{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:02:10Z","timestamp":1790010130184,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Elevated gastric residual volume (GRV) is traditionally read as feeding intolerance, and randomized trials in general intensive care units (ICUs) have discredited its routine use. Whether this holds in neurocritical patients is unknown. Methods: This exploratory, hypothesis-generating single-center retrospective cohort study comprised 355 neurosurgical ICU adults with documented GRV (2022\u20132026)\u2014the exposure was a peak GRV \u2265 250 mL, the institutional feeding-hold threshold (n = 32). Three explanations were examined: prognosis (Firth penalized regression for in-hospital mortality), nutrition (standardized mean differences with causal mediation), and intracranial pathology (rank-based partial correlation between patient-level maxima of GRV and intracranial pressure (ICP) in the same early ICU window, plus trajectory phenotyping). Results: Elevated GRV was not significantly associated with in-hospital mortality (adjusted odds ratio 1.46; 95% confidence interval (CI) 0.52\u20133.65) and was not associated with greater deterioration in laboratory-based systemic inflammatory\/nutritional indices than in comparators, with null mediation. The patient-level maxima of GRV and ICP were correlated before adjustment (\u03c1 = 0.28) and 0.19 after full adjustment (95% CI \u22120.001 to 0.37, p = 0.051; 10 exposed of 109), and intracranial hypertension (ICP &gt; 22 mmHg) occurred in 90% of exposed versus 61% of unexposed monitored patients. A high-GRV trajectory phenotype was the youngest class yet showed the most frequent intracranial hypertension, although its membership and persistence were highly sensitive to missing-data handling. Conclusions: In neurocritical patients receiving enteral tube feeding with documented GRV monitoring, elevated GRV was not associated with greater deterioration in laboratory-based systemic inflammatory\/nutritional indices, whereas a possible association with higher early ICP was observed in a small, monitored subset. Because the ICP-monitored subset was small, these exploratory, hypothesis-generating findings do not establish a brain\u2013gut signal. They raise the hypothesis that elevated GRV in this setting may reflect intracranial rather than solely gastrointestinal processes and require prospective confirmation with temporally paired measurements.<\/jats:p>","DOI":"10.3390\/nu18183103","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:06:51Z","timestamp":1790006811000},"page":"3103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastric Residual Volume as a Candidate Brain\u2013Gut Signal in Neurocritical Care: An Exploratory, Hypothesis-Generating Retrospective Cohort Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5458-0157","authenticated-orcid":false,"given":"Geun-Hee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Jeong-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Su-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6637-1352","authenticated-orcid":false,"given":"Joon-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-3471","authenticated-orcid":false,"given":"Kyeong-Won","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Dietetics, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-848X","authenticated-orcid":false,"given":"Jeong-Am","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"},{"name":"Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.clnu.2018.08.037","article-title":"ESPEN guideline on clinical nutrition in the intensive care unit","volume":"38","author":"Singer","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.4037\/ajcc2008.17.6.512","article-title":"Gastric residual volume and aspiration in critically ill patients receiving gastric feedings","volume":"17","author":"Metheny","year":"2008","journal-title":"Am. J. Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.2012.196377","article-title":"Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: A randomized controlled trial","volume":"309","author":"Reignier","year":"2013","journal-title":"J. Am. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1007\/s00134-010-1856-y","article-title":"Gastric residual volume during enteral nutrition in ICU patients: The REGANE study","volume":"36","author":"Montejo","year":"2010","journal-title":"Intensive Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/0148607115621863","article-title":"Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)","volume":"40","author":"McClave","year":"2016","journal-title":"JPEN J. Parenter. Enteral. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s00134-016-4665-0","article-title":"Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines","volume":"43","author":"Starkopf","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schmidt, E.A., Despas, F., Pavy-Le Traon, A., Czosnyka, Z., Pickard, J.D., Rahmouni, K., Pathak, A., and Senard, J.M. (2018). Intracranial Pressure Is a Determinant of Sympathetic Activity. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00011"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1089\/neu.2013.3301","article-title":"Paroxysmal sympathetic hyperactivity after acquired brain injury: Consensus on conceptual definition, nomenclature, and diagnostic criteria","volume":"31","author":"Baguley","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"254","DOI":"10.4103\/1673-5374.290883","article-title":"Altered physiology of gastrointestinal vagal afferents following neurotrauma","volume":"16","author":"Blanke","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/j.1572-0241.1998.00338.x","article-title":"Gastric emptying in head-injured patients","volume":"93","author":"Kao","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yuan, R., Liu, L., Mi, J., Li, X., Yang, F., and Mao, S. (2024). Development and validation of a risk prediction model for feeding intolerance in neurocritical patients with enteral nutrition. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1481279"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1097\/00005373-199609000-00022","article-title":"Appropriate use of the Glasgow Coma Scale in intubated patients: A linear regression prediction of the Glasgow verbal score from the Glasgow eye and motor scores","volume":"41","author":"Rutledge","year":"1996","journal-title":"J. Trauma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1227\/NEU.0000000000001432","article-title":"Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition","volume":"80","author":"Carney","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1097\/00003246-198510000-00009","article-title":"APACHE II: A severity of disease classification system","volume":"13","author":"Knaus","year":"1985","journal-title":"Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction\/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_16","first-page":"1001","article-title":"[Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients]","volume":"85","author":"Onodera","year":"1984","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"ref_17","first-page":"38","article-title":"CONUT: A tool for controlling nutritional status. First validation in a hospital population","volume":"20","author":"Mancha","year":"2005","journal-title":"Nutr. Hosp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.clnu.2015.01.015","article-title":"Identifying critically-ill patients who will benefit most from nutritional therapy: Further validation of the \u201cmodified NUTRIC\u201d nutritional risk assessment tool","volume":"35","author":"Rahman","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/sim.1047","article-title":"A solution to the problem of separation in logistic regression","volume":"21","author":"Heinze","year":"2002","journal-title":"Stat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"147","author":"Altman","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00180-009-0178-4","article-title":"KmL: K-means for longitudinal data","volume":"25","author":"Genolini","year":"2010","journal-title":"Comput. Stat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1037\/a0020761","article-title":"A general approach to causal mediation analysis","volume":"15","author":"Imai","year":"2010","journal-title":"Psychol. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","article-title":"Mediation Analysis: A Practitioner\u2019s Guide","volume":"37","author":"VanderWeele","year":"2016","journal-title":"Annu. Rev. Public Health"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"M\u0105dra-Gackowska, K., Szewczyk-Golec, K., Gackowski, M., Ho\u0142y\u0144ska-Iwan, I., Parzych, D., Czuczejko, J., Graczyk, M., Husejko, J., Jab\u0142o\u0144ski, T., and K\u0119dziora-Kornatowska, K. (2025). Selected Biochemical, Hematological, and Immunological Blood Parameters for the Identification of Malnutrition in Polish Senile Inpatients: A Cross-Sectional Study. J. Clin. Med., 14.","DOI":"10.3390\/jcm14051494"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1186\/s13054-021-03793-1","article-title":"The effect of opioids on gastrointestinal function in the ICU","volume":"25","author":"Yan","year":"2021","journal-title":"Crit. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/aje\/kwm324","article-title":"Immortal time bias in pharmaco-epidemiology","volume":"167","author":"Suissa","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/S0140-6736(02)08711-1","article-title":"Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: A randomised controlled trial","volume":"359","author":"Lobo","year":"2002","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s00134-011-2459-y","article-title":"Gastrointestinal function in intensive care patients: Terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems","volume":"38","author":"Malbrain","year":"2012","journal-title":"Intensive Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/ije\/dyp334","article-title":"Illustrating bias due to conditioning on a collider","volume":"39","author":"Cole","year":"2010","journal-title":"Int. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/neu.1998.15.573","article-title":"Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: Guidelines for their use","volume":"15","author":"Wilson","year":"1998","journal-title":"J. Neurotrauma"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:11:00Z","timestamp":1790007060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":30,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18183103"],"URL":"https:\/\/doi.org\/10.3390\/nu18183103","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}