Search Results (27)

Background: Local analgesia administered through a wound catheter is widely used for postoperative pain control, yet its effects on wound healing remain incompletely understood. This study examined how levobupivacaine alone or combined with meloxicam or buprenorphine influences inflammatory markers, angiogenesis, apoptosis, and transforming growth factor β1 (TGF-β1) expression during wound healing in rats. Methods: Thirty Sprague Dawley rats were assigned to five groups: control, saline, levobupivacaine (L), levobupivacaine/meloxicam (L/MEL), and levobupivacaine/buprenorphine (L/BUP). Treatments were administered via a wound catheter for three days. Blood and skin samples were collected before surgery and on days 3, 10, and 21. Results: Levobupivacaine combined with meloxicam or buprenorphine caused fluctuations in white blood cell counts, while albumin levels remained stable. Angiogenesis in the L/MEL group was markedly increased compared with the control, saline, and levobupivacaine-only groups, but the newly formed vessels exhibited consistently narrow lumina during the early healing phase. Caspase-3–positive cells were most numerous in L/MEL during inflammatory and proliferative phases, whereas delayed caspase-3 activation was observed in L/BUP. TGF-β1 expression peaked in both adjuvant groups on days 3 and 10. Conclusions: Meloxicam and buprenorphine increased TGF-β1 expression, but their vascular effects differed considerably. Meloxicam induced a marked increase in angiogenesis, but the newly formed vessels were structurally immature, displaying uniformly narrow lumina and poor architectural organisation, which led to their subsequent regression. In contrast, buprenorphine supported the formation of more mature vascular structures, characterised by wider vessel lumina and a more organised vascular network. These findings demonstrate that adjuvants used with levobupivacaine can significantly modify angiogenic and apoptotic responses and should be carefully considered when selecting multimodal local analgesia strategies after surgery. Full article

Perioperative anesthesia might directly alter cancer cell biology. We investigated the effects of levobupivacaine treatment on lung adenocarcinoma cells. A549 cells were treated with levobupivacaine at concentrations of 0.1 mM and 0.5 mM for 2 h. Transfection with angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) was performed 6 h before the levobupivacaine treatment. Cell proliferation was assessed using a cell counting kit 8 (CCK-8), and ATP synthesis was evaluated with the CellTiter-Glo^® 2.0 assay at 0 and 24 h after anesthesia exposure. RT-PCR was performed to examine various biomarkers. The levobupivacaine treatment suppressed ATP synthesis without affecting cell proliferation. This was associated with the upregulation of ACE2 and the downregulation of pro-cancer biomarkers, including HIF-1α, MMP-9, and β-catenin. The anticancer effect of levobupivacaine was negated when ACE2 siRNA was introduced, and it was further suppressed when combined with levobupivacaine. The RT-PCR results indicated that the expressions of B-cell/CLL lymphoma 2 (BCL2) and wingless/integrated 1 (WNT1) were reduced after levobupivacaine treatment, but these effects were reversed with ACE2 siRNA induction. The administration of levobupivacaine suppressed A549 cell metabolism and downregulated HIF-1α, MMP-9, WNT1, EGFR, and BCL2 in an ACE2-dependent manner. Full article

Background and Clinical significance: Single-shot spinal anesthesia for intrapartum Cesarean section has recently been incriminated in carrying a high risk of high neuraxial block (HNB) occurrence in parturients receiving labor epidural analgesia. The so-called volume effect of the epidurally injected solution causes a contraction of the dural sack and unexpected HNB. Case presentation: We present two cases of HNB in parturients receiving epidural analgesia. The first case describes the 36-year-old patient G3P2, who was administered a repeated rescue analgesia single-shot spinal injection with low-dose local anesthetic (levobupivacaine, 3 mg) following non-functional combined spinal–epidural analgesia. The second case describes the 28-year-old parturient G1P0, who experienced HNB after single-shot spinal anesthesia with hyperbaric bupivacaine (7.5 mg) following labor epidural analgesia. Conclusions: Intrathecal administration of local anesthetic for the purpose of spinal analgesia or anesthesia in a parturient with epidural analgesia can cause unexpected HNB and could occur even at low doses of intrathecally administered medications. The interplay of numerous variables and circumstances in the specific case can result in the occurrence of HNB. We assume that in our first case, the volume effect and repeated dural puncture, and in the second case, the low height of the parturient coupled with the volume effect, played significant role in the occurrence of HNB. Full article

Background/Objectives: The objective is to assess if transvaginal infiltration with anaesthetic only is non-inferior compared to anaesthetic plus corticosteroid for the treatment of myofascial pelvic pain. Methods: A randomised, double-blind, parallel-group (1:1) clinical trial was set at the Department of Obstetrics and Gynaecology, Hospital Universitario “Príncipe de Asturias” from December 2017 to June 2023. Women presenting myofascial perineal pain ≥ 4 on the visual analogue scale (VAS) 2 months after delivery, with instrumental delivery or prolonged second stage (>3 h) or foetal weight > 4000 g, were randomised into two groups to receive levobupivacaine 5 mg/mL or levobupivacaine 5 mg/mL plus betamethasone 3 mg/mL. For each trigger point detected, a transvaginal infiltration was performed using the corresponding treatment. The patients were followed up to 6 months. The primary endpoint was a change in the VAS score from baseline at 6 months. Results: A total of 114 women were enrolled, with 57 randomly assigned to each group. The median (IQR) VAS 2 weeks after infiltration decreased by a similar magnitude: median (IQR) 2 (1–3) in the levobupivacaine group and 2 (1–4) in the levobupivacaine + betamethasone group (p-value = 0.33). The same trend was observed at 6 months: median (IQR) 1 (1–4) in the levobupivacaine group and 1 (1–2) in the levobupivacaine + betamethasone group (p-value = 0.85). Conclusions: This study provides evidence that the use of anaesthetic-only infiltration is non-inferior compared to anaesthetic plus corticosteroid for the treatment of myofascial perineal pain. Full article

Local anesthetics are commonly used in various clinical settings for both prevention and symptom relief. Numerous clinical studies have demonstrated that intra-articular injections of local anesthetics achieve high success rates in orthopedic practices. However, several widely used local anesthetics, including bupivacaine, lidocaine, and ropivacaine, have been shown to exhibit toxicity to chondrocytes, with the underlying mechanisms of chondrotoxicity remaining poorly understood. In this study, we aimed to investigate the cytotoxic effects of local anesthetics, specifically focusing on the consequences of a single intra-articular injection in human chondrocyte cells. Our results reveal that lidocaine, levobupivacaine, bupivacaine, and ropivacaine induced cell death, characterized by the induction of apoptosis and the suppression of cellular proliferation. These effects were mediated through mechanisms involving oxidative stress, mitochondrial dysfunction, and autophagy pathways. We found that the toxic effects of local anesthetics were concentration-dependent, with lidocaine exhibiting the lowest cytotoxicity among the tested agents in TC28a cells. Notably, bupivacaine and levobupivacaine displayed significant cytotoxic effects related to apoptosis, cellular proliferation, reactive oxygen species generation, mitochondrial membrane potential depolarization, and autophagy in human chondrocyte cells. Our findings not only support existing clinical studies but also highlight potential targets for developing protective agents to mitigate serious side effects associated with their use in orthopedic practices. Full article

Background: External oblique intercostal block (EOIB) is effective in relieving pain in the T6 to T10 dermatomes; however, there is limited evidence comparing EOIB with conventional regional anesthesia. In this randomized controlled trial, it was hypothesized that EOIB would provide more effective analgesia than wound infiltration (WI) in laparoscopic gastrectomy. Methods: Thirty-two patients (aged 20–85 years) with American Society of Anesthesiologists Performance Status of 1 to 2, scheduled for laparoscopic gastrectomy, were randomly divided into EOIB and WI groups. Both procedures were performed using 40 mL of 0.25% levobupivacaine. The primary outcome was the numerical rating scale (NRS) score 12 h postoperatively. Secondary outcomes were NRS at 2, 24, and 48 h postoperatively, variation in quality of recovery-15 score on postoperative days 1 and 2 from preoperative baseline, postoperative fentanyl consumption, and variation in World Health Organization Disability Assessment Scale 2.0 scores between baseline and 3 months postoperatively. Plasma concentrations of levobupivacaine and pinprick sensation in the T4–11 dermatomes post-EOIB were evaluated to determine the exploratory endpoints. Results: There were no differences in the NRS scores 12 h postoperatively at rest and during movement between the EOIB and WI groups (mean standard deviation 1.3 [1.1] vs. 1.5 [1.4] and 3.1 [1.6] vs. 3.8 [1.7], respectively). Secondary outcomes did not differ significantly between the groups. The time to peak plasma concentration of levobupivacaine following EOIB was 45 min. Conclusions: No significant differences in NRS scores were observed between the analgesic effects of EOIB and WI at 12 h postoperatively. Full article

The current case report describes a successful ultrasound-guided mid-femur sciatic nerve block in an emu. A 2-month-old emu suffering from acute-onset lameness was referred to the University Clinic of Liège, where he was diagnosed with a lateral luxation of the Achilles tendon on both hind limbs. Two surgical procedures were performed for treatment. Both surgical procedures were performed under general anaesthesia with butorphanol, ketamine, midazolam and isoflurane in oxygen. The anaesthesia was continuously monitored. An ultrasound-guided sciatic nerve block was performed to prevent and treat surgically induced nociception. The technique was adapted from what is already described in other species. Levobupivacaine was injected perineurally under ultrasound-guidance. Intraoperative nociception was assessed based on the heart rate and mean arterial pressure changes. The recovery was uneventful and with no clinical signs of postoperative pain. Full article

Background: Lung resection using video-assisted thoracoscopic surgery (VATS) improves surgical accuracy and postoperative recovery. Unfortunately, moderate-to-severe acute postoperative pain is still inherent to the procedure, and a technique of choice has not been established for the appropriate control of pain. In this study, we aimed to compare the efficacy and safety of intrathecal morphine (ITM) with that of intercostal levobupivacaine (ICL). Methods: We conducted a single-center, prospective, randomized, observer-blinded, controlled trial among 181 adult patients undergoing VATS (ISRCTN12771155). Participants were randomized to receive ITM or ICL. Primary outcomes were the intensity of pain, assessed by a numeric rating scale (NRS) over the first 48 h after surgery, and the amount of intravenous morphine used. Secondary outcomes included the incidence of adverse effects, length of hospital stay, mortality, and chronic post-surgical pain at 6 and 12 months after surgery. Results: There are no statistically significant differences between ITM and ICL groups in pain intensity and evolution at rest. In cough-related pain, differences in pain trajectories over time are observed. Upon admission to the PACU, cough-related pain was higher in the ITM group, but the trend reversed after 6 h. There are no significant differences in adverse effects. The rate of chronic pain was low and did not differ significantly between groups. Conclusions: ITM can be considered an adequate and satisfactory regional technique for the control of acute postoperative pain in VATS, compatible with the multimodal rehabilitation and early discharge protocols used in these types of surgeries. Full article

Previous studies have compared levobupivacaine versus ropivacaine in various peripheral nerve blocks in terms of block duration, quality of analgesia, and onset time, but this has not occurred in the PENG block. Here, a single-center, randomized, and controlled clinical trial is presented. One hundred and twenty patients older than 65 years suffering from hip fractures and surgically treated at our institution under spinal anesthesia were eligible for participation; of them, one hundred and eight were analyzed. Patients were randomized to receive ultrasound-guided PENG blocks using 20 mL of either 0.25% levobupivacaine or 0.375% ropivacaine (both of which are equipotent concentrations). The primary endpoint was to compare the analgesic duration (time to first rescue) and analgesic quality (pain scores using the VAS, PAINAD, and AlgoPlus scales) between the groups. Secondary endpoints included comparing the onset time, describing the need for and type of rescue analgesics, and possible associated adverse effects. There were no statistically significant differences in analgesic duration between levobupivacaine (median 861.0, IQR 960) and ropivacaine (median 1205.0, IQR 1379; p = 0.069). Likewise, the quality of analgesia and onset time were comparable among the groups. A small number of patients required opioids as rescue analgesics (4.6%). The possible associated adverse effects included postoperative infection (11.1%) and delirium (2.8%). Full article

Modified thoracoabdominal nerves block through a perichondrial approach (M-TAPA) provides a wide analgesic range. Herein, we examined the quality of recovery (QoR) of M-TAPA for total laparoscopic hysterectomy (TLH) compared with oblique subcostal transversus abdominis plane block (OSTAPB) and measured plasma levobupivacaine concentrations (PC_levo). Forty female patients undergoing TLH were randomized to each group. Nerve blocks were performed bilaterally with 25 mL of 0.25% levobupivacaine administered per side. The primary outcome was changes in QoR-15 scores on postoperative days (POD) 1 and 2 from the preoperative baseline. The main secondary outcomes were PC_levo at 15, 30, 45, 60, and 120 min after performing nerve block. Group differences (M-TAPA—OSTAPB) in mean changes from baseline in QoR-15 scores on POD 1 and 2 were −11.3 (95% confidence interval (CI), −24.9 to 2.4, p = 0.104; standard deviation (SD), 22.8) and −7.0 (95% CI, −20.5 to 6.6, p = 0.307; SD, 18.7), respectively. Changes in PC_levo were similar in both groups. The post hoc analysis using Bayesian statistics revealed that posterior probabilities of M-TAPA being clinically more effective than OSTAPB were up to 22.4 and 24.4% for POD 1 and 2, respectively. In conclusion, M-TAPA may not be superior to OSTAPB for TLH. Full article

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients. Full article

In this study, we not only optimized and improved the synthesis process of levobupivacaine hydrochloride (21) but also conducted a comprehensive exploration of critical industrial-scale production details, and a novel high-performance liquid chromatography (HPLC) analysis method was developed. Starting with the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) as the initial material and utilizing l-(–)-dibenzoyl tartaric acid (29) for chiral separation, and then through substitution and a salting reaction, levobupivacaine hydrochloride (21) was obtained with high purity (chemical purity of 99.90% and enantiomeric excess (ee) values of 99.30%). The total yield of the three steps was 45%. Structures of intermediates and the final product were confirmed using nuclear magnetic resonance (NMR) (¹H NMR, ¹³C NMR), mass spectrometry (MS), and elemental analysis. The crystal structure of the final product was determined through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Furthermore, we evaluated the risk of the substitution reaction using a reaction calorimeter and accelerating rate calorimetry (ARC). This process offers the advantages of simple operation, greenness, safety, controllable quality, and cost-effectiveness. It provides reliable technical support for the industrial-scale production of levobupivacaine hydrochloride (21), which is of significant importance in meeting clinical demands. Pilot-scale production has already been successfully completed by China National Medicines Guorui Pharmaceutical Co., Ltd., with a production scale of 20 kg. Full article

Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith–Wiedemann syndrome undergoing a partial glossectomy procedure in a patient with surgical indication for obstructive sleep apnea syndrome (OSAS), difficulty swallowing, feeding, and speech. On surgery day, Clonidine (4 µg/kg) was administered. Following this, a general anesthesia induction was performed by administering Sevoflurane, Fentanyl, continuous intravenous Remifentanil, and lidocaine to the vocal cords, and a rhinotracheal intubation with a size 4.5 tube was carried out. Before starting the procedure, a block of the Lingual Nerve was performed with Levobupivacaine. Analgosedation was maintained with 3% Sevoflurane in air and oxygen (FiO₂ of 40%) and Remifentanil in continuous intravenous infusion at a rate of 0.08–0.15 µg/kg/min. The surgical procedure lasted 2 h and 32 min. At the end of the surgery, the patient was under close observation during the first 72 h. In the pediatric patient with Beckwith–Wiedemann syndrome submitted to major maxillofacial surgery, the difficulty in managing the airways in the preoperative phase during intubation and in the post-operative phase during extubation should be considered. Full article

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. The levobupivacaine PCA group had the best-preserved HGS after 1 year (P = 0.022). The most significant predictor of the 5-year outcome was HGS (P = 0.03). Survival at 10 years was 85%, 92%, and 77% in the diclofenac, levobupivacaine bolus, and levobupivacaine PCA groups (ns. P = 0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival (P = 0.03). A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study—trial number NCT05829707. Full article

Various functions of polymorphonuclear neutrophils (PMNs) are related to diseases and postoperative plasma changes. The influence of some local anesthetics (LAs) on PMNs obtained by conventional isolation methods and their functions has already been demonstrated. This study investigates the effect of selected LAs on PMNs, comparing a new isolation method with conventional ones. To obtain the PMNs, we performed either gelafundin sedimentation, hypotonic lysis or density gradient centrifugation. Subsequently, PMNs were mixed with different concentrations of bupivacaine, levobupivacaine, lidocaine or ropivacaine. Live cell imaging and flow cytometry were performed to quantify the migration, ROS production, NETosis and antigen expression of PMNs. We found the inhibition of chemotaxis and ROS production by LAs. PMNs showed a strong reduction in time to half maximal NETosis in response to bupivacaine and lidocaine, but not to levobupivacaine and ropivacaine. We also found distinct differences in survival time and migration duration between the isolation methods. This suggests that the careful selection of LAs has a short-term impact on in vitro PMNs. Full article