{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:44:38Z","timestamp":1792637078685,"version":"4.5.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"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. Surg."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the safety and efficacy of the combination of continuous intravenous infusion of esketamine with sacral block for postoperative analgesia in pediatric patients undergoing surgery for hypospadias<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pediatric patients (<jats:italic>n\u2009<\/jats:italic>=\u200977) undergoing surgery for hypospadias were randomized into two groups: a hydromorphone group (H group, initial dose, 0.02\u2005mg\/kg; maintenance dose, 0.01\u2005mg\/kg\/h) or an esketamine group (E group, initial dose, 0.3\u2005mg\/kg; maintenance dose 0.15\u2005mg\/kg\/h). Caudal epidural block involved injection of 0.2% ropivacaine 1\u2005ml\/kg through the sacral hiatus. Age, weight, grade of hypospadias, intraoperative blood loss, operative time, and awaking time of patients were recorded. The Face, Legs, Activity, Cry and Consolability (FLACC) scale and Ramsay sedation scores were recorded when leaving the PACU (0\u2005h) and at postoperative 2, 6, 12, 24, 36, and 48\u2005h. The Pediatric Anesthesia Emergence Delirium Scale (PAED), incidence of hypotension, respiratory depression, nausea and vomiting and pruritus, and the time to first bowel movement after surgery were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no significant differences in demographic and clinical characteristics between the H group and the E group. There were no significant differences in FLACC scores at postoperative 0, 2, 6, 12, 24, 36, and 48\u2005h in intra-group and inter-group comparisons. There were no significant differences in Ramsay sedation scores at postoperative 0, 2, 6, 12, 24, 36, and 48\u2005h in the intra-group comparisons. Ramsay sedation scores were significantly lower at postoperative 2, 12, and 36\u2005h in the H group compared to the E group. There were no significant differences in the PAED scale or incidence of nausea and vomiting or pruritus between the H group and the E group. The incidence of hypotension and respiratory depression was significantly lower, and the time to first bowel movement was significantly shorter in the E group compared to the H group. Urinary tryptophan, 5-hydroxytryptamine and substance P levels were significantly lower but arginine was significantly higher in the E group compared to the H group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of continuous intravenous infusion of esketamine with sacral block provided safe and effective postoperative analgesia for pediatric patients undergoing surgery for hypospadias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>Chinese Clinical Trial Register ChiCTR2200066967. Clinical trial registry URL: <jats:ext-link>http:\/\/www.chictr.org.cn\/edit.aspx?pid=185042&amp;amp;htm=4<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.3389\/fsurg.2023.1131137","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T05:26:26Z","timestamp":1680585986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety and efficacy of esketamine for postoperative analgesia in pediatric patients with hypospadias"],"prefix":"10.3389","volume":"10","author":[{"given":"Yong","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingrong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jopan.2019.09.007","article-title":"Effects of nonpharmacologic distraction methods on children\u2019s postoperative pain-A nonmatched case-control study","volume":"35","author":"Olsen","year":"2020","journal-title":"J Perianesth Nurs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/pan.12546","article-title":"Treating perioperative anxiety and pain in children: a tailored and innovative approach","volume":"25","author":"Fortier","year":"2015","journal-title":"Paediatr Anaesth"},{"key":"B3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1002\/ejp.1313","article-title":"Outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain in children and adolescents","volume":"23","author":"Boric","year":"2019","journal-title":"Eur J Pain"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e90854","DOI":"10.5812\/aapm.90854","article-title":"The effect of glossopharyngeal nerve block on post-tonsillectomy pain of children; randomized controlled trial","volume":"9","author":"Ahmed","year":"2019","journal-title":"Anesth Pain Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.4103\/0970-1591.40622","article-title":"Acute postoperative complications of hypospadias repair","volume":"24","author":"Bhat","year":"2008","journal-title":"Indian J Urol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1111\/pan.13226","article-title":"Effects of esketamine sedation compared to morphine analgesia on hydrostatic reduction of intussusception: a case-cohort comparison study","volume":"27","author":"van de Bunt","year":"2017","journal-title":"Paediatr Anaesth"},{"key":"B7","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1093\/bja\/aei215","article-title":"Low dose of S+-ketamine prevents long-term potentiation in pain pathways under strong opioid analgesia in the rat spinal cord in vivo","volume":"95","author":"Benrath","year":"2005","journal-title":"Br J Anaesth"},{"key":"B8","doi-asserted-by":"publisher","first-page":"E15","DOI":"10.5489\/cuaj.3944","article-title":"Efficacy of using zaontz urethral stent in hypospadias repair by the face, legs, activity, cry, consolability (FLACC) scale: a prospective study","volume":"11","author":"Ozcan","year":"2017","journal-title":"Can Urol Assoc J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12871-021-01412-8","article-title":"Effectiveness of analgesia with hydromorphone hydrochloride for postoperative pain following surgical repair of structural congenital malformations in children: a randomized controlled trial","volume":"21","author":"Pan","year":"2021","journal-title":"BMC Anesthesiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1007\/s00134-011-2244-y","article-title":"On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the pediatric anesthesia emergence delirium scale, the delirium rating scale 88, and the delirium rating scale-revised R-98","volume":"37","author":"Janssen","year":"2011","journal-title":"Intensive Care Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e115","DOI":"10.1016\/j.anclin.2017.01.018","article-title":"Essential elements of multimodal analgesia in enhanced recovery after surgery (ERAS) guidelines","volume":"35","author":"Beverly","year":"2017","journal-title":"Anesthesiol Clin"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1037\/a0028204","article-title":"Sleep, cognition, and behavioral problems in school-age children: a century of research meta-analyzed","volume":"138","author":"Astill","year":"2012","journal-title":"Psychol Bull"},{"key":"B13","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1097\/aco.0000000000000916","article-title":"Ketamine: a versatile tool for anesthesia and analgesia","volume":"33","author":"Barrett","year":"2020","journal-title":"Curr Opin Anaesthesiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1097\/aln.0000000000001798","article-title":"Pharmacokinetics and bioavailability of inhaled esketamine in healthy volunteers","volume":"127","author":"Jonkman","year":"2017","journal-title":"Anesthesiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tacc.2014.03.002","article-title":"Ketamine\u2014more mechanisms of action than just NMDA blockade","volume":"4","author":"Sleigh","year":"2014","journal-title":"Trends Anaesth Crit Care"},{"key":"B16","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/ejp.1317","article-title":"Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: a randomized clinical trial of opioid-dependent patients","volume":"23","author":"Nielsen","year":"2019","journal-title":"Eur J Pain"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e030580","DOI":"10.1136\/bmjopen-2019-030580","article-title":"Assessing the effectiveness of perioperative s-ketamine on new-onset headache after resective epilepsy surgery (ESPAIN-trial): protocol for a randomised, double-blind, placebo-controlled trial","volume":"9","author":"Sloekers","year":"2019","journal-title":"BMJ Open"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12904-019-0499-1","article-title":"A rapid positive influence of S-ketamine on the anxiety of patients in palliative care: a retrospective pilot study","volume":"19","author":"Falk","year":"2020","journal-title":"BMC Palliat Care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"276","DOI":"10.5005\/jp-journals-10071-23410","article-title":"Is chronic opioid abuse associated with cerebral atrophy? An observational study","volume":"24","author":"Singla","year":"2020","journal-title":"Indian J Crit Care Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e52694","DOI":"10.7554\/eLife.52694","article-title":"Opioids depress breathing through two small brainstem sites","volume":"9","author":"Bachmutsky","year":"2020","journal-title":"Elife"},{"key":"B21","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0361-9230(00)00252-5","article-title":"Serotonergic and kynurenic pathways in rats exposed to foot shock","volume":"52","author":"Pawlak","year":"2000","journal-title":"Brain Res Bull"},{"key":"B22","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.jep.2013.05.011","article-title":"Antidepressant-like effect of ethanol extract from Zuojin Pill, containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae, is explained by modulating the monoaminergic neurotransmitter system in mice","volume":"148","author":"Wang","year":"2013","journal-title":"J Ethnopharmacol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.nutres.2018.05.007","article-title":"Fink-Gremmels J. l-arginine supplementation prevents intestinal epithelial barrier breakdown under heat stress conditions by promoting nitric oxide synthesis","volume":"57","author":"Varasteh","year":"2018","journal-title":"Nutr Res"}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2023.1131137\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T05:26:29Z","timestamp":1680585989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2023.1131137\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,4]]},"references-count":23,"alternative-id":["10.3389\/fsurg.2023.1131137"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2023.1131137","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,4]]},"article-number":"1131137"}}