4% articaine and a pressure syringe system, is not a suitable method of anesthesia in the posterior mandible.

Management of Chronic Pain of Cervical Disc Herniation and Radiculitis with Fluoroscopic Cervical Interlaminar Epidural Injections

PubMed Central

Manchikanti, Laxmaiah; Cash, Kimberly A.; Pampati, Vidyasagar; Wargo, Bradley W.; Malla, Yogesh

2012-01-01

Study Design: A randomized, double-blind, active controlled trial. Objective: To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis. Summary of Background Data: Epidural injections in managing chronic neck and upper extremity pain are commonly employed interventions. However, their long-term effectiveness, indications, and medical necessity, of their use and their role in various pathologies responsible for persistent neck and upper extremity pain continue to be debated, even though, neck and upper extremity pain secondary to disc herniation and radiculitis, is described as the common indication. There is also paucity of high quality literature. Methods: One-hundred twenty patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL); Group II patients received 0.5% lidocaine, 4 mL, mixed with 1 mL of nonparticulate betamethasone. Primary outcome measure was ≥ 50 improvement in pain and function. Outcome assessments included Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), opioid intake, employment, and changes in weight. Results: Significant pain relief and functional status improvement (≥ 50%) was demonstrated in 72% of patients who received local anesthetic only and 68% who received local anesthetic and steroids. In the successful group of participants, significant improvement was illustrated in 77% in local anesthetic group and 82% in local anesthetic with steroid group. Conclusions: Cervical interlaminar epidural injections with or without steroids may provide significant improvement in pain and function for patients with cervical disc herniation and radiculitis. PMID:22859902

Management of chronic pain of cervical disc herniation and radiculitis with fluoroscopic cervical interlaminar epidural injections.

PubMed

Manchikanti, Laxmaiah; Cash, Kimberly A; Pampati, Vidyasagar; Wargo, Bradley W; Malla, Yogesh

2012-01-01

A randomized, double-blind, active controlled trial. To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis. Epidural injections in managing chronic neck and upper extremity pain are commonly employed interventions. However, their long-term effectiveness, indications, and medical necessity, of their use and their role in various pathologies responsible for persistent neck and upper extremity pain continue to be debated, even though, neck and upper extremity pain secondary to disc herniation and radiculitis, is described as the common indication. There is also paucity of high quality literature. One-hundred twenty patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL); Group II patients received 0.5% lidocaine, 4 mL, mixed with 1 mL of nonparticulate betamethasone. Primary outcome measure was ≥ 50 improvement in pain and function. Outcome assessments included Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), opioid intake, employment, and changes in weight. Significant pain relief and functional status improvement (≥ 50%) was demonstrated in 72% of patients who received local anesthetic only and 68% who received local anesthetic and steroids. In the successful group of participants, significant improvement was illustrated in 77% in local anesthetic group and 82% in local anesthetic with steroid group. Cervical interlaminar epidural injections with or without steroids may provide significant improvement in pain and function for patients with cervical disc herniation and radiculitis.

Comparison of analgesic efficacy and safety of continuous epidural infusion versus local infiltration and systemic opioids in video-assisted thoracoscopic surgery decortication in pediatric empyema patients.

PubMed

Karnik, Priyanka Pradeep; Dave, Nandini Malay; Garasia, Madhu

2018-01-01

The stripping of the densely innervated and inflamed parietal pleura in empyema during video-assisted thoracoscopic surgery (VATS) decortication can lead to significant pain and major postoperative respiratory compromise. Hence, we compared the analgesic efficacy of continuous epidural infusion versus local infiltration and systemic opioids in children undergoing VATS decortications. Following ethics approval and informed consent, forty patients from 1 to 12 years of age were randomized into two groups, Group E (epidural) and Group L (local infiltration) after induction of anesthesia. In Group E, a thoracic epidural catheter was inserted between T4 and T8. A bolus dose of 0.5 ml/kg of 0.25% injection bupivacaine was given epidurally before incision. Postoperatively, the patients received epidural infusion with bupivacaine and fentanyl up to 48 h using an elastomeric balloon pump. In Group L, patients received local infiltration of bupivacaine (2 mg/kg) and lignocaine (5 mg/kg) at the port sites before incision and at the end of surgery. They also received injection tramadol 1 mg/kg intravenously TDS with thrice daily postoperatively. The pain scores (Face, Legs, Activity, Cry, Consolability/ Wong-Baker FACES scale) were assessed every 4 h on the 1 st day and 6 h on the 2 nd day. Injection diclofenac 1 mg/kg intravenous was used as a rescue analgesic for pain scores more than 4. Side effects such as nausea, vomiting, constipation, and motor blockade were noted. Quantitative and categorical data were assessed using t -test and Chi-square test, respectively. The pain scores were lower in the epidural group than in the local infiltration group at 0, 4, and 20 h postoperatively ( P = 0.001, 0.01, and 0.038, respectively). Seventeen out of nineteen patients required rescue analgesia in the local infiltration group in the postoperative period as compared to five patients in the epidural group with a P value of 0.000081. Epidural analgesia can be considered as an effective modality of reducing pain in patients undergoing VATS decortication for empyema in pediatric patients.

Ultrasound-guided injection of triamcinolone and bupivacaine in the management of De Quervain's disease.

PubMed

Jeyapalan, Kanagaratnam; Choudhary, Surabhi

2009-11-01

The aim of this study was to describe the technique and usefulness of ultrasound-guided intrasynovial injection of triamcinolone and bupivacaine in treatment of de Quervain's disease. A total of 17 patients with symptomatic De Quervain's disease were included in this study. The procedure involved confirmation of diagnosis with ultrasound followed by guided injection of a mixture of 20 mg of triamcinolone (40 mg/ml) and 1 ml of 0.5% bupivacaine. Ultrasound guidance with a high resolution 15-Mhz footprint probe was used for injection into the first dorsal extensor compartment tendon sheath (E1). The response to ultrasound-guided injection was ascertained at the post procedure outpatient clinic appointment according to the follow-up clinic notes. There were 14 female and 3 male patients aged 29 to 74 years. Mean duration of symptoms was 8.9 months. One patient had an atypical septum in the first extensor compartment and the extensor pollicis brevis alone was involved. The mean post-injection follow-up was at 6.75 weeks. One patient was lost to follow-up. Fifteen out of 16 patients had significant symptomatic relief (93.75%). There were no immediate or delayed complications. Recurrence of symptoms was seen in 3 (20%) patients. Ultrasound-guided injection of triamcinolone and bupivacaine is safe and useful in controlling symptoms of De Quervain's disease. Correct needle placement with ultrasound guidance avoids intratendinous injection as well as local complications like fat atrophy and depigmentation.

An emphasis on the wide usage and important role of local anesthesia in dentistry: A strategic review.

PubMed

Singh, Preetinder

2012-03-01

Local anesthesia forms the major part of pain-control techniques in dentistry. The prevention and elimination of pain during dental treatment has benefited patients, their doctors and dental hygienists, enabling the dental profession to make tremendous therapeutic advances that would otherwise have been impossible. Introduced in the late 1940s, the amide local anesthetics represent the most used drugs in dentistry. Local anesthetics also represent the safest and most effective drugs in all of medicine for the prevention and management of pain. They are also accompanied by various adverse effects which should be well known and be able to be controlled by the clinician. The article reviews the types of agents used as local anesthetics and their effects on the human body.

Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration.

PubMed

Gavrilovska-Brzanov, Aleksandra; Kuzmanovska, Biljana; Kartalov, Andrijan; Donev, Ljupco; Lleshi, Albert; Jovanovski-Srceva, Marija; Spirovska, Tatjana; Brzanov, Nikola; Simeonov, Risto

2016-03-15

The aim of this study is to evaluate anesthesia and recovery profile in pediatric patients after inguinal hernia repair with caudal block or local wound infiltration. In this prospective interventional clinical study, the anesthesia and recovery profile was assessed in sixty pediatric patients undergoing inguinal hernia repair. Enrolled children were randomly assigned to either Group Caudal or Group Local infiltration. For caudal blocks, Caudal Group received 1 ml/kg of 0.25% bupivacaine; Local Infiltration Group received 0.2 ml/kg 0.25% bupivacaine. Investigator who was blinded to group allocation provided postoperative care and assessments. Postoperative pain was assessed. Motor functions and sedation were assessed as well. The two groups did not differ in terms of patient characteristic data and surgical profiles and there weren't any hemodynamic changes between groups. Regarding the difference between groups for analgesic requirement there were two major points - on one hand it was statistically significant p < 0.05 whereas on the other hand time to first analgesic administration was not statistically significant p = 0.40. There were significant differences in the incidence of adverse effects in caudal and local group including: vomiting, delirium and urinary retention. Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common.

The Ganglioside GM-1 Inhibits Bupivacaine-Induced Neurotoxicity in Mouse Neuroblastoma Neuro2a Cells.

PubMed

Liang, Yujie; Ji, Jiemei; Lin, Yunan; He, Yajun; Liu, Jingchen

2016-08-01

Studies indicate that bupivacaine-induced neurotoxicity results from apoptosis. Gangliosides have been shown to promote neuronal repair and recovery of neurological function after spinal cord injury. Previously, we confirmed that in vivo administration of the ganglioside GM-1 attenuated bupivacaine-induced neurotoxicity in various animal models; however, the underlying mechanism remains unclear. Cells of the neuroblastoma line N2a (Neuro2a cells) were divided into three experimental groups: control, bupivacaine-treated, and bupivacaine-treated with GM-1 pretreatment. Cell viability and apoptosis were assessed through CCK-8 assays, Hoechst staining, and flow cytometry analysis of Annexin-V/propidium iodide double labeling. Real-time polymerase chain reaction and western blotting assessed the expression of caspase-3, caspase-8, and caspase-9. Bupivacaine-induced apoptosis worsened with increasing dose and exposure time. Bupivacaine induced increased expression of caspase-3 and caspase-9, but not caspase-8, indicating that the mitochondrial pathway but not the death receptor apoptosis pathway was activated. GM-1 pretreatment inhibited bupivacaine-induced apoptosis and the expression of caspase-3 and caspase-9 in a dose-dependent manner. Bupivacaine induced neurotoxicity by activating apoptosis via the mitochondrial pathway, and this was inhibited by GM-1 pretreatment. Copyright © 2016 John Wiley & Sons, Ltd.

Advances in local anesthesia in dentistry.

PubMed

Ogle, Orrett E; Mahjoubi, Ghazal

2011-07-01

Local pain management is the most critical aspect of patient care in dentistry. The improvements in agents and techniques for local anesthesia are probably the most significant advances that have occurred in dental science. This article provides an update on the most recently introduced local anesthetic agents along with new technologies used to deliver local anesthetics. Safety devices are also discussed, along with an innovative method for reducing the annoying numbness of the lip and tongue following local anesthesia. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinically Enhancing Local Anesthesia Techniques for Endodontic Treatment.

PubMed

Bahcall, James; Xie, Qian

2017-02-01

Local anesthesia is one of the most important drugs given to patients who undergo endodontic treatment. Yet, clinicians often do not view local anesthetic agents as drugs and, therefore, struggle clinically to consistently achieve profound pulpal anesthesia. To improve the clinical effects of local anesthesia for endodontic treatment, in conjunction with selecting the correct type of local anesthesia, clinicians need to thoroughly understand how the local anesthetic process works and how to objectively test for clinical signs of pulpal anesthesia and integrate supplemental anesthesia when appropriate.

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

PubMed

Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Plasma bupivacaine concentrations following orbital injections in cats.

PubMed

Shilo-Benjamini, Yael; Pypendop, Bruno H; Newbold, Georgina; Pascoe, Peter J

2017-01-01

To determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats. Randomized, crossover, experimental trial with a 2 week washout period. Six adult healthy cats, aged 1-2 years, weighing 4.6 ± 0.7 kg. Cats were sedated by intramuscular injection of dexmedetomidine (36-56 μg kg -1 ) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography-mass spectrometry. Bupivacaine maximum plasma concentration (C max ) and time to C max (T max ) were determined from the data. The bupivacaine median (range) C max and T max were 1.4 (0.9-2.5) μg mL -1 and 17 (4-60) minutes, and 1.7 (1.0-2.4) μg mL -1 , and 28 (8-49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05-0.21 μg mL -1 . In healthy cats, at doses up to 2 mg kg -1 , bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension. Copyright © 2016 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial.

PubMed

Glenn, Brandon; Drum, Melissa; Reader, Al; Fowler, Sara; Nusstein, John; Beck, Mike

2016-09-01

Medical studies have shown some potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA), a slow-release bupivacaine solution, to extend postoperative benefits of numbness/pain relief for up to several days. Because the Food and Drug Administration has approved Exparel only for infiltrations, we wanted to evaluate if it would be effective as an infiltration to control postoperative pain. The purpose of this study was to compare an infiltration of bupivacaine with liposomal bupivacaine for postoperative numbness and pain in symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain. One hundred patients randomly received a 4.0-mL buccal infiltration of either bupivacaine or liposomal bupivacaine after endodontic debridement. For postoperative pain, patients were given ibuprofen/acetaminophen, and they could receive narcotic pain medication as an escape. Patients recorded their level of numbness, pain, and medication use the night of the appointment and over the next 5 days. Success was defined as no or mild postoperative pain and no narcotic use. The success rate was 29% for the liposomal group and 22% for the bupivacaine group, with no significant difference (P = .4684) between the groups. Liposomal bupivacaine had some effect on soft tissue numbness, pain, and use of non-narcotic medications, but it was not clinically significant. There was no significant difference in the need for escape medication. For symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain, a 4.0-mL infiltration of liposomal bupivacaine did not result in a statistically significant increase in postoperative success compared with an infiltration of 4.0 mL bupivacaine. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Stable gastric pentadecapeptide BPC 157 and bupivacaine.

PubMed

Zivanovic-Posilovic, Gordana; Balenovic, Diana; Barisic, Ivan; Strinic, Dean; Stambolija, Vasilije; Udovicic, Mario; Uzun, Sandra; Drmic, Domagoj; Vlainic, Josipa; Bencic, Martina Lovric; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag

2016-12-15

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the bupivacaine injection. When BPC 157 was given 6min after bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with BPC 157 (1µm), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

PubMed Central

Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

2013-01-01

Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to evaluate whether intra-articular injection of a mixture of bupivacaine and hyaluronan after arthroscopic surgery may protect against bupivacaine’s chondrotoxicity. PMID:22427617

Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model.

PubMed

Wilsey, Jared T; Block, Julie H

2018-01-01

Previous research suggests that the α 2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action. The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model. The depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone) polymer film containing 3% (w/w) clonidine HCl (MDT3). Fifty-two young adult mix Landrace pigs (9-11 kg) were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8). Group 2 received three placebo strips (PBO, n=8), placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8), Group 4 received two MDT3 and one PBO (n=8), and Group 5 received three MDT3 (n=8). Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8) or clonidine solution (Group 7, 225 µg/day, n=4). The surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg), but not clonidine (up to 225 µg), completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7. These data suggest that a sustained-release clonidine depot may be a viable nonopioid, nonamide anesthetic therapy for the treatment of acute postsurgical nociceptive sensitization.

Local anesthetic systemic toxicity: update on mechanisms and treatment.

PubMed

Wolfe, John W; Butterworth, John F

2011-10-01

With increases in use of regional anesthesia, local anesthetic systemic toxicity (LAST) has been a topic of interest and debate. Despite many years of research, the exact cause and best treatment of LAST (particularly local anesthetic cardiotoxicity) remain unclear. This review will summarize what is known and what remains uncertain about LAST and its treatment, including information published in the past 12-18 months. Several authorities, including the American Society of Regional Anesthesia and Pain Medicine, have published guidelines on prevention and treatment of LAST. Experimental data continue to add to better understanding of LAST and its treatment. The data are not entirely consistent, but themes include continued evidence to support the ideas that LAST cardiotoxicity occurs primarily at sodium channels, lipid emulsion is a reasonably well tolerated and effective treatment, and there may be qualitative differences in cardiotoxicity caused by low and high-potency local anesthetics. Regarding mechanism(s) of LAST, the evidence remains mixed, but it is likely that local anesthetic cardiotoxicity primarily arises from a blockade of sodium channels. As for treatment, in addition to ventilation, oxygenation, and chest compressions, lipid emulsion therapy should be a primary element in the treatment of cardiovascular LAST. The use of epinephrine and vasopressin should be tailored to specifics of an episode of LAST, and doses should be kept as low as possible while still achieving the desired effects.

Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

PubMed

Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

2002-01-01

Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

The Effects of Local Anaesthetics on QT Parameters during Thoracic Epidural Anaesthesia Combined with General Anaesthesia: Ropivacaine versus Bupivacaine

PubMed Central

Güven, Özlem; Sazak, Hilal; Alagöz, Ali; Şavkılıoğlu, Eser; Demirbaş, Çilsem Sevgen; Yıldız, Ali; Karabulut, Erdem

2013-01-01

Background: Many studies focusing on the effects of local anaesthetics on QT intervals have been performed, but the articles evaluating the relationship between thoracic epidural anaesthesia combined with general anaesthesia and QT parameters are very limited. Aims: We aimed to compare the effects of bupivacaine and ropivacaine on QT interval, corrected QT, dispersion of QT, and corrected dispersion of QT in patients undergoing lung resection under thoracic epidural anaesthesia combined with general anaesthesia. Study Design: Prospective clinical study. Methods: Thirty ASA physical status 1–3 patients requiring thoracic epidural anaesthesia combined with general anaesthesia for thoracic surgery. Patients were randomly assigned to two groups, which were allocated to receive either bupivacaine (Group B) or ropivacaine (Group R) during thoracic epidural anaesthesia. Following haemodynamic monitoring, a thoracic epidural catheter was inserted. Local anaesthetic at an average dose of 1.5 mL/ segment was given through an epidural catheter. The same general anaesthesia protocol was administered in both groups. Records and measurements were performed on 10 phases that were between the thoracic epidural catheter insertion to the 5th min of endobronchial intubation. In all phases, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, peripheral O2 saturation, and electrocardiogram monitoring were performed in patients. All QT parameters were recorded by 12-lead electrocardiogram and analysed manually by a cardiologist. Results: QT intervals were similar between two groups. In Group R, corrected QT values at the 20th min of local anaesthetic injection and the 5th min of endobronchial intubation were shorter than those in Group B (p<0.05). The basal dispersion of QT and dispersion of QT values at the 1st min of propofol injection were shorter than those in Group R (p<0.05). The corrected dispersion of QT value at the 1st min of propofol injection was shorter in Group R (p<0.05). In Group R, the decrease in mean arterial pressure at the 1st min of fentanyl injection was significant compared with Group B (p<0.05). There was no significant difference between the groups with respect to heart rate and complications. Conclusion: The corrected QT, dispersion of QT, and corrected dispersion of QT intervals were slightly longer in the patients receiving bupivacaine compared with those receiving ropivacaine in various phases of the present study. PMID:25207150

Comparison of pain perception during miniscrew placement in orthodontic patients with a visual analog scale survey between compound topical and needle-injected anesthetics: A crossover, prospective, randomized clinical trial.

PubMed

Lamberton, Jordan A; Oesterle, Larry J; Shellhart, W Craig; Newman, Sheldon M; Harrell, Ricky E; Tilliss, Terri; Singh, Neha; Carey, Clifton M

2016-01-01

The use of a compound topical anesthetic (CTA) instead of an injection of a local anesthetic for placing miniscrew implants offers advantages to both the clinician and the patient. The purpose of this crossover, prospective, randomized clinical trial was to compare the clinical effectiveness of a CTA with that of a needle injection of local anesthetic for miniscrew placement. Twenty-four orthodontic patients in a university clinic were recruited; they required bilateral buccal miniscrews for orthodontic anchorage. Eligibility criteria included healthy patients with no special needs; over 8 years of age and 25 pounds; not taking sulfonamides, monoamine oxidase inhibitors, tricyclic antidepressants, or phenothiazines; and not allergic to ester-type local anesthetics or any of the other materials used in the study. A computer generated a randomization list. The allocation was randomized by anesthetic protocol and side of the mouth, and was restricted to achieve balance by treatment and side of the mouth. No allocation concealment was applied. Associated with each randomized number was the subjects' assignment into 1 of 4 groups divided by the side of first miniscrew placement and the type of anesthetic. Blinding was done only for data analysis because of clinical limitations. Each patient received a CTA on one side and an injection of anesthetic on the other before miniscrew placement in a crossover study design. The outcome was assessed by measuring pain levels with a 100-mm visual analog scale at 5 time points. Anesthetic failures occurred when the miniscrew could not be fully comfortably placed with a given anesthetic. Data were organized by visual analog scale time points, and descriptive statistics were calculated. A factorial repeated-measures analysis of variance was used to determine any differences. Twenty-seven patients were assessed for eligibility, and 24 agreed to participate in the study. Patients did not distinguish any differences in pain between the application of the CTA and the injection before or during anesthetic placement, but they experienced more pain with the CTA during miniscrew placement. The mean difference for the entire procedure between the 2 anesthesia types was 24.6 units, and the 95% confidence interval was 18.8 to 30.4, a statistically significant finding (P = 0.0002). The CTA was still viewed as more painful 1 month after the procedures. Significantly more anesthetic failures occurred with the CTA (41.6%) than with the injection (0%). No serious harm was observed in any patient; when significant pain was observed with the CTA, a needle injection of local anesthetic was administered. CTAs provided less predictable, often inadequate, and less comfortable anesthesia than an injection of a local anesthetic for managing patient discomfort during miniscrew placement in buccal sites. This trial was not registered. The protocol was determined and approved by the research committee and institutional review board before the trial. No external funding was used other than the donation of the miniscrews from Rocky Mountain Orthodontics, and no conflict of interest was declared. Copyright © 2016. Published by Elsevier Inc.

General anesthesia versus segmental thoracic or conventional lumbar spinal anesthesia for patients undergoing laparoscopic cholecystectomy

PubMed Central

Yousef, Gamal T.; Lasheen, Ahmed E.

2012-01-01

Background: Laparoscopic cholecystectomy became the standard surgery for gallstone disease because of causing less postoperative pain, respiratory compromise and early ambulation. Objective: This study was designed to compare spinal anesthesia, (segmental thoracic or conventional lumbar) vs the gold standard general anesthesia as three anesthetic techniques for healthy patients scheduled for elective laparoscopic cholecystectomy, evaluating intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction. Materials and Methods: A total of 90 patients undergoing elective laparoscopic cholecystectomy, between January 2010 and May 2011, were randomized into three equal groups to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under segmental thoracic (TSA group) or conventional lumbar (LSA group) spinal anesthesia or general anesthesia (GA group). To achieve a T3 sensory level we used (hyperbaric bupivacaine 15 mg, and fentanyl 25 mg at L2/L3) for LSAgroup, and (hyperbaric bupivacaine 7.5 mg, and fentanyl 25 mg at T10/T11) for TSAgroup. Propofol, fentanyl, atracurium, sevoflurane, and tracheal intubation were used for GA group. Intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction were compared between the three groups. Results: All procedures were completed laparoscopically by the allocated method of anesthesia with no anesthetic conversions. The time for the blockade to reach T3 level, intraoperative hypotensive and bradycardic events and vasopressor use were significantly lower in (TSA group) than in (LSA group). Postoperative pain scores as assessed throughout any time, postoperative right shoulder pain and hospital stay was lower for both (TSA group) and (LSA group) compared with (GA group). The higher degree of patients satisfaction scores were recorded in patients under segmental TSA. Conclusion: The present study not only confirmed that both segmental TSA and conventional lumber spinal anesthesia (LSA) are safe and good alternatives to general anesthesia (GA) in healthy patients undergoing laparoscopic cholecystectomy but also showed better postoperative pain control of both spinal techniques when compared with general anesthesia. Segmental TSA provides better hemodynamic stability, lesser vasopressor use and early ambulation and discharge with higher degree of patient satisfaction making it excellent for day case surgery compared with conventional lumbar spinal anesthesia. PMID:25885611

The newer aspect of dexmedetomidine use in dentistry: As an additive to local anesthesia, initial experience, and review of literature.

PubMed

Kumar, Prashant; Thepra, Manju; Bhagol, Amrish; Priya, Kannu; Singh, Virendra

2016-01-01

Despite the availability of a wide variety of pharmacological agents in the field of anesthesia, there has always been a continuous search for newer local anesthetic agents with improved efficacy, potency, and better handling properties. Dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, is an emerging agent for provision of additive local anesthetic effect if used with conventional local anesthetics, which can be implicated in dentistry for performing many minor oral surgical procedures. The present paper reports a pilot study comparing clinical efficacy and potency of this newer emerging drug in combination with lignocaine. Ten patients undergoing orthodontic extraction for correction of malocclusion and other dentofacial deformities requiring orthodontic treatment were locally infiltrated with 2% lignocaine plus dexmedetomidine 1μ/ml and 2% lignocaine plus adrenaline in 1:200,000 dilution at two different appointments. The onset of action, duration of action, and pain threshold were assessed. Onset of action was found to be faster with longer duration of action with the newer drug dexmedetomidine and lignocaine combination when compared with combination of lignocaine and adrenaline. The study demonstrated that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine without significant systemic effects when locally injected into oral mucosa.

Liposomal Bupivacaine vs Interscalene Nerve Block for Pain Control After Shoulder Arthroplasty: A Retrospective Cohort Analysis.

PubMed

Hannan, Casey V; Albrecht, Matthew J; Petersen, Steve A; Srikumaran, Uma

The aim of this study was to compare liposomal bupivacaine and interscalene nerve block (ISNB) for analgesia after shoulder arthroplasty. We compared 37 patients who received liposomal bupivacaine vs 21 who received ISNB after shoulder arthroplasty by length of hospital stay (LOS), opioid consumption, and postoperative pain. Pain was the same in both groups for time intervals of 1 hour and 8 to 14 hours postoperatively. Compared with ISNB patients, liposomal bupivacaine patients reported less pain at 18 to 24 hours (P = .001) and 27 to 36 hours (P = .029) and had lower opioid consumption on postoperative days 2 (P = .001) and 3 (P = .002). Mean LOS for liposomal bupivacaine patients was 46 ± 20 hours vs 57 ± 14 hours for ISNB patients (P = .012). Sixteen of 37 liposomal bupivacaine patients vs 2 of 21 ISNB patients were discharged on the first postoperative day (P = .010). Liposomal bupivacaine was associated with less pain, less opioid consumption, and shorter hospital stays after shoulder arthroplasty compared with ISNB.

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles.

PubMed

Giangarra, Jenna E; Barry, Sabrina L; Dahlgren, Linda A; Lanz, Otto I; Benitez, Marian E; Werre, Stephen R

2018-04-25

To identify if synovial fluid prostaglandin E 2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle. There were no significant differences in synovial fluid prostaglandin E 2 (PGE 2 ) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE 2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE 2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE 2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.

Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence.

PubMed

Kim, Ryungsa

2018-01-18

The relationship between surgery and anesthetic-induced immunosuppression and cancer recurrence remains unresolved. Surgery and anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) to cause immunosuppression through several tumor-derived soluble factors. The potential impact of surgery and anesthesia on cancer recurrence was reviewed to provide guidance for cancer surgical treatment. PubMed was searched up to December 31, 2016 using search terms such as, "anesthetic technique and cancer recurrence," "regional anesthesia and cancer recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and immunosuppression," and "anesthetic technique and oncologic surgery." Surgery-induced stress responses and surgical manipulation enhance tumor metastasis via release of angiogenic factors and suppression of natural killer (NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes. Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis, and enhance angiogenesis through hypoxia inducible factor-1α (HIF-1α) activity. Opioids suppress NK cell activity and increase regulatory T cells. Local anesthetics such as lidocaine increase NK cell activity. Anesthetics such as propofol and locoregional anesthesia, which decrease surgery-induced neuroendocrine responses through HPA-axis and SNS suppression, may cause less immunosuppression and recurrence of certain types of cancer compared to volatile anesthetics and opioids.

Can we use lower volume of local anesthetic for infraclavicular brachial plexus nerve block under ultrasound guidance in children?

PubMed

Ince, Ilker; Aksoy, Mehmet; Dostbil, Aysenur; Tuncer, Kutsi

2017-09-01

To determine if the infraclavicular brachial plexus block can be applied with lower volume of local anesthetic. Randomised, double-blinded clinical trial. 60 patients aged 5-15years with ASA I-II who underwent emergent or elective arm, forearm or hand operations were included in the study. Patients were divided into two groups randomly; standard volume local anesthetic administered group (Group S, n=30) and low volume anesthetic administered group (Group L, n=30). Postoperative pain scores, sensory and motor block durations were noted. Pain scores (Wong-Baker Face Scale) were evaluated and the results were detected to be similar at all times (30min, 1, 2, 4, 8, 12, 24h). Durations of motor block were 168(±16) minutes and 268(±15) minutes in Group L and Group S respectively and the difference was statistically significant (p<0.001). Durations of sensory block were 385(±26) and 402(±39) in Group L and Group S respectively and no statistically significant difference was detected (p=0.064). Similar block success, postoperative sensory block durations and pain scores could be obtained during infraclavicular brachial plexus in pediatric patients with lower local anesthetic volumes. Copyright © 2016 Elsevier Inc. All rights reserved.

In vivo effects of bupivacaine and gadobutrol on the intervertebral disc following discoblock and discography: a histological analysis.

PubMed

Strube, Patrick; Pfitzner, Berit M; Streitparth, Florian; Hartwig, Tony; Putzier, Michael

2017-01-01

The aim of the present study was to histologically compare chondrotoxicity in surgically harvested intervertebral discs (IVDs) of patients following discoblock, discography, or no preoperative intervention. Thirty patients (IVD degeneration Modic ≥ 2°, Pfirrmann 3° or 4°) at L4/5 or L5/S1 who were planned for anterior lumbar interbody fusion were randomly assigned to three groups (open MRI: group DG - discography with gadobutrol; group DB - discoblock with bupivacaine at 4 weeks prior to surgery; group C - no intervention). The intervertebral discs were histologically evaluated and compared using ANOVA and Bonferroni tests for cell count, apoptosis, and proliferation. A reduced cell count (groups DG vs. DB vs. C: 14.9 ± 7.1, 9.2 ± 3.8, and 16.6 ± 5.2 cells/mm 2 , respectively; p ANOVA  = 0.016), increased apoptosis (groups DG vs. DB vs. C: 34.9 ± 10.2, 47.4 ± 16.3, 32.6 ± 12.2 %, respectively; p ANOVA  = 0.039) and increased cell proliferation (post hoc pDB vs. DG or C p < 0.001; for 3-7 cell monoclonal cell nests: groups DG vs. DB vs. C: 2.4 ± 1, 3.9 ± 1, 2.2 ± 1.1, respectively; p intervention x nest size  = 0.006) were found in the IVDs of patients in group DB. This in vivo study suggests that chondrotoxic effects occur in IVD cells after the intradiscal injection of bupivacaine but not after gadobutrol administration. • Local bupivacaine administration to intervertebral discs leads to cell toxicity and proliferation. • Gadobutrol demonstrated no significant effect on cell count, apoptosis, or cell proliferation. • In vivo cytotoxicity was demonstrated histologically in humans for the first time. • Addition/administration of bupivacaine during discographies must be judged critically.

Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A case series

PubMed Central

Mane, Rajesh S.; Patil, Manjunath C.; Kedareshvara, K. S.; Sanikop, C. S.

2012-01-01

Background: Laparoscopy is one of the most common surgical procedures and is the procedure of choice for most of the elective abdominal surgeries performed preferably under endotracheal general anesthesia. Technical advances in the field of laparoscopy have helped to reduce surgical trauma and discomfort, reduce anesthetic requirement resulting in shortened hospital stay. Recently, regional anaesthetic techniques have been found beneficial, especially in patients at a high risk to receive general anesthesia. Herewith we present a case series of laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA) I and II patients performed under spinal-epidural anaesthesia. Methods: Eight ASA Grade I and II adult patients undergoing elective Laparoscopic appendectomy received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed at L2-L3 interspace using 2 ml of 0.5% (10 mg) hyperbaric Bupivacaine mixed with 0.5ml (25 micrograms) of Fentanyl. Epidural catheter was inserted at T10-T11 interspace for inadequate spinal anaesthesia and postoperative pain relief. Perioperative events and operative difficulty were studied. Systemic drugs were administered if patients complained of shoulder pain, abdominal discomfort, nausea or hypotension. Results: Spinal anaesthesia was adequate for surgery with no operative difficulty in all the patients. Intraoperatively, two patients experienced right shoulder pain and received Fentanyl, one patient was given Midazolam for anxiety and two were given Ephedrine for hypotension. The postoperative period was uneventful. Conclusion: Spinal anaesthesia with Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective laparoscopic appendectomy in healthy patients but careful evaluation of the method is needed particularly in compromised cardio respiratory conditions. PMID:22412773

Benzocaine-loaded polymeric nanocapsules: study of the anesthetic activities.

PubMed

De Melo, Nathalie Ferreira Silva; De Araújo, Daniele Ribeiro; Grillo, Renato; Moraes, Carolina Morales; De Matos, Angélica Prado; de Paula, Eneida; Rosa, André Henrique; Fraceto, Leonardo Fernandes

2012-03-01

This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs). Copyright © 2011 Wiley Periodicals, Inc.

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses... local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii) The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is...

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses... local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii) The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is...

A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: a clinical evaluation.

PubMed

Kosaraju, Amar; Vandewalle, Kraig S

2009-01-01

The authors used a split-mouth design to determine the effectiveness of a refrigerant compared with that of a topical anesthetic gel in reducing the pain experienced during a posterior palatal anesthetic injection. Sixteen participants received a five-second application of a refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluoroethane) and a two-minute application of a topical anesthetic gel (20 percent benzocaine gel) in the posterior palatal area before an injection of a local anesthetic solution was administered with a 30-gauge needle. Participants rated the pain they experienced after each injection by using a 100-millimeter visual analog scale (VAS) with endpoints of "no pain" and "worst possible pain." The authors calculated VAS scores by measuring the distance in millimeters from the no pain end of the scale. They analyzed data with a paired t test (alpha = .05). The group receiving the refrigerant had a mean VAS score of 17.7 +/- 15.3 mm, and the group receiving the topical anesthetic gel had a VAS score of 26.2 +/- 18.0 mm. The use of the refrigerant compared with the use of topical anesthetic gel significantly reduced the pain experienced during administration of local anesthetic injections (P = .02). The use of a refrigerant as a preinjection anesthetic was more effective compared with the use of a topical anesthetic gel in reducing the pain experienced by participants who received a posterior palatal injection. The potential benefits of using a refrigerant rather than a topical anesthetic gel are pain reduction, decreased application time, ease of application and avoidance of displeasing taste.

Use of liposomal bupivacaine in the postoperative management of posterior spinal decompression.

PubMed

Grieff, Anthony N; Ghobrial, George M; Jallo, Jack

2016-07-01

OBJECTIVE The aim in this paper was to evaluate the efficacy of long-acting liposomal bupivacaine in comparison with bupivacaine hydrochloride for lowering postoperative analgesic usage in the management of posterior cervical and lumbar decompression and fusion. METHODS A retrospective cohort-matched chart review of 531 consecutive cases over 17 months (October 2013 to February 2015) for posterior cervical and lumbar spinal surgery procedures performed by a single surgeon (J.J.) was performed. Inclusion criteria for the analysis were limited to those patients who received posterior approach decompression and fusion for cervical or lumbar spondylolisthesis and/or stenosis. Patients from October 1, 2013, through December 31, 2013, received periincisional injections of bupivacaine hydrochloride, whereas after January 1, 2014, liposomal bupivacaine was solely administered to all patients undergoing posterior approach cervical and lumbar spinal surgery through the duration of treatment. Patients were separated into 2 groups for further analysis: posterior cervical and posterior lumbar spinal surgery. RESULTS One hundred sixteen patients were identified: 52 in the cervical cohort and 64 in the lumbar cohort. For both cervical and lumbar cases, patients who received bupivacaine hydrochloride required approximately twice the adjusted morphine milligram equivalent (MME) per day in comparison with the liposomal bupivacaine groups (5.7 vs 2.7 MME, p = 0.27 [cervical] and 17.3 vs 7.1 MME, p = 0.30 [lumbar]). The amounts of intravenous rescue analgesic requirements were greater for bupivacaine hydrochloride in comparison with liposomal bupivacaine in both the cervical (1.0 vs 0.39 MME, p = 0.31) and lumbar (1.0 vs 0.37 MME, p = 0.08) cohorts as well. None of these differences was found to be statistically significant. There were also no significant differences in lengths of stay, complication rates, or infection rates. A subgroup analysis of both cohorts of opiate-naive versus opiate-dependent patients found that those patients who were naive had no difference in opiate requirements. In chronic opiate users, there was a trend toward higher opiate requirements for the bupivacaine hydrochloride group than for the liposomal bupivacaine group; however, this trend did not achieve statistical significance. CONCLUSIONS Liposomal bupivacaine did not appear to significantly decrease perioperative narcotic use or length of hospitalization, although there was a trend toward decreased narcotic use in comparison with bupivacaine hydrochloride. While the results of this study do not support the routine use of liposomal bupivacaine, there may be a benefit in the subgroup of patients who are chronic opiate users. Future prospective randomized controlled trials, ideally with dose-response parameters, must be performed to fully explore the efficacy of liposomal bupivacaine, as the prior literature suggests that clinically relevant effects require a minimum tissue concentration.

Abdominal Incision Injection of Liposomal Bupivacaine and Opioid Use After Laparotomy for Gynecologic Malignancies.

PubMed

Kalogera, Eleftheria; Bakkum-Gamez, Jamie N; Weaver, Amy L; Moriarty, James P; Borah, Bijan J; Langstraat, Carrie L; Jankowski, Christopher J; Lovely, Jenna K; Cliby, William A; Dowdy, Sean C

2016-11-01

To investigate opioid use and pain scores associated with incisional injection of liposomal bupivacaine compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies. A retrospective cohort study was conducted to compare abdominal incision infiltration with liposomal bupivacaine with bupivacaine hydrochloride after modification of a pre-existing enhanced recovery pathway. Patients undergoing staging laparotomy or complex cytoreductive surgery under the updated pathway were compared with patients treated under the original pathway (historic controls). Endpoints included cumulative opioid use (primary outcome) in oral morphine equivalents and cumulative pain score. In the complex cytoreductive cohort, median oral morphine equivalents were lower in the liposomal bupivacaine group through 24 hours (30 compared with 53.5 mg, P=.002), 48 hours (37.5 compared with 82.5 mg, P=.005), and the length of stay (62 compared with 100.5 mg, P=.006). Fewer liposomal bupivacaine patients required intravenous rescue opioids (28.9% compared with 55.6%, P<.001) or patient-controlled analgesia (4.1% compared with 33.3%, P<.001). Cumulative pain score was no different between groups through 48 hours (161 compared with 158, P=.69). Postoperative nausea and ileus were less frequent in patients receiving liposomal bupivacaine. Median hospital stay was 5 days in both groups. In the staging laparotomy cohort, cumulative opioids and cumulative pain score were no different between groups (through 48 hours: 162 compared with 161, P=.62; 38 compared with 38, P=.68, respectively). Intravenous rescue opioids (15.3% compared with 28.6%, P=.05) and patient-controlled analgesia (1.4% compared with 8.3%, P=.05) were used less frequently in the liposomal bupivacaine group. Median hospital stay was 4 days in both groups. Despite the higher cost of liposomal bupivacaine, total pharmacy costs did not differ between groups. Abdominal incision infiltration with liposomal bupivacaine was associated with less opioid and patient-controlled analgesia use with no change in pain scores compared with bupivacaine hydrochloride after complex cytoreductive surgery for gynecologic malignancies. Improvements were also seen in patients undergoing staging laparotomy.

Host-guest complexes of local anesthetics with cucurbit[6]uril and para-sulphonatocalix[8]arene in the solid state

NASA Astrophysics Data System (ADS)

Danylyuk, Oksana; Butkiewicz, Helena; Coleman, Anthony W.; Suwinska, Kinga

2017-12-01

Here we describe the host-guest inclusion complexes of local anesthetic drugs with two macrocyclic hosts cucurbit[6]uril and para-sulphonatocalix[8]arene in the solid state. The anesthetic agents used in the co-crystallization with the supramolecular hosts are lidocaine, procaine, procainamide, prilocaine and proparacaine. Both macrocycles encapsulate the alkylammonium moieties of anestetics guests into their cavities although the mechanism of complexation, host-guest stoichiometry and geometry differ depending on the nature of the supramolecular host.

Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

PubMed

Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

2017-03-01

The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), 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. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p < 0.0001). As far as safety, there was no significant difference in side effects between the two groups (RR 1.10, 95 % CI 0.59-2.04, n.s.). Sensitivity analyses suggested that the results of these two primary outcomes were stable and reliable. However, the current evidence did not suggest a superior effect with respect to the time to first analgesic request (WMD 51.33, 95 % CI -110.99 to 213.65, n.s.) and the number of patients requiring supplementary analgesia (RR 1.13, 95 % CI 0.92-1.39, n.s.). On the basis of the currently available literature, this study is the first to suggest that single-dose intra-articular bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: A meta-analysis.

PubMed

Yan, Zeng; Chen, Zong; Ma, Chuangen

2017-07-01

Postoperative pain control after total shoulder arthroplasty (TSA) can be challenging. Liposomal bupivacaine and interscalene nerve block are 2 common pain control protocol for TSA patients. However, whether liposomal bupivacaine was superior than interscalene nerve block was unknown. This meta-analysis aimed to illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain control in patients undergoing TSA. In May 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, and 2 weeks, total morphine consumption at 24 hours, and the length of hospital stay. Software of Stata 12.0 was used for pooling the final outcomes. Five clinical studies with 573 patients (liposomal bupivacaine group = 239, interscalene nerve block group = 334) were ultimately included in the meta-analysis. There was no significant difference between the VAS at 4 hours, 8 hours, and 2 weeks between liposomal bupivacaine group and interscalene nerve block group (P > .05). Compared with interscalene nerve block group, liposomal bupivacaine was associated with a reduction of VAS score at 12 hours, 24 hours by appropriately 3.31 points and 6.42 points respectively on a 100-point VAS. Furthermore, liposomal bupivacaine was associated with a significantly reduction of the length of hospital stay by appropriately by 0.16 days compared with interscalene nerve block group. Current meta-analysis indicates that compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and the length of hospital stay. However, studies with more patients and better-designed methods are needed to establish the optimal regimen and the safety of liposomal bupivacaine in TSA patients.

Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty

PubMed Central

Yan, Zeng; Chen, Zong; Ma, Chuangen

2017-01-01

Abstract Background: Postoperative pain control after total shoulder arthroplasty (TSA) can be challenging. Liposomal bupivacaine and interscalene nerve block are 2 common pain control protocol for TSA patients. However, whether liposomal bupivacaine was superior than interscalene nerve block was unknown. This meta-analysis aimed to illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain control in patients undergoing TSA. Methods: In May 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, and 2 weeks, total morphine consumption at 24 hours, and the length of hospital stay. Software of Stata 12.0 was used for pooling the final outcomes. Results: Five clinical studies with 573 patients (liposomal bupivacaine group = 239, interscalene nerve block group = 334) were ultimately included in the meta-analysis. There was no significant difference between the VAS at 4 hours, 8 hours, and 2 weeks between liposomal bupivacaine group and interscalene nerve block group (P > .05). Compared with interscalene nerve block group, liposomal bupivacaine was associated with a reduction of VAS score at 12 hours, 24 hours by appropriately 3.31 points and 6.42 points respectively on a 100-point VAS. Furthermore, liposomal bupivacaine was associated with a significantly reduction of the length of hospital stay by appropriately by 0.16 days compared with interscalene nerve block group. Conclusion: Current meta-analysis indicates that compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and the length of hospital stay. However, studies with more patients and better-designed methods are needed to establish the optimal regimen and the safety of liposomal bupivacaine in TSA patients. PMID:28682872

Injectable Nanocomposite Analgesic Delivery System for Musculoskeletal Pain Management.

PubMed

Khanal, Manakamana; Gohil, Shalini V; Kuyinu, Emmanuel; Kan, Ho-Man; Knight, Brittany E; Baumbauer, Kyle M; Lo, Kevin W-H; Walker, Joseph; Laurencin, Cato T; Nair, Lakshmi S

2018-05-24

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/ or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo. A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain. Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model. Copyright © 2018. Published by Elsevier Ltd.

Pharmacokinetics of bupivacaine after bilateral ultrasound-guided transversus abdominis plane block following cesarean delivery under spinal anesthesia.

PubMed

Trabelsi, B; Charfi, R; Bennasr, L; Marzouk, S Ben; Eljebari, H; Jebabli, N; Sassi, M Ben; Trabelsi, S; Maghrebi, H

2017-11-01

Transversus abdominis plane block is an effective method of post-cesarean analgesia. There are no data available about plasma bupivacaine levels after this block in adults. This study aimed to assess bupivacaine pharmacokinetic parameters after ultrasound-guided transversus abdominis plane blocks following cesarean delivery under spinal anesthesia. A prospective observational study in parturients undergoing elective cesarean delivery under hyperbaric bupivacaine spinal anesthesia was conducted. After surgery, patients received bilateral transversus abdominis plane block (50mg bupivacaine each side). Venous blood samples were collected immediately before performing the block and at 10, 20, 30, 45, 60, 90, 120, 180, 240, 720 and 1440minutes. High performance liquid chromatography was used to measure total plasma bupivacaine concentrations. Mean bupivacaine area under the curve (AUC) was calculated from 0 to 24hours. Data were collected from 17 parturients. Mean age and body mass index were 31±6y and 30±4kg/m 2 respectively. Mean plasma bupivacaine concentration before the block was 171ng/mL. Mean peak concentration was 802.36ng/mL (range 231.8 to 3504.5ng/mL). Mean time to peak concentration was 30min and mean area-under-the-curve (0-24h) was 4505.4h.ng/mL. Mean elimination half-life was 8.75h. Three subjects had concentrations above the quoted toxic threshold and mild symptoms suggestive of neurotoxicity were reported by two subjects, but no treatment was required. Single-dose bilateral transversus abdominis plane block using 100mg of bupivacaine, after spinal anesthesia for cesarean delivery, can result in toxic plasma bupivacaine concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
.

Enhanced Expression of WD Repeat-Containing Protein 35 via CaMKK/AMPK Activation in Bupivacaine-Treated Neuro2a Cells

PubMed Central

Huang, Lei; Kondo, Fumio; Gosho, Masahiko; Feng, Guo-Gang; Harato, Misako; Xia, Zhong-yuan; Ishikawa, Naohisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

We previously reported that bupivacaine induces reactive oxygen species (ROS) generation, p38 mitogen-activated protein kinase (MAPK) activation and nuclear factor-kappa B activation, resulting in an increase in expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. However, the identity of signaling upstream of p38 MAPK pathways to WDR35 expression remains unclear. It has been shown that AMP-activated protein kinase (AMPK) can activate p38 MAPK through diverse mechanisms. In addition, several kinases acting upstream of AMPK have been identified including Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Recent studies reported that AMPK may be involved in bupivacaine-induced cytotoxicity in Schwann cells and in human neuroblastoma SH-SY5Y cells. The present study was undertaken to test whether CaMKK and AMPK are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Our results showed that bupivacaine induced activation of AMPK and p38 MAPK in Neuro2a cells. The AMPK inhibitors, compound C and iodotubercidin, attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. Treatment with the CaMKK inhibitor STO-609 also attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. These results suggest that bupivacaine activates AMPK and p38 MAPK via CaMKK in Neuro2a cells, and that the CaMKK/AMPK/p38 MAPK pathway is involved in regulating WDR35 expression. PMID:24859235

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

PubMed

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia.

PubMed

Vyas, Krishna S; Rajendran, Sibi; Morrison, Shane D; Shakir, Afaaf; Mardini, Samir; Lemaine, Valerie; Nahabedian, Maurice Y; Baker, Stephen B; Rinker, Brian D; Vasconez, Henry C

2016-10-01

Management of postoperative pain often requires multimodal approaches. Suboptimal dosages of current therapies can leave patients experiencing periods of insufficient analgesia, often requiring rescue therapy. With absence of a validated and standardized approach to pain management, further refinement of treatment protocols and targeted therapeutics is needed. Liposomal bupivacaine (Exparel) is a longer acting form of traditional bupivacaine that delivers the drug by means of a multivesicular liposomal system. The effectiveness of liposomal bupivacaine has not been systematically analyzed relative to conventional treatments in plastic surgery. A comprehensive literature search of the MEDLINE, PubMed, and Google Scholar databases was conducted for studies published through October of 2015 with search terms related to liposomal bupivacaine and filtered for relevance to postoperative pain control in plastic surgery. Data on techniques, outcomes, complications, and patient satisfaction were collected. A total of eight articles were selected and reviewed from 160 identified. Articles covered a variety of techniques using liposomal bupivacaine for postoperative pain management. Four hundred five patients underwent procedures (including breast reconstruction, augmentation mammaplasty, abdominal wall reconstruction, mastectomy, and abdominoplasty) where pain was managed with liposomal bupivacaine and compared with those receiving traditional pain management. Liposomal bupivacaine use showed adequate safety and tolerability and, compared to traditional protocols, was equivalent or more effective in postoperative pain management. Liposomal bupivacaine is a safe method for postoperative pain control in the setting of plastic surgery and may represent an alternative to more invasive pain management systems such as patient-controlled analgesia, epidurals, peripheral nerve catheters, or intravenous narcotics.

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

PubMed

Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Evaluation of local anesthetic effects of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles in Male Swiss mice.

PubMed

Jiang, Qiliang; Yu, Shashuang; Li, Xingwang; Ma, Chuangen; Li, Aixiang

2018-01-01

A simple approach for the synthesis of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles (IL-AgNPs) was reported in this work. The shape, size and surface morphology of the Lidocaine-Ibuprofen ionic liquid stabilized AgNPs were characterized by using spectroscopic and microscopic techniques such as Ultraviolet-visible spectroscopy (UV-Visible), X-ray diffraction (XRD) analysis, Selected area electron diffraction (SAED), Transmission electron microscopy (TEM). TEM analysis showed the formation of 20-30nm size of IL-AgNPs with very clear lattice fringes. SAED pattern confirmed the highly crystalline nature of fabricated IL stabilized AgNPs. EDS results confirmed the formation of nanosilver. The fabricated IL-AgNPs were studied for their local anesthetic effect in rats. The results of local anesthetic effect showed that the time for onset of action by IL-AgNPs is 10min, which is significantly higher than that for EMLA. Further, tactile test results confirmed the stronger and faster local anesthetic effect of IL-AgNPs when compared to that of EMLA. Copyright © 2017. Published by Elsevier B.V.

Surgical Site Infiltration for Abdominal Surgery: A Novel Neuroanatomical-based Approach

PubMed Central

Janis, Jeffrey E.; Haas, Eric M.; Ramshaw, Bruce J.; Nihira, Mikio A.; Dunkin, Brian J.

2016-01-01

Background: Provision of optimal postoperative analgesia should facilitate postoperative ambulation and rehabilitation. An optimal multimodal analgesia technique would include the use of nonopioid analgesics, including local/regional analgesic techniques such as surgical site local anesthetic infiltration. This article presents a novel approach to surgical site infiltration techniques for abdominal surgery based upon neuroanatomy. Methods: Literature searches were conducted for studies reporting the neuroanatomical sources of pain after abdominal surgery. Also, studies identified by preceding search were reviewed for relevant publications and manually retrieved. Results: Based on neuroanatomy, an optimal surgical site infiltration technique would consist of systematic, extensive, meticulous administration of local anesthetic into the peritoneum (or preperitoneum), subfascial, and subdermal tissue planes. The volume of local anesthetic would depend on the size of the incision such that 1 to 1.5 mL is injected every 1 to 2 cm of surgical incision per layer. It is best to infiltrate with a 22-gauge, 1.5-inch needle. The needle is inserted approximately 0.5 to 1 cm into the tissue plane, and local anesthetic solution is injected while slowly withdrawing the needle, which should reduce the risk of intravascular injection. Conclusions: Meticulous, systematic, and extensive surgical site local anesthetic infiltration in the various tissue planes including the peritoneal, musculofascial, and subdermal tissues, where pain foci originate, provides excellent postoperative pain relief. This approach should be combined with use of other nonopioid analgesics with opioids reserved for rescue. Further well-designed studies are necessary to assess the analgesic efficacy of the proposed infiltration technique. PMID:28293525

Analgesic Effect of Intraperitoneal Bupivacaine Hydrochloride After Laparoscopic Sleeve Gastrectomy: a Randomized Clinical Trial.

PubMed

Alamdari, Nasser Malekpour; Bakhtiyari, Mahmood; Gholizadeh, Barmak; Shariati, Catrine

2018-03-01

The indications for sleeve gastrectomy as a primary procedure for the surgical treatment of morbid obesity have increased worldwide. Pain is the most common complaint for patients on the first day after laparoscopic sleeve gastrectomy. There are various methods for decreasing pain after laparoscopic sleeve gastrectomy such as the use of intraperitoneal bupivacaine hydrochloride. This clinical trial was an attempt to discover the effects of intraperitoneal bupivacaine hydrochloride on alleviating postoperative pain after laparoscopic sleeve gastrectomy. In general, 120 patients meeting the inclusion criteria were enrolled. Patients were randomly allocated into two interventions and control groups using a balanced block randomization technique. One group received intraperitoneal bupivacaine hydrochloride (30 cm 3 ), and the other group served as the control one and did not receive bupivacaine hydrochloride. Diclofenac suppository and paracetamol injection were administered to both groups for postoperative pain management. The mean subjective postoperative pain score was significantly decreased in patients who received intraperitoneal bupivacaine hydrochloride within the first 24 h after the surgery; thus, the instillation of bupivacaine hydrochloride was beneficial in managing postoperative pain. The intraoperative peritoneal irrigation of bupivacaine hydrochloride (30 cm 3 , 0.25%) in sleeve gastrectomy patients was safe and effective in reducing postoperative pain, nausea, and vomiting (IRCT2016120329181N4).

Concurrent In Vitro Release of Silver Sulfadiazine and Bupivacaine From Semi-Interpenetrating Networks for Wound Management

PubMed Central

Kleinbeck, Kyle R.; Bader, Rebecca A.; Kao, Weiyuan John

2013-01-01

In situ photopolymerized semi-interpenetrating networks (sIPNs) composed of poly(ethylene glycol) and gelatin are promising multifunctional matrices for a regenerative medicine approach to dermal wound treatment. In addition to previously demonstrated efficacy in critical defects, sIPNs also function as drug delivery matrices for compounds loaded as either soluble or covalently linked components. Simultaneous release of silver sulfadiazine and bupivacaine from the sIPN would provide multiple-hit management of dermal wounds that minimizes infection, and manages pain along with sIPN absorption of exudates and facilitation of epidermal regrowth. We characterized the release of soluble silver sulfadiazine and bupivacaine and compared it with an established release model. Efficacy of released silver sulfadiazine was confirmed in vitro on Staphylococcus aureus, methicillin resistant S. aureus, and Pseudomonas aeruginosa. Bupivacaine loaded without silver sulfadiazine showed incomplete release, whereas simultaneous loading with silver sulfadiazine facilitated 100% bupivacaine release. Silver sulfadiazine released at 98% without bupivacaine and 96% with bupivacaine. Silver sulfadiazine released onto bacterial cultures inhibited all three strains dose dependently. sIPNs effectively release bupivacaine and silver sulfadiazine while maintaining the antimicrobial activity of silver sulfadiazine. Drug loaded sIPNs have potential to improve wound management by providing multi-drug delivery along with an effective wound treatment. PMID:19060724

Retrospective review of voluntary reports of nonsurgical paresthesia in dentistry.

PubMed

Gaffen, Andrew S; Haas, Daniel A

2009-10-01

Paresthesia is an adverse event that may be associated with the administration of local anesthetics in dentistry. The purpose of this retrospective study was to analyze cases of paresthesia associated with local anesthetic injection that were voluntarily reported to Ontario"s Professional Liability Program (PLP) from 1999 to 2008 inclusive, to see if the findings were consistent with those from 1973 to 1998 from this same source. All cases of nonsurgical paresthesia reported from 1999 to 2008 were reviewed; cases involving surgical procedures were excluded. Variables examined included patient age and gender, type and volume of local anesthetic, anatomic site of nerve injury, affected side and pain on injection or any other symptoms. During the study period, 182 PLP reports of paresthesia following nonsurgical procedures were made; all but 2 were associated with mandibular block injection. There was no significant gender predilection, but the lingual nerve was affected more than twice as frequently as the inferior alveolar nerve. During 2006-2008 alone, 64 cases of nonsurgical paresthesia were reported to PLP, a reported incidence of 1 in 609,000 injections. For the 2 local anesthetic drugs available in dental cartridges as 4% solutions, i.e., articaine and prilocaine, the frequencies of reporting of paresthesia were significantly greater than expected (chi2, exact binomial distribution; p < 0.01) based on their level of use by Ontario dentists. These data suggest that local anesthetic neurotoxicity may be at least partly involved in the development of postinjection paresthesia.

Effects of analgesia of the distal interphalangeal joint or palmar digital nerves on lameness caused by solar pain in horses.

PubMed

Schumacher, J; Steiger, R; Schumacher, J; de Graves, F; Schramme, M; Smith, R; Coker, M

2000-01-01

To determine if pain of the dorsal margin of the sole in horses can be attenuated by anesthesia of either the distal interphalangeal (DIP) joint or the palmar digital (PD) nerves. A unilateral forelimb lameness was induced by creating solar pain. Response to administration of local anesthetic or saline solution into the DIP joint and to administration of local anesthetic around the PD nerves was evaluated. Six horses. Lameness was induced by creating pressure on the dorsal margin of the sole by screwing set-screws into a nut welded to the inside of each branch of a shoe. Gaits were evaluated before and after application of set-screws and after a local anesthetic or saline solution was administered into the DIP joint and, in a second trial, after a local anesthetic was injected around the PD nerves. Gaits recorded on videotape were evaluated, and lameness scores were assigned to each gait. Lameness scores were high after application of set-screws and remained high after saline solution was administered into the DIP joint. Scores decreased significantly (P < or = .05) after a local anesthetic was administered into the DIP joint or around the PD nerves. Analgesia of the DIP joint or the PD nerves desensitizes at least a portion of the sole. Pain arising from the sole should not be excluded as a cause of lameness when lameness is attenuated by analgesia of the DIP joint or PD nerves.

[The effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy: a randomized controlled study].

PubMed

Karaman, Tugba; Ozsoy, Asker Zeki; Karaman, Serkan; Dogru, Serkan; Tapar, Hakan; Sahin, Aynur; Dogru, Hatice; Suren, Mustafa

A transversus abdominis plane block is a peripheral block method that has been used successfully for pain relief after total abdominal hysterectomy. However, the effects of the combination of the transversus abdominis plane block and general anesthesia on analgesic and anesthetic requirements remain unclear. This randomized placebo-controlled study is aimed to evaluate the effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy under general anesthesia. Sixty-six women undergoing total abdominal hysterectomy were randomized into two groups to receive general anesthesia alone (control group) or with transversus abdominis plane block using 20mL of 0.25% bupivacaine (transversus abdominis plane group). Intraoperative remifentanil and sevoflurane consumption were recorded. We also evaluated the postoperative pain, nausea, quality of recovery scores and rescue analgesic requirement during postoperative 24hours. The total remifentanil and sevoflurane consumption is significantly lower in transversus abdominis plane group; respectively mean (SD) 0.130 (0.25) vs. 0.094 (0.02) mcg.kg -1 .min -1 ; p<0.01 and 0.295 (0.05) vs. 0.243 (0.06) mL.min -1 ; p<0.01. In the postoperative period, pain scores were significantly reduced in transversus abdominis plane group soon after surgery; median (range) 6 (2-10) vs. 3 (0-5); p<0.001, at 2h (5 [3-9] vs. 2.5 [0-6]; p<0.001), at 6h (4 [2-7] vs. 3[0-6], p<0.001), at 12h (3.5 [1-6] vs. 2 [1-5]; p=0.003). The patients in the transversus abdominis plane group had significantly higher QoR-40 scores 190.5 (175-197) vs. 176.5 (141-187); p<0.001). Combining transversus abdominis plane block with general anesthesia can provide reduced opioid and anesthetic consumption and can improve postoperative pain and quality of recovery scores in patients undergoing total abdominal hysterectomy. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses, it is usually given at a lower dose to cause sedation and hypnosis and may be supplemented with a local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii...

Epidural labour analgesia using Bupivacaine and Clonidine

PubMed Central

Syal, K; Dogra, RK; Ohri, A; Chauhan, G; Goel, A

2011-01-01

Background: To compare the effects of addition of Clonidine (60 μg) to Epidural Bupivacaine (0.125%) for labour analgesia, with regard to duration of analgesia, duration of labour, ambulation, incidence of instrumentation and caesarean section, foetal outcome, patient satisfaction and side effects. Patients & Methods: On demand, epidural labour analgesia was given to 50 nulliparous healthy term parturients (cephalic presentation), divided in two groups randomly. Group I received bupivacaine (0.125%) alone, whereas Group II received bupivacaine (0.125%) along with Clonidine (60 μg). 10 ml of 0.125% bupivacaine was injected as first dose and further doses titrated with patient relief (Numerical Rating Scale <3). Top ups were given whenever Numerical Rating Scale went above 5. Results: There was statistically significant prolongation of duration of analgesia in Group II, with no difference in duration of labour, ambulation, incidence of instrumentation and caesarean section or foetal outcome. Also clonidine gave dose sparing effect to bupivacaine and there was better patient satisfaction without any significant side effects in Group II. Conclusion: Clonidine is a useful adjunct to bupivacaine for epidural labour analgesia and can be considered as alternative to opioids. PMID:21804714

The Role of Liposomal Bupivacaine in Value-Based Care.

PubMed

Iorio, Richard

Multimodal pain control strategies are crucial in reducing opioid use and delivering effective pain management to facilitate improved surgical outcomes. The utility of liposomal bupivacaine in enabling effective pain control in multimodal strategies has been demonstrated in several studies, but others have found the value of liposomal bupivacaine in such approaches to be insignificant. At New York University Langone Medical Center, liposomal bupivacaine injection and femoral nerve block were compared in their delivery of efficacious and cost-effective multimodal analgesia among patients undergoing total joint arthroplasty (TJA). Retrospective analysis revealed that including liposomal bupivacaine in a multimodal pain control protocol for TJA resulted in improved quality and efficiency metrics, decreased narcotic use, and faster mobilization, all relative to femoral nerve block, and without a significant increase in admission costs. In addition, liposomal bupivacaine use was associated with elimination of the need for patient-controlled analgesia in TJA. Thus, at Langone Medical Center, the introduction of liposomal bupivacaine to TJA has been instrumental in achieving adequate pain control, delivering high-level quality of care, and controlling costs.

Membrane permeable local anesthetics modulate NaV1.5 mechanosensitivity

PubMed Central

Beyder, Arthur; Strege, Peter R.; Bernard, Cheryl; Farrugia, Gianrico

2012-01-01

Voltage-gated sodium selective ion channel NaV1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. NaV1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon NaV1.5 to modulate activity by multiple mechanisms. This study examined whether NaV1.5 mechanosensitivity is modulated by local anesthetics. NaV1.5 channels wereexpressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V1/2a) and inactivation (V1/2i) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V1/2a but not V1/2i. Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V1/2a. Lidocaine inhibited mechanosensitivity in NaV1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A NaV1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of NaV1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions. PMID:22874086

Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration

PubMed Central

Gavrilovska-Brzanov, Aleksandra; Kuzmanovska, Biljana; Kartalov, Andrijan; Donev, Ljupco; Lleshi, Albert; Jovanovski-Srceva, Marija; Spirovska, Tatjana; Brzanov, Nikola; Simeonov, Risto

2016-01-01

AIM: The aim of this study is to evaluate anesthesia and recovery profile in pediatric patients after inguinal hernia repair with caudal block or local wound infiltration. MATERIAL AND METHODS: In this prospective interventional clinical study, the anesthesia and recovery profile was assessed in sixty pediatric patients undergoing inguinal hernia repair. Enrolled children were randomly assigned to either Group Caudal or Group Local infiltration. For caudal blocks, Caudal Group received 1 ml/kg of 0.25% bupivacaine; Local Infiltration Group received 0.2 ml/kg 0.25% bupivacaine. Investigator who was blinded to group allocation provided postoperative care and assessments. Postoperative pain was assessed. Motor functions and sedation were assessed as well. RESULTS: The two groups did not differ in terms of patient characteristic data and surgical profiles and there weren’t any hemodynamic changes between groups. Regarding the difference between groups for analgesic requirement there were two major points - on one hand it was statistically significant p < 0.05 whereas on the other hand time to first analgesic administration was not statistically significant p = 0.40. There were significant differences in the incidence of adverse effects in caudal and local group including: vomiting, delirium and urinary retention. CONCLUSIONS: Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common. PMID:27275337

[Comparison of clinical effectiveness of thoracic epidural and intravenous patient-controlled analgesia for the treatment of rib fractures pain in intensive care unit].

PubMed

Topçu, Ismet; Ekici, Zeynep; Sakarya, Melek

2007-07-01

The results of thoracic epidural and systemic patient controlled analgesia practice were evaluated retrospectively in patients with thoracic trauma. Patients who were admitted to the intensive care unit between 1997 and 2003, with a diagnosis of multiple rib fractures related to thoracic trauma were evaluated retrospectively. Data were recorded from 49 patients who met the following criteria; three or more rib fractures, initiation of PCA with I.V. phentanyl or thoracic epidural analgesia with phentanyl and bupivacaine. There were no significant differences between the groups concerning injury severity score. APACHE II score (8.1+/-1.6 and 9.2+/-1.7) and the number of rib fractures (4+/-1.1 and 6.8+/-2.7) were higher in thoracic epidural analgesia group (p<0.05). Pain scores of patients who received thoracic epidural analgesia were significantly lower as from 6th hour during whole therapy (p<0.05). Length of intensive care unit stay (15.6+/-5.9 and 12.1+/-4.4 day) was found to be shorter in thoracic epidural analgesia group (p<0.05). There were no differences between the groups regarding mechanical ventilation requirement, pulmonary and cardiac complications. We suggest that the use of thoracic epidural analgesia with infusion of local anesthetics and opioids are more appropriate as they provide more effective analgesia and shorten length of intensive care unit stay in chest trauma patients with more than three rib fractures who require intensive care.

[Neurolitic block of the lumbar sympathetic chain improves chronic pain in a patient with critical lower limb ischemia].

PubMed

Barreto Junior, Elton Pereira de Sá; Nascimento, Jedson Dos Santos; de Castro, Anita Perpetua Carvalho Rocha

Sympathectomy is one of the therapies used in the treatment of chronic obstructive arterial disease (COAD). Although not considered as first-line strategy, it should be considered in the management of pain difficult to control. This clinical case describes the evolution of a patient with inoperable COAD who responded properly to the lumbar sympathetic block. A female patient, afro-descendant, 69 years old, ASA II, admitted to the algology service due to refractory ischemic pain in the lower limbs. The patient had undergone several surgical procedures and conservative treatments without success. Vascular surgery considered the case as out of therapeutic possibility, unless limb amputation. At that time, sympathectomy was indicated. After admission to the operating room, the patient was monitored, positioned and sedated. The blockade was performed with the aid of radioscopy, bilaterally, at L2-L3-L4 right and L3 left levels. On the right side, at each level cited, 3mL of absolute alcohol with 0.25% bupivacaine were injected without vasoconstrictor, and on the left side only local anesthetic. The procedure was performed uneventfully. The patient was discharged with complete remission of the pain. Neurolitic block of the lumbar sympathetic chain is an effective and safe treatment option for pain control in patients with critical limb ischemia patients in whom the only possible intervention would be limb amputation. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Anesthetics mechanism on a DMPC lipid membrane model: Insights from molecular dynamics simulations.

PubMed

Saeedi, Marzieh; Lyubartsev, Alexander P; Jalili, Seifollah

2017-07-01

To provide insight into the molecular mechanisms of local anesthetic action, we have carried out an extensive investigation of two amide type local anesthetics, lidocaine and articaine in both charged and uncharged forms, interacting with DMPC lipid membrane. We have applied both standard molecular dynamics simulations and metadynamics simulations to provide a detailed description of the free energy landscape of anesthetics embedded in the lipid bilayer. The global minimum of the free energy surface (equilibrium position of anesthetics in the lipid membrane) occurred around 1nm of the bilayer center. The uncharged anesthetics show more affinity to bind to this region compared to the charged drugs. The binding free energy of uncharged lidocaine in the membrane (-30.3kJ/mol) is higher than uncharged articaine (-24.0kJ/mol), which is in good agreement with higher lipid solubility of lidocaine relative to the articaine. The octanol/water partition coefficient of uncharged drugs was also investigated using expanded ensemble simulations. In addition, complementary standard MD simulations were carried out to study the partitioning behavior of multiple anesthetics inside the lipid bilayer. The results obtained here are in line with previously reported simulations and suggest that the different forms of anesthetics induce different structural modifications in the lipid bilayer, which can provide new insights into their complex membrane translocation phenomena. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative study of fentanyl and morphine in addition to hyperbaric or isobaric bupivacaine in combined spinal anaesthesia for caesarean section

PubMed Central

Saracoglu, Ayten; Saracoglu, Kemal T.; Eti, Zeynep

2011-01-01

Introduction The aim of our study was to compare the effects of isobaric and hyperbaric bupivacaine combined with morphine or fentanyl in patients undergoing caesarean section. We assessed quality and spread of analgesia and anaesthesia, postoperative analgesic requirement and side effects. Material and methods Hundred patients with American Society of Anesthesiologists physical status (ASA) I-II, age 18 to 40 years, were randomized to 4 groups. The intrathecal solutions were isobaric bupivacaine + morphine (group A), isobaric bupivacaine + fentanyl (group B), heavy bupivacaine + + morphine (group C) and heavy bupivacaine + fentanyl (group D). Mean arterial pressure, heart rate, oxygen saturation, ephedrine consumption, analgesic requirement time and additional analgesic needs were recorded. Results The 1st min value of mean arterial pressure was the lowest one in all groups. Heart rate decreased significantly in group A at the 10th min but not in the other groups. The decrease of visual analogue scale (VAS) pain scores began in the groups after the 4th postoperative h (p < 0.05) and the VAS value of group B at the 8th h was significantly higher than the other groups. The first analgesic requirement time in the postoperative period was longer in patients who had intrathecal morphine than those who had fentanyl. The duration of analgesia with isobaric bupivacaine and morphine was the longest one. Conclusions We concluded that intrathecal morphine provides a long duration of postoperative analgesia but the duration gets longer when it is combined with plain bupivacaine instead of heavy bupivacaine. PMID:22291807

Systematic review of spinal anaesthesia using bupivacaine for ambulatory knee arthroscopy.

PubMed

Nair, G S; Abrishami, A; Lermitte, J; Chung, F

2009-03-01

The use of lidocaine in spinal anaesthesia is associated with transient neurological syndrome (TNS). Bupivacaine has a lower incidence of TNS as an alternative but it may have a prolonged action. This study systematically reviews the literature about the recovery profile of patients undergoing spinal anaesthesia, using bupivacaine for arthroscopic knee surgery. We identified 17 eligible randomized clinical trials (RCTs) (1268 patients). All the articles in this review, except one, used hyperbaric bupivacaine. Five trials compared different doses of bupivacaine (range 3-15 mg). Large doses of bupivacaine (10 and 15 mg) were associated with delayed recovery, and supine positioning was associated with a high incidence of failure. With unilateral positioning, a dose as low as 4-5 mg seems to be sufficient. Five trials comparing bupivacaine or levobupivacaine with ropivacaine showed no significant difference in the time to home discharge. When bupivacaine was combined with fentanyl in two trials, marginal delay in recovery was found [time to discharge (min); weighted mean difference (WMD) 14.1, 95% CI 11.9-40.1] and increased nausea and pruritus but had reduced postoperative pain. Unilateral and bilateral spinal anaesthesia were assessed in two trials, and the latter group was associated with early recovery and discharge [time to discharge (min); WMD -41.6, 95% CI -63.6 to -19.6). The results of our systematic review suggest that 4-5 mg of hyperbaric bupivacaine can effectively produce spinal anaesthesia for knee arthroscopy with unilateral positioning. Ropivacaine or the addition of adjuvants did not improve the recovery time. There is a need for tighter RCTs with more consistent endpoints.

Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course

ERIC Educational Resources Information Center

Demare, Patricia; Regla, Ignacio

2012-01-01

This article describes one of the projects in the advanced undergraduate organic chemistry laboratory course concerning the synthesis of two local anesthetic drugs, prilocaine and benzocaine, with a common three-step sequence starting from toluene. Students undertake, in a several-week independent project, the multistep synthesis of a…

Complex regional pain syndrome (CRPS) with resistance to local anesthetic block: a case report.

PubMed

Maneksha, F R; Mirza, H; Poppers, P J

2000-02-01

We present a case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl. The patient did not respond to the usual therapeutic modalities used to treat CRPS, including physical therapy, lumbar sympathetic block, epidural local anesthetic block, intravenous lidocaine infusion, or other oral medications. Of note is the fact that, during epidural block, the patient demonstrated a resistance to local anesthetic neural blockade in the area of the body involved with the pain problem. The mechanism of this resistance could be related to the changes in the dorsal horn cells of the spinal cord, secondary to activation of N-methyl-D-aspartate receptors, which may play a role in the pathophysiology of this pain syndrome.

Lipid Emulsion in Treatment of Local Anesthetic Toxicity.

PubMed

Collins, Shawn; Neubrander, Judy; Vorst, Zachary; Sheffield, Brad

2015-08-01

Epidural, spinal, regional, local, and intravenous administration of local anesthetics (LAs) is a cornerstone of anesthetic practice. LA toxicity is a grave consequence that is of great significance to anesthesia providers. Outcomes of LA toxicity range from inconvenient symptoms such as tinnitus, twitching, and hypotension to seizures; cardiovascular or respiratory collapse; and death. Lipid emulsion has emerged as a potential "magic bullet" in treating LA toxicity. This literature review provides background information and proposed mechanisms of action for LAs and lipid emulsion as well as animal experiments and a case report that speak to the effectiveness of lipid emulsion in the face of LA toxicity. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Periodontal ligament and intraosseous anesthetic injection techniques: alternatives to mandibular nerve blocks.

PubMed

Moore, Paul A; Cuddy, Michael A; Cooke, Matthew R; Sokolowski, Chester J

2011-09-01

and Overview. The provision of mandibular anesthesia traditionally has relied on nerve block anesthetic techniques such as the Halsted, the Gow-Gates and the Akinosi-Vazirani methods. The authors present two alternative techniques to provide local anesthesia in mandibular teeth: the periodontal ligament (PDL) injection and the intraosseous (IO) injection. The authors also present indications for and complications associated with these techniques. The PDL injection and the IO injection are effective anesthetic techniques for managing nerve block failures and for providing localized anesthesia in the mandible. Dentists may find these techniques to be useful alternatives to nerve block anesthesia.