A. The four conditions related to severely disordered glucose metabolism and often associated with altered consciousness and coma are the following:

1. Diabetic ketoacidosis (DKA).

2. Hyperglycemic hyperosmolar syndrome (HHS).

3. Alcoholic ketoacidosis.

4. Hypoglycemia.

B. These four diagnoses should be considered during the evaluation of any patient with altered mental status.

1. DKA may be the first sign of new-onset type 1 diabetes mellitus but more commonly occurs in those with preexisting type 1 diabetes due to the following:

a. Omission of insulin therapy.

b. Infection.

c. Major stressors (e.g., myocardial infarction, trauma).

d. Medication (e.g., high-dose glucocorticoid therapy).

2. DKA occurs less commonly in patients with type 2 diabetes in the presence of severe infection, trauma, or myocardial infarction. Among individuals with type 2 diabetes, African Americans and ethnic minorities seem to be more prone to DKA than Caucasians.

1. Caused by a total or near-total absence of circulating insulin, coupled with increased secretion of glucagon.

2. These hormonal changes are responsible for the following:

a. Inability of glucose to enter cells and unrestrained hepatic glucose production leading to severe hyperglycemia.

b. Acceleration of lipolysis and release of large quantities of free fatty acids, which are metabolized to ketone bodies.

3. The large amounts of ketones generated result in the accumulation of hydrogen ions and metabolic acidosis.

4. Hyperglycemia causes an osmotic diuresis resulting in a loss of free water and depletion of electrolytes.

5. Other stress hormones such as cortisol facilitate the above changes in glucose and lipid metabolism.

1. Clinical manifestations.

a. Most patients with DKA are lethargic; approximately 10% are comatose.

b. Postural hypotension is common, but shock is rare.

c. There is a rapid, deep (Kussmaul) respiration, and a sweet, fruity odor in the breath.

d. Presence of fever should alert to the presence of an intercurrent illness. Hypothermia may be a sign of sepsis.

e. Abdominal pain and nausea are common and may be accompanied by guarding and diminished bowel sounds. Patients may vomit guaiac-positive, coffee ground-like material.

f. Pleuritic chest pain may be present. Hepatic enlargement with fatty infiltration may occur.

2. Laboratory.

a. Plasma glucose is typically in the range of 250 to 800 mg/dL in DKA.

b. Electrolytes.

i. Serum sodium concentration can vary from 125 to 165 mEq/L. It usually decreases due to osmotic diuresis and dilution by the osmotic effect of hyperglycemia. For every 100 mg increase in glucose the dilutional effect accounts for a 1.6-mEq/L drop in sodium concentration.

(a) Example: The “corrected” serum sodium in a patient with a measured concentration of 135 mEq/L and a glucose of 600 mg/dL is 1.6 × (600 − 100) + 135, or 143 mEq/L. Hypertriglyceridemia can cause a factitiously low sodium concentration.

ii. Potassium concentration is usually elevated at presentation but can vary from 2.2 to 8.4 mEq/L. It can drop during treatment to the point of being life threatening.

(a) A total body potassium deficit in the range of 200 to 700 mEq is typical even when the potassium is moderately elevated.

(b) A normal or low concentration of potassium at presentation often signals a very severe potassium deficit.

iii. Phosphorus concentrations are commonly elevated in untreated DKA. After therapy, there is a precipitous decline to subnormal levels.

c. Anion gap acidosis is seen at presentation.

i. Arterial pH measurements are preferred, but venous pH may also be used.

ii. Chronic ketoacidotic states may be associated with hyperchloremic acidosis, probably as a consequence of the loss of neutralized ketone body salts.

iii. Rarely, metabolic alkalosis is observed from severe vomiting.

d. Plasma ketone levels by the nitroprusside test may not reflect the full extent of ketogenesis, and direct β-hydroxybutyrate (BOHB) measurements may be more helpful in establishing the diagnosis and assessing severity.

i. The nitroprusside test measures only acetoacetate (AcAc) and acetone. BOHB, the predominant “ketone body” produced from AcAc, is not measured by this test.

ii. Normally, the BOHB:AcAc ratio is 3:1, but acidosis increases the ratio to 6:1 or even 12:1.

iii. Ketone measurements by nitroprusside may initially rise due to conversion of BOHB back to AcAc as acidosis resolves. Clearance occurs slowly; measurement more often than every 12 hours is generally unnecessary.

e. A mixed anion gap acidosis may occur in patients with DKA. This can be due, for example, to intercurrent lactic acidosis or salicylate intoxication.

i. If the total ketoacid concentration (the sum of BOHB and estimated AcAc concentrations) is much lower than the increase in anion gap, a non-ketone body anion may be contributing to this difference (e.g., lactate, salicylate, uremic compounds, methanol, ethylene glycol).

ii. Direct measurement of these substances may also be helpful (e.g., lactate).

f. Other laboratory findings.

i. Renal. The blood urea nitrogen (BUN) is typically elevated due to prerenal azotemia and increased ureagenesis. AcAc can interfere with some creatinine assays.

ii. Hematology. Hematocrit and hemoglobin are usually high. Low values suggest preexisting anemia or acute blood loss. Leukocytosis with a left shift often occurs in the absence of intercurrent illness.

iii. Lipids. There is usually marked elevation of serum triglyceride concentrations; this reverses with insulin therapy.

iv. Serum amylase, lipase, and creatine phosphokinase (CPK) are sometimes elevated. Uric acid may be elevated. Ketone bodies interfere with certain transaminase assays.

1. Treatment is directed at four main problems: (1) hypovolemia, (2) electrolyte disturbances, (3) insulin, and (4) identification of the precipitating event. Institutional protocols may be helpful to ensure uniformity and efficacy of treatment.

2. Hypovolemia is always present. Fluid and electrolyte therapy takes precedence over insulin therapy; the latter shifts glucose, salt, and water from the extracellular and intravascular compartments to the intracellular space.

a. The free water deficit ranges between 5 and 11 L, approximately 100 mL/kg.

b. Initial fluid resuscitation should be with 0.9% saline.

c. Approximately 2 L should be given during the first hour to stabilize blood pressure and establish urine flow.

d. Another liter can usually be given during the next 2 hours.

e. During the first 24 hours, 75% of the estimated free water deficit should be replaced. Urine flow should be maintained at approximately 30 to 60 mL/hour.

f. After the first 2 L, consider changing to 0.45% saline if hypernatremia is present.

3. Electrolytes.

a. Sodium and chloride are replaced in conjunction with free water as described above.

b. The initial serum potassium level does not accurately reflect the total-body potassium deficit. Potassium replacement must always be initiated early in treatment.

i. Potassium replacement should begin as soon as the serum K⁺ concentration is ≤5.5 mEq/L, because potassium concentration often falls precipitously after starting therapy. Reasons for this include the following:

(a) Insulin shifts K⁺ intracellularly.

(b) As acidemia resolves, buffered intracellular H⁺ exchanges for extracellular K⁺.

(c) Gastric suctioning via a nasogastric tube may result in the loss of electrolytes.

ii. A sudden reduction in the serum potassium concentration can cause flaccid paralysis, respiratory failure, and life-threatening cardiac arrhythmias.

iii. The typical rate of repletion is 20 mEq/hour as KCl or K₃PO₄

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