{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:22:44Z","timestamp":1781198564333,"version":"3.54.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Midazolam and \u03b12-adrenoceptor agonists have been widely used off-label as intranasal sedatives for children. The present meta-analysis aimed to evaluate the effects of two interventions in pediatric sedation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>PubMed, Embase, and Cochrane Library were searched from inception to April 2022. All randomized controlled trials used intranasal \u03b12-adrenoceptor agonists and midazolam as sedatives in children were enrolled. Parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as outcomes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Totally 21 studies with 1,495 patients were included. Only one study reported comparison between midazolam and clonidine met the inclusion criteria, and patients in clonidine group had significantly better mask acceptance compared to midazolam group. Compared with midazolam, using of dexmedetomidine was associated with higher rate of satisfactory parental separation (52.88% vs 75.18%, RR = 0.70, with 95%CI [0.55, 0.90]), anesthesia induction or facemask acceptance (60.92% vs 81.47%, RR = 0.76, 95% CI [0.68, 0.84]) and less incidence of postoperative pain and nasal irritation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Compared with midazolam, dexmedetomidine should be considered as the preferred intranasal sedative option for pediatric patients, since it provides more satisfactory sedative level with less incidence of several side effects. But insufficient evidences about effects of intranasal clonidine and overall low and moderate quality evidences evaluated by GRADE system indicate that superiority of intranasal \u03b12-adrenoceptor agonists in pediatric sedation needs to be validated by more studies with high quality and large sample size in future.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0281751","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T18:24:06Z","timestamp":1676399046000},"page":"e0281751","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["A comparative evaluation of intranasal \u03b12-adrenoceptor agonists and intranasal midazolam as premedication in pediatric sedation: A meta-analysis of randomized controlled 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Mason","year":"2008","journal-title":"Paediatr Anaesth"},{"key":"pone.0281751.ref039","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/pan.12030","article-title":"Efficacy and safety of intraoperative dexmedetomidine for acute postoperative pain in children: a meta-analysis of randomized controlled trials","volume":"23","author":"A Schnabel","year":"2013","journal-title":"Pediatr Anesth"},{"issue":"1","key":"pone.0281751.ref040","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00000539-200101000-00011","article-title":"A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient","volume":"92","author":"SJ Lee-Kim","year":"2001","journal-title":"Anesth Analg"},{"issue":"2","key":"pone.0281751.ref041","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/pan.12025","article-title":"Comparison of buccal and nasal dexmedetomidine premedication for pediatric patients","volume":"23","author":"ZS 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