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Failure of sub-arachnoid block (SAB), due to resistance to bupivacaine after a recent scorpion sting can lead to multiple block attempts and subsequent conversion to general anaesthesia. We report this case series of 10 patients with successful SAB with newly launched 0.75% hyperbaric ropivacaine, in patients with recent scorpion sting. Thus, intrathecal hyperbaric ropivacaine may be considered as the local anaesthetic agent of choice in patients with scorpion sting to prevent failure of SAB., (© Copyright 2024, Sultan Qaboos University Medical Journal, All Rights Reserved.)

The development of local anesthetics revolutionized the performance of painful interventions. Local anesthetics have an effect on voltage-gated sodium channels in nerve fibers and modulate the conduction of impulses. With respect to the chemical structure, local anesthetics can be divided into amide and ester types. The structural differences of local anesthetics have an influence on the duration of action, the degradation pathways and specific side effects. Severe adverse events include cardiotoxicity and neurotoxicity. In addition to basic measures, such as the monitoring and securing of vital parameters, lipid infusion represents a treatment option in cases of intoxication. The recent developments of local anesthetics are particularly concerned with the reduction of toxicity and prolonging the duration of action., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Long-lasting local anesthetic use for perioperative pain control is limited by possible cardiotoxicity (e.g., arrhythmias and contractile depression), potentially leading to cardiac arrest. Off-target cardiac sodium channel blockade is considered the canonical mechanism behind cardiotoxicity; however, it does not fully explain the observed toxicity variability between anesthetics. The authors hypothesize that more cardiotoxic anesthetics (e.g., bupivacaine) differentially perturb other important cardiomyocyte functions (e.g., calcium dynamics), which may be exploited to mitigate drug toxicity., Methods: The authors investigated the effects of clinically relevant concentrations of racemic bupivacaine, levobupivacaine, or ropivacaine on human stem cell-derived cardiomyocyte tissue function. Contractility, rhythm, electromechanical coupling, field potential profile, and intracellular calcium dynamics were quantified using multielectrode arrays and optical imaging. Calcium flux differences between bupivacaine and ropivacaine were probed with pharmacologic calcium supplementation or blockade. In vitro findings were correlated in vivo using an anesthetic cardiotoxicity rat model (females; n = 5 per group)., Results: Bupivacaine more severely dysregulated calcium dynamics than ropivacaine in vitro (e.g., contraction calcium amplitude to 52 ± 11% and calcium-mediated repolarization duration to 122 ± 7% of ropivacaine effects, model estimate ± standard error). Calcium supplementation improved tissue contractility and restored normal beating rhythm (to 101 ± 6%, and 101 ± 26% of control, respectively) for bupivacaine-treated tissues, but not ropivacaine (e.g., contractility at 80 ± 6% of control). Similarly, calcium pretreatment mitigated anesthetic-induced arrhythmias and cardiac depression in rats, improving animal survival for bupivacaine by 8.3 ± 2.4 min, but exacerbating ropivacaine adverse effects (reduced survival by 13.8 ± 3.4 min and time to first arrhythmia by 12.0 ± 2.9 min). Calcium channel blocker nifedipine coadministration with bupivacaine, but not ropivacaine, exacerbated cardiotoxicity, supporting the role of calcium flux in differentiating toxicity., Conclusions: Our data illustrate differences in calcium dynamics between anesthetics and how calcium may mitigate bupivacaine cardiotoxicity. Moreover, our findings suggest that bupivacaine cardiotoxicity risk may be higher than for ropivacaine in a calcium deficiency context., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them, the use of amide-type local anesthetics seems promising since in vitro studies and animal models have shown their potential to inhibit the Intercellular Adhesion Molecule 1 (ICAM-1) expression and Src activity, which are clearly implicated in the process of inflammation and cancer metastases. This review emphasizes the potential of amide-type local anesthetics in this context.

During lung resection surgery, the blood supply to the lungs increases the intrapulmonary shunt and reduces arterial oxygenation in patients. Ventilation anesthesia of a lung may affect oxygenation. The present study aimed to compare intravenous anesthesia with and without thoracic epidural block (dezocine and ropivacaine) on oxygen saturation during lung ventilation in patients undergoing lung resection surgery. For this purpose, this study was performed as a double-blind, randomized clinical trial. Sixty patients who were candidates for lung resection were divided into two intervention groups (thoracic epidural block with dezocine and ropivacaine and intravenous anesthesia) and a control group (placebo thoracic epidural block and intravenous anesthesia). Hemodynamic variables, Aldert score, and possible complications were compared between the two groups before surgery and after recovery. Also, the expression level of the IDO gene was evaluated using the real-time PCR technique. SPSS, t-test, Mann-Whitney U, Chi-square, and Fisher performed data analysis and comparison.  The results showed that the changes in hemodynamic variables and PaO2, SaO2, and ETCO2 were not statistically significant between the two groups. Aldrete's score at entry and exit of recovery was similar between the two groups. During the recovery period, the percentage of pain or chills in the group under complete intravenous anesthesia was significantly higher. There was no significant difference between the two groups regarding the frequency of nausea and hypotension. Also, the results of IDO gene expression showed that general anesthesia with the thoracic epidural block (dezocine and ropivacaine), which is involved in inducing immunological tolerance and suppressing immune responses, has no significant effect. The stress of performing surgery before surgery can play a role in suppressing the patient's immunity, and anesthesia of the thoracic epidural block (dezocine and ropivacaine) has no significant effect on IDO expression. In general, thoracic epidural block with complete intravenous anesthesia has no significant effect on oxygen saturation in ventilated lungs compared with intravenous anesthesia alone. Nevertheless, this combination significantly reduces postoperative pain and chills.

Ropivacaine-induced myotoxicity in surgically incised muscles has not been fully investigated. We evaluated the effects of infiltration anesthesia with ropivacaine on damage, inflammation and regeneration in the incised muscles of rats undergoing laparotomy. Ropivacaine or saline was infiltrated below the muscle fascia over the incised muscles. Pain-related behaviors and histological muscle damage were assessed. Macrophage infiltration at days 2 and 5 and proliferation of satellite cells at day 5 were detected by CD68 and MyoD immunostaining, respectively. Pain-related behaviors were inhibited by 0.25% and 0.5% of ropivacaine for 2 h after surgery. Single infiltration of 0.5% ropivacaine did not induce injury in intact muscles without incision, but single and repeated infiltration of 0.5% ropivacaine significantly augmented laparotomy-induced muscle injury and increased the numbers of CD68-positve macrophages and MyoD-positive cells compared to those in rats with infiltration of saline or 0.25% ropivacaine. In contrast, there were no significant differences in them between rats with saline infusion and rats with 0.25% ropivacaine infiltration. In conclusion, single or repeated subfascial infiltration of 0.25% ropivacaine can be used without exacerbating the damage and inflammation in surgically incised muscles, but the use of 0.5% ropivacaine may be a concern because of potentially increased muscle damage., (© 2022. The Author(s).)

Purpose: Neuraxial (spinal and epidural) anesthesia is the cornerstone of ensuring the satisfaction rate of painless delivery; however, whether it prolongs the first stage of labor remains controversial. Although current clinical research results tend to be negative, the conclusions are not convincing due to the lack of basic research. This study was conducted to provide a theoretical reference for this controversy through basic research., Materials and Methods: A spinal anesthesia model was established by the intrathecal injection of 0.1% ropivacaine in late-pregnant rats (day 22). The cervical resistance test was used to measure the tension of different groups of isolated cervical tissues. Western blotting and cervical tissue cyclic AMP (cAMP) enzyme-linked immunosorbent assay were performed to clarify the possible related mechanisms., Results: Cervical resistance experiments showed that the intrathecal injection of ropivacaine decreased the cervical resistance, and norepinephrine injection reversed this effect. Western blotting showed that α2A adrenergic receptor (α 2A -AR) levels gradually increased over time in pregnant rats. The cAMP enzyme-linked immunosorbent assay revealed that the intrathecal injection of norepinephrine reversed the increase in cervical tissue cAMP concentration caused by ropivacaine injection., Conclusion: Ropivacaine relaxes the cervix. Further, α 2 -AR may be involved in the process of cervical contraction., Competing Interests: The authors declare that they have no competing interests in this work., (© 2022 Hu et al.)

Local anesthetics are often used at the site of injury or mixed with platelet-rich plasma to reduce pain when treating orthopedic and sports-related injuries. Local anesthetics have been shown to have deleterious effects on stromal cells, but their impact on platelets has not been investigated. In this study, we aimed to assess the effects of lidocaine, bupivacaine, and ropivacaine on platelet health. Based on the deleterious effects of local anesthetics on nucleated cells, we hypothesized that these compounds would affect platelet viability, intracellular physiology, and function. Platelet preparations were derived from randomly selected donors and exposed to lidocaine 1%, bupivacaine 0.75%, ropivacaine 0.5%, and saline at 1:1 and 1:3 ratios. Platelet morphology, viability, intracellular calcium, production of radical oxygen species (ROS), apoptosis, and adhesion were assessed via fluorescent microscopy and flow cytometry. Bupivacaine resulted in increased ROS production, calcium dysregulation, apoptosis, and reduced platelet adhesion. By contrast, ropivacaine and lidocaine were similar to saline in most assays, except for a low degree of mitochondrial stress as evidenced by increased ROS production. Ultimately, bupivacaine 0.75% was harmful to platelets as evidenced by reduced platelet viability, adhesion, and increased apoptosis, whereas lidocaine 1% and ropivacaine 0.5% were relatively safe at the 1:1 and 1:3 dilutions. Clinical significance: Lidocaine 1% and ropivacaine 0.5% can be used at up to a 1:1 ratio with platelet preparations to reduce the pain and discomfort of PRP procedures while maintaining platelet therapeutic potential., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Objective: To investigate the in vitro effects of clinically relevant concentrations of the local anesthetics (LAs) bupivacaine, lidocaine, lidocaine with preservative (LP), mepivacaine, and ropivacaine on equine chondrocyte and fibroblast-like synoviocyte (FLS) viability., Samples: Chondrocytes and FLSs of the metacarpophalangeal joints of 4 healthy adult horses., Procedures: Viability of chondrocytes and FLSs was determined with 3 assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and trypan blue (TB) exclusion (only FLS). Viability was assessed after 30- and 60-minute exposures to 0.0625%, 0.125%, and 0.25% bupivacaine; 0.25%, 0.5%, and 1% lidocaine; 0.25%, 0.5%, and 1% LP; 0.25%, 0.5%, and 1% mepivacaine; and 0.125%, 0.25%, and 0.5% ropivacaine., Results: Viability of chondrocytes was significantly decreased with exposure to 0.25% bupivacaine, 1% lidocaine, 1% LP, 1% mepivacaine, and 0.25% ropivacaine. Viability of FLSs was significantly decreased with exposure to 0.25% bupivacaine, 1% mepivacaine, 1% LP, and 0.5% ropivacaine., Conclusions and Clinical Relevance: Clinically relevant concentrations of LAs had in vitro time- and concentration-dependent cytotoxicity for chondrocytes and FLSs isolated from the metacarpophalangeal joints of healthy horses. Bupivacaine was more toxic to chondrocytes than lidocaine, mepivacaine, and ropivacaine, whereas bupivacaine, LP, mepivacaine, and ropivacaine were more toxic to FLSs than preservative-free lidocaine. Several LAs may negatively affect chondrocyte and FLS viability.

Background: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy., Objective: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care., Design: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720)., Settings: This study was conducted at 3 hospital sites in South Australia., Patients: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups., Interventions: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent., Main Outcome Measures: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded., Results: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent., Limitations: This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control., Conclusions: We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698.

Background: Apart from the known anesthetic and antiarrhythmic effects, recent studies also highlight the anticancer activities of local anesthetics. In line with the findings, our work shows that ropivacaine, an amide-linked local anesthetic drug, targets chronic myeloid leukemia (CML) via inhibiting PI3K/Akt/mTOR., Materials and Methods: The effects of ropivacaine in CML cell lines and primary stem or progenitor cells were investigated using apoptosis, proliferation and colony formation assays. The effects of ropivacaine on proliferation and survival pathways were analyzed using Western blot., Results: We demonstrate that ropivacaine dose and time dependently inhibits proliferation in CML cell lines via arresting cell at G2/M stage. Ropivacaine induces apoptosis in CML cells. In addition, the anti-CML activity of ropivacaine is mainly through growth arrest rather than apoptosis induction. We further demonstrate that ropivacaine induces apoptosis and inhibits colony formation in CD34 progenitor or stem cells derived from patients with blast phase-CML. Importantly, combination of ropivacaine with imatinib or dasatinib (Bcr-Abl tyrosine kinase inhibitors) is significantly more effective in targeting CML cell lines as well as blast phase-CML CD34 cells than imatinib or dasatinib alone. We further demonstrate that ropivacaine inhibits phosphorylation of essential molecules involved in PI3K/Akt/mTOR signaling pathways in CML cells. Akt overexpression significantly reverses the effects of ropivacaine, further confirming that ropivacaine acts on CML cells via inhibition of PI3K/Akt/mTOR., Conclusions: Our work provide rationales on clinical trials for the use of local anesthetics in CML by demonstrating the anti-CML effects of ropivacaine and the molecular mechanism of its action., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: The sympathetic block of upper limb leading to increased blood flow has important clinical implication in microvascular surgery. However, little is known regarding the relationship between concentration of local anesthetic and blood flow of upper limb. The aim of this dose-response study was to determine the ED 50 and ED 95 of ropivacaine in blood flow after supraclavicular block (SB)., Methods: Patients undergoing upper limb surgery and supraclavicular block were randomly assigned to receive 30ml ropivacaine in concentrations of 0.125%(A Group), 0.2%(B Group), 0.25%(C Group), 0.375%(D Group), 0.5%(E Group), or 0.75%(F Group) (n=13 per group). All patients received supraclavicular block (SB). Time average maximum velocity (TAMAX), cross-sectional area (CSA) of brachial artery and skin temperatures (T s ) were measured repeatedly at the same marked points, they were taken at baseline (before block, t 0 ) and at 30min after SB (t 1 ). Blood flow(BF) = TAMAX× CSA×60 sec.. Relative blood flow (ΔBF) = BF t1 / BF t0 . Success of SB was assessed simultaneously. Supplementary anesthesia and other adverse events (AE) were recorded., Results: Significant increase in TAMAX, CSA, BF and T s were seen in all concentration groups at t 1 comparing with t 0 (P<0.001). There was an upward trend of TAMAX, CSA, BF with the increasing concentration of ropivacaine except T s . There was no significant different of T s at t 1 among different concentration group. The dose-response formula of ropivacaine on ΔBF was Y=1+3.188/(1+10^((-2.451-X) × 1.730)) and ED 50 /ED 95 (95%CI) were 0.35/1.94%(0.25-0.45/0.83-4.52), and R 2 (coefficient of determination) =0.85. ED 50 /ED 95 (95%CI) values of sensory block were 0.18/0.33% (0.15-0.21/0.27-0.51), R 2 =0.904., Conclusions: The dose-response curve between SB ropivacaine and the changes of BF was determined. The ED 50 /ED 95 of ropivacaine of ΔBF are 0.35/1.94% (0.25-0.45/0.83-4.52). TAMAX, CSA and BF consistently increased with ropivacaine concentration. The maximal sympathetic block needs higher concentration than that complete sensation block needs which may benefit for microvascular surgery., Trial Registration: Clinicaltrials.gov NCT02139982 . Retrospectively registered (Date of registration: May, 2014).

Background: Studies have reported that prophylactic continuous infusion of phenylephrine during spinal anesthesia for cesarean section can decrease the spread of local anesthetics. We investigated the ED50 of intrathecal hyperbaric ropivacaine in parturient women undergoing cesarean section under prophylactic infusion of phenylephrine., Methods: Sixty parturient women were allocated into 2 groups in this prospective study. Group P received 0.5 mL kg h of phenylephrine (5 mg/50 mL) at the start of intrathecal injection, and Group C (control group) received the same volume of saline. The dose of intrathecal ropivacaine for each subject was decided through up-down allocation method. The initial dose was set as 7.5 mg. Successful anesthesia was defined as the level of T6 or above achieved within 15 minutes after intrathecal injection and no additional epidural drug or venous analgesia to complete operation. The Massey formula was applied to calculate the ED50 of intrathecal ropivacaine in both groups., Results: The ED50 of hyperbaric ropivacaine determined by up-and-down method was 7.2 mg (95% confidence interval (CI), 6.8-7.6 mg) in the Group P, and 6.8 mg (95% CI, 6.4-7.2 mg) in the Group C, there was significant difference between the 2 groups (P < .5). The ED50 of intrathecal ropivacaine increases compared with Group C when phenylephrine is prophylactic infused to prevent spinal induced hypotension in cesarean section., Conclusion: The ED50 of intrathecal hyperbaric ropivacaine is 7.2 mg when phenylephrine is prophylactic infused to prevent spinal induced hypotension in cesarean section, and more ropivacaine demands on spinal anesthesia for cesarean section (www.chictr.org.cn, registration number: ChiCTR-RIC-17011650).

Background: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells., Methods: The effects of 2 LAs (lidocaine and ropivacaine) (10 to 10 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes., Results: We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P < .001] at 5 × 10 M to 40% [P = .02] at 10 M with ropivacaine and from 87% [P < .001] to 37% [P = .02] with lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10 M [P < .001] to 29% at 10 M [P = .04] with lidocaine and 59% [P < .001] with ropivacaine 5 × 10 M) in concentration-dependent manner. LAs have no effect on well-differentiated HepaRG. Ropivacaine decreased the mRNA level of key cell cycle regulators, namely cyclin A2, cyclin B1, cyclin B2, and cyclin-dependent kinase 1, and the expression of the nuclear marker of cell proliferation MKI67. Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01)., Conclusions: The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle-related genes that result in a cytostatic effect and induction of apoptosis.

Objective: The aim of the present study was to evaluate the optimum dose of ropivacaine by comparing three different dosing regimens of isobaric ropivacaine 1% (naropin 10 mg/ml, Astra Zeneca) administered intrathecally and to demonstrate the effects of anesthesia in pregnant women scheduled for cesarean section., Patients and Methods: Sixty ASA grade I-II patients were scheduled to undergo elective cesarean sections under spinal anesthesia. The patients were randomly assigned into three groups. Group 1 received 15 mg ropivacaine 1%, Group 2 received 20 mg ropivacaine 1%, and Group 3 received 25 mg ropivacaine 1%., Results: Intraoperative hemodynamic variables were not significantly different between the three groups, and sensory block time, motor block time and time to reach maximal sensory block time, and motor block time were similar between the three groups. The time to two-segment regression of sensory block was longer in Group 3 compared to other groups, and the difference was statistically significant (p < 0.05). The motor block time was longer with higher doses of ropivacaine; however, the difference was not statistically significant., Conclusion: Ropivacaine administration produced rapid induction of anesthesia and satisfactory anesthesia level, ropivacaine 15 mg and 20 mg dosing regimens are satisfactory for spinal anesthesia.

Background: Gender differences in absorption, distribution, and metabolism of a number of anesthetic agents have been identified in adults. Clinically, adult studies suggest women demonstrate slower onset of opioid analgesic effects, lower spinal and epidural dose requirements, and greater sensitivity to neuromuscular blocking agents. Sex-related differences in the pharmacokinetics and pharmacodynamics of local anesthetics in neonates and infants, however, have not been well documented. As a result, it is not known whether modification of the dose of local anesthetic for awake spinal anesthesia in infants is required., Aims: Our aim was to determine whether the ED50 and ED95 of local anesthetics used for infant spinal anesthesia are different between sexes., Methods: This was a retrospective analysis of data previously collected during dose-response studies of levobupivacaine and ropivacaine spinal anesthetics. The doses were reanalyzed using generalized linear regression analysis to determine whether there is a discernible difference in dose requirements between male and female infants., Results: One hundred and twenty infant spinal anesthetics were reviewed. For levobupivacaine, the ED50 (95% CI) was 0.69 (0.49-0.88) mg vs 0.49 (0.33-0.65), whereas the ED95(95% CI) was 1.07 (0.73-1.41) vs 0.93 (0.64-1.22) for girls and boys, respectively. For ropivacaine spinal anesthesia, the ED50 (95% CI) was 0.64 (0.35-0.92) mg vs 0.30 (-0.32-0.92), whereas the ED95 (95% CI) was 1.30 (0.73-1.87) vs 1.66 (0.55-2.76) for girls and boys, respectively., Conclusion: There is no evidence that sex differences occur at the ED50 dose range or at the clinically relevant ED95 dose. Modification of spinal anesthetic dose is not required for infant girls., (© 2017 John Wiley & Sons Ltd.)

Background: The transversus abdominis plane (TAP) block is a relatively straightforward regional technique used for postoperative analgesia in patients undergoing abdominal surgeries. Various adjuvants have been used in past to prolong the duration of action of analgesia in peripheral nerve blocks. Several studies investigating the analgesic efficacy of dexamethasone added to local anesthetic agents, such as bupivacaine, have shown promising results. However, there are few studies comparing the efficacy of dexamethasone with ropivacaine., Objectives: To determine if the addition of dexamethasone 8 mg to ropivacaine 0.2% in a TAP block would prolong the analgesic effect when compared with ropivacaine 0.2% alone after inguinal hernia repair and spermatocelectomy., Study Design: A randomized, double blinded, placebo-controlled, prospective study., Setting: Teaching hospital., Methods: A total of 82 patients undergoing inguinal hernia repair or spermatocelectomy were enrolled in the study, of which 41 patients received TAP block with ropivacaine with saline, and the other 41 received ropivacaine with dexamethasone immediately following surgery. Both the proceduralist (resident) and the patient were blinded to the solution used. Visual analog pain scores (0 - 10) were obtained pre-block and immediately post block. Our primary endpoint was visual analog pain score at 12 hours, with 24 and 48-hour pain scores as the secondary endpoints., Results: The averaged pre-block pain score was 7.6 ± 1.7 in the saline group and 7.7 ± 2.2 in the dexamethasone group. There was an improvement in the pain scores from the baseline, at 12 hours after the administration of the block in both the groups. Although the dexamethasone group had a greater change in pain score (-3.2) than the saline group (-2.2), the difference between the 2 groups was not statistically significant (0.08). We did not observe significant differences in change from baseline at 24 hours and 48 hours between the 2 groups (P value = 0.74 and 0.44, respectively)., Limitations: We did not assess the total dose of analgesics used during the surgery with the assumption that the effect of intraoperative analgesics should wear off by the time we collect the 12-hour pain score. We did not control for the expertise of the provider that performed the block, as some of the providers may have been junior residents with limited experience and expertise in the area. Additionally, we were unable to include postoperative opioid consumption due to concerns of inconsistencies during patient reporting and data quality., Conclusions: In conclusion, we could not show a statistically significant prolongation of analgesia for TAP blocks with ropivacaine when dexamethasone was added, though there was a one point drop in pain score at 12 hours post block when dexamethasone was added to the block solution. This decrease in pain scores at 12 hours may still be beneficial to patient satisfaction given the low side effect profile of dexamethasone. As ropivacaine has a lower pH than other local anesthetic agents, further well designed studies are needed to investigate the combination of this drug with more alkaline drugs like corticosteroids., Key Words: Regional anesthesia, transversus abdominis plane, dexamethasone, ropivacaine.

Purpose: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Axillary plexus block is a common method for regional anesthesia, especially in hand and wrist surgery. Local anesthetics (e.g., mepivacaine) are injected around the peripheral nerves in the axilla. A vasodilatory effect due to sympathicolysis has been described, but not quantified., Materials and Methods: In a prospective controlled study between October 2012 and July 2013, we analyzed 20 patients with saddle joint arthritis undergoing trapeziectomy under axillary plexus block. Patients received a mixture of mepivacaine 1% and ropivacaine 0.75% in a 3:1 ratio. The measurements were carried out on the plexus side and the contralateral hand, which acted as the control. Laser-Doppler spectrophotometry (oxygen to see [O2C] device) was used to measure various perfusion factors before and after the plexus block, after surgery and in 2-h intervals until 6 h postoperatively., Results: Compared with the contralateral side, the plexus block produced an enhancement of tissue oxygen saturation of 117.35 ± 34.99% (cf. control SO 2 : 92.92 ± 22.30%, P < 0.010) of the baseline value. Furthermore, blood filling of microvessels (rHb: 131.36 ± 48.64% versus 109.12 ± 33.25%, P < 0.0062), peripheral blood flow (219.85 ± 165.59% versus 129.55 ± 77.12%, P < 0.018), and velocity (163.86 ± 58.18% versus 117.16 ± 45.05%, P < 0.006) showed an increase of values., Conclusions: Axillary plexus block produces an improvement of peripheral tissue oxygen saturation of the upper extremity over the first 4 h after the inception of anesthesia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Dexmedetomidine prolongs sensory block of ropivacaine. Our objective was to study whether this extension would produce better postoperative pain control compared to that produced by clonidine in patients undergoing arthroscopic shoulder., Materials and Methods: Study comparative, longitudinal, controlled, randomized into 3 groups. Control group I: ropivacaine 0.75% clonidine group II: 0.75% ropivacaine plus clonidine 1mg/kg group iiidexmedetomidine: 0.75% ropivacaine more dexmedetomidine 1mg/kg. Interscalene block single dose ultrasound-guided. Sensory and motor blockade, pain intensity, sedation level, heart rate, respiratory rate, blood pressure at 6, 12 and 24hours was measured., Results: Pain intensity at 6hours in groups I and II moderate to severe pain, mild pain group iii. At 12hours the groups IIand II showed moderate to severe pain by more than 60% of patients, and in group iiionly 10%. At 24hours I and II group 20% of patients they continued to moderate pain., Conclusion: The prolonged interscalene block produced by dexmedetomidine provided better postoperative pain control during the first 24hours., (Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Dexmedetomidine used as an adjuvant to local anesthetics may prolong the duration of peripheral nerve blocks. Whether this is mediated by a perineural or systemic mechanism remains unknown. The authors hypothesized that dexmedetomidine has a peripheral mechanism of action., Methods: The authors conducted a randomized, paired, triple-blind trial in healthy volunteers. All received bilateral saphenous nerve blocks with 20 ml ropivacaine, 0.5%, plus 1 ml dexmedetomidine, 100 µg/ml, in one thigh and 20 ml ropivacaine 0.5% plus 1 ml saline in the other thigh. The primary outcome measure was the duration of block assessed by temperature sensation (alcohol swab). The secondary outcome measure was the duration of block assessed by pinprick, pain during tonic heat stimulation, warmth detection threshold, and heat pain detection threshold., Results: All 21 enrolled volunteers completed the trial. The mean duration of block assessed by temperature sensation in the leg receiving ropivacaine plus dexmedetomidine was 22 h (95% CI, 21 to 24) compared to 20 h (95% CI, 19 to 21) in the leg receiving ropivacaine plus placebo with a mean difference of 2 h (95% CI, 1 to 3; P = 0.001). The duration of block was also significantly longer in the leg receiving dexmedetomidine when assessed by pinprick, pain during tonic heat stimulation, and warmth detection threshold but not heat pain detection threshold. One participant experienced numbness in an area in the leg receiving dexmedetomidine., Conclusions: Dexmedetomidine prolongs the duration of a saphenous nerve block by a peripheral mechanism when controlling for systemic effects but not necessarily to a clinically relevant extent.

In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK II α , CaMK II β , CaMK II δ , CaMK II γ , can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK II β , CaMK II δ , CaMK II g mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Because of its rapid onset time, recent years have seen an increase in the use of ultrasound (US)-guided popliteal sciatic nerve block (PSNB) via subparaneural injection for induction of surgical anesthesia. Moreover, in below-knee surgery, combined blocks, as opposed to sciatic nerve block alone, have become more common. These combined blocks often require a large volume of local anesthetic (LA), thus increasing the risk of local-anesthetic systemic toxicity (LAST). Thus, to decrease the risk of LAST, it is important to know the minimum effective volume (MEV) required for an adequate block. We, therefore, aimed to determine the MEV of ropivacaine 0.75% for induction of surgical anesthesia by the method of US-guided popliteal sciatic nerve block via subparaneural injection.Thirty patients underwent a US-guided PSNB with ropivacaine 0.75% at a 20-mL starting volume. Using a step-up/step-down method, we determined injection volumes for consecutive patients from the preceding patient's outcome. When an effective block was achieved within 40 minutes after injection, the next patient's volume was decreased by 2 mL. If the block failed, the next patient's volume was increased by 2 mL. The sensory and motor blockade was graded according to a 4-point scale. The block was considered a success if a combination of anesthesia and paresis (a score of 3 for both the sensory and motor nerves) was achieved within 40 minutes. The primary outcome measure was the MEV resulting in a successful subparaneural block of the sciatic nerve in 50% of patients (MEV50). Additionally, the data were processed with a probit regression analysis to determine the volume required to produce a complete sciatic nerve block in 90% of subjects (ED90).The MEV50 of 0.75% ropivacaine is 6.14 mL (95% confidence interval, 4.33-7.94 mL). The ED90 by probit analysis for a subparaneural injection was 8.9 mL (95% CI, 7.09-21.75 mL).The 6.14-mL MEV50 of ropivacaine 0.75% represents a 71% reduction in volume compared with neurostimulation techniques and a 14.7% reduction in volume compared with US-guided PSNB using the alternative perineural injection technique.

The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs.

Purpose: The analgesic effect of ropivacaine (Rop) for nerve block lasts only ~3-6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats., Materials and Methods: Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA). One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each): Con (control group; 0.9% saline, 200 µL), PELA (PELA group; 10 mg), Rop (Rop group; 0.5%, 200 µL), and Rop-PELA (Rop-PELA group; 10%, 10 mg). Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days., Results: The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours) than that of the Rop group (4 hours). Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours-3 days). c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological change was found in the major organs after Rop-PELA administration at 7 days., Conclusion: Rop-PELA provides an effective analgesia for nerve block over 3 days after single administration, and the analgesic mechanism might be mediated by the regulation of spinal c-FOS expression. However, its potential long-term tissue toxicity needs to be further investigated.

Objective: 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., Design: A primary, experimental, analytical, prospective, self-controlled, blinded study., Setting: The study is set in a university research center., Interventions: 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., Main Outcome Measures: Quantification of CGRP and SP by Western blotting., Results: 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., Conclusions: Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.

Background: Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells., Methods: NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed., Results: Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM)., Conclusions: At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasis., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The purposes of this study were to assess whether local anesthetics (LAs), such as ropivacaine and bupivacaine, could induce apoptosis of rabbit annulus fibrosus (AF) cells in vitro and further to explore the possible underlying mechanism., Methods: Rabbit AF cells at second passage were treated with saline solution and various concentrations of LAs. Apoptosis of AF cells were examined by cell counting kit-8 (CCK-8), Annexin V assays, Hoechst 33342 staining, and Caspase-3, -9 activity assays. The expression of apoptosis-related markers was detected by real-time PCR (RT-PCR) and Western Blot. The JC-1 staining was used to evaluate the change of mitochondrial membrane potential (MMP). Moreover, the levels of reactive oxygen species (ROS) were determined with fluorescent probe DCFH-DA., Results: The results of flow cytometry indicated that LAs could induce apoptosis of rabbit AF cells in a dose-dependent manner. Apoptosis was confirmed by cell morphology, condensed nuclei and activation of Caspase-3 and -9. In addition, the molecular data showed that LAs could significantly up-regulate the expression of Bax, accompanied by a significant down-regulation of Bcl-2 expression. Furthermore, we also observed that LAs resulted in alteration of MMP and accumulation of intracellular ROS in AF cells. Blockade of ROS production by N-acetyl-l-cysteine (NAC) inhibited LAs-induced apoptosis., Conclusions: These findings suggest that LAs in clinically relevant concentrations could induce apoptosis of rabbit AF cells in vitro, and the mitochondrial pathway was, at least in part, involved in the LAs-mediated apoptosis. Further investigations focusing on the potential cytotoxicity of LAs on IVD cells are needed., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

We injected 15 ml epidural ropivacaine in 30 men and 30 women to determine the median dose required to impair a straight-leg raise. We started at a concentration of 0.425%, increasing the concentration by 0.025% after an ineffective injection and decreasing the concentration by 0.025% after an effective injection. The median (95% CI) concentration of ropivacaine that prevented straight-leg raise within 30 min of injection was 0.43% (0.41-0.45%) in men and 0.40% (0.39-0.41%) in women, p = 0.001. There were no differences in dermatome levels for loss of pinprick and cold sensation between men and women., (© 2015 The Association of Anaesthetists of Great Britain and Ireland.)

Purpose: 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)]., Method: 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., Results: 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., Conclusion: 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.

Purpose: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility., Methods: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation., Results: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2., Conclusions: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine.

The perioperative period is supposed to be a vulnerable period for cancer progression. Results of clinical studies indicate that the use of regional anesthesia can influence and improve oncological outcome of cancer patients. Uncontrolled cell proliferation and resistance to apoptotic cell death are important characteristics of solid tumors. The aim of this study was to investigate the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon (HT 29 and SW 480) and pancreatic (PaTu 8988t and PANC 1) cancer cell lines in vitro. Cell proliferation was measured by Cell Proliferation ELISA BrdU Assay. Apoptosis was analyzed by annexin V staining and cell cycle distribution was detected by flow cytometry. Ropivacaine, bupivacaine and sufentanil did not change apoptosis rate and cell cycle distribution in clinically concentration. Only high concentrations of ropivacaine or bupivacaine revealed antiproliferative potency. Protective effects of epidural anesthesia observed in clinical studies seem not to be based on direct effects of these drugs on cancer cells., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Even though ropivacaine is frequently used during orthopedic surgery, the relationship between plasma concentrations and degree of sensory anesthesia after a peripheral nerve block is currently unknown. The aim of this study was to characterize this relation using population pharmacokinetic-pharmacodynamic modeling., Methods: Femoral nerve block was performed by the anterior approach using a single injection (20 ml) of 0.5% ropivacaine hydrochloride in 20 patients scheduled for total knee arthroplasty under spinal anesthesia. Sensory thresholds in response to a gradual increase in transcutaneous electrical stimulation (primary endpoints), loss and recovery of ice-cold sensation, as well as total ropivacaine plasma concentrations were determined up to 4 days after administration of the local anesthetic. Using NONMEM (ICON, USA), sensory block was modeled by assuming an equilibration delay (ke0) between amount in the depot and effect-site compartments., Results: Mean effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 mg. At 2 × AE90, the sigmoid Emax model predicted a mean onset time of 23.4 min and mean duration of 22.9 h. Interindividual variability (IIV) for AE50 was 49%. Typical ke0 half-life was 34.7 min (IIV = 52%) and steepness parameter 8.7 (IIV = 48%). None of the pharmacodynamic model parameters showed sex, age, or body weight dependency., Conclusions: A population pharmacokinetic/pharmacodynamic model was developed that quantitatively describes the sensory component of a femoral nerve block in orthopedic patients. Further clinical studies will be needed to validate the clinical relevance of this finding.

The aim of this study was to investigate the myotoxic effects of bupivacaine, ropivacaine, and levobupivacaine which were applied intramuscularly to rat skeletal muscle. Forty Wistar-Albino rats were divided into four groups. In the study, .5% bupivacaine (Group B), .5% ropivacaine (Group R), .5% levobupivacaine (Group L), or .9% normal saline (Group SF) was applied intramuscularly to the right gastrocnemius muscle of rats. The rats in each group were sacrificed on the second day after injection. Sections of muscle samples were stained with hematoxylin-eosin for light microscopic investigation and prepared for the evaluation of ultrastructural changes in the subcellular level with transmission electron microscopy. All three local anesthetic agents caused qualitatively similar skeletal muscle damage. The most observed muscle damage was in Group B, muscle damage of Group R was less than that of Group B, and the least damage was seen in Group L quantitatively. Electron microscopic examination of each group that caused cellular damage was qualitatively similar. The most subcellular damage was observed in the group receiving bupivacaine, less was seen in the ropivacaine group, and the least was observed in the levobupivacaine group. The results indicated that bupivacaine caused more myotoxic damage than the other two agents in the skeletal muscle of rats and that levobupivacaine caused less myotoxic damage than both bupivacaine and ropivacaine at the cell and tissue levels.

Ropivacaine is a local anesthetic widely used for regional anesthesia and epidural analgesia, but its relatively short duration limits its clinical use. A novel sustained release lipid formulation of ropivacaine has been recently developed to prolong its duration. We examined the epidural anti-hypersensitivity and preemptive effects of ropivacaine in mesylate injection and sustained release suspension forms in a rat model of neuropathy produced by peripheral nerve injury. Epidural administration of ropivacaine mesylate injection specifically blocked mechanical allodynia and thermal hyperalgesia by approximately 50% with a biological half-effective duration of approximately 3 hrs. The equivalent dose of ropivacaine free-base in sustained release suspension significantly prolonged the duration of anti-allodynia and anti-hyperalgesia by approximately 2 times. Multiple daily epidural injections of ropivacaine in both the mesylate injection and sustained-release suspension forms did not induce tolerance or potentiation to anti-allodynia or anti-hyperalgesia. Moreover, the single or multiple daily administration of ropivacaine mesylate injection before surgery in particular, markedly blocked the initiation and development of neuropathic pain, increasing the biological half-effective duration from less than 4 hrs up to 1 or 2 days. The single and multiple daily epidural injection of ropivacaine sustained release suspension further delayed the biological half-lives to 2 and 3 days, respectively. Our results indicate that the epidural administration of ropivacaine effectively blocks neuropathic pain without the induction of analgesic tolerance, and significantly delays the development of neuropathy produced by peripheral nerve injury. Epidural ropivacaine sustained release suspension produces much longer blockade effects of mechanical allodynia and heat hyperalgesia, and more significantly delays the development of neuropathic pain.

Background: It remains unknown whether local anaesthetic dose is the only factor influencing continuous popliteal-sciatic nerve block effects, or whether concentration, volume, or both exert an influence as well., Methods: Bilateral sciatic catheters were inserted in volunteers (n=24). Catheters were randomly assigned to ropivacaine of either 0.1% (8 ml h(-1)) or 0.4% (2 ml h(-1)) for 6 h. The primary endpoint was the tolerance to transcutaneous electrical stimulation within the tibial nerve distribution at hour 6. Secondary endpoints included current tolerance at other time points and plantar flexion maximum voluntary isometric contraction (22 h total)., Results: At hour 6, tolerance to cutaneous stimulation for limbs receiving 0.1% ropivacaine was [mean (standard deviation)] 27.0 (20.2) vs26.9 (20.4) mA for limbs receiving 0.4% [estimated mean difference 0.2 mA; 90% confidence interval (CI) -8.2 to 8.5; P=0.02 and 0.03 for lower and upper boundaries, respectively]. Because the 90% CI fell within the prespecified tolerance ±10 mA, we conclude that the effect of the two concentration/volume combinations were equivalent. Similar negative findings were found for the secondary outcomes., Conclusions: For continuous popliteal-sciatic nerve blocks, we found no evidence that local anaesthetic concentration and volume influence block characteristics, suggesting that local anaesthetic dose (mass) is the primary determinant of perineural infusion effects in this anatomic location. These findings suggest that for ambulatory perineural local anaesthetic infusion-for which there is usually a finite local anaesthetic reservoir-decreasing the basal rate while increasing the local anaesthetic concentration may allow for increased infusion duration without compromising postoperative analgesia., Clinical Trial Registration: NCT01898689., (© 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 objective of the present study was to prepare and evaluate a ropivacaine-loaded microemulsion (ME) formulation and microemulsion-based Carbopol gel (ME-gel) for transdermal delivery. Pseudo-ternary phase diagrams and a simplex lattice experiment design were utilized to screen and optimize the ME formulation. In the process, drug solubility and particle size were inspected as dependent variables whilst Capryol(®) 90 (X1), Smix (X2, Labrasol(®): absolute ethanol=1:2 w/w), water (X3) as independent variables. Following the optimization, the optimal ME formulation was comprised of 15% Capryol(®) 90, 53% Smix, and 32% water, respectively. Ropivacaine loaded ME appeared to be spherical under transmission electron microscope, and the average particle size was 58.79 nm. The results of ex vivo permeation study showed that ropivacaine had a significant higher cumulative amount from ME than that from ME-gel. Histopathology study elucidated that the microstructure of skin surface was significantly changed by the treatment of ME formulation. Skin irritation study indicated that neither ME nor ME-gel caused any irritation responses. Both ME and ME-gel presented a remarkable analgesic activity on acetic acid-induced writhing in mice. In conclusion, ME could be a promising formulation for ropivacaine transdermally administration., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To compare the anesthetic efficacy and adverse effects associated with peribulbar injection of ropivacaine (1% solution) performed with and without ultrasound guidance (UG) in dogs., Animals: 15 dogs without ophthalmologic abnormalities., Procedures: Each dog was sedated and anesthetized. A peribulbar injection of ropivacaine (1% solution; 0.3 mL/kg) was performed with UG in 1 eye and without UG in the contralateral eye (control). For each eye, the intraocular pressure (IOP) immediately after eye centralization and number of punctures were recorded; ophthalmic complications, postinjection corneal sensitivity (determined by Cochet-Bonnet esthesiometry), durations of the sensory and motor blockades (the latter determined as the interval to restoration of the vestibuloocular reflex, pupillary light reflex, and conjugate eye movement), and blockade quality were assessed in both eyes following anesthetic recovery., Results: Needle placement was fully visualized in 8 of the 15 eyes injected with UG. For eyes injected with or without UG, there was no difference with regard to the number of punctures, postinjection corneal sensitivity, and sensory or motor blockade duration and quality; however, restoration of conjugate eye movement occurred later in control eyes. For eyes injected with UG, mean IOP was 18.6 mm Hg, compared with 23.3 mm Hg for control eyes. Incidence of subconjunctival hemorrhage was higher for control eyes; severity of chemosis and hyperemia varied over time within both groups of eyes., Conclusion and Clinical Relevance: In dogs, peribulbar injection of ropivacaine with UG is feasible in dogs and provides effective sensory and motor blockades similar to those achieved with conventional techniques.

Background: Levobupivacaine has less toxic potential on both the cardiovascular and central nervous system and has been widely used for postoperative epidural analgesia in surgical patients. However, there are few reports on the efficacy of epidural levobupivacaine in outpatients with lumbosacral radiculopathy. This study was carried out to evaluate the comparative efficacy of levobupivacaine and ropivacaine for epidural block in outpatients with degenerative spinal disease and sciatica., Objective: We studied 32 patients (19 men and 13 women) with degenerative spinal disease and sciatica., Study Design: The study was performed in a prospective, randomized, double blind, and crossover fashion., Setting: Treatment room for outpatients., Methods: The epidural block was produced with a caudal approach (0.125% levobupivacaine or 0.2% ropivacaine, 15 mL). The upper level of analgesia, lumbosacral pain, motor blockade, and hemodynamic changes were evaluated by pin prick, visual analogue scale (VAS), Bromage scale, and arterial blood pressure and heart rate at 15, 30, 60, and 90 minutes after epidural block, respectively. The recovery time to mobilization, ambulation, and spontaneous micturition were measured., Results: There were no significant differences (P < 0.05) in the upper level of analgesia, VAS, and Bromage scale between 0.125% levobupivacaine and 0.2% ropivacaine throughout the time course. There were no significant differences in the recovery times to mobilization, ambulation, and spontaneous micturition between 0.125% levobupivacaine and 0.2% ropivacaine. There were no significant differences in arterial blood pressure and heart rate between the 2 trials throughout the time course., Conclusion: The results showed that 0.125% levobupivacaine and 0.2% ropivacaine for epidural block by a caudal approach provide similar lumbosacral pain relief, hemodynamic effects, and the degree and the recovery of motor blockade in outpatients with degenerative spinal disease and sciatica.

Anesthesia is a loss of sensation or consciousness and mechanisms by which drugs can produce this state are not clear. Recent studies gave insight show anesthetic agents may lead to loss of consciousness at the molecular level. The objective of this study was to determine whether ropivacaine can influence antioxidant defense system.To analyze the response of the antioxidant defense system to ropivacaine samples were taken from the vein before anesthesia (0 min) and 5 min, 15 min, and 60 min after anesthesia. Subsequently, the levels of lipid peroxidation as melaninedialdehyde (MDA) and glutathione (GSH), as well as superoxide dismutase (SOD) and catalase (CAT) activities were measured.We observed moderate increase in lipid peroxidation and glutathione levels. More-over, the activity of superoxide dismutase was slightly enhanced. These alterations occurred 5 min after spinal injection of ropivacaine and this phenomenon was maintained throughout anesthesia. We measured decreased catalase activity starting from 5 min after anesthesia and activity of this antioxidant enzyme was not recovered even after 60 min of anesthesia.We found that spinal injection of ropivacaine results in increased levels of free radicals in spinal fluid, which may stimulate antioxidant defense system of spinal fluid during anesthesia., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes., (Copyright © 2014. Published by Elsevier B.V.)

We reviewed the Chinese and English literature for efficacy and tolerability data as well as pharmacological properties of ropivacaine in Chinese patients. Ropivacaine is a long-acting amide local anesthetic agent that elicits nerve block via reversible inhibition of sodium ion influx in nerve fibers. The available evidence in the literature on anesthesia practice indicates that ropivacaine produces equally surgical sensory block and postoperative and obstetrics analgesia with good maternal and fetal outcome to those of bupivacaine or levobupivacaine. It appears to be associated with comparable onset, quality, and duration of sensory block, but with a lower incidence or grade of motor block, compared to bupivacaine. The satisfaction of both patients and surgeons is high when ropivacaine is used. Thus, ropivacaine appears to be an important option for regional anesthesia and for the management of postoperative and labor pain, with its enhanced sensorimotor differentiation blockage at lower concentrations and enhanced safety at higher concentrations.

Background: Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a crucial role in the development of protein-/neutrophil-rich pulmonary edema, the hallmark of ALI. Amide-linked local anesthetics, such as ropivacaine, have anti-inflammatory properties in experimental ALI. We hypothesized ropivacaine may attenuate inflammation in a "double-hit" model of ALI triggered by bacterial endotoxin plus hyperinflation via inhibition of Src-dependent signaling., Methods: C57BL/6 (WT) and ICAM-1 (-/-) mice were exposed to either nebulized normal saline (NS) or lipopolysaccharide (LPS, 10 mg) for 1 hour. An intravenous bolus of 0.33 mg/kg ropivacaine or vehicle was followed by mechanical ventilation with normal (7 ml/kg, NTV) or high tidal volume (28 ml/kg, HTV) for 2 hours. Measures of ALI (excess lung water (ELW), extravascular plasma equivalents, permeability index, myeloperoxidase activity) were assessed and lungs were homogenized for Western blot analysis of phosphorylated and total Src, ICAM-1 and caveolin-1. Additional experiments evaluated effects of ropivacaine on LPS-induced phosphorylation/expression of Src, ICAM-1 and caveolin-1 in human lung microvascular endothelial cells (HLMVEC)., Results: WT mice treated with LPS alone showed a 49% increase in ELW compared to control animals (p = 0.001), which was attenuated by ropivacaine (p = 0.001). HTV ventilation alone increased measures of ALI even more than LPS, an effect which was not altered by ropivacaine. LPS plus hyperinflation ("double-hit") increased all ALI parameters (ELW, EVPE, permeability index, MPO activity) by 3-4 fold compared to control, which were again decreased by ropivacaine. Western blot analyses of lung homogenates as well as HLMVEC treated in culture with LPS alone showed a reduction in Src activation/expression, as well as ICAM-1 expression and caveolin-1 phosphorylation. In ICAM-1 (-/-) mice, neither addition of LPS to HTV ventilation alone nor ropivacaine had an effect on the development of ALI., Conclusions: Ropivacaine may be a promising therapeutic agent for treating the cause of pulmonary edema by blocking inflammatory Src signaling, ICAM-1 expression, leukocyte infiltration, and vascular hyperpermeability.

Background: Metastatic breast and colon cancer cells express neonatal and adult splice variants of NaV1.5 voltage-activated Na(+) channels (VASCs). Block of VASCs inhibits cell invasion. Local anaesthetics used during surgical tumour excision inhibit VASC activity on nociceptive neurones providing regional anaesthesia. Inhibition of VASCs on circulating metastatic cancer cells may also be beneficial during the perioperative period. However, ropivacaine, frequently used to provide analgesia during tumour resection, has not been tested on colon cancer cell VASC function or invasion., Methods: We used reverse transcription-polymerase chain reaction and sequencing to identify NaV1.5 variants in the SW620 metastatic colon cancer cell line. Recombinant adult and neonatal NaV1.5 variants were expressed in human embryonic kidney cells. Voltage-clamp recordings and invasion assays were used to examine the effects of ropivacaine on recombinant NaV1.5 channels and the metastatic potential of SW620 cells, respectively., Results: SW620 cells expressed adult and neonatal NaV1.5 variants, which had similar steady-state inactivation profiles, but distinctive activation curves with the neonatal variant having a V1/2 of activation 7.8 mV more depolarized than the adult variant. Ropivacaine caused a concentration-dependent block of both NaV1.5 variants, with IC50 values of 2.5 and 3.9 µM, respectively. However, the reduction in available steady-state current was selective for neonatal NaV1.5 channels. Ropivacaine inhibited SW620 invasion, with a potency similar to that of inhibition of NaV1.5 channels (3.8 µM)., Conclusions: Ropivacaine is a potent inhibitor of both NaV1.5 channel activity and metastatic colon cancer cell invasion, which may be beneficial during surgical colon cancer excision., (© 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.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.)

In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.01 to 300 μmol/L and the amplitude and frequency of contraction were recorded. All four compounds caused a concentration-dependent inhibition of the contractility of pregnant and non-pregnant uterine muscle. In pregnant myometrium, the concentration that caused 50% inhibition (IC(50)) was 100 μmol/L for bupivacaine, 157 μmol/L for ropivacaine, > 1000 μmol/L for lidocaine, and 26.3 μmol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9 μmol/L for bupivacaine, 40 μmol/L for ropivacaine, 384 μmol/L for lidocaine, and 7.4 μmol/L for tetracaine. These results suggested that local anesthetics do inhibit myometrial contractions in pregnant and non-pregnant rats in a concentration-dependent manner.

Background: Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase-Akt-nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability., Methods: Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed., Results: Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10 M for ropivacaine; IC50 = 5.864 × 10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10 M for ropivacaine; IC50 = 6.377 × 10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated., Conclusions: Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory "side-effect" of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease.

The objective of this study was to describe and compare the efficacy and duration of topical anaesthesia induced by 2 per cent lidocaine (L), 0.5 per cent bupivacaine (B) and 1 per cent ropivacaine (R) in the dog using 24 clinically healthy beagles with normal ocular examination. Dogs were randomly divided into three groups: 2 per cent lidocaine (n=8), 0.5 per cent bupivacaine (n=8) and 1 per cent ropivacaine (n=8). The baseline corneal touch threshold (CTT) was measured using a Cochet-Bonnet aesthesiometer. Following baseline CTT measurement, a single drop of the assigned anaesthetic was applied to each eye and the CTT was measured bilaterally within one minute after administration and every five minutes until the basal CTT value was restored. Data were analysed with non-parametric analysis of variance models and Dunnet's test for post hoc analysis. One per cent ropivacaine was the most effective drug (LCTTmax=3 cm, BCTTmax=2 cm, RCTTmax=0 cm; P<0.001), and had the shortest latency (LLatency=5 minutes, BLatency=5 minutes, RLatency=1 minute; P<0.001) and the smallest AUC (LAUC=80 cm×minute, BAUC=68.25 cm×minute, RAUC=36.88 cm×minute; P<0.001). There was no statistical difference in the duration of corneal anaesthesia between the groups (P=0.09) and all topical anaesthetics tested reduced corneal sensitivity, although 1 per cent ropivacaine had the maximal and quickest anaesthetic effect. This drug could be used for specific diagnostic procedures where quick and short, but effective, corneal anaesthesia is needed.

Background Context: It has been shown that bupivacaine, the most commonly used local anesthetic to relieve or control pain in interventional spine procedures, is cytotoxic to intervertebral disc (IVD) cells in vitro. However, some other common local anesthetics, such as ropivacaine and lidocaine, are also frequently used in the treatment of spine-related pain, and the potential effects of these agents remain unclear., Purpose: The purpose of this study was to evaluate the effect of various local anesthetics on rabbit IVD cells in vitro and further compare the cytotoxicity of ropivacaine, bupivacaine, lidocaine, and saline solution control., Study Design: Controlled laboratory study., Subjects: Rabbit annulus fibrosus (AF) and nucleus pulposus (NP) cells were isolated from Japanese white rabbits., Methods: Both AF and NP cells at the second generation maintained in monolayer were exposed to various concentrations of local anesthetics (eg, bupivacaine) or different durations of exposure and evaluated for cell viability by use of cell counting kit-8 (CCK-8). In addition, to compare the cytotoxicity of ropivacaine, bupivacaine, lidocaine, and saline solution control in commercial concentration, the viability was analyzed by flow cytometry after 60-minute exposure, and the morphologic changes were observed by the phase-contrast microscopy. Apoptosis and necrosis of IVD cells were confirmed by using fluorescence microscopy with double staining of Hoechst 33342 and propidium iodide., Results: Rabbit IVD cell death demonstrated a time and dose dependence in response to bupivacaine and lidocaine. However, ropivacaine only exerted a significant time-dependent effect on IVD cells. There was no significant difference in IVD viability after treatment with different doses of ropivacaine. In addition, the results showed that lidocaine was the most toxic of the three local anesthetics and that ropivacaine presented less cytotoxicity than lidocaine and bupivacaine. Fluorescence microscopy also confirmed that the short-term toxic effect of local anesthetics on both AF and NP cells was mainly caused by necrosis rather than apoptosis., Conclusions: Results show that bupivacaine and lidocaine decrease cell viability in rabbit IVD cells in a dose- and time-dependent manner. All local anesthetics should be avoided if at all possible. Ropivacaine may be a choice if necessary, but it is also toxic. The increase in cell death is more related with cell necrosis rather than cell apoptosis. If these results can be corroborated in tissue explant models or animal studies, caution regarding diagnosing, treating, and controlling spine-related pain with local anesthetics is prompted., (Copyright © 2014 Elsevier Inc. All rights reserved.)