{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:10:43Z","timestamp":1773889843514,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Emergence delirium, a manifestation of acute postoperative brain dysfunction, is frequently observed after pediatric anesthesia and has been associated with the use of sevoflurane. Both xenon and dexmedetomidine possess numerous desirable properties for the anesthesia of children with congenital heart disease, including hemodynamic stability, lack of neurotoxicity, and a reduced incidence of emergence delirium. Combining both drugs has never been studied as a balanced-anesthesia technique. This combination allows the provision of anesthesia without administering anesthetic drugs against which the Food and Drug Administration (FDA) issued a warning for the use in young children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/Design<\/jats:title><jats:p>In this phase-II, mono-center, prospective, single-blinded, randomized, controlled pilot trial, we will include a total of 80 children aged 0\u20133\u2009years suffering from congenital heart disease and undergoing general anesthesia for elective diagnostic and\/or interventional cardiac catheterization. Patients are randomized into two study groups, receiving either a combination of xenon and dexmedetomidine or mono-anesthesia with sevoflurane for the maintenance of anesthesia.<\/jats:p><jats:p>The purpose of this study is to estimate the effect size for xenon-dexmedetomidine versus sevoflurane anesthesia with respect to the incidence of emergence delirium in children. We will also describe group differences for a variety of secondary outcome parameters including peri-interventional hemodynamics, emergence characteristics, incidence of postoperative vomiting, and the feasibility of a combined xenon-dexmedetomidine anesthesia in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Sevoflurane is the most frequently used\u00a0anesthetic in young children, but has been indicated as an independent risk factor in the development of emergence delirium. Xenon and dexmedetomidine have both been associated with a reduction in the incidence of emergence delirium. Combining xenon and dexmedetomidine has never been described as a balanced-anesthesia technique in children. Our pilot study will therefore deliver important data required for future prospective clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>EudraCT, 2018\u2013002258-56. Registered on 20 August 2018.<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\">https:\/\/www.clinicaltrialsregister.eu<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13063-020-4231-5","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T14:02:49Z","timestamp":1585922569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of xenon and dexmedetomidine as adjuncts for general anesthesia on postoperative emergence delirium after elective cardiac catheterization in children: study protocol for a randomized, controlled, pilot trial"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-7891","authenticated-orcid":false,"given":"Sarah","family":"Devroe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Devriese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik","family":"Debuck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Fieuws","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjorn","family":"Cools","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Gewillig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Van de Velde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Rex","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"issue":"4","key":"4231_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/anae.13043","volume":"70","author":"DDL Wong","year":"2015","unstructured":"Wong DDL, Bailey CR. Emergence delirium in children. Anaesthesia. 2015;70(4):383\u20137.","journal-title":"Anaesthesia."},{"issue":"3","key":"4231_CR2","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/ACO.0000000000000076","volume":"27","author":"S Dahmani","year":"2014","unstructured":"Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol. 2014;27(3):309\u201315.","journal-title":"Curr Opin Anaesthesiol"},{"issue":"4","key":"4231_CR3","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/pan.12090","volume":"23","author":"JR Chandler","year":"2013","unstructured":"Chandler JR, Myers D, Mehta D, Whyte E, Groberman MK, Montgomery CJ, et al. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Paediatr Anaesth. 2013;23(4):309\u201315.","journal-title":"Paediatr Anaesth"},{"key":"4231_CR4","first-page":"CD007084","volume":"9","author":"D Costi","year":"2014","unstructured":"Costi D, Cyna AM, Ahmed S, Stephens K, Strickland P, Ellwood J, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Costi D, editor. Cochrane Database Syst Rev. 2014;9:CD007084.","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"4231_CR5","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1213\/ANE.0000000000000914","volume":"122","author":"LS-C Law","year":"2016","unstructured":"Law LS-C, Lo EA-G, Gan TJ. Xenon anesthesia: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2016;122(3):678\u201397.","journal-title":"Anesth Analg"},{"key":"4231_CR6","doi-asserted-by":"crossref","unstructured":"Van Hese L, Al tmimi L, Devroe S, Sanders RD, Fieuws S, Rex S. Neuroprotective properties of xenon in different types of CNS injury. Br J Anaesth. 2018;121(6):1365\u201368.","DOI":"10.1016\/j.bja.2018.08.014"},{"issue":"4","key":"4231_CR7","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1097\/01.anes.0000264762.48920.80","volume":"106","author":"D Ma","year":"2007","unstructured":"Ma D, Williamson P, Januszewski A, Nogaro M-C, Hossain M, Ong LP, et al. Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. Anesthesiology. 2007;106(4):746\u201353.","journal-title":"Anesthesiology."},{"issue":"4","key":"4231_CR8","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1097\/00000542-200104000-00014","volume":"94","author":"Y Nakata","year":"2001","unstructured":"Nakata Y, Goto T, Ishiguro Y, Terui K, Kawakami H, Santo M, et al. Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans. Anesthesiology. 2001;94(4):611\u20134.","journal-title":"Anesthesiology."},{"issue":"2","key":"4231_CR9","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/bja\/76.2.179","volume":"76","author":"WW Mapleson","year":"1996","unstructured":"Mapleson WW. Effect of age on MAC in humans: a meta-analysis. Br J Anaesth. 1996;76(2):179\u201385.","journal-title":"Br J Anaesth"},{"issue":"2","key":"4231_CR10","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1161\/01.STR.0000198867.31134.ac","volume":"37","author":"J Dingley","year":"2006","unstructured":"Dingley J, Tooley J, Porter H, Thoresen M. Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke. 2006;37(2):501\u20136.","journal-title":"Stroke."},{"issue":"12","key":"4231_CR11","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/pan.13230","volume":"27","author":"S Devroe","year":"2017","unstructured":"Devroe S, Meeusen R, Gewillig M, Cools B, Poesen K, Sanders R, et al. Xenon as an adjuvant to sevoflurane anesthesia in children younger than 4 years of age, undergoing interventional or diagnostic cardiac catheterization: A randomized controlled clinical trial. Paediatr Anaesth. 2017;27(12):1210\u20139.","journal-title":"Paediatr Anaesth"},{"issue":"8","key":"4231_CR12","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1111\/pan.13444","volume":"28","author":"S Devroe","year":"2018","unstructured":"Devroe S, Lemiere J, Van Hese L, Gewillig M, Boshoff D, Poesen K, et al. The effect of xenon-augmented sevoflurane anesthesia on intraoperative hemodynamics and early postoperative neurocognitive function in children undergoing cardiac catheterization: A randomized controlled pilot trial. Paediatr Anaesth. 2018;28(8):726\u201338.","journal-title":"Paediatr Anaesth"},{"issue":"3","key":"4231_CR13","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/pan.12820","volume":"26","author":"W Pan","year":"2016","unstructured":"Pan W, Wang Y, Lin L, Zhou G, Hua X, Mo L. Outcomes of dexmedetomidine treatment in pediatric patients undergoing congenital heart disease surgery: a meta-analysis. Paediatr Anaesth. 2016;26(3):239\u201348.","journal-title":"Paediatr Anaesth"},{"issue":"3","key":"4231_CR14","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1213\/ANE.0000000000001314","volume":"123","author":"LI Schwartz","year":"2016","unstructured":"Schwartz LI, Twite M, Gulack B, Hill K, Kim S, Vener DF. The perioperative use of dexmedetomidine in pediatric patients with congenital heart disease: an analysis from the Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Congenital Heart Disease Database. Anesth Analg. 2016;123(3):715\u201321.","journal-title":"Anesth Analg"},{"issue":"2","key":"4231_CR15","first-page":"117","volume":"6","author":"SS Ahmed","year":"2017","unstructured":"Ahmed SS, Unland TL, Slaven JE, Nitu ME. Dexmedetomidine versus propofol: is one better than the other for MRI sedation in children? J Pediatr Intensive Care. 2017;6(2):117\u201322.","journal-title":"J Pediatr Intensive Care"},{"issue":"6","key":"4231_CR16","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/S0952-8180(99)00081-1","volume":"11","author":"RJ Fragen","year":"1999","unstructured":"Fragen RJ, Fitzgerald PC. Effect of dexmedetomidine on the minimum alveolar concentration (MAC) of sevoflurane in adults age 55 to 70 years. J Clin Anesth. 1999;11(6):466\u201370.","journal-title":"J Clin Anesth"},{"issue":"9","key":"4231_CR17","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1111\/pan.12430","volume":"24","author":"L He","year":"2014","unstructured":"He L, Wang X, Zheng S. Effects of dexmedetomidine on sevoflurane requirement for 50% excellent tracheal intubation in children: a randomized, double-blind comparison. Paediatr Anaesth. 2014;24(9):987\u201393.","journal-title":"Paediatr Anaesth"},{"issue":"6","key":"4231_CR18","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1111\/j.1399-6576.2009.02177.x","volume":"54","author":"RD Sanders","year":"2010","unstructured":"Sanders RD, SUN P, PATEL S, Li M, Maze M, Ma D. Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol Scand. 2010;54(6):710\u20136.","journal-title":"Acta Anaesthesiol Scand"},{"key":"4231_CR19","volume-title":"FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women","author":"FDA Drug Safety Communication","year":"2016","unstructured":"FDA Drug Safety Communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. 2016. http:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/UCM533197.pdf. Accessed 5 Mar 2017."},{"key":"4231_CR20","first-page":"200","volume-title":"SPIRIT 2013 statement: defining standard protocol items for clinical trials","author":"A-W Chan","year":"2013","unstructured":"Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, G\u00f8tzsche PC, Krle\u017ea-Jeri\u0107 K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Washington, DC: American College of Physicians; 2013. p. 200\u20137."},{"issue":"7","key":"4231_CR21","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1007\/BF03008224","volume":"39","author":"MF Watcha","year":"1992","unstructured":"Watcha MF, Ramirez-Ruiz M, White PF, Jones MB, Lagueruela RG, Terkonda RP. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth. 1992;39(7):649\u201354.","journal-title":"Can J Anaesth"},{"issue":"8","key":"4231_CR22","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1111\/j.1460-9592.2010.03328.x","volume":"20","author":"SA Bajwa","year":"2010","unstructured":"Bajwa SA, Costi D, Cyna AM. A comparison of emergence delirium scales following general anesthesia in children. Pediatr Anesth. 2010;20(8):704\u201311.","journal-title":"Pediatr Anesth"},{"issue":"5","key":"4231_CR23","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1097\/00000542-200405000-00015","volume":"100","author":"N Sikich","year":"2004","unstructured":"Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004;100(5):1138\u201345.","journal-title":"Anesthesiology."},{"issue":"1","key":"4231_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0952-8180(94)00001-K","volume":"7","author":"JA Aldrete","year":"1995","unstructured":"Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth. 1995;7(1):89\u201391.","journal-title":"J Clin Anesth"},{"issue":"1","key":"4231_CR25","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1097\/00000542-200301000-00005","volume":"98","author":"R Rossaint","year":"2003","unstructured":"Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, et al. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology. 2003;98(1):6\u201313.","journal-title":"Anesthesiology"},{"issue":"6","key":"4231_CR26","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1093\/bja\/aeu093","volume":"112","author":"A Pickard","year":"2014","unstructured":"Pickard A, Davies P, Birnie K, Beringer R. Systematic review and meta-analysis of the effect of intraoperative \u03b12-adrenergic agonists on postoperative behaviour in children. Br J Anaesth. 2014;112(6):982\u201390.","journal-title":"Br J Anaesth"},{"issue":"4","key":"4231_CR27","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1097\/00000542-198010000-00020","volume":"53","author":"TH Oh","year":"1980","unstructured":"Oh TH. Formulas for calculating fluid maintenance requirements. Anesthesiology. 1980;53(4):351.","journal-title":"Anesthesiology."},{"issue":"1","key":"4231_CR28","first-page":"74","volume":"16","author":"S Devroe","year":"2015","unstructured":"Devroe S, Lemiere J, van de Velde M, Gewillig M, Boshoff D, Rex S. Safety and feasibility of xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: study protocol for a randomised controlled trial. Trials BioMed Central. 2015;16(1):74.","journal-title":"Trials BioMed Central"},{"issue":"3","key":"4231_CR29","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1093\/bja\/aev552","volume":"116","author":"M Somaini","year":"2016","unstructured":"Somaini M, Engelhardt T, Fumagalli R, Ingelmo PM. Emergence delirium or pain after anaesthesia-how to distinguish between the two in young children: a retrospective analysis of observational studies. Br J Anaesth. 2016;116(3):377\u201383.","journal-title":"Br J Anaesth"},{"issue":"3","key":"4231_CR30","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/bja\/aew477","volume":"118","author":"KP Mason","year":"2017","unstructured":"Mason KP. Paediatric emergence delirium: a comprehensive review and interpretation of the literature. Br J Anaesth. 2017;118(3):335\u201343.","journal-title":"Br J Anaesth"},{"issue":"10","key":"4231_CR31","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1097\/EJA.0b013e32833d1289","volume":"27","author":"AV Fahlenkamp","year":"2010","unstructured":"Fahlenkamp AV, Krebber F, Rex S, Grottke O, Fries M, Rossaint R, et al. Bispectral index monitoring during balanced xenon or sevoflurane anaesthesia in elderly patients. Eur J Anaesthesiol. 2010;27(10):906\u201311.","journal-title":"Eur J Anaesthesiol"},{"issue":"1","key":"4231_CR32","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1093\/bja\/aer393","volume":"108","author":"C Stoppe","year":"2012","unstructured":"Stoppe C, Peters D, Fahlenkamp AV, Cremer J, Rex S, Sch\u00e4lte G, et al. aepEX monitor for the measurement of hypnotic depth in patients undergoing balanced xenon anaesthesia. Br J Anaesth. 2012;108(1):80\u20138.","journal-title":"Br J Anaesth"},{"issue":"1","key":"4231_CR33","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1097\/01.anes.0000296106.52472.a6","volume":"108","author":"RM Laitio","year":"2008","unstructured":"Laitio RM, Kaskinoro K, S\u00e4rkel\u00e4 MOK, Kaisti KK, Salmi E, Maksimow A, et al. Bispectral index, entropy, and quantitative electroencephalogram during single-agent xenon anesthesia. Anesthesiology. 2008;108(1):63\u201370.","journal-title":"Anesthesiology"},{"issue":"6","key":"4231_CR34","first-page":"807","volume":"36","author":"AJ Davidson","year":"2008","unstructured":"Davidson AJ, Kwok T. Performance of BIS in children using the paediatric BIS Quattro sensor. Anaesth Intensive Care. 2008;36(6):807\u201313.","journal-title":"Anaesth Intensive Care"},{"issue":"4","key":"4231_CR35","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/pan.13086","volume":"27","author":"A Sciusco","year":"2017","unstructured":"Sciusco A, Standing JF, Sheng Y, Raimondo P, Cinnella G, Dambrosio M. Effect of age on the performance of bispectral and entropy indices during sevoflurane pediatric anesthesia: a pharmacometric study. Paediatr Anaesth. 2017;27(4):399\u2013408.","journal-title":"Paediatr Anaesth"},{"issue":"10","key":"4231_CR36","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1515\/cclm-2015-1012","volume":"54","author":"L Tmimi Al","year":"2016","unstructured":"Tmimi Al L, van de Velde M, Meyns B, Meuris B, Sergeant P, Milisen K, et al. Serum protein S100 as marker of postoperative delirium after off-pump coronary artery bypass surgery: secondary analysis of two prospective randomized controlled trials. Clin Chem Lab Med. 2016;54(10):1671\u201380.","journal-title":"Clin Chem Lab Med"},{"issue":"3","key":"4231_CR37","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1097\/PCC.0000000000000055","volume":"15","author":"S Abu-Sultaneh","year":"2014","unstructured":"Abu-Sultaneh S, Hehir DA, Murkowski K, Ghanayem NS, Liedel J, Hoffmann RG, et al. Changes in cerebral oxygen saturation correlate with S100B in infants undergoing cardiac surgery with cardiopulmonary bypass. Pediatr Crit Care Med. 2014;15(3):219\u201328.","journal-title":"Pediatr Crit Care Med"},{"issue":"4","key":"4231_CR38","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1213\/00000539-200210000-00018","volume":"95","author":"PM Bokesch","year":"2002","unstructured":"Bokesch PM, Appachi E, Cavaglia M, Mossad E, Mee RBB. A glial-derived protein, S100B, in neonates and infants with congenital heart disease: evidence for preexisting neurologic injury. Anesth Analg. 2002;95(4):889\u201392.","journal-title":"Anesth Analg"},{"issue":"11","key":"4231_CR39","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1161\/01.STR.31.11.2670","volume":"31","author":"M Herrmann","year":"2000","unstructured":"Herrmann M, Vos P, Wunderlich MT, de Bruijn CH, Lamers KJ. Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke. 2000;31(11):2670\u20137.","journal-title":"Stroke"},{"key":"4231_CR40","doi-asserted-by":"crossref","unstructured":"Alam A, Suen KC, Hana Z, Sanders RD, Mervyn M, Ma D. Neuroprotection and neurotoxicity in the developing brain: an update on the effects of dexmedetomidine and xenon. Neurotoxicol Teratol. 2017;60:102\u201316.","DOI":"10.1016\/j.ntt.2017.01.001"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-4231-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-020-4231-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-4231-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T14:35:54Z","timestamp":1666276554000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-4231-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,3]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4231"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-4231-5","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,3]]},"assertion":[{"value":"7 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The protocol (version SD-DXP: 2 06-08-2018) and related documents were approved by the Ethics Committee of the University Hospitals Leuven (S61690, 18 August 2018). Informed consent will be obtained from all study participants.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The study is being funded solely by institutional and departmental sources. In the past, SR received an unrestricted research grant from Air Liquide. The sponsor of this clinical trial is UZ Leuven, Belgium. Neither sponsor or funders have any role in study design, collection\/management\/analysis\/interpretation of data, writing the report, decision to submit the report for publication, and have no authority over any of these activities.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"310"}}