WORKUP	Section 5 of 10
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Lab Studies:

• Serum electrolytes (sodium, potassium, chloride, bicarbonate) and calcium, magnesium, and phosphate

• Hyponatremia or hypernatremia may be present.

• In the setting of hyperglycemia, hyponatremia is common due to the osmotic effect of glucose drawing water into the vascular space. Measured serum sodium can be corrected upward 1.6 mEq/L for every 100 mg/dL increase in serum glucose to give an estimate of what the serum sodium level would be in the absence of hyperglycemia and its associated osmotic effect.

• Total body potassium is likely low regardless of its serum value; a low measured serum potassium suggests profound total body losses.

• An anion gap metabolic acidosis may be present because of dehydration (lactic acidosis) but usually is less profound than that observed in DKA.

• Some patients who have primarily a hyperosmolar, hyperglycemic nonketotic state have a component of DKA; therefore, ketoacidosis contributes to the anion gap acidosis.

• Renal function (BUN and creatinine levels)

• BUN and creatinine levels are likely to be elevated initially due to dehydration.

• When possible, they should be compared to previous values, as many patients with diabetes have renal insufficiency at baseline.

• Serum glucose usually is elevated dramatically, often to greater than 800 mg/dL.

• Serum osmolarity usually is greater than 320 mOsm/dL.

• Osmolarity can be measured directly. Predicted osmolarity is calculated using the following formula: Osm = (2 X Na) + (BUN/2.8) + (glucose/18)

• If the calculated value is significantly lower than the measured value, consider toxic alcohol ingestion as a source of unmeasured osmoles that can trigger HHNC.

• Serum ketones can be normal in pure HHNC, but mild-to-moderate ketosis can be present when the disease has features both of HHNC and of DKA ("overlap cases").

• Creatine phosphokinase (CPK) with isoenzymes should be measured routinely because both MI and rhabdomyolysis can trigger HHNC, and both can be secondary complications of HHNC.

• Acute MI frequently is associated with HHNC.

• Coagulation studies (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) are useful as part of a screen for disseminated intravascular coagulation (DIC).

• Blood cultures should be obtained to search for bacteremia.

• Arterial blood gases

• ABG is the most accurate indicator of serum pH.

• A venous blood gas (VBG) may be substituted in patients without any respiratory symptoms who have normal results from a heart/lung exam and normal oxygen saturation on room air. Venous blood gases provide comparable information (assuming that oxygenation and ventilation are adequate) and are easier to draw.

• In most cases of HHNC, the pH is greater than 7.25.

• Urinalysis reveals elevated specific gravity (evidence of dehydration), glucosuria, ketonuria, and evidence of UTI.

• Urine cultures are useful because UTIs may be underdetected by urinalysis alone, particularly in patients with diabetes.

• Cerebrospinal fluid (CSF) cell count, glucose, protein, and culture are indicated in patients with an acute alteration of consciousness and clinical features suggestive of possible CNS infection. Patients who are immunocompromised may require additional studies of the CSF such as polymerase chain reaction (PCR) for herpes simplex virus (HSV) and cryptococcal antigen.

• Send for cultures of stool, cervical mucus, and other substances when clinical evidence suggests a potential area of infection.

• Although not useful in the acute phase of therapy, hemoglobin A1C (glycosylated hemoglobin) may be ordered as an indicator of the patient's glucose control over the previous several weeks.

Imaging Studies:

• A chest radiograph is useful to screen for pneumonia. Abdominal radiographs are indicated if the patient has abdominal pain or is vomiting.

• CT scan of the head

• Indicated in many patients with focal or global neurologic changes

• May be useful for patients who show no clinical improvement after several hours of treatment, even in the absence of clinical signs of intracranial pathology

• Indications for head CT scans controversial

Procedures:

• Venous access

• Large-bore intravenous (IV) or central venous access is used, especially in cases in which hemorrhage is a precipitant and blood products are likely to be required or when inotropic agents may be necessary.

• Swan-Ganz catheterization may be helpful in monitoring intravascular volumes.

• Urethral catheterization is useful to obtain a clean urine specimen. This is especially important if the urine dipstick shows signs of infection.

• An indwelling Foley catheter indicates urine output and response to fluid therapy.

• An arterial line provides access for repeated blood draws, particularly in patients who are intubated or require admission to the ICU.

• When meningitis or subarachnoid hemorrhage is suspected, lumbar puncture (LP) is indicated. If meningitis is suspected clinically, do not withhold antibiotics while waiting for the LP to be completed.

	TREATMENT	Section 6 of 10
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Prehospital Care: Standard care for dehydration and altered mental status is appropriate, including airway management, IV access, crystalloid, and any medications routinely given to coma patients.

• Airway management is the top priority. In comatose patients in whom airway protection is of concern, endotracheal intubation may be indicated. Cervical spine immobilization is necessary if head or neck injury is a possibility.

• IV access, large bore if possible, is useful, provided that attempts to obtain it do not significantly delay transfer to the nearest ED.

• Bolus of 500 mL isotonic saline is appropriate for nearly all adults who are clinically dehydrated. A 250 mL bolus may be more appropriate in patients with a history of CHF and/or renal insufficiency.

• Basic medications given to coma patients in the field may include thiamine 100 mg IV, dextrose (50 mL of D50), and naloxone (0.4-2 mg IV). This combination is of benefit to many comatose patients with few adverse effects.

• When possible, fingerstick glucose measurement is obtained prior to dextrose administration. In any case in which fingerstick glucose measurement is unavailable or likely to be delayed, empiric D50 must be administered to comatose patients without delay. Undiagnosed and untreated hypoglycemia, which may present with signs and symptoms very similar to those of HHNC, is readily reversible but can be rapidly lethal if not treated promptly.

• Whenever possible, contact the receiving facility while en route to ensure preparation for a comatose, dehydrated, and/or hyperglycemic patient.

• Notify facility of possible brain attack when appropriate.

• Use antibiotics as indicated based on clinical situation and likelihood of infection.

Emergency Department Care:

• Manage airway as needed, establish IV access, initiate vigorous fluid resuscitation, and obtain appropriate laboratory and radiographic studies.

• Fluid deficits in HHNC are large; the fluid deficit of an adult may be 10 L or more.

• Administer 1-2 L of isotonic saline in the first 2 hours. A higher initial volume may be necessary in patients with severe volume depletion. Slower initial rates may be appropriate in patients with significant cardiac or renal disease or in those who are not urinating.

• After the initial bolus, some clinicians recommend changing to half-normal saline, while others continue with isotonic saline.

• Either fluid likely will replenish intravascular volume and correct hyperosmolarity; a good standard is to switch to half-normal saline once blood pressure and urine output are adequate.

• Once serum glucose drops to 250 mg/dL, the patient must receive dextrose in the IV fluid.

• Initiate insulin therapy in the ED.

• Although many patients with HHNC respond to fluids alone, IV insulin in dosages similar to those used in DKA can facilitate correction of hyperglycemia.

• Insulin utilized without concomitant vigorous fluid replacement increases risk of shock.

• Frequent reevaluation of clinical and laboratory parameters is necessary.

Consultations:

• Generally, no consultation is required to manage HHNC in the ED. After ED management, refer patient to a primary care physician, internist, or intensivist for further care.

• In occasional cases, endocrinology, neurology, or infectious disease consultation may be useful.

• Psychiatry consultation may be useful during the hospitalization.

	MEDICATION	Section 7 of 10
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Fluids, insulin, and electrolytes (especially potassium) are the cornerstones of management. Antipyretics, antiemetics, and antibiotics are added when appropriate to control fever and nausea/vomiting.

	MISCELLANEOUS	Section 9 of 10
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Medical/Legal Pitfalls:

• Failure to manage the airway with endotracheal intubation when necessary

• Failure to provide adequate fluid resuscitation (leading to shock)

• Cerebral edema (more common in children) secondary to overly rapid hydration (especially with hypotonic fluids) or failure to add glucose to fluids when the level falls to less than 250 mg/dL

• Hypoglycemia due to excessive insulin use without the initiation of glucose-containing fluids

• Failure to replete potassium in patients who have a total body potassium deficit but an initially normal serum potassium level (On the other hand, administration of IV potassium has been associated with significant morbidity and death, especially with iatrogenic errors.)

• Failure to treat empirically and early with broad-spectrum antibiotics when sepsis appears to be a possible precipitant