Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer.

BACKGROUND: Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. METHODS: The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently. RESULTS: Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells. CONCLUSION: Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

Background: Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods: A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 µg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results: The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P < 0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions: A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

Perioperative analgesic efficacy of lumbar erector spinae plane block in dogs undergoing hemilaminectomy: a randomized blinded clinical trial.

OBJECTIVE: To evaluate the perioperative analgesic effect of the unilateral lumbar erector spinae plane block (ESPBL) in dogs undergoing hemilaminectomy. STUDY DESIGN: Randomized, blinded clinical study. ANIMALS: A total of 30 client-owned dogs undergoing thoracolumbar or lumbar hemilaminectomy for intervertebral disc extrusion (IVDE). METHODS: Dogs were randomly assigned to receive a unilateral ESPBL, performed either with 0.4 mL kg-1 ropivacaine 0.5% [group ROPI (n = 15)] or with saline solution [CNT group (n = 15)]. Dogs were premedicated intravenously (IV) with acepromazine 5 µg kg-1 and methadone 0.2 mg kg-1, general anaesthesia was induced by administering IV midazolam 0.2 mg kg-1 and propofol to effect and maintained with isoflurane. Fentanyl was administered as rescue analgesia. Bradycardia [heart rate (HR) < 60 beats minute-1] with hypotension was treated with atropine IV. The Short-Form of the Glasgow Composite Pain Scale was used pre- and postoperatively at 1, 2, 4, 8, 12, 16, 20 and 24 hours after extubation, and methadone 0.2 mg kg-1 was administered IV when pain score was ≥ 5/20. HR and end-tidal concentration of isoflurane (Fe'Iso) were compared between groups with anova combined with a Dunnet's post hoc test. Time to the first rescue methadone and total dose of fentanyl (FENtot, µg kg-1 hour-1) and methadone (METtot, mg kg-1) in the first 24 postoperative hours were compared using unpaired Student's t test. Postoperative pain scores were compared with the Mann-Whitney test and atropine administration with a Fisher's exact test; p < 0.05. RESULTS: HR, Fe'Iso, FENtot, METtot and atropine administration were significantly lower in group ROPI compared to CNT. Postoperative analgesic effect was significantly longer, and pain scores were significantly lower in group ROPI for all time points. CONCLUSIONS AND CLINICAL RELEVANCE: Unilateral ESPBL with ropivacaine reduced perioperative opioid consumption and the occurrence of bradycardia in dogs undergoing hemilaminectomy.

The Role of TAP/RS Block in Minor Gynecologic Laparoscopic Surgery: A Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.

Calcium Carbonate/Polydopamine Composite Nanoplatform Based on TGF-ß Blockade for Comfortable Cancer Immunotherapy.

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO3/PDA nanoparticles (CaPNMCUR+Ropi) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNMCUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-ß) and inflammatory factor (IL-6, IL-1ß, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-ß leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.

Effectiveness of acupuncture for postoperative gastrointestinal recovery in patients undergoing thoracoscopic surgery: a prospective randomized controlled study.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications among patients who have undergone thoracic surgery. Acupuncture has long been used in traditional Chinese medicine to treat gastrointestinal diseases and has shown benefit as an alternative therapy for the management of digestive ailments. This study aimed to explore the therapeutic effectiveness of acupuncture as a means to aid postoperative recovery of gastrointestinal function in patients undergoing thoracoscopic surgery. METHODS: In total, 112 patients aged 18-70 years undergoing thoracoscopic surgery between 15 June 2022 and 30 August 2022 were randomized into two groups. Patients in the acupuncture group (AG) first received acupuncture treatment 4 h after surgery, and treatment was repeated at 24 and 48 h. Patients in the control group (CG) did not receive any acupuncture treatment. Both groups received the same anesthetic protocol. Ultrasound-guided thoracic paravertebral block (TPVB) was performed in the paravertebral spaces between T4 and T5 with administration of 20 mL of 0.33% ropivacaine. All patients received patient-controlled intravenous analgesia (PCIA) after surgery. RESULTS: Median time to first flatus [interquartile range] in the AG was significantly less than in the CG (23.25 [18.13, 29.75] vs 30.75 [24.13, 45.38] h, p < 0.001). Time to first fluid intake after surgery was significantly less in the AG, as compared with the CG (4 [3, 7] vs 6.5 [4.13, 10.75] h, p = 0.003). Static pain, measured by visual analog scale (VAS) score, was significantly different on the third day after surgery (p = 0.018). Dynamic pain VAS scores were lower in the AG versus CG on the first three postoperative days (p = 0.014, 0.003 and 0.041, respectively). CONCLUSION: Addition of acupuncture appeared to improve recovery of postoperative gastrointestinal function and alleviate posteoperative pain in patients undergoing thoracoscopic surgery. Acupuncture may represent a feasible strategy for the prevention of PGD occurrence. TRIAL REGISTRATION NUMBER: ChiCTR2200060888 (Chinese Clinical Trial Registry).

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway.

Gastric cancer currently has no effective treatment due to its high metastasis and heterogeneity. It has been reported that ropivacaine (Rop) can inhibit the growth, migration, and invasion of gastric cancer. However, the therapeutic mechanism of Rop still needs to be further explored to provide insights for its clinical application. This study aimed to explore the effects of Rop on the growth, migration, and invasion of gastric cancer cells and the underlying mechanisms. The expression levels of SNX10 were assessed in gastric cancer tissues and cell line AGS by qRT-PCR. Cell Counting Kit-8 (CCK8) assay, wound-healing assay, and transwell assay were then used to examine the effects of Rop on the AGS cell viability, migration, invasion, and proliferation, respectively. Additionally, colony formation assay was used to measure cell proliferation ability, and flow cytometry was used to detect apoptosis level. Protein levels of SNX10, SRC, and STAT3 were detected by western blot. According to the experimental results, the decreased SNX10 mRNA expression was observed in gastric cancer tissue and cell line AGS. Rop inhibited the proliferation, migration, and invasion of AGS cells, but promoted apoptosis and upregulated SNX10 expression. Moreover, Rop inhibited the expression of MMP-2 and MMP-9, phosphorylation of SRC and STAT3. SNX10 knockdown could reverse Rop-induced anticancer effects. Collectively, Rop showed a potential role in preventing proliferation and metastasis of gastric cancer. The action mechanism of Rop may be related to the upregulation of SNX10 expression and further inhibition of SRC/STAT3 signaling pathway. Our findings provide new insights into the anticancer properties of Rop.

Effects of Subcostal Anterior Quadratus Lumborum Block with and without Dexmedetomidine on Postoperative Rehabilitation in Patients Undergoing Laparoscopic Renal Surgery: A Prospective Double-Blinded Randomized Controlled Study.

Background: The combination of different anesthesia techniques or adjuvant drugs can relieve the stress response to surgery, reduce adverse reactions and improve the clinical outcome. We investigated the effects of subcostal anterior quadratus lumborum block (SQLB) with and without dexmedetomidine (DEX) on postoperative rehabilitation for laparoscopic renal surgery (LRS). Methods: We included 90 patients in this single-center study. All were scheduled for elective laparoscopic radical or partial nephrectomy under general anesthesia (GA). We randomly and evenly assigned them to three groups: Group GA (GA alone), Group QG (SQLB with 30 mL of 0.25% ropivacaine and GA), and Group DQG (SQLB with 30 mL of 0.25% ropivacaine plus 1 µg/kg DEX and GA). The primary outcomes were serum creatinine (Cr) and blood urea nitrogen (BUN) levels; the secondary outcomes included the average numeric rating scale (NRS) scores at rest and during activity within 48 h postoperatively; perioperative opioid consumption; the time to first ambulation, exhaust, and fluid intake, and postoperative adverse reactions. Results: The serum Cr and BUN levels in Group DQG decreased significantly compared with Group GA (P < 0.05). The average NRS scores in Group DQG were significantly lower than other two groups (P < 0.05). Furthermore, the indexes reduced significantly in Group QG compared with Group GA (P < 0.05). Groups DQG and QG had lower consumption of opioid compared with Group GA (P < 0.05). The recovery indicators in Groups DQG and QG were higher quality than Group GA (P < 0.05). The incidences of adverse reactions in Group DQG was significantly lower than the other groups (P < 0.05). Conclusion: SQLB with and without DEX could attenuate postoperative pain, reduce opioids requirement and side effects, as well as facilitate postoperative early rehabilitation. More interesting, SQLB with DEX could confer kidney protection. Clinical Trial Registration Number: The Chinese Clinical Trial Registry (ChiCTR2200061554).

Efficacy and safety of stellate ganglion block with different volumes of ropivacaine to improve sleep quality in patients with insomnia: a comparative study.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasound-guided stellate ganglion block (SGB) with different volumes of 0.375% ropivacaine on sleep quality in patients with insomnia. PATIENTS AND METHODS: A total of 80 patients who were selected to undergo SGB for the treatment of insomnia were enrolled. The patients were divided into saline control group, and low-volume (4 mL), medium-volume (6 mL), and high-volume (8 mL) ropivacaine injection groups according to the random table method. The treatment included 7 blocks with once every three days. The left and right stellate ganglions are alternately blocked. The onset and maintenance time of Horner syndrome, the degree of carotid artery dilation and blood flow velocity before and 20 minutes after the first block, the occurrence of complications such as drug crossing of the midline of the artery and hoarse throat were recorded, and the improvement of sleep disorders was evaluated with the Pittsburgh Sleep Quality Index Scale. RESULTS: Horner syndrome occurred in 100% of all volumes of ropivacaine block. The ipsilateral internal carotid artery was dilated and was accompanied by increased blood flow. The degree of dilation and increase in blood flow were not affected by the volumes of drug injection. There were no serious complications in any group, but the incidences of hoarseness and dysphagia were higher in the medium- and high-volume groups than those in the low-volume group (all p < 0.05). Compared with the low- and medium-volume groups, the high-volume group had a faster onset of action, longer maintenance time, and the highest chance of the drug crossing the artery (all p < 0.05). Compared to those before the pre-block and in the control groups, insomnia was improved in all volume groups after the block with nonsignificant intergroup differences. CONCLUSIONS: 4 mL of 0.375% ropivacaine for ultrasound-guided SGB is sufficient to improve the sleep quality of insomnia patients, whose overall risk is lower than block with 6 mL or 8 mL of ropivacaine.

The Median Effective Volume of 0.375% Ropivacaine for Ultrasound-guided Anterior Suprascapular Nerve Block in Arthroscopic Shoulder Surgery.

BACKGROUND: The suprascapular nerve (SSN) is an important nerve that contributes to shoulder joint sensation and movement. The anterior suprascapular nerve block (aSSNB) has the potential for noninferior analgesic effect compared with the interscalene block while preserving respiratory function. This study investigated the median effective volume (MEV) of 0.375% ropivacaine in aSSNB for analgesic effect among patients undergoing arthroscopic shoulder surgery. OBJECTIVES: Our primary objective was the MEV. The secondary objectives included the 24 hour sufentanil consumption, 24 hour patient-controlled analgesia (PCA) presses, and incidences of diaphragm impairment. STUDY DESIGN: Prospective registered (ChiCTR2300070129), single-armed, volume-finding study. SETTING: This study was conducted in a tertiary, single center. METHODS: There were 23 patients who completed the study. Using an up-and-down process, patients enrolled in the study received different volumes of 0.375% ropivacaine for an aSSNB adjusted based on the success or failure of the previous patient in the study's block by increasing or decreasing the volume by 3 mL. The first patient received 15 mL of 0.375% ropivacaine. The nerve blocks were evaluated by the sensory score of the C5 and C6 dermatomes. RESULTS: MEV50 (50% of the patients) was 6 mL (95% CI, 5.78 - 6.78 mL), and MEV95 (95% of the patients) was 13.88 mL (95% CI, 13.37 - 14.87 mL). There was no significant difference in the PCA presses, 24 hour sufentanil consumption, and incidences of diaphragm impairments between successful and unsuccessful blocks. LIMITATIONS: Our study focused on the analgesic effect rather than hemi-diaphragmatic paralysis with 0.375% ropivacaine for an aSSNB. The study also did not test varying ropivacaine concentrations while keeping the volume constant. Further investigation with varying concentrations and a larger sample size is indicated to address the optimal volume and concentration to balance analgesia and diaphragm function. CONCLUSIONS: To produce effective analgesic effect, the MEV50 is 6 mL, and the MEV95 is 13.88 mL in patients undergoing arthroscopic shoulder surgery who receive an aSSNB using 0.375% ropivacaine for analgesia.

Nanocrystals Slow-Releasing Ropivacaine and Doxorubicin to Synergistically Suppress Tumor Recurrence and Relieve Postoperative Pain.

Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to be two big problems associated with this treatment. To resolve these problems, a nanocrystal composite slow-releasing ropivacaine and doxorubicin was fabricated in this study. Briefly, a self-assembling peptide was used to form nanoparticle complexes with the two drugs, based on which homogeneous nanocrystals were obtained by adjusting the pH. In cultured human melanoma cells, the nanocrystals exhibited improved antitumor activity due to a synergistic effect and enhanced cellular uptake of the two drugs. On the other hand, the nanocrystals could slowly release ropivacaine in vitro and in vivo, generating long-acting analgesia on the rat sciatic nerve block model and incisional pain model. On a nude mouse tumor resection model, the nanocrystals simultaneously suppressed the recurrence of solid tumor and relieved postoperative pain, indicating a potential postoperative treatment for tumor resection patients. This nanocrystal system also suggested a promising and facile strategy for developing multifunctional formulations combining different drugs, which could achieve better therapeutic outcomes in a synergistic and sustained manner.

The 90% minimum effective volume of 0.5 ropivacaine for ultrasound-guided supraclavicular brachial plexus block : A biased coin up-and-down design.

BACKGROUND: Ultrasound-guided supraclavicular brachial plexus block is widely used in upper limb surgery; however, it requires a higher dose (20-30 mL) of local anesthetic. In this study, we aimed to determine the 90% minimum effective volume for ultrasound-guided supraclavicular brachial plexus block. METHODS: All patients received an ultrasound-guided two-point injection of 0.5% ropivacaine at a starting volume of 0.18 mL/mm2 cross-sectional nerve area. In cases of a successful block, the next patient had the same volume with a probability of 0.89, and the volume was reduced by 0.04 mL/mm2 cross-sectional nerve area with a probability of 0.11. When the block failed, the dose was increased by 0.04 mL/mm2 cross-sectional nerve area. After 45 cases of successful blocks, the 90% minimum effective volume of local anesthetic was calculated using the centered isotonic regression function. RESULTS: Centered isotonic regression analysis resulted in a 90% minimum effective volume and a 95% confidence interval of 0.189 mL/mm2 and 0.176-0.225 mL/mm2 for the supraclavicular brachial plexus block. CONCLUSION: A good blocking effect can be achieved with 0.189 mL/mm2 of 0.5% ropivacaine with more precise dosing, thereby reducing the risk of local anesthetic poisoning.

Intraperitoneal and incisional ropivacaine did not improve postoperative analgesia after multimodal anaesthesia compared with saline in dogs undergoing ovariohysterectomy.

INTRODUCTION: Intraperitoneal administration of local anaesthetics may reduce postoperative pain after ovariohysterectomy in dogs. The aim of this prospective, randomised, blinded, placebo-controlled clinical trial was to compare postoperative analgesia and opioid requirements after intraperitoneal and incisional administration of ropivacaine versus 0,9 % NaCl (saline). Forty-three client-owned dogs were enrolled in the study and anaesthetised using a standardized protocol that included premedication with acepromazine (0,03-0,05 mg/kg) and dexmedetomidine (0,01 mg/kg) intramuscularly. Anaesthesia was induced with propofol titrated to effect and ketamine (1 mg/kg) intravenously and maintained with isoflurane in oxygen. The analgesic regimen included carprofen (4 mg/kg) subcutaneously and morphine (0,2 mg/kg) intravenously. Depending on group assignment, each dog received either an intraperitoneal and incisional splash with ropivacaine (2 mg/kg and 1 mg/kg, respectively) (group R), or an equal volume of saline (group S). Buprenorphine (0,02 mg/kg) was administered intramuscularly once the uterus was removed. Sedation and pain were assessed 0,5, 1, 2, 4, 6 and 8 hours after extubation using a sedation scale, the short form of the Glasgow Composite Pain Scale (CMPS-SF) and a dynamic interactive visual analogue scale (DIVAS). Postoperatively, buprenorphine (0,01 mg/kg) was administered intravenously if dogs scored 6/24 on CMPS-SF. The ordinal mixed model showed no difference in pain scores between groups. Fisher's exact test showed no significant difference in postoperative buprenorphine requirements between group S (3/22 dogs) and group R (1/21 dogs) at the doses used. In addition, lower sedation scores were associated with higher DIVAS scores. In this multimodal analgesic protocol, ropivacaine could not improve analgesia compared to saline.

INTRODUCTION: L'administration intrapéritonéale d'anesthésiques locaux peut réduire la douleur postopératoire après une ovariohystérectomie chez la chienne. L'objectif de cet essai clinique prospectif, randomisé, en aveugle et contrôlé par placebo était de comparer l'analgésie postopératoire et les besoins en opioïdes après l'administration intrapéritonéale et incisionnelle de ropivacaïne par rapport à du NaCl 0,9 % (sérum physiologique). Quarante-trois chiennes appartenant à des clients ont été enrôlés dans l'étude et anesthésiés selon un protocole standardisé comprenant une prémédication par acépromazine (0,03 - 0,05 mg/kg) et dexmedetomidine (0,01 mg/kg) par voie intramusculaire. L'anesthésie a été induite avec du propofol dosé à l'effet et de la kétamine (1 mg/kg) par voie intraveineuse et maintenue avec de l'isoflurane dans de l'oxygène. Le traitement analgésique comprenait du carprofène (4 mg/kg) par voie sous-cutanée et de la morphine (0,2 mg/kg) par voie intraveineuse. En fonction de son affectation à un groupe, chaque chien a reçu soit une injection intrapéritonéale et incisionnelle de ropivacaïne (2 mg/kg et 1 mg/kg, respectivement) (groupe R), soit un volume égal de solution saline (groupe S). La buprénorphine (0,02 mg/kg) a été administrée par voie intramusculaire après l'ablation de l'utérus. La sédation et la douleur ont été évaluées 0,5, 1, 2, 4, 6 et 8 heures après l'extubation à l'aide d'une échelle de sédation, de la forme courte de l'échelle composite de douleur de Glasgow (CMPS-SF) et d'une échelle visuelle analogique interactive dynamique (DIVAS). En postopératoire, de la buprénorphine (0,01 mg/kg) a été administrée par voie intraveineuse si les chiens obtenaient un score de 6/24 sur l'échelle CMPS-SF. Le modèle mixte ordinal n'a montré aucune différence dans les scores de douleur entre les groupes. Le test exact de Fisher n'a pas montré de différence significative dans les besoins postopératoires en buprénorphine entre le groupe S (3/22 chiens) et le groupe R (1/21 chiens) aux doses utilisées. De plus, des scores de sédation plus faibles étaient associés à des scores DIVAS plus élevés. Dans ce protocole d'analgésie multimodale, la ropivacaïne n'a pas permis d'améliorer l'analgésie par rapport au sérum physiologique.

Serum lidocaine (lignocaine) concentrations during prolonged perioperative infusion in patients undergoing breast cancer surgery: A secondary analysis of a randomised controlled trial.

Perioperative lidocaine (lignocaine) infusions are being employed with increasing frequency. The determinants of systemic lidocaine concentrations during prolonged administration are unclear. In the Long-term Outcomes after Lidocaine Infusions for PostOperative Pain (LOLIPOP) pilot trial, the impact of infusion duration and body size metrics on serum lidocaine concentrations was examined with regression models in 48 women undergoing breast cancer surgery. Lidocaine was delivered as an intravenous bolus (1.5 mg/kg) and infusion (2 mg/kg per h) intraoperatively, followed by a 12-h subcutaneous infusion (1.33 mg/kg per h) postoperatively. Dosing was based on total body weight. Wound infiltration with other long-acting local anaesthetics was permitted. Protein binding and pharmacogenomic data were also collected. Lidocaine concentrations (median (interquartile range) (range)) during prolonged administration were in the safe and potentially therapeutic range: post-anaesthesia care unit 2.16 (1.73-2.82) (1.12-6.06) µg/ml; ward 1.41 (1.22-1.75) (0.64-2.81) µg/ml. Concentrations increased non-linearly during the early intravenous phase of administration (mean rise 1.21 µg/ml per hour of infusion, P = 0.007) but reached a pseudo steady-state during the later subcutaneous phase. Higher dose rates received per kilogram of lean (P = 0.004), adjusted (P = 0.006) and ideal body weight (P = 0.009) were associated with higher steady-state concentrations. The lidocaine free fraction was unaffected by the presence of ropivacaine, and phenotypes linked to slow metabolism were infrequent. Serum lidocaine concentrations reached a pseudo steady-state during a 12-h postoperative infusion. Greater precision in steady-state concentrations can be achieved by dosing on lean body weight versus adjusted or ideal body weight (equivalent lean body weight doses: intravenous bolus 2.5 mg/kg; intravenous infusion 3.33 mg/kg per h; subcutaneous infusion 2.22 mg/kg per h.

A Comparative Analysis of Pain Control Methods after Ankle Fracture Surgery with a Peripheral Nerve Block: A Single-Center Randomized Controlled Prospective Study.

Background and Objectives: Patients experience severe pain after surgical correction of ankle fractures. Although their exact mechanism is unknown, dexamethasone and epinephrine increase the analgesic effect of anesthetics in peripheral nerve blocks. This study aimed to compare the postoperative pain control efficacy of peripheral nerve blocks with ropivacaine combined with dexamethasone/epinephrine and peripheral nerve blocks with only ropivacaine and added patient-controlled analgesia in patients with ankle fractures. Materials and Methods: This randomized, controlled prospective study included patients aged 18-70 years surgically treated for ankle fractures between December 2021 and September 2022. The patients were divided into group A (n = 30), wherein pain was controlled using patient-controlled analgesia after lower extremity peripheral nerve block, and group B (n = 30), wherein dexamethasone/epinephrine was combined with the anesthetic solution during peripheral nerve block. In both groups, ropivacaine was used as the anesthetic solution for peripheral nerve block, and this peripheral nerve block was performed just before ankle surgery for the purpose of anesthesia for surgery. Pain (visual analog scale), patient satisfaction, and side effects were assessed and compared between the two groups. Results: The patients' demographic data were similar between groups. Pain scores were significantly lower in group B than in group A postoperatively. Satisfaction scores were significantly higher in group B (p = 0.003). There were no anesthesia-related complications in either group. Conclusions: Dexamethasone and epinephrine as adjuvant anesthetic solutions can effectively control pain when performing surgery using peripheral nerve blocks for patients with ankle fractures.

Comparing postoperative analgesia of bilateral serratus anterior plane block and thoracic paravertebral block for children following the Nuss procedure: protocol for a randomised, double-blind, non-inferiority clinical trial.

INTRODUCTION: The Nuss procedure, despite being a minimally invasive surgery, is regarded as one of the most painful surgical procedures in children, and postoperative pain control remains a major clinical issue in this population. Thoracic paravertebral nerve block (TPVB) is reported as excellent pain relief for the Nuss procedure despite its challenging performance and associated adverse effects. Serratus anterior plane block (SAPB) is a simplified and effective method for managing thoracic pain as an alternative to TPVB. However, whether SAPB can provide analgesia comparable with that provided by the TPVB approach in children undergoing the Nuss procedure is unknown. METHODS AND ANALYSIS: This will be a prospective, randomised, double-blind, single-centre, non-inferiority trial that will enrol children aged 7-16 years subjected to the Nuss operation for pectus excavatum. In total, 74 paediatric patients will be randomly assigned to either the SAPB or TPVB group after general anaesthesia to receive ultrasound-guided regional nerve blocks (0.25% ropivacaine 2.5 mg/kg). The primary outcome will be the assessment of postoperative pain intensity at predetermined time points. The secondary outcomes will include assessing intraoperative opioid intake, consumption of analgesics within 24 hours postoperatively, time of first use of rescue analgesics, extubation time, perioperative adverse events and plasma ropivacaine concentrations across the block groups. Demographic and clinical characteristics (eg, pectus severity and the number of bars used) of the patients will be recorded. All data will be collected by investigators who are blinded to the treatment. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee on Biomedical Research of the West China Hospital of Sichuan University (2021-1275). During the period of the study, all procedures will be conducted following the principles of the Declaration of Helsinki. The results of the trial will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ChiCTR2200056596.

Opioid-Free Versus Opioid-Based Anesthesia on Postoperative Pain After Thoracoscopic Surgery: The Use of Intravenous and Epidural Esketamine.

BACKGROUND: The effectiveness and safety of opioid-free anesthesia (OFA) regimens in distinct types of surgeries remain controversial. In this study, we investigated whether OFA could reduce the occurrence of chronic postoperative pain in patients receiving video-assisted thoracoscopic surgery (VATS). METHODS: We conducted a 2-center, randomized, controlled trial from September 2021 to January 2022. A total of 162 lung tumor patients scheduled to undergo VATS were randomly divided into an opioid-based anesthesia (OA) group and an OFA group. The OA group received general anesthesia combined with thoracic epidural block using morphine, while the OFA group received general anesthesia combined with thoracic epidural block using esketamine. Patient-controlled epidural analgesia (PCEA) was used after surgery (ropivacaine and morphine for the OA group versus ropivacaine and esketamine for the OFA group). The primary end point was chronic pain rates at 3 months after VATS, which were analyzed using a logistic regression model. The secondary end points were chronic pain rates at 6 months, acute pain rates at 24 hours and 48 hours postoperatively, postoperative side effects, and perioperative variables. RESULTS: The final analysis included 159 patients. Acute postoperative pain at 24 hours occurred in 0 of the 79 (0%) patients in the OA group and 10 of the 80 (17.5%) patients in the OFA group (odds ratio, 52.14; 95% confidence interval [CI], 6.47-420.10; P < .001). Acute postoperative pain at 48 hours occurred in 3 of the 79 (3.8%) patients in the OA group and 2 of the 80 (2.5%) patients in the OFA group (odds ratio, 2.07; 95% CI, 0.99-4.32; P = .053). In this study, none of the patients had moderate or severe pain in either group at 3 and 6 months postsurgically. Mild chronic postoperative pain at 3 months occurred in 27 of the 79 (34.2%) patients in the OA group and 14 of the 80 (17.5%) patients in the OFA group (odds ratio, 3.52; 95% CI, 1.49-8.31; P = .004). At 6 months, mild chronic pain still occurred in 23 of the 79 (29.1%) patients in the OA group and 9 of the 80 (11.3%) patients in the OFA group (odds ratio, 5.55; 95% CI, 2.01-15.33; P = .001). In addition, the OFA group included fewer patients with side effects, including nausea, vomiting, and pruritus, within 48 hours after surgery. CONCLUSIONS: Replacement of opioids by esketamine, intraoperatively as intravenous injection and epidural infusion and postoperatively as epidural infusion, reduces the incidence of mild chronic postoperative pain and side effects in patients after VATS.

Ropivacaine-Epinephrine-Clonidine-Ketorolac Cocktail as a Local Anesthetic for Lumbar Decompression Surgery: A Single Institutional Experience.

OBJECTIVE: The goal of this study is to discuss our initial experience with a multimodal opioid-sparing cocktail containing ropivacaine, epinephrine, clonidine, and ketorolac (RECK) in the postoperative management of lumbar decompression surgeries. METHODS: Patients were either administered no local anesthetic at the incision site or were administered a weight-based amount of RECK into the paraspinal musculature and subdermal space surrounding the operative site once the fascia was closed. We performed a retrospective chart review of all patients 18 years of age or older undergoing lumbar laminectomy and lumbar diskectomy surgeries between December 2019 and April 2021. Outcomes including total opioid use, measured as morphine milligram equivalent, length of stay, and postoperative visual analog scores for pain, were collected. Relationships between variables were analyzed with Student's t-test, chi-square tests, and Fisher exact tests. RESULTS: A total of 121 patients undergoing 52 lumbar laminectomy and 69 lumbar diskectomy surgeries were identified. For lumbar laminectomy, patients who were administered RECK had decreased opioid use in the postoperative period (11.47 ± 12.32 vs. 78.51 ± 106.10 morphine milligram equivalents, P = 0.019). For patients undergoing lumbar diskectomies, RECK administration led to a shorter length of stay (0.17 ± 0.51 vs. 0.79 ± 1.45 days, P = 0.019) and a lower 2-hour postoperative pain score (3.69 ± 2.56 vs. 5.41 ± 2.28, P = 0.006). CONCLUSIONS: The RECK cocktail has potential to be an effective therapeutic option for the postoperative management of lumbar decompression surgeries.

Intravenous Versus Perineural Dexamethasone for Reducing Rebound Pain After Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair. METHODS: Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0-10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance. RESULTS: A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, P = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2-23.1] hours) than the intravenous group (15.1 [13.7-15.9] hours, P < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, P = 0.028; sleep disturbance: 55.6% vs. 25.7%, P = 0.011). The duration and intensity of rebound pain were similar between the two groups. CONCLUSION: Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006795.

Periarticular injection in addition to interscalene nerve block can decrease opioid consumption and pain following total shoulder arthroplasty: a comparison cohort study.

BACKGROUND: Interscalene nerve block (INB) is an effective technique to provide postoperative analgesia for total shoulder arthroplasty (TSA). However, the analgesic effects of the block typically resolve between 8 and 24 hours postadministration, which results in rebound pain and subsequent increased opioid use. The objective of this study was to address this issue by determining how adding an intraoperative periarticular injection (PAI) in combination with INB affects acute postoperative opioid consumption and pain scores in patients undergoing TSA. We hypothesized that compared with INB alone, INB + PAI will significantly reduce opioid consumption and pain scores for the first 24 hours postsurgery. METHODS: We reviewed 130 consecutive patients who underwent elective primary TSA at a single tertiary institution. The first 65 patients were treated with INB alone, followed by 65 patients treated with INB + PAI. The INB used was 15-20 mL of 0.5% ropivacaine. The PAI used was 50 mL of a combination of ropivacaine (123 mg), epinephrine (0.25 mg), clonidine (40 µg), and ketorolac (15 mg). The PAI was injected using a standardized protocol: 10 mL into the subcutaneous tissues prior to incision, 15 mL into the supraspinatus fossa, 15 mL at the base of the coracoid process, and 10 mL into the deltoid and pectoralis muscles-a protocol analogous with a previously described technique. For all patients, a standardized postoperative oral pain medication protocol was used. The primary outcome was acute postoperative opioid consumption represented by morphine equivalent units (MEUs), whereas the secondary outcome was visual analog scale (VAS) pain scores over the first 24 hours postsurgery, operative time, length of stay, and acute perioperative complications. RESULTS: No significant differences in demographics existed between patients who received INB alone vs. INB + PAI. Patients who received INB + PAI had a significantly lower 24-hour postoperative opioid consumption compared to the INB alone group (38.6 ± 30.5 MEU vs. 60.5 ± 37.3 MEU, P < .001). Additionally, VAS pain scores for the first 24 hours postsurgery in the INB + PAI group were significantly lower compared to those for the INB alone group (2.9 ± 1.5 vs. 4.3 ± 1.6, P ≤ .001). No differences existed between groups regarding operative time, length of inpatient stay, and acute perioperative complications. CONCLUSION: Patients undergoing TSA with INB + PAI demonstrated significantly decreased 24-hour postoperative total opioid consumption and 24-hour postoperative pain scores compared to the group treated with INB alone. No increase in acute perioperative complications related to PAI was observed. Thus, compared to an INB, the addition of an intraoperative periarticular cocktail injection appears to be a safe and effective method to reduce acute postoperative pain following TSA.