{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:34:01Z","timestamp":1790444041294,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"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. Pharmacol."],"abstract":"<jats:p>Children are exposed to drug-drug interactions (DDI) risks due to their organism\u2019s complexity and the need for several medicines prescriptions in pediatric intensive care units (PICU). This study aimed to assess the prevalence of potential DDIs in a Brazilian PICU. We carried out a cross-sectional study at a pediatric teaching hospital from Rio de Janeiro (Brazil) over one year. Potential DDIs (pDDIs) between prescribed medicines for hospitalized children in PICU (<jats:italic>n<\/jats:italic> = 143) were analyzed according to severity using Micromedex<jats:sup>\u00ae<\/jats:sup>. Sex, age group, number of drugs prescribed, vasoactive amines use (a proxy of clinical complexity), and the PICU length of stay were summarized using descriptive statistics. Association between the PICU length stay, and variables sex, age, clinical condition complexity, number of drugs prescribed, and severity of pDDI were examined by univariate and multiple linear regression. Seventy percent of patients aged three days to 14\u00a0years old were exposed at least one potential DDIs during PICU stay. Two hundred eighty-four different types of pDDIs were identified, occurring 1,123 times. Nervous system drugs were implicated in 55% of the interactions, and fentanyl (10%) was most involving in pDDIs. Most pDDIs were classified as higher severity (56.2%), with reasonable documentation (64.6%) and unspecified onset time (63.8%). Worse clinical condition, ten or more drugs prescribed, and most severe pDDIs were associated with a longer PICU length of stay. Multiple linear regression analysis showed an increase of 9.83\u00a0days (95% confidence interval: 3.61\u201316.05; <jats:italic>p<\/jats:italic> = 0.002) in the PICU length of stay in children with major or contraindicated pDDIs. The results of this research may support the monitoring and prevention of pDDIs related to adverse events in children in intensive care and the design and conduction of new studies.<\/jats:p>","DOI":"10.3389\/fphar.2020.555407","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T08:33:41Z","timestamp":1606984421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Severe Potential Drug-Drug Interactions and the Increased Length of Stay of Children in Intensive Care Unit"],"prefix":"10.3389","volume":"11","author":[{"given":"Elisangela da Costa","family":"Lima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Dias","family":"Camarinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia Cristina","family":"Ferreira Bezerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Gon\u00e7alves","family":"Panisset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Belmino de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Tolentino","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciane Cruz","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.4025\/cienccuidsaude.v13i2.21912","article-title":"Perfil dos pacientes internados em uma unidade de terapia intensiva pedi\u00e1trica de um hospital escola do interior de S\u00e3o Paulo","volume":"13","author":"Alves","year":"2014","journal-title":"Ci\u00eancia, Cuid. Sa\u00fade"},{"key":"B2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.5935\/0103-507X.20150060","article-title":"Eventos adversos por intera\u00e7\u00f5es medicamentosas potenciais em unidade de terapia intensiva de um hospital de ensino","volume":"27","author":"Alvim","year":"2015","journal-title":"Revista Brasileira de Terapia Intensiva"},{"key":"B3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1590\/s0021-75572010000600014","article-title":"Stress ulcer prophylaxis in pediatric intensive care units","volume":"86","author":"Araujo","year":"2010","journal-title":"J Pediatr., Rio de Janeiro."},{"key":"B4","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/aas.12257","article-title":"Drug-induced long QT syndrome and fatal arrhythmias in the intensive care unit","volume":"58","author":"Beitland","year":"2014","journal-title":"Acta Anaesthesiol. Scand."},{"key":"B5","first-page":"1808","article-title":"Goodman, and Gilman\u2019s","volume-title":"The Pharmacological basis of therapeutics","author":"Brunton","year":"2010"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e000788","DOI":"10.1136\/openhrt-2018-000788","article-title":"Strengths and weaknesses of \u2018real-world\u2019 studies involving non-vitamin K antagonist oral anticoagulants","volume":"5","author":"Camm","year":"2018","journal-title":"Open Heart"},{"key":"B7","doi-asserted-by":"publisher","first-page":"128","DOI":"10.20959\/wjpps20188-12050","article-title":"Characterization of polypharmacy and drug interactions in pediatric patients in a hospital in Pachuca Mexico","volume":"7","author":"Carrillo-Alarcon","year":"2018","journal-title":"World J. Pharm. Pharmaceut. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1590\/S0021-75572003000500006","article-title":"Identifica\u00e7\u00e3o de medicamentos \u201cn\u00e3o apropriados para crian\u00e7as\u201d em prescri\u00e7\u00f5es de unidade de tratamento intensivo pedi\u00e1trica","volume":"79","author":"Carvalho","year":"2003","journal-title":"J. Pediatr."},{"key":"B9","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1590\/S0103-21002013000200008","article-title":"Preval\u00eancia de intera\u00e7\u00f5es medicamentosas em unidades de terapia intensiva no Brasil","volume":"26","author":"Carvalho","year":"2013","journal-title":"Acta Paul. Enferm."},{"key":"B10","volume-title":"Perfil epidemiol\u00f3gico de uma UTI pedi\u00e1trica no sul do Brasil","author":"Corull\u00f3n","year":"2007"},{"key":"B11","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/PCC.0000000000000684","article-title":"Epidemiology of polypharmacy and potential drug-drug interactions among pediatric patients in intensive care units of U.S. children\u2019s hospitals","volume":"17","author":"Dai","year":"2016","journal-title":"Pediatr. Crit. Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e99","DOI":"10.1542\/peds.2014-2015","article-title":"Potential drug\u2212drug interactions in infant, child, and adolescent patients in children\u2019s hospitals","volume":"135","author":"Feinstein","year":"2015","journal-title":"Pediatrics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/pharmaceutics3010053","article-title":"Factors and mechanisms for pharmacokinetic differences between pediatric population and adults","volume":"3","author":"Fernandez","year":"2011","journal-title":"Pharmaceutics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1590\/s0104-42302012000100019","article-title":"A alta preval\u00eancia de prescri\u00e7\u00f5es de medicamentos off-label e n\u00e3o licenciados em uma unidade de terapia intensiva pedi\u00e1trica brasileira","volume":"58","author":"Ferreira","year":"2012","journal-title":"Revista Associa\u00e7\u00e3o M\u00e9dica Brasileira"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1007\/s40264-019-00829-y","article-title":"Evaluation of potential drug\u2013drug interactions in adults in the intensive care unit: a systematic review and meta-analysis","volume":"42","author":"Fitzmaurice","year":"2019","journal-title":"Drug Saf."},{"key":"B16","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1590\/s0080-62342008000400013","article-title":"Medicamentos utilizados em transplante de medula \u00f3ssea: um estudo sobre combina\u00e7\u00f5es dos antimicrobianos potencialmente interativos","volume":"42","author":"Fonseca","year":"2008","journal-title":"Revista da Escola de Enfermagem da USP, S\u00e3o Paulo."},{"key":"B17","volume-title":"Guia Pr\u00e1tico de UTI","author":"Guimar\u00e3es","year":"2008"},{"key":"B18","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1590\/S0103-507X2008000400006","article-title":"Potential drug interactions prevalence in intensive care units","volume":"20","author":"Hammes","year":"2008","journal-title":"Revista Brasileira de Terapia Intensiva"},{"key":"B19","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jcrc.2017.04.028","article-title":"Potential drug-drug interactions in pediatric patients admitted to intensive care unit of Khyber Teaching Hospital, Peshawar, Pakistan: a cross-sectional study","volume":"40","author":"Ismail","year":"2017","journal-title":"J. Crit. Care"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1007\/s00228-013-1563-z","article-title":"Comparative epidemiology of hospital-acquired adverse drug reactions in adults and children and their impact on cost and hospital stay\u2013a systematic review","volume":"69","author":"Khan","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1590\/S1679-45082012000100005","article-title":"O perfil epidemiol\u00f3gico do centro de terapia intensiva pedi\u00e1trico do hospital Israelita Albert Einstein","volume":"10","author":"Lanetzki","year":"2012","journal-title":"Einstein"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.2307\/4484794","article-title":"Serotonin toxicity associated with the use of linezolid: a review of postmarketing data","volume":"42","author":"Lawrence","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1590\/s0104-11692009000200013","article-title":"Potential drug interactions in intensive care patients at a teaching hospital","volume":"17","author":"Lima","year":"2009","journal-title":"Rev. Latino-Am. Enferm."},{"key":"B24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.4321\/s1886-36552007000400003","article-title":"Profile of drugs interactions in hospitalized children","volume":"5","author":"Martinbiancho","year":"2007","journal-title":"Pharm. Pract."},{"key":"B25","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.pedneo.2019.11.006","article-title":"Pilot study: evaluation of potential drug\u2013drug interactions in hospitalized pediatric patients","volume":"61","author":"Medina-Barajas","year":"2020","journal-title":"Pediatr. Neonatol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1590\/s0104-42302001000400036","article-title":"Prescri\u00e7\u00e3o de medicamentos para crian\u00e7as hospitalizadas: como avaliar a qualidade?","volume":"47","author":"Meiners","year":"2001","journal-title":"Revista da Associa\u00e7\u00e3o M\u00e9dica Brasileira, S\u00e3o Paulo."},{"key":"B27","unstructured":"Greenwood village (Colorado): Thomson healthcare2019"},{"key":"B28","doi-asserted-by":"publisher","first-page":"112","DOI":"10.4025\/cienccuidsaude.v7i0.6581","article-title":"Caracteriza\u00e7\u00e3o das interna\u00e7\u00f5es em uma unidade de terapia intensiva pedi\u00e1trica, em um hospital-escola na regi\u00e3o sul do Brasil","volume":"7","author":"Molina","year":"2008","journal-title":"Ci\u00eancia, Cuid. Sa\u00fade"},{"key":"B29","doi-asserted-by":"publisher","first-page":"266","DOI":"10.18433\/j35c7z","article-title":"Drug-drug interactions associated with the length of stay and cost of hospitalization","volume":"12","author":"Moura","year":"2009","journal-title":"J. Pharm. Pharmaceut. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/BF03256929","article-title":"Potential drug-drug interactions associated with prolonged stays in the intensive care unit: a retrospective cohort study","volume":"31","author":"Moura","year":"2011","journal-title":"Clin. Drug Invest."},{"key":"B31","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1002\/pds.4041","article-title":"Pharmacoepidemiological safety studies in children: a systematic review","volume":"25","author":"Osokogu","year":"2016","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B32","first-page":"12","article-title":"FC PICU Guidelines. Clinical pharmacy for paediatric critical care","year":"2011"},{"key":"B33","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1097\/PCC.0000000000001425","article-title":"Pediatric intensive care unit (PICU) length of stay: factors associated with bed utilization and development of a benchmarking model","volume":"19","author":"Pollack","year":"2018","journal-title":"Pediatr. Crit. Care Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.17921\/2447-8938.2014v16n3p%25p","article-title":"Drug interactions on the neonatal prescription at ICU-HGU","volume":"16","author":"Queiroz","year":"2014","journal-title":"UNOPAR Cient Ci\u00eanc Biol Sa\u00fade"},{"key":"B35","doi-asserted-by":"publisher","first-page":"63","DOI":"10.4103\/jpp.JPP_27_19","article-title":"Potential drug\u2013 drug interactions in the pediatric intensive care unit of a tertiary care hospital","volume":"10","author":"Rao","year":"2019","journal-title":"J. Pharmacol. Pharmacother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1590\/S1807-59322011000100003","article-title":"Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil","volume":"66","author":"Reis","year":"2011","journal-title":"Clinics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e16109","DOI":"10.1590\/s2175-97902017000116109","article-title":"Prevalence of potential drug-drug interactions in the intensive care unit of Brazilian teaching hospital","volume":"53","author":"Rodrigues","year":"2017","journal-title":"Braz J Pharm Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e00081815","DOI":"10.1590\/0102-311X00081815","article-title":"Adverse events in the intensive care unit: impact on mortality and length of stay in a prospective study","volume":"32","author":"Roque","year":"2016","journal-title":"Cad. Sa\u00fade P\u00fablica."},{"key":"B39","doi-asserted-by":"publisher","first-page":"546","DOI":"10.4067\/S0370-41062014000500004","article-title":"Characteristics of drug interactions in a pediatric intensive care unit","volume":"85","author":"Santib\u00e1\u00f1ez","year":"2014","journal-title":"Rev. Chil. Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e001868","DOI":"10.1136\/bmjopen-2012-001868","article-title":"Adverse drug events in a paediatric intensive care unit: a prospective cohort","volume":"3","author":"Silva","year":"2013","journal-title":"BMJ Open"},{"key":"B41","doi-asserted-by":"crossref","DOI":"10.11606\/T.5.2012.tde-01032013-141918","article-title":"Eventos adversos medicamentosos em unidade de terapia intensiva pedi\u00e1trica","author":"Silva","year":"2012"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e24061","DOI":"10.1371\/journal.pone.0024061","article-title":"Adverse drug reactions in children\u2014a systematic review","volume":"7","author":"Smyth","year":"2012","journal-title":"PloS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00134-008-1383-2","article-title":"Mini-series: II.clinical aspects. Clinically relevant CYP450-mediated drug interactions in the ICU","volume":"35","author":"Spriet","year":"2009","journal-title":"Intensive Care Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s11096-008-9191-x","article-title":"Evaluation of frequently used drug interaction screening programs","volume":"30","author":"Vonbach","year":"2008","journal-title":"Pharm. World Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.555407\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T08:33:48Z","timestamp":1606984428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.555407\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":44,"alternative-id":["10.3389\/fphar.2020.555407"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.555407","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]},"article-number":"555407"}}