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.

Effect of dexmedetomidine added to retrobulbar blockade with lignocaine and bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate the effect of the addition of dexmedetomidine (BLD) to retrobulbar blockade with combined lignocaine and bupivacaine on nociception. ANIMALS: A total of 17 eyes from 15 dogs. METHODS: Prospective, randomized, masked clinical comparison study. Dogs undergoing unilateral enucleation were randomly assigned into two groups; a retrobulbar administration of lignocaine and bupivacaine in a 1:2 volume ratio combined with either BLD or 0.9% saline (BLS). The total volume of the intraconal injection was calculated at 0.1 mL/cm cranial length. Intraoperative parameters were recorded: heart rate (HR), respiratory rate (RR), end-tidal CO2 (EtCO2 ) arterial blood pressure (BP), and inspired isoflurane concentration (ISOinsp). Pain scores, heart rate and RR were recorded postoperatively. RESULTS: Dogs receiving BLD (n = 8) had significantly lower intraoperative RR (p = 0.007), and significantly lower ISOinsp (p = 0.037) than dogs in the BLS group (n = 9). Postoperatively heart rate was significantly lower in the BLD group at 1 min (p = 0.025) and 1 h (p = 0.022). There were no other significant differences in intraoperative or postoperative parameters, or in postoperative pain scores (p = 0.354). Dogs receiving BLD had a higher rate of anesthetic events of bradycardia and hypertension (p = 0.027). Analgesic rescue was not needed in either group. CONCLUSIONS: The addition of BLD to retrobulbar anesthesia did not result in a detectable difference in pain scores relative to blockade with lignocaine and bupivacaine alone. Dogs receiving retrobulbar BLD had a significantly lower intraoperative RR and isoflurane requirement and an increased incidence of intraoperative bradycardia and hypertension.

Physiological variables for the objective detection of nerve block failure in dogs.

OBJECTIVE: To identify physiological variables for objectively detecting nociception indicative of intraoperative peripheral nerve block failure. STUDY DESIGN: A double-blinded randomized clinical study. ANIMALS: A sample of 14 male (40.8 ± 12 kg; mean ± standard deviation) and 16 female (34.3 ± 11.4 kg) client-owned dogs. METHODS: Dogs were randomly assigned to one of three groups for psoas compartment and proximal sciatic nerve blocks (0.2 mL kg-1 per site): guided bupivacaine (GBB), or saline (GSB) block or a blind bupivacaine block (BBB). Guided blocks were performed using an ultrasound-peripheral nerve locator combination. Premedication consisted of medetomidine 0.01 mg kg-1 and morphine 0.3 mg kg-1. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Receiver operator characteristic curve analysis was used to compare actual values and change in values of physiological variables between GSB and GBB. The Youden index and associated criterion for each physiological variable were used to determine an objective measure for nociception. Fisher's exact t test, McNemar's test and Cohen's kappa statistical analysis were used to determine association, differences and inter-score reliability between the objective and subjective scoring for BBB. RESULTS: Cardiovascular variables had good discriminating ability to identify a nociceptive response (p < 0.01). The Youden indices for mean (MAP) and diastolic (DAP) arterial pressure were most reliable in detecting nociception. The highest sensitivity was that of ΔMAP (100%) with good agreement between the subjective and objective scores of Δheart rate or systolic arterial pressure (SAP). The use of ΔMAP, ΔSAP, ΔDAP had the best ability in indicating peripheral nerve block failure (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Blood pressure values can detect a response to surgical stimulus in adequately anaesthetized dogs. The use of ΔMAP, ΔSAP or ΔDAP may be considered as objective measures to detect nerve block failure.

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.

A comparison of the motor effects and analgesic efficacy following lumbar plexus block combined with sciatic nerve block or epidural in dogs undergoing tibial plateau leveling osteotomy.

OBJECTIVE: To compare motor effects and analgesic efficacy following an ultrasound-guided lateral approach to lumbar plexus blockade at L7 and sciatic nerve blockade (LPSNB) against epidural injection in dogs undergoing tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: A total of 27 healthy adult dogs undergoing unilateral TPLO surgery. METHODS: Dogs were allocated to either LPSNB (bupivacaine 2 mg kg-1, 0.75%) or epidural (morphine PF 0.1 mg kg-1 and bupivacaine 0.5 mg kg-1, 0.75%). Other aspects of clinical management were identical, including anesthetic drug protocol, area of presurgical clipping and bladder care. Time to perform the block, response to surgical stimuli, pain scores, rescue analgesia, time to stand and walk, motor score and time to first urination were recorded. One evaluator, unaware of treatment status, performed all evaluations. Student's t-test or Mann-Whitney U test was used to compare continuous variables between groups, and Fisher's exact test for categorical variables. RESULTS: Median (range) times to stand and walk were shorter for LPSNB [60 (40-120) minutes and 90 (60-150) minutes, respectively, p = 0.003] than for epidural [150 (120-240) minutes and 180 (120-360) minutes, respectively, p = 0.006]. Four dogs required rescue intraoperatively (three in epidural group, one in LPSNB group, p = 0.438). Pain scores over the 24 hour evaluation period were similar, and not significantly different, for each group. Time to spontaneous urination [LPSNB, 330 (240-360) minutes; epidural, 300 (120-1440) minutes, p = 1.0] did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: An ultrasound-guided lateral paravertebral approach to the lumbar plexus within the psoas compartment at L7, combined with sciatic nerve blockade, allows faster return to normal motor function, with similar pain control and impact on urination when compared with epidural in dogs after TPLO surgery.

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.

'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.

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.

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.

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.

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.

Interscalene Brachial Plexus Block with Liposomal Bupivacaine versus Standard Bupivacaine with Perineural Dexamethasone: A Noninferiority Trial.

BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery. To extend block duration, provide adequate analgesia, and minimize opioid consumption, the use of adjuvants such as dexamethasone as well as the application of perineural liposomal bupivacaine have been proposed. This randomized, double-blinded, noninferiority trial hypothesized that perineural liposomal bupivacaine is noninferior to standard bupivacaine with perineural dexamethasone in respect to average pain scores in the first 72 h after surgery. METHODS: A total of 112 patients undergoing ambulatory shoulder surgery were randomized into two groups. The liposomal bupivacaine group received a 15-ml premixed admixture of 10 ml of 133 mg liposomal bupivacaine and 5 ml of 0.5% bupivacaine (n = 55), while the bupivacaine with dexamethasone group received an admixture of 15 ml of 0.5% standard bupivacaine with 4 mg dexamethasone (n = 56), respectively. The primary outcome was the average numerical rating scale pain scores at rest over 72 h. The mean difference between the two groups was compared against a noninferiority margin of 1.3. Secondary outcomes were analgesic block duration, motor and sensory resolution, opioid consumption, numerical rating scale pain scores at rest and movement on postoperative days 1 to 4 and again on postoperative day 7, patient satisfaction, readiness for postanesthesia care unit discharge, and adverse events. RESULTS: A liposomal bupivacaine group average numerical rating scale pain score over 72 h was not inferior to the bupivacaine with dexamethasone group (mean [SD], 2.4 [1.9] vs. 3.4 [1.9]; mean difference [95% CI], -1.1 [-1.8, -0.4]; P < 0.001 for noninferiority). There was no significant difference in duration of analgesia between the groups (26 [20, 42] h vs. 27 [20, 39] h; P = 0.851). Motor and sensory resolutions were similar in both groups: 27 (21, 48) h versus 27 (19, 40) h (P = 0.436) and 27 [21, 44] h versus 31 (20, 42) h (P = 0.862), respectively. There was no difference in opioid consumption, readiness for postanesthesia care unit discharge, or adverse events. CONCLUSIONS: Interscalene nerve blocks with perineural liposomal bupivacaine provided effective analgesia similar to the perineural standard bupivacaine with dexamethasone. The results show that bupivacaine with dexamethasone can be used interchangeably with liposomal bupivacaine for analgesia after shoulder surgery.

The Effect of Commonly Used Local Anesthetic on Bacterial Growth.

INTRODUCTION: Liposomal bupivacaine (LB) has emerged as a superior form of local anesthetic across numerous surgical subspecialties. The purpose of this study is to evaluate the ex-vivo antimicrobial effects of LB in comparison with traditional local anesthetics. METHODS: A standardized inoculum of bacteria commonly associated with surgical site infection was inoculated into a suspension of 1% lidocaine, 0.25% bupivacaine, Exparel (proprietary liposomally packaged 1.3% bupivacaine), and normal saline as a growth control. RESULTS: In all five bacteria tested, the medium inoculated with traditional local anesthetics reduced growth to a greater degree than LB-inoculated plates. Both conventional local anesthetics reduced the growth of all bacteria when compared with the control with the exception of methicillin-susceptible Staphylococcus aureus growth in bupivacaine. LB-inoculated plates had equivalent growth to the control in all plates with the exception of Escherichia coli plates which demonstrated superior growth. CONCLUSIONS: The results of this simple ex-vivo model suggest that the liposomal packaging of bupivacaine may decrease this local anesthetic's innate antibacterial properties.

Fascia Iliaca Block in Hip and Femur Fractures to Reduce Opioid Use.

BACKGROUND: Fascia iliaca compartment block (FICB) has become a keystone technique for acute pain management in patients with hip and proximal femur fractures. OBJECTIVES: To demonstrate that administering FICB preoperatively to patients with hip or proximal femur fractures in the emergency department (ED) is likely to reduce opioid use and related complications, and to decrease hospital length of stay (LOS). METHODS: An unblinded study of adult patients with hip and proximal femur fractures who consented to receive an FICB with 30 cc of bupivacaine with epinephrine administered in the ED. We compared this group with a contemporaneous group of controls who only received systemic opioids. Over the course of approximately 6 months, main outcome measured between the two groups was amount of morphine equivalents given from block administration until 8 h after. We also compared complications such as delirium, constipation, and bleeding rates (oozing from injection site or hematoma formation). RESULTS: A total of 166 patients with hip and proximal femur fractures from August 12, 2018 to April 25, 2021; 81 received FICB plus systemic opioids, and 85 received only systemic opioids. Among the FICB group, morphine equivalents were reduced by 0.6 mg/h with no significant difference in LOS. A statistically significant difference in opioid-related adverse outcomes was found between the anticoagulated group vs. the no anticoagulation group. CONCLUSIONS: FICB is a safe and effective preoperative technique for initial pain management in patients with hip and proximal femur fractures, as it can also be used with additional systemic opioids. FICB administration may reduce systemic opioid use preoperatively, thus reducing opioid-related adverse effects with no significant impact on hospital LOS.

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples.

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44−61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, "responders"). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.

Preventive Intrathecal Injection of Bupivacaine Alleviated Microglia Activation and Neuropathic Pain in a Rat Model of Chronic Constriction Injury.

Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic administration of bupivacaine have been previously reported. In this study, the preventive effects of intrathecal bupivacaine administration against neuropathic pain were revealed in a rat model of sciatic nerve chronic constriction injury (CCI). Using a CCI rat model, pain hypersensitivity, characterized by mechanical allodynia and thermal hyperalgesia, correlated well with microglia M1 polarization, activation and pro-inflammatory cytokine expression in both spinal cord dorsal horns and sciatic nerves. Bupivacaine attenuated pain behaviors and inflammatory alternations. We further identified that the Interferon Regulatory Factor 5 (IRF5)/P2X Purinoceptor 4 (P2X4R) and High Mobility Group Box 1 (HMGB1)/Toll-Like Receptor 4 (TLR4)/NF-κB inflammatory axes may each play pivotal roles in the acquisition of microglia M1 polarization and pro-inflammatory cytokine expression under CCI insult. The relief of pain paralleled with the suppression of microglia M1 polarization, elevation of microglia M2 polarization, and inhibition of IRF5/P2X4R and HMGB1/TLR4/NF-κB in both the spinal cord dorsal horns and sciatic nerve. Our findings provide molecular and biochemical evidence for the anti-neuropathic effect of preventive bupivacaine.

HEMODYNAMIC FUNCTION IN COMPARISON OF TWO TYPES OF LOCAL ANESTHESIA WITH VASOCONSTRICTOR IN DAY SURGERY: RETROSPECTIVE STUDY.

Introduction: Hemodynamic changes and cardiac arrhythmias are not uncommon in clinical practice, depending on including patient features, surgical treatment and drugs administered. We describe hemodynamic changes developed in young patients, soon after a local infiltration anesthesia in day surgery. Methods: We retrospectively assessed the hemodynamic effect of 2% lidocaine with 0,0125mg/ml adrenaline (Li & AD) administered for septorhinoplasty in 44 participants and combination of 0.5% bupivacaine and 2% lidocaine with 0.0125mg/ml adrenaline (BLi & AD) for breast augmentation in 48 participants. Blood pressure and heart rate were recorded before the introduction of general anesthesia, immediately 5.10 and 20 minutes after administration of local infiltration, anesthetic (LIA) and data were analyzed. Results: The mean systolic blood pressure (SBP) in all observed measurements before general anesthesia (0), immediately, 5 minutes, 10 minutes and 20 minutes after local infiltration anesthesia was higher among patients who underwent septorinoplasty (Li & AD), in relation to patients who underwent breast augmentation (BLi & AD) (p <05). The level of diastolic blood pressure (DBP) in measurement 20 minutes compared to measurement in 10 minutes was increased by 9,52 mmHg. The septorhinoplasty group showed a significant increase in heart rate measured 20 minutes after local infiltration anesthesia with adrenaline. Conclusions: Measured transitory changes in heart rate and blood pressure after local infiltration of vasoconstrictor anesthetics in healthy patients prior to septorinoplasty and breast augmentation may be induced by endogenous and / or exogenous epinephrine. Bupivacaine solution for local infiltration analgesia reduces hemodynamic disturbances and prolongs analgesic effect. We highlight the need for careful preoperative evaluation, including anxiety assessment and treatment in all patients in day surgery.

L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons.

BACKGROUND: Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified. METHODS: The authors performed electrophysiologic analysis on rat dorsal root ganglion neurons in vitro and on spinal transmissions in vivo. RESULTS: In the dorsal root ganglion, these anesthetics decreased the amplitudes of action potentials. The half-maximum inhibitory concentrations of D-enantiomer D-bupivacaine were almost equal for Aß (29.5 µM), Aδ (29.7µM), and C (29.8 µM) neurons. However, the half-maximum inhibitory concentrations of L-bupivacaine was lower for Aδ (19.35 µM) and C (19.5 µM) neurons than for A ß (79.4 µM) neurons. Moreover, D-bupivacaine almost equally inhibited tetrodotoxin-resistant (mean ± SD: 15.8 ± 10.9% of the control, n = 14, P < 0.001) and tetrodotoxin-sensitive (15.4 ± 15.6% of the control, n = 11, P = 0.004) sodium currents. In contrast, L-bupivacaine suppressed tetrodotoxin-resistant sodium currents (26.1 ± 19.5% of the control, n = 18, P < 0.001) but not tetrodotoxin-sensitive sodium currents (74.5 ± 18.2% of the control, n = 11, P = 0.477). In the spinal dorsal horn, L-bupivacaine decreased the area of pinch-evoked excitatory postsynaptic currents (39.4 ± 11.3% of the control, n = 7, P < 0.001) but not touch-evoked responses (84.2 ± 14.5% of the control, n = 6, P = 0.826). In contrast, D-bupivacaine equally decreased pinch- and touch-evoked responses (38.8 ± 9.5% of the control, n = 6, P = 0.001, 42.9 ± 11.8% of the control, n = 6, P = 0.013, respectively). CONCLUSIONS: These results suggest that the L-enantiomer of bupivacaine (L-bupivacaine) effectively inhibits noxious transmission to the spinal dorsal horn by blocking action potential conduction through C and Aδ afferent fibers.

KLF9 regulates PRDX6 expression in hyperglycemia-aggravated bupivacaine neurotoxicity.

BACKGROUND: Neurotoxicity induced by local anesthetics (LAs) is potentially life threatening, especially for patients with underlying diseases like diabetes. The anesthetic bupivacaine (Bup) has been reported to induce neurotoxicity mediated by reactive oxygen species (ROS), which is aggravated by hyperglycemia. Krüppel-like factor 9 (KLF9), an axon growth-suppressing transcription factor, plays a key role in neuronal maturation and promotes oxidative stress. This study was designed to investigate whether and how KLF9 regulates ROS levels related to LA neurotoxicity under hyperglycemic conditions. METHODS: Klf9/GFP ShRNA (LV Sh-Klf9) was used to achieve stable Klf9 knockdown in the SH-SY5Y cell line. KLF9-deficient and normal cells were cultured under normal or high-glucose (HG) culture conditions and then exposed to Bup. Cell viability, intracellular and mitochondrial ROS, and mitochondrial membrane potential (ΔΨm) were detected to examine the role of KLF9. Thereafter, KLF9-deficient and normal cells were pretreated with small-interfering RNA targeting peroxiredoxin 6 (siRNA-Prdx6) to determine if PRDX6 was the target protein in HG-aggravated Bup neurotoxicity. RESULTS: The mRNA and protein levels of KLF9 were increased after Bup and hyperglycemia treatment. In addition, cell survival and mitochondrial function were significantly improved, and ROS production was decreased after Sh-Klf9 treatment compared with Sh-Ctrl. Furthermore, the expression of PRDX6 was suppressed by Bup in hyperglycemic cultures and was upregulated in the Sh-Klf9 group. Moreover, the protection provided by KLF9 deficiency for cell survival, the increase in ROS production in cells and mitochondria, and the disruption of mitochondrial function were abolished by Prdx6 knockdown. CONCLUSIONS: The results of this study demonstrated that hyperglycemia aggravated Bup neurotoxicity by upregulating KLF9 expression, which repressed the antioxidant PRDX6 and led to mitochondrial dysfunction, ROS burst, and cell death. Understanding this mechanism may, thus, offer valuable insights for the prevention and treatment of neurotoxicity induced by LAs, especially in diabetic patients.

Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose.

Hyperglycemia is considered a risk factor for the enhancement of local anesthetic-induced neurotoxicity. Transient receptor potential melastatin 7 (TRPM7), a kinase-coupled cation channel, has been implicated in a variety of neuropathological processes, including intracellular calcium disturbance and high glucose-induced neuropathy. In this study, we investigated whether TRPM7-related pathophysiology is involved in bupivacaine-induced neurotoxicity in SH-SY5Y cells and how hyperglycemia acts as a risk factor. For initial neurotoxicity evaluation, it was confirmed that cell damage and apoptosis induced by acute exposure to bupivacaine were dependent on its concentration and glucose preconditioning. High glucose preconditioning facilitated the bupivacaine-induced fast and temporary rise in intracellular free calcium concentration ([Ca2+ ]i ), which was attributed to both calcium influx through TRPM7 and calcium store release. Additionally, bupivacaine was shown to increase TRPM7-like currents, particularly in cells preconditioned with high glucose. Bupivacaine-induced neurotoxicity in hyperglycemia was correlated with extracellular signal-regulated kinase (ERK), but not protein kinase B (AKT) activation. Inhibition of TRPM7 and ERK activity alleviates bupivacaine neurotoxicity. These results suggest that therapeutically targeting TRPM7-related pathophysiological changes could be a potential strategy for treating local anesthetic-induced neurotoxicity exacerbated by hyperglycemia.