{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T21:14:30Z","timestamp":1770758070450,"version":"3.50.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Furosemide is approved in full term neonates to treat edema associated with congestive heart failure, cirrhosis and renal diseases. It is often administered off-label in premature neonates, to treat respiratory conditions and at doses greater-than-recommended. We conducted a national survey on behalf of the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology (SIN), to investigate its use in Italian neonatal intensive care units (NICUs), in conformity with current guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between December 2016 and June 2017, a 14-item multiple-choice online questionnaire was sent to all NICU directors from the SIN directory.<\/jats:p><jats:p><jats:italic>G<\/jats:italic>estational age, route of administration, posology, indications, referenced guidelines, adverse effects monitoring and the presence of Paediatric Cardiology or Cardiosurgery service on site were assessed. A chi-square test was performed 1) to evaluate differences in the distribution of responses between NICUs administering furosemide at doses higher-than-recommended; 2) to compare the proportion of NICUs administering furosemide at high doses in institutions with versus without a Paediatric Cardiology or Cardiosurgery service.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The response rate was 50% (57\/114). The intravenous and oral routes were chosen primarily; the intravenous administration in single doses predominated over continuous infusion. Its main therapeutic indications were congestive heart failure\/overload (94.7%) and oligo-anuria (87.7%) however furosemide was also frequently used for broncopulmonary dysplasia (50.9%) and respiratory distress syndrome and\/or transient tachypnea of the newborn (24.6%).<\/jats:p><jats:p>In 28\/57 NICUs furosemide was administered at doses higher-than-recommended. In most NICUs the same posology was used in term and preterm neonates. Compared to the total sample, a larger proportion of NICUs administering doses greater-than-recommended referenced current literature for reasons to do so (19.3 and 32.1% respectively). The presence of a Paediatric Cardiology or Cardiosurgery service on site did not correlate with the chosen posology.<\/jats:p><jats:p>The majority of NICUs performed acoustic test and renal ultrasound for furosemide exposure greater than 2\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In Italian NICUs, furosemide is commonly prescribed to term and preterm newborns for label and unlabeled indications. Doses greater-than-recommended are frequently administered. Such use is not necessarily inappropriate. More research is required to assess the efficacy and safety of unlabeled use.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13052-020-00851-2","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T11:03:02Z","timestamp":1592823782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Furosemide use in Italian neonatal intensive care units: a national survey"],"prefix":"10.1186","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-9827","authenticated-orcid":false,"given":"Valeria Anna","family":"Manfredini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cerini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Clavenna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Dotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Letizia","family":"Caccamo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Staffler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Massenzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossano Massimo","family":"Rezzonico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on the behalf of study Group of Neonatal Pharmacoterapy of the Italian Society of Neonatology","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"key":"851_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13052-017-0354-z","volume":"43","author":"A Girardi","year":"2017","unstructured":"Girardi A. Pattern of drug use among preterm neonates: results from an Italian neonatal intensive care unit. Ital J Pediatr. 2017;43:37.","journal-title":"Ital J Pediatr"},{"key":"851_CR2","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1542\/neo.6-8-e392","volume":"6","author":"M Bestic","year":"2005","unstructured":"Bestic M, Reed MD. Common diuretics used in the preterm and term infant. NeoReviews. 2005;6:392\u20138.","journal-title":"NeoReviews."},{"key":"851_CR3","first-page":"49","volume":"32","author":"MM Laughon","year":"2015","unstructured":"Laughon MM, Chantala K. Diuretic exposure in premature infants from 1997 to 2011. Am J Perinatol. 2015;32:49\u201356.","journal-title":"Am J Perinatol"},{"key":"851_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1177\/00369330740190S103","volume":"19","author":"W Rupp","year":"1974","unstructured":"Rupp W. Parmacokinetics and pharmacodynamics of lasix. Scott Med J. 1974;19:5\u201313.","journal-title":"Scott Med J"},{"key":"851_CR5","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.3390\/ph6091094","volume":"6","author":"GM Pacifici","year":"2013","unstructured":"Pacifici GM. Clinical pharmacology of furosemide in neonates: a review. Pharmaceuticals (Basel). 2013;6:1094\u2013129.","journal-title":"Pharmaceuticals (Basel)"},{"key":"851_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jpeds.2018.01.066","volume":"197","author":"CJ Blaisdell","year":"2018","unstructured":"Blaisdell CJ, Troendle J, Zajicek A. Acute responses to diuretic therapy in extremely low gestational age newborns: results from the PROP cohort study. J Pediatr. 2018;197:42\u20137.","journal-title":"J Pediatr"},{"key":"851_CR7","first-page":"CD001454","volume":"12","author":"A Stewart","year":"2011","unstructured":"Stewart A, Brion LP. Diuretics for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2011;12:CD001454.","journal-title":"Cochrane Database Syst Rev"},{"key":"851_CR8","first-page":"CD001694","volume":"3","author":"LP Brion","year":"2006","unstructured":"Brion LP, Primhak RA, Yong W. Aerosolized diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2006;3:CD001694.","journal-title":"Cochrane Database Syst Rev"},{"key":"851_CR9","first-page":"CD003064","volume":"11","author":"M Kassab","year":"2015","unstructured":"Kassab M, Khriesat WM, Anabrees J. Diuretics for transient tachypnoea of the newborn. Cochrane Database Syst Rev. 2015;11:CD003064.","journal-title":"Cochrane Database Syst Rev"},{"key":"851_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1097\/00045391-200207000-00009","volume":"9","author":"J Prandota","year":"2002","unstructured":"Prandota J. Furosemide: progress in understanding its diuretic, antiinflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases. Am J Ther. 2002;9:317\u201328.","journal-title":"Am J Ther"},{"key":"851_CR11","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1164\/ajrccm\/145.5.990","volume":"145","author":"JP Mitchell","year":"1992","unstructured":"Mitchell JP, Schuller D, Calandrino FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis. 1992;145:990\u20138.","journal-title":"Am Rev Respir Dis"},{"key":"851_CR12","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.jpeds.2004.06.028","volume":"145","author":"EW Adams","year":"2004","unstructured":"Adams EW, Harrison MC, et al. Increased lung water and tissue damage in bronchopulmonary dysplasia. J Pediatr. 2004;145:503\u20137.","journal-title":"J Pediatr"},{"key":"851_CR13","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1055\/s-0033-1361933","volume":"31","author":"EM Hsieh","year":"2014","unstructured":"Hsieh EM, Hornik CP, Clark RH. Medication use in the neonatal intensive care unit. Am J Perinatol. 2014;31:811\u201321.","journal-title":"Am J Perinatol"},{"key":"851_CR14","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/jcu.1870140408","volume":"14","author":"MR Myracle","year":"1986","unstructured":"Myracle MR, McGahan JP, Goetzman BW, Adelman RD. Ultrasound diagnosis of renal calcification in infants on chronic furosemide therapy. J Clin Ultrasound. 1986;14:281\u20137.","journal-title":"J Clin Ultrasound"},{"key":"851_CR15","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00467-008-0908-9","volume":"25","author":"EA Schell-Feith","year":"2010","unstructured":"Schell-Feith EA, Kist-van Holthe JE, Van Der Heijden AJ. Nephrocalcinosis in preterm neonates. Pediatr Nephrol. 2010;25:221\u201330.","journal-title":"Pediatr Nephrol"},{"key":"851_CR16","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1056\/NEJM198303313081303","volume":"308","author":"TP Green","year":"1983","unstructured":"Green TP, Thompson TR, Johnson DE. Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome. N Engl J Med. 1983;308:743\u20138.","journal-title":"N Engl J Med"},{"key":"851_CR17","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/00045391-200107000-00010","volume":"8","author":"J Prandota","year":"2001","unstructured":"Prandota J. Clinical pharmacology of furosemide in children: a supplement. Am J Ther. 2001;8:275\u201389.","journal-title":"Am J Ther"},{"key":"851_CR18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S0022-3476(80)80154-5","volume":"97","author":"R Peterson","year":"1980","unstructured":"Peterson R. Pharmacology of furosemide in the premature newborn infant. J Pediatr. 1980;97:139\u201343.","journal-title":"J Pediatr"},{"key":"851_CR19","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.jpeds.2018.11.043","volume":"208","author":"RG Greenberg","year":"2019","unstructured":"Greenberg RG, Gayam S, Savage D. Furosemide Exposure and Prevention of Bronchopulmonary Dysplasia in Premature Infants. J Pediatr. 2019;208:134\u201340.","journal-title":"J Pediatr"},{"key":"851_CR20","doi-asserted-by":"crossref","unstructured":"Moghal NE, Shenoy M. Furosemide and acute kidney injury in neonates. Arch Dis Child Fetal Neonatal Ed. 2008:F313\u20136.","DOI":"10.1136\/adc.2006.108860"},{"key":"851_CR21","doi-asserted-by":"crossref","unstructured":"Luciani GB, Nichani S. Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations. Ann Thorac Surg. 1997:1133\u20139.","DOI":"10.1016\/S0003-4975(97)00714-5"},{"key":"851_CR22","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/j.1365-2125.2007.02913.x","volume":"64","author":"MM Van der Vorst","year":"2007","unstructured":"Van der Vorst MM. Absence of tolerance and toxicity to high-dose continuous intravenous furosemide in haemodynamically unstable infants after cardiac surgery. Br J Clin Pharmacol. 2007;64:796\u2013803.","journal-title":"Br J Clin Pharmacol"},{"key":"851_CR23","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s001340050395","volume":"23","author":"JM Klinge","year":"1997","unstructured":"Klinge JM, Scharf J, Hofbeck M, Gerling S, Bonakdar S, Singer H. Intermittent administration of furosemide versus continuous infusion in the postoperative management of children following open heart surgery. Intensive Care Med. 1997;23:693\u20137.","journal-title":"Intensive Care Med"},{"key":"851_CR24","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/00003246-199201000-00010","volume":"20","author":"NC Singh","year":"1992","unstructured":"Singh NC, Kissoon N, Mofada S, Bennett M, Bohn DJ. Comparison of continuous versus intermittent furosemide administration in postoperative pediatric cardiac patients. Crit Care Med. 1992;20:17\u201321.","journal-title":"Crit Care Med"},{"key":"851_CR25","first-page":"1711","volume":"42","author":"DC Brater","year":"1983","unstructured":"Brater DC. Determinants of the overall response to furosemide: pharmacokinetics and pharmacodynamics. Fed Proc. 1983;42:1711\u20133.","journal-title":"Fed Proc"},{"key":"851_CR26","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/bdd.2510070603","volume":"67","author":"MG Lee","year":"1986","unstructured":"Lee MG, Li T. Effect of intravenous infusion time in the pharmacokinetics and dynamics of the same total dose of furosemide. Biopharm Drug Dispos. 1986;67:537\u201344.","journal-title":"Biopharm Drug Dispos"},{"key":"851_CR27","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1056\/NEJM197006182822506","volume":"282","author":"GH Schwartz","year":"1970","unstructured":"Schwartz GH, David DS, Riggio RR, Stenzel KH, Rubin AL. Ototoxicity induced by furosemide. N Engl J Med. 1970;282:1413\u20134.","journal-title":"N Engl J Med"},{"issue":"Suppl","key":"851_CR28","first-page":"54","volume":"4","author":"ME Wigand","year":"1971","unstructured":"Wigand ME, Heidland A. Ototoxic side-effects of high doses of furosemide in patients with uraemia. Postgrad Med J. 1971;4(Suppl):54\u20136.","journal-title":"Postgrad Med J"},{"key":"851_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000244391","volume":"71","author":"C Borradori","year":"1997","unstructured":"Borradori C, Fawer CL, Buclin T, Calame A. Risk factors of sensorineural hearing loss in preterm infants. Biol Neonate. 1997;71:1\u201310.","journal-title":"Biol Neonate"},{"key":"851_CR30","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1111\/j.1469-8749.1991.tb14966.x","volume":"33","author":"DR Brown","year":"1991","unstructured":"Brown DR, Watchko JF, Sabo D. Neonatal sensorineural hearing loss associated with furosemide: a case-control study. Dev Med Child Neurol. 1991;33:816\u201323.","journal-title":"Dev Med Child Neurol"},{"key":"851_CR31","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1542\/peds.70.3.360","volume":"70","author":"KG Hufnagle","year":"1982","unstructured":"Hufnagle KG, Khan SN. Penn, D. renal calcifications: a complication of long-term furosemide therapy in preterm infants. Pediatrics. 1982;70:360\u20133.","journal-title":"Pediatrics."},{"key":"851_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1288\/00005537-198509010-00001","volume":"95","author":"LP Rybak","year":"1985","unstructured":"Rybak LP. Furosemide ototoxicity: clinical and experimental aspects. Laryngoscope. 1985;95:1\u201314.","journal-title":"Laryngoscope."},{"key":"851_CR33","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/S0022-3476(82)80319-3","volume":"101","author":"JV Aranda","year":"1982","unstructured":"Aranda JV, Lambert C, Perez J, Turmen T, Sitar DS. Metabolism and renal elimination of furosemide in the newborn infant. J Pediatr. 1982;101:777\u201381.","journal-title":"J Pediatr"},{"key":"851_CR34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/BF00606423","volume":"22","author":"P Vert","year":"1982","unstructured":"Vert P, Broquaire M, Legagneur M, Morselli PL. Pharmacokinetics of furosemide in neonates. Eur J Clin Pharmacol. 1982;22:39\u201345.","journal-title":"Eur J Clin Pharmacol"},{"key":"851_CR35","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/S0022-3476(83)80433-8","volume":"103","author":"S Tuck","year":"1983","unstructured":"Tuck S, Morselli P, Broquaire M, Vert P. Plasma and urinary kinetics of furosemide in newborn infants. J Pediatr. 1983;103:481\u20135.","journal-title":"J Pediatr"},{"key":"851_CR36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.earlhumdev.2018.08.009","volume":"125","author":"LA Wang","year":"2018","unstructured":"Wang LA, Smith PB. Prolonged furosemide exposure and risk of abnormal newborn hearing screen in premature infants. Early Hum Dev. 2018;125:26\u201330.","journal-title":"Early Hum Dev"},{"key":"851_CR37","first-page":"4","volume":"19","author":"W Jackson","year":"2018","unstructured":"Jackson W, Taylor G, Selewski D, et al. Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review. Matern Health Neonatol Perinatol. 2018;19:4\u201323.","journal-title":"Matern Health Neonatol Perinatol"},{"key":"851_CR38","doi-asserted-by":"publisher","first-page":"43","DOI":"10.5688\/aj720243","volume":"72","author":"JE Fincham","year":"2008","unstructured":"Fincham JE. Response Rates and Responsiveness for Surveys, Standards, and the Journal. Am J Pharm Educ. 2008;72:43.","journal-title":"Am J Pharm Educ"},{"key":"851_CR39","unstructured":"ClinicalTrials.gov. Safety of furosemide in premature infants at risk of Bronchopulmonary Dysplasia (BPD). ClinicalTrials.gov identifier NCT02527798. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02527798."},{"key":"851_CR40","first-page":"1","volume":"13","author":"HTM De Lima Costa","year":"2018","unstructured":"De Lima Costa HTM, Costa TX, Martins RR, Oliveira AG. Use of off-label and unlicensed medicines in neonatal intensive care. PLoS One. 2018;13:1\u201312.","journal-title":"PLoS One"},{"key":"851_CR41","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/ped.12190","volume":"56","author":"N Laforgia","year":"2014","unstructured":"Laforgia N, Nuccio MM, Schettini F. Off-label and unlicensed drug use among neonatal intensive care units in southern Italy. Pediatr Int. 2014;56:57\u20139.","journal-title":"Pediatr Int"},{"key":"851_CR42","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/ped.12190","volume":"56","author":"MT Gidey","year":"2014","unstructured":"Gidey MT, Gebretsadkan YG, Tsadik AG. Off-label and unlicensed drug use in Ayder comprehensive specialized hospital neonatal intensive care unit. Pediatr Int. 2014;56:57\u20139.","journal-title":"Pediatr Int"},{"key":"851_CR43","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/jcpt.12440","volume":"41","author":"N Krzy\u017caniak","year":"2016","unstructured":"Krzy\u017caniak N, Paw\u0142owska I, Bajorek B. Review of drug utilization patterns in NICUs worldwide. J Clin Pharm Ther. 2016;41:612\u201320.","journal-title":"J Clin Pharm Ther"}],"container-title":["Italian Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-020-00851-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13052-020-00851-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-020-00851-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T03:34:16Z","timestamp":1723088056000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-020-00851-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["851"],"URL":"https:\/\/doi.org\/10.1186\/s13052-020-00851-2","relation":{},"ISSN":["1824-7288"],"issn-type":[{"value":"1824-7288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]},"assertion":[{"value":"10 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}