Chitosan Membranes Stabilized with Varying Acyl Lengths Release Cis-2-Decenoic Acid and Bupivacaine at Controlled Rates and Inhibit Pathogenic Biofilm.

BACKGROUND: Adherence of complex bacterial biofilm communities to burned tissue creates a challenge for treatment, with infection causing 51% of burn victim deaths. This study evaluated the release of therapeutics from wound care biomaterials and their antimicrobial activity against pathogens Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. METHODS: Electrospun chitosan membranes (ESCMs) were fabricated and acylated with chain lengths ranging from 6-10 carbons then loaded with 0.15 mg of anti-biofilm agent, cis-2-decenoic acid (C2DA), and 0.5 mg of local anesthetic, bupivacaine. RESULTS: Combinations of therapeutics released from modified ESCMs at a cumulative amount of 45-70% of bupivacaine and less than 20% of C2DA. Results from bacterial studies suggest that this combination reduced biofilm 10-fold for S. aureus, 2-fold for Acinetobacter baumannii, and 2-3-fold for Pseudomonas aeruginosa by 24 hours. Additionally, dual loaded groups reduced planktonic Staphylococcus aureus ~4-fold by 24 hours as well as Acinetobacter baumannii ~3-fold by 48 hours. CONCLUSIONS: The combination of therapeutics used has a significant role in biofilm prevention for selected strains via direct contact or diffusion in aqueous solutions.

Population pharmacokinetic-pharmacodynamic model of subcutaneous bupivacaine in a novel extended-release microparticle formulation.

The objective of this study was to develop a population pharmacokinetic-pharmacodynamic model of subcutaneously administered bupivacaine in a novel extended-release microparticle formulation for postoperative pain management. Bupivacaine was administered subcutaneously in the lower leg to 28 healthy male subjects in doses from 150 to 600 mg in a phase 1 randomized, placebo-controlled, double-blind, dose-ascending study with two different microparticle formulations, LIQ865A and LIQ865B. Warmth detection threshold was used as a surrogate pharmacodynamic endpoint. Population pharmacokinetic-pharmacodynamic models were fitted to plasma concentration-effect-time data using non-linear mixed-effects modelling. The pharmacokinetics were best described by a two-compartment model with biphasic absorption as two parallel absorption processes: a fast, zero-order process and a slower, first-order process with two transit compartments. The slow absorption process was found to be dose-dependent and rate-limiting for elimination at higher doses. Apparent bupivacaine clearance and the transit rate constant describing the slow absorption process both appeared to decrease with increasing doses following a power function with a shared covariate effect. The pharmacokinetic-pharmacodynamic relationship between plasma concentrations and effect was best described by a linear function. This model gives new insight into the pharmacokinetics and pharmacodynamics of microparticle formulations of bupivacaine and the biphasic absorption seen for several local anaesthetics.

Ultrasound-guided sciatic nerve block in Wistar rat cadavers: Relevant anatomy and injection distribution.

OBJECTIVE: To investigate the feasibility of an ultrasound-guided sciatic nerve block by describing the sonoanatomy and comparing the distribution of two volumes of bupivacaine dye solution for nerve staining. STUDY DESIGN: Randomized, experimental, assessor-blinded cadaveric study. ANIMALS: A total of 40 adult female Wistar rat cadavers. METHODS: After studying the sonoanatomy of the sciatic nerve and adjacent structures using a high-resolution linear transducer (19-5 MHz), rat cadavers were randomly divided into two groups that were administered either 0.1 mL (group 0.1) or 0.2 mL (group 0.2) of bupivacaine dye solution per nerve, delivered via an in-plane technique. The extent of nerve staining was subsequently evaluated following dissection. Statistical analysis consisted of assessing data distribution using the Shapiro-Wilk test, followed by paired t-tests for continuous data, Mann-Whitney U test and McNemar's test for categorical data. Statistical significance was defined as p < 0.05. RESULTS: The sciatic nerve was identified bilaterally as a double ellipsoid-shaped image, surrounded by a hyperechoic fascia separating the biceps femoris from the adductor muscle. The hypoechoic structure formed by the bupivacaine dye solution around the nerve was effectively visualized using ultrasound imaging. Sciatic nerve staining was successfully achieved in all pelvic limbs, with dye spread of 4.82 ± 1.55 mm and 5.47 ± 2.18 mm in groups 0.1 and 0.2, respectively (p = 0.128). CONCLUSIONS AND CLINICAL RELEVANCE: This study achieved a detailed understanding of the sonoanatomy of the sciatic nerve and its adjacent structures, highlighting the feasibility of the ultrasound-guided technique for injection in Wistar rats. Furthermore, the results show a comparable distribution of dye solution in both groups. Use of the ultrasound-guided sciatic nerve block technique in rats not only exhibits substantial potential for regional anesthesia but also opens avenues for translational studies.

Dose effect and duration of action of liposomal bupivacaine administered as a perineural analgesic in a reversible and adjustable frog-pressure model of equine lameness.

OBJECTIVE: To determine the dose effect of peri-neural liposomal bupivacaine (LB) in an induced forelimb lameness model. ANIMALS: 12 clinically normal adult horses. METHODS: A randomized cross-over design was performed with 1 limb receiving saline and the other LB: low dose (6), high dose (6). Lameness was induced in 1 forelimb using a frog-pressure model. In the lame limb, peri-neural injection of the palmar nerves at the proximal sesamoid bones was performed using saline, low dose LB (0.25 mg/kg) (LDLB), or high dose LB (0.5mg/kg) (HDLB) in random order with a 1-week washout period between treatments. Distal limb swelling, mechanical nociceptive thresholds (MNT), and objective lameness data were collected before and up to 72 hours after peri-neural anesthesia. Data analysis was performed with mixed model ANOVA, equality of medians test, and Kaplan Meier survival analysis. RESULTS: Compared with baseline, horses treated with LDLB and HDLB had improvements in MNT and lameness (P < .001). In the LDLB group, the median duration of analgesia was 4.5 hours (range = 3-6 hours) and the median return to lameness was 7 hours (range = 4-24 hours). In the HDLB group, the median duration of analgesia was 12 hours (range = 4-48 hours) and the median return to lameness was 9 hours (range = 3-48 hours). Mild to moderate swelling was identified in 11/12 (92%) LB limbs. CLINICAL RELEVANCE: Both LDLB and HDLB resulted in loss of skin sensation and improvement of lameness. There was high variability among horses in duration of action for both doses.

Bupivacaine liposomal injectable suspension does not provide improved pain control in dogs undergoing abdominal surgery.

OBJECTIVE: To evaluate the difference in postoperative pain scores of dogs undergoing abdominal surgery receiving surgical incision infiltration of saline or bupivacaine liposomal injectable suspension (BLIS). ANIMALS: 40 dogs undergoing exploratory laparotomy. METHODS: Dogs were prospectively enrolled and randomized to receive either BLIS or saline surgical incision infiltration. All dogs received 5.3 mg of BLIS/kg or an equal volume of saline infiltrated in the muscle/fascia, subcutaneous tissue, and intradermal layer during closure. All dogs received a standardized postoperative pain management protocol. Pain assessment was performed at select time points postoperatively by blinded observers with an electronic algometer, short version of the Glasgow Composite Measure Pain Scale (GCMPS), and indirect measures of pain, including systolic blood pressure, heart rate, and serum cortisol levels. RESULTS: At day 0, blood pressure was higher in the saline group (149.6 vs 125.8 mm Hg; P = .006). At day 3, GCMPS was lower in the BLIS group (BLIS = 1, saline = 2, P = .027), though both average GCMPS scores were low and only 10 dogs were available for day 3 assessments (6 BLIS and 4 saline). No other differences in algometer readings, GCMPS scores, other measured parameters, or need for rescue analgesia were present between BLIS and saline groups at any time point. There was no difference in postoperative incisional infection rate or complications. CLINICAL RELEVANCE: Use of BLIS for exploratory laparotomy did not provide improved pain control over postoperative opioid administration alone. Patients that received BLIS had no increase in short-term complications.

The impact of the transversus abdominis plane block (TAP) on stress response measured through the complete blood- derived inflammatory markers.

This study aims to evaluate the effect of the transversus abdominis plane (TAP) block on the blood cells and the inflammatory markers neutrophil- to- lymphocyte ratio (NLR), platelet- to- lymphocyte ratio (PLR), and systemic immune- inflammation index (SII) after the laparoscopic ovariectomy (LapOV) in dogs. 72 healthy bitches undergoing LapOV were randomly allocated to the no- TAP group of dogs under inhaled anesthesia (IA), the TAP- S group (IA and TAP with saline), and the TAP- B group (IA and TAP with bupivacaine). The NLR, PLR, and SII were calculated 1 h before ovariectomy (T0) and at 2-3 h (T1), 6-8 h (T2), and 20-24 h (T3) post- surgery. The number of dogs requiring postoperative analgesic rescue with buprenorphine and the doses administered in each group were recorded. Significant changes were observed in all groups' postoperative NLR, PLR, and SII over time. Between groups, no differences were observed in any of the ratios at any control point (NLR at T0-T3: p = 0.17, 0.36, 0.80, and 0.95; PLR at T0-T3: p = 0.70, 0.62, 0.21, 0.87; SII at T0-T3: p = 0.29, 0.65, 0.09, and 0.34). A significantly lower number of dogs required analgesic rescue in the TAP-B group (p = 0.0001) and a lower number of doses were administered (p = 0.001). There is no difference in the inflammatory response measured through the complete blood- derived inflammatory markers after the LapOV in dogs when the postoperative pain is managed entirely with opioids or with the TAP block with bupivacaine. The hydrodissection associated with the TAP block technique does not increase the inflammatory response.

The use of granisetron on bupivacaine induced sciatic nerve block in rats.

PURPOSE: The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonists on regional anaesthesia are complex and unclear. The present study was designed to test the hypothesis that granisetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor block, sensory block, and proprioception in a dose-dependent fashion in a rat model of bupivacaine-induced sciatic nerve blockade. MATERIALS AND METHODS: Thirty-eight male Wistar Albino rats that received unilateral sciatic nerve blocks were randomly divided into five experimental groups. Group B received a perineural of 0.3 ml of bupivacaine alone; Group BG800 received perineural 0.3 ml of bupivacaine and 800 µg of granisetron 10 min later; Group BG1200 received perineural 0.3 ml of bupivacaine and 1200 µg of granisetron 10 min later; Group BG1200IP received a perineural 0.3 ml of bupivacaine and an intraperitoneal injection of 1200 µg of granisetron 10 min later; and Group S was sham operated. A blinded investigator assessed motor, sensory and proprioception function every 10 min until the return of normal function. RESULTS: The medians for recovery times in Group B, Group BG800, Group BG1200, and Group BG1200IP were 105, 64, 85, and 120 min for motor function, respectively; 80, 64, 84, and 104 min for sensory function; 80, 63, 85, and 108 min were calculated for the proprioception function. The time to the return of normal motor, sensory, and proprioception function was not statistically significantly different between the groups (p > 0.05). Motor block did not develop in any of the rats in Group S. CONCLUSIONS: Local and systemic application of granisetron was not significantly decrease the duration of bupivacaine induced motor, sensory, and proprioception block of sciatic nerve in rat.

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury.

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

Comparison of the effect of scalp block analgesia bupivacaine 0.25% and clonidine 2 µg/kg with bupivacaine 0.25% and dexamethasone 8 mg on cortisol levels and Numeric Rating Scale in craniotomy tumour.

INTRODUCTION: Craniotomy tumour is brain surgery that can induce a stress response. The stress response can be measured using haemodynamic parameters and plasma cortisol concentration. The stress response that occurs can affect an increase in sympathetic response, such as blood pressure and heart rate, which can lead to an increase in intracranial pressure. Scalp block can reduce the stress response to surgery and post-operative craniotomy tumour pain. The local anaesthetic drug bupivacaine 0.25% is effective in reducing post-operative pain and stress in the form of reducing plasma cortisol levels. The adjuvant addition of clonidine 2 µg/kg or dexamethasone may be beneficial. MATERIALS AND METHODS: A randomised control clinical trial was conducted at the Central Surgery Installation and Hasan Sadikin General Hospital Bandung and Dr. Mohammad Husein Hospital Palembang from December 2022 to June 2023. A total of 40 participants were divided into two groups using block randomisation. Group I receives bupivacaine 0.25% and clonidine 2 µg/kg, and group II receives bupivacaine 0.25% and dexamethasone 8 mg. The plasma cortisol levels of the patient will be assessed at (T0, T1 and T2). All the patient were intubated under general anesthaesia and received the drug for scalp block based on the group being randomised. Haemodynamic monitoring was carried out. RESULTS: There was a significant difference in administering bupivacaine 0.25% and clonidine 2µg/kg compared to administering bupivacaine 0.25% and dexamethasone 8 mg/kg as analgesia for scalp block in tumour craniotomy patients on cortisol levels at 12 hours post-operatively (T1) (p=0.048) and 24 hours post-surgery (T2) (p=0.027), while post-intubation cortisol levels (T0) found no significant difference (p=0.756). There is a significant difference in Numeric Rating Scale (NRS) at post-intubation (T0) (p=0.003), 12 hours post-operatively (T1) (p=0.002) and 24 hours post-surgery (T2) (p=0.004), There were no postprocedure scalp block side effects in both groups. CONCLUSION: The study found that scalp block with 0.25% bupivacaine and 2µg/kg clonidine is more effective in reducing NRS scores and cortisol levels compared bupivacaine 0.25% and dexamethasone 8mg in tumour craniotomy patients.

Effect of clonidine on heart rate variability during spinal anaesthesia: randomized clinical trial.

INTRODUCTION: Spinal anaesthesia consists of administering a local anaesthetic in the subarachnoid space, thus causing sensory, motor, and autonomic nerve conduction block. Currently, recovery from spinal anaesthesia is evaluated by the return of motor function, without considering the autonomic blockade, which is responsible for most complications of the technique. Heart rate variability (HRV) is an indirect method to measure the autonomic nervous system and may be useful in assessing autonomic recovery after spinal anaesthesia. The study objective was to evaluate the autonomic function, through HRV, at the moment of return of motor function in patients who received spinal anaesthesia when clonidine is used as an adjuvant. MATERIAL AND METHODS: This was a randomised, double-blind clinical trial. The sample consisted of 64 ASA I-II patients who underwent spinal anaesthesia and were divided into 2 groups. Group C received 20 mg of bupivacaine with 75 mcg of clonidine, and group B received 20 mg of bupivacaine. HRV was evaluated at rest (T1) and at the time of motor function recovery (T2). Data were collected using a Polar V800® heart rate monitor and then analysed and filtered using Kubios 3.0® software. RESULTS: There was no difference in the values of the low-frequency/high-frequency (LF/HF) ratio, Poincaré plot standard deviation (SD2/SD1), detrended fluctuation analysis (DFAα1, DFAα2), or correlation dimension (D2) indices in any of the groups between the 2 moments. In the clonidine group, there was a difference only in approximate entropy (ApEn), where a P of 0.0124 was obtained considering a 95% confidence interval ranging from 17.83 to 141.47. CONCLUSIONS: There was no significant difference between the duration of sympathetic blockade and motor blockade in spinal anaesthesia.

'Walking epidural': comparison of the analgesic efficacy of levobupivacaine 0.0625% + fentanyl 2mcg/mL versus ropivacaine 0.075% + fentanyl 2mcg/mL.

INTRODUCTION: Epidural infusion with low local anesthetic concentrations with opiates decrease the severity of the motor blockade associated. The present study aims to compare the analgesic efficacy and the motor blockade between two local anesthetic epidural infusions: levobupivacaine 0.0625% + fentanyl 2mcg/mL versus ropivacaine 0.075% + fentanyl 2mcg/mL. MATERIALS AND METHODS: In a single-blind prospective randomized study, 60 laboring parturient had continuous epidural analgesia as follows: 30 of them received levobupivacaine 0.0625% + fentanyl 2mcg/mL and 30 of them received ropivacaine 0.075% + fentanyl 2mcg/mL and rates of infusion were adjusted to the height. Analgesic, motor blockade and satisfaction records were collected as well as maternal and neonate adverse events. RESULTS: After 2 h of the catheter placement, patients who received levobupivacaine showed a mean VAS of 3.2 [1.8-4.6] versus 1.8 [1.2-2.5] (p = 0.05) in patients who received ropivacaine. In addition, patients who received levobupivacaine showed a punctuation in Bromage scale of 0.0 [0.0-1.0] versus 0.0 [0.0-0.0] (p = 0.04) in patients who received ropivacaine. Finally, the parturient who received levobupivacaine scored a mean satisfaction index of 8.1 [7.3-8.9] versus 9.3 [8.7-9.8] (p = 0.02) in those who received ropivacaine. We did not register maternal nor neonate adverse events. CONCLUSION: Both infusions (levobupivacaine 0.0625% + fentanyl 2mcg/mL and ropivacaine 0.075% + fentanyl 2mcg/mL) are effective for labor analgesia. However, ropivacaine would present a better pharmacodynamic profile with less motor blockade and decreased need for analgesic rescue hence improving patient's satisfaction.

Adequate Anesthesia and More Effective Analgesia by Adjusted Doses of Bupivacaine during Cesarean Section: A Randomized Double-blind Clinical Trial.

Background: Several adjuvants, added to local anesthetics, were suggested to induce an ideal regional block with high-quality analgesia. The purpose of this study was to evaluate the particular blocking properties of low-dose bupivacaine in combination with meperidine and fentanyl in spinal anesthesia during Cesarean sections. Methods: A randomized, double-blind clinical trial was conducted at Hafez Hospital affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from February 2015 to February 2016. A total of 120 pregnant women, who underwent spinal anesthesia during elective Cesarean section were enrolled in the study. Based on block-wise randomization, the patients were randomly assigned to three groups, namely "B" group received 2 mL bupivacaine 0.5% (10 mg), "BM" group received 8 mg bupivacaine and 10 mg meperidine, and "BF" group received 8 mg bupivacaine and 15 µg fentanyl intrathecally. The block onset, the duration of analgesia, and the time of discharge from the post-anesthesia care unit (PACU) were all assessed. Data were analyzed using SPSS software version 21, and P<0.05 were considered statistically significant. Results: The mean duration of motor blocks in the B group (150 min) were significantly higher than the BM (102 min) and BF (105 min) groups (P<0.0001). In both the BM and BF groups, the duration of sensory and motor blocks was the same. The length of stay in the PACU was significantly longer in the B group (P<0.001) than the BM and BF groups. When meperidine or fentanyl was added to bupivacaine, the duration of the analgesia lengthened (P<0.001). Conclusion: Intrathecal low-dose spinal anesthesia induced by bupivacaine (8 mg) in combination with meperidine and/or fentanyl for Cesarean section increased maternal hemodynamic stability, while ensuring effective anesthetic conditions, extending effective analgesia, and reducing the length of stay in PACU.Trial Registration Number: IRCT2015013119470N14.

Nano-invasomes for simultaneous topical delivery of buprenorphine and bupivacaine for dermal analgesia.

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid-based nanovesicles for the co-delivery of buprenorphine and bupivacaine to efficiently target skin-concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in-vitro drug release of vesicles were characterized. Ex-vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full-thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex-vivo fluorescent dye tracking. Estimation of in-vivo pain responses by the tail-flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug-free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex-vivo and in-vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.

Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses.

OBJECTIVE: To evaluate a regional anesthetic technique for blocking the abdominal midline in horses. STUDY DESIGN: Anatomical description and prospective, crossover, placebo-controlled, blinded study. ANIMALS: Adult horses; two cadavers, six healthy animals. METHODS: In stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg-1) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg-1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded. RESULTS: The cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9-L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Antinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies.

A bilayer mupirocin/bupivacaine-loaded wound dressing based on chitosan/poly (vinyl alcohol) nanofibrous mat: Preparation, characterization, and controlled drug release.

An infected skin wound caused by external injury remains a serious challenge. Electrospun drug-loaded nanofibers with antibacterial properties based on biopolymers have been widely explored for wound healing. In this study, the double-layer CS/PVA/mupirocin (CPM) + CS/PVA/bupivacaine (CPB) mats were prepared by electrospinning method (20 % polymer weight) and then crosslinked with glutaraldehyde (GA) to optimize the water-resistant and biodegradation properties for wound dressing applications. The morphology of mats was characterized as defect-free and interconnected nanofibers by Scanning Electron Microscope (SEM) and Atomic Force Microscopy (AFM). Fourier Transform Infrared Spectrometry (FTIR) analysis also assessed the chemical structural properties. The porosity, surface wettability, and swelling degree of the dual-drug loaded mats were improved by about 20 %, 12°, and 200 % of the CS/PVA sample to provide a moist environment for efficient wound breathing and repairing. This highly porous mat facilitated the wound exudates absorption and air permeability excellently, reducing the chance of bacterial infections by inhibiting the growth of S. aureus bacterial colonies with a zone of 71.3 mm diameter. In vitro drug release results showed a high-burst release of 80 % and a continuous release profile for bupivacaine and mupirocin, respectively. MTT assay and in vivo tests indicated >90 % of cell viability and improvement in cell proliferation. It triply accelerated wound closure compared to the control group, reaching nearly full closure after 21 days as a potential clinical wound treatment.

Effects of a Single Intra-Articular Injection of 2% Lidocaine or 0.5% Bupivacaine on Synovial Fluid Acute Phase Protein Concentrations in Healthy Horses.

The purpose of this study was to compare the extent of inflammation response in the middle carpal joints of healthy horses following intra-articular injection of 2% lidocaine, 0.5% bupivacaine, or 0.9% saline solution. The right middle carpal joint of 20 horses was injected with 5 mL of 0.5% bupivacaine (GB, n = 10) or 5 mL of 2% lidocaine (GL, n = 10). The left middle carpal joint of horses was used as a control (5 mL 0.9% saline). Serum and synovial fluid (SF) were aseptically collected before and at predetermined times after each injection. Serum and synovial fluid protein, albumin, transferrin, haptoglobin, ceruloplasmin, α1-antitripsin, and α1-acid glycoprotein concentrations were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared among treatments. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (P < .05). Both lidocaine and bupivacaine induced serum and SF changes indicative of inflammation, but the magnitude of those changes was more pronounced for lidocaine. Administration of 0.9% saline also induced an inflammatory reaction, but the magnitude of these changes was less pronounced than those caused by GB and GL. The results suggested that bupivacaine is safer than lidocaine for intra-articular injection in horses. Saline solution should not be used as an adjunct to intra-articular injections in horses.

Histological and Biomechanical Effects of Local Anesthetics and Steroids on Achilles Tendon: A Study in Rats.

BACKGROUND: Peritendinous injection of local anesthetics, alone or in combination with corticosteroids, is widely used in the treatment of tendinopathies. Toxicity of local anesthetics has been demonstrated in many cells, including myocytes, chondrocytes, and neurons. Bupivacaine and lidocaine are known to have time- and dose-dependent cytotoxicity in these cells. The effects of these agents on the tendon remain unknown. PURPOSE: To show histological and biomechanical effects after the injection of different local anesthetics and steroids, both single and combined, at different concentrations into the peritendinous sheath of rat Achilles tendon. STUDY DESIGN: Controlled laboratory study. METHODS: In the study, 100 rats were divided into 10 groups with equal body weights. Inflammation was induced in both Achilles tendons of each rat by means of the ball drop technique; 7 hours later, injections were made into the peritendinous sheaths of both Achilles tendons using lidocaine, bupivacaine, and dexamethasone as appropriate for the rat's group. At the end of the first week, the right Achilles tendons of the rats were removed for histological study. Left Achilles tendons were evaluated in terms of biomechanics. RESULTS: Histological findings demonstrated that the group with the most toxicity to the tendon was the group that received injection of dexamethasone alone. The groups with the least toxicity were those receiving dexamethasone combined with low- or high-dose bupivacaine. Biomechanical findings showed that the experimental groups had similar results to each other with the exception of the groups receiving 0.25% bupivacaine alone and dexamethasone alone, in which tendons revealed higher tensile strength. CONCLUSION: Local anesthetic and steroid applications have different histological and biomechanical effects on the tendon. Although the dexamethasone-injected group was the most affected in terms of histology, these changes could not be demonstrated biomechanically. CLINICAL RELEVANCE: In future clinical studies, the effect of steroids on the tendon should be investigated more comprehensively. Whether biomechanical results overlap with histological results should be investigated further.

Buprenorphine has a concentration-dependent cytotoxic effect on equine chondrocytes in vitro.

OBJECTIVE: To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. SAMPLE: Primary cultured equine articular chondrocytes from 3 healthy adult horses. PROCEDURES: Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-soluble tetrazolium salt-8 (WST-8) cytotoxic assay, LDH assay, and flow cytometry. All continuous variables were evaluated with a mixed ANOVA with treatment, time, and their interactions as the fixed effects and each horse as the random effect. RESULTS: Buprenorphine showed a concentration-dependent chondrotoxic effect. The viability of chondrocytes was significantly decreased with exposure to HBUPRE and BUPI compared to CON, MOR, and LBUPRE. CLINICAL RELEVANCE: Negligible chondrotoxic effects were observed in healthy cultured equine chondrocytes exposed to 0.05 mg/mL of buprenorphine, whereas higher concentrations (0.12 mg/mL) showed a marked cytotoxic effect. Based on these results, low concentrations of buprenorphine appear to be safe for intra-articular administration. Further evaluation of this dose in vivo is needed before recommending its clinical use.

Intraperitoneal instillation versus wound infiltration for postoperative pain relief after cesarean delivery: A prospective, randomized, double-blind, placebo-controlled trial.

AIM: To compare local anesthetic wound infiltration with intraperitoneal instillation of local anesthetic for analgesia after cesarean section under spinal anesthesia. METHODS: This study was conducted on 150 pregnant women undergoing elective cesarean section under spinal anesthesia. Spinal anesthesia was performed with 7 mg isobaric bupivacaine and 15 µcg fentanyl. The patients were randomized into three groups of 50 patients each: Group local anesthetic wound infiltration (LWI): 20 ml local anesthetic solution (10 ml 0.5% bupivacaine and 10 ml 2% lidocaine mixture) was administered subcutaneous wound infiltration at the end of surgery prior to skin closure and 20 ml saline was instilled into the uterine peritoneal area before fascia closure. Group intraperitoneal local anesthetic (IPLA): 20 ml local anesthetic solution (10 ml 0.5% bupivacaine and 10 ml 2% lidocaine mixture) was instilled into the uterine peritoneal area and 20 ml saline was administered subcutaneous wound infiltration. Group Placebo: 20 ml saline was instilled into the uterine peritoneal area and 20 ml saline was administered local subcutaneous wound infiltration. Pain scores at rest and on movement, total fentanyl consumption at 24 h, maternal satisfaction, and the time to first analgesic request were recorded. RESULTS: No statistically significant difference was observed in the postoperative pain scores at rest at 2, 12, and 24 h (p = 0.314, 0.343, and 0.735, respectively) and on movement at 12 and 24 h (p = 0.318 and 0.642, respectively) between the groups. The pain scores on movement at 2 h were significantly lower in Group IPLA compared with Group Placebo (p = 0.047). There were no significant differences between the groups in terms of total fentanyl consumption and the time to first analgesic request. CONCLUSION: The use of intraperitoneal instillation of bupivacaine and lidocaine reduces early the pain score on movement in women undergoing cesarean section under spinal anesthesia.

Local application of a transcutaneous carbon dioxide paste prevents excessive scarring and promotes muscle regeneration in a bupivacaine-induced rat model of muscle injury.

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2 ) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non-gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine-induced rat model of muscle injury. Forty-eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post-surgery to examine the following: (1) inflammatory (interleukin [IL]-1ß, IL-6), and transforming growth factor (TGF)-ß and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL-1ß, IL-6, and TGF-ß expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL-1ß, IL-6, and TGF-ß. The paste is inexpensive and non-invasive. Thus, it may be the treatment of choice for patients with muscle damage.