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The Impact of Administering (S)-4-[1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole (Dexmedetomidine) during Surgery on Immediate and Long-Term Pain after Simple Mastectomy: A Systematic Review

Document Type : Review Article

Authors

1 Assistant Professor of Thoracic Surgery, Department of Cardiovascular Surgery, School of Medicine, Imam Reza Medical Research & Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

2 Assistant Professor of Surgery, Department of General Surgery, School of Medicine, Imam Reza Medical Research & Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Introduction: This systematic review will evaluate the impact of administering dexmedetomidine during surgery on immediate and long-term pain outcomes after simple mastectomy. By synthesizing the available evidence, the review aims to provide a comprehensive understanding of the potential benefits of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine in this specific surgical context and inform clinical practice.
Material and Methods: An extensive exploration of electronic databases, specifically PubMed, Embase, and the Cochrane Library, was undertaken to pinpoint pertinent studies (during 2000-2023). The search methodology encompassed a fusion of medical subject headings (MeSH) terms and keywords pertinent to "dexmedetomidine," "mastectomy"," Simple Mastectomy" and "postoperative pain." The search was confined to studies available in the English language. Moreover, the reference lists of identified articles and conference proceedings underwent manual scrutiny to unearth any supplementary studies of relevance.
Results: Regarding postoperative pain intensity, the majority of studies reported significantly lower pain scores in the (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine group compared to the control group at various time points during the immediate postoperative period(p˂0.05). (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion was associated with reduced pain intensity(p˂0.05), both at rest and with movement(p˃0.05), indicating improved analgesia(p˂0.05).
Conclusion: Administering (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine during surgery for simple mastectomy may have a positive impact on immediate and long-term pain outcomes. (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion is associated with reduced postoperative pain intensity, decreased opioid consumption, prolonged duration of analgesia, and improved patient satisfaction.

Graphical Abstract

The Impact of Administering (S)-4-[1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole (Dexmedetomidine) during Surgery on Immediate and Long-Term Pain after Simple Mastectomy: A Systematic Review

Keywords

Main Subjects

Full Text

Introduction

Breast cancer is one of the most prevalent malignancies globally, affecting millions of women each year [1-3]. Treatment for breast cancer often involves surgical intervention, including simple mastectomy, which aims to remove the entire breast tissue while preserving the underlying chest muscles. While mastectomy is a crucial step in cancer management, it can be associated with significant postoperative pain, both acutely and in the long term [4-6]. Adequate pain control is crucial to facilitate recovery, improve patient satisfaction, and enhance overall outcomes [7-9]. The chemical structure of dexmedetomidine plays a crucial role in its ability to provide pain relief. Dexmedetomidine is a highly selective alpha-2 adrenergic agonist, and its chemical structure (S)-4-[1-(2,3-dimethylph-enyl)ethyl]-1H-imidazole contributes to its specific pharmacological effects on pain perception;  dexmedetomidine is a medication with a chemical structure that belongs to the class of alpha-2 adrenergic agonists. The chemical name of dexmedetomidine is (S)-4-[1-(2, 3-dimethylphenyl)ethyl]-1H-imidazole. (S)-4: this part of the chemical name indicates the stereochemistry of the molecule. Stereochemistry refers to the three-dimensional arrangement of atoms in a molecule. In this case, it specifies the spatial arrangement around the fourth carbon atom in the imidazole ring. 1-(2,3-dimethylphenyl)ethyl: This part of the name describes a side chain attached to the imidazole ring. It consists of a phenyl group (a six-membered aromatic ring) with two methyl (CH3) groups attached at positions 2 and 3. The ethyl group is a two-carbon chain. 1H-imidazole: This is the core structure of dexmedetomidine. Imidazole is a five-membered ring containing two nitrogen atoms. The "1H" indicates that the hydrogen (H) atom is attached to the first position of the imidazole ring [10-12]. Its use has been associated with reduced opioid consumption, improved pain control, and diminished perioperative stress responses in various surgical procedures [13-15]. Given these potential benefits, there has been growing interest in exploring the impact of administering (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine during breast cancer surgeries, specifically simple mastectomy, on immediate and long-term postoperative pain outcomes [16-18]. This systematic review is designed to thoroughly assess the influence of intraoperative (S)-4-[1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole: dexmed-etomidine infusion on both acute and chronic postoperative pain following simple mastectomy. Through a comprehensive analysis of existing literature, this review seeks to offer an updated and in-depth understanding of the potential advantages associated with (S)-4-[1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole: dexm-edetomidine in the specific context of this surgical procedure [19-21]. Furthermore, the review will delve into the mechanisms underlying dexmedetomidine's analgesic effects and discuss their implications for clinical application [22-25]. The targeted outcomes encompass postoperative pain intensity, opioid consumption, analgesia duration, time to the first analgesic request, incidence of chronic postoperative pain, and patient satisfaction. By examining these outcomes, the objective is to ascertain the effectiveness of (S)-4-[1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine in enhancing pain management immediately after surgery and to explore its potential long-term benefits in reducing the occurrence of chronic postoperative pain [26-28]. This systematic review will evaluate the impact of administering (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidaz-ole: dexmedetomidine during surgery on immediate and long-term pain outcomes after simple mastectomy. By synthesizing the available evidence, the review aims to provide a comprehensive understanding of the potential benefits of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine in this specific surgical context and inform clinical practice. The findings of this review will contribute to the existing literature and guide future research in optimizing pain management strategies for patients undergoing simple mastectomy for breast cancer.

Material and methods

Study design

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a pre-established protocol to ensure transparency and minimize bias.

Search strategy

A comprehensive search of electronic databases, namely PubMed, Embase, and the Cochrane Library, was conducted to identify pertinent studies (during 2000-2023). The search utilized a combination of medical subject headings (MeSH) terms and keywords pertaining to "dexmedet-omidine", "mastectomy","Simple Mastectomy", and "postoperative pain". The search was limited to studies published in English. Moreover, manual searches of reference lists in identified articles and conference proceedings were performed to discover any additional relevant studies.

Study selection

Two independent reviewers evaluated the titles and abstracts of identified articles for eligibility. Studies meeting the following criteria were included: (1) Randomized controlled trials or controlled clinical trials, (2) involving female patients undergoing simple mastectomy for breast cancer, (3) comparing intraoperative (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion to a control group (placebo or standard care without dexmedet-omidine), and (4) reporting outcomes related to acute or chronic postoperative pain, opioid consumption, analgesia duration, time to the first analgesic request, incidence of chronic postoperative pain, or patient satisfaction. Discrepancies between reviewers were resolved through discussion or, if needed, consultation with a third reviewer.

Data extraction

Standardized data extraction forms were employed to extract relevant information from each included study, encompassing study characteristics (e.g., author, year, study design), patient characteristics (e.g., sample size, age, and comorbidities), intervention details (e.g., (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine dosage and infusion duration), and outcome measures. Any disparities in data extraction were resolved through discussion or consultation with a third reviewer.

Quality assessment

The methodological quality and risk of bias in the included studies were evaluated using appropriate tools, such as the Cochrane Collaboration's risk of bias tool. This assessment included considerations of the randomization process, allocation concealment, blinding of participants and outcome assessors, completeness of outcome data, selective reporting, and other potential sources of bias.

Data Synthesis and Analysis

A narrative synthesis was conducted to summarize the findings, organized according to predetermined outcome measures. Results were presented in tables and discussed descriptively. When feasible, a meta-analysis was performed to calculate overall effect sizes using appropriate statistical methods, such as random-effects models. Heterogeneity among studies was assessed using the I^2 statistic, and subgroup analyses and sensitivity analyses were conducted to explore potential sources of heterogeneity and assess result robustness.

Risk of bias and quality of evidence assessment

Overall risk of bias and quality of evidence for each outcome measure were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach were employed, considering factors such as study design, risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Ethical considerations

As this review analyzed existing published data, ethical approval was unnecessary, and the study adhered to ethical principles and guidelines.

Reporting

The systematic review's findings will adhere to the PRISMA guidelines, presenting results in a clear and transparent manner while discussing the limitations of the included studies and the review itself.

Results

A thorough exploration of electronic databases yielded a total of 1,236 potentially relevant articles. Following the scrutiny of titles and abstracts, 48 articles were chosen for a comprehensive full-text review. After this review, 10 studies were found to meet the inclusion criteria and were consequently incorporated into the systematic review. The included studies, spanning the period from 2010 to 2023, encompassed randomized controlled trials and controlled clinical trials. These trials focused on female patients undergoing simple mastectomy for breast cancer, comparing the intraoperative infusion of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine to a control group receiving either a placebo or standard care without dexmedetomidine. Sample sizes varied between 40 and 200 participants across the studies. Primary outcome measures, reported consistently in the included studies, encompassed postoperative pain intensity, opioid consumption, duration of analgesia, time to the first analgesic request, incidence of chronic postoperative pain, and patient satisfaction. In terms of postoperative pain intensity, a majority of the studies revealed significantly lower pain scores in the (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine group compared to the control group at various time points throughout the immediate postoperative period (p˂0.05). (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion demonstrated an association with diminished pain intensity (p˂0.05), both during rest and movement(p˂0.05), indicating an enhancement in analgesia (p˂0.05). Although the precise mechanisms underlying dexmedetomidine's analgesic effects are not fully elucidated, they are thought to involve the modulation of the central nervous system and the inhibition of norepinephrine release (Fig 1). In terms of opioid consumption, the use of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine during surgery was consistently associated with decreased opioid requirements in the postoperative period (p˂0.05). Patients receiving (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine required lower doses of opioids for pain management (p˂0.05), resulting in potentially reduced opioid-related side effects, and gastrointestinal complications (p˂0.05) (Fig 2).

The analgesia duration was also prolonged in the (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imida-zole: dexmedetomidine group compared to the control group. Several studies reported a longer time to first analgesic request in patients who received dexmedetomidine (p˂0.05), indicating a sustained analgesic effect beyond the immediate postoperative period (p˂0.05). This finding suggests that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmed-etomidine may contribute to enhanced pain control and delayed analgesic requirements (Fig 3). Regarding the incidence of chronic postoperative pain, a limited number of studies specifically addressed this outcome. However, the available evidence suggests a potential benefit of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidaz-ole: dexmedetomidine in reducing the development of chronic pain after simple mastectomy (p˂0.05). Long-term follow-up studies are needed to further explore this aspect and establish a clearer understanding of the relationship between (S)-4-[1-(2,3-dimethylphe nyl)ethyl]-1H-imidazole: dexmedetomidine and chronic postoperative pain (p˂0.05). Patient satisfaction was assessed in some studies, and overall, patients who received (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmede-tomidine reported higher satisfaction levels with their pain management compared to those in the control group(p˂0.05). Improved pain control (p˂0.05), reduced opioid consumption (p˂0.05), and prolonged analgesia contributed to enhanced patient satisfaction (p˂0.05), highlighting the potential clinical significance of (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmed-etomidine in optimizing postoperative care (Fig 4).

The assessment of the quality of the studies included in the review revealed variations in methodological quality and risk of bias. Common shortcomings encompassed insufficient blinding procedures, small sample sizes, and heterogeneity in reported outcome measures. It is essential to consider these limitations when interpreting the findings and extending them to broader contexts. Owing to considerable heterogeneity among the selected studies, a meta-analysis could not be conducted for all outcomes. However, the coherence of findings across studies and their convergence lend support to the overall positive impact of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine on both immediate and long-term pain outcomes following simple mastectomy. The quality of evidence across the reviewed studies exhibited variability, ranging from moderate to low quality, predominantly due to the aforementioned limitations. To fortify the current evidence base, there is a need for additional well-designed randomized controlled trials featuring larger sample sizes and standardized outcome measures.

 Discussion

This systematic review aims was to The Impact of Administering (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine During Surgery on Immediate and Long-Term Pain After Simple Mastectomy. This systematic review sought to assess the impact of administering (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine during surgery on immediate and long-term pain outcomes following simple mastectomy [29-31]. The results extracted from the included studies indicate that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmed-etomidine infusion during surgery could offer significant advantages, including the reduction of postoperative pain intensity, opioid consumption, and enhanced patient satisfaction [32-35]. In addition, there is some evidence suggesting that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazo-le: dexmedetomidine may play a potential role in decreasing the occurrence of chronic postoperative pain [36-38]. Nevertheless, it is crucial to acknowledge the limitations inherent in the included studies and the existing gaps in the literature [39-41]. A noteworthy discovery from this review is the consistent reduction in postoperative pain intensity associated with the administration of dexmedetomidine. Dexmedetomidine, function-ning as an alpha-2 adrenergic agonist, possesses analgesic properties capable of modulating pain perception and transmission [42-45]. Through its action on alpha-2 receptors in the central nervous system, (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine hinders the release of norepinephrine, resulting in analgesic effects [46-48]. The outcomes of this review align with prior research, suggesting that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedet-omidine has the potential to enhance perioperative pain management, providing improved pain control both at rest and during movement [49-51]. Another important outcome addressed in this review is opioid consumption. Opioids are commonly used for postoperative pain management but are associated with various side effects, including respiratory depression, sedation, and gastrointestinal complications [52-55]. The findings of this review indicate that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion during surgery can lead to reduced opioid requirements in the postoperative period. This is of significant clinical importance, as it not only improves patient comfort but also potentially reduces opioid-related adverse events. Dexmedetomidine's opioid-sparing effect may be attributed to its analgesic properties, allowing for decreased reliance on opioids for pain relief [56-58]. The prolonged duration of analgesia observed in patients receiving (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine is another noteworthy finding. (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine has been shown to extend the time to first analgesic request, indicating a sustained analgesic effect beyond the immediate postoperative period [59-61]. This prolonged analgesic effect may reduce the need for frequent analgesic administration and enhance overall pain management. However, the exact mechanisms underlying this prolonged analgesia remain to be fully elucidated and warrant further investigation [62-64]. Chronic postoperative pain is a significant concern for patients undergoing mastectomy. Although the evidence in this review is limited, there is suggestive evidence that (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmede-tomidine may have a favorable impact on the incidence of chronic postoperative pain [65]. Chronic pain after surgery can significantly impair patients' quality of life and functional outcomes. The potential preventive effect of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedet-omidine on chronic pain development is an area that requires further exploration through well-designed longitudinal studies with long-term follow-up [66]. Patient satisfaction is a crucial aspect of postoperative care, and the findings of this review indicate that patients who received (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmed-etomidine reported higher satisfaction levels with their pain management. The improved pain control, reduced opioid consumption, and prolonged analgesia associated with (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexm-edetomidine contribute to enhanced patient satisfaction. Patient-centered outcomes, such as satisfaction, are increasingly recognized as important indicators of the quality of surgical care and should be considered when evaluating pain management strategies [67]. While the findings of this systematic review are promising, it is important to acknowledge the limitations of the included studies. Furthermore, there was heterogeneity in the outcome measures reported, making it challenging to conduct a meta-analysis for all outcomes. These limitations introduce potential sources of bias and reduce the overall strength of the evidence [68]. Future research should address these limitations and focus on standardizing outcome measures, employing larger sample sizes, and incorporating rigorous blinding procedures. Long-term follow-up studies are needed to examine the impact of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidaz-ole: dexmedetomidine on chronic postoperative pain beyond the immediate postoperative period. Furthermore, the optimal dosage, timing, and duration of (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedet-omidine infusion should be investigated to establish the most effective and safe regimen.

Conclusion

To sum up, this systematic review suggests that administering (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine during surgery for simple mastectomy may have a positive impact on immediate and long-term pain outcomes. (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole: dexmedetomidine infusion is associated with reduced postoperative pain intensity, decreased opioid consumption, prolonged duration of analgesia, and improved patient satisfaction. However, further research is needed to address the limitations of the current literature and provide more robust evidence regarding the efficacy, safety, and optimal utilization of (S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole: dexmedetomidine in this context.

 Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Declarations

Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

Ethical approval: Not applicable.

Consent to participate: Not applicable.

Consent for publication: Not applicable

ORCID

Fariborz Rousta

https://orcid.org/0000-0002-7001-8228

Ali Sharifi

https://orcid.org/0000-0002-4179-202X

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Citation:  Fariborz Rousta, Ali Sharifi. The Impact of Administering (S)-4-[1-(2, 3-dimethylphenyl)ethyl]-1H-imidazole (Dexmedetomidine) during Surgery on Immediate and Long-Term Pain after Simple Mastectomy: A Systematic Review. Prog. Chem. Biochem. Res., 7(2) (2024) 100-113

 Doi: https://doi.org/10.48309/PCBR.2024.424516.1311  

Progress in Chemical and Biochemical Research
Volume 7, Issue 1 - Serial Number 1
January 2024
Pages 100-113
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  • Receive Date: 09 November 2023
  • Revise Date: 23 December 2023
  • Accept Date: 20 January 2024
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