{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:39:43Z","timestamp":1789663183564,"version":"4.0.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\"Thousand\" level talents of high-level innovative talents in Guizhou Province","award":["gzwjrs 2023-037"],"award-info":[{"award-number":["gzwjrs 2023-037"]}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["No.gzwkj2024-560"],"award-info":[{"award-number":["No.gzwkj2024-560"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zunyi Science and Technology Plan Project in Guizhou Provinc","award":["ZunShi KeHe No. HZ[2023] 318"],"award-info":[{"award-number":["ZunShi KeHe No. HZ[2023] 318"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with severe acute pancreatitis (SAP) often experience intense pain that significantly impacts their quality of life and may hinder recovery. Current pain management approaches have limitations. Although continuous thoracic epidural analgesia (TEA) is generally effective, some patients still need additional intermittent injections of local anesthetics for sufficient pain relief. In the ICU, nurses are the primary providers responsible for pain management. Symptom Management Theory (SMT), though used in various fields, has not yet been fully validated for nurse-led pain management employing different TEA administration methods in SAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This protocol aims to assess the effectiveness and safety of SMT-based nurse-led TEA administration methods in patients with SAP, with the goal of optimizing pain management protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This single-center, randomized, controlled clinical trial will enroll 76 patients with SAP, randomized into two groups (N\u2009=\u200938 each). The control group will receive continuous TEA with a 50\u2009ml mixture containing nalbuphine 40\u2009mg, ropivacaine 225\u2009mg, lidocaine 0.2\u2009g, and 6\u2009ml of 0.9% saline, administered at 3\u20135\u2009ml\/h. If the patient\u2019s pain score (VAS-P) exceeds 3 or becomes intolerable, the infusion rate will be increased by 1\u20132\u2009ml\/h. In the experimental group, under SMT-guided nurse-led TEA management, nurses will report pain scores exceeding 3 to physicians, and intermittent epidural injections of 5\u2009ml of the same mixture will be administered according to medical prescription, at intervals of \u22652 hours. Pain responses and patient feedback will be continuously monitored to guide timely adjustments of analgesics.<\/jats:p>\n                    <jats:p>The primary outcome is VAS-P. Secondary outcomes include intra-abdominal pressure (IAP), total dose of combined medication, number of additional interventions, duration of epidural placement, and incidence of 16 predefined adverse events. Endpoint outcomes consist of puncture success rate, ICU length of stay, 28-day mortality, and patient satisfaction with analgesia.<\/jats:p>\n                    <jats:p>Data will be analyzed using SPSS. Repeated measures data (e.g., VAS-P and IAP at 0\u2009h, 1\u2009h, 6\u2009h, 12\u2009h, 24\u2009h, 48\u2009h, and 72\u2009h) will be examined with a multivariate mixed-effects repeated measures model (MMRM), which appropriately handles data missing at random. Other secondary outcomes, adverse events, and endpoint measures will be analyzed with descriptive statistics, and between-group comparisons will be conducted using t-tests, Mann-Whitney U tests, \u03c7\u00b2 tests, or Fisher\u2019s exact tests, as appropriate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Expected conclusion<\/jats:title>\n                    <jats:p>The experimental group is anticipated to demonstrate superior pain management outcomes compared to the control group, with no increase in adverse events. The SMT-based nurse-led TEA protocol is expected to be safe and effective in improving analgesia, reducing ICU length of stay, decreasing 28-day mortality, and enhancing patient satisfaction. This study will provide new insights and methods for pain management in SAP patients, thereby promoting optimization of clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0337803","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:24:22Z","timestamp":1767378262000},"page":"e0337803","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effectiveness and safety of nurse-led different epidural analgesia methods based on symptom management theory in patients with severe acute pancreatitis: A single-center RCT protocol"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2303-8041","authenticated-orcid":true,"given":"You","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"pone.0337803.ref001","doi-asserted-by":"crossref","first-page":"1331438","DOI":"10.3389\/fnmol.2023.1331438","article-title":"Molecular mechanisms of pain in acute pancreatitis: recent basic research advances and therapeutic implications","volume":"16","author":"Y Wu","year":"2023","journal-title":"Front Mol Neurosci"},{"issue":"6","key":"pone.0337803.ref002","doi-asserted-by":"crossref","DOI":"10.1111\/eci.13740","article-title":"Impact of early thoracic epidural analgesia in patients with severe acute pancreatitis","volume":"52","author":"Q Wang","year":"2022","journal-title":"Eur J Clin Invest"},{"key":"pone.0337803.ref003","doi-asserted-by":"crossref","first-page":"782151","DOI":"10.3389\/fmed.2021.782151","article-title":"Pain Management in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"8","author":"W Cai","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"4","key":"pone.0337803.ref004","doi-asserted-by":"crossref","DOI":"10.1097\/MPA.0000000000002444","article-title":"The Effect of Epidural Analgesia on In-hospital Outcomes in Patients With Acute Pancreatitis: A Systematic Review and Meta-analysis of Randomized Clinical Trials","volume":"54","author":"B Moazzami","year":"2025","journal-title":"Pancreas"},{"issue":"4","key":"pone.0337803.ref005","doi-asserted-by":"crossref","first-page":"281","DOI":"10.5455\/medarh.2023.77.281-287","article-title":"The Efficacy and Safety of Using Opioids in Acute Pancreatitis: an Update on Systematic Review and Meta-Analysis","volume":"77","author":"M Almulhim","year":"2023","journal-title":"Med Arch"},{"issue":"3","key":"pone.0337803.ref006","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/ueg2.12542","article-title":"Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis","volume":"12","author":"S Pandanaboyana","year":"2024","journal-title":"United European Gastroenterol J"},{"issue":"4","key":"pone.0337803.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/bjsopen\/zrad067","article-title":"Quality of life after severe acute pancreatitis: systematic review","volume":"7","author":"A Giorga","year":"2023","journal-title":"BJS Open"},{"issue":"4","key":"pone.0337803.ref008","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s00268-021-06420-w","article-title":"Analgesia in the Initial Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"46","author":"N Thavanesan","year":"2022","journal-title":"World J Surg"},{"issue":"43","key":"pone.0337803.ref009","doi-asserted-by":"crossref","first-page":"12448","DOI":"10.3748\/wjg.v21.i43.12448","article-title":"Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis","volume":"21","author":"SM Sadowski","year":"2015","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0337803.ref010","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/cc13718","article-title":"The role of thoracic epidural anesthesia in severe acute pancreatitis","volume":"18","author":"D Harper","year":"2014","journal-title":"Crit Care"},{"issue":"2","key":"pone.0337803.ref011","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.hpb.2022.12.004","article-title":"The safety and efficacy of epidural anaesthesia in acute pancreatitis: a systematic review and meta-analysis","volume":"25","author":"D Al-Leswas","year":"2023","journal-title":"HPB (Oxford)"},{"issue":"1","key":"pone.0337803.ref012","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13054-016-1292-7","article-title":"Thoracic epidural analgesia: a new approach for the treatment of acute pancreatitis?","volume":"20","author":"O Windisch","year":"2016","journal-title":"Crit Care"},{"issue":"4","key":"pone.0337803.ref013","first-page":"217","article-title":"Epidural analgesia in the intensive care unit: An observational series of 121 patients","volume":"34","author":"M Jabaudon","year":"2015","journal-title":"Anaesth Crit Care Pain Med"},{"issue":"3","key":"pone.0337803.ref014","article-title":"Efficacy and Safety of Thoracic Epidural Analgesia in Patients With Acute Pancreatitis: A Narrative Review","volume":"14","author":"A Nair","year":"2022","journal-title":"Cureus"},{"issue":"3","key":"pone.0337803.ref015","doi-asserted-by":"crossref","DOI":"10.1097\/CCM.0000000000002874","article-title":"Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter Propensity Analysis","volume":"46","author":"M Jabaudon","year":"2018","journal-title":"Crit Care Med"},{"issue":"1","key":"pone.0337803.ref016","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12904-022-00904-9","article-title":"Conceptualising effective symptom management in palliative care: a novel model derived from qualitative data","volume":"21","author":"EJ Chapman","year":"2022","journal-title":"BMC Palliat Care"},{"issue":"1","key":"pone.0337803.ref017","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1590\/S0080-623420150000100016","article-title":"Perioperative thirst: an analysis from the perspective of the Symptom Management Theory","volume":"49","author":"MF Conchon","year":"2015","journal-title":"Rev Esc Enferm USP"},{"issue":"3","key":"pone.0337803.ref018","doi-asserted-by":"crossref","DOI":"10.1097\/ANS.0000000000000347","article-title":"Symptom Management Theory: Analysis, Evaluation, and Implications for Caring for Adults With Cancer","volume":"44","author":"A Mathew","year":"2021","journal-title":"ANS Adv Nurs Sci"},{"key":"pone.0337803.ref019","doi-asserted-by":"crossref","first-page":"3816768","DOI":"10.1155\/2022\/3816768","article-title":"Application of Nursing Intervention Plan Based on Symptom Management Theory among Breast Cancer Patients","volume":"2022","author":"Q Xu","year":"2022","journal-title":"Contrast Media Mol Imaging"},{"issue":"8","key":"pone.0337803.ref020","first-page":"108","article-title":"The Effectiveness of Symptom Management Theory in Guiding Clinical Practice-A Systematic Review","volume":"30","author":"J Wei","year":"2024","journal-title":"Altern Ther Health Med"},{"key":"pone.0337803.ref021","doi-asserted-by":"crossref","first-page":"104012","DOI":"10.1016\/j.iccn.2025.104012","article-title":"Efficacy and safety of different methods and doses for thirst management in orotracheally intubated and mechanically ventilated patients with \u201cnothing by mouth\u201d: A randomized, controlled three-arm trial","volume":"89","author":"Y Yuan","year":"2025","journal-title":"Intensive Crit Care Nurs"},{"issue":"3","key":"pone.0337803.ref022","article-title":"Symptom management theory applied to nursing care: scoping review","volume":"74","author":"LAGP da Silva","year":"2021","journal-title":"Rev Bras Enferm"},{"issue":"1","key":"pone.0337803.ref023","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1365-2648.2009.05179.x","article-title":"Building dynamic models and theories to advance the science of symptom management research","volume":"66","author":"JM Brant","year":"2010","journal-title":"J Adv Nurs"},{"issue":"6","key":"pone.0337803.ref024","article-title":"A Concept Development for the Symptom Science Model 2.0","volume":"71","author":"EL Kurnat-Thoma","year":"2022","journal-title":"Nurs Res"},{"issue":"1","key":"pone.0337803.ref025","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4103\/apjon.apjon_39_19","article-title":"Evaluation of Pain as A Fifth Vital Sign: Nurses\u2019 Opinions and Beliefs","volume":"7","author":"S Kutlut\u00fcrkan","year":"2019","journal-title":"Asia Pac J Oncol Nurs"},{"issue":"11","key":"pone.0337803.ref026","doi-asserted-by":"crossref","first-page":"7737","DOI":"10.1111\/jan.16500","article-title":"What Enables Implementation of Pain Management Interventions in Intensive Care Units and Why: A Realist Evaluation to Refine Program Theory","volume":"81","author":"S Hamadeh","year":"2025","journal-title":"J Adv Nurs"},{"issue":"1","key":"pone.0337803.ref027","doi-asserted-by":"crossref","first-page":"101076","DOI":"10.1016\/j.aucc.2024.05.013","article-title":"Nurses\u2019 perceptions of patient pain, delirium, and sedation assessments in the intensive care unit: A qualitative study","volume":"38","author":"A Correya","year":"2025","journal-title":"Aust Crit Care"},{"issue":"5","key":"pone.0337803.ref028","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.aucc.2022.09.002","article-title":"Barriers to nurse-led pain management for adult patients in intensive care units: An integrative review","volume":"36","author":"M Alotni","year":"2023","journal-title":"Aust Crit Care"},{"issue":"1","key":"pone.0337803.ref029","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pmn.2017.10.007","article-title":"Transcultural Pain Management: Theory, Practice, and Nurse-Client Partnerships","volume":"19","author":"WE Rosa","year":"2018","journal-title":"Pain Manag Nurs"},{"key":"pone.0337803.ref030","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"A-W Chan","year":"2013","journal-title":"BMJ"},{"issue":"6","key":"pone.0337803.ref031","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3390\/medicina58060785","article-title":"Intra-Abdominal Hypertension: A Systemic Complication of Severe Acute Pancreatitis","volume":"58","author":"C Mancilla Asencio","year":"2022","journal-title":"Medicina (Kaunas)"},{"issue":"19","key":"pone.0337803.ref032","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.3889\/oamjms.2019.720","article-title":"Management of Severe Acute Pancreatitis","volume":"7","author":"GA Siregar","year":"2019","journal-title":"Open Access Maced J Med Sci"},{"issue":"1","key":"pone.0337803.ref033","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"PA Banks","year":"2013","journal-title":"Gut"},{"issue":"3","key":"pone.0337803.ref034","first-page":"101060","article-title":"Guidelines for the management of patients with severe acute pancreatitis, 2021","volume":"41","author":"S Jaber","year":"2022","journal-title":"Anaesth Crit Care Pain Med"},{"issue":"6","key":"pone.0337803.ref035","article-title":"Towards a neurobiological understanding of pain in chronic pancreatitis: mechanisms and implications for treatment","volume":"2","author":"SS Olesen","year":"2017","journal-title":"Pain Rep"},{"issue":"1","key":"pone.0337803.ref036","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bpg.2007.10.016","article-title":"Pancreatic pain","volume":"22","author":"GO Ceyhan","year":"2008","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"11","key":"pone.0337803.ref037","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1136\/gut.2007.146621","article-title":"Pain in chronic pancreatitis: the role of neuropathic pain mechanisms","volume":"57","author":"AM Drewes","year":"2008","journal-title":"Gut"},{"key":"pone.0337803.ref038","doi-asserted-by":"crossref","first-page":"104754","DOI":"10.1016\/j.jpain.2024.104754","article-title":"Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients","volume":"27","author":"EK Dunbar","year":"2025","journal-title":"J Pain"},{"issue":"5","key":"pone.0337803.ref039","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-015280","article-title":"Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol","volume":"7","author":"S Bulyez","year":"2017","journal-title":"BMJ Open"},{"issue":"4","key":"pone.0337803.ref040","doi-asserted-by":"crossref","first-page":"978","DOI":"10.3390\/jcm13040978","article-title":"Recent Treatment Strategies for Acute Pancreatitis","volume":"13","author":"Y Song","year":"2024","journal-title":"J Clin Med"},{"issue":"4","key":"pone.0337803.ref041","doi-asserted-by":"crossref","first-page":"413","DOI":"10.4037\/aacnacc2021511","article-title":"Clinical Nurse Specialist: A Critical Member of the ICU Team","volume":"32","author":"ER Gabbard","year":"2021","journal-title":"AACN Adv Crit Care"},{"issue":"6","key":"pone.0337803.ref042","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.pmn.2021.05.002","article-title":"The Pain Nurse Practitioner and Pain Nurse\u2019s Role and Views on Opioid Management in Australia: A National Questionnaire Survey","volume":"22","author":"O Sonneborn","year":"2021","journal-title":"Pain Manag Nurs"},{"key":"pone.0337803.ref043","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.2147\/JPR.S332423","article-title":"Nurses\u2019 Perceived Barriers to and Facilitators of Pain Assessment and Management in Critical Care Patients: A Systematic Review","volume":"14","author":"M Rababa","year":"2021","journal-title":"J Pain Res"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:24:28Z","timestamp":1767378268000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337803"}},"subtitle":[],"editor":[{"given":"Regina (Rianne) L.M.","family":"van Boekel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0337803","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]}}}