Preoperative Carbohydrate Loading vs Fasting: Effects on Postoperative Recovery and Outcomes in General Surgery

Preoperative Carbohydrate Loading vs Fasting: Effects on Postoperative Recovery and Outcomes in General Surgery | 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 Systematic Review Preoperative Carbohydrate Loading vs Fasting: Effects on Postoperative Recovery and Outcomes in General Surgery Joseph Marcuccilli, Nathan Jatczak This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6779516/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Traditional preoperative fasting aims to reduce aspiration risk but may exacerbate catabolism and insulin resistance. Enhanced Recovery After Surgery (ERAS) guidelines often endorse preoperative carbohydrate loading (PCL) in lieu of prolonged fasting. We systematically identified all peer-reviewed, blinded, PubMed-indexed studies (2020–2025) in general surgery comparing preoperative oral carbohydrate loading versus standard fasting, with outcomes focusing on postoperative recovery time (e.g. time to flatus, oral intake, ambulation, hospital stay) and overall patient outcomes (e.g. complications, insulin resistance, patient comfort). We extracted key insights from each randomized controlled trial (RCT) and synthesized common findings and discrepancies. Six RCTs met inclusion criteria (bariatric, colorectal, and general gastrointestinal surgery). Common findings were that PCL is safe, improves perioperative comfort (reduced hunger, thirst, fatigue, anxiety), and attenuates insulin resistance and inflammatory stress responses [ 1 ]. However, effects on recovery metrics and complications varied: some trials reported shorter time to bowel function and hospital stay with PCL [ 2 , 4 ], whereas others found no significant benefit [ 1 ]. In comparative synthesis, we identified five frequent commonalities (e.g. enhanced patient comfort, reduced metabolic stress) and five frequent divergences (e.g. mixed effects on length of stay and complications). Trend analysis revealed areas moving toward consensus (e.g. PCL’s safety and metabolic benefits) and away (e.g. LOS reduction), as well as emerging insights (e.g. benefits for diabetic patients when combined with insulin management). These findings were integrated into a formal meta-analysis-style report. All cited studies are RCTs in PubMed-indexed journals focusing on general surgery outcomes. preoperative fasting carbohydrate loading enhanced recovery after surgery insulin resistance postoperative recovery Figures Figure 1 Introduction Prolonged preoperative fasting has historically been mandated to minimize aspiration risk, but this can increase patient discomfort and metabolic stress [ 2 , 4 ]. Modern ERAS protocols generally recommend allowing clear carbohydrate-rich fluids up to 2 hours before anesthesia to mitigate catabolism, insulin resistance, and thirst, potentially improving recovery [ 6 ]. However, the extent to which preoperative carbohydrate loading (PCL) improves objective recovery endpoints (e.g. time to flatus, length of stay, complication rates) in general surgery remains debated. We conducted a comprehensive review of all blinded RCTs (2020–2025) in general surgery comparing PCL versus conventional fasting, focusing on postoperative recovery metrics and patient outcomes. This report summarizes each trial’s design and findings, then synthesizes overarching patterns, differences, and emerging trends among the studies. Methods We searched PubMed and PMC for randomized controlled trials (2020–2025) of oral preoperative carbohydrate loading (versus fasting/placebo) in general surgery populations. Inclusion criteria were: peer-reviewed, human RCTs with blinding of at least patients or assessors, focused on general/abdominal surgery (including colorectal and bariatric). Excluded were orthopedic, obstetric, cardiac, or purely elective day-case surgeries. Relevant trials were identified via keywords (e.g. “preoperative carbohydrate randomized controlled trial”, surgical outcomes, fasting) and cross-references from systematic reviews. For each trial, we extracted methodology (population, surgery type, carbohydrate regimen vs control) and results (recovery endpoints, metabolic markers, complications). A comparative synthesis identified common conclusions and conflicts across studies. Results Individual Study Summaries Suh et al., 2021 (Bariatric Surgery) – Single-center RCT (N = 134) in minimally invasive Roux-en-Y gastric bypass or sleeve gastrectomy patients [ 1 ]. Intervention: two 400 mL carbohydrate drinks (evening before and 3 h pre-op); Control: NPO after midnight. Primary outcomes were postoperative nausea/vomiting (PONV), length of stay (LOS), and complications. Results showed no significant differences in LOS or overall complications [ 1 ]. No aspiration occurred in the PCL group. Among RYGB patients, PCL shortened the duration of nausea. Glycemic control (even in diabetic patients) was similar between groups. Conclusion : Pre-op CHO drinks are safe and can reduce PONV duration, but had no detectable effect on LOS or major outcomes [ 1 ]. Liu et al. (Fan et al.), 2021 (Open GI Surgery, Elderly) – Prospective RCT (N = 120, age ≥ 65) undergoing open gastrointestinal surgery [ 2 ]. All patients had standard anesthesia. Intervention (GDFT group): 200 mL CHO drink 2 h pre-op + goal-directed intraoperative fluid therapy (guided by advanced monitors). Control (CFT group): traditional fasting + liberal IV fluids. Compared intra/postoperative fluids, time to flatus and oral intake, complications, and LOS. The GDFT + CHO group used significantly less intra-op crystalloids and had shorter time to first flatus (56 ± 14 h vs 64 ± 22 h, p = 0.002) and oral intake (72 ± 17 h vs 85 ± 27 h, p = 0.011) [ 2 ]. Postoperative complication rate was lower in the GDFT + CHO group (25% vs 48%, p = 0.013) [ 2 ]. Conclusion : Combined perioperative optimizations (CHO + GDFT) improved GI recovery and reduced complications [ 2 ]. (Note: The study changed two variables, so CHO’s isolated effect is confounded by fluid strategy.) Li et al., 2022 (Diabetic GI Surgery) – Single-center RCT (N = 63) of type-2 diabetic patients undergoing elective GI surgery [ 3 ]. Intervention: 50 g dextrose + individualized insulin dosing 2 h pre-op; Control: standard overnight fasting. Primary outcome: time to first flatus. Secondary: patient comfort scores (thirst, hunger, fatigue by VAS) and PONV. Time to flatus was not different (median 41 h vs 43 h; hazard ratio 1.24, p = 0.411) [ 3 ]. However, the PCL group reported significantly lower scores for preoperative thirst, hunger, and fatigue, and postoperative thirst and hunger (all p < 0.01) [ 3 ]. They also had less intraoperative hypotension (16% vs 41%, p = 0.031) and less PONV in 24 h (9.7% vs 31.3%, p = 0.034) [ 3 ]. Conclusion : In diabetic patients, PCL (with insulin) did not hasten GI recovery but improved perioperative comfort and reduced PONV and hypotension [ 3 ]. Vishak et al., 2023 (General Elective Surgery) – Prospective RCT (N = 240, age 40–65, mixed surgeries under regional anesthesia) [ 4 ]. Patients stratified by diabetes. Intervention: 400 mL drink with 50 g dextrose 2 h pre-op; Control: 400 mL plain water. Outcomes: gastric volume (ultrasound), blood glucose, thirst/discomfort (Likert). Gastric volume was similar between CHO and water groups for both diabetic and non-diabetic patients (no significant difference) [ 4 ], confirming safety. As expected, diabetic subjects receiving CHO had a transient blood glucose rise (183 vs 139 mg/dL after 2 h) that normalized by 6 h (managed with insulin) [ 4 ]. Importantly, the CHO groups (both diabetic and non) reported significantly less preoperative thirst and discomfort (Likert scales) than fasting groups [ 4 ]. Conclusion : Pre-op CHO is safe (no delayed gastric emptying) and markedly improves patient comfort, even in diabetics [ 4 ], without adverse glycemic or safety issues. Rizvanović et al., 2023 (Open Colorectal Cancer Surgery) – RCT (N = 60) for open colorectal resection [ 5 ]. Intervention: CHO solution night before and 2 h pre-op; Control: NPO after midnight. Primary outcomes: neutrophil/lymphocyte ratio (NLR) as a marker of inflammatory stress, and postoperative complications (Clavien–Dindo up to 30 days). Postoperative NLR and ΔNLR were significantly lower in the CHO group (p < 0.001) [ 5 ]. The control (fasting) group had 6 major complications (5 grade IV, 1 grade V), whereas the CHO group had no major complications [ 5 ]. Conclusion : Pre-op CHO loading substantially dampened inflammatory response (lower NLR) and was associated with fewer and less severe complications [ 5 ]. Kumar et al., 2024 (Elective Colorectal Surgery) – Open-label RCT (N = 72) in elective colorectal procedures [ 6 ]. Intervention: standard ERAS CHO drink 2 h pre-op; Control: fasting. Measured insulin resistance (IR), IL-6, clinical well-being (thirst, hunger, etc.), intestinal recovery, ambulation, morbidity, and LOS. Results: The CHO group had significantly reduced postoperative IR on day-of-surgery and POD1/3 (p = 0.0336) [ 6 ], and markedly lower inflammatory markers and GPS (p < 0.001). They also reported less thirst, hunger, and dry mouth and had a shorter hospital stay [ 6 ]. Conclusion : PCL in colorectal surgery significantly reduced metabolic stress and improved multiple clinical outcomes, including shortened LOS and better patient comfort [ 6 ]. Comparative Synthesis Commonalities (Top 5) : Safety : PCL did not increase gastric volume or aspiration risk [ 1 ]. Patient Comfort : Consistent reductions in preop discomfort (hunger, thirst, anxiety) [ 1 ]. Metabolic Effects : Lower postoperative insulin resistance/inflammation [ 1 ]. Early GI Recovery : Several studies noted earlier return of GI function [ 6 ]. Enhanced ERAS Integration : PCL aligns as a key ERAS component [ 1 ]. Divergences (Top 5) : LOS : Mixed results—shorter in some (Kumar, Rizvanović [ 6 ]) vs. no change in others (Suh, Li [ 1 ]). Complications : Reduced in some (Fan, Rizvanović [ 2 , 5 ]) vs. unchanged in others (Suh, Li [ 1 ]). Diabetics : Variable insulin protocols and outcomes [ 3 , 4 ]. Study Designs : Differences in CHO dosing, adjunctive therapies (GDFT confounder) [ 2 ]. Endpoints : Focus ranged from metabolic markers to patient-reported outcomes. Trends Toward Consensus Safety of PCL; metabolic benefits; improved patient-centered outcomes. Trends Away from Consensus Consistent LOS reduction; universal complication reduction; clear long-term glycemic benefits. Emerging Insights Subgroup (elderly/diabetic) benefits; PCL’s role in holistic ERAS bundles. Discussion The collective evidence from recent RCTs supports the safety of allowing carbohydrate-rich clear fluids up to ~ 2 hours before surgery, aligning with ASA fasting guidelines. Notably, no trial reported increased aspiration or delayed gastric emptying with PCL [ 1 ]. The metabolic rationale is confirmed: consistent reductions in postoperative insulin resistance and inflammation (lower NLR, IL-6, GPS) were observed [ 1 ]. Such biochemical improvements correlate with clinical signals of faster recovery (earlier bowel movements) in several studies [ 2 ]. However, the trials also underscore that PCL is not a panacea. Merely drinking a CHO solution will not automatically shorten a hospital stay or eliminate complications unless integrated into comprehensive protocols. The dramatic finding of zero severe complications in Rizvanović’s CHO arm [ 5 ] must be interpreted cautiously, as other cohorts did not replicate such stark differences. The elderly GI surgery trial by Liu et al. suggests that combining PCL with goal-directed fluid management yields stronger benefits than CHO alone [ 2 ], pointing to synergy between nutritional and hemodynamic optimization. Diabetic patients merit special consideration: historically, clinicians were hesitant to give CHO to diabetics. Recent evidence [ 3 ] shows that with insulin protocols, diabetics can safely receive pre-op CHO, improving comfort and reducing PONV, though without obvious GI recovery acceleration. This emerging approach could reconcile enhanced-recovery nutrition with glycemic safety. Comparing outcomes across studies reveals that patient-centered measures (comfort, nausea, readiness) consistently favor CHO, even when traditional metrics (LOS, complications) show null results. Future research might increasingly focus on such patient-reported outcomes and short-term functional recovery, as hidden but clinically relevant benefits of PCL. Moreover, the combination of PCL with other ERAS elements seems to be an important trend: studies suggest that the sum of multiple optimizations (carb drink, regional anesthesia, early feeding) may yield disproportionately better results than any single intervention. Limitations The examined studies vary in size and surgical type, limiting generalizability. Blinding was incomplete in most trials (inevitable, given taste of CHO drink). Meta-analytic pooling is precluded by heterogeneity in protocols. Nevertheless, the consistent safety profile and recurrent findings on metabolic stress and comfort bolster confidence in key conclusions. Conclusion In general surgery, replacing prolonged fasting with a preoperative carbohydrate drink is safe and well-tolerated, and yields clear metabolic and comfort advantages [ 1 ]. The evidence increasingly supports consensus that PCL should be a standard ERAS component. Its effects on objective recovery endpoints (LOS, complication rates) are variable, suggesting that CHO loading is helpful but not solely determinative of outcomes. The most robust benefits appear in reducing perioperative insulin resistance and enhancing patient well-being. Moving forward, optimal protocols may involve personalization (e.g. insulin-assisted CHO for diabetics) and bundling with other ERAS measures. Overall, the shift toward consensus on the benefits of carbohydrate loading – coupled with ongoing investigation into its most effective application – represents a significant evolution in perioperative care. Declarations Competing Interests The authors declare no competing financial or non-financial interests. Author Contribution All authors contributed to the study conception and design. Literature search and data analysis were performed by Joseph Marcuccilli and Nathan Jatczak. The first draft of the manuscript was written by Joey Marcuccilli and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References 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. Surg Obes Relat Dis. 2021;17(8):1480–8. Liu X, Zhang P, Liu MX, Ma JL, Wei XC, Fan D. Preoperative carbohydrate loading and intraoperative goal-directed fluid therapy for elderly patients undergoing open gastrointestinal surgery: a prospective randomized controlled trial. BMC Anesthesiol. 2021;21:157. Li X, Liu L, Liang XQ, Li YT, Wang DX. Preoperative carbohydrate loading with individualized supplemental insulin in diabetic patients undergoing gastrointestinal surgery: a randomized trial. Int J Surg. 2022;98:106215. Vishak M, Gayathri B, Chandrasekhar G, et al. Effects of preoperative oral carbohydrate drink on gastric volume, glycemia, and perioperative comfort in diabetic and non-diabetic patients. Cureus. 2023;15(11):e49213. Rizvanović N, Nesek Adam V, Kalajdžija M, et al. Effects of preoperative oral carbohydrate loading on neutrophil/lymphocyte ratio and postoperative complications following colorectal cancer surgery: a randomized controlled study. Eur Surg Res. 2023;64(2):278–85. Kumar SM, Anandhi A, Sureshkumar S, et al. Effect of preoperative oral carbohydrate loading on postoperative insulin resistance, patient-perceived well-being, and surgical outcomes in elective colorectal surgery: a randomized controlled trial. J Gastrointest Surg. 2024;28(10):1654–60. Additional Declarations No competing interests reported. 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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-6779516","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":464944686,"identity":"8c7750a8-b752-4d31-808e-55316da8e058","order_by":0,"name":"Joseph Marcuccilli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYBAC9hkJEAYbO3PDgQ9QUQl8WhjnPIBqYWZsODiDwYAILfOhWhiAWph5iNIyO/nZh59tdvJ8zIyNh21q/tgbHGA+eJsHr5Y045m9bcmGbUBbDuccM0jccIAt2Rq/lgRjZsa2AwlsYC1sBgkGB3jMpPFqmZH+GaHF4p8B0GH83/BqEZyRg2QLY5sB44YDPGx4tUhL5BQz9pyD+OVgb59x4szDbMaWc/Bo4ZNI38zwo8xOXr69+fCHH9/k7PmONz+88QaPFiyAmTTlo2AUjIJRMAqwAABv3Ef4Q8O+owAAAABJRU5ErkJggg==","orcid":"","institution":"A.T. Still University","correspondingAuthor":true,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Marcuccilli","suffix":""},{"id":464944687,"identity":"1a335588-eb26-4727-8cd1-536e6a0f586c","order_by":1,"name":"Nathan Jatczak","email":"","orcid":"","institution":"A.T. Still University","correspondingAuthor":false,"prefix":"","firstName":"Nathan","middleName":"","lastName":"Jatczak","suffix":""}],"badges":[],"createdAt":"2025-05-29 21:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6779516/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6779516/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85304634,"identity":"b3ae1c8c-4861-4326-8874-97ccac160f93","added_by":"auto","created_at":"2025-06-24 12:37:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":297425,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSummary of randomized controlled trials evaluating the effects of preoperative carbohydrate loading (PCL).\u003c/strong\u003e This table presents key design elements, interventions, outcomes, and conclusions across six recent RCTs investigating PCL. Common findings include improved patient comfort and reduced postoperative nausea and metabolic stress, while effects on length of stay and complications vary by study design and patient population.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6779516/v1/5770b8b271e1072689949282.png"},{"id":88904120,"identity":"1288c3ba-0db3-4267-b204-2b04eea0e110","added_by":"auto","created_at":"2025-08-12 14:09:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":889404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6779516/v1/751f347a-9b00-446a-9ffb-05ba39d3d7f8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preoperative Carbohydrate Loading vs Fasting: Effects on Postoperative Recovery and Outcomes in General Surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProlonged preoperative fasting has historically been mandated to minimize aspiration risk, but this can increase patient discomfort and metabolic stress [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Modern ERAS protocols generally recommend allowing clear carbohydrate-rich fluids up to 2 hours before anesthesia to mitigate catabolism, insulin resistance, and thirst, potentially improving recovery [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, the extent to which preoperative carbohydrate loading (PCL) improves objective recovery endpoints (e.g. time to flatus, length of stay, complication rates) in general surgery remains debated. We conducted a comprehensive review of all blinded RCTs (2020\u0026ndash;2025) in general surgery comparing PCL versus conventional fasting, focusing on postoperative recovery metrics and patient outcomes. This report summarizes each trial\u0026rsquo;s design and findings, then synthesizes overarching patterns, differences, and emerging trends among the studies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe searched PubMed and PMC for randomized controlled trials (2020\u0026ndash;2025) of oral preoperative carbohydrate loading (versus fasting/placebo) in general surgery populations. Inclusion criteria were: peer-reviewed, human RCTs with blinding of at least patients or assessors, focused on general/abdominal surgery (including colorectal and bariatric). Excluded were orthopedic, obstetric, cardiac, or purely elective day-case surgeries. Relevant trials were identified via keywords (e.g. \u0026ldquo;preoperative carbohydrate randomized controlled trial\u0026rdquo;, surgical outcomes, fasting) and cross-references from systematic reviews. For each trial, we extracted methodology (population, surgery type, carbohydrate regimen vs control) and results (recovery endpoints, metabolic markers, complications). A comparative synthesis identified common conclusions and conflicts across studies.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eIndividual Study Summaries\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSuh et al., 2021 (Bariatric Surgery)\u003c/b\u003e \u0026ndash; Single-center RCT (N\u0026thinsp;=\u0026thinsp;134) in minimally invasive Roux-en-Y gastric bypass or sleeve gastrectomy patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Intervention: two 400 mL carbohydrate drinks (evening before and 3 h pre-op); Control: NPO after midnight. Primary outcomes were postoperative nausea/vomiting (PONV), length of stay (LOS), and complications. Results showed no significant differences in LOS or overall complications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. No aspiration occurred in the PCL group. Among RYGB patients, PCL shortened the duration of nausea. Glycemic control (even in diabetic patients) was similar between groups. \u003cb\u003eConclusion\u003c/b\u003e: Pre-op CHO drinks are safe and can reduce PONV duration, but had no detectable effect on LOS or major outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLiu et al. (Fan et al.), 2021 (Open GI Surgery, Elderly)\u003c/b\u003e \u0026ndash; Prospective RCT (N\u0026thinsp;=\u0026thinsp;120, age\u0026thinsp;\u0026ge;\u0026thinsp;65) undergoing open gastrointestinal surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. All patients had standard anesthesia. Intervention (GDFT group): 200 mL CHO drink 2 h pre-op\u0026thinsp;+\u0026thinsp;goal-directed intraoperative fluid therapy (guided by advanced monitors). Control (CFT group): traditional fasting\u0026thinsp;+\u0026thinsp;liberal IV fluids. Compared intra/postoperative fluids, time to flatus and oral intake, complications, and LOS. The GDFT\u0026thinsp;+\u0026thinsp;CHO group used significantly less intra-op crystalloids and had shorter time to first flatus (56\u0026thinsp;\u0026plusmn;\u0026thinsp;14 h vs 64\u0026thinsp;\u0026plusmn;\u0026thinsp;22 h, p\u0026thinsp;=\u0026thinsp;0.002) and oral intake (72\u0026thinsp;\u0026plusmn;\u0026thinsp;17 h vs 85\u0026thinsp;\u0026plusmn;\u0026thinsp;27 h, p\u0026thinsp;=\u0026thinsp;0.011) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Postoperative complication rate was lower in the GDFT\u0026thinsp;+\u0026thinsp;CHO group (25% vs 48%, p\u0026thinsp;=\u0026thinsp;0.013) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. \u003cb\u003eConclusion\u003c/b\u003e: Combined perioperative optimizations (CHO\u0026thinsp;+\u0026thinsp;GDFT) improved GI recovery and reduced complications [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. (Note: The study changed two variables, so CHO\u0026rsquo;s isolated effect is confounded by fluid strategy.)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLi et al., 2022 (Diabetic GI Surgery)\u003c/b\u003e \u0026ndash; Single-center RCT (N\u0026thinsp;=\u0026thinsp;63) of type-2 diabetic patients undergoing elective GI surgery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Intervention: 50 g dextrose\u0026thinsp;+\u0026thinsp;individualized insulin dosing 2 h pre-op; Control: standard overnight fasting. Primary outcome: time to first flatus. Secondary: patient comfort scores (thirst, hunger, fatigue by VAS) and PONV. Time to flatus was not different (median 41 h vs 43 h; hazard ratio 1.24, p\u0026thinsp;=\u0026thinsp;0.411) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the PCL group reported significantly lower scores for preoperative thirst, hunger, and fatigue, and postoperative thirst and hunger (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. They also had less intraoperative hypotension (16% vs 41%, p\u0026thinsp;=\u0026thinsp;0.031) and less PONV in 24 h (9.7% vs 31.3%, p\u0026thinsp;=\u0026thinsp;0.034) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. \u003cb\u003eConclusion\u003c/b\u003e: In diabetic patients, PCL (with insulin) did not hasten GI recovery but improved perioperative comfort and reduced PONV and hypotension [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eVishak et al., 2023 (General Elective Surgery)\u003c/b\u003e \u0026ndash; Prospective RCT (N\u0026thinsp;=\u0026thinsp;240, age 40\u0026ndash;65, mixed surgeries under regional anesthesia) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Patients stratified by diabetes. Intervention: 400 mL drink with 50 g dextrose 2 h pre-op; Control: 400 mL plain water. Outcomes: gastric volume (ultrasound), blood glucose, thirst/discomfort (Likert). Gastric volume was similar between CHO and water groups for both diabetic and non-diabetic patients (no significant difference) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], confirming safety. As expected, diabetic subjects receiving CHO had a transient blood glucose rise (183 vs 139 mg/dL after 2 h) that normalized by 6 h (managed with insulin) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Importantly, the CHO groups (both diabetic and non) reported significantly less preoperative thirst and discomfort (Likert scales) than fasting groups [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. \u003cb\u003eConclusion\u003c/b\u003e: Pre-op CHO is safe (no delayed gastric emptying) and markedly improves patient comfort, even in diabetics [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], without adverse glycemic or safety issues.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eRizvanović et al., 2023 (Open Colorectal Cancer Surgery)\u003c/b\u003e \u0026ndash; RCT (N\u0026thinsp;=\u0026thinsp;60) for open colorectal resection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Intervention: CHO solution night before and 2 h pre-op; Control: NPO after midnight. Primary outcomes: neutrophil/lymphocyte ratio (NLR) as a marker of inflammatory stress, and postoperative complications (Clavien\u0026ndash;Dindo up to 30 days). Postoperative NLR and ΔNLR were significantly lower in the CHO group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The control (fasting) group had 6 major complications (5 grade IV, 1 grade V), whereas the CHO group had no major complications [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. \u003cb\u003eConclusion\u003c/b\u003e: Pre-op CHO loading substantially dampened inflammatory response (lower NLR) and was associated with fewer and less severe complications [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eKumar et al., 2024 (Elective Colorectal Surgery)\u003c/b\u003e \u0026ndash; Open-label RCT (N\u0026thinsp;=\u0026thinsp;72) in elective colorectal procedures [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Intervention: standard ERAS CHO drink 2 h pre-op; Control: fasting. Measured insulin resistance (IR), IL-6, clinical well-being (thirst, hunger, etc.), intestinal recovery, ambulation, morbidity, and LOS. Results: The CHO group had significantly reduced postoperative IR on day-of-surgery and POD1/3 (p\u0026thinsp;=\u0026thinsp;0.0336) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and markedly lower inflammatory markers and GPS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). They also reported less thirst, hunger, and dry mouth and had a shorter hospital stay [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. \u003cb\u003eConclusion\u003c/b\u003e: PCL in colorectal surgery significantly reduced metabolic stress and improved multiple clinical outcomes, including shortened LOS and better patient comfort [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eComparative Synthesis\u003c/h3\u003e\n\u003cp\u003e \u003cb\u003eCommonalities (Top 5)\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSafety\u003c/b\u003e: PCL did not increase gastric volume or aspiration risk [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePatient Comfort\u003c/b\u003e: Consistent reductions in preop discomfort (hunger, thirst, anxiety) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMetabolic Effects\u003c/b\u003e: Lower postoperative insulin resistance/inflammation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eEarly GI Recovery\u003c/b\u003e: Several studies noted earlier return of GI function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eEnhanced ERAS Integration\u003c/b\u003e: PCL aligns as a key ERAS component [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eDivergences (Top 5)\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLOS\u003c/b\u003e: Mixed results\u0026mdash;shorter in some (Kumar, Rizvanović [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]) vs. no change in others (Suh, Li [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eComplications\u003c/b\u003e: Reduced in some (Fan, Rizvanović [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]) vs. unchanged in others (Suh, Li [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eDiabetics\u003c/b\u003e: Variable insulin protocols and outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eStudy Designs\u003c/b\u003e: Differences in CHO dosing, adjunctive therapies (GDFT confounder) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eEndpoints\u003c/b\u003e: Focus ranged from metabolic markers to patient-reported outcomes.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eTrends Toward Consensus\u003c/strong\u003e \u003cp\u003eSafety of PCL; metabolic benefits; improved patient-centered outcomes.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eTrends Away from Consensus\u003c/strong\u003e \u003cp\u003eConsistent LOS reduction; universal complication reduction; clear long-term glycemic benefits.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEmerging Insights\u003c/strong\u003e \u003cp\u003eSubgroup (elderly/diabetic) benefits; PCL\u0026rsquo;s role in holistic ERAS bundles.\u003c/p\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe collective evidence from recent RCTs supports the safety of allowing carbohydrate-rich clear fluids up to ~\u0026thinsp;2 hours before surgery, aligning with ASA fasting guidelines. Notably, no trial reported increased aspiration or delayed gastric emptying with PCL [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The metabolic rationale is confirmed: consistent reductions in postoperative insulin resistance and inflammation (lower NLR, IL-6, GPS) were observed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Such biochemical improvements correlate with clinical signals of faster recovery (earlier bowel movements) in several studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the trials also underscore that PCL is not a panacea. Merely drinking a CHO solution will not automatically shorten a hospital stay or eliminate complications unless integrated into comprehensive protocols. The dramatic finding of zero severe complications in Rizvanović\u0026rsquo;s CHO arm [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] must be interpreted cautiously, as other cohorts did not replicate such stark differences. The elderly GI surgery trial by Liu et al. suggests that combining PCL with goal-directed fluid management yields stronger benefits than CHO alone [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], pointing to synergy between nutritional and hemodynamic optimization.\u003c/p\u003e \u003cp\u003eDiabetic patients merit special consideration: historically, clinicians were hesitant to give CHO to diabetics. Recent evidence [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] shows that with insulin protocols, diabetics can safely receive pre-op CHO, improving comfort and reducing PONV, though without obvious GI recovery acceleration. This emerging approach could reconcile enhanced-recovery nutrition with glycemic safety.\u003c/p\u003e \u003cp\u003eComparing outcomes across studies reveals that patient-centered measures (comfort, nausea, readiness) consistently favor CHO, even when traditional metrics (LOS, complications) show null results. Future research might increasingly focus on such patient-reported outcomes and short-term functional recovery, as hidden but clinically relevant benefits of PCL. Moreover, the combination of PCL with other ERAS elements seems to be an important trend: studies suggest that the sum of multiple optimizations (carb drink, regional anesthesia, early feeding) may yield disproportionately better results than any single intervention.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations\u003c/strong\u003e \u003cp\u003eThe examined studies vary in size and surgical type, limiting generalizability. Blinding was incomplete in most trials (inevitable, given taste of CHO drink). Meta-analytic pooling is precluded by heterogeneity in protocols. Nevertheless, the consistent safety profile and recurrent findings on metabolic stress and comfort bolster confidence in key conclusions.\u003c/p\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn general surgery, replacing prolonged fasting with a preoperative carbohydrate drink is safe and well-tolerated, and yields clear metabolic and comfort advantages [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The evidence increasingly supports consensus that PCL should be a standard ERAS component. Its effects on objective recovery endpoints (LOS, complication rates) are variable, suggesting that CHO loading is helpful but not solely determinative of outcomes. The most robust benefits appear in reducing perioperative insulin resistance and enhancing patient well-being. Moving forward, optimal protocols may involve personalization (e.g. insulin-assisted CHO for diabetics) and bundling with other ERAS measures. Overall, the shift toward consensus on the benefits of carbohydrate loading \u0026ndash; coupled with ongoing investigation into its most effective application \u0026ndash; represents a significant evolution in perioperative care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting Interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing financial or non-financial interests.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Literature search and data analysis were performed by Joseph Marcuccilli and Nathan Jatczak. The first draft of the manuscript was written by Joey Marcuccilli and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\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. Surg Obes Relat Dis. 2021;17(8):1480\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X, Zhang P, Liu MX, Ma JL, Wei XC, Fan D. Preoperative carbohydrate loading and intraoperative goal-directed fluid therapy for elderly patients undergoing open gastrointestinal surgery: a prospective randomized controlled trial. BMC Anesthesiol. 2021;21:157.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X, Liu L, Liang XQ, Li YT, Wang DX. Preoperative carbohydrate loading with individualized supplemental insulin in diabetic patients undergoing gastrointestinal surgery: a randomized trial. Int J Surg. 2022;98:106215.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVishak M, Gayathri B, Chandrasekhar G, et al. Effects of preoperative oral carbohydrate drink on gastric volume, glycemia, and perioperative comfort in diabetic and non-diabetic patients. Cureus. 2023;15(11):e49213.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRizvanović N, Nesek Adam V, Kalajdžija M, et al. Effects of preoperative oral carbohydrate loading on neutrophil/lymphocyte ratio and postoperative complications following colorectal cancer surgery: a randomized controlled study. Eur Surg Res. 2023;64(2):278\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar SM, Anandhi A, Sureshkumar S, et al. Effect of preoperative oral carbohydrate loading on postoperative insulin resistance, patient-perceived well-being, and surgical outcomes in elective colorectal surgery: a randomized controlled trial. J Gastrointest Surg. 2024;28(10):1654\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"preoperative fasting, carbohydrate loading, enhanced recovery after surgery, insulin resistance, postoperative recovery","lastPublishedDoi":"10.21203/rs.3.rs-6779516/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6779516/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTraditional preoperative fasting aims to reduce aspiration risk but may exacerbate catabolism and insulin resistance. Enhanced Recovery After Surgery (ERAS) guidelines often endorse preoperative carbohydrate loading (PCL) in lieu of prolonged fasting. We systematically identified all peer-reviewed, blinded, PubMed-indexed studies (2020\u0026ndash;2025) in general surgery comparing preoperative oral carbohydrate loading versus standard fasting, with outcomes focusing on postoperative recovery time (e.g. time to flatus, oral intake, ambulation, hospital stay) and overall patient outcomes (e.g. complications, insulin resistance, patient comfort). We extracted key insights from each randomized controlled trial (RCT) and synthesized common findings and discrepancies. Six RCTs met inclusion criteria (bariatric, colorectal, and general gastrointestinal surgery). Common findings were that PCL is safe, improves perioperative comfort (reduced hunger, thirst, fatigue, anxiety), and attenuates insulin resistance and inflammatory stress responses [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, effects on recovery metrics and complications varied: some trials reported shorter time to bowel function and hospital stay with PCL [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], whereas others found no significant benefit [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In comparative synthesis, we identified five frequent commonalities (e.g. enhanced patient comfort, reduced metabolic stress) and five frequent divergences (e.g. mixed effects on length of stay and complications). Trend analysis revealed areas moving toward consensus (e.g. PCL\u0026rsquo;s safety and metabolic benefits) and away (e.g. LOS reduction), as well as emerging insights (e.g. benefits for diabetic patients when combined with insulin management). These findings were integrated into a formal meta-analysis-style report. All cited studies are RCTs in PubMed-indexed journals focusing on general surgery outcomes.\u003c/p\u003e","manuscriptTitle":"Preoperative Carbohydrate Loading vs Fasting: Effects on Postoperative Recovery and Outcomes in General Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-24 12:37:01","doi":"10.21203/rs.3.rs-6779516/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bca6d9dc-b5c9-4647-8bdf-d43bb32cbd2f","owner":[],"postedDate":"June 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-12T14:08:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-24 12:37:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6779516","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6779516","identity":"rs-6779516","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}