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Extreme hyperglycemia and hyperosmolar hyperglycemic syndrome

Appel, Susan J. PhD, ACNP-BC, FNP-BC, CCRN, FAHA, FAANP

doi: 10.1097/01.NPR.0000508175.20325.ca
Online exclusive: Clinical Case Report

Susan J. Appel is a professor at Capstone College of Nursing, University of Alabama, Tuscaloosa, Ala.

The author has disclosed that she has no financial relationships related to this article.

Mr. T's glucose registered as “high” on his home glucose meter. Because he was not feeling well and was perceived by his family as confused, his son brought him to the ED, where his blood glucose measured 1,596 mg/dL. A noncontrast computed tomography (CT) scan of the head was negative for acute intracranial pathology. Mr. T was diagnosed with hyperglycemia by the ED provider and was admitted to the hospitalist service. After obtaining a history and physical, the NP for the hospitalist service diagnosed him with hyperosmolar hyperglycemic syndrome (HHS) and uncontrolled diabetes mellitus because of his elevated blood glucose level and his A1c was 13.5%. A hallmark feature of HHS is extreme hyperglycemia greater than 600 mg/dL (see Mr. T's electronic medical record and Mr. T's fasting labs).

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Background

Other names for HHS have included hyperglycemic hyperosmolar coma; hyperglycemic hyperosmolar nonketotic state or syndrome; nonketotic hyperglycemic hyperosmolar coma; and hyperosmolar nonketotic coma. However, because only about 20% of patients manifest a coma, the term “coma” is no longer used.1 Patients who develop HHS are often already ill, usually with an infection or recent pathology, such as myocardial infarction (MI) or stroke.

The mortality with HHS is as high as 20% to 40%, which is 10 times higher than diabetic ketoacidosis (DKA).2,3 The high mortality of HHS is partly due to the syndrome occurring more commonly in older adults and among long-term care residents, along with the lack of prompt identification of the syndrome and failure to administer aggressive fluid resuscitation.2,4

However, the cause of mortality in DKA is metabolic acidosis; in HHS, it is profound hypovolemia. Often, HHS is misdiagnosed as DKA, and adequate fluid is not administered.5,6 For these reasons, a differential diagnosis between DKA and HHS should always be made (see Differentiating DKA from HHS).3,5,7,8

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Review of the case

It is clear Mr. T did not have DKA because his ketones were low and his glucose level was over 600 mg/dL with a normal level of C-peptide, which indicated type 2 diabetes mellitus (T2DM). The hallmark presence of a hyperosmotic state and nonanion gap are defining manifestations of HHS.9

Adult patients with T2DM are most likely to manifest HHS. Mr. T had hallmark findings of T2DM: adequate C-peptide level, metabolic syndrome, and signs of insulin resistance (acanthosis nigricans and acrochordons).9 C-peptide levels are precursors to insulin and are used to assess the degree of insulin secretion; they are commonly used to differentiate between type 1 diabetes mellitus (T1DM) and T2DM.10

In T1DM, the C-peptide levels are nondetectable to low. Mr. T's C-peptide levels were within normal limits of 1.5 ng/mL, indicating that his body is making insulin, but he is insulin resistant and has T2DM. Both acanthosis nigricans and acrochordons are commonly seen in insulin-resistant states such as T2DM and develop secondary to stimulation of melanocytes by hyperinsulinemia.9 Mr. T's arterial blood gas results showed findings of HHS, including an absence of metabolic acidosis and a pH greater than 7.30. Likewise, his serum osmolality was high, indicating HHS; his serum creatinine was also high, indicating dehydration from osmotic diuresis. Mr. T's lipid profile was also consistent with T2DM because he presented with a mixed dyslipidemia (elevated low-density lipoprotein [LDL] cholesterol and hypertriglyceridemia). All of these findings help to differentially diagnose HHS from DKA.

Mr. T's glucose logbook revealed he had been testing his blood glucose twice a day (before breakfast and dinner each day). The range was 120 to 200 mg/dL, with an average fasting blood glucose of 170 mg/dL. He reports adhering to his diet, exercise, and pharmacology therapy. There were no signs of infection upon review of his fasting labs.

Likewise, Mr. T's chest X-ray and urinalysis were free from signs of bacterial infection; however, the urinalysis revealed yeast, which is indicative of poorly controlled diabetes. Therefore, the NP reinterviewed him, starting with his list of medications and asking if he had taken any corticosteroids, diuretics, or antiseizure medications. Mr. T then stated that he recently received injections in his back (interlaminar epidural corticosteroid injections: between L5 and S1) 2 days prior to admission. The corticosteroid injections were given due to his chronic low back pain from foraminal stenosis and lumbar radiculitis. Corticosteroids may trigger hyperglycemia, especially among patients with diabetes mellitus (see Predisposing factors for HHS).1

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Treatment and management

Initial differential diagnosis of any hyperglycemic crises is imperative. In Mr. T's case, HHS was likely due to the multiple interlaminar epidural corticosteroid injections versus any discernable infection or other acute illness. An I.V. insulin drip was started in the ED. Oral diabetes agents were held while receiving the insulin drip. Isotonic 0.9% sodium chloride and rapid intravascular volume replacement was the next crucial step. Because mortality in HHS is secondary to hypovolemic shock, as much as 2 L of 0.9% sodium chloride may be infused within the first hour of therapy and then reduced.2 Many NPs at this time may change the fluids to half normal saline to minimize the risk of cerebral edema.2,6 Cerebral edema is rare, but evidence suggests that most patients being treated for diabetes mellitus-related hyperglycemic emergencies develop some degree of increased intracranial pressure.11,12 Rapid reduction of blood glucose levels in hyperglycemic states has been associated with a fluid shift, leading to increased cerebrospinal fluid. In these cases, once cerebral edema develops and is coupled with increased intracranial pressure, mortality is 100%.4,12

Table

Table

Table Diffe

Table Diffe

If available, knowing the patient's normal weight can be helpful in judging adequate fluid resuscitation. By comparing the patient's current weight to normal weight, the effectiveness of fluid resuscitation can be gauged because it assists in determining the degree of rehydration needed to achieve euvolemia. The goal is to replace half of fluid deficit in the next 12 hours, and in HHS, it is common for the level of dehydration to be 10 L or more.2 Once blood glucose levels reach 300 mg/dL to 250 mg/dL, I.V. insulin is discontinued, and S.C. insulin may be initiated while frequent monitoring of glucose and electrolytes continues.2

After 48 hours in the ICU, Mr. T's labs were normalized. He was transferred to the telemetry unit and started on insulin detemir [rDNA origin] injection, 20 units subcutaneously each morning and 5 units subcutaneously of insulin aspart [rDNA origin] injection with meals. The certified diabetes educator counseled Mr. T and his wife on diet and medication management. On day four, he was discharged home on those same medications. Upon follow-up 1 week later with his primary practitioner, Mr. T was restarted on metformin hydrochloride extended-release 1,000 mg orally each evening because it had fewer subjective gastrointestinal adverse reactions. In 3 months, his A1c had decreased to 9.0% and in another 3 months reached 7%.5

Hyperglycemia among patients with T2DM is often misdiagnosed as DKA.13 Metabolic acidosis is the major complication in DKA that can lead to death, whereas hypovolemic shock is the critical complication that can lead to death in HHS. The practitioner must be able to correctly differentially diagnose HHS from DKA in order to anticipate and implement appropriate treatment. In HHS, fluid resuscitation is lifesaving, as HHS carries a higher morbidity than DKA.

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Mr. T's electronic medical record

Chief complaint

  • Confusion and altered consciousness

History of present illness

  • The patient is a 67-year-old White male admitted with shortness of breath and confusion via emergency medical services through ED to ICU.
  • CT of the head was negative. On arrival, it was noted his blood glucose was 1,596 mg/dL.
  • He denies any chest pain or shortness of breath.
  • A urinalysis, chest X-ray, and complete blood cell count were obtained. The urinalysis did not appear to show any infection; no white blood cells were present, but some yeast and +1 ketones were present. Mild kidney dysfunction was noted.
  • An insulin drip was started, and the patient was admitted to the ICU.

Past medical history

  • Type 2 diabetes for 10 years
  • Hypothyroidism
  • Hypertension
  • Prostate cancer diagnosed 2 years ago
  • Dyslipidemia
  • Unipolar depression for 7 years
  • Osteoarthritis in both knees
  • Carpal tunnel syndrome
  • Chronic low back pain (with foraminal stenosis and lumbar radiculitis, greater on the right)

Surgical history

  • Cervical laminectomy
  • Prostatectomy

Social history

  • Married for 30 years with three adult children
  • Has run a family-owned restaurant with oldest son for 30 years
  • Denies use of alcohol, tobacco, or street drugs
  • Has exposure to secondhand smoke at the restaurant

Medications

  • Atorvastatin 10 mg orally, every evening
  • Amitriptyline 25 mg orally, once daily
  • Metformin 500 mg orally, twice daily
  • Lisinopril 10 mg orally, once daily
  • Enteric-coated aspirin 81 mg orally, once daily
  • Levothyroxine 25 mcg orally, once daily
  • Glucosamine sulfate 500 mg orally, three times daily
  • Naproxen 220 mg, 2 tablets orally every 12 hours p.r.n. for pain

Physical exam

  • General: White male, morbidly obese, in no acute distress
  • Vital signs: Temperature 98.8° (37.1° C); heart rate 80; respirations 18; BP 148/92; oxygen saturation on room air 98%; body mass index 43; waist circumference 46 inches
  • Head, ears, eyes, nose, throat: Pupils equal and equally reactive to light; full extraocular movements; right and left fundal exam without retinopathy
  • Cardiac: Regular rate and rhythm without murmurs, rubs, or gallops
  • Respiratory: Lungs clear to auscultation bilaterally
  • Abdomen: Non-tender and no costovertebral angle tenderness
  • Genitourinary/rectal: Deferred
  • Musculoskeletal/peripheral vascular: Peripheral pulses 2+, no signs and symptoms of clubbing, cyanosis, and edema
  • Neurologic: Alert, but initially confused as to the year; deep tendon reflex 2+, feet with normal sensation (5.07 monofilament) and vibration
  • Skin: Acanthosis on elbows, knees, and back of neck; acrochordons under the arms
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Predisposing factors for HHS3

  • Infection
  • Other illness (such as MI, heart failure, stroke, or kidney disease)
  • Medications that decrease the effect of insulin in the body (such as corticosteroids or the antiseizure medication phenytoin)
  • Medications (such as diuretics) or conditions that increase fluid loss
  • Stopping insulin or other medications that lower glucose levels
  • Limited access to water (patients with dementia or those who are bedbound)
  • Total parenteral nutrition
  • Unrecognized new-onset T2DM
  • Age >65
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REFERENCES

1. Hemphill RR. Hyperosmolar hyperglycemic state. 2016. http://emedicine.medscape.com/article/1914705-overview1.
2. Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care. 2014;37(11):3124–3131.
3. Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 2011;94(3):340–351.
4. Huang CC, Weng SF, Tsai KT, et al. Long-term mortality risk after hyperglycemic crisis episodes in geriatric patients with diabetes: a national population-based cohort study. Diabetes Care. 2015;38(5):746–751.
5. McCombs DG, Appel SJ, Ward ME. Expedited diagnosis and management of inpatient hyperosmolar hyperglycemic nonketotic syndrome. J Am Assoc Nurse Pract. 2015;27(8):426–432.
6. Wolfsdorf JI, Allgrove J, Craig ME, et al. ISPAD clinical practice consensus guidelines 2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2014;15(suppl 20):154–179.
7. Steenkamp D, Alexanian S, Sternthal E. Atypical diabetes: clarifying the muddy waters. CMAJ. 2014;186(18):1397–1398.
8. Appel SJ, Wadas TM, Rosenthal RS, Ovalle F. Latent autoimmune diabetes of adulthood (LADA): an often misdiagnosed type of diabetes mellitus. J Am Acad Nurse Pract. 2009;21(3):156–159.
9. Saraiya A, Al-Shoha A, Brodell RT. Hyperinsulinemia associated with acanthosis nigricans, finger pebbles, acrochordons, and the sign of Leser-Trélat. Endocr Pract. 2013;19(3):522–525.
10. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803–817.
11. Arieff AI, Kleeman CR. Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J Clin Endocrinol Metab. 1974;38(6):1057–1067.
12. Arieff AI, Kleeman CR. Studies on mechanisms of cerebral edema in diabetic comas: Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits (J. clin. invest. 52:571–583, 1973). J Am Soc Nephrol. 2000;11(9):1776–1788.
13. McCombs DG, Appel SJ, Ward ME. Expedited diagnosis and management of inpatient hyperosmolar hyperglycemic nonketotic syndrome. J Am Assoc Nurse Pract. 2015;27(8):426–432.
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