{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:02:14Z","timestamp":1771545734744,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"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":["Pediatr Res"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We examined the underlying mechanisms of whether hyponatremia could be induced by hypotonic solution administration after the postoperative invasive phase (POIP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included patients who had undergone surgery with expected oral feeding resumption after postoperative day (POD) 3. In this open-label, randomized controlled trial, 100 patients were assigned to three groups by sodium concentrations ([Na]) used for maintenance infusions: 136\u2009mEq\/L (ISO) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934), 68\u2009mEq\/L (HYPO) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200933), and 34 mEq\/L (exHYPO) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200933). Potassium (20 mEq\/L) and glucose (60\u2009g\/L) were added to each infusion. Ringer\u2019s solution was used in all groups for the first 12\u2009h postoperatively, then switched to a maintenance solution. Blood samples were drawn and evaluated on POD 3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hyponatremia frequencies on POD 3 were 3.6, 18, and 39% in the ISO, HYPO, and exHYPO groups, respectively, with a significant difference between the ISO and exHYPO groups. Additionally, 90% of the patients still had excessive antidiuretic hormone (ADH) secretion on POD 3. There were no remarkable adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The persistence of surgical stress-induced ADH secretion until POD 3 suggested that hyponatremia was induced by exHYPO administration. However, using Ringer\u2019s solution during the POIP might prevent hyponatremia in HYPO patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration number<\/jats:title>\n                    <jats:p>\n                      UMIN000029057 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.umin.ac.jp\/ctr\/index.htm\" ext-link-type=\"uri\">https:\/\/www.umin.ac.jp\/ctr\/index.htm<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Date of first registration<\/jats:title>\n                    <jats:p>01\/11\/2017<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>After the postoperative invasive phase, non-osmotic antidiuretic hormone (ADH) secretion due to surgical stress persisted, resulting in an excess ADH state for at least 3 postoperative days (PODs).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Administration of extremely hypotonic electrolyte infusions under such circumstances might induce hyponatremia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Adequate extracellular fluid administration during the invasive phase after major pediatric laparoscopic surgery did not cause further increases in ADH secretion or hyponatremia, even for HYPO maintenance fluid.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04124-8","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:48:24Z","timestamp":1747788504000},"page":"263-269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyponatremia after pediatric surgery: Randomized trial of fluid composition on antidiuretic hormone response"],"prefix":"10.1038","volume":"99","author":[{"given":"Kazuki","family":"Yokota","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroo","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsunori","family":"Manaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yachiyo","family":"Kuwatsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Ando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimitoshi","family":"Nishiwaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahisa","family":"Tainaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiyoe","family":"Shirota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Sumida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Makita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hizuru","family":"Amano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinari","family":"Hinoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"4124_CR1","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1542\/peds.19.5.823","volume":"19","author":"MA Holliday","year":"1957","unstructured":"Holliday, M. A. & Segar, W. E. The maintenance need for water in parenteral fluid therapy. Pediatrics 19, 823\u2013832 (1957).","journal-title":"Pediatrics"},{"key":"4124_CR2","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1542\/peds.111.2.227","volume":"111","author":"ML Moritz","year":"2003","unstructured":"Moritz, M. L. & Ayus, J. C. Prevention of hospital-acquired hyponatremia: a case for using isotonic saline. Pediatrics 111, 227\u2013230 (2003).","journal-title":"Pediatrics"},{"key":"4124_CR3","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/children8090785","volume":"8","author":"N Hasim","year":"2021","unstructured":"Hasim, N., Bakar, M. A. A. & Islam, M. A. Efficacy and safety of isotonic and hypotonic intravenous maintenance fluids in hospitalised children: a systematic review and meta-analysis of randomised controlled trials. Child. 8, 785 (2021).","journal-title":"Child."},{"key":"4124_CR4","doi-asserted-by":"publisher","first-page":"e000385","DOI":"10.1136\/bmjpo-2018-000385","volume":"3","author":"SF Torres","year":"2019","unstructured":"Torres, S. F. et al. Hypotonic and isotonic intravenous maintenance fluids in hospitalised paediatric patients: a randomised controlled trial. BMJ Paediatr. Open 3, e000385 (2019).","journal-title":"BMJ Paediatr. Open"},{"key":"4124_CR5","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/S0140-6736(14)61459-8","volume":"385","author":"S McNab","year":"2015","unstructured":"McNab, S. et al. 140 mmol\/L of sodium versus 77 mmol\/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet 385, 1190\u20131197 (2015).","journal-title":"Lancet"},{"key":"4124_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.4103\/sja.SJA_258_17","volume":"12","author":"MF Khan","year":"2018","unstructured":"Khan, M. F., Siddiqui, K. M. & Asghar, M. A. Fluid choice during perioperative care in children: a survey of present-day proposing practice by anesthesiologists in a tertiary care hospital. Saudi J. Anaesth. 12, 42\u201345 (2018).","journal-title":"Saudi J. Anaesth."},{"key":"4124_CR7","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.jpeds.2009.07.059","volume":"156","author":"KA Neville","year":"2010","unstructured":"Neville, K. A. et al. Prevention of hyponatremia during maintenance intravenous fluid administration: a prospective randomized study of fluid type versus fluid rate. J. Pediatr. 156, 313\u20139.e1 (2010).","journal-title":"J. Pediatr."},{"key":"4124_CR8","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1016\/j.jpeds.2013.07.020","volume":"163","author":"F Carandang","year":"2013","unstructured":"Carandang, F. et al. Association between maintenance fluid tonicity and hospital-acquired hyponatremia. J. Pediatr. 163, 1646\u20131651 (2013).","journal-title":"J. Pediatr."},{"key":"4124_CR9","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1136\/archdischild-2011-300221","volume":"97","author":"MG Coulthard","year":"2012","unstructured":"Coulthard, M. G., Long, D. A., Ullman, A. J. & Ware, R. S. A randomised controlled trial of Hartmann\u2019s solution versus half normal saline in postoperative paediatric spinal instrumentation and craniotomy patients. Arch. Dis. Child. 97, 491\u2013496 (2012).","journal-title":"Arch. Dis. Child."},{"key":"4124_CR10","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1542\/peds.2011-0415","volume":"128","author":"K Choong","year":"2011","unstructured":"Choong, K. et al. Hypotonic versus isotonic maintenance fluids after surgery for children: a randomized controlled trial. Pediatrics 128, 857\u2013866 (2011).","journal-title":"Pediatrics"},{"key":"4124_CR11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1001\/jamapediatrics.2020.3383","volume":"175","author":"S Lehtiranta","year":"2021","unstructured":"Lehtiranta, S. et al. Risk of electrolyte disorders in acutely ill children receiving commercially available plasmalike isotonic fluids: a randomized clinical trial. JAMA Pediatr. 175, 28\u201335 (2021).","journal-title":"JAMA Pediatr."},{"key":"4124_CR12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4103\/ajps.AJPS_40_16","volume":"15","author":"CE Omoifo","year":"2018","unstructured":"Omoifo, C. E., Edomwonyi, N. P. & Idogun, S. E. Incidence of hyponatraemia following the use of three different intravenous fluids in paediatric surgery. Afr. J. Paediatr. Surg. 15, 69\u201372 (2018).","journal-title":"Afr. J. Paediatr. Surg."},{"key":"4124_CR13","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1471-2431-11-61","volume":"11","author":"U Fl\u00e4ring","year":"2011","unstructured":"Fl\u00e4ring, U. et al. The efficacy of hypotonic and near-isotonic saline for parenteral fluid therapy given at low maintenance rate in preventing significant change in plasma sodium in post-operative pediatric patients: protocol for a prospective randomized non-blinded study. BMC Pediatr. 11, 61 (2011).","journal-title":"BMC Pediatr."},{"key":"4124_CR14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00467-015-3081-y","volume":"31","author":"GJ Oh","year":"2016","unstructured":"Oh, G. J. & Sutherland, S. M. Perioperative fluid management and postoperative hyponatremia in children. Pediatr. Nephrol. 31, 53\u201360 (2016).","journal-title":"Pediatr. Nephrol."},{"key":"4124_CR15","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/1471-2431-11-82","volume":"11","author":"TG Saba","year":"2011","unstructured":"Saba, T. G., Fairbairn, J., Houghton, F., Laforte, D. & Foster, B. J. A randomized controlled trial of isotonic versus hypotonic maintenance intravenous fluids in hospitalized children. BMC Pediatr. 11, 82 (2011).","journal-title":"BMC Pediatr."},{"key":"4124_CR16","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s12098-014-1436-1","volume":"82","author":"HK Pemde","year":"2015","unstructured":"Pemde, H. K., Dutta, A. K., Sodani, R. & Mishra, K. Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections. Indian J. Pediatr. 82, 13\u201318 (2015).","journal-title":"Indian J. Pediatr."},{"key":"4124_CR17","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1007\/s00467-010-1600-4","volume":"25","author":"L Kannan","year":"2010","unstructured":"Kannan, L. et al. Intravenous fluid regimen and hyponatraemia among children: a randomized controlled trial. Pediatr. Nephrol. 25, 2303\u20132309 (2010).","journal-title":"Pediatr. Nephrol."},{"key":"4124_CR18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jpeds.2014.01.040","volume":"165","author":"BA Foster","year":"2014","unstructured":"Foster, B. A., Tom, D. & Hill, V. Hypotonic versus isotonic fluids in hospitalized children: a systematic review and meta-analysis. J. Pediatr. 165, 163\u2013169.e2 (2014).","journal-title":"J. Pediatr."},{"key":"4124_CR19","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1097\/00007632-199603150-00013","volume":"21","author":"PW Brazel","year":"1996","unstructured":"Brazel, P. W. & McPhee, I. B. Inappropriate secretion of antidiuretic hormone in postoperative scoliosis patients: the role of fluid management. Spine 21, 724\u2013727 (1996).","journal-title":"Spine"},{"key":"4124_CR20","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1159\/000098028","volume":"26","author":"A Rai","year":"2006","unstructured":"Rai, A., Whaley-Connell, A., McFarlane, S. & Sowers, J. R. Hyponatremia, arginine vasopressin dysregulation, and vasopressin receptor antagonism. Am. J. Nephrol. 26, 579\u2013589 (2006).","journal-title":"Am. J. Nephrol."},{"key":"4124_CR21","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1007\/s10143-020-01450-9","volume":"44","author":"M Castle-Kirszbaum","year":"2021","unstructured":"Castle-Kirszbaum, M. et al. Hyponatraemia and hypernatraemia: disorders of water balance in neurosurgery. Neurosurg. Rev. 44, 2433\u20132458 (2021).","journal-title":"Neurosurg. Rev."},{"key":"4124_CR22","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-3083","volume":"142","author":"LG Feld","year":"2018","unstructured":"Feld, L. G. et al. Clinical Practice Guideline: Maintenance Intravenous Fluids in Children. Pediatrics 142, e20183083 (2018).","journal-title":"Pediatrics"},{"key":"4124_CR23","first-page":"232","volume":"63","author":"Y Ooiso","year":"2005","unstructured":"Ooiso, Y. Endocrinologic testing vasopressin (AVP) (in Japanese). Jpn. J. Clin. Med. 63, 232\u2013234 (2005).","journal-title":"Jpn. J. Clin. Med."},{"key":"4124_CR24","first-page":"694","volume":"54","author":"K Yokota","year":"2018","unstructured":"Yokota, K. et al. Is it right to use hypotonic fluids as maintenance fluid? They induce hyponatremia (in Japanese). J. Jpn. Soc. Pediatr. Surg. 54, 694 (2018).","journal-title":"J. Jpn. Soc. Pediatr. Surg."},{"key":"4124_CR25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.jped.2014.12.003","volume":"91","author":"HI Almeida","year":"2015","unstructured":"Almeida, H. I. et al. The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population. J. Pediatr. 91, 499\u2013505 (2015).","journal-title":"J. Pediatr."},{"key":"4124_CR26","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00467-010-1647-2","volume":"26","author":"K Kanda","year":"2011","unstructured":"Kanda, K. et al. The relationship between arginine vasopressin levels and hyponatremia following a percutaneous renal biopsy in children receiving hypotonic or isotonic intravenous fluids. Pediatr. Nephrol. 26, 99\u2013104 (2011).","journal-title":"Pediatr. Nephrol."},{"key":"4124_CR27","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/j.0953-8194.2004.01172.x","volume":"16","author":"K Itoi","year":"2004","unstructured":"Itoi, K., Jiang, Y. Q., Iwasaki, Y. & Watson, S. J. Regulatory mechanisms of corticotropin-releasing hormone and vasopressin gene expression in the hypothalamus. J. Neuroendocrinol. 16, 348\u2013355 (2004).","journal-title":"J. Neuroendocrinol."},{"key":"4124_CR28","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.jpeds.2004.06.077","volume":"145","author":"MA Holliday","year":"2004","unstructured":"Holliday, M. A., Friedman, A. L., Segar, W. E., Chesney, R. & Finberg, L. Acute hospital-induced hyponatremia in children: a physiologic approach. J. Pediatr. 145, 584\u2013587 (2004).","journal-title":"J. Pediatr."},{"key":"4124_CR29","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1440-1754.2007.01254.x","volume":"45","author":"M Yung","year":"2009","unstructured":"Yung, M. & Keeley, S. Randomised controlled trial of intravenous maintenance fluids. J. Paediatr. Child Health 45, 9\u201314 (2009).","journal-title":"J. Paediatr. Child Health"},{"key":"4124_CR30","doi-asserted-by":"publisher","first-page":"281","DOI":"10.5546\/aap.2013.eng.281","volume":"111","author":"FAJ Jorro Bar\u00f3n","year":"2013","unstructured":"Jorro Bar\u00f3n, F. A. J. et al. Hypotonic versus isotonic maintenance fluids in critically ill pediatric patients: a randomized controlled trial. Arch. Argent. Pediatr. 111, 281\u2013287 (2013).","journal-title":"Arch. Argent. Pediatr."},{"key":"4124_CR31","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1097\/PEC.0000000000000352","volume":"31","author":"G Yang","year":"2015","unstructured":"Yang, G., Jiang, W., Wang, X. & Liu, W. The efficacy of isotonic and hypotonic intravenous maintenance fluid for pediatric patients: a meta-analysis of randomized controlled trials. Pediatr. Emerg. Care 31, 122\u2013126 (2015).","journal-title":"Pediatr. Emerg. Care"},{"key":"4124_CR32","doi-asserted-by":"publisher","first-page":"700","DOI":"10.3390\/nu9070700","volume":"9","author":"T Iwahori","year":"2017","unstructured":"Iwahori, T., Miura, K. & Ueshima, H. Time to consider use of the sodium-to-potassium ratio for practical sodium reduction and potassium increase. Nutrients 9, 700 (2017).","journal-title":"Nutrients"},{"key":"4124_CR33","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3390\/nu8080496","volume":"8","author":"SA O\u2019halloran","year":"2016","unstructured":"O\u2019halloran, S. A., Grimes, C. A., Lacy, K. E., Campbell, K. J. & Nowson, C. A. Dietary intake and sources of potassium and the relationship to dietary sodium in a sample of Australian pre-school children. Nutrients 8, 496 (2016).","journal-title":"Nutrients"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04124-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04124-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04124-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:04:44Z","timestamp":1771542284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04124-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["4124"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-04124-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"29 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Informed consent was obtained from the patients and\/or their legal guardians. Informed assent was given in person to patients aged \u22655 years.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}