{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:25:18Z","timestamp":1788715518623,"version":"build-2803163510"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Teijin Pharma Limited"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2\u2009g\/kg of IVIG is administered over 10\u201324\u2009h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12\u2009h (12H group, double speed), and one that received IVIG over 24\u2009h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21\u2009h vs. 21.5\u2009h, <jats:italic>p<\/jats:italic>\u00a0=\u20090.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037\u2009\u00b1\u2009648\u2009mg\/dl vs. 2414\u2009\u00b1\u2009248\u2009mg\/dl, <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The efficacy and safety of IVIG administered over 12\u2009h (double speed) were similar to those administered over 24\u2009h (reference speed).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>University Hospital Medical Information Network (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000017058\">UMIN000014665<\/jats:ext-link>). Registered 27 July 2014 \u2013 Prospectively registered, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr\/ctr_view.cgi?recptno=R000017058\">https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr\/ctr_view.cgi?recptno=R000017058<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-021-00601-6","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T13:02:29Z","timestamp":1625317349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial"],"prefix":"10.1186","volume":"19","author":[{"given":"Saori","family":"Fukui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-9330","authenticated-orcid":false,"given":"Mitsuru","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi","family":"Minami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Kotani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Yokomizo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukifumi","family":"Monden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Yamagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,3]]},"reference":[{"issue":"3","key":"601_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2188\/jea.JE20140089","volume":"25","author":"N Makino","year":"2015","unstructured":"Makino N, Nakamura Y, Yashiro M, Ae R, Tsuboi S, Aoyama Y, et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011\u20132012: from the results of the 22nd nationwide survey. J Epidemiol. 2015;25(3):239\u201345. https:\/\/doi.org\/10.2188\/jea.JE20140089.","journal-title":"J Epidemiol"},{"issue":"14","key":"601_CR2","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1016\/j.jacc.2015.12.073","volume":"67","author":"JW Newburger","year":"2016","unstructured":"Newburger JW, Takahashi M, Burns JC. Kawasaki disease. J Am Coll Cardiol. 2016;67(14):1738\u201349. https:\/\/doi.org\/10.1016\/j.jacc.2015.12.073.","journal-title":"J Am Coll Cardiol"},{"key":"601_CR3","doi-asserted-by":"publisher","unstructured":"Oates-Whitehead RM, Baumer JH, Haines L, Love S, Maconochie IK, Gupta A et al. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;(4):CD004000. https:\/\/doi.org\/10.1002\/14651858.CD004000.","DOI":"10.1002\/14651858.CD004000"},{"issue":"23","key":"601_CR4","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1056\/NEJM199106063242305","volume":"324","author":"JW Newburger","year":"1991","unstructured":"Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324(23):1633\u20139. https:\/\/doi.org\/10.1056\/NEJM199106063242305.","journal-title":"N Engl J Med"},{"issue":"17","key":"601_CR5","doi-asserted-by":"publisher","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","volume":"135","author":"BW McCrindle","year":"2017","unstructured":"McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927\u201399. https:\/\/doi.org\/10.1161\/CIR.0000000000000484.","journal-title":"Circulation."},{"issue":"2","key":"601_CR6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1111\/j.1442-200x.2005.02033.x","volume":"47","author":"M Ayusawa","year":"2005","unstructured":"Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 2005;47(2):232\u20134. https:\/\/doi.org\/10.1111\/j.1442-200x.2005.02033.x.","journal-title":"Pediatr Int"},{"issue":"22","key":"601_CR7","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1161\/CIRCULATIONAHA.105.592865","volume":"113","author":"T Kobayashi","year":"2006","unstructured":"Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113(22):2606\u201312. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.105.592865.","journal-title":"Circulation."},{"issue":"3","key":"601_CR8","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","volume":"48","author":"Y Kanda","year":"2013","unstructured":"Kanda Y. Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics. Bone Marrow Transplant. 2013;48(3):452\u20138. https:\/\/doi.org\/10.1038\/bmt.2012.244.","journal-title":"Bone Marrow Transplant"},{"key":"601_CR9","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.jpeds.2019.06.018","volume":"214","author":"T Oda","year":"2019","unstructured":"Oda T, Nagata H, Nakashima Y, Nanishi E, Takada Y, Nishimura M, et al. Clinical utility of highly purified 10% liquid intravenous immunoglobulin in Kawasaki disease. J Pediatr. 2019;214:227\u201330. https:\/\/doi.org\/10.1016\/j.jpeds.2019.06.018.","journal-title":"J Pediatr"},{"issue":"4","key":"601_CR10","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1093\/jpids\/piw081","volume":"6","author":"JE Schuster","year":"2017","unstructured":"Schuster JE, Palac HL, Innocentini N, Rowley AH, Young LT, Shulman ST. Hyponatremia is a feature of Kawasaki disease shock syndrome: a case-control study. J Pediatr Infect Dis Soc. 2017;6(4):386\u20138. https:\/\/doi.org\/10.1093\/jpids\/piw081.","journal-title":"J Pediatr Infect Dis Soc"},{"issue":"3","key":"601_CR11","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s10067-018-4339-0","volume":"38","author":"MA Yamazaki-Nakashimada","year":"2019","unstructured":"Yamazaki-Nakashimada MA, G\u00e1mez-Gonz\u00e1lez LB, Murata C, Honda T, Yasukawa K, Hamada H. IgG levels in Kawasaki disease and its association with clinical outcomes. Clin Rheumatol. 2019;38(3):749\u201354. https:\/\/doi.org\/10.1007\/s10067-018-4339-0.","journal-title":"Clin Rheumatol"},{"issue":"3","key":"601_CR12","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1161\/01.CIR.0000079166.93475.5F","volume":"108","author":"M Terai","year":"2003","unstructured":"Terai M, Honda T, Yasukawa K, Higashi K, Hamada H, Kohno Y. Prognostic impact of vascular leakage in acute Kawasaki disease. Circulation. 2003;108(3):325\u201330. https:\/\/doi.org\/10.1161\/01.CIR.0000079166.93475.5F.","journal-title":"Circulation."},{"issue":"5","key":"601_CR13","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1046\/j.1442-200x.2000.01288.x","volume":"42","author":"Y Morikawa","year":"2000","unstructured":"Morikawa Y, Ohashi Y, Harada K, Asai T, Okawa S, Nagashima M, et al. Coronary risks after high-dose \u03b3-globulin in children with Kawasaki disease. Pediatr Int. 2000;42(5):464\u20139. https:\/\/doi.org\/10.1046\/j.1442-200x.2000.01288.x.","journal-title":"Pediatr Int"},{"issue":"7","key":"601_CR14","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1586\/1744666X.2015.1044980","volume":"11","author":"JC Burns","year":"2015","unstructured":"Burns JC, Franco A. The immunomodulatory effects of intravenous immunoglobulin therapy in Kawasaki disease. Expert Rev Clin Immunol. 2015;11(7):819\u201325. https:\/\/doi.org\/10.1586\/1744666X.2015.1044980.","journal-title":"Expert Rev Clin Immunol"},{"issue":"2","key":"601_CR15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3978\/j.issn.2224-4336.2012.04.05","volume":"1","author":"J Chen","year":"2012","unstructured":"Chen J, Ma B, Lin LX, Xue YM. Treatment of Kawasaki disease by different doses of immunoglobulin: a meta-analysis of efficacy and safety. Transl Pediatr. 2012;1(2):99\u2013107. https:\/\/doi.org\/10.3978\/j.issn.2224-4336.2012.04.05.","journal-title":"Transl Pediatr"},{"key":"601_CR16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1385\/CRIAI:29:3:173","volume":"29","author":"O Hedi","year":"2005","unstructured":"Hedi O, Uriel K, Yaniv S, Yehuda S. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29:173\u201384.","journal-title":"Clin Rev Allergy Immunol"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00601-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-021-00601-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00601-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T13:10:01Z","timestamp":1625317801000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-021-00601-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,3]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["601"],"URL":"https:\/\/doi.org\/10.1186\/s12969-021-00601-6","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,3]]},"assertion":[{"value":"15 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients or their legal guardians received adequate information using an informed consent form, and written informed consent was obtained from all legal guardians of the patients before enrollment. This study was approved by the institutional review boards of all participating institutions (number CB13\u201349).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"107"}}