Hyperglycemic Hyperosmotic Syndrome in Children

Once again, I am reminded at how little I actually know. I am also reminded at how awesome it is (and incredibly brilliant!) to be surrounded by people who are talented, dedicated, and intelligent (often much more than myself). Last week, one of my stellar third year Pediatric EM Fellows taught me something that I had not even considered – Hyperglycemic, Hyperosmotic Syndrome occurring in children… and now I will share that with you. Much appreciation and thanks to Dr. Vanessa Goff!!

We are taught to be on the lookout for diabetic ketoacidosis in kids. Whether it’s a kid with vague abdominal pain and vomiting, a kid with vomiting and no diarrhea, or a kid with recurrent candida diaper rashes.  We’re given a healthy fear of the complications associated with DKA (ex. Hamman’s Syndrome and Cerebral Edema). Did you know there is another hyperglycemic emergency in kids to be on the lookout for as well? Kids can also get hyperglycemic, hyperosmotic syndrome (HHS). They can even have both DKA and HHS at the same time. How do we differentiate DKA, HHS and a mixed presentation and how do we manage them? Let’s take a minute to digest a morsel on that:

Hyperglycemic Emergencies: Basics

• There is a critical deficit in the action of insulin, resulting in hyperglycemia
• Counter-regulatory hormones glucagon, catecholamines, cortisol and growth hormone are released with other pro-inflammatory cytokines
• Hepatic and renal glucose production via gluconeogenesis and glycogenolysis is stimulated
• Insulin-dependent peripheral tissues reduce their glucose utilization
• DKA
  • There is increased lipolysis and ketogenesis
  • Hyperglycemia and hyperketonemia cause osmotic diuresis with electrolyte wasting
• HHS
  • There is a disordered renal response with reduced cationic exchange
  • Initially unbalanced free water loss in urine and increased serum osmolarity
  • Intravascular volume preserved initially secondary to hyperosmolarity

Presentation Distinction between DKA and HHS

Presentation for Diabetic Ketoacidosis (DKA)

• Presents with dehydration and acidosis 
  • > 5-10% body weight
• Classic symptoms include polyuria, polydipsia, polyphagia, weight loss
• Commonly occurs with new onset diabetes in children
  • 30% of children with type 1 diabetes
  • 10% of children with type 2 diabetes
• Often triggered by intercurrent illnesses or inadequate insulin administration
  • Risk in kids with known DKA is 1-10% per patient year
• Can also be triggered by high-dose steroids, atypical antipsychotics, diazoxide and immunosuppressants even in kids without underlying diabetes

Presentation for Hyperglycemic Hyperosmolar syndrome (HHS)

• Profound dehydration
  • > 12-15% body weight
  • Often will be hypernatremic (need to correct sodium level for hyperglycemia)
• Can present with vomiting and abdominal pain and/or polyuria and polydipsia
• More likely to present with altered mental status
• More likely to develop complications than patients with DKA
• Often occurs with new onset diabetes in children
  • Male:Female ratio of 3.5 : 1

Diagnosis of DKA vs HHS vs Mixed

• DKA
  • Blood glucose ≥ 200mg/dL
  • pH ≤ 7.3 or bicarbonate ≤ 15
  • Ketonuria and or elevated serum beta hydroxybutyrate
• HHS
  • Osmolarity ≥ 320mOsm/kg
  • Blood glucose ≥ 600mg/dL
  • Absence of acidosis with pH >7.3
  • Absence of large ketosis
• Mixed DKA/HHS
  • Osmolarity ≥ 320mOsm/kg
  • Blood glucose ≥ 600mg/dL
  • pH ≤ 7.3 or bicarbonate ≤ 15
  • Ketonuria and or elevated serum beta hydroxybutyrate

Basic Management Concepts

• DKA
  • Fluid resuscitate first with isotonic fluid bolus
    • Usually 10-20cc/kg bolus
  • Initiate insulin at 0.05-0.1u/kg/hr
    • Expect glucose decline of 36-90mg/dL/hr
  • Transition insulin therapy once acidosis and ketosis improve
• HHS
  • Aggressively fluid resuscitate with isotonic fluids
  • Initiate insulin at 0.025-0.05u/kg/hr once glucose declines <50mg/dL/hr with fluids alone
    • Early insulin initiation can result in vascular collapse from fluid shifting out of intravascular space
  • Stop insulin therapy once hyperglycemia improves
• Mixed DKA/HHS
  • Aggressive fluid resuscitation
    • Increased morbidity and mortality if <40ml/kg given in first 6 hours
    • Fluid rate for multi-bag system generally exceeds that used in DKA
  • Initiate insulin after initial fluid bolus
  • Electrolyte repletion as necessary
  • Transition insulin therapy once acidosis and ketosis improve

Moral of the Morsel

• Kids can get HHS. If your glucose is a bit higher than your typical DKA and the (corrected) sodium is elevated, calculate your osmolarity.
• Kids can have both HHS and DKA at the same time. If you meet osmolarity criteria of HHS and acidosis/ketosis criteria of DKA, you likely have a mixed picture.
• A mixed picture needs a mixed management. Aggressively fluid resuscitation the HHS component and provide insulin infusion until the DKA component corrects.

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Bassham, B., Estrada, C., & Abramo, T. (2012). Hyperglycemic hyperosmolar syndrome in the pediatric patient a case report and review of the literature. Pediatric Emergency Care, 28(7), 699–702. https://doi.org/10.1097/PEC.0b013e31825d23c9 

Cashen, K., & Petersen, T. (2019). Diabetic ketoacidosis. Pediatrics in Review, 40(8), 412–420. https://doi.org/10.1542/pir.2018-0231 

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Szmygel, Lukasz, Kosiak, W., Zorena, K., & My|liwiec, M. (2016). Optic Nerve and Cerebral Edema in the Course of Diabetic Ketoacidosis. Current Neuropharmacology, 14(8), 784–791. https://doi.org/10.2174/1570159×14666160225155151 

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Zeitler, P., Haqq, A., Rosenbloom, A., & Glaser, N. (2011). Hyperglycemic hyperosmolar syndrome in children: Pathophysiological considerations and suggested guidelines for treatment. Journal of Pediatrics, 158(1), 9-14.e2. https://doi.org/10.1016/j.jpeds.2010.09.048