In a recent study published in Journal of Clinical Medicine, researchers systematically reviewed and analyzed the therapeutic efficacy of low-dose local anesthetics (LAs) in various clinical conditions, highlighting gaps in current research for future exploration.
Study: Therapeutic Use of Low-Dose Local Anesthetics in Pain, Inflammation, and Other Clinical Conditions: A Systematic Scoping Review. Image Credit: daniiD/Shutterstock.com
Background
Since the first use of cocaine as an LA by Carl Koller in 1894, LAs have evolved significantly in therapeutic applications. Initially utilized for their immediate pain-relieving properties, their scope expanded with the discovery of procaine in 1905 and its inflammation-reducing effects.
This evolution gave rise to neural therapy (NT), predominantly in Europe, employing LAs for more than just pain management. Modern applications extend to targeting the autonomic nervous system (ANS) to provide sustained relief from pain and other dysfunctions.
Further research is needed to comprehensively understand the scope, efficacy, and safety of low-dose local anesthetics in various conditions, as current studies vary in design, and a unified understanding is yet to be established.
About the study
In the present study, the researchers conducted a systematic scoping review using the Arksey and O’Malley framework, comprising five stages: defining the research question, identifying relevant studies, selecting studies, charting data, and summarizing and reporting results.
The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR) guidelines, and the research question sought to understand the therapeutic applications of low-dose LAs in various medical conditions.
The team selected studies focusing solely on LAs, emphasizing measuring efficacy or safety. The review included a wide array of study designs, from experimental setups like randomized controlled trials (RCTs) to observational analyses including cohort and case-control studies. Systematic reviews, qualitative studies, and meta-analyses that met the inclusion criteria were also considered, excluding narrative reviews, expert opinions, and studies involving LAs combined with other treatments.
The literature search was comprehensive, covering major databases like MEDLINE, Cochrane Library, and LILACS, with no language or publication date restrictions. They supplemented this with searches on Google Scholar and references from included studies.
Two reviewers independently screened titles and abstracts, with full-text reviews for those meeting the inclusion criteria. Conflicts were resolved through discussion or a third reviewer's input. The study used Rayyan Qatar Computing Research Institute (QCRI) for data management during the screening phases.
Data extraction was thorough, capturing key information such as authorship, publication year, study objectives, population characteristics, study type, intervention details, outcomes, and main findings. Special attention was given to data on the safety of the interventions. A third reviewer resolved any discrepancies in data extraction.
Finally, the team performed a narrative synthesis of the results, using text and tables from the studies for a descriptive summary.
This synthesis not only outlined the characteristics and findings of the studies but also highlighted gaps in the evidence and offered potential interpretations and implications of the results.
Study results
The initial search across Medline, LILACS, and the Cochrane Library yielded 9614 publications, supplemented by 52 articles from citation searches and grey literature.
After duplicate removal, 7,670 publications were manually screened based on titles and abstracts, excluding 7,250 publications. This process left 420 articles for full-text assessment, with ten being inaccessible, and after thorough evaluation, 315 studies were further excluded.
The researchers also considered 52 publications identified through citation searching, of which six could not be retrieved. Out of the 46 assessed for eligibility, 12 were excluded for being opinion articles, and 129 studies were included in the review.
These included studies comprising 49 clinical trials (both non-randomized and randomized), 71 observational studies, and nine systematic reviews. The observational studies varied, including case reports or series, cohort studies, qualitative studies, and before-and-after studies.
The median patient number across these studies was 44. The studies primarily reported on procaine, lidocaine, and bupivacaine, focusing on their therapeutic applications and potential adverse effects.
Geographically, the studies spanned multiple countries, with the most contributions from Türkiye, Germany, the United States, and Cuba, among others. The median publication year was 2016, with a concentration of studies published between 2011 and March 2022.
These studies were predominantly published in general medical journals, although some appeared in specialized journals focused on pain management, neurology, psychiatry, and anesthesiology.
Regarding indications, the primary use of low-dose, short-acting LAs was in managing chronic pain, followed by acute pain. The most common conditions treated were musculoskeletal and/or myofascial pain and migraines. Additionally, 14% of the studies focused on non-pain-related indications.
In the studies, LAs were applied in various ways, including segmental application, local application, ganglion injections, and mixed approaches. The study’s Figure 5 highlights the evidence gaps in the literature regarding the types of indications and study designs.
The review found that 96.12% of the studies primarily assessed the efficacy of LAs, with a smaller portion focusing on safety. The key outcomes included pain relief, improvements in quality of life, reduced analgesic intake, and better scores on anxiety and depression scales.
While 53.48% of these studies also considered safety, reporting mild and transient adverse reactions, no severe adverse allergic responses or reactions were documented.
The study revealed that lidocaine and procaine were the most researched LAs, with lidocaine showing a slightly higher frequency of adverse events, though neither exhibited major adverse effects.
The interventions predominantly showed positive or potentially positive effects, with a minority reporting no effect or providing unclear evidence. A specific focus on acute stress revealed positive impacts, with studies on anxiety and depression as secondary outcomes showing varying degrees of improvement.
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