{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:52:36Z","timestamp":1785351156423,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objective<\/jats:title>\n                    <jats:p>Withdrawal syndrome (WS) may be a critical drawback of opioid\/benzodiazepine weaning in children. The most effective intervention to reduce WS prevalence is yet to be determined. Dexmedetomidine (DEX) was estimated to be effective in reducing WS\u2010related symptoms, but no randomized trial has been conducted to prove its efficacy so far.<\/jats:p>\n                    <jats:p>We aimed to evaluate the efficacy and safety of DEX in reducing the occurrence of WS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Setting<\/jats:title>\n                    <jats:p>This was an adaptive randomized double\u2010blind placebo\u2010controlled trial conducted at three Italian Pediatric Intensive Care Units (PICUs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>It included children admitted to PICU, undergoing at least five days of opioids\/benzodiazepines continuous infusion, and ready to start the analgosedation weaning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Twenty\u2010four hours before the start of weaning, an infusion of DEX\/placebo was started. WS symptoms were monitored using the Withdrawal\u2010Assessment\u2010Tool\u2010version\u20101 (WAT\u20101). In case of WS symptoms (WAT\u20101\u00a0\u2265\u00a03) an opioid\/benzodiazepine bolus was given and the DEX\/placebo infusion\u2010rate was increased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>The primary outcome measure was the prevalence of WS. Secondary outcomes were the trend of WAT\u20101 over time, number of rescue doses, length of weaning and PICU\u2010stay, and onset of adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Results<\/jats:title>\n                    <jats:p>\n                      Forty\u2010five patients were enrolled, of whom 5 dropped\u2010out and 40 entered the interim analysis. There were no significant baseline differences between groups. WS prevalence did not significantly differ between groups (77.8% DEX vs 90.9% placebo,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.381). By generalized linear mixed modeling, the WAT\u20101 trend showed a significant increase per unit of time in the DEX arm (estimate 0.27, CI 0.07\u20130.47,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.009) compared to placebo. Most frequent AEs were hemodynamic, and all of them happened in the DEX arm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A continuous infusion of DEX, started 24\u00a0h before the analgosedation weaning and increased based on WS signs, was not able to significantly modify the prevalence of WS in children who received at least five days of opioids\/benzodiazepines treatment compared to placebo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2654","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T08:01:03Z","timestamp":1639036863000},"page":"145-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Dexmedetomidine for prevention of opioid\/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-3166","authenticated-orcid":false,"given":"Maria Cristina","family":"Mondardini","sequence":"first","affiliation":[{"name":"Pediatric Anesthesia and Intensive Care Unit Department of Woman\u2019s and Child\u2019s Health University Hospital of Bologna IRCCS S. Orsola Polyclinic Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Daverio","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Department of Woman\u2019s and Child\u2019s Health University\u2010Hospital Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Caramelli","sequence":"additional","affiliation":[{"name":"Pediatric Anesthesia and Intensive Care Unit Department of Woman\u2019s and Child\u2019s Health University Hospital of Bologna IRCCS S. Orsola Polyclinic Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Conti","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit and Pediatric Trauma Center Department of Anesthesia and Intensive Care Catholic University of Rome A Gemelli Polyclinic Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Zaggia","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Department of Woman\u2019s and Child\u2019s Health University\u2010Hospital Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Lazzarini","sequence":"additional","affiliation":[{"name":"Pediatric Anesthesia and Intensive Care Unit Department of Woman\u2019s and Child\u2019s Health University Hospital of Bologna IRCCS S. Orsola Polyclinic Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Muscheri","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit and Pediatric Trauma Center Department of Anesthesia and Intensive Care Catholic University of Rome A Gemelli Polyclinic Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danila","family":"Azzolina","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health Department of Cardiac, Thoracic, Vascular Sciences and Public Health University\u2010Hospital of Padua Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Gregori","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health Department of Cardiac, Thoracic, Vascular Sciences and Public Health University\u2010Hospital of Padua Padua 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