eMedicine Specialties > Endocrinology > Diabetes Mellitus

Hyperosmolar Coma: Differential Diagnoses & Workup

Author: J Michael Gonzalez-Campoy, MD, PhD, FACE, Medical Director and CEO, MN Center for Obesity, Metabolism, and Endocrinology
Contributor Information and Disclosures

Updated: Jun 1, 2009

Differential Diagnoses

Diabetes Insipidus
Diabetic Ketoacidosis
Myocardial Infarction
Pulmonary Embolism

Other Problems to Be Considered

MS change and/or level of consciousness
Intoxication (eg, with ethanol, narcotics, other drugs)
Postictal state
CNS infections
Arrhythmia

Hypotension
Sepsis
Other causes of dehydration
Acute blood loss (GI, other)

Polyuria
Excessive diuretic use

Workup

Laboratory Studies

• Plasma glucose
  • Hyperglycemia defines HNS. The degree of hyperglycemia in HNS is usually extreme. Many patients present with glucose concentrations greater than 1000 mg/dL.
  • The concentration of glucose in the plasma is directly proportional to the degree of dehydration. Higher concentrations of glucose relate to higher degrees of dehydration, higher plasma osmolality, and a worse prognosis.
  • Monitor the plasma glucose concentration hourly during the first 24-48 hours of treatment. 
• Arterial blood gases (pH)
  • Document arterial plasma pH early in the treatment of patients with hyperglycemia presenting with an altered level of consciousness. A pH of 7.3 or higher defines HNS.
  • The arterial blood gas values also indicate underlying diseases associated with HNS. Hypoxemia may be observed in association with cardiac or pulmonary diseases. Hypocarbia may be due to respiratory alkalosis as a compensatory mechanism to a primary metabolic acidosis. Hypocarbia also may be due to tachypnea in response to an elevated alveolar-arterial oxygen gradient from pulmonary disease. A low plasma bicarbonate level is commonly observed in persons with HNS, but very low levels (£15 mEq/L) indicate DKA.
• Plasma ketones
  • A mild degree of ketosis is usually observed in any patient who is dehydrated.
  • In those with HNS, despite the significant degree of dehydration, ketosis is mild and responds readily to treatment. Profound ketosis that does not respond readily to intravenous rehydration is the norm in persons with DKA.
• Serum osmolality and calculated serum osmolality
  • Normal serum osmolality ranges from 280-290 mOsm/kg. A serum osmolality of 320 mOsm/kg or more defines HNS. Rarely, serum osmolality may be greater than 400 mOsm/kg. In HNS, higher serum osmolality relates to worse impairment of the level of consciousness.
  • The serum osmolality may be calculated by adding Na⁺ and K⁺, multiplying by 2, adding glucose (mg/dL) divided by 18, and adding BUN divided by 2.8 (ie, 2 [Na⁺ + K⁺] + [mg/dL of glucose/18] + [BUN/2.8]).
  • Urea is freely permeable across cell membranes and therefore does not create an osmotic gradient between the intracellular and extracellular fluids. The last term of the serum osmolality equation may be dropped, giving the effective serum osmolality.
  • The effective serum osmolality may be used to calculate a patient's osmolality quickly at the bedside but should be confirmed by a measured value.
• Urinalysis
  • Urine for analysis may be difficult to obtain in a severely dehydrated patient with HNS. Catheterization of the urinary bladder may be necessary.
  • Exclude urinary tract infection in the evaluation of a patient with HNS.
  • Urinalysis may provide further information about the patient's metabolic state. Ketones are rarely present in persons with HNS, due mostly to dehydration. Gross proteinuria suggests the presence of underlying renal disease. The urinary osmolality and the urine specific gravity should be very high in patients with HNS. Occasionally, a patient presents with a low urine specific gravity. This is diagnostic of coexisting diabetes insipidus, prompts a more thorough evaluation of pituitary and renal function, and requires aggressive fluid resuscitation and central pressure monitoring.
• Plasma electrolytes
  • Early in the course of HNS, before significant osmotic diuresis has occurred, the elevated plasma glucose level exerts an osmotic drag. This results in the movement of water from the intracellular to the extracellular space, with dilution of all electrolytes in the plasma. Patients with renal insufficiency who may not establish an osmotic diuresis may effectively present with hyponatremia and hypochloremia. As HNS progresses and osmotic diuresis occurs, electrolytes are lost in the urine. All electrolytes are extremely deficient at the time of presentation, at which time the relative deficiencies of water and electrolytes determine their plasma concentrations. Additionally, the presence of hypertriglyceridemia affects the concentration of electrolytes. Triglycerides also exert an osmotic drag and displace electrolytes in the plasma.
  • Potassium does not enter insulin-sensitive tissues in HNS and remains in the extracellular space. The concentration of potassium at presentation depends on water loss, but frequently is high. Realize that despite the high concentration of potassium at presentation, patients experience profound losses. During treatment, insulin drives potassium into cells, and intravenous hydration dilutes potassium in the circulation. Aggressively replace potassium to maintain plasma levels in the normal range during treatment.
  • Monitor plasma electrolyte levels at least every 4 hours during the first 24-48 hours of treatment.
  • Bartoli and colleagues described a mathematical model and formulas that, according to the authors, improve the estimation of the plasma sodium concentrations that patients will have following treatment for hyperosmolar coma.^3,4 Such estimations are important for avoiding sodium imbalances following coma treatment. The model estimates the amount of glucose added to the plasma, along with associated water loss, but excludes concomitant sodium loss.
• Calculated anion gap
  • The anion gap is calculated by adding Na⁺ and K⁺ and subtracting the sum of CL^- and HCO₃ ^- (ie, [Na⁺ + K⁺] - [Cl^- + HCO₃ ^-]).
  • A wide anion gap is observed in most patients with HNS, reflecting mild metabolic acidosis. Bicarbonate levels greater than 15 mEq/L define HNS. The mild acidosis in HNS is often multifactorial and results, in part, from the accumulation of ketoacids in the absence of effective insulin activity. Some patients with profound dehydration may have high anion gaps, reflecting the additional contribution of lactic acid produced by hypoperfusion of tissues. Underlying renal disease with uremia also may contribute to a high anion gap.
• Creatinine and BUN
  • Patients with HNS present with prerenal azotemia. The initial BUN-to-creatinine ratio may exceed 30:1.
  • The renal function of many patients does not normalize after treatment, indicative of irreversible or underlying renal damage.
• CBC count and differential
  • Hemoglobin and hematocrit values are usually elevated because of volume contraction.
  • Leukocytosis is frequently present, with counts often greater than 20,000/mL. Stress, dehydration, and demargination of leukocytes contribute to leukocytosis. Given that infections commonly precipitate HNS, consider leukocytosis secondary to an infectious process until proven otherwise. Obtain a chest radiograph and urine and blood cultures from all patients with leukocytosis.
• Creatine kinase (rhabdomyolysis)
  • Dehydration causes a rise in the plasma levels of albumin, amylase, bilirubin, calcium, total protein, lactate dehydrogenase, transaminases, and creatine kinase (CK). Up to two thirds of patients with HNS have elevated serum enzyme levels.
  • Avoid the assumption that enzyme level elevation is due to dehydration. Exclude underlying disease associated with each of these abnormal blood levels in patients with HNS. This is especially true in the case of CK elevations. 
• Order additional tests as appropriate in the evaluation and management of patients with HNS.

Imaging Studies

• Chest radiograph
  • A chest radiograph (CXR) is almost always advisable in the initial evaluation of patients with HNS to exclude pneumonitis. CXR findings may be falsely negative at first because of the profound dehydration in some patients, and serial studies may document the pneumonitis process as rehydration proceeds.
  • Cardiomegaly in the presence of dehydration implies a severely compromised heart, which is probably affected by cardiomyopathy.
• CT scan of the head
  • Patients with HNS presenting with an altered MS may have an underlying CNS disease. CT scan is indicated to help exclude hemorrhagic strokes, subdural hematoma, subarachnoid bleeding, intracranial abscesses, and intracranial masses.
  • Repeat CT scanning is indicated if cerebral edema is a concern during the treatment of HNS.

Other Tests

• Electrocardiogram
  • ECG is indicated in all patients with HNS because MI and pulmonary emboli frequently precipitate HNS.
  • The height of the T waves in the ECG tracings may point to a potassium derangement. The duration of the QT interval may be abnormal due to calcium abnormalities.

Procedures

• Central venous pressure monitoring
  • Insertion of a central venous catheter is the only procedure that should be considered routinely in patients with HNS.
  • Findings from monitoring of the pulmonary capillary wedge pressure or the central venous pressure may help guide intravenous rehydration therapy.
  • A centrally placed catheter offers an avenue for vigorous rehydration.
• Endotracheal intubation and mechanical ventilation
  • Protection of the airway is mandatory in patients with obtundation or unconsciousness. Many patients present with respiratory failure and circulatory collapse and must be ventilated mechanically.
  • Because of the underlying metabolic acidosis that is frequently present, take care to hyperventilate patients when mechanical ventilation is instituted. Hyperventilation generates respiratory alkalosis, which compensates for the metabolic acidosis and also decreases the risk of cerebral edema.
• In patients with HNS, consider other procedures, including nasogastric tube placement, thoracentesis, paracentesis, and spinal tap, as appropriate.

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