{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:37:44Z","timestamp":1792028264113,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emergence delirium (ED) is a common complication in pediatric anesthesia. Although intranasal dexmedetomidine (DEX) is widely used, its application is constrained by a slow onset, residual risk of ED in some patients, and risks such as bradycardia and hypotension. Esketamine (ESK), an NMDA receptor antagonist, may provide a faster onset and reduce these side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study compared the efficacy and safety of intranasal DEX\u2010ESK combination versus DEX alone as premedication for anesthesia induction in pediatric patients undergoing surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Electronic databases (PubMed, Web of Science, Scopus, CINAHL, and Embase) were systematically searched for randomized controlled trials (RCTs). The primary outcomes included the ED incidence and the onset of sedation. Secondary outcomes included mask acceptance score, FLACC pain score, post\u2010anesthesia care unit (PACU) length of stay, and adverse events. A random\u2010effects model generated pooled effect estimates\u2014risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Prediction intervals were also reported to reflect the expected range of effects in future similar studies. Trial Sequential Analysis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five RCTs encompassing 466 pediatric patients were included in the quantitative synthesis. The DEX\u2010ESK combination was associated with a reduction in ED incidence (RR\u2009=\u20090.58; 95% CI: 0.35\u20130.97;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and a shorter time to sedation onset (MD\u2009=\u2009\u22123.95\u2009min; 95% CI: \u22124.77 to \u22123.14;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Secondary analyses demonstrated improved mask acceptance (MD\u2009=\u2009\u22120.77; 95% CI: \u22121.27 to \u22120.27;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), reduced FLACC pain scores (MD\u2009=\u2009\u22120.36; 95% CI: \u22120.70 to \u22120.02;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04), and shorter PACU length of stay (MD\u2009=\u2009\u22121.83\u2009min; 95% CI: \u22122.75 to \u22120.91;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Adverse event incidence did not differ significantly between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The intranasal DEX\u2010ESK combination was associated with improved outcomes compared with DEX monotherapy for pediatric premedication including reductions in ED incidence, a modest acceleration in sedation onset, improved mask acceptance, and slightly shorter PACU length of stay, without an increased risk of adverse events. This combination may represent a feasible and safe premedication option for pediatric patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>PROSPERO: CRD420251236740<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pan.70159","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:44:57Z","timestamp":1773157497000},"page":"617-627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and Safety of Dexmedetomidine\u2010Esketamine Versus Dexmedetomidine Alone as Premedication for Pediatric Anesthesia Induction: A Systematic Review, Meta\u2010Analysis, and Trial Sequential Analysis"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4082-1949","authenticated-orcid":false,"given":"Munder","family":"Lateiresh","sequence":"first","affiliation":[{"name":"Faculty of Medicine Fo\u010da University of East Sarajevo  Fo\u010da Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4905-8775","authenticated-orcid":false,"given":"Alhasan","family":"Altayf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Azzaytuna University  Tarhuna Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0424-2037","authenticated-orcid":false,"given":"Ayham","family":"Qatza","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Hama University  Hama Syria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1205-8220","authenticated-orcid":false,"given":"Abubaker","family":"Alghazal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Benghazi  Benghazi Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3093-6884","authenticated-orcid":false,"given":"Hasan","family":"Al\u2010sakkaf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Hadhramout University  Mukalla Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-4212","authenticated-orcid":false,"given":"Muhammed","family":"Elhadi","sequence":"additional","affiliation":[{"name":"College of Medicine Korea University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jopan.2012.01.003"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.5152\/TJAR.2021.1104"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0375-9393.19.13038-6"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9592.2000.00560.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200405000-00015"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-016-0201-5"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199212000-00013"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200612000-00009"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199206000-00013"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11207190-000000000-00000"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-025-06589-y"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2024.03.016"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-017-1299-3"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000032280"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.02.021"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.37349\/emed.2025.1001291"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.808930"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-025-03203-x"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.12.011"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S488706"},{"key":"e_1_2_13_22_1","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page M. 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