UNASSIGNED: There is no consensus on the appropriate use of mixtures of local anaesthetic drugs in various combinations for nerve blocks. We intended to compare short-acting lignocaine and long-acting ropivacaine as a mixture versus undiluted sequential injections on block characteristics of ultrasound-guided (USG) supraclavicular brachial plexus block for upper limb surgeries.
UNASSIGNED: A double-blinded randomised study was conducted on 64 adult patients scheduled for upper limb surgery who received 15 mL each of 2% lignocaine with adrenaline and 0.75% ropivacaine as a 1:1 mixture in the mixed group (Group M) or sequential injections in the sequential group (Group S) by using a USG technique. The primary outcome was the percentage of participants with complete four nerve sensory blocks at 10 minutes post block injection. Secondary outcomes were sensory and motor block characteristics till 30 minutes, total duration of analgesia, sensory and motor block, and complications.
UNASSIGNED: Demographic characteristics and time taken for the procedure were similar. The percentage of participants with a complete four-nerve sensory block at 10 minutes was higher in Group S (69%) versus Group M (41%) (P = 0.04). Complete sensory and motor block rates were similar at 30 minutes. The block procedure time, total duration of analgesia, and sensory and motor block were similar in both groups. There were no major complications.
UNASSIGNED: Sequential lignocaine-ropivacaine, compared to the mixed injection technique, has a higher initial rate of sensory and motor block onset with a similar total block duration.

Local anaesthetics (LAs) can have detrimental effects on rat, bovine, canine, and human tendon tissues and cells. Currently, there has been no available data on the impact of these drugs on equine tenocytes. Even if LA injection for managing painful tendon conditions in horses is limited, it is usually used via intra-articular, intrasynovial, perineural, and intrathecal as well as for lameness examinations. In this in vitro study, the cytotoxic effects of LAs, including lidocaine, mepivacaine, and bupivacaine on equine tenocytes, in the presence and absence of platelet rich plasma (PRP), were investigated. PRP accelerates tissue healing and can exert cytoprotective effects on different cell types exposed to different stressful conditions, including drugs. Results indicated that the exposure to LAs significantly reduced tenocytes viability in dose- and time-dependent manners while PRP was able to counteract their cytotoxic effects. Furthermore, microscopy and flow cytometry analyses revealed apoptosis and necrosis in equine tenocytes exposed to these drugs, that were both reduced when PRP was in the medium. These findings highlight the importance of considering the tenocyte toxicity associated with intrathecal and intraneural LA injections, as they might affect tenocytes or reduce the efficacy of associated therapies. Moreover, this study also highlights the protective effects of PRP, which could make LA injections safer.

UNASSIGNED: Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications.
UNASSIGNED: A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture in vitro, in vivo, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies.
UNASSIGNED: Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. In vitro studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of in vitro studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported.
UNASSIGNED: Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together.
UNASSIGNED: Open Science Framework (OSF, project link: https://osf.io/r2u4z).

BACKGROUND: Failed spinal anaesthesia causes prolonging of operation time, insufficient analgesia for surgery and needs repeating spinal anaesthesia which in turn causes local anaesthesia toxicity, high spinal and total spinal, and conversion to general anaesthesia. However, the problem remains unexplored in Amhara regional state comprehensive specialized hospitals.
OBJECTIVE: To determine incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery in selected Amhara National Regional State comprehensive specialized hospitals, Northwest Ethiopia, 2023.
METHODS: Multi-center prospective observational study was conducted. Data was collected using questionnaire and checklist. All consecutive scheduled emergency and elective patients were included in the study. Data was transformed from Epi data to SPSS and logistic regression analysis was done. Both crude and adjusted odds ratio were used to assess the strength of association. Variables with a p-value of less than 0.05 were considered as statistically significant.
RESULTS: A total of 532 patients were included in this study with a response rate of 98%. Incidence of failed spinal anaesthesia was 22.4% (CI = 19-25.9). Emergency surgery (AOR = 7.01, CI = 4.5-12.7), dose of bupivacaine of ≤ 10 mg (AOR = 3.02, CI = 1.3-10.2), work experience of anaesthetist < 2 years (AOR = 3.1, CI = 1.7-5.72), bloody CSF (AOR = 8.5, CI = 2.53-18.5), hyperbaric local anaesthetic drug (AOR = 3.3, 95% CI = 3.2-8.2) and local anaesthetist without adjuvants (AOR = 5.25, CI = 2.62-14.2) were associated failed spinal anaesthesia.
CONCLUSIONS: The incidence of failed spinal anaesthesia was high in Amhara Region comprehensive specialized hospitals. We suggest that anaesthesia providers should minimize failure by using adjuvants and appropriate dose of local anaesthetic. Additionally, simulation training should be given for anaesthesia trainees to improve their skills and to produce competent professionals.

Neuronal electrochemical signals involve the flux of sodium ions through voltage-gated sodium channels (NaV) located in the neurolemma. Of the nine sodium channel subtypes, NaV-1.7, 1.8, and 1.9 are predominantly located on nociceptors, making them prime targets to control pain. This review highlights some of the latest discoveries targeting NaV channel activity, including: (1) charged local anaesthetic derivatives; (2) NaV channel toxins and associated small peptide blockers; (3) regulation of NaV channel accessory proteins; and (4) genetic manipulation of NaV channel function. While the translation of preclinical findings to a viable treatment in humans has remained a challenge, a greater understanding of NaV channel physiology could lead to the development of a new stream of therapies aimed at alleviating chronic pain.

UNASSIGNED: The use of local anaesthetics (LAs) is usually associated with few adverse effects, but local anaesthetic systemic toxicity (LAST) can result in serious harm and even death. However, practitioner awareness regarding this risk has been little studied.
UNASSIGNED: This was a closed, web-based study carried out at two Swiss university hospitals using a fully automated questionnaire. The main objective was to evaluate LAST awareness and LA use among various medical practitioners. The secondary objective was to determine whether these physicians felt that a tool designed to compute maximum safe LA doses should be developed.
UNASSIGNED: The overall participation rate was 40.2 % and was higher among anaesthesiologists (154/249, 61.8 % vs 159/530, 30.0 %; P < .001). Anaesthesiologists identified the risk of LAST and the systems involved more frequently than non-anaesthesiologists (85.1 % vs 43.4 %, P < .001). After adjusting for years of clinical experience, age, country of diploma, frequency of LA use, clinical position and being an anaesthesiologist, the only significant associations were this latter factor (P < .001) and clinical position (P = .016 for fellows and P = .046 for consultants, respectively). Most respondents supported the development of a tool designed to compute maximum safe LA doses (251/313, 80.2 %) and particularly of a mobile app (190/251, 75.7 %).
UNASSIGNED: LAST awareness is limited among practitioners who use LAs on a regular basis. Educational interventions should be created, and tools designed to help calculate maximum safe LA doses developed. The actual frequency of unsafe LA doses administration would also deserve further study.

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OBJECTIVE: This study was conducted to explore the preference and experience of paediatric dentists based in Switzerland regarding the use of articaine and other local and topical anaesthesia.
METHODS: An 18-question survey was developed, piloted, and distributed to the members of the Swiss association of paediatric dentistry (n = 460). The following information were collected: most used local anaesthetic in different age groups, time needed to inject a full ampule, frequency of observed local and systemic side effects, application of topical anaesthetic prior to injection, time waited between application and the injection, and perceived effectiveness of topical anaesthetic. The dentists\' responses were analysed with logistic regressions reporting odds ratios (OR) and 95% confidence intervals (CI) at 5%.
RESULTS: The response rate was 37% (n = 168) out of the 460 questionnaires sent, with the responders being predominantly female (67%) and 47-year-old on average. More than 80% of the dentists used articaine in all age groups. 45% of responders took longer than 60 s to inject a full ampule. Local and systemic side-effects were observed by 82% and 28% of respondents respectively, although the nature and the significance of those were not detailed due to the anonymous nature of the questionnaire. Significantly less local adverse effects were seen for older children (p = 0.04) and among dentists with more years of experience (p = 0.01). Most responders applied topical anaesthetic and half of them waited longer than 60 s before injection.
CONCLUSIONS: Articaine is a widely used local anaesthetic by the studied group of Swiss paediatric dentists regardless of patient\'s age. The use of topical anaesthetic before injection is a common practice with good perceived effectiveness.

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster® and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.

OBJECTIVE: We aimed to compare the efficacy of intra-operative lidocaine hematoma block (HB) to ropivacaine HB and to compare the efficacy of different timings of ropivacaine HB in controlling post-operative pain in dogs undergoing the osteosynthesis of long-bone fractures.
METHODS: We conducted a randomized, blinded, prospective clinical study.
METHODS: Forty-eight dogs with long-bone fractures were included and were randomly allocated to four groups: lidocaine (L), ropivacaine (Rmid), ropivacaine pre- (Rpre) and ropivacaine post- (Rpost) groups.
METHODS: The dogs in group L (n = 14) and in group Rmid (n = 11) received a lidocaine or ropivacaine HB, respectively, after fracture reduction and before osteosynthesis material placement. Rpre dogs (n = 11) received ropivacaine HB before fracture reduction, and Rpost dogs (n = 12) received ropivacaine HB after osteosynthesis material placement. Eight post-operative pain assessments were performed using the University of Melbourne Pain Scale (UMPS) and an algometer. Rescue analgesia was administered based on UMPS scoring. For data analysis, the Shapiro-Wilk test of normality, chi-square, Student t test and Split Plot analysis were used. The level of significance was set at α = 0.05.
RESULTS: Rescue analgesia was administered to one dog in group L, one in group Rmid and one in group Rpost, with no significant differences detected. Compared to group Rmid, group L dogs exhibited significantly higher mean mechanical pain thresholds (p = 0.049) and lower mean UMPS scores (p = 0.001). Group Rpost dogs had statistically significantly higher mean pain thresholds compared to group Rmid (p = 0.009).
CONCLUSIONS: When performed after fracture reduction and before osteosynthesis material placement, lidocaine HB seems to be more effective than ropivacaine HB in controlling post-operative pain in dogs undergoing osteosynthesis of long-bone fractures. The administration of ropivacaine HB after osteosynthesis material placement seems to be more effective than administration after fracture reduction and before osteosynthesis material placement or administration before fracture reduction in controlling post-operative pain in dogs undergoing osteosynthesis of long-bone fractures.