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).

Spinal anaesthesia is an established and frequently used anaesthetic technique in adults. However, this versatile regional anaesthetic technique is less frequently used in paediatric anaesthesia even though it can be used for minor (e.g. inguinal hernia repair) and major (e.g. cardiac surgery) surgical procedures. The aim of this narrative review was to summarize the current literature with regard to technical aspects, surgical context, choice of drugs, potential complications, as well as the effects of the neuroendocrine surgical stress response and potential long-term effects of anaesthesia during infancy. In summary, spinal anaesthesia represents a valid alternative in the paediatric anaesthesia setting also.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

Pain following brain surgery can compromise the result of surgery. Several pharmacological interventions have been used to prevent postoperative pain in adults undergoing brain surgery. Pain following craniotomy is considered to be moderate to severe during the first two post-operative days. Opioids have been historically the mainstay and are the current prominent strategy for pain treatment. They produce analgesia, but may alter respiratory, cardiovascular, gastrointestinal and neuroendocrine functions. All these side effects may affect the normal postoperative course of craniotomy, by affecting neurological function and increasing intracranial pressure. Therefore their use in neurosurgery is limited and opioids are used in case of strict necessity or as rescue medication. In addition to opioids, drugs with differing mechanisms of actions target pain pathways resulting in additive and/or synergistic effects. Some of these agents inclde acetaminophen/non-steroidal anti-inflammatory drugs (NSAIDs), alpha 2 agonists, NMDA receptor antagonists, gabapentinoids, and local anesthesia techniques. Multimodal analgesia should be a balance between adequate analgesia and less drug induced sedation, respiratory depression, hypercapnia, nausea and vomiting, which may increase intracranial pressure. Non-opioid analgesics can be an useful pharmacological alternative in multimodal regimes to manage post craniotomy pain. This narrative review aims to outline the current clinical evidence of multimodal analgesia for post craniotomy pain control.

Cancer is a major global health problem and the second leading cause of death worldwide. When detected early, surgery provides a potentially curative intervention for many solid organ tumours. Unfortunately, cancer frequently recurs postoperatively. Evidence from laboratory and retrospective clinical studies suggests that the choice of anaesthetic and analgesic agents used perioperatively may influence the activity of residual cancer cells and thus affect subsequent recurrence risk. The amide local anaesthetic lidocaine has a well-established role in perioperative therapeutics, whether used systemically as an analgesic agent or in the provision of regional anaesthesia. Under laboratory conditions, lidocaine has been shown to inhibit cancer cell behaviour and exerts beneficial effects on components of the inflammatory and immune responses which are known to affect cancer biology. These findings raise the possibility that lidocaine administered perioperatively as a safe and inexpensive intravenous infusion may provide significant benefits in terms of long term cancer outcomes. However, despite the volume of promising laboratory data, robust prospective clinical evidence supporting beneficial anti-cancer effects of perioperative lidocaine treatment is lacking, although trials are planned to address this. This review provides a state of the art summary of the current knowledge base and recent advances regarding perioperative lidocaine therapy, its biological effects and influence on postoperative cancer outcomes.

Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8-14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1-0.2 mg.kg-1 for all patients undergoing surgery associated with significant postoperative pain.

Over the past century, there is perhaps no greater contribution to the practice of clinical dentistry than the development and application of local anaesthesia. What were once considered painful procedures have now been made routine by the deposition and action of local anaesthetics. This article will serve as a review of basic pharmacological principles of local anaesthesia, subsequent sequelae that can arise from their use, considerations when using local anaesthetics, and recent advances in the delivery of local anaesthetics.

OBJECTIVE: Pain management for the extraction of the mandibular third molar is a challenge as compelling evidence in comparative anaesthetics is currently lacking.
METHODS: Thorough literature searches took place in PubMed, ScienceDirect, CENTRAL, Embase, Web of Science, CBM, and CNKI. Thirty-three trials were meta-analysed using a Bayesian statistical approach within the random-effects model. Grading of Recommendations Assessment, Development, and Evaluation was performed to determine the overall quality of evidence across all comparisons.
RESULTS: In terms of success rate, an inferior alveolar nerve block (IANB) injection of 2% lidocaine with epinephrine was less effective than a combined injection of buccal infiltration (BI) and lingual infiltration (LI) with a 4% articaine (RR = 0.85 [0.75, 0.96], P = 0.611). According to visual analogue scale (VAS), 2% lidocaine-IANB with epinephrine caused higher VAS scores than 4% articaine-IANB with epinephrine (MD = 0.84 [0.28, 1.40], P = 0.057), whereas 0.5% levobupivacaine-IANB showed lower scores than 2% lidocaine-IANB (MD = - 1.62 [- 2.97, - 0.28], P = 0.045). Also, 2% lidocaine-IANB with epinephrine presented longer latency than both 4% articaine-IANB with epinephrine (MD = 39.44 [16.97, 61.90], P < 0.001) and 4% articaine-BI + LI with epinephrine (MD = 164.41 [16.23, 312.58], P < 0.001); 4% articaine-IANB with epinephrine produced shorter latency than 0.5% bupivacaine-IANB with epinephrine (MD = - 42.92 [- 70.28, - 15.56], P = 0.106); 0.75% ropivacaine-IANB caused shorter onset of action compared with 2% lidocaine-IANB (MD = - 40.88 [- 65.50, - 16.26], P < 0.001). In addition, 2% lidocaine-IANB with epinephrine produced significantly shorter duration than both 4% articaine-IANB with epinephrine (MD = - 47.33 [- 57.88, - 36.77], P = 0.265) and 2% mepivacaine-IANB with epinephrine (MD = - 10.01 [- 19.59, - 0.44], P = 0.769). The duration of action triggered by 4% articaine-IANB with epinephrine was shorter compared with 0.5% bupivacaine-IANB with epinephrine (MD = - 64.17 [- 74.65, - 53.69], P = 0.926). Both 0.5% levobupivacaine-IANB and 0.75% ropivacaine-IANB produced longer duration of action than 2% lidocaine-IANB (MD = 333.70 [267.33, 400.07], P < 0.001) and (MD = 288.01 [287.67, 288.34], P = 0.634, respectively).
CONCLUSIONS: The network meta-analysis demonstrated that the intraosseous injection of 4% articaine with epinephrine had the most noteworthy success rate. However, the combination of BI and LI of 4% articaine with epinephrine, and IANB of 0.5% bupivacaine were, according to a VAS, the most effective. It should be noted that a rapid onset of action was produced by BI combined with LI of 4% articaine with epinephrine and IANB of 2% mepivacaine with epinephrine, while the most prolonged duration of action was generated by IANB of 0.5% levobupivacaine or 0.5% bupivacaine.
CONCLUSIONS: For a better understanding of local anaesthesia for the extraction of the third molar, our study was aimed to provide evidence to guide better dental practices in pain management for clinicians.

暂无摘要。

Local anaesthetics (LAs) are considered the most effective drugs for prevention and management of pain associated with dental procedures. Lignocaine is the most preferred LA worldwide. Adverse drug reactions reported with lignocaine use are usually mild, however severe complications have been encountered. This article reports a case of lignocaine-induced seizure in a child. We also reviewed similar cases encountered over the last 10 years. The possible explanations could be placement of the needle in a small vein or hypersensitivity to lignocaine. We hereby reinforce the fact that seemingly safe LA\'s can cause life-threatening complications and rapid identification of clinical symptoms can drastically change the clinical course. Hence it is vital that primary care physicians and other healthcare professionals should to be aware, alert and be able to diagnose and manage these reactions immediately.