{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:22:51Z","timestamp":1789147371482,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>This paper focuses on hyperglycemic hyperosmolar syndrome (HHS), a unique hyperglycemic state requiring divergent diagnosis and treatment approaches from diabetic ketoacidosis (DKA) despite some shared characteristics. We introduce the mnemonic DI-FF-ER-EN-CE-S to encapsulate unique HHS management and complications. \u2018DI\u2019 emphasizes the need to delay and decrease initial insulin therapy until serum glucose decline is managed by fluid resuscitation alone. \u2018FF\u2019 stresses the importance of double fluid replacement compared to DKA due to severe dehydration and \u2018ER\u2019 electrolyte replacement due to profound losses and imbalances. \u2018EN\u2019 denotes the potential for encephalopathy and the requirement for a controlled serum osmolality reduction. \u2018CE\u2019 indicates cerebral edema, a rare complication in HHS. \u2018S\u2019 signifies systemic multiorgan failure. We categorize the associated risks into three mnemonic groups: the 3Rs (renal failure, respiratory distress, rhabdomyolysis), the 3Hs (heart failure, hypercoagulation, hyperthermia), and AP (arrhythmias, pancreatitis) to facilitate awareness and screening of HHS.<\/jats:p>","DOI":"10.3390\/children10111773","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:44:03Z","timestamp":1698756243000},"page":"1773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pediatric Hyperglycemic Hyperosmolar Syndrome: A Comprehensive Approach to Diagnosis, Management, and Complications Utilizing Novel Summarizing Acronyms"],"prefix":"10.3390","volume":"10","author":[{"given":"Naser Amin","family":"Zahran","sequence":"first","affiliation":[{"name":"Lurie Children\u2019s at Northwestern Medicine Central DuPage Hospital, Winfield, IL 60190, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-9864","authenticated-orcid":false,"given":"Shaheen","family":"Jadidi","sequence":"additional","affiliation":[{"name":"Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). Standards of medical care in diabetes\u20142013. Diabetes Care, 36, S11\u2013S66.","DOI":"10.2337\/dc13-S011"},{"key":"ref_2","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2000). Endotext, MDText.com Inc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.2337\/dci18-0023","article-title":"Type 1 Diabetes in Children and Adolescents: A Position Statement by the American Diabetes Association","volume":"41","author":"Chiang","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.2337\/dc14-0984","article-title":"Hyperosmolar hyperglycemic state: A historic review of the clinical presentation, diagnosis, and treatment","volume":"37","author":"Pasquel","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11702","DOI":"10.12998\/wjcc.v10.i32.11702","article-title":"Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state","volume":"10","author":"Hassan","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.7748\/ns.2019.e11387","article-title":"Prevention and management of hyperglycaemic crisis","volume":"34","author":"Broadley","year":"2019","journal-title":"Nurs. Stand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"726","DOI":"10.4158\/EP-2018-0120","article-title":"Pediatric Diabetic Ketoacidosis With Hyperosmolarity: Clinical Characteristics and Outcomes","volume":"24","author":"Agrawal","year":"2018","journal-title":"Endocr. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11892-019-1205-7","article-title":"Care of Children and Adolescents with Diabetes Mellitus and Hyperglycemia in the Inpatient Setting","volume":"19","author":"Kharode","year":"2019","journal-title":"Curr. Diab. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1210\/jc.2007-2577","article-title":"Thirty years of personal experience in hyperglycemic crises: Diabetic ketoacidosis and hyperglycemic hyperosmolar state","volume":"93","author":"Kitabchi","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s41969-022-00164-1","article-title":"Hyperosmolar hyperglycemic state in children: Case report and review of the literature","volume":"15","author":"Shahramian","year":"2022","journal-title":"J. Klin. Endokrinol. Stoffwechs."},{"key":"ref_11","unstructured":"Sperling, M.A. (2021). Sperling Pediatric Endocrinology, Elsevier. [5th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e16992","DOI":"10.1097\/MD.0000000000016992","article-title":"Tacrolimus-induced diabetic ketoacidosis with subsequent rapid recovery of endogenous insulin secretion after cessation of tacrolimus: A case report with review of literature","volume":"98","author":"Maruyama","year":"2019","journal-title":"Medicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.4103\/0366-6999.191855","article-title":"Diagnosis and Management of Kearns-Sayre Syndrome Rely on Comprehensive Clinical Evaluation","volume":"129","author":"Yu","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1097\/PEC.0b013e31825d23c9","article-title":"Hyperglycemic hyperosmolar syndrome in the pediatric patient: A case report and review of the literature","volume":"28","author":"Bassham","year":"2012","journal-title":"Pediatr. Emerg. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.mcna.2016.12.011","article-title":"Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State","volume":"101","author":"Fayfman","year":"2017","journal-title":"Med. Clin. N. Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107869","DOI":"10.1016\/j.diabres.2019.107869","article-title":"Hospital admissions for hyperglycemic emergencies in young adults at an inner-city hospital","volume":"157","author":"Wolf","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_17","unstructured":"Adeyinka, A., and Kondamudi, N.P. (2023). StatPearls, StatPearls Publishing LLC."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2333794x16671391","DOI":"10.1177\/2333794X16671391","article-title":"Rhabdomyolysis in Pediatric Patients with Diabetic Ketoacidosis or Hyperglycemic Hyperosmolar State: A Case Series","volume":"3","author":"Mercer","year":"2016","journal-title":"Glob. Pediatr. Health"},{"key":"ref_19","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2000). Endotext, MDText.com, Inc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1016\/j.jcjd.2017.10.013","article-title":"Hyperglycemic Emergencies in Adults","volume":"42","author":"Goguen","year":"2018","journal-title":"Can. J. Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.emc.2005.03.006","article-title":"Hyperosmolar hyperglycemic state","volume":"23","author":"Nugent","year":"2005","journal-title":"Emerg. Med. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"488","DOI":"10.12998\/wjcc.v2.i10.488","article-title":"Diabetes mellitus and electrolyte disorders","volume":"2","author":"Liamis","year":"2014","journal-title":"World J. Clin. Cases WJCC"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2337\/diaspect.15.1.28","article-title":"Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome","volume":"15","author":"Umpierrez","year":"2002","journal-title":"Diabetes Spectr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.2337\/diacare.27.7.1541","article-title":"Cerebral edema in childhood diabetic ketoacidosis: Natural history, radiographic findings, and early identification","volume":"27","author":"Muir","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/pgmj.2002.004291","article-title":"Hyperglycaemic crises and lactic acidosis in diabetes mellitus","volume":"80","author":"English","year":"2004","journal-title":"Postgrad. Med. J."},{"key":"ref_26","first-page":"332","article-title":"Change in blood\u2013brain barrier permeability during pediatric diabetic ketoacidosis treatment","volume":"11","author":"Vavilala","year":"2010","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_27","unstructured":"Rose, K.L. (2009). Cerebral Edema in Diabetic Ketoacidosis. [Ph.D. Thesis, The University of Western Ontario]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.eprac.2022.06.001","article-title":"What Is the Optimal Speed of correction of the Hyperosmolar Hyperglycemic State in Diabetic Ketoacidosis? An Observational Cohort Study of US Intensive Care Patients","volume":"28","author":"Blank","year":"2022","journal-title":"Endocr. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sasb\u00f3n, J.S., and Arroyo, H. (2014). Toxic Metabolic Encephalopathy. Pediatric Critical Care Medicine: Volume 2: Respiratory, Cardiovascular and Central Nervous Systems, Northwestern University.","DOI":"10.1007\/978-1-4471-6356-5_39"},{"key":"ref_30","unstructured":"Pituitary, P. (2011). CHAPTER 10. Williams Textbook of Endocrinology E-Book, Elsevier."},{"key":"ref_31","unstructured":"Adrogu\u00e9, H.J., and Madias, N.E. (2007). Diseases of the Kidney and Urinary Tract, Lippincott Williams & Wilkins. [8th ed.]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jpeds.2004.03.045","article-title":"Mechanism of cerebral edema in children with diabetic ketoacidosis","volume":"145","author":"Glaser","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_33","first-page":"2280","article-title":"Hyperglycemic Crises: A General Review","volume":"4","author":"Salamanca","year":"2022","journal-title":"Open Access J. Biomed. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/08860229509037610","article-title":"The clinical and biochemical features of acute renal failure due to rhabdomyolysis","volume":"17","author":"Woodrow","year":"1995","journal-title":"Ren. Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jemermed.2004.04.006","article-title":"Electrocardiographic manifestations: Electrolyte abnormalities","volume":"27","author":"Diercks","year":"2004","journal-title":"J. Emerg. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: A review","volume":"10","author":"Rosenberg","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1097\/00000542-199606000-00014","article-title":"Chlorocresol, an additive to commercial succinylcholine, induces contracture of human malignant hyperthermia-susceptible muscles via activation of the ryanodine receptor calcium sup 2+ channel","volume":"84","author":"Tegazzin","year":"1996","journal-title":"J. Am. Soc. Anesthesiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.2337\/diacare.26.2007.S109","article-title":"Hyperglycemic crises in patients with diabetes mellitus","volume":"26","author":"Kitabchi","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_39","first-page":"859","article-title":"Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state","volume":"168","author":"Chiasson","year":"2003","journal-title":"Can. Med. Assoc. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0749-0704(05)70153-6","article-title":"Management of decompensated diabetes: Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome","volume":"17","author":"Magee","year":"2001","journal-title":"Crit. Care Clin."},{"key":"ref_41","unstructured":"Rewers, A. (2021). Acute Metabolic Complications in Diabetes."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/pedi.13406","article-title":"ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state","volume":"23","author":"Glaser","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_43","unstructured":"Assadi, F. (2023). Pediatric Fluid, Electrolyte, and Acid-Base Disorders: A Case-Based Approach, Elsevier Health Sciences."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11154-019-09483-2","article-title":"Therapeutic hypernatremia management during continuous renal replacement therapy with elevated intracranial pressures and respiratory failure","volume":"20","author":"Zsom","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.jemermed.2013.03.040","article-title":"Hyperglycemic crisis","volume":"45","author":"Hack","year":"2013","journal-title":"J. Emerg. Med."},{"key":"ref_46","unstructured":"Pope, A., French, G., and Longnecker, D.E. (1999). Fluid Resuscitation: State of the Science for Treating Combat Casualties and Civilian Injuries, National Academies Press."},{"key":"ref_47","unstructured":"Fleisher, G.R., and Ludwig, S. (2010). Textbook of Pediatric Emergency Medicine, Lippincott Williams & Wilkins."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101418","DOI":"10.1016\/j.disamonth.2022.101418","article-title":"Diabetic ketoacidosis","volume":"69","author":"Calimag","year":"2023","journal-title":"Dis. Mon."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18S","DOI":"10.1592\/phco.31.5.18S","article-title":"Current therapeutic options for hyponatremia: Indications, limitations, and confounding variables","volume":"31","author":"Human","year":"2011","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jpeds.2010.09.048","article-title":"Hyperglycemic hyperosmolar syndrome in children: Pathophysiological considerations and suggested guidelines for treatment","volume":"158","author":"Zeitler","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1213\/ANE.0b013e318222af2e","article-title":"Future directions in malignant hyperthermia research and patient care","volume":"113","author":"Dirksen","year":"2011","journal-title":"Anesth. Analg."},{"key":"ref_52","first-page":"1","article-title":"Management of venous thromboembolisms: Part I. The consensus for deep vein thrombosis","volume":"32","author":"Wang","year":"2016","journal-title":"Acta Cardiol. Sin."},{"key":"ref_53","first-page":"1","article-title":"Diabetic emergencies: New strategies for an old disease","volume":"16","author":"Beltran","year":"2014","journal-title":"Emerg. Med. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1515\/jpem-2017-0183","article-title":"Severe complications after initial management of hyperglycemic hyperosmolar syndrome and diabetic ketoacidosis with a standard diabetic ketoacidosis protocol","volume":"30","author":"Nambam","year":"2017","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1016\/j.ejim.2011.06.014","article-title":"Serum osmolarity as an outcome predictor in hospital emergency medical admissions","volume":"23","author":"Nicholson","year":"2012","journal-title":"Eur. J. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yosypiv, I.V. (2014). Diabetes in Children and Adolescents. Diabetes Kidney Dis., 63\u201375.","DOI":"10.1007\/978-1-4939-0793-9_6"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jpeds.2009.11.057","article-title":"Hyperglycemic hyperosmolar state: An emerging pediatric problem","volume":"156","author":"Rosenbloom","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/jpc.12980","article-title":"Hyperglycaemic hyperosmolar syndrome in children: Patient characteristics, diagnostic delays and associated complications","volume":"52","author":"Price","year":"2016","journal-title":"J. Paediatr. Child Health"},{"key":"ref_59","first-page":"100140","article-title":"Hyperglycemia and multiple organ failure in a male adolescent","volume":"28","author":"Zahran","year":"2023","journal-title":"J. Clin. Transl. Endocrinol. Case Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1399-5448.2009.00569.x","article-title":"Diabetic ketoacidosis in children and adolescents with diabetes","volume":"10","author":"Wolfsdorf","year":"2009","journal-title":"Pediatr. Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1755-7682-7-50","article-title":"Serum C-peptide assay of patients with hyperglycemic emergencies at the Lagos State University Teaching Hospital (LASUTH), Ikeja","volume":"7","author":"Akinlade","year":"2014","journal-title":"Int. Arch. Med."},{"key":"ref_62","unstructured":"Philips, B. (2010). Core Topics in Endocrinology in Anaesthesia and Critical Care, Cambridge University Press."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/11\/1773\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:15:17Z","timestamp":1760130917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/11\/1773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["children10111773"],"URL":"https:\/\/doi.org\/10.3390\/children10111773","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]}}}