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Diabetic Emergencies, Diagnosis and Clinical Management: Hyperosmolar non-ketotic hyperglycemia, Part 2

Apr 22, 2013
 
Diabetic_Emergencies

Konstantinos Makrilakis, MD, PhD

Nikolaos Katsilambros, MD, PhD.

The earliest symptoms of marked hyperglycemia are polyuria, polydipsia, and weight loss. Unlike DKA, which usually evolves rapidly over a 24-hour period, symptoms in HHS develop more insidiously, often persisting for several days or even weeks before people seek medical attention and require hospital admission. As the degree or duration of hyperglycemia progresses, neurological symptoms, including lethargy, focal signs, and obtundation, which can progress to coma in later stages, can be seen. Neurological symptoms are most common in HHS (because of higher degrees of dehydration and hyperosmolality — or because of a cerebrovascular accident that precipitated the hyperglycemic crisis), while hyperventilation and abdominal pain are primarily limited to patients with DKA.1

Summary Box

Decreased mental state is the commonest reason why people with HHS are brought to the hospital.

The clinical picture is related to the degree of dehydration and hypovolemia, the degree of hyperosmolality, and the precipitating factor that led to HHS. Polyuria, polydipsia, and weight loss are the usual prodromal symptoms. Due to hypovolemia, patients exhibit impaired peripheral circulation, tachycardia, hypotension, and cold extremities. Mental status may vary from slight confusion/ obtundation to coma. Serum osmolality has been shown to correlate significantly with mental status, both in DKA and HHS, and is the most important determinant of mental status. 7 The severity of hyperosmolality can be evaluated by calculating effective serum osmolality (normal values: 285 ± 5), using the formula 7:

Effective osmolality(mOsm/kg) = 2 ×[measured serum Na+ (mEq/L)] + glucose(mg/dl)/18

In the calculation of effective serum osmolality, the urea concentration is not taken into account because urea is freely permeable and its accumulation does not induce major changes in intracellular (including brain) volume or the osmotic gradient across the cell membrane.

Total serum osmolality (normal values: 290 ± 5) is calculated by the formula:

Total osmolality (mOsm/kg) = 2 x [measured serum Na+ (mEq/L)] + gucose (mg/dl)/18 + BUN (mg/dl)/2.8

Neurological deterioration primarily occurs in patients with an effective serum osmolality > 320-330 mOsm/kg. If the patient ‘s mental status is out of proportion to the effective osmolality, another etiology for impaired mental status should be sought. The rise in serum osmolality is only in part due to the rise in serum glucose. The increase in serum osmolality pulls water out of the cells, which tends to reduce the serum osmolality toward normal and lower the serum sodium. The marked hyperosmolality seen in HHS is primarily due to the glucose-induced osmotic diuresis that causes water loss in excess of sodium and potassium. This is the reason why patients with end-stage renal disease (who do not produce any urine) can develop severe hyperglycemia, with serum glucose concentrations that can exceed 1000-1500 mg/dl (56-83 mmol/L), but because there is little or no osmotic diuresis the rise in serum osmolality is limited, hyponatremia is present, and they develop few or no neurological symptoms. 11

 

Summary Box

The presence of stupor or coma in a diabetic patient with an effective plasma osmolality < 320 mOsm/kg demands immediate consideration of other causes of the mental status change.

Because HHS is a medical emergency that requires prompt recognition and management, an initial history and rapid but careful physical examination should focus on airway, breathing, and circulation (ABC), mental status, possible precipitating events (e.g., source of infection, myocardial infarction, etc.), and volume status. These steps should allow determination of the degree of urgency and priority with which various laboratory results should be obtained, so that treatment can start without delay.

Physical examination reveals signs of volume depletion, including decreased skin turgor, dry axillae and oral mucosa, low jugular venous pressure, and, if severe, hypotension. The neurological findings noted above (confusion/obtundation, coma) also may be seen, or even focal neurological signs such as convulsions, motor or sensory deficits, delirium, or chorea. Fever is rare, even in the presence of infection, because of peripheral vasoconstriction due to the hypovolemia.

The easiest and most urgent laboratory tests after a prompt history and physical examination are determination of blood glucose by finger-stick and urinalysis with reagent strips to assess qualitative amounts of glucose, ketones, nitrite, and leukocyte esterase in the urine.

The initial laboratory evaluation of a patient with suspected DKA or HHS should include:

  • Serum glucose
  • Serum electrolytes (with calculation of the anion gap), blood urea nitrogen (BUN), and plasma creatinine
  • Complete blood count with differential
  • Urinalysis and urine ketones by dipstick
  • Plasma osmolality
  • Serum ketones (if urine ketones are present)
  • Arterial blood gas if the serum bicarbonate is substantially reduced
  • Electrocardiogram.

Additional testing, such as cultures of urine, sputum, and blood, serum lipase and amylase, and chest X-ray or X-ray of other organs (foot, etc.), should be performed on an individual basis.

Laboratory findings are dominated by signs of uncontrolled diabetes and dehydration. Plasma glucose concentrations are particularly high ( > 1000 mg/dl [56 mmol/L] in two thirds of cases) and usually range between 800 and 2400 mg/dl (44-133 mmol/L).2 Renal function is often impaired, with elevated BUN and creatinine levels. Even acute renal failure may sometimes ensue, the main cause of which is usually the rhabdomyolysis attributed to hypophosphatemia and prolonged muscle compression in a comatose patient. Hemoglobin and hematocrit may be increased (due to hemoconcentration) and liver function tests may be abnormal (due to fatty infiltration of the liver). The majority of patients present with leukocytosis due to the stress of the underlying condition that led to HHS (as a result of hypercortisolemia and increased catecholamine secretion). However, a white blood cell count > 25,000/ μ L or a band count > 10% may indicate infection and a need for further work-up.

The serum sodium concentration may vary, as factors are present that can both lower or raise it. The final serum sodium concentration will reflect the balance between dilution of sodium due to osmotic water movement out of the cells, and concentration of sodium due to glucosuria-induced osmotic diuresis, resulting in water loss in excess of sodium. The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia. An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss (from the urine or occasionally also due to gastrointestinal losses). To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1.6 mEq/L to the measured serum sodium for each 100 mg/dl of glucose above 100 mg/dl. 12

Patients at presentation have a potassium deficit that averages 3-5 mg/kg. A number of factors contribute to this deficit, particularly increased urinary losses due both to the glucose osmotic dieresis and to the need to maintain electroneutrality as ketoacid anions are excreted. Gastrointestinal losses and the loss of potassium from the cells due to glycogenolysis and proteolysis also may play a contributory role. Despite these potassium losses, the serum potassium concentration is usually normal or, in one third of patients, elevated on admission. It is thought that hyperosmolality and insulin deficiency are primarily responsible for the relative rise in the serum potassium concentration in this setting. The rise in plasma osmolality leads to osmotic water movement out of the cells. This can promote the parallel movement of potassium into the extracellular fluid. Also, since insulin normally promotes potassium uptake by the cells, insulin deficiency contributes to elevated serum potassium levels. Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia.13

Patients with uncontrolled hyperglycemia are typically in negative phosphate balance because of decreased phosphate intake and phosphaturia caused by osmotic diuresis. 9,14 Despite phosphate depletion, the serum phosphate concentration at presentation is usually normal or even high, because both insulin deficiency and metabolic acidosis cause a shift of phosphate out of the cells.

Occasionally, marked hyperlipidemia and lactescent serum are observed, due to the marked hyperglycemia.

By definition, patients with HHS have no or only mild ketonemia and ketonuria. However, approximately 50% of patients may have an elevated anion gap acidosis because of concomitant ketoacidosis or lactic acidosis.

Next Text: Clinical management

 

References
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  2. Daugirdas JT, Kronfol NO, Tzalaloukas AH, et al. Hyperosmolar coma: Cellular dehydration and the serum sodium concentration. Ann Intern Med 1989; 110: 855-7.
  3. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2009; 32: 1335-43.
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  5. www.cdc.gov/diabetes/statistics/ (accessed August 1, 2010).
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  9. Kitabchi AE, Fisher JN, Murphy MB, et al. Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. In: Kahn CR, Weir GC (ed), Joslin’s Diabetes Mellitus, 13th edn, Philadelphia, USA: Lea & Febiger, 1994: 738-70.
  10. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29: 2739-48.
  11. Al-Kudsi RR, Daugirdas JT, Ing TS, et al. Extreme hyperglycemia in dialysis patients. Clin Nephrol 1982; 17: 228-31.
  12. Katz, MA. Hyperglycemia-induced hyponatremia: Calculation of expected sodium depression. N Engl J Med 1973; 289: 843-4
  13. Adrogue HJ, Lederer ED, Suki WN, et al. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine (Baltimore) 1986; 65: 163-72.
  14. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med 1985; 79: 571-6.

 

Nikolaos Katsilambros, MD, PhD, FACP
SCOPE Founding Fellow
Professor of Internal Medicine
Athens University Medical School
Evgenideion Hospital and Research Laboratory ‘Christeas Hall’
Athens, Greece
Christina Kanaka-Gantenbein, MD, PhD
Associate Professor of Pediatric Endocrinology and Diabetology
First Department of Pediatrics, University of Athens
Agia Sofia Children’s Hospital
Athens, Greece
Stavros Liatis, MD
Consultant in Internal Medicine and Diabetology
Laiko General Hospital
Konstantinos Makrilakis, MD, MPH, PhD
Assistant Professor of Internal Medicine and Diabetology
Athens University Medical School
Laiko General Hospital
Athens, Greece
Nikolaos Tentolouris, MD, PhD
Assistant Professor of Internal Medicine and Diabetology
University of Athens
Laiko General Hospital
Athens, Greece
 
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Diabetic Emergencies: Diagnosis and Clinical Management provides emergency room staff, diabetes specialists and endocrinologists with highly practical, clear-cut clinical guidance on both the presentation of serious diabetic emergencies like ketoacidosis, hyperosmolar coma and severe hyper- and hypoglycemia, and the best methods of both managing the emergencies and administering appropriate follow-up care.
 
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