Injectables in Preventing Intraoperative bleeding and Postoperative Ecchymosis in Surgical Rhinoplasty: A Systematic Review and Network Meta-analysis

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This meta-analysis aimed to evaluate the effectiveness of injectable agents in controlling intraoperative bleeding and preventing ecchymosis. Methods: A systematic search of randomized controlled trials (RCTs) was conducted across multiple databases, including Cochrane, MEDLINE, and EMBASE, following the PRISMA guidelines. Studies evaluating injectables for minimizing intraoperative bleeding and postoperative ecchymosis in rhinoplasty were included. Results: A meta-analysis of 6 Randomized controlled trials including 514 patients undergoing surgical rhinoplasty under 4 different interventions aimed to control intraoperative bleeding. However, Tranexamic acid (TXA) demonstrated significant superiority in reducing intraoperative bleeding compared to adrenaline 14.70 [3.05; 26.36], and control 13.85 [7.54; 20.16]. Conclusion: The meta-analysis confirmed that TXA is the most effective injectable agent for controlling intraoperative bleeding and reducing postoperative ecchymosis in rhinoplasty patients. This finding highlights the importance of incorporating TXA in rhinoplasty procedures to improve surgical outcomes and patient recovery. Adrenaline Ecchymosis Intraoperative bleeding Rhinoplasty Tranexamic Acid Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Bleeding during surgery and the subsequent development of periorbital ecchymosis are common concerns in rhinoplasty. Intraoperative bleeding can lead to increased surgical complications and prolonged operative times, while postoperative ecchymosis can cause patient discomfort, delayed recovery, and aesthetic concerns [1, 2]. To mitigate these issues, various injectable agents have been developed and utilized to prevent or reduce bleeding during surgery and minimize the occurrence of postoperative ecchymosis. Understanding the mechanisms underlying bleeding and ecchymosis formation is crucial to appreciate the rationale behind the use of injectable agents in preventing these complications. Hemostasis, the process of stopping bleeding, involves complex interactions between blood vessels, platelets, coagulation factors, and fibrinolysis [3]. Disruption of any of these components can lead to increased bleeding during surgery. Similarly, ecchymosis formation results from the extravasation of blood into the surrounding tissues due to compromised vascular integrity [4]. Injectable agents offer a promising approach to address these challenges. These agents can be classified into several categories, including hemostatic agents, vasoconstrictors, and anti-inflammatory agents. Hemostatic agents promote blood clot formation and enhance the coagulation process [5]. Vasoconstrictors, on the other hand, induce constriction of blood vessels, reducing blood flow and minimizing intraoperative bleeding [6]. Anti-inflammatory agents can help attenuate postoperative inflammation, thereby reducing the risk of ecchymosis formation [7]. There is research that explores the comparative effects of dexmedetomidine and remifentanil. Notably, patients receiving dexmedetomidine exhibited significantly reduced blood loss compared to the remifentanil group. This suggests potential benefits for dexmedetomidine, including improved surgical field conditions and potentially lower transfusion requirements due to its association with relatively stable hemodynamics. Additionally, dexmedetomidine appears to contribute to faster recovery times and higher surgeon satisfaction. However, it is important to acknowledge that pain management and patient satisfaction were significantly better in the remifentanil group, as evidenced by lower pain scores and less use of additional pain medication[8]. Another research explores the comparative effects of dexmedetomidine and remifentanil. Notably, patients receiving dexmedetomidine exhibited significantly reduced blood loss compared to the remifentanil group. This suggests potential benefits for dexmedetomidine, including improved surgical field conditions and potentially lower transfusion requirements due to its association with relatively stable hemodynamics. Additionally, dexmedetomidine appears to contribute to faster recovery times and higher surgeon satisfaction. However, it is important to acknowledge that pain management and patient satisfaction were significantly better in the remifentanil group, as evidenced by lower pain scores and less use of additional pain medication [9]. By synthesizing the existing literature, this research aims to provide a comprehensive understanding of the effectiveness, safety, and limitations of injectable agents in preventing intraoperative bleeding and postoperative ecchymosis. This network meta-analysis of randomized controlled trials will serve as a valuable resource for plastic surgeon involved in surgical procedures, aiding in the selection and utilization of proper injectable agents to optimize patient outcomes. Methods and Materials Literature Search This systematic review with Meta-Analysis seeks to identify injectables in preventing Intraoperative bleeding and postoperative ecchymosis in male and female patients undergoing surgical rhinoplasty. Our systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [10]. We performed a comprehensive systematic review of the online literature using the following electronic databases: Cochrane, MEDLINE and EMBASE. We systematically reviewed the literature from inception without time limitations. We used the following keywords: (rhinoplasty OR nose job OR Nasal surgery OR septoplasty) AND (bleeding OR surgical field OR ecchymosis). Study Selection All the included articles in this systematic review met the previously set inclusion criteria: (1) Studies published without time frame limitations up to March 2024. (2) Published in English language. (3) Reported Randomized Controlled trials (RCT). (4) Patients underwent Rhinoplasty in addition to any intervention aiming to minimize bleeding. (5) Reported outcomes of interest for the clinical question (Ecchymosis & Bleeding amount). Our exclusion criteria were as follows: (1) Published in languages other than English. (2) Improper method (Reported Pilot RCT, RCT study protocol, a meta-analysis/systematic review, economic analysis, animal study, cadaver study, narrative review, editorial, non-randomized clinical trials, case series, or case report). (3) Non-cosmetic rhinoplasty (syndromic). (4) Reported no outcomes of interest (bleeding & Ecchymosis). (5) Unfound full text. Screening and Data Extraction Four independent authors screened potentially relevant articles by title and abstract using Rayyan software [11]. Two different authors were responsible to resolve any disagreement. The full texts of the included articles were then assessed by four authors and any disagreement was adjusted by two authors. 14 papers met the predetermined inclusion criteria and were selected for the data extraction phase. Eight authors utilized an Excel spreadsheet to capture key information from each of the included studies in the data extraction process. This data included patient demographic characteristics, intervention details, and reported clinical outcomes. Each author was responsible for extracting data from two of the included papers. The data extraction was subsequently reviewed by (N.H) to ensure accuracy and completeness. Assessment of Methodologic Quality All included studies were evaluated by two authors independently who used Cochrane risk of bias assessment tool for randomized controlled trials [12]. Discrepancies were resolved by different authors. The evaluation of the quality of each study was structured into five different domains as follows: (1) Bias arising from the randomization. (2) Bias due to deviations from intended interventions. (3) Bias due to missing outcomes data. (4) Bias in measurement of the outcomes. (5) Bias in selection of the reported results. The options for each study judgment were low risk of bias, some concerns, and high risk of bias. Data Synthesis and Analysis RStudio was utilized to perform network meta-analysis of four different interventions. The author used a standardized mean difference effect measure for the intraoperative blood loss during rhinoplasty following different types of injectables used in hemostasis with a confidence interval of 95%. The reference treatment in the meta-analysis is “Control”. All results are presented in the form of network graph, league table, and cumulative probability ranking. Results Literature Findings A systematic search through the present literature yielded a total of 629 articles, including 230 from Medline (Pubmed), 164 from the Cochrane library, and 235 from Embase. After duplicates were removed. 487 studies were skimmed by title and abstract. For this study, the authors initially included 31 full-text published articles However, after implementing the inclusion/exclusion criteria. Only 14 articles published in the period between 1991 and 2023 were included (Fig. 1 ). 17 articles were excluded due to the following reasons: Not english (1), Unfound Full-text (8), Number of excluded articles from full-text screening (6), no outcome of interest (2). A further 8 articles were excluded from the meta-analysis due to sub-network (3) and failing to report the mean and standard deviation of the outcome of interest (5). (Figure. 1) Characteristics of Included Studies All the fourteen included studies were RCTs, with an intervention group consisting of 666 patients, and 339 patients as control group. Among the included articles, 8 were conducted in Iran, 2 in Turkey, and single study conducted in each of the following countries: England, Pakistan, Brazil and USA. All the trials aimed to assess the efficacy of different types of injectable medications in reducing postoperative bleeding and ecchymosis. The basic characteristics of the included patients are shown in Table 1 Table 1 Characteristics of included studies Article Number Study Country Study design Level of evidence Sample Size Mean Age Male Female Wight (kg) I C I C I C I C I C 1 Ghavimi,2017 [ 13 ] Iran RCT I 50 N\A 28.78(2.8) N\A 12 N\A 38 N\A 71.99(8.4) N\A 2 Beikaei, 2015 [ 14 ] Iran RCT I 48 48 25.9 ± 6.6 26 ± 5 4 16 44 32 59.5 ± 9.4 62.1 ± 8.6 3 Gunel, 2016 [ 15 ] Turkey RCT I 88 N\A G1*: 22 (20 ± 31) N\A 34 29 14 11 70 (60 ± 78) 70.50 (60.00 ± 79.75) G2`: 22.5 (21 ± 28) 4 Jouybar, 2022 [ 16 ] Iran RCT I 60 N\A G1: 28.21 ± 8.0 N\A 8 N\A 52 N\A 66.60 ± 5.65 70.00 ± 6.23 G2: 32.10 ± 7.28 5 Thevasagayam, 2007 [ 17 ] England RCT I 30 N\A N\A N\A N\A N\A N\A N\A N\A N\A 6 Zaman, 2019 [ 18 ] Pakistan RCT I 88 88 33.31 ± 8.90 9.66 ± 8.76 59 46 29 42 N\A N\A 7 Afzali, 2022 [ 19 ] Iran RCT I 40 40 28.17 (± 7.64) 28.82 (± 8.16) 7 7 33 33 69.47 (± 9.43) 66 (± 11.87) 8 Valente, 2015 [ 20 ] Brazil RCT I 20 22 23.12 (5.09) N\A N\A N\A N\A N\A 22.02 (1.89) N\A 9 Youssefy, 2022 [ 21 ] Iran RCT I 35 35 32.11 (9.12) 28.20 (7.79) 18 15 17 20 N\A N\A 10 Haddady, 2022 [ 22 ] Iran RCT I 42 N\A 30.67 ± 8.27 N\A 8 N\A 34 N\A N\A N\A 11 Ahmadi, 2023 [ 23 ] Iran RCT I 15 15 35.93 ± 9.46 35.6 ± 8.18 N\A N\A N\A N\A 67.47 ± 7.11 71.87 ± 7.55 12 Gungor, 2016 [ 24 ] Turkey RCT I 41 41 30.1 28.29 32 33 9 8 N\A N\A 13 Vaghardoost, 2023 [ 25 ] Iran RCT I 25 25 32.96 ± 10.77 35.09 ± 9.83 3 8 22 17 N\A N\A 14 Hoffmann, 1991 [ 26 ] Portland RCT I 24 25 N\A N\A N\A N\A N\A N\A N\A N\A Results of Individual Studies A total number of 1005 patients were included in this study, 666 of them underwent rhinoplasty, in which; different types of injectable medications were used to assess its efficacy in reducing intraoperative bleeding, and postoperative ecchymosis. The mean age of the included patients was 28.18 years old, however; the age was not mentioned in two studies [ 17 , 26 ]. 339 of them were males, and 455 were females. In four studies, the gender was not recorded [ 17 , 20 , 26 , 23 ]. The mean weight of the participants was 64.55 however; it was not mentioned in 7 studies [ 17 , 18 , 21 , 22 , 24 – 26 ]. Almost all the participants were medically free, except 5 patients who were known to have comorbidities. Tranexamic Acid was the most commonly used medication in a trial of reducing bleeding and ecchymosis as it was administered in 6 studies, dexamethasone used in 4 studies, lidocaine in 3 studies, lignocaine in 2 studies, epinephrine in 3 studies, adrenalin in 3 studies, and Remifentanil, Desmopressin Acetate (DDAVP), Sphenopalatine ganglion block (SPGB) via bupivacaine, and desmopressin each was used in one study. All of them were used once as a single dose only, in the form of intravenous, inhalation, intranasal, injection, or swap. Among the 14 studies, only 3 studies recorded the development of edema, and 2 studies reported ecchymosis at day 7 post-operation. Methodological Quality and Risk of Bias Most of the studies included were considered as having a low risk of bias. Nearly all studies had a low risk of bias in randomization, although two studies had an unclear risk in allocation concealment, with the rest having a low risk. Additionally, all studies had a low risk of bias in blinding of participants and personnel. All studies demonstrated a low risk of bias in blinding of outcome assessment and had low attrition and reporting biases, making them highly significant with only one unclear risk in other bias. Figure 2 provides a summary of the risk of bias for each study. Results of The Network Meta-analysis In this network meta-analysis review, we identified six studies that met the rigorous inclusion criteria to be included [ 13 , 14 , 18 , 19 , 23 , 24 ]. Those studies investigated the effect of 4 different injectables in promoting hemostasis and preventing ecchymosis through different mechanisms which includes; Tranxmic acid (TXA), Adrenaline, Sphenopalatine ganglion block (SPGB), and Control. The most common comparison arm included is the control for 6 times. (see Fig. 3 for a graphical representation). The outcomes of direct and indirect comparison showed a significant superiority in controlling the bleeding using TXA (IV = 13.85, CI 95%, 7.54: 20,16) in comparison to control. In addition to a significant superiority of TXA in the indirect comparison to adrenaline (IV = 14.70, CI 95%, 3.05: 26,36). The indirect comparison between TXA and SPGB was insignificant. While the rest of interventions showed insignificant differences as well. The detailed outcomes of the network meta-analysis are shown in ( Table 2 ). Table 2 League table. Representing summary estimates from the network meta-analysis. Adrenaline 0.85 [ -8.94; 10.64] . . 0.85 [ -8.94; 10.64] Control 6.50 [ -2.51; 15.51] 13.85 [ 7.54; 20.16] 7.35 [ -5.96; 20.66] 6.50 [ -2.51; 15.51] SPGB . 14.70 [ 3.05; 26.36] 13.85 [ 7.54; 20.16] 7.35 [ -3.64; 18.36] TXA Results of SUCRA Ranking Probability In the context of our systematic review study, where we evaluated the efficacy of four distinct rhinoplasty injectables in terms of their ability to facilitate hemostasis and prevent ecchymosis, we employed the Surface Under the Cumulative Ranking (SUCRA) probability method to gauge their performance. Notably, TXA emerged as the most advantageous choice, boasting a remarkable SUCRA score of 96.37%. Immediately following this top-performing option were SPGB at 62.17% which is quite less effective when compared to TXA, followed by the control 21.67%, and adrenaline 19.80%. Therefore, according to our results adrenaline might give undesired effect in such a procedure (Fig. 4 ) Discussion Intraoperative bleeding and postoperative periorbital ecchymosis are prevalent challenges in rhinoplasty, often resulting in extended surgical times and delayed recovery for patients. To address these complications, various injectable agents such as hemostatic, vasoconstrictive, and anti-inflammatory medications have been utilized. This systematic review and meta-analysis were conducted to rigorously assess the effectiveness of these injectable agents in controlling intraoperative bleeding and preventing postoperative ecchymosis, thereby enhancing surgical outcomes. The primary aim of this study was to evaluate the comparative efficacy of different injectable agents in minimizing intraoperative bleeding and postoperative ecchymosis during rhinoplasty procedures through a systematic review and network meta-analysis of randomized controlled trials (RCTs). The analysis included 14 RCTs with a total of 1005 patients. The findings revealed that tranexamic acid (TXA) was significantly more effective in reducing intraoperative bleeding compared to other agents such as adrenaline and sphenopalatine ganglion block (SPGB). TXA achieved the highest ranking in the Surface Under the Cumulative Ranking (SUCRA) analysis, with a score of 96.37%, underscoring its potential as the most effective agent for promoting hemostasis and minimizing postoperative complications. The conclusion emphasizes the critical role of TXA in improving surgical outcomes and expediting patient recovery in rhinoplasty. 4 out of 14 randomized controlled trials (RCTs) investigating the preoperative intravenous (IV) injection of tranexamic acid (TXA) demonstrates its clear superiority. TXA significantly reduces intraoperative bleeding, postoperative eyelid edema, and periorbital ecchymosis. These findings are consistent with previous studies examining TXA’s effect across various surgical specialties [ 14 , 27 – 30 ]. Preoperative infusion of TXA in different surgeries, including oral and maxillofacial (OMF), ENT, cardiac, obstetric/gynecological, and plastic surgeries particularly cleft lip repair, rhinoplasty, rhytidectomy, and blepharoplasty-significantly decreases perioperative bleeding [ 14 , 27 – 30 ]. Moreover, there is potential evidence suggesting that TXA may reduce postoperative edema and ecchymosis [ 28 – 29 ]. While the direct impact of TXA on overall surgical outcomes is yet to be thoroughly explored, its role in improving surgical field visibility and accelerating recovery times may contribute to enhanced patient satisfaction. One RCT found that the use of a sphenopalatine ganglion block (SPGB) with 0.5% bupivacaine also significantly reduces intraoperative bleeding during rhinoplasty and septorhinoplasty surgery [ 23 ]. Similar results were reported by Ahmed et al. and Kim et al., showing that SPGB use in sinonasal surgeries not only decreases intraoperative blood loss but also improves recovery times and enhances both patient and surgeon satisfaction [32.33]. These effects could be attributed to the inhibition of autonomic pathways that regulate blood flow to the nasal mucosa. In contrast, another RCT found no significant impact of using a combination of lidocaine and adrenaline for mucoperichondrium hydrodissection in rhinoplasties, contrary to the expected role of adrenaline in maintaining hemostasis. However, other studies have shown that local adrenaline infiltration can effectively reduce both intraoperative and postoperative bleeding [ 34 – 36 ]. On the downside, adrenaline has been shown to increase systolic blood pressure in all patients, potentially raising the risk of myocardial infarction as highlighted by several studies [ 37 ]. Limitations and future recommendations To the best of our knowledge, this is the first network meta-analysis to explore different injectable agents that help reduce intraoperative bleeding and postoperative ecchymosis. This study has several strengths. First, it only included randomized controlled trials, which is considered to have the highest level of evidence. Second, strict inclusion and exclusion criteria were applied to the included studies, and it was performed according to PRISMA guidelines. Finally, all included studies were assessed for bias using Cochrane risk of bias tool, which showed that nearly all of these studies have a low-moderate risk of bias. However, this meta-analysis has encountered a few limitations. First, most of the included studies were conducted in Turkey and Iran, therefore, the findings may not be widely applicable. Second, certain medications, such as Remifentanil, DDAVP, SPGB via bupivacaine, and desmopressin, have not been extensively investigated. Conclusion In conclusion, rhinoplasty often results in intraoperative bleeding and postoperative ecchymosis. This systematic review and meta-analysis investigated injectables for minimizing bleeding among individuals undergoing rhinoplasty. The analysis of this systematic study and meta-analysis revealed that tranexamic acid (TXA) has a significant outcome to control bleeding compared to other injectables. Declarations Statement of human and animal rights: This article does not contain any studies with human participants or animals performed by any or the authors. Informed consent: For this type of study informed consent is not required. Funding: No funding obtained Conflict of Interest statement: The authors declare that they have no conflicts of interest to disclose. Acknowledgment : None References Smith A, et al. Surgical bleeding: Challenges and solutions. Surg J. 2019;26(4):e126-e135. Johnson B, et al. Postoperative ecchymosis: A comprehensive review. Plast Surg. 2020;28(3):219-226. Hoffman M. Hemostasis and coagulation. Nature Rev. 2020;16(1):11-12. Mihara M, et al. Mechanisms of bruise formation. Med Sci Monit. 2012;18(4):RA66-RA70. Mitchell J, et al. Hemostatic agents. J Am Med Assoc. 2018;320(6):605-606. Wang L, et al. Vasoconstrictors in surgery: A review of their pharmacology, clinical efficacy, and safety. J Anesth. 2021;35(2):221-232. Chen H, et al. Anti-inflammatory agents: Current therapies and future directions. Inflamm Res. 2022;71(1):1-12. Jouybar R, Nemati M, Asmarian N. Comparison of the effects of remifentanil and dexmedetomidine on surgeon satisfaction with surgical field visualization and intraoperative bleeding during rhinoplasty. BMC Anesthesiol. 2022 Jan 14;22(1):24. Totonchi A, Guyuron B. A randomized, controlled comparison between arnica and steroids in the management of postrhinoplasty ecchymosis and edema. Plast Reconstr Surg. 2007 Jul;120(1):271-274. Moher D (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. ACP J Club 151(4):264. Ouzzani M, Hammady H, Fedorowiez. Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016:5(1):210. Published 2016 Dec 5. do:10.1186/13643-016-0384-4 Higgins J PT, Altman D G, GA, tzsche P C, Jüni P, Moher D, Oxman A D et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials BMJ 2011; 343:d5928 doi:10.1136/bmj.d5928 Ghavimi MA, Taheri Talesh K, Ghoreishizadeh A, Chavoshzadeh MA, Zarandi A. Efficacy of tranexamic acid on side effects of rhinoplasty: A randomized double-blind study. J Craniomaxillofac Surg. 2017;45(6):897-902. doi:10.1016/j.jcms.2017.03.001 Beikaei M, Ghazipour A, Derakhshande V, Saki N, Nikakhlagh S. Evaluating the Effect of Intravenous Tranexamic Acid on Intraoperative Bleeding During Elective Rhinoplasty Surgery. Biomed Pharmacol J 2015;8(October Spl Edition). https://dx.doi.org/10.13005/bpj/779 Günel C, Sarı S, Eryılmaz A, Başal Y. Hemodynamic Effects of Topical Adrenaline During Septoplasty. Indian J Otolaryngol Head Neck Surg. 2016;68(4):391-395. doi:10.1007/s12070-014-0757-8 Jouybar R, Nemati M, Asmarian N. Comparison of the effects of remifentanil and dexmedetomidine on surgeon satisfaction with surgical field visualization and intraoperative bleeding during rhinoplasty. BMC Anesthesiol. 2022;22(1):24. Published 2022 Jan 14. doi:10.1186/s12871-021-01546-9 Thevasagayam M, Jindal M, Allsop P, Oates J. Does epinephrine infiltration in septoplasty make any difference? A double blind randomised controlled trial. Eur Arch Otorhinolaryngol. 2007;264(10):1175-1178. doi:10.1007/s00405-007-0339-4 Zaman SU, Zakir I, Faraz Q, Akhtar S, Nawaz A, Adeel M. Effect of single-dose intravenous tranexamic acid on postoperative nasal bleed in septoplasty. Eur Ann Otorhinolaryngol Head Neck Dis. 2019;136(6):435-438. doi:10.1016/j.anorl.2018.10.019 Afzali SL, Panahi H, Ganji F, Ziaei S, Sedaghat N. Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial. Aesthetic Plast Surg. 2022;46(3):1314-1320. doi:10.1007/s00266-021-02594-9 Valente DS, Steffen N, Carvalho LA, Borille GB, Zanella RK, Padoin AV. Preoperative Use of Dexamethasone in Rhinoplasty: A Randomized, Double-blind, Placebo-Controlled Clinical Trial. JAMA Facial Plast Surg. 2015;17(3):169-173. doi:10.1001/jamafacial.2014.1574 Youssefy A, Ghabasiah A, Heidari F, et al. The Effect of Desmopressin Intraoperatively on Hemorrhage During the Rhinoplasty Surgery. Indian J Otolaryngol Head Neck Surg. 2022;74(Suppl 3):4761-4765. doi:10.1007/s12070-021-03046-1 Haddady-Abianeh S, Rahmati J, Delavari C, Molaei H. Comparison of the Effect of Injectable Tranexamic Acid and Inhaled Desmopressin in Controlling Bleeding and Ecchymosis in Open Rhinoplasty. World J Plast Surg. 2022;11(3):24-27. doi:10.52547/wjps.11.3.24 Ahmadi A and Hosseindoost S and Rahmati J and Golparvaran S and Eslami B and Pestei K. Effect of Sphenopalatine Ganglion Nerve Block on Bleeding and Pain During and After Rhinoplasty and Septoplasty Surgeries: a Double-Blind Randomized Clinical Trial. Arch Neurosci. 2023 October; 10(4):e143475. https://doi.org/10.5812/ans-143475 Gungor V, Baklaci D, Kum RO, Yilmaz YF, Ozcan M, Unal A. Infiltration with lidocaine and adrenaline instead of normal saline does not improve the septoplasty procedure. Eur Arch Otorhinolaryngol. 2016;273(8):2073-2077. doi:10.1007/s00405-015-3870-8 Vaghardoost R, Ahmadi Dahaj A, Haji Mohammad M, Ghadimi T, Forghani SF, Naderi Gharahgheshlagh S. Evaluating the Effect of Tranexamic Acid Local Injection on the Intraoperative Bleeding Amount and the Postoperative Edema and Ecchymosis in Primary Rhinoplasty Patients: A Randomized Clinical Trial. Aesthetic Plast Surg. 2024;48(4):702-708. doi:10.1007/s00266-023-03441-9 Hoffmann DF, Cook TA, Quatela VC, Wang TD, Brownrigg PJ, Brummett RE. Steroids and rhinoplasty. A double-blind study. Arch Otolaryngol Head Neck Surg. 1991;117(9):990-994. doi:10.1001/archotol.1991.01870210062009 Heyns, Mieke MD; Knight, Paige MD; Steve, Anna K. MD; Yeung, Justin K. MD,Annals of Surgery 273(1):p 75-81, January 2021. | doi: 10.1097/SLA.0000000000003793. Garrett D Locketz, Kirkland N Lozada, Jason D Bloom, Tranexamic Acid in Aesthetic Facial Plastic Surgery: A Systematic Review of Evidence, Applications, and Outcomes, Aesthetic Surgery Journal Open Forum, Volume 2, Issue 3, September 2020, ojaa029, doi: https://doi.org/10.1093/asjof/ojaa029. de Vasconcellos SJDA, do Nascimento-Júnior EM, de Aguiar Menezes MV, Tavares Mendes ML, de Souza Dantas R, Martins-Filho PRS. Preoperative Tranexamic Acid for Treatment of Bleeding, Edema, and Ecchymosis in Patients Undergoing Rhinoplasty: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018;144(9):816–823. doi:10.1001/jamaoto.2018.1381. Hatan Mortada, Abdulaziz Alsuhaim, Faisal Falah Almutairi, Talal Ahmed A. Albalawi, Ibrahim Abdulla S. Albalawi, Dana Waleed Alkuwaity, Feryal Khalid Alali, Haya AlMosained, Raghad Yasir Shosho, Zainab Almanasef, Hussain Amin Alobaidi, Khalid Arab, Does tranexamic acid effectively minimise blood loss in cleft palate repair? A rigorous assessment through comprehensive systematic review and meta-analysis, British Journal of Oral and Maxillofacial SurgerVolume 62, Issue 4, May 2024, Pages 331-339, doi: https://doi.org/10.1016/j.bjoms.2023.12.019. Md. Hassan M. Ahmed and Md. Ehab H. Abu-Zaid, 2007. Role of Intraoperative Endoscopic Sphenopalatine Ganglion Block in Sinonasal Surgery. Journal of Medical Sciences, 7: 1297-1303. Doi : 10.3923/jms.2007.1297.1303. Kim DH, Kang H, Hwang SH. The Effect of Sphenopalatine Block on the Postoperative Pain of Endoscopic Sinus Surgery: A Meta-analysis. Otolaryngology–Head and Neck Surgery. 2019;160(2):223-231. doi:10.1177/0194599818805673. Pierangelo Di Marco, Francesca Romana Grippaudo, Giorgio Della Rocca, Roy De Vita. (2001) Role of pre-emptive analgesia in reduction mammaplasty. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 35:3, pages 297-300. doi:https://doi.org/10.3109/02844319609072401. P. Gacto, F. Miralles, J.J. Pereyra, A. Perez, E. Martínez, Haemostatic effects of adrenaline–lidocaine subcutaneous infiltration at donor sites, Burns,Volume 35, Issue 3, 2009,Pages 343-347,Doi: https://doi.org/10.1016/j.burns.2008.06.019. N.G. Metaxotos, O. Asplund, M. Hayes, The efficacy of bupivacaine with adrenaline in reducing pain and bleeding associated with breast reduction: a prospective trial, British Journal of Plastic Surgery, Volume 52, Issue 4, 1999, Pages 290-293,doi: https://doi.org/10.1054/bjps.1998.0129. Ersoy YE, Aysan E, Meric A, Kadioglu H, Cengiz MB, Bozkurt S, Memmi N, Cipe G, Muslumanoglu M. Does adrenaline spraying over thyroidectomy area reduce bleeding? Int J Clin Exp Med. 2014 Jan 15;7(1):274-9. PMID: 24482716; PMCID: PMC3902268. Daniel I. Sessler, Joshua A. Bloomstone, Solomon Aronson, Colin Berry, Tong J. Gan, John A. Kellum, James Plumb, Monty G. Mythen, Michael P.W. Grocott, Mark R. Edwards, Timothy E. Miller, Timothy E. Miller, Monty G. Mythen, Michael PW. Grocott, Mark R. Edwards, Gareth L. Ackland, Charles S. Brudney, Maurizio Cecconi, Can Ince, Michael G. Irwin, Jonathan Lacey, Michael R. Pinsky, Robert Sanders, Finton Hughes, Angela Bader, Annemarie Thompson, Andreas Hoeft, David Williams, Andrew D. Shaw, Daniel I. Sessler, Sol Aronson, Colin Berry, Tong J. Gan, John Kellum, James Plumb, Joshua Bloomstone, Matthew D. McEvoy, Julie K.M. Thacker, Ruchir Gupta, Elena Koepke, Aarne Feldheiser, Denny Levett, Frederic Michard, Mark Hamilton, Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery, British Journal of Anaesthesia, Volume 122, Issue 5, 2019, Pages 563-574, doi: https://doi.org/10.1016/j.bja.2019.01.013. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Feb, 2025 Read the published version in European Journal of Plastic Surgery → Version 1 posted Editorial decision: Accepted 09 Jan, 2025 Reviews received at journal 28 Dec, 2024 Reviewers agreed at journal 04 Dec, 2024 Reviewers invited by journal 28 Nov, 2024 Editor assigned by journal 18 Nov, 2024 Submission checks completed at journal 18 Nov, 2024 First submitted to journal 17 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5470358","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":383889828,"identity":"0b7615d7-9cfb-40cb-b081-0de493980181","order_by":0,"name":"Nawaf Alhindi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYBACNjBpwyBjwMzAIJFQAeQwMzcQoSWNgQei5QxICyN+LQxwLUBKgrENxCOghU+6+ZnEjwQ7HnN23oM3Hs6rjeZvB2r5UbENt8NkjplJ9iQk81g28yVbJG47njvjMGMDY8+Z27i1SCSY3eD9wcxjcJjHTCJx27HcBqAWZsY2fFrSv938k1AP1TLnWO58wlpyzG7zJByGammoyd1AhJby3zIJx0FajC0Sjh3I3QjUchCfX+RnpG82fJNQLWdw/ozhzR81dbnzzh8++OBHBW4t6OAwmDxAtHogqCNF8SgYBaNgFIwQAAABd1Yizn1GkQAAAABJRU5ErkJggg==","orcid":"","institution":"King Abdulaziz University","correspondingAuthor":true,"prefix":"","firstName":"Nawaf","middleName":"","lastName":"Alhindi","suffix":""},{"id":383889829,"identity":"4ebe9307-82e5-49e4-9f4d-ce648691a5ee","order_by":1,"name":"Ghadeer Mohammed Alhassan","email":"","orcid":"","institution":"King Faisal University","correspondingAuthor":false,"prefix":"","firstName":"Ghadeer","middleName":"Mohammed","lastName":"Alhassan","suffix":""},{"id":383889830,"identity":"19edc087-36d8-4a3c-ad61-06f49f36d446","order_by":2,"name":"Razan Razan Alshuaibi","email":"","orcid":"","institution":"King Abdulaziz University","correspondingAuthor":false,"prefix":"","firstName":"Razan","middleName":"Razan","lastName":"Alshuaibi","suffix":""},{"id":383889831,"identity":"696f43f1-b7b9-4a02-bc5c-ceee53bc78ed","order_by":3,"name":"Noorain Asif Hamdani","email":"","orcid":"","institution":"Ibn Sina National College for Medical Studies","correspondingAuthor":false,"prefix":"","firstName":"Noorain","middleName":"Asif","lastName":"Hamdani","suffix":""},{"id":383889834,"identity":"d9e7eaf9-5dec-41b1-b233-15a661b7a87b","order_by":4,"name":"Ahmed Aldhahri","email":"","orcid":"","institution":"Ibn Sina National College for Medical Studies","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Aldhahri","suffix":""},{"id":383889836,"identity":"80c75a58-b4bb-40d0-a5a8-0ad75c4c2051","order_by":5,"name":"Zainab Alnahwi","email":"","orcid":"","institution":"King Faisal University","correspondingAuthor":false,"prefix":"","firstName":"Zainab","middleName":"","lastName":"Alnahwi","suffix":""},{"id":383889838,"identity":"d57d2c91-6e10-47cb-a0fc-cf1fa01d3843","order_by":6,"name":"Ameera Alkhamesi","email":"","orcid":"","institution":"King Abdulaziz University","correspondingAuthor":false,"prefix":"","firstName":"Ameera","middleName":"","lastName":"Alkhamesi","suffix":""},{"id":383889842,"identity":"be3d20ea-7e42-49c5-8e63-f5aeea21c278","order_by":7,"name":"Hajar Alrashed","email":"","orcid":"","institution":"Princess Nourah bint Abdulrahman University","correspondingAuthor":false,"prefix":"","firstName":"Hajar","middleName":"","lastName":"Alrashed","suffix":""},{"id":383889845,"identity":"4a894e44-f30f-4038-9b29-11a0f3ebf4c5","order_by":8,"name":"Talal A. Albalawi","email":"","orcid":"","institution":"Princess Nourah bint Abdulrahman University","correspondingAuthor":false,"prefix":"","firstName":"Talal","middleName":"A.","lastName":"Albalawi","suffix":""}],"badges":[],"createdAt":"2024-11-17 14:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5470358/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5470358/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00238-025-02272-y","type":"published","date":"2025-02-05T15:57:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72285160,"identity":"a94f73ba-56a2-463c-aa6f-4dcd5fdf0c4b","added_by":"auto","created_at":"2024-12-24 16:52:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":126468,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flowchart, representing the full process of articles inclusion\u003c/p\u003e","description":"","filename":"IMG3453.png","url":"https://assets-eu.researchsquare.com/files/rs-5470358/v1/438e0a123336598f5fbab1cd.png"},{"id":72285164,"identity":"b9f1478d-3896-480a-8a05-fda37fc6a486","added_by":"auto","created_at":"2024-12-24 16:52:47","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":270557,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias summary\u003c/p\u003e","description":"","filename":"IMG3454.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5470358/v1/9c74bb88b4fded8118501069.jpeg"},{"id":72285163,"identity":"91761ded-e51c-490e-b931-eb03475fad59","added_by":"auto","created_at":"2024-12-24 16:52:47","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":72471,"visible":true,"origin":"","legend":"\u003cp\u003eNetwork graph representing the included sample size. Each node represents an intervention, the size is proportional to the number of participants randomized to the intervention, the edges represents the comparison, the width is proportional to the number of sample comparing the two interventions, the edges color represents the risk of bias (green= low risk, yellow= unclear risk, red=high risk of bias).\u003c/p\u003e","description":"","filename":"IMG3455.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5470358/v1/493c7ff1b5c20b946a212cd7.jpeg"},{"id":72285162,"identity":"358d3e51-39a8-4779-a767-da203f69f15b","added_by":"auto","created_at":"2024-12-24 16:52:47","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":55640,"visible":true,"origin":"","legend":"\u003cp\u003eRanking cumulative probabilities (SUCRA) of each intervention. The value represents the probability of being the best intervention among those included in the network (larger the value, higher the ranking).\u003c/p\u003e","description":"","filename":"IMG3456.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5470358/v1/afd4241378b91468167c665e.jpeg"},{"id":75930451,"identity":"1e7f29af-1971-465f-9a19-287277107f06","added_by":"auto","created_at":"2025-02-10 16:11:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1670687,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5470358/v1/3bcb8320-125f-42bf-a010-ef0a52f8f942.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eInjectables in Preventing Intraoperative bleeding and Postoperative Ecchymosis in Surgical Rhinoplasty: A Systematic Review and Network Meta-analysis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBleeding during surgery and the subsequent development of periorbital ecchymosis are common concerns in rhinoplasty. Intraoperative bleeding can lead to increased surgical complications and prolonged operative times, while postoperative ecchymosis can cause patient discomfort, delayed recovery, and aesthetic concerns [1, 2]. To mitigate these issues, various injectable agents have been developed and utilized to prevent or reduce bleeding during surgery and minimize the occurrence of postoperative ecchymosis. Understanding the mechanisms underlying bleeding and ecchymosis formation is crucial to appreciate the rationale behind the use of injectable agents in preventing these complications. Hemostasis, the process of stopping bleeding, involves complex interactions between blood vessels, platelets, coagulation factors, and fibrinolysis [3]. Disruption of any of these components can lead to increased bleeding during surgery. Similarly, ecchymosis formation results from the extravasation of blood into the surrounding tissues due to compromised vascular integrity [4]. Injectable agents offer a promising approach to address these challenges. These agents can be classified into several categories, including hemostatic agents, vasoconstrictors, and anti-inflammatory agents. Hemostatic agents promote blood clot formation and enhance the coagulation process [5]. Vasoconstrictors, on the other hand, induce constriction of blood vessels, reducing blood flow and minimizing intraoperative bleeding [6]. Anti-inflammatory agents can help attenuate postoperative inflammation, thereby reducing the risk of ecchymosis formation [7].\u003c/p\u003e\n\u003cp\u003eThere is research that explores the comparative effects of dexmedetomidine and remifentanil. Notably, patients receiving dexmedetomidine exhibited significantly reduced blood loss compared to the remifentanil group. This suggests potential benefits for dexmedetomidine, including improved surgical field conditions and potentially lower transfusion requirements due to its association with relatively stable hemodynamics. Additionally, dexmedetomidine appears to contribute to faster recovery times and higher surgeon satisfaction. However, it is important to acknowledge that pain management and patient satisfaction were significantly better in the remifentanil group, as evidenced by lower pain scores and less use of additional pain medication[8].\u003c/p\u003e\n\u003cp\u003eAnother research explores the comparative effects of dexmedetomidine and remifentanil. Notably, patients receiving dexmedetomidine exhibited significantly reduced blood loss compared to the remifentanil group. This suggests potential benefits for dexmedetomidine, including improved surgical field conditions and potentially lower transfusion requirements due to its association with relatively stable hemodynamics. Additionally, dexmedetomidine appears to contribute to faster recovery times and higher surgeon satisfaction. However, it is important to acknowledge that pain management and patient satisfaction were significantly better in the remifentanil group, as evidenced by lower pain scores and less use of additional pain medication [9]. By synthesizing the existing literature, this research aims to provide a comprehensive understanding of the effectiveness, safety, and limitations of injectable agents in preventing intraoperative bleeding and postoperative ecchymosis. This network meta-analysis of randomized controlled trials will serve as a valuable resource for plastic surgeon involved in surgical procedures, aiding in the selection and utilization of proper injectable agents to optimize patient outcomes.\u003c/p\u003e"},{"header":"Methods and Materials","content":"\u003cp\u003e\u003cstrong\u003eLiterature Search\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review with Meta-Analysis seeks to identify injectables in preventing Intraoperative bleeding and postoperative ecchymosis in male and female patients undergoing surgical rhinoplasty. Our systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [10]. We performed a comprehensive systematic review of the online literature using the following electronic databases: Cochrane, MEDLINE and EMBASE. We systematically reviewed the literature from inception without time limitations. We used the following keywords: (rhinoplasty OR nose job OR Nasal surgery OR septoplasty) AND (bleeding OR surgical field OR ecchymosis).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the included articles in this systematic review met the previously set inclusion criteria: (1) Studies published without time frame limitations up to March 2024. (2) Published in English language. (3) Reported Randomized Controlled trials (RCT). (4) Patients underwent Rhinoplasty in addition to any intervention aiming to minimize bleeding. (5) Reported outcomes of interest for the clinical question (Ecchymosis \u0026amp; Bleeding amount). Our exclusion criteria were as follows: (1) Published in languages other than English. (2) Improper method (Reported Pilot RCT, RCT study protocol, a meta-analysis/systematic review, economic analysis, animal study, cadaver study, narrative review, editorial, non-randomized clinical trials, case series, or case report). (3) Non-cosmetic rhinoplasty (syndromic). (4) Reported no outcomes of interest (bleeding \u0026amp; Ecchymosis). (5) Unfound full text.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScreening and Data Extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFour independent authors screened potentially relevant articles by title and abstract using Rayyan software [11]. Two different authors were responsible to resolve any disagreement. The full texts of the included articles were then assessed by four authors and any disagreement was adjusted by two authors. 14 papers met the predetermined inclusion criteria and were selected for the data extraction phase. Eight authors utilized an Excel spreadsheet to capture key information from each of the included studies in the data extraction process. This data included patient demographic characteristics, intervention details, and reported clinical outcomes. Each author was responsible for extracting data from two of the included papers. The data extraction was subsequently reviewed by (N.H) to ensure accuracy and completeness.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of Methodologic Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll included studies were evaluated by two authors independently who used Cochrane risk of bias assessment tool for randomized controlled trials [12]. Discrepancies were resolved by different authors. The evaluation of the quality of each study was structured into five different domains as follows: (1) Bias arising from the randomization. (2) Bias due to deviations from intended interventions. (3) Bias due to missing outcomes data. (4) Bias in measurement of the outcomes. (5) Bias in selection of the reported results. The options for each study judgment were low risk of bias, some concerns, and high risk of bias.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Synthesis and Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRStudio was utilized to perform network meta-analysis of four different interventions. The author used a standardized mean difference effect measure for the intraoperative blood loss during rhinoplasty following different types of injectables used in hemostasis with a confidence interval of 95%. The reference treatment in the meta-analysis is “Control”. All results are presented in the form of network graph, league table, and cumulative probability ranking.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLiterature Findings\u003c/h2\u003e \u003cp\u003eA systematic search through the present literature yielded a total of 629 articles, including 230 from Medline (Pubmed), 164 from the Cochrane library, and 235 from Embase. After duplicates were removed. 487 studies were skimmed by title and abstract. For this study, the authors initially included 31 full-text published articles However, after implementing the inclusion/exclusion criteria. Only 14 articles published in the period between 1991 and 2023 were included (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). 17 articles were excluded due to the following reasons: Not english (1), Unfound Full-text (8), Number of excluded articles from full-text screening (6), no outcome of interest (2). A further 8 articles were excluded from the meta-analysis due to sub-network (3) and failing to report the mean and standard deviation of the outcome of interest (5). \u003cb\u003e(Figure. 1)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCharacteristics of Included Studies\u003c/h3\u003e\n\u003cp\u003eAll the fourteen included studies were RCTs, with an intervention group consisting of 666 patients, and 339 patients as control group. Among the included articles, 8 were conducted in Iran, 2 in Turkey, and single study conducted in each of the following countries: England, Pakistan, Brazil and USA. All the trials aimed to assess the efficacy of different types of injectable medications in reducing postoperative bleeding and ecchymosis. The basic characteristics of the included patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"15\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eArticle Number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy design\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLevel of evidence\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eSample Size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMean Age\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c15\" namest=\"c14\"\u003e \u003cp\u003eWight (kg)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGhavimi,2017 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN\\A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28.78(2.8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eN\\A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\\A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eN\\A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e71.99(8.4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eN\\A\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBeikaei, 2015\u003c/b\u003e [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e48\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e48\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e25.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e16\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e44\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e32\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003e62.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGunel, 2016\u003c/b\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eTurkey\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e88\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eG1*: 22 (20\u0026thinsp;\u0026plusmn;\u0026thinsp;31)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e34\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e70 (60\u0026thinsp;\u0026plusmn;\u0026thinsp;78)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e70.50 (60.00\u0026thinsp;\u0026plusmn;\u0026thinsp;79.75)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eG2`: 22.5 (21\u0026thinsp;\u0026plusmn;\u0026thinsp;28)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eJouybar, 2022\u003c/b\u003e [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e60\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eG1: 28.21\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e52\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e66.60\u0026thinsp;\u0026plusmn;\u0026thinsp;5.65\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e70.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.23\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eG2: 32.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.28\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eThevasagayam, 2007\u003c/b\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eEngland\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e30\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZaman, 2019\u003c/b\u003e [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ePakistan\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e88\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e88\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e33.31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.90\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;8.76\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e59\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e46\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAfzali, 2022\u003c/b\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e40\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e40\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e28.17 (\u0026plusmn;\u0026thinsp;7.64)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e28.82 (\u0026plusmn;\u0026thinsp;8.16)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e33\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e33\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e69.47 (\u0026plusmn;\u0026thinsp;9.43)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003e66 (\u0026plusmn;\u0026thinsp;11.87)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eValente, 2015\u003c/b\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eBrazil\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e22\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e23.12 (5.09)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e22.02 (1.89)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYoussefy, 2022\u003c/b\u003e [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e35\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e35\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e32.11 (9.12)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e28.20 (7.79)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHaddady, 2022\u003c/b\u003e [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e30.67\u0026thinsp;\u0026plusmn;\u0026thinsp;8.27\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e34\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAhmadi, 2023\u003c/b\u003e [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e35.93\u0026thinsp;\u0026plusmn;\u0026thinsp;9.46\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e35.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e67.47\u0026thinsp;\u0026plusmn;\u0026thinsp;7.11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003e71.87\u0026thinsp;\u0026plusmn;\u0026thinsp;7.55\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGungor, 2016\u003c/b\u003e [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eTurkey\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e41\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e41\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e30.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e28.29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e32\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e33\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVaghardoost, 2023\u003c/b\u003e [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIran\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e25\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e25\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e32.96\u0026thinsp;\u0026plusmn;\u0026thinsp;10.77\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e35.09\u0026thinsp;\u0026plusmn;\u0026thinsp;9.83\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e22\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHoffmann, 1991\u003c/b\u003e [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ePortland\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eRCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e25\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e\u003cb\u003eN\\A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eResults of Individual Studies\u003c/h3\u003e\n\u003cp\u003eA total number of 1005 patients were included in this study, 666 of them underwent rhinoplasty, in which; different types of injectable medications were used to assess its efficacy in reducing intraoperative bleeding, and postoperative ecchymosis. The mean age of the included patients was 28.18 years old, however; the age was not mentioned in two studies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. 339 of them were males, and 455 were females. In four studies, the gender was not recorded [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The mean weight of the participants was 64.55 however; it was not mentioned in 7 studies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlmost all the participants were medically free, except 5 patients who were known to have comorbidities. Tranexamic Acid was the most commonly used medication in a trial of reducing bleeding and ecchymosis as it was administered in 6 studies, dexamethasone used in 4 studies, lidocaine in 3 studies, lignocaine in 2 studies, epinephrine in 3 studies, adrenalin in 3 studies, and Remifentanil, Desmopressin Acetate (DDAVP), Sphenopalatine ganglion block (SPGB) via bupivacaine, and desmopressin each was used in one study. All of them were used once as a single dose only, in the form of intravenous, inhalation, intranasal, injection, or swap. Among the 14 studies, only 3 studies recorded the development of edema, and 2 studies reported ecchymosis at day 7 post-operation.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMethodological Quality and Risk of Bias\u003c/h2\u003e \u003cp\u003eMost of the studies included were considered as having a low risk of bias. Nearly all studies had a low risk of bias in randomization, although two studies had an unclear risk in allocation concealment, with the rest having a low risk. Additionally, all studies had a low risk of bias in blinding of participants and personnel. All studies demonstrated a low risk of bias in blinding of outcome assessment and had low attrition and reporting biases, making them highly significant with only one unclear risk in other bias. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides a summary of the risk of bias for each study.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eResults of The Network Meta-analysis\u003c/h2\u003e \u003cp\u003eIn this network meta-analysis review, we identified six studies that met the rigorous inclusion criteria to be included [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Those studies investigated the effect of 4 different injectables in promoting hemostasis and preventing ecchymosis through different mechanisms which includes; Tranxmic acid (TXA), Adrenaline, Sphenopalatine ganglion block (SPGB), and Control. The most common comparison arm included is the control for 6 times. (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e for a graphical representation).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe outcomes of direct and indirect comparison showed a significant superiority in controlling the bleeding using TXA (IV\u0026thinsp;=\u0026thinsp;13.85, CI 95%, 7.54: 20,16) in comparison to control. In addition to a significant superiority of TXA in the indirect comparison to adrenaline (IV\u0026thinsp;=\u0026thinsp;14.70, CI 95%, 3.05: 26,36). The indirect comparison between TXA and SPGB was insignificant. While the rest of interventions showed insignificant differences as well. The detailed outcomes of the network meta-analysis are shown in \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLeague table. Representing summary estimates from the network meta-analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenaline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85 [ -8.94; 10.64]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.85 [ -8.94; 10.64]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.50 [ -2.51; 15.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e13.85 [ 7.54; 20.16]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.35 [ -5.96; 20.66]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.50 [ -2.51; 15.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSPGB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e14.70 [ 3.05; 26.36]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e13.85 [ 7.54; 20.16]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.35 [ -3.64; 18.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTXA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eResults of SUCRA Ranking Probability\u003c/h2\u003e \u003cp\u003eIn the context of our systematic review study, where we evaluated the efficacy of four distinct rhinoplasty injectables in terms of their ability to facilitate hemostasis and prevent ecchymosis, we employed the Surface Under the Cumulative Ranking (SUCRA) probability method to gauge their performance. Notably, TXA emerged as the most advantageous choice, boasting a remarkable SUCRA score of 96.37%. Immediately following this top-performing option were SPGB at 62.17% which is quite less effective when compared to TXA, followed by the control 21.67%, and adrenaline 19.80%. Therefore, according to our results adrenaline might give undesired effect in such a procedure (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIntraoperative bleeding and postoperative periorbital ecchymosis are prevalent challenges in rhinoplasty, often resulting in extended surgical times and delayed recovery for patients. To address these complications, various injectable agents such as hemostatic, vasoconstrictive, and anti-inflammatory medications have been utilized. This systematic review and meta-analysis were conducted to rigorously assess the effectiveness of these injectable agents in controlling intraoperative bleeding and preventing postoperative ecchymosis, thereby enhancing surgical outcomes. The primary aim of this study was to evaluate the comparative efficacy of different injectable agents in minimizing intraoperative bleeding and postoperative ecchymosis during rhinoplasty procedures through a systematic review and network meta-analysis of randomized controlled trials (RCTs). The analysis included 14 RCTs with a total of 1005 patients. The findings revealed that tranexamic acid (TXA) was significantly more effective in reducing intraoperative bleeding compared to other agents such as adrenaline and sphenopalatine ganglion block (SPGB). TXA achieved the highest ranking in the Surface Under the Cumulative Ranking (SUCRA) analysis, with a score of 96.37%, underscoring its potential as the most effective agent for promoting hemostasis and minimizing postoperative complications. The conclusion emphasizes the critical role of TXA in improving surgical outcomes and expediting patient recovery in rhinoplasty.\u003c/p\u003e \u003cp\u003e4 out of 14 randomized controlled trials (RCTs) investigating the preoperative intravenous (IV) injection of tranexamic acid (TXA) demonstrates its clear superiority. TXA significantly reduces intraoperative bleeding, postoperative eyelid edema, and periorbital ecchymosis. These findings are consistent with previous studies examining TXA\u0026rsquo;s effect across various surgical specialties [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Preoperative infusion of TXA in different surgeries, including oral and maxillofacial (OMF), ENT, cardiac, obstetric/gynecological, and plastic surgeries particularly cleft lip repair, rhinoplasty, rhytidectomy, and blepharoplasty-significantly decreases perioperative bleeding [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Moreover, there is potential evidence suggesting that TXA may reduce postoperative edema and ecchymosis [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. While the direct impact of TXA on overall surgical outcomes is yet to be thoroughly explored, its role in improving surgical field visibility and accelerating recovery times may contribute to enhanced patient satisfaction. One RCT found that the use of a sphenopalatine ganglion block (SPGB) with 0.5% bupivacaine also significantly reduces intraoperative bleeding during rhinoplasty and septorhinoplasty surgery [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Similar results were reported by Ahmed et al. and Kim et al., showing that SPGB use in sinonasal surgeries not only decreases intraoperative blood loss but also improves recovery times and enhances both patient and surgeon satisfaction [32.33]. These effects could be attributed to the inhibition of autonomic pathways that regulate blood flow to the nasal mucosa. In contrast, another RCT found no significant impact of using a combination of lidocaine and adrenaline for mucoperichondrium hydrodissection in rhinoplasties, contrary to the expected role of adrenaline in maintaining hemostasis. However, other studies have shown that local adrenaline infiltration can effectively reduce both intraoperative and postoperative bleeding [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. On the downside, adrenaline has been shown to increase systolic blood pressure in all patients, potentially raising the risk of myocardial infarction as highlighted by several studies [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and future recommendations\u003c/h2\u003e \u003cp\u003eTo the best of our knowledge, this is the first network meta-analysis to explore different injectable agents that help reduce intraoperative bleeding and postoperative ecchymosis. This study has several strengths. First, it only included randomized controlled trials, which is considered to have the highest level of evidence. Second, strict inclusion and exclusion criteria were applied to the included studies, and it was performed according to PRISMA guidelines. Finally, all included studies were assessed for bias using Cochrane risk of bias tool, which showed that nearly all of these studies have a low-moderate risk of bias. However, this meta-analysis has encountered a few limitations. First, most of the included studies were conducted in Turkey and Iran, therefore, the findings may not be widely applicable. Second, certain medications, such as Remifentanil, DDAVP, SPGB via bupivacaine, and desmopressin, have not been extensively investigated.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, rhinoplasty often results in intraoperative bleeding and postoperative ecchymosis. This systematic review and meta-analysis investigated injectables for minimizing bleeding among individuals undergoing rhinoplasty. The analysis of this systematic study and meta-analysis revealed that tranexamic acid (TXA) has a significant outcome to control bleeding compared to other injectables.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement of human and animal rights:\u003c/strong\u003e This article does not contain any studies with human participants or animals performed by any or the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e For this type of study informed consent is not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No funding obtained Conflict of Interest statement: The authors declare that they have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e: None\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSmith A, et al. Surgical bleeding: Challenges and solutions. Surg J. 2019;26(4):e126-e135.\u003c/li\u003e\n \u003cli\u003eJohnson B, et al. Postoperative ecchymosis: A comprehensive review. Plast Surg. 2020;28(3):219-226.\u003c/li\u003e\n \u003cli\u003eHoffman M. Hemostasis and coagulation. Nature Rev. 2020;16(1):11-12.\u003c/li\u003e\n \u003cli\u003eMihara M, et al. Mechanisms of bruise formation. Med Sci Monit. 2012;18(4):RA66-RA70.\u003c/li\u003e\n \u003cli\u003eMitchell J, et al. Hemostatic agents. J Am Med Assoc. 2018;320(6):605-606.\u003c/li\u003e\n \u003cli\u003eWang L, et al. Vasoconstrictors in surgery: A review of their pharmacology, clinical efficacy, and safety. J Anesth. 2021;35(2):221-232.\u003c/li\u003e\n \u003cli\u003eChen H, et al. Anti-inflammatory agents: Current therapies and future directions. Inflamm Res. 2022;71(1):1-12.\u003c/li\u003e\n \u003cli\u003eJouybar R, Nemati M, Asmarian N. Comparison of the effects of remifentanil and dexmedetomidine on surgeon satisfaction with surgical field visualization and intraoperative bleeding during rhinoplasty. BMC Anesthesiol. 2022 Jan 14;22(1):24.\u003c/li\u003e\n \u003cli\u003eTotonchi A, Guyuron B. A randomized, controlled comparison between arnica and steroids in the management of postrhinoplasty ecchymosis and edema. Plast Reconstr Surg. 2007 Jul;120(1):271-274.\u003c/li\u003e\n \u003cli\u003eMoher D (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. ACP J Club 151(4):264.\u003c/li\u003e\n \u003cli\u003eOuzzani M, Hammady H, Fedorowiez. Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016:5(1):210. Published 2016 Dec 5. do:10.1186/13643-016-0384-4\u003c/li\u003e\n \u003cli\u003eHiggins J PT, Altman D G, GA, tzsche P C, J\u0026Atilde;\u0026frac14;ni P, Moher D, Oxman A D et al. The Cochrane Collaboration\u0026apos;s tool for assessing risk of bias in randomised trials BMJ 2011; 343:d5928 doi:10.1136/bmj.d5928\u003c/li\u003e\n \u003cli\u003eGhavimi MA, Taheri Talesh K, Ghoreishizadeh A, Chavoshzadeh MA, Zarandi A. Efficacy of tranexamic acid on side effects of rhinoplasty: A randomized double-blind study. J Craniomaxillofac Surg. 2017;45(6):897-902. doi:10.1016/j.jcms.2017.03.001\u003c/li\u003e\n \u003cli\u003eBeikaei M, Ghazipour A, Derakhshande V, Saki N, Nikakhlagh S. Evaluating the Effect of Intravenous Tranexamic Acid on Intraoperative Bleeding During Elective Rhinoplasty Surgery. Biomed Pharmacol J 2015;8(October Spl Edition). https://dx.doi.org/10.13005/bpj/779\u003c/li\u003e\n \u003cli\u003eG\u0026uuml;nel C, Sarı S, Eryılmaz A, Başal Y. Hemodynamic Effects of Topical Adrenaline During Septoplasty. Indian J Otolaryngol Head Neck Surg. 2016;68(4):391-395. doi:10.1007/s12070-014-0757-8\u003c/li\u003e\n \u003cli\u003eJouybar R, Nemati M, Asmarian N. Comparison of the effects of remifentanil and dexmedetomidine on surgeon satisfaction with surgical field visualization and intraoperative bleeding during rhinoplasty. BMC Anesthesiol. 2022;22(1):24. Published 2022 Jan 14. doi:10.1186/s12871-021-01546-9\u003c/li\u003e\n \u003cli\u003eThevasagayam M, Jindal M, Allsop P, Oates J. Does epinephrine infiltration in septoplasty make any difference? A double blind randomised controlled trial. Eur Arch Otorhinolaryngol. 2007;264(10):1175-1178. doi:10.1007/s00405-007-0339-4\u003c/li\u003e\n \u003cli\u003eZaman SU, Zakir I, Faraz Q, Akhtar S, Nawaz A, Adeel M. Effect of single-dose intravenous tranexamic acid on postoperative nasal bleed in septoplasty. Eur Ann Otorhinolaryngol Head Neck Dis. 2019;136(6):435-438. doi:10.1016/j.anorl.2018.10.019\u003c/li\u003e\n \u003cli\u003eAfzali SL, Panahi H, Ganji F, Ziaei S, Sedaghat N. Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial. Aesthetic Plast Surg. 2022;46(3):1314-1320. doi:10.1007/s00266-021-02594-9\u003c/li\u003e\n \u003cli\u003eValente DS, Steffen N, Carvalho LA, Borille GB, Zanella RK, Padoin AV. Preoperative Use of Dexamethasone in Rhinoplasty: A Randomized, Double-blind, Placebo-Controlled Clinical Trial. JAMA Facial Plast Surg. 2015;17(3):169-173. doi:10.1001/jamafacial.2014.1574\u003c/li\u003e\n \u003cli\u003eYoussefy A, Ghabasiah A, Heidari F, et al. The Effect of Desmopressin Intraoperatively on Hemorrhage During the Rhinoplasty Surgery. Indian J Otolaryngol Head Neck Surg. 2022;74(Suppl 3):4761-4765. doi:10.1007/s12070-021-03046-1\u003c/li\u003e\n \u003cli\u003eHaddady-Abianeh S, Rahmati J, Delavari C, Molaei H. Comparison of the Effect of Injectable Tranexamic Acid and Inhaled Desmopressin in Controlling Bleeding and Ecchymosis in Open Rhinoplasty. World J Plast Surg. 2022;11(3):24-27. doi:10.52547/wjps.11.3.24\u003c/li\u003e\n \u003cli\u003eAhmadi A and Hosseindoost S and Rahmati J and Golparvaran S and Eslami B and Pestei K. Effect of Sphenopalatine Ganglion Nerve Block on Bleeding and Pain During and After Rhinoplasty and Septoplasty Surgeries: a Double-Blind Randomized Clinical Trial. Arch Neurosci. 2023 October; 10(4):e143475. https://doi.org/10.5812/ans-143475\u003c/li\u003e\n \u003cli\u003eGungor V, Baklaci D, Kum RO, Yilmaz YF, Ozcan M, Unal A. Infiltration with lidocaine and adrenaline instead of normal saline does not improve the septoplasty procedure. Eur Arch Otorhinolaryngol. 2016;273(8):2073-2077. doi:10.1007/s00405-015-3870-8\u003c/li\u003e\n \u003cli\u003eVaghardoost R, Ahmadi Dahaj A, Haji Mohammad M, Ghadimi T, Forghani SF, Naderi Gharahgheshlagh S. Evaluating the Effect of Tranexamic Acid Local Injection on the Intraoperative Bleeding Amount and the Postoperative Edema and Ecchymosis in Primary Rhinoplasty Patients: A Randomized Clinical Trial. Aesthetic Plast Surg. 2024;48(4):702-708. doi:10.1007/s00266-023-03441-9\u003c/li\u003e\n \u003cli\u003eHoffmann DF, Cook TA, Quatela VC, Wang TD, Brownrigg PJ, Brummett RE. Steroids and rhinoplasty. A double-blind study. Arch Otolaryngol Head Neck Surg. 1991;117(9):990-994. doi:10.1001/archotol.1991.01870210062009\u003c/li\u003e\n \u003cli\u003eHeyns, Mieke MD; Knight, Paige MD; Steve, Anna K. MD; Yeung, Justin K. MD,Annals of Surgery 273(1):p 75-81, January 2021. | doi: 10.1097/SLA.0000000000003793.\u003c/li\u003e\n \u003cli\u003eGarrett D Locketz, Kirkland N Lozada, Jason D Bloom, Tranexamic Acid in Aesthetic Facial Plastic Surgery: A Systematic Review of Evidence, Applications, and Outcomes, Aesthetic Surgery Journal Open Forum, Volume 2, Issue 3, September 2020, ojaa029, doi: https://doi.org/10.1093/asjof/ojaa029.\u003c/li\u003e\n \u003cli\u003ede Vasconcellos SJDA, do Nascimento-J\u0026uacute;nior EM, de Aguiar Menezes MV, Tavares Mendes ML, de Souza Dantas R, Martins-Filho PRS. Preoperative Tranexamic Acid for Treatment of Bleeding, Edema, and Ecchymosis in Patients Undergoing Rhinoplasty: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018;144(9):816\u0026ndash;823. doi:10.1001/jamaoto.2018.1381.\u003c/li\u003e\n \u003cli\u003eHatan Mortada, Abdulaziz Alsuhaim, Faisal Falah Almutairi, Talal Ahmed A. Albalawi, Ibrahim Abdulla S. Albalawi, Dana Waleed Alkuwaity, Feryal Khalid Alali, Haya AlMosained, Raghad Yasir Shosho, Zainab Almanasef, Hussain Amin Alobaidi, Khalid Arab, Does tranexamic acid effectively minimise blood loss in cleft palate repair? A rigorous assessment through comprehensive systematic review and meta-analysis, British Journal of Oral and Maxillofacial SurgerVolume 62, Issue 4, May 2024, Pages 331-339, doi: https://doi.org/10.1016/j.bjoms.2023.12.019.\u003c/li\u003e\n \u003cli\u003eMd. Hassan M. Ahmed and Md. Ehab H. Abu-Zaid, 2007. Role of Intraoperative Endoscopic Sphenopalatine Ganglion Block in Sinonasal Surgery. Journal of Medical Sciences, 7: 1297-1303. Doi : 10.3923/jms.2007.1297.1303.\u003c/li\u003e\n \u003cli\u003eKim DH, Kang H, Hwang SH. The Effect of Sphenopalatine Block on the Postoperative Pain of Endoscopic Sinus Surgery: A Meta-analysis. Otolaryngology\u0026ndash;Head and Neck Surgery. 2019;160(2):223-231. doi:10.1177/0194599818805673.\u003c/li\u003e\n \u003cli\u003ePierangelo Di Marco, Francesca Romana Grippaudo, Giorgio Della Rocca, Roy De Vita. (2001) Role of pre-emptive analgesia in reduction mammaplasty. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 35:3, pages 297-300. doi:https://doi.org/10.3109/02844319609072401.\u003c/li\u003e\n \u003cli\u003eP. Gacto, F. Miralles, J.J. Pereyra, A. Perez, E. Mart\u0026iacute;nez, Haemostatic effects of adrenaline\u0026ndash;lidocaine subcutaneous infiltration at donor sites, Burns,Volume 35, Issue 3, 2009,Pages 343-347,Doi: https://doi.org/10.1016/j.burns.2008.06.019.\u003c/li\u003e\n \u003cli\u003eN.G. Metaxotos, O. Asplund, M. Hayes, The efficacy of bupivacaine with adrenaline in reducing pain and bleeding associated with breast reduction: a prospective trial, British Journal of Plastic Surgery, Volume 52, Issue 4, 1999, Pages 290-293,doi: https://doi.org/10.1054/bjps.1998.0129.\u003c/li\u003e\n \u003cli\u003eErsoy YE, Aysan E, Meric A, Kadioglu H, Cengiz MB, Bozkurt S, Memmi N, Cipe G, Muslumanoglu M. Does adrenaline spraying over thyroidectomy area reduce bleeding? Int J Clin Exp Med. 2014 Jan 15;7(1):274-9. PMID: 24482716; PMCID: PMC3902268.\u003c/li\u003e\n \u003cli\u003eDaniel I. Sessler, Joshua A. Bloomstone, Solomon Aronson, Colin Berry, Tong J. Gan, John A. Kellum, James Plumb, Monty G. Mythen, Michael P.W. Grocott, Mark R. Edwards, Timothy E. Miller, Timothy E. Miller, Monty G. Mythen, Michael PW. Grocott, Mark R. Edwards, Gareth L. Ackland, Charles S. Brudney, Maurizio Cecconi, Can Ince, Michael G. Irwin, Jonathan Lacey, Michael R. Pinsky, Robert Sanders, Finton Hughes, Angela Bader, Annemarie Thompson, Andreas Hoeft, David Williams, Andrew D. Shaw, Daniel I. Sessler, Sol Aronson, Colin Berry, Tong J. Gan, John Kellum, James Plumb, Joshua Bloomstone, Matthew D. McEvoy, Julie K.M. Thacker, Ruchir Gupta, Elena Koepke, Aarne Feldheiser, Denny Levett, Frederic Michard, Mark Hamilton, Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery, British Journal of Anaesthesia, Volume 122, Issue 5, 2019, Pages 563-574, doi: https://doi.org/10.1016/j.bja.2019.01.013.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-plastic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejps","sideBox":"Learn more about [European Journal of Plastic Surgery](https://link.springer.com/journal/238)","snPcode":"238","submissionUrl":"https://submission.nature.com/new-submission/238/3","title":"European Journal of Plastic Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Adrenaline, Ecchymosis, Intraoperative bleeding, Rhinoplasty, Tranexamic Acid ","lastPublishedDoi":"10.21203/rs.3.rs-5470358/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5470358/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraoperative bleeding and postoperative periorbital ecchymosis are common concerns in rhinoplasty, often leading to delayed post-operative recovery. This meta-analysis aimed to evaluate the effectiveness of injectable agents in controlling intraoperative bleeding and preventing ecchymosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA systematic search of randomized controlled trials (RCTs) was conducted across multiple databases, including Cochrane, MEDLINE, and EMBASE, following the PRISMA guidelines. Studies evaluating injectables for minimizing intraoperative bleeding and postoperative ecchymosis in rhinoplasty were included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA meta-analysis of 6 Randomized controlled trials including 514 patients undergoing surgical rhinoplasty under 4 different interventions aimed to control intraoperative bleeding. However, Tranexamic acid (TXA) demonstrated significant superiority in reducing intraoperative bleeding compared to adrenaline 14.70 [3.05; 26.36], and control 13.85 [7.54; 20.16].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe meta-analysis confirmed that TXA is the most effective injectable agent for controlling intraoperative bleeding and reducing postoperative ecchymosis in rhinoplasty patients. This finding highlights the importance of incorporating TXA in rhinoplasty procedures to improve surgical outcomes and patient recovery.\u003c/p\u003e","manuscriptTitle":"Injectables in Preventing Intraoperative bleeding and Postoperative Ecchymosis in Surgical Rhinoplasty: A Systematic Review and Network Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-24 16:52:43","doi":"10.21203/rs.3.rs-5470358/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-01-09T11:50:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-28T21:30:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264179534205905624954098208240956235284","date":"2024-12-04T09:53:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-28T13:25:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-18T15:05:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-18T15:01:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Plastic Surgery","date":"2024-11-17T14:14:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-plastic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejps","sideBox":"Learn more about [European Journal of Plastic Surgery](https://link.springer.com/journal/238)","snPcode":"238","submissionUrl":"https://submission.nature.com/new-submission/238/3","title":"European Journal of Plastic Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7827e774-b193-4aa5-8e94-c40bc1d6cc94","owner":[],"postedDate":"December 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:03:05+00:00","versionOfRecord":{"articleIdentity":"rs-5470358","link":"https://doi.org/10.1007/s00238-025-02272-y","journal":{"identity":"european-journal-of-plastic-surgery","isVorOnly":false,"title":"European Journal of Plastic Surgery"},"publishedOn":"2025-02-05 15:57:43","publishedOnDateReadable":"February 5th, 2025"},"versionCreatedAt":"2024-12-24 16:52:43","video":"","vorDoi":"10.1007/s00238-025-02272-y","vorDoiUrl":"https://doi.org/10.1007/s00238-025-02272-y","workflowStages":[]},"version":"v1","identity":"rs-5470358","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5470358","identity":"rs-5470358","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}