{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T22:25:38Z","timestamp":1787264738516,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anticholinergic drugs are commonly used as premedication in clinical practice. The effects of premedication of atropine, penehyclidine, and glycopyrrolate on postoperative delirium in older patients remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to observe the effects of premedication with atropine, penehyclidine, and glycopyrrolate on postoperative delirium (POD) in older patients undergoing endoscopic gastric or esophageal submucosal dissection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Older patients undergoing endoscopic gastric or esophageal submucosal dissection were randomly divided into atropine group (A group), glycopyrrolate group (G group), penehyclidine group (P group), and normal saline group (NS group), with 144 cases in each group. The primary outcome was the incidence of POD 24\u00a0h after surgery. The secondary outcomes were the incidence of POD 48\u00a0h and 72\u00a0h after surgery, perioperative saliva secretion levels, RASS scores, QoR-15 scores, VAS scores of dry mouth, postoperative nausea VAS scores, and severity of postoperative vomiting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The incidence of POD 24\u00a0h after surgery was significantly higher in the A (20.1%) and P (23.6%) groups than in the NS group (9%) (95% CI, 0.030\u20130.191,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006, and 95% CI, 0.062\u20130.229,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001, respectively), and the incidence of POD between the NS group (9.0%) and G group (10.4%) was comparable (95% CI, \u22120.054\u20130.082,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.843). Oral saliva secretion in the A, G, and P groups at T\n                      <jats:sub>1<\/jats:sub>\n                      \u2013T\n                      <jats:sub>5<\/jats:sub>\n                      was significantly lower than that in the NS group (all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Twenty four hours after surgery, the QoR-15 score in the A group (124.0 \u00b1 13.3) was significantly lower than that in the NS group (132.4 \u00b1 12.1) (95% CI, \u221211.338 to \u22125.397,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glycopyrrolate is more suitable as a premedication for older patients without aggravating postoperative delirium or prolonging dry mouth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>http:\/\/www.chictr.org.cn\/showproj.html?proj=212300<\/jats:ext-link>\n                      ; Registration number: ChiCTR2300078413.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1905662","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T22:10:19Z","timestamp":1787263819000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of premedication with atropine, penehyclidine, and glycopyrrolate on postoperative delirium in older patients undergoing endoscopic gastric or esophageal submucosal dissection: a randomized, double-blind, multicenter, controlled clinical trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Wen Lin","family":"Xian","sequence":"first","affiliation":[{"name":"The Affiliated Hospital, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxian","family":"Wei","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Liangshan Yi Autonomous Prefecture","place":["Xichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Pei","family":"Gao","sequence":"additional","affiliation":[{"name":"The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Zeng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of the Chinese Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ye","sequence":"additional","affiliation":[{"name":"The Zigong Fourth People\u2019s Hospital","place":["Zigong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu Chang","family":"Fu","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital)","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.gie.2023.03.030","article-title":"American society for gastrointestinal endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence","volume":"98","author":"Al-Haddad","year":"2023","journal-title":"Gastrointest. Endosc."},{"key":"B2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ebiom.2018.10.021","article-title":"Surgery, neuroinflammation and cognitive impairment","volume":"37","author":"Alam","year":"2018","journal-title":"EBioMedicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00540-022-03119-7","article-title":"Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: a prospective cohort study","volume":"37","author":"Aoki","year":"2023","journal-title":"J. Anesth."},{"key":"B4","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1177\/0310057X1704500508","article-title":"Effect of sugammadex neostigmine\/atropine combination on postoperative cognitive dysfunction after elective surgery","volume":"45","author":"Batistaki","year":"2017","journal-title":"Anaesth. Intensive Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.2147\/COPD.S285867","article-title":"The impact of muscarinic receptor antagonists on airway inflammation: a systematic review","volume":"16","author":"Calzetta","year":"2021","journal-title":"Int. J. Chron. Obstruct Pulmon Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.1111\/dom.15238","article-title":"Prevalence of obesity and associated complications in China: a cross-sectional, real-world study in 15.8 million adults","volume":"25","author":"Chen","year":"2023","journal-title":"Diabetes Obes. Metab."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e171505","DOI":"10.1001\/jamasurg.2017.1505","article-title":"Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial","volume":"152","author":"Deiner","year":"2017","journal-title":"JAMA Surg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12871-023-02078-0","article-title":"Penehyclidine hydrochloride for treating postoperative nausea and vomiting after laparoscopic bariatric surgery: a double-blinded randomized controlled trial","volume":"23","author":"Ding","year":"2023","journal-title":"BMC Anesthesiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.2147\/CIA.S372400","article-title":"A high postoperative atropinic burden is associated with postoperative delirium in elderly patients with hip fracture: results of the prospective, observational, ATROPAGE trial","volume":"17","author":"Ferr\u00e9","year":"2022","journal-title":"Clin. Interv. Aging"},{"key":"B10","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.conb.2006.09.002","article-title":"The role of acetylcholine in learning and memory","volume":"16","author":"Hasselmo","year":"2006","journal-title":"Curr. Opin. Neurobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"118","DOI":"10.18773\/austprescr.2022.031","article-title":"The anticholinergic burden: from research to practice","volume":"45","author":"Hilmer","year":"2022","journal-title":"Aust. Prescr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"109246","DOI":"10.1016\/j.mehy.2019.109246","article-title":"Penehyclidine hydrochloride on postoperatively cognitive function","volume":"129","author":"Hongyu","year":"2019","journal-title":"Med. Hypotheses"},{"key":"B13","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1177\/0300060515595649","article-title":"Anticholinergic premedication-induced fever in paediatric ambulatory ketamine anaesthesia","volume":"44","author":"Kim","year":"2016","journal-title":"J. Int. Med. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1055\/s-0043-112491","article-title":"Safety and efficacy of glycopyrrolate as a premedication for endoscopic submucosal dissection: a randomized, double-blind, placebo-controlled study","volume":"49","author":"Kim","year":"2017","journal-title":"Endoscopy"},{"key":"B15","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/j.1365-2125.2004.02232.x","article-title":"Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID study","volume":"59","author":"Lechevallier-Michel","year":"2005","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1001\/jama.2021.22647","article-title":"Effect of regional vs general anaesthesia on incidence of postoperative delirium in older patients undergoing hip fracture surgery: the RAGA randomized trial","volume":"327","author":"Li","year":"2022","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3389\/fphar.2019.00043","article-title":"Atropine premedication facilitates ultrasound-guided reduction by saline enema in children with intussusception","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"8150444","DOI":"10.1155\/2022\/8150444","article-title":"Clinical efficacy of Budesonide\/Glycopyrrolate\/Formoterol in the treatment of patients with acute respiratory distress syndrome and its effect on inflammatory factors","volume":"2022","author":"Liu","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1034\/j.1399-6576.2001.045004495.x","article-title":"Neostigmine 50 microg kg(-1) with glycopyrrolate increases postoperative nausea in women after laparoscopic gynaecological surgery","volume":"45","author":"L\u00f8vstad","year":"2001","journal-title":"Acta Anaesthesiol. Scand."},{"key":"B20","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12871-022-01857-5","article-title":"Evaluation of penehyclidine for prevention of post operative nausea and vomitting in patients undergoing total thyroidectomy under total intravenous anaesthesia with propofol-remifentanil","volume":"22","author":"Lu","year":"2022","journal-title":"BMC Anesthesiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1378\/chest.08-2924","article-title":"Anticholinergic premedication for flexible bronchoscopy: a randomized, double-blind, placebo-controlled study of atropine and glycopyrrolate","volume":"136","author":"Malik","year":"2009","journal-title":"Chest"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1007\/s00784-021-04182-2","article-title":"Analysis of medication-induced xerostomia in elderly Japanese patients","volume":"26","author":"Minagi","year":"2022","journal-title":"Clin. Oral Investig."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s00228-012-1286-6","article-title":"Relative bioavailability and pharmacodynamic effects of methantheline compared with atropine in healthy subjects","volume":"68","author":"M\u00fcller","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e20220053","DOI":"10.1590\/1980-5764-dn-2022-0053","article-title":"Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis","volume":"17","author":"Naseri","year":"2023","journal-title":"Dement. Neuropsychol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1093\/bja\/aeq091","article-title":"Incidence of postoperative nausea and vomiting after paediatric strabismus surgery with sevoflurane or remifentanil-sevoflurane","volume":"104","author":"Oh","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"B26","first-page":"236","article-title":"Pharmacokinetics of atropine in children","volume":"24","author":"Pihlajam\u00e4ki","year":"1986","journal-title":"Int. J. Clin. Pharmacol. Ther. Toxicol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/01.anes.0000296072.02527.18","article-title":"Type and severity of cognitive decline in older adults after noncardiac surgery","volume":"108","author":"Price","year":"2008","journal-title":"Anesthesiology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e11780","DOI":"10.7759\/cureus.11780","article-title":"Effect of intramuscular atropine sulphate and glycopyrrolate on heart rate and salivary secretion in patients undergoing minor oral surgical procedure","volume":"12","author":"Rachana","year":"2020","journal-title":"Cureus"},{"key":"B29","doi-asserted-by":"publisher","first-page":"105801","DOI":"10.1016\/j.phrs.2021.105801","article-title":"Indacaterol, glycopyrronium, and mometasone: pharmacological interaction and anti-inflammatory profile in hyperresponsive airways","volume":"172","author":"Rogliani","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.3390\/cells11192954","article-title":"Epigenetic mechanisms of postoperative cognitive impairment induced by Anesthesia and neuroinflammation","volume":"11","author":"Rump","year":"2022","journal-title":"Cells"},{"key":"B31","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s13318-015-0300-7","article-title":"Pharmacokinetics of glycopyrronium following repeated once-daily inhalation in healthy Chinese subjects","volume":"41","author":"Sechaud","year":"2016","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1213\/01.ane.0000243333.96141.40","article-title":"Glycopyrrolate does not reduce the incidence of perioperative adverse events in children with upper respiratory tract infections","volume":"104","author":"Tait","year":"2007","journal-title":"Anesth. Analg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"108680","DOI":"10.1016\/j.intimp.2022.108680","article-title":"Penehyclidine hydrochloride suppresses inflammation response and reduces podocyte injury in diabetic nephropathy by targeting fibrinogen-like protein 2","volume":"107","author":"Tan","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2018.09.012","article-title":"Penehyclidine hydrochloride preconditioning provides pulmonary and systemic protection in a rat model of lung ischaemia reperfusion injury","volume":"839","author":"Wang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13063-022-06121-2","article-title":"The effects of remifentanil-propofol combined with dexmedetomidine on cognitive dysfunction in elderly patients after ureteroscopic holmium laser lithotripsy: a double-blind randomized controlled trial","volume":"23","author":"Wang","year":"2022","journal-title":"Trials"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3946320231192175","DOI":"10.1177\/03946320231192175","article-title":"Penehyclidine hydrochloride protects against lipopolysaccharide-induced acute lung injury by promoting the PI3K\/Akt pathway","volume":"37","author":"Weng","year":"2023","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"121","DOI":"10.24920\/003630","article-title":"Penehyclidine hydrochloride premedication is not associated with increased incidence of post-operative cognitive dysfunction or delirium:a systemic review and meta-analysis","volume":"35","author":"Yao","year":"2020","journal-title":"Chin. Med. Sci. J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"486","DOI":"10.14109\/j.cnki.xyylc.2020.08.08","article-title":"Application of penehyclidine as preanesthetic medication in gynecological laparoscopic surgery under laryngeal mask airway general anesthesia","volume":"39","author":"Ye","year":"2020","journal-title":"Chin. J. New Drugs Clin. Remedies"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1905662\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T22:10:21Z","timestamp":1787263821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1905662\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":38,"alternative-id":["10.3389\/fphar.2026.1905662"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1905662","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1905662"}}