RESUMO
The study aimed to compare the quality of perioperative analgesia, the motor block duration, and the effects on main cardiovascular parameters of dexmedetomidine (1 µg/kg/nerve block) or magnesium sulphate (2 mg/kg/nerve block) as adjuvants to 0.3% ropivacaine for sciatic and saphenous nerves block in dogs undergoing tibial plateau leveling osteotomy (TPLO). Dogs randomly received perineural dexmedetomidine-ropivacaine (D group), magnesium sulphate-ropivacaine (M group), or ropivacaine (C group). Fentanyl was administered in case of intraoperative nociception. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale (SF-GCMPS) and VAS scale. The duration of motor blockade and intra- and postoperative cardiovascular parameters were also recorded. Group M required significantly more fentanyl than D group (p = 0.04). Group M had a significantly higher SF-GCMPS score than group C at 4 (p = 0.002) and 5 h after extubation (p = 0.01), and a significantly higher VAS score than group D at 3 h after extubation (p = 0.03), and at 4 h if compared to group C (p = 0.009). No significant differences regarding the duration of motor blockade were detected between groups (p = 0.07). The heart rate was significantly lower in group D than in M and C groups intraoperatively and during the first 1.5 h post extubation. The addition of dexmedetomidine or magnesium sulphate as adjuvants to perineural ropivacaine did not improve the quality of perioperative analgesia and did not prolong the motor blockade in dogs undergoing sciatic and saphenous nerves block for TPLO surgery.
Assuntos
Dexmedetomidina , Sulfato de Magnésio , Bloqueio Nervoso , Osteotomia , Dor Pós-Operatória , Ropivacaina , Animais , Cães , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Ropivacaina/administração & dosagem , Ropivacaina/farmacologia , Sulfato de Magnésio/farmacologia , Sulfato de Magnésio/administração & dosagem , Osteotomia/veterinária , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Masculino , Feminino , Bloqueio Nervoso/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Tíbia/cirurgiaRESUMO
Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.
Assuntos
Anestésicos Locais , Dor Crônica , Lidocaína , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dor Crônica/tratamento farmacológico , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Infusões IntravenosasRESUMO
BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) is a key enzyme in the sulfation process and is associated with the development and metastasis of various tumors. This study aimed to explore the mechanism by which bupivacaine inhibits melanoma proliferation and metastasis by targeting PAPSS2. METHODS: The effects of bupivacaine on the proliferation of A375 and A2058 melanoma cells were evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labeling, and clonogenic assays. Cell migration, invasion, and PAPSS2 expression were evaluated using Transwell experiments and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. Additionally, an in vivo melanoma tumor model in nude mice was constructed to evaluate the impact of bupivacaine on melanoma growth and metastasis. Immunohistochemistry was used to assess tumor metastasis and PAPSS2 expression levels in the nude mouse model. RESULTS: Experimental results demonstrated that bupivacaine significantly inhibited melanoma proliferation and invasion compared to the control group. Notably, this inhibitory effect was partially reversed by PAPSS2 overexpression. In vivo experiments demonstrated that bupivacaine-treated nude mice exhibited reduced tumor volumes, weights, and fewer lung metastatic foci. Molecular analysis via qRT-PCR and immunohistochemistry analysis further indicated that bupivacaine significantly reduced PAPSS2 in tumor tissues. CONCLUSION: This study confirms that bupivacaine, a local anesthetic, can inhibit melanoma proliferation and metastasis by targeting the PAPSS2 signaling pathway. These findings suggest its potential as an anti-tumor medication and present new treatment strategies for melanoma.
Assuntos
Anestésicos Locais , Bupivacaína , Proliferação de Células , Melanoma , Camundongos Nus , Animais , Humanos , Proliferação de Células/efeitos dos fármacos , Melanoma/patologia , Melanoma/tratamento farmacológico , Bupivacaína/farmacologia , Camundongos , Linhagem Celular Tumoral , Anestésicos Locais/farmacologia , Metástase Neoplásica , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).
Assuntos
Analgésicos Opioides , Dexmedetomidina , Gastrectomia , Lidocaína , Dor Pós-Operatória , Remifentanil , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Analgésicos Opioides/administração & dosagem , Idoso , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Remifentanil/farmacologia , Laparoscopia , Catastrofização , Adulto , Limiar da Dor/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologiaRESUMO
BACKGROUND: Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures. METHODS: We performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups. RESULTS: All calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products. CONCLUSION: In high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.
Assuntos
Anestésicos Locais , Pressão Sanguínea , Lidocaína , Procedimentos Cirúrgicos Vasculares , Humanos , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Masculino , Feminino , Pressão Sanguínea/efeitos dos fármacos , Idoso , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Procedimentos Cirúrgicos Vasculares/métodos , Pessoa de Meia-Idade , Método Duplo-Cego , Infusões Intravenosas , Anestesia Geral/métodos , Monitorização Intraoperatória/métodosRESUMO
BACKGROUND: Previous research has shown that levobupivacaine is as effective as bupivacaine but carries a lower risk of cardiac and central nervous system toxicity. This study explores whether levobupivacaine and bupivacaine are preferable for all patients, includ-ing those with comorbidities, particularly focusing on their effects on colonic anastomosis. The primary objective is to examine the influence of levobupivacaine and bupivacaine on colonic anastomosis. Additionally, the study will assess their impact on wound healing and their anti-adhesive properties. METHODS: Conducted between July 28, 2022, to August 4, 2022, at the Hamidiye Animal Experiments Laboratory, this study was approved by the University Science Health, Hamidiye Animal Experiments Local Ethics Committee. This study was conducted using 21 male Sprague rats aged 16-20 weeks. The rats were allocated into three equal groups of seven each: Group C: pre-incisional isotonic; Group B: pre-incisional bupivacaine; and Group L: pre-incisional levobupivacaine. Macroscopic adhesion scores (MAS) were recorded during laparotomy and tissue samples were taken for histopathological examination and hydroxyproline levels measurement. Wound tensile strength along the middle incision line and anastomotic burst pressure were also assessed. RESULTS: MAS was statistically significantly lower in Groups B and L compared to Group C (p<0.001). The wound histopathology score (WHS) was significantly higher in Group L than in Group B (p=0.021). Colon histopathology scores (CHSs) were also signifi-cantly higher in Group L compared to Group C (p=0.011). CONCLUSION: TThe study found that bupivacaine and levobupivacaine did not significantly enhance wound healing, although le-vobupivacaine significantly improved WHS relative to bupivacaine. According to the findings of this study, levobupivacaine can enhance clinical practice by being used in patients undergoing colon anastomosis. It contributes significantly to the durability of colon anasto-mosis, has a more positive effect on wound healing compared to bupivacaine, and exhibits anti-adhesive properties. Additional clinical trials are necessary to validate these results further.
Assuntos
Anastomose Cirúrgica , Anestésicos Locais , Bupivacaína , Colo , Levobupivacaína , Ratos Sprague-Dawley , Cicatrização , Animais , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Masculino , Ratos , Cicatrização/efeitos dos fármacos , Colo/cirurgia , Colo/patologia , Levobupivacaína/administração & dosagem , Bupivacaína/análogos & derivados , Bupivacaína/administração & dosagem , Bupivacaína/farmacologia , Aderências Teciduais/prevenção & controleRESUMO
Since its development in 1943, lidocaine has been one of the most commonly used local anesthesia agents for surgical procedures. Lidocaine alters neuronal signal transmission by prolonging the inactivation of fast voltage-gated sodium channels in the cell membrane of neurons, which are responsible for action potential propagation. Recently, it has attracted attention due to emerging evidence suggesting its potential antitumor properties, particularly in the in vitro setting. Further, local administration of lidocaine around the tumor immediately prior to surgical removal has been shown to improve overall survival in breast cancer patients. However, the exact mechanisms driving these antitumor effects remain largely unclear. In this article, we will review the existing literature on the mechanism of lidocaine as a local anesthetic, its effects on the cancer cells and the tumor microenvironment, involved pathways, and cancer progression. Additionally, we will explore recent reports highlighting its impact on clinical outcomes in cancer patients. Taken together, there remains significant ambiguity surrounding lidocaine's functions and roles in cancer biology, particularly in perioperative setting.
Assuntos
Anestésicos Locais , Progressão da Doença , Lidocaína , Neoplasias , Humanos , Lidocaína/uso terapêutico , Lidocaína/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Anestésicos Locais/uso terapêutico , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Animais , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Extended-release (ER) local anesthetics are often incorporated in multi-modal analgesia or as an alternative when the effect of systemic analgesics may confound research. In this study, we compared the analgesic efficacy of 2 ER bupivacaine anesthetics with different ER mechanisms, a slow-release bupivacaine-meloxicam polymer (BMP) and a sucrose acetate isobutyrate bupivacaine (SABER-B) system. We used a full-thickness unilateral skin incision porcine model to evaluate the efficacy of these 2 ER bupivacaine analgesics. Eighteen male swine were randomized into 3 groups: control (saline; n = 6), bupivacaine:meloxicam (10 mg/kg, 0.3 mg/kg; n = 6), and SABER-B (10 mg/kg; n = 6). After surgery, pigs were assessed for changes in body weight, salivary cortisol level, and response to von Frey testing at 1, 3, 6, 24, 48, 72, 96, 120, and 168 h. Body weight and salivary cortisol levels were not significantly different between groups. Based on the von Frey testing, the pigs that received analgesics showed a significantly higher withdrawal threshold of nociceptive stimulus than those that received saline at 1, 3, 6, and 24 h after the surgery. At 48 h after surgery, the SABER-B group had a significantly higher withdrawal threshold than the saline group. The withdrawal threshold was not significantly different from the baseline measurement on intact skin at 3 and 6 h after surgery in the BMP group or 1 and 3 h for the SABERB group. The analgesic effects of BMP were greatest at 3 and 6 h after surgery and that of SABER-B as 1 and 3 h SABER-B provided an earlier onset of analgesia and longer analgesia duration than did BMP. This study demonstrates that ER bupivacaine can provide pigs with 24 to 48 h of analgesia for incisional pain.
Assuntos
Anestésicos Locais , Bupivacaína , Preparações de Ação Retardada , Dor Pós-Operatória , Animais , Bupivacaína/administração & dosagem , Bupivacaína/farmacologia , Masculino , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Suínos , Meloxicam/administração & dosagem , Hidrocortisona , Distribuição AleatóriaRESUMO
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.
Assuntos
Neoplasias da Mama , NF-kappa B , Humanos , Feminino , NF-kappa B/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ropivacaina/farmacologia , Ropivacaina/uso terapêutico , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
OBJECTIVE: To evaluate the difference in postoperative pain scores of dogs undergoing abdominal surgery receiving surgical incision infiltration of saline or bupivacaine liposomal injectable suspension (BLIS). ANIMALS: 40 dogs undergoing exploratory laparotomy. METHODS: Dogs were prospectively enrolled and randomized to receive either BLIS or saline surgical incision infiltration. All dogs received 5.3 mg of BLIS/kg or an equal volume of saline infiltrated in the muscle/fascia, subcutaneous tissue, and intradermal layer during closure. All dogs received a standardized postoperative pain management protocol. Pain assessment was performed at select time points postoperatively by blinded observers with an electronic algometer, short version of the Glasgow Composite Measure Pain Scale (GCMPS), and indirect measures of pain, including systolic blood pressure, heart rate, and serum cortisol levels. RESULTS: At day 0, blood pressure was higher in the saline group (149.6 vs 125.8 mm Hg; P = .006). At day 3, GCMPS was lower in the BLIS group (BLIS = 1, saline = 2, P = .027), though both average GCMPS scores were low and only 10 dogs were available for day 3 assessments (6 BLIS and 4 saline). No other differences in algometer readings, GCMPS scores, other measured parameters, or need for rescue analgesia were present between BLIS and saline groups at any time point. There was no difference in postoperative incisional infection rate or complications. CLINICAL RELEVANCE: Use of BLIS for exploratory laparotomy did not provide improved pain control over postoperative opioid administration alone. Patients that received BLIS had no increase in short-term complications.
Assuntos
Analgesia , Doenças do Cão , Dor Pós-Operatória , Ferida Cirúrgica , Animais , Cães , Analgesia/veterinária , Analgésicos Opioides , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Bupivacaína/farmacologia , Bupivacaína/uso terapêutico , Doenças do Cão/cirurgia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/veterinária , Ferida Cirúrgica/veterináriaRESUMO
There is increasing evidence, mostly from breast cancer, that use of local anaesthetics during surgery can inhibit disease recurrence by suppressing the motility of the cancer cells dependent on inherent voltage-gated sodium channels (VGSCs). Here, the possibility that lidocaine could affect cellular behaviours associated with metastasis was tested using the Dunning cell model of rat prostate cancer. Mostly, the strongly metastatic (VGSC-expressing) Mat-LyLu cells were used under both normoxic and hypoxic conditions. The weakly metastatic AT-2 cells served for comparison in some experiments. Lidocaine (1-500 µM) had no effect on cell viability or growth but suppressed Matrigel invasion dose dependently in both normoxia and hypoxia. Used as a control, tetrodotoxin produced similar effects. Exposure to hypoxia increased Nav1.7 mRNA expression but VGSCα protein level in plasma membrane was reduced. Lidocaine under both normoxia and hypoxia had no effect on Nav1.7 mRNA expression. VGSCα protein expression was suppressed by lidocaine under normoxia but no effect was seen in hypoxia. It is concluded that lidocaine can suppress prostate cancer invasiveness without effecting cellular growth or viability. Extended to the clinic, the results would suggest that use of lidocaine, and possibly other local anaesthetics, during surgery can suppress any tendency for post-operative progression of prostate cancer.
Assuntos
Neoplasias da Próstata , Canais de Sódio Disparados por Voltagem , Humanos , Masculino , Animais , Ratos , Lidocaína/farmacologia , Anestésicos Locais/farmacologia , Linhagem Celular Tumoral , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Canais de Sódio Disparados por Voltagem/genética , Membrana Celular/metabolismo , RNA Mensageiro/metabolismo , HipóxiaRESUMO
OBJECTIVE: To investigate the effect of the addition of dexmedetomidine (BLD) to retrobulbar blockade with combined lignocaine and bupivacaine on nociception. ANIMALS: A total of 17 eyes from 15 dogs. METHODS: Prospective, randomized, masked clinical comparison study. Dogs undergoing unilateral enucleation were randomly assigned into two groups; a retrobulbar administration of lignocaine and bupivacaine in a 1:2 volume ratio combined with either BLD or 0.9% saline (BLS). The total volume of the intraconal injection was calculated at 0.1 mL/cm cranial length. Intraoperative parameters were recorded: heart rate (HR), respiratory rate (RR), end-tidal CO2 (EtCO2 ) arterial blood pressure (BP), and inspired isoflurane concentration (ISOinsp). Pain scores, heart rate and RR were recorded postoperatively. RESULTS: Dogs receiving BLD (n = 8) had significantly lower intraoperative RR (p = 0.007), and significantly lower ISOinsp (p = 0.037) than dogs in the BLS group (n = 9). Postoperatively heart rate was significantly lower in the BLD group at 1 min (p = 0.025) and 1 h (p = 0.022). There were no other significant differences in intraoperative or postoperative parameters, or in postoperative pain scores (p = 0.354). Dogs receiving BLD had a higher rate of anesthetic events of bradycardia and hypertension (p = 0.027). Analgesic rescue was not needed in either group. CONCLUSIONS: The addition of BLD to retrobulbar anesthesia did not result in a detectable difference in pain scores relative to blockade with lignocaine and bupivacaine alone. Dogs receiving retrobulbar BLD had a significantly lower intraoperative RR and isoflurane requirement and an increased incidence of intraoperative bradycardia and hypertension.
Assuntos
Dexmedetomidina , Doenças do Cão , Hipertensão , Isoflurano , Cães , Animais , Bupivacaína/farmacologia , Lidocaína/farmacologia , Dexmedetomidina/farmacologia , Enucleação Ocular/veterinária , Estudos Prospectivos , Bradicardia/cirurgia , Bradicardia/veterinária , Anestésicos Locais/farmacologia , Dor Pós-Operatória/veterinária , Hipertensão/veterinária , Doenças do Cão/cirurgiaRESUMO
Breast cancer, as the most prevalent female malignancy, leads the cancer-related death in women worldwide. Local anesthetic chloroprocaine exhibits antitumor potential, but its specific functions and underlying molecular mechanisms in breast cancer remain unclear. Here, we demonstrated chloroprocaine significantly inhibited proliferation, invasion and induced apoptosis of breast cancer cells in vitro. Tumor growth and pulmonary metastasis were also suppressed in BABL/c nude mice model with chloroprocaine treatment. LINC00494 was identified as one of the most downregulated long noncoding RNAs in chloroprocaine-treated breast cancer cells by high-throughput sequencing. Futhermore, high level of LINC00494 was positively associated with poor outcome of breast cancer patients. LINC00494 acted as a "miRNAs sponge" to compete with MED19 for the biding of miR-3619-5p, led to the upregulation of MED19. LINC00494/miR-3619-5p/MED19 axis participated in chloroprocaine-mediated inhibition of proliferation, invasion and promotion of apoptosis of breast cancer cells. Consequently, our finding suggested local anesthetic chloroprocaine attenuated breast cancer aggressiveness through LINC00494-mediated signaling pathway, which detailly revealed the clinical value of chloroprocaine during breast cancer treatment.
Assuntos
Neoplasias da Mama , MicroRNAs , Procaína/análogos & derivados , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/metabolismo , Camundongos Nus , Anestésicos Locais/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Complexo Mediador/genética , Complexo Mediador/metabolismoRESUMO
OBJECTIVE: To compare motor effects and analgesic efficacy following an ultrasound-guided lateral approach to lumbar plexus blockade at L7 and sciatic nerve blockade (LPSNB) against epidural injection in dogs undergoing tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: A total of 27 healthy adult dogs undergoing unilateral TPLO surgery. METHODS: Dogs were allocated to either LPSNB (bupivacaine 2 mg kg-1, 0.75%) or epidural (morphine PF 0.1 mg kg-1 and bupivacaine 0.5 mg kg-1, 0.75%). Other aspects of clinical management were identical, including anesthetic drug protocol, area of presurgical clipping and bladder care. Time to perform the block, response to surgical stimuli, pain scores, rescue analgesia, time to stand and walk, motor score and time to first urination were recorded. One evaluator, unaware of treatment status, performed all evaluations. Student's t-test or Mann-Whitney U test was used to compare continuous variables between groups, and Fisher's exact test for categorical variables. RESULTS: Median (range) times to stand and walk were shorter for LPSNB [60 (40-120) minutes and 90 (60-150) minutes, respectively, p = 0.003] than for epidural [150 (120-240) minutes and 180 (120-360) minutes, respectively, p = 0.006]. Four dogs required rescue intraoperatively (three in epidural group, one in LPSNB group, p = 0.438). Pain scores over the 24 hour evaluation period were similar, and not significantly different, for each group. Time to spontaneous urination [LPSNB, 330 (240-360) minutes; epidural, 300 (120-1440) minutes, p = 1.0] did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: An ultrasound-guided lateral paravertebral approach to the lumbar plexus within the psoas compartment at L7, combined with sciatic nerve blockade, allows faster return to normal motor function, with similar pain control and impact on urination when compared with epidural in dogs after TPLO surgery.
Assuntos
Plexo Lombossacral , Bloqueio Nervoso , Osteotomia , Nervo Isquiático , Animais , Cães , Bloqueio Nervoso/veterinária , Bloqueio Nervoso/métodos , Nervo Isquiático/efeitos dos fármacos , Osteotomia/veterinária , Masculino , Feminino , Plexo Lombossacral/efeitos dos fármacos , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/prevenção & controle , Tíbia/cirurgia , Analgesia Epidural/veterinária , Analgesia Epidural/métodos , Estudos Prospectivos , Bupivacaína/administração & dosagem , Bupivacaína/farmacologia , Ultrassonografia de Intervenção/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologiaRESUMO
INTRODUCTION: Local anesthetics (LAs) are routinely administered in plastic and reconstructive surgery, e.g., as tumescent anesthesia adjunct in liposuction. Historically, these substances were assumed to act cytotoxically. Thus, the application of LA was avoided when handling adipose stem cells (ASCs). We recently determined that most LAs are not cytotoxic when ASCs are exposed to concentrations used for tumescent liposuction. However, there is limited information when combining LA with epinephrine and about the effects of prilocaine on ASCs. METHODS: We analyzed the effects of prilocaine or lidocaine in co-exposure with epinephrine on the viability of primary human ASCs, i.e., proliferation, metabolic activity, and cytotoxicity, using crystal violet-staining, PrestoBlue®-, and WST-1 assay. We quantified the impact of short-term incubation of lidocaine and epinephrine on the differentiation of ASCs into the adipogenic, chondrogenic, and osteogenic lineage. RESULTS: After 2 h, prilocaine (10 mM) significantly reduced metabolic activity and cell numbers, whereas lidocaine only inhibited metabolic activity. After 6 h, prilocaine (10 mM) and lidocaine significantly decreased metabolic activity as well as cell numbers. The application of high concentrations of epinephrine did not affect cell numbers but diminished metabolic activity. Combining lidocaine with epinephrine had no additional cytotoxic effect. Differentiation into the chondrogenic lineage was significantly inhibited by epinephrine. CONCLUSIONS: Deducing from our data, neither lidocaine combined with epinephrine nor prilocaine has a cytotoxic impact on ASCs in vitro at concentrations equivalent to those in tumescent anesthesia and has no long-lasting effect on the differentiation capacity of ASCs into the osteogenic and adipogenic lineage.
Assuntos
Lidocaína , Prilocaína , Humanos , Lidocaína/farmacologia , Prilocaína/farmacologia , Anestésicos Locais/farmacologia , Epinefrina/farmacologia , Anestesia Local , Diferenciação Celular , Células-TroncoRESUMO
BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30â and the group R received 30 ml of ropivacaine 0.5% at 23â. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30â accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).
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Amidas , Nervo Isquiático , Humanos , Ropivacaina/farmacologia , Amidas/farmacologia , Nervo Isquiático/diagnóstico por imagem , Anestésicos Locais/farmacologia , Ultrassonografia de IntervençãoRESUMO
During cancer surgery, the perioperative period is characterized by stress response and immunosuppression that can lead to further worsening of the disease and metastatic spread. Local anesthetics have antiproliferative, cytotoxic and antimetastatic effects on cancer cells in vitro. There is scientific evidence that local anesthetics possess anti-inflammatory effects, help to preserve normal immune function and reduce the possibility of metastatic spread. Anesthetic care affects pain, inflammation, and immunosuppression, which may have a great impact on the outcome of oncological patients. The use of local anesthetics during the perioperative period in oncological patients may have a beneficial effect on their survival and cancer recurrence. This article summarizes the effects of local anesthetics in vitro (Tab. 1, Fig. 1, Ref. 36). Keywords: local anesthetics, cancer cells.
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Anestesia , Anestésicos Locais , Humanos , Anestésicos Locais/farmacologia , Anestesia/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Dor , Tolerância ImunológicaRESUMO
INTRODUCTION: Craniotomy tumour is brain surgery that can induce a stress response. The stress response can be measured using haemodynamic parameters and plasma cortisol concentration. The stress response that occurs can affect an increase in sympathetic response, such as blood pressure and heart rate, which can lead to an increase in intracranial pressure. Scalp block can reduce the stress response to surgery and post-operative craniotomy tumour pain. The local anaesthetic drug bupivacaine 0.25% is effective in reducing post-operative pain and stress in the form of reducing plasma cortisol levels. The adjuvant addition of clonidine 2 µg/kg or dexamethasone may be beneficial. MATERIALS AND METHODS: A randomised control clinical trial was conducted at the Central Surgery Installation and Hasan Sadikin General Hospital Bandung and Dr. Mohammad Husein Hospital Palembang from December 2022 to June 2023. A total of 40 participants were divided into two groups using block randomisation. Group I receives bupivacaine 0.25% and clonidine 2 µg/kg, and group II receives bupivacaine 0.25% and dexamethasone 8 mg. The plasma cortisol levels of the patient will be assessed at (T0, T1 and T2). All the patient were intubated under general anesthaesia and received the drug for scalp block based on the group being randomised. Haemodynamic monitoring was carried out. RESULTS: There was a significant difference in administering bupivacaine 0.25% and clonidine 2µg/kg compared to administering bupivacaine 0.25% and dexamethasone 8 mg/kg as analgesia for scalp block in tumour craniotomy patients on cortisol levels at 12 hours post-operatively (T1) (p=0.048) and 24 hours post-surgery (T2) (p=0.027), while post-intubation cortisol levels (T0) found no significant difference (p=0.756). There is a significant difference in Numeric Rating Scale (NRS) at post-intubation (T0) (p=0.003), 12 hours post-operatively (T1) (p=0.002) and 24 hours post-surgery (T2) (p=0.004), There were no postprocedure scalp block side effects in both groups. CONCLUSION: The study found that scalp block with 0.25% bupivacaine and 2µg/kg clonidine is more effective in reducing NRS scores and cortisol levels compared bupivacaine 0.25% and dexamethasone 8mg in tumour craniotomy patients.
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Analgesia , Neoplasias , Bloqueio Nervoso , Humanos , Bupivacaína/farmacologia , Bupivacaína/uso terapêutico , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Clonidina/farmacologia , Clonidina/uso terapêutico , Hidrocortisona/uso terapêutico , Couro Cabeludo/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Craniotomia/efeitos adversos , Craniotomia/métodos , DexametasonaRESUMO
OBJECTIVES: A randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100,000. MATERIALS AND METHODS: Twenty patients were divided into control (CG - normotensive patients) and experimental groups (EG - hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (SO2), systolic and diastolic blood pressure (SBP and DBP), serum catecholamine concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans, and final). Blood samples were taken to measure the catecholamines, and a Holter device was used to measure data from the electrocardiogram including a 24-h postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups, and the Friedman test with the adjusted Wilcoxon posttest was used for intragroup evaluation for repeated measures. RESULTS: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES was higher for the EG during the 24-h postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystole evaluation showed that the 24-h postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups. CONCLUSIONS: Teeth extraction with LAVC can be safely executed in hypertensive patients. Blood pressure should be monitored in these patients since the sysBP presented significant differences during the surgical procedures. Cardiac arrhythmia and the serum catecholamines concentration levels seem not to be altered by the surgical procedure. Also, serum catecholamines do not influence cardiovascular changes in this type of surgery. CLINICAL RELEVANCE: LAVC can be safely used in hypertensive patients and does not increase the risk of arrhythmias or cardiac ischemia.