Preoperative carbohydrate loading reduces length of hospital stay compared to fasting in patients undergoing major elective, non-cardiac surgery: A systematic Review and Meta- Analysis

Preoperative carbohydrate loading reduces length of hospital stay compared to fasting in patients undergoing major elective, non-cardiac surgery: A systematic Review and Meta- Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Preoperative carbohydrate loading reduces length of hospital stay compared to fasting in patients undergoing major elective, non-cardiac surgery: A systematic Review and Meta- Analysis Anna Réka Sebestyén, Ambrus Szemere, Marcell Virág, Klementina Ocskay, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4085704/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 May, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Introduction Preoperative fasting is a worldwide routine even though the most recent Enhanced Recovery After Surgery (ERAS) Guidelines recommend preoperative carbohydrate loading instead of fasting, but with low quality of evidence. Our aim was to compare the effects of preoperative carbohydrate loading to fasting and placebo in patients undergoing elective major non-cardiac surgery under general anaesthesia. Methods Our systematic search was conducted on 15 th of October 2021 in five databases, Medline, Embase, Central, Web of Science and Scopus. We included randomized controlled trials that compared the carbohydrate loading (CHO-group) with fasting (Fasting-group) and with placebo (Placebo-group). Main outcomes were length of hospital stay (LOS), postoperative glucose levels on postoperative day 1 and 2, postoperative insulin levels on postoperative day 1, and C-reactive protein (CRP) levels on postoperative day 1. Results Our search revealed 55 eligible articles for the data extraction. LOS was almost two days shorter in the CHO-group as compared to the Fasting-group (MD: -1,71 [95% CI: -3.04, -0,38] days), but there was no significant result when compared to the Placebo-group (-0.01 [-0.16; 0.16]). There were no significant differences between the CHO-group and Fasting-group and CHO-group and Placebo-group regarding the postoperative glucose, insulin and CRP levels. Conclusion This meta-analysis found that preoperative CHO-loading as compared to preoperative fasting shortened the length of hospital stay in patients undergoing major elective, non-cardiac surgery. Although several details are still to be unveiled, these data provide further support that preoperative fluid intake with CHO-loading could be beneficial in this patient population. Health sciences/Diseases Health sciences/Medical research Preoperative fasting oral carbohydrate loading major surgery non-cardiac surgery length of stay Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Preoperative fasting, when patients are forbidden to consume food and drink after midnight prior to surgery, is still a common practice worldwide (1). The reason behind this strategy is to reduce the risk of aspiration of stomach contents during induction of and emergence from anaesthesia (2). Despite the increasing evidence that fasting may increase the risk of postoperative complications, such as metabolic stress manifesting in hyperglycemia, insulin resistance and a more pronounced inflammatory response, preoperative fasting remains a common practice (3). However, the most recent Enhanced Recovery After Surgery (ERAS) Guidelines recommend the intake of solid food 5-6 hours before surgery, clear fluids up to 2 hours and even strongly recommend preoperative carbohydrate loading (CHO) (4). Carbohydrate loading may have several potential benefits such as less metabolic stress, and less pronounced inflammatory response and shorter hospital stay, however, clear evidence is still lacking (5). Although the recommendation is strong, the quality of the evidence remains low or moderate in the majority of the guidelines (4). Therefore, our aim was to synthetize and re-analyze all relevant literature to assist policymakers and guideline authors by generating the highest level of evidence in decision making. METHODS We report our systematic review and meta-analysis based on the recommendations of the PRISMA 2020 guideline (6), while we followed the Cochrane Handbook (7). The protocol of the study was registered on PROSPERO (CRD42021284663) and we fully adhered to it. Eligibility criteria Randomized controlled trials (RCTs) were included, reporting on patients undergoing elective major non-cardiac surgery under general anaesthesia. Case series, case reports, editorials, commentaries, qualitative studies were excluded. Articles available only in abstract form or meeting reports were also excluded. We applied no filters, no restrictions on methodological quality, publication date or language. Major surgery was defined as any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. Non-cardiac surgery was defined as every type of major surgery except cardiac. We defined preoperative carbohydrate loading (CHO) as a carbohydrate, mineral and vitamin containing amount of fluid which is consumed maximum 2 hours prior surgery (CHO-group). Those studies that utilized more interventions of the ERAS guideline were excluded to investigate the effect of carbohydrates only. Preoperative fasting was defined as no food consuming after midnight prior surgery, which means, no breakfast was allowed even when the surgeries were scheduled in the afternoon, making some of the patients fast for 12-15 hours. We defined placebo as a fluid, with artificial sweeteners, vitamins, and minerals. Basic characteristics of the patient population are included in the Supplementary material (Supplementary Table S1.). Information sources Our systematic search was conducted on 15 th of October, 2021 in five databases, Medline (via Pudmed), Embase, Cochrane Central Register for Controlled Trials (CENTRAL), Web of Science and Scopus. Search strategy During the systematic search the following search key was used: (preoperative AND ('carbohydrate'/exp OR carbohydrate) OR 'fasting abbreviation') AND random* in Embase. In the other four databases, we used ((preoperative AND carbohydrate) OR "fasting abbreviation") AND random* . Selection process The selection was performed by two independent authors (AS and ASz using Endnote X20), disagreements were resolved by consensus. After automatic and manual duplicate removal, we screened the records based on title and abstract, and after this step, we screened the remaining records based on full text against the predefined eligibility criteria. There were cases, when multiple studies used the same patient database for the same outcomes. In these cases, we recruited only one study with the largest sample in our analysis. Data collection process Data collection phase was performed by two independent authors (AS and ASz). The following data were extracted: first author, the year of publications, study population, study period, country, intervention, fasting and placebo group, number of patients, baseline characteristics, LOS, postoperative glucose and insulin levels, postoperative CRP levels. Study risk of bias assessment We assessed the risk of bias by a Cochrane-recommended bias tool for randomized trials (RoB 2.0) for RCTs (8). Risk of bias assessment was performed by two independent review (AS and ASz) authors and disagreements resolved by consensus. Quality of evidence evaluation was executed following the guidance of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) workgroup. Assessment of the quality of evidence was arranged in tables, that were prepared with the GRADEPro Guideline Development Tool (9). Statistics Data synthesis was performed by using the methods recommended by the Cochrane Collaboration (7) For continuous outcomes pooled MDs with their 95% CI were calculated to investigate the differences between the compared arms. The restricted maximum likelihood estimator was used. The random effects model was applied for meta-analyses. If the study number for the given outcome was over five, the Hartung–Knapp adjustment (10, 11) was applied. Statistical heterogeneity across trials was assessed by means of the Cochrane Q test, and the I2 values, where p < 0.1 was considered as statistically significant. The statistical analyses were carried out by R (R Core Team 2021, v 4 1.1, R Foundation for Statistical Computing, Vienna, Austria) (12) using the meta Schwarzer G. General package for meta-analysis (12) and Dmetar (14) packages. Forest plots were used to visualize the findings of the meta-analytical calculations. RESULTS Search and selection Altogether 9698 studies were identified during our search in Medline (via Pubmed), Embase, World of Science, Cochrane CentralRegoster of Controlled Trials (Central) and Scopus databases, and 55 studies were found eligible for inclusion in the meta-analysis and systematic review. The exact details of selection are outlined in the PRISMA flowchart (Fig. 1). Figure 1. PRISMA flowchart of selection process Basic characteristics of included studies Baseline characteristics of the enrolled analyses are detailed in Supplementary Table (Figure 1). Length of hospital stay Twenty studies (15-33), including 2116 patients, used LOS as an outcome, when investigating effects of CHO-loading. Fourteen (15-28) of these studies used fasting and seven applied placebos in the control groups (19, 27, 29-33), and two of them used both comparisons (19, 27). LOS in the CHO-group vs the Fasting-group was shorter (MD: -1,71 [95% CI: -3.04, -0,38] p<0.01) (Fig. 2/A). When compared to the Placebo-group, we did not find a statistically significant difference, as the LOS was only (-0.01) day shorter in the CHO-group (Fig. 2/B). Considerable statictical heterogenity was detected in both cases. Figure 2. Length of hospital stay (A: CHO vs fasting; B: CHO vs placebo) CHO, carbohydrate loading; Glucose and insulin levels Across six studies (15, 18, 24, 34, 35, 36) of 745 patients glucose levels were measured on postoperative day 1 and 2. Glucose levels on postoperative day 1 (18, 24, 34, 35, 36) and day 2 (15, 18, 24, 35) showed no significant differences (-1.10 [-0.48;0.46], 0,21 [-0.31;0.72]) between the CHO-group and Fasting-group (Supplementary Fig.2 and Fig.3). Four studies, (29, 30, 31, 37) including 267 patients compared the effects of carbohydrate loading on postoperative glucose levels to placebo on postoperative day 1. There was a non-significant difference between the groups (Supplementary Fig.6). Four studies including 133 patients measured insulin levels on postoperative day 1 (19, 32, 36) and on postoperative day 2 (15, 18, 35), and compared CHO loading to fasting. There were no significant difference neither on postoperative day 1(MD: -3.36 μU/mL, 95% CI [-8.15; 1.44] I 2 =94% χ²=14.013 p<0.01) (Supplementary Fig. 4), nor on postoperative day 2 (MD: -1.99 μU/mL, 95% CI [-5.05 ; 1.07) I 2 =91%, χ²=5.732, p<0.01) (Supplementary Fig. 4). Three studies including 59 patients used placebo as comparison (30, 31, 37), and reported insulin levels on day 1. We found no significant difference between the groups (Supplementary Fig. 5). CRP levels Three studies (36, 39, 40) including 126 patients, investigated the effect of carbohydrate loading on postoperative CRP levels measured in mg/L, and compared CHO loading to fasting, and three studies including (30, 38, 40) 63 patients compared it to placebo. The point estimate showed lower CRP levels in the CHO-group in both comparisons, but it did not reach statistical significance (Fig. 3 and 4). Figure 3. Forest plot of C reactive protein levels on postoperative day 1 (CHO vs fasting) Figure 4. Forest plot of C reactive protein levels on postoperative day 1 (CHO vs placebo) CHO, carbohydrate loading; Risk of bias assessment and level of evidence The risk of bias assesement revealed that there are some concerns regarding biasing factors. The overall risk of bias was low in 17 RCTS regarding all the outcomes, some concerns came up at 17 studies and one studies found high risk regarding biasing factors (S8-17 in Supplementary Table). The GRADE assessment resulted in moderate certainty about LOS when comparing CHO-group with Fasting-group and Placebo-group. All the other outcomes were appeared to have very low certainty (S18-19 in Supplementary Table). DISCUSSION Length of hospital stay We considered the LOS as our primary outcome, as in our opinion this may represent the overall effects of preoperative CHO-loading best, due to the potential beneficial effects on several important confounders such as better postoperative blood sugar control, faster gastro-intestinal recovery, lesser chance of nosocomial infections and also the reduction of hospital costs (41). Other safety outcomes were not assessed in this study. We found that LOS of those patients who received CHO loading was significantly shorter by a mean of 1.7 [-3.04;-0.38] days when compared to preoperative fasting that should be considered as a clinically relevant difference. Although difficult to explain, but some authors believe that CHO-loading could result in a more balanced glucose homeostasis that is the main reason for reduced LOS (15, 21). However, our data did not provide satisfactory support to this hypothesis. More detailed assessment of glucose homeostasis should be considered in the future. Liu et al., found that the loss of muscle mass was lower in the CHO-group, which was considered responsible for the faster recovery (18). Unfortunately, based on the available data on postoperative blood sugar and insulin levels, but also on CRP levels – as the only reported and poolable marker of postoperative inflammation – we found no significant differences between the groups. Hospital LOS is influenced by multiple factors, such as adequate pain and fluid management, early mobilization, earlier start of oral food and fluid intake, etc., not analyzed in the current meta-analysis as data was either scarce or not reported at all (16, 18, 19, 20, 24). It is also important to note that there is a difference in the terms of ‘length of hospital stay’, ‘total lengths of hospital stay’ (18) and ‘readiness to discharge’ (26) that was also inconsistently defined in the articles. LOS may also be affected by local organizational issues such as timing of surgery after hospital admission and the timing of patient discharge. Therefore, we entirely agree with Cho et al (26), who suggested to use the term, “time to ready to discharge” in the future as an outcome measure instead of the actual LOS. There was no significant difference in the hospital LOS when CHO-loading was compared to placebo. In fact, the pooled results were almost identical with a very narrow confidence interval (0.01 [-0.18;0.16]). Regarding the type of the placebo in general, plain water is one option (19, 30, 31, 38, 42, 43, 44), but in this case, patients could be able to identify the difference between the drug and placebo by its sweetness, hence blinding is questionable. An alternative option is the use of artificial sweeteners (27, 29, 33, 34, 45, 46, 47, 48, but in this case, one cannot exclude their metabolic effects (19). In our meta-analysis, the used placebos differed greatly in the studies. In some cases, the authors used plain water (31, 32), while Yuill et al. (37) used fluid with minerals that was not flavored either, so double-blindness cannot be guaranteed which is a biasing factor all in general. Nevertheless, in our opinion, this is the most suitable placebo for investigating the effects of carbohydrates in a placebo-controlled trial design. Although it remains difficult to give an exact explanation of the difference between the fasting and placebo comparisons, but one cannot exclude that it is not necessarily the CHO-loading but the fasting that is responsible for the worse outcome. A hypothesis that is worth further investigation in the future. Postoperative blood sugar and insulin levels Postoperative hypo- and hyperglycemia should be avoided due to several potential adverse effects both surgical a general that may delay recovery in general after surgery (2). In the current study we found that the postoperative metabolic status as indicated by serum glucose and insulin levels did not differ significantly between the groups and showed similar tendency in both comparisons to fasting or placebo. When CHO-loading was compared to fasting, there was a minimal mean difference on postoperative day 1(-0.01 [-0.49; 0.46]) and on postoperative day 2 (0.21[-0.30;0.72]) between the groups in the blood glucose levels, but patients in the CHO-group had a tendency of lower serum insulin levels, but the difference did not reach statistical difference. When compared CHO-loading to placebo, the results were similar, with a tendency of favoring CHO-loading, but without statistical significance. However, we were only able to pool data from 3 studies for each comparison, with a high heterogeneity. It is important to note that the used amount, composition, and timing of administration of CHO-loading fluids notably differed in the included studies. Another reason for heterogeneity is that several studies used different timepoints for measuring insulin and glucose levels. Some even recorded these parameters on postoperative day 3 (22) and 7 (22, 49). We believe that expecting such a long-term effect of a relatively low dose CHO-loading preoperatively do not really make sense. Even measuring blood sugar levels on day 1 and 2 is questionable, especially if patients are fed already on day one. As for future research, we believe that timing of postoperative glucose and insulin level measurements should be standardized. A possible approach could be one that was applied by Rizavnovic et al, where they measured glucose levels two hours prior surgery, six hours after surgery, and in the mornings of postoperative day 1 and 2 (35). C-reactive protein CRP is the most commonly used inflammatory biomarker that may also be used for assessing postoperative inflammatory response (41). In both comparisons (to fasting or placebo) there was a similar tendency of lower CRP levels in the CHO-group, but it did not reach statistical significance. How CHO loading could affect postoperative inflammatory response remains uncertain and detailed description of the current hypotheses are beyond the scope of this manuscript. Strengths and limitation The main strength of our analysis is that we strictly followed our protocol, which was registered in advance. Both univariate and multivariate analyses were performed to achieve objectivity. Rigorous methodology was applied, and our results were derived from randomized controlled trials only. However, because of the different methodology that was used in most studies, we were unable to pool all 55 identified studies that were eligible for data extraction, and only 26 (15-40) of them could be used for pooled analyses. The other 29 studies could not be included in any analysis (41-69) (Supplemetary Table). High heterogeneity of data is another limiting factor. We worked with very heterogenous patient population, who were undergoing different types and durations of surgeries. The definition of fasting and placebo also differed to some extent among the studies. The administered carbohydrate fluids varied in contents and amount. The used randomized control trials measured glucose and insulin levels in inappropriate times. Also, the different measuring timepoints seriously limited our study. The main message of this meta-analysis is that CHO-loading as compared to preoperative fasting resulted in significantly shorter length of hospital stay. However, when compared to placebo, this difference disappeared. Based on the non-significant findings in all other outcomes, explanation of these result remains difficult. Implication for practice and research Although our results suggest that preoperative fluid intake with or without CHO is superior to fasting, but the pathophysiology remains unclear. To find out the exact benefits and further details of this intervention renders the need for future research in which circumstances such as timing, dosing, type of fluid, etc. are much more standardized. More information is also needed on glucose homeostasis in order to enable us to determine whether the observed effects are related to the fluid (i.e.: water) intake per se , or its carbohydrate content. Regarding outcomes, we suggest the term “ready to discharge” instead of “length of hospital stay” as some confounding circumstances (i.er.: social background, bed availability, etc.), may affect the time of discharge. Finally, we recognized that postoperative complications are rarely used as an outcome that should also be included as important endpoints on future trials. We would like to highlight the importance of implementing scientific results into daily practice, because with this approach may allow faster recovery and lesser incidence of postoperative complications (70, 71). As compared to the used placebos, such as clear water, water with artificial sweeteners and preformed glucose-free solutions with mineral, we could not find significant differences. CONCLUSION Preoperative carbohydrate loading was found to reduce LOS by an average of 1.71 days compared to fasting. However, LOS of patients in placebo group was similar to those with CHO loading. Although the explanation behind this result is still to be unveiled, these data provide further support that preoperative fluid intake with CHO-loading can be beneficial in this patient population. Declarations Conflict of interest: ZM holds a post as senior medical director at CytoSorbents Europe, Berlin, Germany. CRediT author contribution AS: conceptualization, formal analysis, investigation, resources, writing – original draft, visualization, data curation ASz: conceptualization, resources, investigation, visualization MV: conceptualization, investigation, formal analysis, data curation, visualization, writing – review and editing KO: methodology, validation, data curation, visualization, writing – review and editing FD: methodology, validation, data curation MAE: methodology, validation, data curation, visualization, writing – review and editing LSz: ,software, writing – review and editing CT: conceptualization, writing – review and editing, KH: visualization, supervision, PH: visualization, supervision ZsM: formal analysis, visualization, supervision, writing – review and editing The datasets used in this study can be found in the full-text articles included in the systematic review and meta-analysis. Funding Funding was provided by the Centre for Translational Medicine, Semmelweis University. Sponsors had no role in the design, data collection, analysis, interpretation, and manuscript preparation. Ethical approval No ethical approval was required for this systematic review with meta-analysis, as all data were already published in peer-reviewed journals. No patients were involved in the design, conduct or interpretation of our study. The datasets used in this study can be found in the full-text articles included in the systematic review and meta-analysis. Acknowledgement None to declare. DATA AVAILIBILITY STATEMENT All the data generated an analyzed are included in this article and in its Supplementary table. References Ackerman RS, Tufts CW, DePinto DG, et al. How sweet is this? A review and evaluation of preoperative carbohydrate loading in the enhanced recovery after surgery model. Nutrition in Clinical Practice . 2019;35(2):246-253. doi:10.1002/ncp.10427 Cheng PL, Loh EW, Chen JT, Tam KW. Effects of preoperative oral carbohydrate on postoperative discomfort in patients undergoing elective surgery: A meta-analysis of randomized controlled trials. Langenbeck’s Archives of Surgery . 2021;406(4):993-1005. doi:10.1007/s00423-021-02110-2 Davis G, Fayfman M, Reyes-Umpierrez D, et al. Stress hyperglycemia in general surgery: Why should we care? Journal of Diabetes and its Complications . 2018;32(3):305-309. doi:10.1016/j.jdiacomp.2017.11.010 Gustafsson UO, Scott MJ, Hubner M, et al. Guidelines for perioperative care in elective colorectal surgery: Enhanced recovery after surgery (eras®) society recommendations: 2018. World Journal of Surgery . 2018;43(3):659-695. doi:10.1007/s00268-018-4844-y Noba L, Wakefield A. Are carbohydrate drinks more effective than preoperative fasting: A systematic review of Randomised Controlled Trials. Journal of Clinical Nursing . 2019;28(17-18):3096-3116. doi:10.1111/jocn.14919 Page MJ, McKenzie JE, Bossuyt PM, et al. The Prisma 2020 statement: An updated guideline for reporting systematic reviews. PLOS Medicine . 2021;18(3). doi:10.1371/journal.pmed.1003583 Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions 2nd Edition. Chichester (UK): John Wiley & Sons, 2019. Sterne JA, Savović J, Page MJ, et al. Rob 2: A revised tool for assessing risk of bias in randomised trials. BMJ . Published online 2019:l4898. doi:10.1136/bmj.l4898 GRADEpro Guideline Development Tool. McMaster University; Hamilton, ON, Canada: Evidence Prime; Hamilton, ON, Canada: 2022. [(accessed on19June2022)]. Available online: https://www.gradepro.org/ Knapp G, Hartung J. Improved tests for a random effects meta‐regression with a single covariate. Statistics in Medicine . 2003;22(17):2693-2710. doi:10.1002/sim.1482 IntHout J, Ioannidis JP, Borm GF. The hartung-knapp-sidik-jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard Dersimonian-Laird Method. BMC Medical Research Methodology . 2014;14(1). doi:10.1186/1471-2288-14-25 R core team: A language and environment for statistical computing. 2021. https://cran.r-hub.io/doc/manuals/fullrefman.pdf. Schwarzer G. General package for meta-analysis 2015, 2021. https://github.com/guido-s/meta/ https://link.springer.com/book/10.1007/978-3-319-21416-0 Harrer M, Pim C, Furukawa T, et al. Dmetar: companion R package for the guide doing metaanalysis in R. London: Chapman & Hall/CRC Press, 2020. Pexe-Machado PA, de Oliveira BD, Dock-Nascimento DB, de Aguilar-Nascimento JE. Shrinking preoperative fast time with maltodextrin and protein hydrolysate in gastrointestinal resections due to cancer. Nutrition . 2013;29(7-8):1054-1059. doi:10.1016/j.nut.2013.02.003 Zhao G, Huang Y, Chen X et al. Research on fast track surgery application in lung cancer surgery. Chinese Journal of Lung Cancer. 2010 Feb;13(2):102-6. doi: 10.3779/j.issn.1009-3419.2010.02.04. Panebianco A, Laforgia R, Volpi A et al. Preoperative fasting - "nihil per os" a difficult myth to break down: a randomized controlled study. Journal of the Italian Surgical Association. 2020 Jan-Feb;41(1):84-93 Liu B, Wang Y, Liu S, et al. A randomized controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing elective craniotomy. Clinical Nutrition . 2019;38(5):2106-2112. doi:10.1016/j.clnu.2018.11.008 Noblett SE, Watson DS, Huong H, Davison B, Hainsworth PJ, Horgan AF. Pre‐operative oral carbohydrate loading in colorectal surgery: A randomized controlled trial. Colorectal Disease . 2006;8(7):563-569. doi:10.1111/j.1463-1318.2006.00965.x de Abreu Reis PG, Polakowski C, Lopes M et al. Abbreviated preoperative fasting favours postoperative oral intake at lower hospital admission costs for cancer patients. Journal of Brazilian College of Surgeons 2019 Aug 5;46(3):e20192175. doi: 10.1590/0100-6991e-20192175. Qi L, Wu Y, Shan L, et al. A clinical study of preoperative carbohydrate administration to improve insulin resistance in patients with multiple injuries. Annals of Palliative Medicine . 2020;9(5):3278-3287. doi:10.21037/apm-20-1424 Kaška M, Grosmanová T, Havel E, et al. The impact and safety of preoperative oral or intravenous carbohydrate administration versus fasting in colorectal surgery – a randomized controlled trial. Wiener klinische Wochenschrift . 2010;122(1-2):23-30. doi:10.1007/s00508-009-1291-7 Helminen H, Branders H, Ohtonen P, Saarnio J. Effect of pre-operative oral carbohydrate loading on recovery after day-case cholecystectomy. European Journal of Anaesthesiology . 2019;36(8):605-611. doi:10.1097/eja.0000000000001002 Suh S, Hetzel E, Alter-Troilo K, et al. The influence of preoperative carbohydrate loading on postoperative outcomes in bariatric surgery patients: A randomized, controlled trial. Surgery for Obesity and Related Diseases . 2021;17(8):1480-1488. doi:10.1016/j.soard.2021.04.014 Faria MS, de Aguilar‐Nascimento JE, Pimenta OS, Alvarenga LC, Dock‐Nascimento DB, Slhessarenko N. Preoperative fasting of 2 hours minimizes insulin resistance and organic response to trauma after video‐cholecystectomy: A randomized, controlled, clinical trial. World Journal of Surgery . 2009;33(6). doi:10.1007/s00268-009-0010-x Cho E-A, Lee NH, Ahn J-H, Choi W-J, Byun J-H, Song T. Preoperative oral carbohydrate loading in laparoscopic gynecologic surgery: A randomized controlled trial. Journal of Minimally Invasive Gynecology . 2021;28(5). doi:10.1016/j.jmig.2020.12.002 Sada F, Krasniqi A, Hamza A, Gecaj-Gashi A, Bicaj B, Kavaja F. A randomized trial of preoperative oral carbohydrates in abdominal surgery. BMC Anesthesiology . 2014;14(1). doi:10.1186/1471-2253-14-93 Hamamoto H, Yamamoto M, Masubuchi S, et al. The impact of preoperative carbohydrate loading on intraoperative body temperature: A randomized controlled clinical trial. Surgical Endoscopy . 2018;32(11):4393-4401. doi:10.1007/s00464-018-6273-2 Mathur S, Plank LD, McCall JL, et al. Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery. British Journal of Surgery . 2010;97(4):485-494. doi:10.1002/bjs.7026 Perrone F, da-Silva-Filho AC, Adôrno IF, et al. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial. Nutrition Journal . 2011;10(1). doi:10.1186/1475-2891-10-66 Pędziwiatr M, Pisarska M, Matłok M, et al. Randomized clinical trial to compare the effects of preoperative oral carbohydrate loading versus placebo on insulin resistance and cortisol level after laparoscopic cholecystectomy*. Polish Journal of Surgery . 2015;87(8). doi:10.1515/pjs-2015-0079 Gianotti L, Biffi R, Sandini M, et al. Preoperative oral carbohydrate load versus placebo in major elective abdominal surgery (PROCY). Annals of Surgery . 2018;267(4):623-630. doi:10.1097/sla.0000000000002325 Al-Hirmizy D, Wood N, Ko S, et al. A single centre randomised control study to assess the impact of pre-operative carbohydrate loading on women undergoing major surgery for epithelial ovarian cancer. Cureus . Published online 2020. doi:10.7759/cureus.10169 Wang S, Gao P, Guo X, et al. Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: A prospective randomized trial. BMC Anesthesiology . 2021;21(1). doi:10.1186/s12871-021-01323-8 Rizvanović N, Nesek Adam V, Čaušević S, Dervišević S, Delibegović S. A randomised controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing colorectal surgery. International Journal of Colorectal Disease . 2019;34(9):1551-1561. doi:10.1007/s00384-019-03349-4 Celiksular MC, Saracoglu A, Yentur E. The influence of oral carbohydrate solution intake on stress response before total hip replacement surgery during epidural and general anaesthesia. The Influence of Oral Carbohydrate Solution Intake on Stress Response before Total Hip Replacement Surgery during Epidural and General Anaesthesia . 2016;44(3):117-123. doi:10.5152/tjar.2016.65265 Yuill KA, Richardson RA, Davidson HIM, Garden OJ, Parks RW. The administration of an oral carbohydrate-containing fluid prior to major elective upper-gastrointestinal surgery preserves skeletal muscle mass postoperatively—a randomised clinical trial. Clinical Nutrition . 2005;24(1):32-37. doi:10.1016/j.clnu.2004.06.009 Singh M, Chaudhary M, Vashistha A, Kaur G. Evaluation of effects of a preoperative 2-hour fast with glutamine and carbohydrate rich drink on insulin resistance in maxillofacial surgery. Journal of Oral Biology and Craniofacial Research . 2015;5(1):34-39. doi:10.1016/j.jobcr.2015.02.006 Gumus K, Aydın G. The effect of preoperative nutrition on postoperative CRP and albumin levels in patients undergoing laparoscopic surgery: A surgical nursing perspective. Journal of PeriAnesthesia Nursing . 2020;35(6):592-596. doi:10.1016/j.jopan.2020.06.018 Braga M, Bissolati M, Rocchetti S, Beneduce A, Pecorelli N, Di Carlo V. Oral preoperative antioxidants in pancreatic surgery: A double-blind, randomized, clinical trial. Nutrition . 2011;28(2):160-164. doi:10.1016/j.nut.2011.05.014 Karimian N, Kaneva P, Donatelli F, et al. Simple versus complex preoperative carbohydrate drink to preserve perioperative insulin sensitivity in laparoscopic colectomy. Annals of Surgery . 2020;271(5):819-826. doi:10.1097/sla.0000000000003488 Esaki K, Tsukamoto M, Sakamoto E, Yokoyama T. Effects of preoperative oral carbohydrate therapy on perioperative glucose metabolism during oral– maxillofacial surgery: randomised clinical trial. Asia Pacific Journal of Clinical Nutrition . 2018;27(1):137-143. Dock‐Nascimento DB, de Aguilar‐Nascimento JE, Magalhaes Faria MS, Caporossi C, Slhessarenko N, Waitzberg DL. Evaluation of the effects of a preoperative 2‐hour fast with Maltodextrine and glutamine on insulin resistance, acute‐phase response, nitrogen balance, and serum glutathione after laparoscopic cholecystectomy. Journal of Parenteral and Enteral Nutrition . 2012;36(1):43-52. doi:10.1177/0148607111422719 Wongyingsinn M, Luangchan S, Tungsongsawat S, Trakarnsanga A, Lohsiriwat V. A randomized controlled trial of preoperative carbohydrate drinks on postoperative walking capacity in elective colorectal surgery. Asia Pacific Journal of Clinical Nutrition. 2019;28(4):727-733. doi: 10.6133/apjcn.201912_28(4).0008. van Stijn MF, Soeters MR, van Leeuwen PA, et al. Effects of a carbohydrate‐, glutamine‐, and antioxidant‐enriched oral nutrition supplement on major surgery‐induced insulin resistance: A randomized pilot study. Journal of Parenteral and Enteral Nutrition . 2017;42(4):719-729. doi:10.1177/0148607117711691 Ljunggren S, Hahn RG, Nyström T. Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: A double-blind, randomised controlled clinical trial. Clinical Nutrition . 2014;33(3):392-398. doi:10.1016/j.clnu.2013.08.003 Tewari N, Awad S, Duška F, et al. Postoperative inflammation and insulin resistance in relation to body composition, adiposity and carbohydrate treatment: A randomised controlled study. Clinical Nutrition . 2019;38(1):204-212. doi:10.1016/j.clnu.2018.01.032 Shi M, Hu Z, Yang D, Cai Q, Zhu Z. Preoperative oral carbohydrate reduces postoperative insulin resistance by activating amp-activated protein kinase after colorectal surgery. Digestive Surgery . 2020;37(5):368-375. doi:10.1159/000505515 Libiszewski M, Drozda R, Śmigielski J, Kuzdak K, Kołomecki K. Preparation of patients submitted to thyroidectomy with oral glucose solutions. Polish Journal of Surgery . 2012;84(5): 253-7. doi:10.2478/v10035-012-0042-z Çakar E, Yilmaz E, Çakar E, Baydur H. The effect of preoperative oral carbohydrate solution intake on patient comfort: A randomized controlled study. Journal of PeriAnesthesia Nursing . 2017;32(6):589-599. doi:10.1016/j.jopan.2016.03.008 Lende TH, Austdal M, Bathen TF, et al. Metabolic consequences of perioperative oral carbohydrates in breast cancer patients — an explorative study. BMC Cancer . 2019;19(1). doi:10.1186/s12885-019-6393-7 Doo AR, Hwang H, Ki M-J, Lee J-R, Kim D-C. Effects of preoperative oral carbohydrate administration on patient well-being and satisfaction in thyroid surgery. Korean Journal of Anesthesiology . 2018;71(5):394-400. doi:10.4097/kja.d.18.27143 Tarasova IA, Inviyaeva EV, Bunyatyan KA, Tskhovrebov AT, Nikoda VV, Shestakov AL. The influence of the preoperative preload with carbohydrates upon metabolic, immune and cytokine statuses after reconstructive esophageal surgical interventions. Medical Immunology (Russia) . 2018;20(6):877-888. doi:10.15789/1563-0625-2018-6-877-888 Ravanini G, Portari PE, Povedano A, Luna RA. Organic inflammatory response to reduced preoperative fasting time, with a carbohydrate and protein enriched solution. A randomised trial. Clinical Nutrition ESPEN . 2016;12. doi:10.1016/j.clnesp.2016.02.074 Onalan E, Andsoy II, Ersoy OF. The effect of preoperative oral carbohydrate administration on insulin resistance and comfort level in patients undergoing surgery. Journal of PeriAnesthesia Nursing . 2018;34(3):539-550. doi:10.1016/j.jopan.2018.07.007 Canbay Ö, Adar S, Karagöz AH, Çelebi N, Bilen CY. Effect of preoperative consumption of high carbohydrate drink (Pre-Op®) on postoperative metabolic stress reaction in patients undergoing radical prostatectomy. International Urology and Nephrology . 2014;46(7):1329-1333. doi:10.1007/s11255-013-0612-y Dilmen OK, Yentur E, Tunali Y, Balci H, Bahar M. Does preoperative oral carbohydrate treatment reduce the postoperative surgical stress response in lumbar disc surgery? Clinical Neurology and Neurosurgery . 2017;153:82-86. doi:10.1016/j.clineuro.2016.12.016 Henriksen MG, Hessov I, Dela F, Vind Hansen H, Haraldsted V, Rodt S. Effects of preoperative oral carbohydrates and peptides on postoperative endocrine response, mobilization, nutrition and muscle function in abdominal surgery. Acta Anaesthesiologica Scandinavica . 2003;47(2):191-199. doi:10.1034/j.1399-6576.2003.00047.x Sio CA, Jung K, Kang S-B, Kim D-W, Oh H-K, Yoon M. The evaluation of preoperative oral carbohydrate-rich solution effects on insulin resistance in patients undergoing colectomy. Journal of Clinical Nutrition . 2015;7(2):62-67. doi:10.15747/jcn.2015.7.2.62 Lidder P, Thomas S, Fleming S, Hosie K, Shaw S, Lewis S. A randomized placebo controlled trial of preoperative carbohydrate drinks and early postoperative nutritional supplement drinks in colorectal surgery. Colorectal Disease . 2013;15(6):737-745. doi:10.1111/codi.12130 Michalaki M, Kyriazopoulou V, Mylonas P, et al. Glucose levels and insulin secretion in surgery-induced hyperglycemia in normoglycemic obese patients. Obesity Surgery . 2008;18(11):1460-1466. doi:10.1007/s11695-008-9501-3 Okabayashi T, Nishimori I, Yamashita K, et al. Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: A randomized clinical trial using an artificial pancreas. Amino Acids . 2009;38(3):901-907. doi:10.1007/s00726-009-0297-9 Tran S, Wolever TM, Errett LE, Ahn H, Mazer CD, Keith M. Preoperative carbohydrate loading in patients undergoing coronary artery bypass or spinal surgery. Anesthesia & Analgesia . 2013;117(2):305-313. doi:10.1213/ane.0b013e318295e8d1 Tsutsumi R, Kakuta N, Kadota T, et al. Effects of oral carbohydrate with amino acid solution on the metabolic status of patients in the preoperative period: A randomized, prospective clinical trial. Journal of Anesthesia . 2016;30(5):842-849. doi:10.1007/s00540-016-2217-y Wang ZG, Wang Q, Wang WJ, Qin HL. Randomized clinical trial to compare the effects of preoperative oral carbohydrate versus placebo on insulin resistance after colorectal surgery. British Journal of Surgery . 2010;97(3):317-327. doi:10.1002/bjs.6963 Yagci G, Can MF, Ozturk E, et al. Effects of preoperative carbohydrate loading on glucose metabolism and gastric contents in patients undergoing moderate surgery: A randomized, controlled trial. Nutrition . 2008;24(3):212-216. doi:10.1016/j.nut.2007.11.003 Oyama Y, Iwasaka H, Siihara Keisuke et al. Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients. Middle East journal of anaesthesiology . 2011;21(3):375-83 Dock-Nascimento DB, de Aquilar-Nascimento JE, Linetzky Waitzberg D. Ingestion of glutamine and maltodextrin two hours preoperatively improves insulin sensitivity after surgery: a randomized, double blind, controlled trial. Journal of Brazilian College of Surgeon s. 2012;39(6):449-55. doi: 10.1590/s0100-69912012000600002 Lende TH, Austdal M, Varhaugvik AE, et al. Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients ─ a randomized trial. BMC Cancer . 2019;19(1). doi:10.1186/s12885-019-6275-z Hegyi P, Erőss B, Izbéki F, Párniczky A, Szentesi A. Accelerating the Translational Medicine Cycle: The Academia Europaea Pilot. Nature Medicine . 2021;27(8):1317-1319. doi:10.1038/s41591-021-01458-8 Hegyi P, Petersen OH, Holgate S, et al. Academia Europaea Position Paper on translational medicine: The cycle model for translating scientific results into community benefits. Journal of Clinical Medicine . 2020;9(5):1532. doi:10.3390/jcm9051532 Additional Declarations No competing interests reported. Supplementary Files SupplemetaryTable.docx Cite Share Download PDF Status: Published Journal Publication published 31 May, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 04 Sep, 2024 Reviews received at journal 28 Aug, 2024 Reviewers agreed at journal 06 Aug, 2024 Reviews received at journal 16 Apr, 2024 Reviewers agreed at journal 15 Apr, 2024 Reviewers invited by journal 15 Apr, 2024 Editor assigned by journal 15 Apr, 2024 Editor invited by journal 10 Apr, 2024 Submission checks completed at journal 10 Apr, 2024 First submitted to journal 12 Mar, 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. 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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-4085704","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":290798253,"identity":"ecf64853-a549-41a4-b9b2-f7695a1714f0","order_by":0,"name":"Anna Réka Sebestyén","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"Réka","lastName":"Sebestyén","suffix":""},{"id":290798254,"identity":"514c4327-d323-42c2-a558-6267fc67f28d","order_by":1,"name":"Ambrus Szemere","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Ambrus","middleName":"","lastName":"Szemere","suffix":""},{"id":290798255,"identity":"bc261164-d8be-49e1-aa0d-41c6dbdad782","order_by":2,"name":"Marcell Virág","email":"","orcid":"","institution":"University of Pécs","correspondingAuthor":false,"prefix":"","firstName":"Marcell","middleName":"","lastName":"Virág","suffix":""},{"id":290798256,"identity":"e16d6fa1-dba6-4b15-b0b9-cfdad47767ea","order_by":3,"name":"Klementina Ocskay","email":"","orcid":"","institution":"Heim Pál National Pediatric Institute","correspondingAuthor":false,"prefix":"","firstName":"Klementina","middleName":"","lastName":"Ocskay","suffix":""},{"id":290798257,"identity":"43758cb7-76b4-4574-9c61-df1e9b89d312","order_by":4,"name":"Fanni Dembrovszky","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Fanni","middleName":"","lastName":"Dembrovszky","suffix":""},{"id":290798258,"identity":"ce7ef54c-9b45-4191-9394-58ffdbe831dc","order_by":5,"name":"Marie Anne Engh","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Marie","middleName":"Anne","lastName":"Engh","suffix":""},{"id":290798259,"identity":"c1313d22-8f2a-4f95-bbcd-587648b46c2b","order_by":6,"name":"László Szabó","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"László","middleName":"","lastName":"Szabó","suffix":""},{"id":290798261,"identity":"e1806201-bde4-4c47-8b83-a4c31c5cff23","order_by":7,"name":"Caner Turan","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Caner","middleName":"","lastName":"Turan","suffix":""},{"id":290798262,"identity":"b769b9f1-0143-4d7a-a478-c6ca9317ea59","order_by":8,"name":"Péter Hegyi","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Péter","middleName":"","lastName":"Hegyi","suffix":""},{"id":290798263,"identity":"5968b5bd-3963-41be-a44a-d35c073706c3","order_by":9,"name":"Zsolt Molnár","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYHACxgNAQoaBgRlES8gQpecAUC0PAwNbAkgLDylaeAxAHMJa5PsPHzj8MceGx5z9zOdXN2oseBjYDx/dgE8L44y0hAMHt6XxWPbkbrPOOQZ0GE9a2g18WpgleAyAWg4DydxtxjlsQC0SPGZ4tbDxn4FqOf/mmXHOPyK08DDkQLXcyGF+nNtGhBYJCaBfzgL9YnDjmRlzbp8EDxshvwBD7OCDym02cgbnkx9/zvlWJ8fPfvgYXi0o/pIAk8QqBwHmD6SoHgWjYBSMgpEDAAXCSeSURf69AAAAAElFTkSuQmCC","orcid":"","institution":"Semmelweis University","correspondingAuthor":true,"prefix":"","firstName":"Zsolt","middleName":"","lastName":"Molnár","suffix":""}],"badges":[],"createdAt":"2024-03-12 16:17:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4085704/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4085704/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-00767-z","type":"published","date":"2025-05-31T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54998221,"identity":"5ec94e7e-20a3-440b-904a-b5176695534e","added_by":"auto","created_at":"2024-04-19 18:23:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36922,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA 2020 flowchart representing the study selection process (\u003cem\u003eFrom: \u003c/em\u003e\u0026nbsp;Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71)\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/27e8b454c129824cfa6b1972.jpg"},{"id":54998223,"identity":"46bf8412-00ba-4f01-a128-c5d71292321a","added_by":"auto","created_at":"2024-04-19 18:23:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":168983,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots representing the odds of Length of hospital stay (A: CHO vs fasting, B: CHO vs placebo)\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/831ae90cb40a166c78dabe21.jpg"},{"id":54998224,"identity":"9a8302f0-b087-4318-89a2-68f2c7045fe4","added_by":"auto","created_at":"2024-04-19 18:23:04","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":75284,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots representing the odds of C reactive protein levels on postoperative day 1 (CHO vs fasting)\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/b8923d19242937939100bf7f.jpg"},{"id":54998222,"identity":"6d53466e-b1b7-4fc7-a1e8-f8cb5ad0169a","added_by":"auto","created_at":"2024-04-19 18:23:04","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":47753,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots representing the odds of C reactive protein levels on postoperative day 1 (CHO vs placebo)\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/ccea17c0cf30811fe0d82082.jpg"},{"id":83782772,"identity":"2d315c51-fd25-45c0-a138-33facabae6ef","added_by":"auto","created_at":"2025-06-02 16:04:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1037380,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/108eef0f-b4fa-4ae8-91ae-73c88d70cbda.pdf"},{"id":54998226,"identity":"20309d44-a177-40b5-ab6a-77a3ba902d99","added_by":"auto","created_at":"2024-04-19 18:23:05","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18241289,"visible":true,"origin":"","legend":"","description":"","filename":"SupplemetaryTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-4085704/v1/ad437c03591a24fd16c3e746.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preoperative carbohydrate loading reduces length of hospital stay compared to fasting in patients undergoing major elective, non-cardiac surgery: A systematic Review and Meta- Analysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePreoperative fasting, when patients are forbidden to consume food and drink after midnight prior to surgery, is still a common practice worldwide (1). The reason behind this strategy is to reduce the risk of aspiration of stomach contents during induction of and emergence from anaesthesia (2).\u003c/p\u003e\n\u003cp\u003eDespite the increasing evidence that fasting may increase the risk of postoperative complications, such as metabolic stress manifesting in hyperglycemia, insulin resistance and a more pronounced inflammatory response, preoperative fasting remains a common practice (3). However, the most recent Enhanced Recovery After Surgery (ERAS) Guidelines recommend the intake of solid food 5-6 hours before surgery, clear fluids up to 2 hours and even strongly recommend preoperative carbohydrate loading (CHO) (4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCarbohydrate loading may have several potential benefits such as less metabolic stress, and less pronounced inflammatory response and shorter hospital stay, however, clear evidence is still lacking (5). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough the recommendation is strong, the quality of the evidence remains low or moderate in the majority of the guidelines (4). Therefore, our aim was to synthetize and re-analyze all relevant literature to assist policymakers and guideline authors by generating the highest level of evidence in decision making.\u0026nbsp;\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eWe report our systematic review and meta-analysis based on the recommendations of the PRISMA 2020 guideline (6), while we followed the Cochrane Handbook (7). The protocol of the study was registered on PROSPERO (CRD42021284663) and we fully adhered to it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRandomized controlled trials (RCTs) were included, reporting on patients undergoing elective major non-cardiac surgery under general anaesthesia.\u0026nbsp;Case series, case reports, editorials, commentaries, qualitative studies were excluded. Articles available only in abstract form or meeting reports were also excluded. We applied no filters, no restrictions on methodological quality, publication date or language.\u0026nbsp;Major surgery was defined as\u0026nbsp;any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. Non-cardiac surgery was defined as every type of major surgery except cardiac. We defined preoperative carbohydrate loading (CHO) as a carbohydrate, mineral and vitamin containing amount of fluid which is consumed maximum 2 hours prior surgery (CHO-group). Those studies that utilized more interventions of the ERAS guideline were excluded to investigate the effect of carbohydrates only. Preoperative fasting was defined as no food consuming after midnight prior surgery, which means, no breakfast was allowed even when the surgeries were scheduled in the afternoon, making some of the patients fast for 12-15 hours. We defined placebo as a fluid, with artificial sweeteners, vitamins, and minerals. Basic characteristics of the patient population are included in the Supplementary material (Supplementary Table S1.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformation sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur systematic search was conducted on 15\u003csup\u003eth\u003c/sup\u003e of October, 2021 in five databases, Medline (via Pudmed), Embase, Cochrane Central Register for Controlled Trials (CENTRAL), Web of Science and Scopus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the systematic search the following search key was used:\u0026nbsp;\u003cem\u003e(preoperative AND (\u0026apos;carbohydrate\u0026apos;/exp OR carbohydrate) OR \u0026apos;fasting abbreviation\u0026apos;) AND random*\u003c/em\u003e in Embase. In the other four databases, we used\u0026nbsp;\u003cem\u003e((preoperative AND carbohydrate) OR \u0026quot;fasting abbreviation\u0026quot;) AND random*\u003c/em\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection process\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe selection was performed by two independent authors (AS and ASz using Endnote X20), disagreements were resolved by consensus. After automatic and manual duplicate removal, we screened the records based on title and abstract, and after this step, we screened the remaining records based on full text against the predefined eligibility criteria. There were cases, when multiple studies used the same patient database for the same outcomes. In these cases, we recruited only one study with the largest sample in our analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection phase was performed by two independent authors (AS and ASz). The following data were extracted: first author, the year of publications, study population, study period, country, intervention, fasting and placebo group, number of patients, baseline characteristics, LOS, postoperative glucose and insulin levels, postoperative CRP levels.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy risk of bias assessment\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe assessed the risk of bias by a Cochrane-recommended bias tool for randomized trials (RoB 2.0) for RCTs (8). Risk of bias assessment was performed by two independent review (AS and ASz) authors and disagreements resolved by consensus. Quality of evidence evaluation was executed following the guidance of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) workgroup. Assessment of the quality of evidence was arranged in tables, that were prepared with the GRADEPro Guideline Development Tool (9).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData synthesis was performed by using the methods recommended by the Cochrane Collaboration (7) For continuous outcomes pooled MDs with their 95% CI were calculated to investigate the differences between the compared arms. The restricted maximum likelihood estimator was used. The random effects model was applied for meta-analyses. If the study number for the given outcome was over five, the Hartung\u0026ndash;Knapp adjustment (10, 11) was applied.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical heterogeneity across trials was assessed by means of the Cochrane Q test, and the I2 values, where p \u0026lt; 0.1 was considered as statistically significant.\u003c/p\u003e\n\u003cp\u003eThe statistical analyses were carried out by R (R Core Team 2021, v 4 1.1, R Foundation for Statistical Computing, Vienna, Austria) (12) using the meta Schwarzer G. General package for meta-analysis (12) and Dmetar (14) packages. Forest plots were used to visualize the findings of the meta-analytical calculations.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eSearch and selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAltogether 9698 studies were identified during our search in Medline (via Pubmed), Embase, World of Science, Cochrane CentralRegoster of Controlled Trials (Central) and Scopus databases, and 55 studies were found eligible for inclusion in the meta-analysis and systematic review. The exact details of selection are outlined in the PRISMA flowchart (Fig. 1).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFigure 1. PRISMA flowchart of selection process\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBasic characteristics of included studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline characteristics of the enrolled analyses are detailed in Supplementary Table (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLength of hospital stay \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwenty studies (15-33), including 2116 patients, used LOS as an outcome, when investigating effects of CHO-loading. Fourteen (15-28) of these studies used fasting and seven applied placebos in the control groups (19, 27, 29-33), and two of them used both comparisons (19, 27). LOS in the CHO-group vs the Fasting-group was shorter (MD: -1,71 [95% CI: -3.04, -0,38] p\u0026lt;0.01) (Fig. 2/A). When compared to the Placebo-group, we did not find a statistically significant difference, as the LOS was only (-0.01) day shorter in the CHO-group (Fig. 2/B). Considerable statictical heterogenity was detected in both cases.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFigure 2. Length of hospital stay (A: CHO vs fasting; B: CHO vs placebo)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCHO, carbohydrate loading;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGlucose and insulin levels \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcross six studies (15, 18, 24, 34, 35, 36) of 745 patients glucose levels were measured on postoperative day 1 and 2. Glucose levels on postoperative day 1 (18, 24, 34, 35, 36) and day 2 (15, 18, 24, 35) showed no significant differences (-1.10 [-0.48;0.46], 0,21 [-0.31;0.72]) between the CHO-group and Fasting-group (Supplementary Fig.2 and Fig.3). Four studies, (29, 30, 31, 37) including 267 patients compared the effects of carbohydrate loading on postoperative glucose levels to placebo on postoperative day 1. There was a non-significant difference between the groups (Supplementary Fig.6).\u003c/p\u003e\n\u003cp\u003eFour studies including 133 patients measured insulin levels on postoperative day 1 (19, 32, 36) and on postoperative day 2 (15, 18, 35), and compared CHO loading to fasting. There were no significant difference neither on postoperative day 1(MD: -3.36 \u0026mu;U/mL, 95% CI [-8.15; 1.44] I\u003csup\u003e2\u003c/sup\u003e=94% \u0026chi;\u0026sup2;=14.013 p\u0026lt;0.01) (Supplementary Fig. 4), nor on postoperative day 2 (MD: -1.99 \u0026mu;U/mL, 95% CI [-5.05 ; 1.07) I\u003csup\u003e2\u003c/sup\u003e=91%, \u0026chi;\u0026sup2;=5.732, p\u0026lt;0.01) (Supplementary Fig. 4). Three studies including 59 patients used placebo as comparison (30, 31, 37), and reported insulin levels on day 1. We found no significant difference between the groups (Supplementary Fig. 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRP levels\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree studies (36, 39, 40) including 126 patients, investigated the effect of carbohydrate loading on postoperative CRP levels measured in mg/L, and compared CHO loading to fasting, and three studies including (30, 38, 40) 63 patients compared it to placebo. The point estimate showed lower CRP levels in the CHO-group in both comparisons, but it did not reach statistical significance (Fig. 3 and 4).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFigure 3. Forest plot of C reactive protein levels on postoperative day 1 (CHO vs fasting)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFigure 4. Forest plot of C reactive protein levels on postoperative day 1 (CHO vs placebo)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCHO, carbohydrate loading;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Risk of bias assessment and level of evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe risk of bias assesement revealed that there are some concerns regarding biasing factors. The overall risk of bias was low in 17 RCTS regarding all the outcomes, some concerns came up at 17 studies and one studies found high risk regarding biasing factors (S8-17 in Supplementary Table).\u003c/p\u003e\n\u003cp\u003eThe GRADE assessment resulted in moderate certainty about LOS when comparing CHO-group with Fasting-group and Placebo-group. All the other outcomes were appeared to have very low certainty (S18-19 in Supplementary Table).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e\u003cem\u003eLength of hospital stay\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe considered the LOS as our primary outcome, as in our opinion this may represent the overall effects of preoperative CHO-loading best, due to the potential beneficial effects on several important confounders such as better postoperative blood sugar control, faster gastro-intestinal recovery, lesser chance of nosocomial infections and also the reduction of hospital costs (41). Other safety outcomes were not assessed in this study.\u003c/p\u003e\n\u003cp\u003eWe found that LOS of those patients who received CHO loading was significantly shorter by a mean of 1.7 [-3.04;-0.38] days when compared to preoperative fasting that should be considered as a clinically relevant difference. Although difficult to explain, but some authors believe that CHO-loading could result in a more balanced glucose homeostasis that is the main reason for reduced LOS (15, 21). However, our data did not provide satisfactory support to this hypothesis. More detailed assessment of glucose homeostasis should be considered in the future.\u003c/p\u003e\n\u003cp\u003eLiu et al., found that the loss of muscle mass was lower in the CHO-group, which was considered responsible for the faster recovery (18). Unfortunately, based on the available data on postoperative blood sugar and insulin levels, but also on CRP levels \u0026ndash; as the only reported and poolable marker of postoperative inflammation \u0026ndash; we found no significant differences between the groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHospital LOS is influenced by multiple factors, such as adequate pain and fluid management, early mobilization, earlier start of oral food and fluid intake, etc., not analyzed in the current meta-analysis as data was either scarce or not reported at all (16, 18, 19, 20, 24). It is also important to note that there is a difference in the terms of \u0026lsquo;length of hospital stay\u0026rsquo;, \u0026lsquo;total lengths of hospital stay\u0026rsquo; (18) and \u0026lsquo;readiness to discharge\u0026rsquo; (26) that was also inconsistently defined in the articles. LOS may also be affected by local organizational issues such as timing of surgery after hospital admission and the timing of patient discharge. Therefore, we entirely agree with Cho et al (26), who suggested to use the term, \u0026ldquo;time to ready to discharge\u0026rdquo; in the future as an outcome measure instead of the actual LOS.\u003c/p\u003e\n\u003cp\u003eThere was no significant difference in the hospital LOS when CHO-loading was compared to placebo. In fact, the pooled results were almost identical with a very narrow confidence interval (0.01 [-0.18;0.16]). Regarding the type of the placebo in general, plain water is one option (19, 30, 31, 38, 42, 43, 44), but in this case, patients could be able to identify the difference between the drug and placebo by its sweetness, hence blinding is questionable. An alternative option is the use of artificial sweeteners (27, 29, 33, 34, 45, 46, 47, 48, but in this case, one cannot exclude their metabolic effects (19). In our meta-analysis, the used placebos differed greatly in the studies. In some cases, the authors used plain water (31, 32), while Yuill et al. (37) used fluid with minerals that was not flavored either, so double-blindness cannot be guaranteed which is a biasing factor all in general. Nevertheless, in our opinion, this is the most suitable placebo for investigating the effects of carbohydrates in a placebo-controlled trial design. Although it remains difficult to give an exact explanation of the difference between the fasting and placebo comparisons, but one cannot exclude that it is not necessarily the CHO-loading but the fasting that is responsible for the worse outcome. A hypothesis that is worth further investigation in the future.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePostoperative blood sugar and insulin levels\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePostoperative hypo- and hyperglycemia should be avoided due to several potential adverse effects both surgical a general that may delay recovery in general after surgery (2). In the current study we found that the postoperative metabolic status as indicated by serum glucose and insulin levels did not differ significantly between the groups and showed similar tendency in both comparisons to fasting or placebo.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhen CHO-loading was compared to fasting, there was a minimal mean difference on postoperative day 1(-0.01 [-0.49;\u0026nbsp;0.46]) and on postoperative day 2 (0.21[-0.30;0.72]) between the groups in the blood glucose levels, but patients in the CHO-group had a tendency of lower serum insulin levels, but the difference did not reach statistical difference. When compared CHO-loading to placebo, the results were similar, with a tendency of favoring CHO-loading, but without statistical significance. However, we were only able to pool data from 3 studies for each comparison, with a high heterogeneity.\u003c/p\u003e\n\u003cp\u003eIt is important to note that the used amount, composition, and timing of administration of CHO-loading fluids notably differed in the included studies. Another reason for heterogeneity is that several studies used different timepoints for measuring insulin and glucose levels. Some even recorded these parameters on postoperative day 3 (22) and 7 (22, 49). We believe that expecting such a long-term effect of a relatively low dose CHO-loading preoperatively do not really make sense. Even measuring blood sugar levels on day 1 and 2 is questionable, especially if patients are fed already on day one. As for future research, we believe that timing of postoperative glucose and insulin level measurements should be standardized. A possible approach could be one that was applied by Rizavnovic et al, where they measured glucose levels two hours prior surgery, six hours after surgery, and in the mornings of postoperative day 1 and 2 (35).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eC-reactive protein\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCRP is the most commonly used inflammatory biomarker that may also be used for assessing postoperative inflammatory response (41). In both comparisons (to fasting or placebo) there was a similar tendency of lower CRP levels in the CHO-group, but it did not reach statistical significance. \u0026nbsp;How CHO loading could affect postoperative inflammatory response remains uncertain and detailed description of the current hypotheses are beyond the scope of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe main strength of our analysis is that we strictly followed our protocol, which was registered in advance. Both univariate and multivariate analyses were performed to achieve objectivity. Rigorous methodology was applied, and our results were derived from randomized controlled trials only. However, because of the different methodology that was used in most studies, we were unable to pool all 55 identified studies that were eligible for data extraction, and only 26 (15-40) of them could be used for pooled analyses. The other 29 studies could not be included in any analysis (41-69) (Supplemetary Table).\u003c/p\u003e\n\u003cp\u003eHigh heterogeneity of data is another limiting factor. We worked with very heterogenous patient population, who were undergoing different types and durations of surgeries. The definition of fasting and placebo also differed to some extent among the studies. The administered carbohydrate fluids varied in contents and amount. The used randomized control trials measured glucose and insulin levels in inappropriate times. Also, the different measuring timepoints seriously limited our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main message of this meta-analysis is that CHO-loading as compared to preoperative fasting resulted in significantly shorter length of hospital stay. However, when compared to placebo, this difference disappeared. Based on the non-significant findings in all other outcomes, explanation of these result remains difficult.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplication for practice and research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough our results suggest that preoperative fluid intake with or without CHO is superior to fasting, but the pathophysiology remains unclear. To find out the exact benefits and further details of this intervention renders the need for future research in which circumstances such as timing, dosing, type of fluid, etc. are much more standardized. More information is also needed on glucose homeostasis in order to enable us to determine whether the observed effects are related to the fluid (i.e.: water) intake \u003cem\u003eper se\u003c/em\u003e, or its carbohydrate content. Regarding outcomes, we suggest the term \u0026ldquo;ready to discharge\u0026rdquo; instead of \u0026ldquo;length of hospital stay\u0026rdquo; as some confounding circumstances (i.er.: social background, bed availability, etc.), may affect the time of discharge. Finally, we recognized that postoperative complications are rarely used as an outcome that should also be included as important endpoints on future trials. \u0026nbsp;We would like to highlight the importance of implementing scientific results into daily practice, because with this approach may allow faster recovery and lesser incidence of postoperative complications (70, 71).\u003c/p\u003e\n\u003cp\u003eAs compared to the used placebos, such as clear water, water with artificial sweeteners and preformed glucose-free solutions with mineral, we could not find significant differences.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003ePreoperative carbohydrate loading was found to reduce LOS by an average of 1.71 days compared to fasting. However, LOS of patients in placebo group was similar to those with CHO loading. Although the explanation behind this result is still to be unveiled, these data provide further support that preoperative fluid intake with CHO-loading can be beneficial in this patient population.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZM holds a post as senior medical director at CytoSorbents Europe, Berlin, Germany.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT author contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAS: conceptualization, formal analysis, investigation, resources, writing \u0026ndash; original draft, visualization, data curation ASz: conceptualization, resources, investigation, visualization MV: conceptualization, investigation, formal analysis, data curation, visualization, writing \u0026ndash; review and editing KO: methodology, validation, data curation, visualization, writing \u0026ndash; review and editing FD: methodology, validation, data curation MAE: methodology, validation, data curation, visualization, writing \u0026ndash; review and editing LSz: ,software, writing \u0026ndash; review and editing CT: conceptualization, writing \u0026ndash; review and editing, KH: visualization, supervision, PH: visualization, supervision ZsM: formal analysis, visualization, supervision, writing \u0026ndash; review and editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets used in this study can be found in the full-text articles included in the systematic\u003c/p\u003e\n\u003cp\u003ereview and meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding was provided by the Centre for Translational Medicine, Semmelweis University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSponsors had no role in the design, data collection, analysis, interpretation, and manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval was required for this systematic review with meta-analysis, as all data were already published in peer-reviewed journals. No patients were involved in the design, conduct or interpretation of our study.\u003c/p\u003e\n\u003cp\u003eThe datasets used in this study can be found in the full-text articles included in the systematic review and meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILIBILITY STATEMENT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data generated an analyzed are included in this article and in its Supplementary table.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAckerman RS, Tufts CW, DePinto DG, et al. How sweet is this? A review and evaluation of preoperative carbohydrate loading in the enhanced recovery after surgery model.\u0026nbsp;\u003cem\u003eNutrition in Clinical Practice\u003c/em\u003e. 2019;35(2):246-253. doi:10.1002/ncp.10427\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCheng PL, Loh EW, Chen JT, Tam KW. Effects of preoperative oral carbohydrate on postoperative discomfort in patients undergoing elective surgery: A meta-analysis of randomized controlled trials.\u0026nbsp;\u003cem\u003eLangenbeck\u0026rsquo;s Archives of Surgery\u003c/em\u003e. 2021;406(4):993-1005. doi:10.1007/s00423-021-02110-2\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDavis G, Fayfman M, Reyes-Umpierrez D, et al. Stress hyperglycemia in general surgery: Why should we care?\u0026nbsp;\u003cem\u003eJournal of Diabetes and its Complications\u003c/em\u003e. 2018;32(3):305-309. doi:10.1016/j.jdiacomp.2017.11.010\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGustafsson UO, Scott MJ, Hubner M, et al. Guidelines for perioperative care in elective colorectal surgery: Enhanced recovery after surgery (eras\u0026reg;) society recommendations: 2018.\u0026nbsp;\u003cem\u003eWorld Journal of Surgery\u003c/em\u003e. 2018;43(3):659-695. doi:10.1007/s00268-018-4844-y\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNoba L, Wakefield A. Are carbohydrate drinks more effective than preoperative fasting: A systematic review of Randomised Controlled Trials.\u0026nbsp;\u003cem\u003eJournal of Clinical Nursing\u003c/em\u003e. 2019;28(17-18):3096-3116. doi:10.1111/jocn.14919\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePage MJ, McKenzie JE, Bossuyt PM, et al. The Prisma 2020 statement: An updated guideline for reporting systematic reviews.\u0026nbsp;\u003cem\u003ePLOS Medicine\u003c/em\u003e. 2021;18(3). doi:10.1371/journal.pmed.1003583\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHiggins JPT, Thomas J, Chandler J, et al.\u0026nbsp;\u003cem\u003eCochrane Handbook for Systematic Reviews of Interventions\u003c/em\u003e 2nd Edition. Chichester (UK): John Wiley \u0026amp; Sons, 2019.\u003c/li\u003e\n \u003cli\u003eSterne JA, Savović J, Page MJ, et al. Rob 2: A revised tool for assessing risk of bias in randomised trials.\u0026nbsp;\u003cem\u003eBMJ\u003c/em\u003e. Published online 2019:l4898. doi:10.1136/bmj.l4898\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eGRADEpro Guideline Development Tool.\u003c/em\u003eMcMaster University; Hamilton, ON, Canada: Evidence Prime; Hamilton, ON, Canada: 2022. [(accessed on19June2022)]. Available online:\u0026nbsp;\u003ca href=\"https://www.gradepro.org/\" target=\"_blank\"\u003ehttps://www.gradepro.org/\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eKnapp G, Hartung J. Improved tests for a random effects meta‐regression with a single covariate.\u0026nbsp;\u003cem\u003eStatistics in Medicine\u003c/em\u003e. 2003;22(17):2693-2710. doi:10.1002/sim.1482\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eIntHout J, Ioannidis JP, Borm GF. The hartung-knapp-sidik-jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard Dersimonian-Laird Method.\u0026nbsp;\u003cem\u003eBMC Medical Research Methodology\u003c/em\u003e. 2014;14(1). doi:10.1186/1471-2288-14-25\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eR core team: A language and environment for statistical computing. 2021. https://cran.r-hub.io/doc/manuals/fullrefman.pdf.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSchwarzer G. General package for meta-analysis 2015, 2021. https://github.com/guido-s/meta/\u0026nbsp;\u003ca href=\"https://link.springer.com/book/10.1007/978-3-319-21416-0\"\u003ehttps://link.springer.com/book/10.1007/978-3-319-21416-0\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eHarrer M, Pim C, Furukawa T, et al. Dmetar: companion R package for the guide doing metaanalysis in R. London: Chapman \u0026amp; Hall/CRC Press, 2020.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePexe-Machado PA, de Oliveira BD, Dock-Nascimento DB, de Aguilar-Nascimento JE. Shrinking preoperative fast time with maltodextrin and protein hydrolysate in gastrointestinal resections due to cancer.\u0026nbsp;\u003cem\u003eNutrition\u003c/em\u003e. 2013;29(7-8):1054-1059. doi:10.1016/j.nut.2013.02.003\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZhao G, Huang Y, Chen X et al. Research on fast track surgery application in lung cancer surgery. \u003cem\u003eChinese Journal of Lung Cancer.\u003c/em\u003e 2010 Feb;13(2):102-6.\u0026nbsp;doi: 10.3779/j.issn.1009-3419.2010.02.04.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePanebianco A, Laforgia R, Volpi A et al.\u0026nbsp;Preoperative fasting - \u0026quot;nihil per os\u0026quot; a difficult myth to break down: a randomized controlled study. \u003cem\u003eJournal of the Italian Surgical Association.\u0026nbsp;\u003c/em\u003e 2020 Jan-Feb;41(1):84-93\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLiu B, Wang Y, Liu S, et al. A randomized controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing elective craniotomy.\u0026nbsp;\u003cem\u003eClinical Nutrition\u003c/em\u003e. 2019;38(5):2106-2112. doi:10.1016/j.clnu.2018.11.008\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNoblett SE, Watson DS, Huong H, Davison B, Hainsworth PJ, Horgan AF. Pre‐operative oral carbohydrate loading in colorectal surgery: A randomized controlled trial.\u0026nbsp;\u003cem\u003eColorectal Disease\u003c/em\u003e. 2006;8(7):563-569. doi:10.1111/j.1463-1318.2006.00965.x\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ede Abreu Reis PG, Polakowski C, Lopes M et al. Abbreviated preoperative fasting favours postoperative oral intake at lower hospital admission costs for cancer patients.\u0026nbsp;\u003cem\u003eJournal of Brazilian College of Surgeons\u003c/em\u003e 2019 Aug 5;46(3):e20192175. doi: 10.1590/0100-6991e-20192175.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eQi L, Wu Y, Shan L, et al. A clinical study of preoperative carbohydrate administration to improve insulin resistance in patients with multiple injuries.\u0026nbsp;\u003cem\u003eAnnals of Palliative Medicine\u003c/em\u003e. 2020;9(5):3278-3287. doi:10.21037/apm-20-1424\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKa\u0026scaron;ka M, Grosmanov\u0026aacute; T, Havel E, et al. The impact and safety of preoperative oral or intravenous carbohydrate administration versus fasting in colorectal surgery \u0026ndash; a randomized controlled trial.\u0026nbsp;\u003cem\u003eWiener klinische Wochenschrift\u003c/em\u003e. 2010;122(1-2):23-30. doi:10.1007/s00508-009-1291-7\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHelminen H, Branders H, Ohtonen P, Saarnio J. Effect of pre-operative oral carbohydrate loading on recovery after day-case cholecystectomy.\u0026nbsp;\u003cem\u003eEuropean Journal of Anaesthesiology\u003c/em\u003e. 2019;36(8):605-611. doi:10.1097/eja.0000000000001002\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSuh S, Hetzel E, Alter-Troilo K, et al. The influence of preoperative carbohydrate loading on postoperative outcomes in bariatric surgery patients: A randomized, controlled trial.\u0026nbsp;\u003cem\u003eSurgery for Obesity and Related Diseases\u003c/em\u003e. 2021;17(8):1480-1488. doi:10.1016/j.soard.2021.04.014\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFaria MS, de Aguilar‐Nascimento JE, Pimenta OS, Alvarenga LC, Dock‐Nascimento DB, Slhessarenko N. Preoperative fasting of 2 hours minimizes insulin resistance and organic response to trauma after video‐cholecystectomy: A randomized, controlled, clinical trial.\u0026nbsp;\u003cem\u003eWorld Journal of Surgery\u003c/em\u003e. 2009;33(6). doi:10.1007/s00268-009-0010-x\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCho E-A, Lee NH, Ahn J-H, Choi W-J, Byun J-H, Song T. Preoperative oral carbohydrate loading in laparoscopic gynecologic surgery: A randomized controlled trial.\u0026nbsp;\u003cem\u003eJournal of Minimally Invasive Gynecology\u003c/em\u003e. 2021;28(5). doi:10.1016/j.jmig.2020.12.002\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSada F, Krasniqi A, Hamza A, Gecaj-Gashi A, Bicaj B, Kavaja F. A randomized trial of preoperative oral carbohydrates in abdominal surgery.\u0026nbsp;\u003cem\u003eBMC Anesthesiology\u003c/em\u003e. 2014;14(1). doi:10.1186/1471-2253-14-93\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHamamoto H, Yamamoto M, Masubuchi S, et al. The impact of preoperative carbohydrate loading on intraoperative body temperature: A randomized controlled clinical trial.\u0026nbsp;\u003cem\u003eSurgical Endoscopy\u003c/em\u003e. 2018;32(11):4393-4401. doi:10.1007/s00464-018-6273-2\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMathur S, Plank LD, McCall JL, et al. Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery.\u0026nbsp;\u003cem\u003eBritish Journal of Surgery\u003c/em\u003e. 2010;97(4):485-494. doi:10.1002/bjs.7026\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePerrone F, da-Silva-Filho AC, Ad\u0026ocirc;rno IF, et al. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial.\u0026nbsp;\u003cem\u003eNutrition Journal\u003c/em\u003e. 2011;10(1). doi:10.1186/1475-2891-10-66\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePędziwiatr M, Pisarska M, Matłok M, et al. Randomized clinical trial to compare the effects of preoperative oral carbohydrate loading versus placebo on insulin resistance and cortisol level after laparoscopic cholecystectomy*.\u0026nbsp;\u003cem\u003ePolish Journal of Surgery\u003c/em\u003e. 2015;87(8). doi:10.1515/pjs-2015-0079\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGianotti L, Biffi R, Sandini M, et al. Preoperative oral carbohydrate load versus placebo in major elective abdominal surgery (PROCY).\u0026nbsp;\u003cem\u003eAnnals of Surgery\u003c/em\u003e. 2018;267(4):623-630. doi:10.1097/sla.0000000000002325\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAl-Hirmizy D, Wood N, Ko S, et al. A single centre randomised control study to assess the impact of pre-operative carbohydrate loading on women undergoing major surgery for epithelial ovarian cancer.\u0026nbsp;\u003cem\u003eCureus\u003c/em\u003e. Published online 2020. doi:10.7759/cureus.10169\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWang S, Gao P, Guo X, et al. Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: A prospective randomized trial.\u0026nbsp;\u003cem\u003eBMC Anesthesiology\u003c/em\u003e. 2021;21(1). doi:10.1186/s12871-021-01323-8\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRizvanović N, Nesek Adam V, Čau\u0026scaron;ević S, Dervi\u0026scaron;ević S, Delibegović S. A randomised controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing colorectal surgery.\u0026nbsp;\u003cem\u003eInternational Journal of Colorectal Disease\u003c/em\u003e. 2019;34(9):1551-1561. doi:10.1007/s00384-019-03349-4\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCeliksular MC, Saracoglu A, Yentur E. The influence of oral carbohydrate solution intake on stress response before total hip replacement surgery during epidural and general anaesthesia.\u0026nbsp;\u003cem\u003eThe Influence of Oral Carbohydrate Solution Intake on Stress Response before Total Hip Replacement Surgery during Epidural and General Anaesthesia\u003c/em\u003e. 2016;44(3):117-123. doi:10.5152/tjar.2016.65265\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYuill KA, Richardson RA, Davidson HIM, Garden OJ, Parks RW. The administration of an oral carbohydrate-containing fluid prior to major elective upper-gastrointestinal surgery preserves skeletal muscle mass postoperatively\u0026mdash;a randomised clinical trial.\u0026nbsp;\u003cem\u003eClinical Nutrition\u003c/em\u003e. 2005;24(1):32-37. doi:10.1016/j.clnu.2004.06.009\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSingh M, Chaudhary M, Vashistha A, Kaur G. Evaluation of effects of a preoperative 2-hour fast with glutamine and carbohydrate rich drink on insulin resistance in maxillofacial surgery.\u0026nbsp;\u003cem\u003eJournal of Oral Biology and Craniofacial Research\u003c/em\u003e. 2015;5(1):34-39. doi:10.1016/j.jobcr.2015.02.006\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGumus K, Aydın G. The effect of preoperative nutrition on postoperative CRP and albumin levels in patients undergoing laparoscopic surgery: A surgical nursing perspective.\u0026nbsp;\u003cem\u003eJournal of PeriAnesthesia Nursing\u003c/em\u003e. 2020;35(6):592-596. doi:10.1016/j.jopan.2020.06.018\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBraga M, Bissolati M, Rocchetti S, Beneduce A, Pecorelli N, Di Carlo V. Oral preoperative antioxidants in pancreatic surgery: A double-blind, randomized, clinical trial.\u0026nbsp;\u003cem\u003eNutrition\u003c/em\u003e. 2011;28(2):160-164. doi:10.1016/j.nut.2011.05.014\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKarimian N, Kaneva P, Donatelli F, et al. Simple versus complex preoperative carbohydrate drink to preserve perioperative insulin sensitivity in laparoscopic colectomy.\u0026nbsp;\u003cem\u003eAnnals of Surgery\u003c/em\u003e. 2020;271(5):819-826. doi:10.1097/sla.0000000000003488\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEsaki K, Tsukamoto M, Sakamoto E, Yokoyama T.\u0026nbsp;Effects of preoperative oral carbohydrate therapy on perioperative glucose metabolism during oral\u0026ndash; maxillofacial surgery: randomised clinical trial. \u003cem\u003eAsia Pacific Journal of Clinical Nutrition\u003c/em\u003e. 2018;27(1):137-143.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDock‐Nascimento DB, de Aguilar‐Nascimento JE, Magalhaes Faria MS, Caporossi C, Slhessarenko N, Waitzberg DL. Evaluation of the effects of a preoperative 2‐hour fast with Maltodextrine and glutamine on insulin resistance, acute‐phase response, nitrogen balance, and serum glutathione after laparoscopic cholecystectomy.\u0026nbsp;\u003cem\u003eJournal of Parenteral and Enteral Nutrition\u003c/em\u003e. 2012;36(1):43-52. doi:10.1177/0148607111422719\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Wongyingsinn+M\u0026cauthor_id=31826369\"\u003eWongyingsinn\u003c/a\u003e M,\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Luangchan+S\u0026cauthor_id=31826369\"\u003eLuangchan\u003c/a\u003e S,\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Tungsongsawat+S\u0026cauthor_id=31826369\"\u003eTungsongsawat\u003c/a\u003e S,\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Trakarnsanga+A\u0026cauthor_id=31826369\"\u003eTrakarnsanga\u003c/a\u003e A,\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Lohsiriwat+V\u0026cauthor_id=31826369\"\u003eLohsiriwat\u003c/a\u003e V. A randomized controlled trial of preoperative carbohydrate drinks on postoperative walking capacity in elective colorectal surgery. Asia Pacific Journal of Clinical Nutrition. 2019;28(4):727-733.\u0026nbsp;doi: 10.6133/apjcn.201912_28(4).0008.\u003c/li\u003e\n \u003cli\u003evan Stijn MF, Soeters MR, van Leeuwen PA, et al. Effects of a carbohydrate‐, glutamine‐, and antioxidant‐enriched oral nutrition supplement on major surgery‐induced insulin resistance: A randomized pilot study.\u0026nbsp;\u003cem\u003eJournal of Parenteral and Enteral Nutrition\u003c/em\u003e. 2017;42(4):719-729. doi:10.1177/0148607117711691\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLjunggren S, Hahn RG, Nystr\u0026ouml;m T. Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: A double-blind, randomised controlled clinical trial.\u0026nbsp;\u003cem\u003eClinical Nutrition\u003c/em\u003e. 2014;33(3):392-398. doi:10.1016/j.clnu.2013.08.003\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTewari N, Awad S, Du\u0026scaron;ka F, et al. Postoperative inflammation and insulin resistance in relation to body composition, adiposity and carbohydrate treatment: A randomised controlled study.\u0026nbsp;\u003cem\u003eClinical Nutrition\u003c/em\u003e. 2019;38(1):204-212. doi:10.1016/j.clnu.2018.01.032\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShi M, Hu Z, Yang D, Cai Q, Zhu Z. Preoperative oral carbohydrate reduces postoperative insulin resistance by activating amp-activated protein kinase after colorectal surgery.\u0026nbsp;\u003cem\u003eDigestive Surgery\u003c/em\u003e. 2020;37(5):368-375. doi:10.1159/000505515\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLibiszewski M, Drozda R, Śmigielski J, Kuzdak K, Kołomecki K. Preparation of patients submitted to thyroidectomy with oral glucose solutions.\u0026nbsp;\u003cem\u003ePolish Journal of Surgery\u003c/em\u003e. 2012;84(5): 253-7. doi:10.2478/v10035-012-0042-z\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026Ccedil;akar E, Yilmaz E, \u0026Ccedil;akar E, Baydur H. The effect of preoperative oral carbohydrate solution intake on patient comfort: A randomized controlled study.\u0026nbsp;\u003cem\u003eJournal of PeriAnesthesia Nursing\u003c/em\u003e. 2017;32(6):589-599. doi:10.1016/j.jopan.2016.03.008\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLende TH, Austdal M, Bathen TF, et al. Metabolic consequences of perioperative oral carbohydrates in breast cancer patients \u0026mdash; an explorative study.\u0026nbsp;\u003cem\u003eBMC Cancer\u003c/em\u003e. 2019;19(1). doi:10.1186/s12885-019-6393-7\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDoo AR, Hwang H, Ki M-J, Lee J-R, Kim D-C. Effects of preoperative oral carbohydrate administration on patient well-being and satisfaction in thyroid surgery.\u0026nbsp;\u003cem\u003eKorean Journal of Anesthesiology\u003c/em\u003e. 2018;71(5):394-400. doi:10.4097/kja.d.18.27143\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTarasova IA, Inviyaeva EV, Bunyatyan KA, Tskhovrebov AT, Nikoda VV, Shestakov AL. The influence of the preoperative preload with carbohydrates upon metabolic, immune and cytokine statuses after reconstructive esophageal surgical interventions.\u0026nbsp;\u003cem\u003eMedical Immunology (Russia)\u003c/em\u003e. 2018;20(6):877-888. doi:10.15789/1563-0625-2018-6-877-888\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRavanini G, Portari PE, Povedano A, Luna RA. Organic inflammatory response to reduced preoperative fasting time, with a carbohydrate and protein enriched solution. A randomised trial.\u0026nbsp;\u003cem\u003eClinical Nutrition ESPEN\u003c/em\u003e. 2016;12. doi:10.1016/j.clnesp.2016.02.074\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOnalan E, Andsoy II, Ersoy OF. The effect of preoperative oral carbohydrate administration on insulin resistance and comfort level in patients undergoing surgery.\u0026nbsp;\u003cem\u003eJournal of PeriAnesthesia Nursing\u003c/em\u003e. 2018;34(3):539-550. doi:10.1016/j.jopan.2018.07.007\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCanbay \u0026Ouml;, Adar S, Karag\u0026ouml;z AH, \u0026Ccedil;elebi N, Bilen CY. Effect of preoperative consumption of high carbohydrate drink (Pre-Op\u0026reg;) on postoperative metabolic stress reaction in patients undergoing radical prostatectomy.\u0026nbsp;\u003cem\u003eInternational Urology and Nephrology\u003c/em\u003e. 2014;46(7):1329-1333. doi:10.1007/s11255-013-0612-y\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDilmen OK, Yentur E, Tunali Y, Balci H, Bahar M. Does preoperative oral carbohydrate treatment reduce the postoperative surgical stress response in lumbar disc surgery?\u0026nbsp;\u003cem\u003eClinical Neurology and Neurosurgery\u003c/em\u003e. 2017;153:82-86. doi:10.1016/j.clineuro.2016.12.016\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHenriksen MG, Hessov I, Dela F, Vind Hansen H, Haraldsted V, Rodt S. Effects of preoperative oral carbohydrates and peptides on postoperative endocrine response, mobilization, nutrition and muscle function in abdominal surgery.\u0026nbsp;\u003cem\u003eActa Anaesthesiologica Scandinavica\u003c/em\u003e. 2003;47(2):191-199. doi:10.1034/j.1399-6576.2003.00047.x\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSio CA, Jung K, Kang S-B, Kim D-W, Oh H-K, Yoon M. The evaluation of preoperative oral carbohydrate-rich solution effects on insulin resistance in patients undergoing colectomy.\u0026nbsp;\u003cem\u003eJournal of Clinical Nutrition\u003c/em\u003e. 2015;7(2):62-67. doi:10.15747/jcn.2015.7.2.62\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLidder P, Thomas S, Fleming S, Hosie K, Shaw S, Lewis S. A randomized placebo controlled trial of preoperative carbohydrate drinks and early postoperative nutritional supplement drinks in colorectal surgery.\u0026nbsp;\u003cem\u003eColorectal Disease\u003c/em\u003e. 2013;15(6):737-745. doi:10.1111/codi.12130\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMichalaki M, Kyriazopoulou V, Mylonas P, et al. Glucose levels and insulin secretion in surgery-induced hyperglycemia in normoglycemic obese patients.\u0026nbsp;\u003cem\u003eObesity Surgery\u003c/em\u003e. 2008;18(11):1460-1466. doi:10.1007/s11695-008-9501-3\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOkabayashi T, Nishimori I, Yamashita K, et al. Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: A randomized clinical trial using an artificial pancreas.\u0026nbsp;\u003cem\u003eAmino Acids\u003c/em\u003e. 2009;38(3):901-907. doi:10.1007/s00726-009-0297-9\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTran S, Wolever TM, Errett LE, Ahn H, Mazer CD, Keith M. Preoperative carbohydrate loading in patients undergoing coronary artery bypass or spinal surgery.\u0026nbsp;\u003cem\u003eAnesthesia \u0026amp;amp; Analgesia\u003c/em\u003e. 2013;117(2):305-313. doi:10.1213/ane.0b013e318295e8d1\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTsutsumi R, Kakuta N, Kadota T, et al. Effects of oral carbohydrate with amino acid solution on the metabolic status of patients in the preoperative period: A randomized, prospective clinical trial.\u0026nbsp;\u003cem\u003eJournal of Anesthesia\u003c/em\u003e. 2016;30(5):842-849. doi:10.1007/s00540-016-2217-y\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWang ZG, Wang Q, Wang WJ, Qin HL. Randomized clinical trial to compare the effects of preoperative oral carbohydrate\u0026nbsp;\u003cem\u003eversus\u003c/em\u003e placebo on insulin resistance after colorectal surgery.\u0026nbsp;\u003cem\u003eBritish Journal of Surgery\u003c/em\u003e. 2010;97(3):317-327. doi:10.1002/bjs.6963\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYagci G, Can MF, Ozturk E, et al. Effects of preoperative carbohydrate loading on glucose metabolism and gastric contents in patients undergoing moderate surgery: A randomized, controlled trial.\u0026nbsp;\u003cem\u003eNutrition\u003c/em\u003e. 2008;24(3):212-216. doi:10.1016/j.nut.2007.11.003\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOyama Y, Iwasaka H, Siihara Keisuke et al.\u0026nbsp;Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients. \u003cem\u003eMiddle East journal of anaesthesiology\u003c/em\u003e. 2011;21(3):375-83\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDock-Nascimento DB, de Aquilar-Nascimento JE, Linetzky Waitzberg D. Ingestion of glutamine and maltodextrin two hours preoperatively improves insulin sensitivity after surgery: a randomized, double blind, controlled trial.\u0026nbsp;\u003cem\u003eJournal of Brazilian College of Surgeon\u003c/em\u003es. 2012;39(6):449-55. doi: 10.1590/s0100-69912012000600002\u003c/li\u003e\n \u003cli\u003eLende TH, Austdal M, Varhaugvik AE, et al. Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients ─ a randomized trial. \u003cem\u003eBMC Cancer\u003c/em\u003e. 2019;19(1). doi:10.1186/s12885-019-6275-z\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHegyi P, Erőss B, Izb\u0026eacute;ki F, P\u0026aacute;rniczky A, Szentesi A. Accelerating the Translational Medicine Cycle: The Academia Europaea Pilot. \u003cem\u003eNature Medicine\u003c/em\u003e. 2021;27(8):1317-1319. doi:10.1038/s41591-021-01458-8\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHegyi P, Petersen OH, Holgate S, et al. Academia Europaea Position Paper on translational medicine: The cycle model for translating scientific results into community benefits. \u003cem\u003eJournal of Clinical Medicine\u003c/em\u003e. 2020;9(5):1532. doi:10.3390/jcm9051532\u0026nbsp;\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Preoperative fasting, oral carbohydrate loading, major surgery, non-cardiac surgery, length of stay","lastPublishedDoi":"10.21203/rs.3.rs-4085704/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4085704/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePreoperative fasting is a worldwide routine even though the most recent Enhanced Recovery After Surgery (ERAS) Guidelines recommend preoperative carbohydrate loading instead of fasting, but with low quality of evidence. Our aim was to compare the effects of preoperative carbohydrate loading to fasting and placebo in patients undergoing elective major non-cardiac surgery under general anaesthesia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur systematic search was conducted on 15\u003csup\u003eth\u003c/sup\u003e of October 2021 in five databases, Medline, Embase, Central, Web of Science and Scopus. We included randomized controlled trials that compared the carbohydrate loading (CHO-group) with fasting (Fasting-group) and with placebo (Placebo-group). Main outcomes were length of hospital stay (LOS), postoperative glucose levels on postoperative day 1 and 2, postoperative insulin levels on postoperative day 1, and C-reactive protein (CRP) levels on postoperative day 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur search revealed 55 eligible articles for the data extraction. LOS was almost two days shorter in the CHO-group as compared to the Fasting-group (MD: -1,71 [95% CI: -3.04, -0,38] days), but there was no significant result when compared to the Placebo-group (-0.01 [-0.16; 0.16]). There were no significant differences between the CHO-group and Fasting-group and CHO-group and Placebo-group regarding the postoperative glucose, insulin and CRP levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis meta-analysis found that preoperative CHO-loading as compared to preoperative fasting shortened the length of hospital stay in patients undergoing major elective, non-cardiac surgery. Although several details are still to be unveiled, these data provide further support that preoperative fluid intake with CHO-loading could be beneficial in this patient population.\u003c/p\u003e","manuscriptTitle":"Preoperative carbohydrate loading reduces length of hospital stay compared to fasting in patients undergoing major elective, non-cardiac surgery: A systematic Review and Meta- Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 18:23:00","doi":"10.21203/rs.3.rs-4085704/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-04T06:56:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-28T14:01:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106540240458192696979587874515347586992","date":"2024-08-06T18:30:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-16T14:49:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96a75471-de9b-483a-90dc-2292a291213d_SNPRID","date":"2024-04-15T15:21:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-15T12:22:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-15T11:51:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-10T11:35:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-10T11:32:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-03-12T13:17:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"125ea2f2-39fc-4733-8006-31115682ae03","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":30635254,"name":"Health sciences/Diseases"},{"id":30635255,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-06-02T15:58:38+00:00","versionOfRecord":{"articleIdentity":"rs-4085704","link":"https://doi.org/10.1038/s41598-025-00767-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-05-31 15:56:59","publishedOnDateReadable":"May 31st, 2025"},"versionCreatedAt":"2024-04-19 18:23:00","video":"","vorDoi":"10.1038/s41598-025-00767-z","vorDoiUrl":"https://doi.org/10.1038/s41598-025-00767-z","workflowStages":[]},"version":"v1","identity":"rs-4085704","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4085704","identity":"rs-4085704","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}