Hyperglycemic crises

Last updated: November 18, 2022

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Hyperglycemic crises can be the initial presentation of diabetes mellitus or complications due to other diseases. Inadequate insulin replacement (e.g., due to poor adherence) or increased insulin demand (e.g., during times of acute illness, surgery, or stress) may lead to acute hyperglycemia. In diabetic ketoacidosis (DKA), which is more common in patients with type 1 diabetes, no insulin is available to suppress lipolysis, resulting in ketone formation and acidosis. In a hyperosmolar hyperglycemic state (HHS), which is more common in patients with type 2 diabetes, there is still some insulin available, so there is minimal or no ketone formation. Clinical features of both DKA and HHS include polyuria, polydipsia, nausea and vomiting, volume depletion (e.g., dry oral mucosa, decreased skin turgor), and eventually mental status changes and coma. Features unique to DKA include a fruity odor to the breath, hyperventilation, and abdominal pain. DKA typically has an acute onset (e.g., within hours) while HHS usually develops insidiously (e.g., within days) and manifests with more extreme volume depletion. The mainstay of treatment for both DKA and HHS consists of IV fluid resuscitation, electrolyte repletion, and insulin therapy.

For patients with hyperglycemia without DKA or HHS, see also “Inpatient management of hyperglycemia.”

Comparison of DKA and HHS
Diabetic ketoacidosis Hyperosmolar hyperglycemic state
Insulin
  • Absent
  • Present

Ketones

  • Present
  • Absent

Pathogenesis

Signs/symptoms

Labs

Complications

Treatment

The most important findings of diabetic ketoacidosis (DKA) are: Delirium/psychosis, Dehydration, Kussmaul respirations, Abdominal pain/nausea/vomiting, fruity (Acetone) breath odor.

DKA, often precipitated by infection (e.g., pneumonia, urinary tract infection), is a common initial manifestation of type 1 diabetes mellitus (∼ 30% of cases).

Diabetic ketoacidosis (DKA)

DKA primarily affects patients with type 1 diabetes.

Osmotic diuresis and hypovolemia

Hypovolemia resulting from DKA can lead to acute kidney injury (AKI) due to decreased renal blood flow! Hypovolemic shock may also develop.

Metabolic acidosis with increased anion gap

DKA is an important cause of anion gap metabolic acidosis with respiratory compensation.

Intracellular potassium deficit

  • As a result of hyperglycemic hyperosmolality, potassium shifts along with water from inside cells to the extracellular space and is lost in the urine.
  • Insulin normally promotes cellular potassium uptake but is absent in DKA, compounding the problem.
  • A total body potassium deficit develops in the body, although serum potassium may be normal or even paradoxically elevated.
  • Insulin deficiency → hyperosmolality K+ shift out of cells + lack of insulin to promote K+ uptake → intracellular K+depleted → total body K+ deficit despite normal or even elevated serum K+

There is a total body potassium deficit in DKA. This becomes important during treatment, when insulin replacement leads to rapid potassium uptake by depleted cells and patients may require potassium replacement.

Hyperosmolar hyperglycemic state (HHS)

Signs and symptoms of both DKA and HHS

Patients with known diabetes who present with nausea and/or vomiting should be immediately assessed for DKA/HHS.

Specific findings in DKA [1]

  • Rapid onset (< 24 h) in contrast to HHS
  • Abdominal pain
  • Fruity odor on the breath (from exhaled acetone)
  • Hyperventilation: long, deep breaths (Kussmaul respirations)

Comparison: DKA vs. HHS

Clinical findings of DKA versus HHS
DKA HHS
Diabetes Type 1 Type 2
History of severe stress, illness, hospitalization + +
Polyuria, polydipsia + +
Nausea, vomiting + +/-
Dehydration + ++ (Profound)
Altered mental status Possible Possible
Hyperventilation or Kussmaul breathing + -
Fruity breath + -
Severe abdominal pain + -
Onset Rapid (< 24 h) Insidious (days)

In DKA, absolute insulin deficiency leads to the rapid development of symptomatic acidosis and an early presentation (within hours) with only moderate hyperglycemia (> 250 mg/dL).

In HHS, residual insulin production prevents significant ketoacidosis leading to insidious progression (days to weeks) and profound hypovolemia and hyperglycemia (> 600 mg/dL).

Approach [2][3]

DKA is the diagnosis in patients with type 1 diabetes who have hyperglycemia, ketonuria, and high anion gap metabolic acidosis with decreased bicarbonate!

HHS is the diagnosis in patients with type 2 diabetes who have hyperglycemia and hyperosmolality!

Overview of laboratory findings in hyperglycemic crises [2]

Diagnostic criteria for DKA and HHS
Laboratory test DKA HHS
BMP Glucose
  • < 600 mg/dL (< 33.3 mmol/L)
  • About 10% of patients with DKA will be euglycemic (e.g., glucose ≤ 250 mg/dL) [2]
  • > 600 mg/dL (> 33.3 mmol/L)
Bicarbonate
  • < 18 mEq/L (< 18 mmol/L)
  • > 18 mEq/L (> 18 mmol/L)
Anion gap
Urinalysis
Serum β-hydroxybutyrate
  • Elevated
  • Normal
Blood gas
  • pH ≤ 7.30
  • pH > 7.30
Serum osmolality
  • Normal or mildly elevated
  • Elevated > 320 mosm/kg (> 320 mmol/kg)

Normal serum osmolality in a stuporous patient rules out HHS and should prompt investigation for other causes of altered mental status.

Euglycemia does not rule out DKA! Assess ketone levels in all patients with high anion gap metabolic acidosis to evaluate for euglycemic DKA.

Electrolytes and renal function [2][3]

For anion gap calculation, use the measured serum sodium concentration rather than the corrected serum sodium concentration. [7]

Additional diagnostic workup [2][3][8]

Additional diagnostics are indicated depending on suspected precipitating causes and differential diagnoses.

Infection, myocardial infarction, and pancreatitis should be ruled out in all patients presenting with a hyperglycemic crisis.

Pregnancy and SGLT2-inhibitors can cause euglycemic DKA (i.e., high anion gap metabolic acidosis with normal or near-normal glucose). [9][11]

Severity of DKA [2]

Arterial pH Serum bicarbonate Anion gap Mental status
Mild > 7.24 15–18 mEq/L > 10 mEq/L Alert
Moderate 7.0–7.24 10–15 mEq/L > 12 mEq/L Alert or drowsy
Severe < 7.0 < 10 mEq/L > 12 mEq/L Stuporous

DKA and HHS are both managed by restoring intravascular volume, repleting water and electrolyte deficits, repleting insulin, and treating the underlying cause.

Approach [2][8][12]

The goal of therapy is the resolution of ketonemia and acidosis (i.e., closure of the anion gap) in DKA and of hyperglycemia and hyperosmolarity in HHS.

Monitoring [2][14][15]

  • Hourly vitals and mental status and hydration status
  • POC glucose every 1–2 hours until blood glucose < 250 mg/dL and hourly blood glucose readings are stable for at least 3 hours; then decrease monitoring to every 2–4 hours
  • Serum osmolality every 1–4 hours
  • Blood gas and BMP with electrolytes every 2–4 hours

Monitoring of volume status, serum glucose, serum electrolytes, and acid-base status at regular intervals is essential.

Disposition [2][12][16]

  • Admission
    • Indicated for all patients with HHS and most patients with DKA [17]
    • Consider ICU admission for patients with any of the following:
  • Discharge may be considered for patients with mild DKA and all of the following:
    • Resolved anion gap acidosis
    • No concerning precipitating cause
    • Toleration of oral hydration and nutrition
    • Ability to adhere to discharge instructions, including outpatient follow-up

Pregnant patients with DKA should be assessed by an endocrinologist and obstetrician because of the potential for a high-risk pregnancy.

Fluid resuscitation [2][8][14]

Carefully monitor for signs of fluid overload during fluid resuscitation, especially in patients with comorbidities (e.g., CHF, CKD). [12]

Electrolyte repletion [2]

Serum K+ Recommended dose [18]
< 3.3 mEq/L

3.3–5.2 mEq/L

> 5.2 mEq/L

  • No repletion recommended

It is critical that potassium levels are confirmed to be > 3.3 mEq/L before administering insulin, as insulin will lower serum potassium and potentially cause severe hypokalemia.

Acid-base status [2]

General principles [2][14][19]

  • The administration of insulin is essential in halting lipolysis and ketoacidosis in patients with DKA.
  • Recommended regimens [2]
  • The initial goal is to decrease blood glucose levels by 10% per hour (∼ 50–75 mg/dL/hour).
  • Check glucose level hourly and titrate as needed.
  • In patients requiring ongoing insulin infusion:
    • Switch IV fluids to D5NS or D5½NS infusion when serum glucose falls to ∼ 200 mg/dL (DKA) or 300 mg/dL (HHS).
    • Titrate insulin to a goal serum glucose of 150–200 mg/dL (DKA) or 200–300 mg/dL (HHS).

Resolution and transition to subcutaneous insulin [2]

Criteria for the resolution of hyperglycemic crises [2][3]
DKA HHS
  • Glucose < 200 mg/dL
  • PLUS at least two of the following:
  • Criteria for transitioning to subcutaneous insulin:
    • Resolution of hyperglycemic crisis
    • Precipitating factor identified and treated
    • Patient tolerating oral nutrition and eating consistently
  • Procedure for transitioning to subcutaneous insulin:

All other causes of altered mental status must be considered in the differential diagnosis of DKA/HHS. Intoxication and other endocrine disorders, as well as gastroenteritis, myocardial infarction, pancreatitis, and other causes of high anion gap metabolic acidosis, should all be excluded.

We list the most important complications. The selection is not exhaustive.

  1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. 2009; 32 (7): p.1335-1343. doi: 10.2337/dc09-9032 . | Open in Read by QxMD
  2. Gosmanov AR, Gosmanova EO, Kitabchi AE, et al. Hyperglycemic Crises: Diabetic Ketoacidosis (DKA), And Hyperglycemic Hyperosmolar State (HHS). endotext.org. 2018 .
  3. Van Ness-Otunnu R, Hack JB. Hyperglycemic Crisis. J Emerg Med. 2013; 45 (5): p.797-805. doi: 10.1016/j.jemermed.2013.03.040 . | Open in Read by QxMD
  4. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  5. Cardoso L, Vicente N, Rodrigues D, Gomes L, Carrilho F. Controversies in the management of hyperglycaemic emergencies in adults with diabetes. Metabolism. 2017; 68 : p.43-54. doi: 10.1016/j.metabol.2016.11.010 . | Open in Read by QxMD
  6. Kitabchi AE, Umpierrez GE, Fisher JN, Murphy MB, Stentz FB. Thirty Years of Personal Experience in Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. J Clin Endocrinol Metab. 2008; 93 (5): p.1541-1552. doi: 10.1210/jc.2007-2577 . | Open in Read by QxMD
  7. Westerberg D. Diabetic Ketoacidosis: Evaluation and Treatment. Am Fam Physician. 2013 .
  8. American Diabetes Association. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2017; 41 (Supplement 1): p.S144-S151. doi: 10.2337/dc18-s014 . | Open in Read by QxMD
  9. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis - a systematic review. Ann. Intensive Care. 2011; 1 (1). doi: 10.1186/2110-5820-1-23 . | Open in Read by QxMD
  10. Savage MW, Dhatariya KK, Kilvert A, et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabetic Medicine. 2011; 28 (5): p.508-515. doi: 10.1111/j.1464-5491.2011.03246.x . | Open in Read by QxMD
  11. Tintinalli JE, Stapczynski JS, Ma OJ, Yealy D, Meckler GD, Cline DM. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9th edition. McGraw Hill Professional ; 2019
  12. Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Med Clin North Am. 2017; 101 (3): p.587-606. doi: 10.1016/j.mcna.2016.12.011 . | Open in Read by QxMD
  13. Westerberg DP. Diabetic Ketoacidosis: Evaluation and Treatment. Am Fam Physician. 2013; 87 (5): p.337-346.
  14. Trachtenbarg DE. Diabetic ketoacidosis.. Am Fam Physician. 2005; 71 (9): p.1705-14.
  15. Kelly A-M. The case for venous rather than arterial blood gases in diabetic ketoacidosis. Emergency Medicine Australasia. 2006; 18 (1): p.64-67. doi: 10.1111/j.1742-6723.2006.00803.x . | Open in Read by QxMD
  16. Orban JC, Maizière EM, Ghaddab A, Van Obberghen E, Ichai C. Incidence and characteristics of acute kidney injury in severe diabetic ketoacidosis.. PLoS ONE. 2014; 9 (10): p.e110925. doi: 10.1371/journal.pone.0110925 . | Open in Read by QxMD
  17. Beck LH. Should the actual or the corrected serum sodium be used to calculate the anion gap in diabetic ketoacidosis?. Cleve Clin J Med. 2001; 68 (8): p.673-674. doi: 10.3949/ccjm.68.8.673 . | Open in Read by QxMD
  18. Kamalakannan D. Diabetic ketoacidosis in pregnancy. Postgrad Med J. 2003; 79 (934): p.454-457. doi: 10.1136/pmj.79.934.454 . | Open in Read by QxMD
  19. Yadav D, Nair S, Norkus EP, Pitchumoni CS. Nonspecific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: incidence and correlation with biochemical abnormalities. Am J Gastroenterol. 2000; 95 (11): p.3123-3128. doi: 10.1111/j.1572-0241.2000.03279.x . | Open in Read by QxMD
  20. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of Sglt-2 Inhibitors and Diabetic Ketoacidosis. Endocr Pract. 2016; 22 (6): p.753-762. doi: 10.4158/ep161292.ps . | Open in Read by QxMD

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