Hyperosmolar Hyperglycemic State Treatment & Management

Diagnosis and management guidelines for hyperglycemic crises are available from the American Diabetes Association. ^{[8, 13, 36]}

The main goals in the treatment of hyperosmolar hyperglycemic state (HHS) are as follows:

• To vigorously rehydrate the patient while maintaining electrolyte homeostasis
• To correct hyperglycemia
• To treat underlying diseases
• To monitor and assist cardiovascular, pulmonary, renal, and central nervous system (CNS) function

In an emergency situation, whenever possible, contact the receiving facility while en route to ensure preparation for a comatose, dehydrated, or hyperglycemic patient. When appropriate, notify the facility of a possible cerebrovascular accident or myocardial infarction (MI). Initiation of insulin therapy in the emergency department (ED) through a subcutaneous insulin pump may be an alternative to intravenous (IV) insulin infusion. ^[37]

Airway management is the top priority. In comatose patients in whom airway protection is of concern, endotracheal intubation may be indicated.

Rapid and aggressive intravascular volume replacement is always indicated as the first line of therapy for patients with HHS. Isotonic sodium chloride solution is the fluid of choice for initial treatment because sodium and water must be replaced in these severely dehydrated patients.

Although many patients with HHS respond to fluids alone, IV insulin in dosages similar to those used in diabetic ketoacidosis (DKA) can facilitate correction of hyperglycemia. ^[38] Insulin used without concomitant vigorous fluid replacement increases the risk of shock. Adjust insulin or oral hypoglycemic therapy on the basis of the patient’s insulin requirement once serum glucose level has been relatively stabilized.

All patients diagnosed with HHS require hospitalization; virtually all need admission to a monitored unit managed by medicine, pediatrics, or the intensive care unit (ICU) for close monitoring. When available, an endocrinologist should direct the care of these patients.

Frequent reevaluation of the patient’s clinical and laboratory parameters is necessary. Recheck glucose concentrations every hour. Electrolytes and venous blood gases should be monitored every 2-4 hours or as clinically indicated.

When an underlying disease is responsible for HHS, it must be promptly identified and treated. Resolution of HHS often lags while the underlying process remains unresolved. Some authors advocate prophylactic heparin treatment and broad-spectrum antibiotic coverage, but these measures have not yet been studied thoroughly enough to allow recommendation of their use.

Standard care for dehydration and altered mental status is appropriate, including airway management, IV access, crystalloid fluid replacement, and administration of any medications routinely given to coma patients.

Airway management

Protection of the airway is mandatory in patients presenting with mental status changes, obtundation, or unconsciousness. Patients may present with respiratory failure and circulatory collapse and must be ventilated mechanically.

If patients are presenting with metabolic acidosis, take care to hyperventilate them when mechanical ventilation is instituted. Hyperventilation generates respiratory alkalosis, which compensates for the metabolic acidosis and also decreases the risk of cerebral edema.

Intravenous access

IV access, large bore if possible, or central venous access is useful, provided attempts to obtain it do not significantly delay transfer to the nearest emergency department (ED). A centrally placed catheter offers an avenue for vigorous rehydration, especially if means for intravenous (IV) access are difficult secondary to profound dehydration.

Fluid resuscitation

Aggressive fluid resuscitation is key in the treatment of HHS. This is to avoid cardiovascular collapse and to perfuse vital organs. Fluid deficits in adults are large in HHS, being about 9 L on average.

According to American Diabetes Association guidelines, fluid resuscitation with 0.9% saline at the rate of 15-20 mL/kg/h or greater is indicated to expand the extracellular volume quickly in the first hour. This amounts to about 1-1.5 L in an average-sized person. (In patients with contraindications to rapid fluid resuscitation [ie, cardiac or renal disease], slower rates are indicated.) A greater rate of fluid resuscitation is needed in patients with severe volume depletion but should not exceed 50 mL/kg in the first 4 hours. The choice of fluids after initial resuscitation depends on the patient's hydration status, serum electrolytes, and urinary output. If the patient's sodium level is normal or elevated, 0.45% normal saline may be used at a rate of 10 mL/kg/h. If the patient is hyponatremic, 0.9% normal saline may be used instead. In the first 18-24 hours, the first half of the patient's fluid deficit should be corrected. The plasma osmolality should not change over 3 mmol/kg/hr during fluid resuscitation. ^[7]

When the blood glucose concentration, initially checked hourly, reaches 250 mg/dL, change the infusion to 5% dextrose in 0.45-0.7% normal saline. This helps to prevent a precipitous fall in glucose, which may be associated with cerebral edema. ^[3]  In pediatric patients with suspected HHS, correcting fluid deficits over a longer period (48 h) may help to reduce the risk of cerebral edema. ^[18]

The IV fluids should also include 20-40 mEq/L of potassium chloride to treat hypokalemia, which is seen in patients with HHS. 

Patients with persistent hypotension may require pressor support in the ICU while rehydration is being accomplished.

Medications for coma patients

Basic medications given to coma patients in the field may include dextrose (50 mL of 50% dextrose in water [D50]). This is of benefit to many comatose patients with few adverse effects.

When possible, fingerstick glucose measurement is obtained before dextrose administration. Whenever fingerstick glucose measurement is unavailable or is likely to be delayed, D50 must be administered to comatose patients on an empiric basis without delay. Undiagnosed and untreated hypoglycemia, which may present with signs and symptoms very similar to those of HHS, is readily reversible but can be rapidly lethal if not treated promptly.

All patients with HHS require IV insulin therapy; however, immediate treatment with insulin is contraindicated in the initial management of patients with HHS. The osmotic pressure that glucose exerts within the vascular space contributes to the maintenance of circulating volume in these severely dehydrated patients. Institution of insulin therapy drives glucose, potassium, and water into cells. This results in circulatory collapse if fluid has not been replaced first.

IV insulin administration is accomplished most effectively in the ICU, where cardiovascular and respiratory support is available if needed. Infuse insulin separately from other fluids, and do not interrupt or suspend the infusion of insulin once therapy has been started.

The following steps may be used as a guideline for insulin infusion, as per American Diabetes Association recommendations ^{[7, 39]} : 

• If hypokalemia (K < 3.3mEq/L) has been excluded, an IV bolus of regular insulin of 0.10 U/kg/h should be administered.
• Begin a continuous insulin infusion of 0.1 U/kg/h.
• Monitor blood glucose by means of bedside testing every hour; if glucose levels are stable for 3 hours, decrease the frequency of testing to every 2 hours.
• If plasma glucose levels do not achieve a reduction of 50 mg/dL in the first hour, check volume status. If volume status is normal, it is okay to double insulin infusion every hour until a drop in glucose of 50-75 mg/dL is obtained.
• Set the target blood glucose level at 300 mg/dL; this target level may be adjusted downward after the patient is stabilized.
• Once blood glucose concentration reaches 300 mg/dL, decrease the insulin infusion rate by 0.5-1.0 U/h. Add dextrose to the IV fluids.
• Do not discontinue the insulin drip. Continue IV insulin at a goal glucose level of 250-300 mg/dL until the patient becomes more alert and hyperosmolarity has resolved.

Once the patient is alert and able to eat, an insulin regimen consisting of short-/rapid-acting insulin and long-acting insulin is needed to wean the patient off of IV insulin therapy and to control glucose levels. If the patient already had an insulin regimen before the onset of HHS, it is okay to continue the current regimen and adjust to better glycemic control. If the patient is new to insulin or a newly diagnosed diabetic, total subcutaneous insulin dosages should not exceed 0.5-1 U/kg/day. The IV insulin infusion should be continued for about 1-2 hours after subcutaneous insulin administration to avoid hyperglycemia. 

When the glucose level has been between 200 and 300 mg/dL for at least 1 day and the patient’s level of consciousness has improved, glycemic control may be tightened. The recommended level of glycemia for most patients with type 2 diabetes mellitus (DM) is 80-120 mg/dL. This correlates to the hemoglobin A_1c value of 7% recommended by the American Diabetes Association.

All patients who have experienced HHS will probably require intensive management of their diabetes initially, and this includes insulin therapy. The severe hyperglycemia with which these patients present implies profound beta cell dysfunction. In most instances, sufficient recovery of endogenous insulin production is a reasonable expectation, with safe dismissal of the patient from the hospital on oral therapy. After maintaining adequate glycemic control with insulin for several weeks after HHS, consider switching patients to an oral regimen.

Profound potassium depletion necessitates careful replacement. Patients may initially present with normal or elevated potassium levels. With rehydration, the potassium concentration is diluted. With the institution of insulin therapy, potassium is driven into cells, exacerbating hypokalemia. A precipitous drop in the potassium concentration may lead to cardiac arrhythmia.

Potassium may be added to the infusion fluid and should be started at a level of 3.5 mEq/L or less and with adequate urine output. Usually, replenishing potassium with 20-30 mEq of potassium chloride in each liter of IV fluid is sufficient. The goal is to keep a potassium level of between 4 and 5 mEq. It is important to replenish potassium before starting insulin infusion, especially when levels are below 3.5 mEq, to avoid cardiovascular compromise. Check the potassium level at least every 4 hours until the blood glucose concentration is stabilized.

Phosphate, magnesium, and calcium are not replaced routinely, even though patients may have whole body deficits in these electrolytes. A patient who is symptomatic with tetany requires replacement therapy for calcium.

The mortality associated with HHS remains high. The profound electrolyte and metabolic abnormalities present during treatment warrant careful cardiorespiratory monitoring. When gas exchange has been compromised, endotracheal intubation and mechanical ventilation are indicated.

Neurologic monitoring is indicated in all patients with HHS who present with altered mental status. Hyperosmolarity may trigger many neurologic syndromes. If a patient has seizures, phenytoin is not the agent of choice, because it inhibits endogenous insulin secretion and because, in general, it is ineffective in persons with HHS. Volume resuscitation and appropriate decrease is osmolality will decrease the chance of seizures.

Telemetry monitoring may be required in patients with electrolyte imbalances while treatment occurs. This is especially important with potassium abnormalities and electrocardiographic changes. Patients with HHS may also require telemetry monitoring if cardiac workup suggests a cardiac etiology, such as MI, for HHS. 

Provide adequate nutritional support for all patients. Once the patient's mental status is back to normal and the patient is able to eat, starting an oral diet is indicated. Some HHS patients are unable to eat for several days as a consequence of the comorbidities with which they present.

Patients in the ICU who require prolonged mechanical ventilation, patients with impaired airway defenses, and all patients with prolonged mental status changes are candidates for enteral or parenteral nutrition. The use of parenteral nutrition often induces insulin resistance and leads to increased insulin requirements.

Once HHS is resolved, provide dietary counseling for all patients. This probably is most effectively delivered by a registered dietitian who has expertise in counseling patients with diabetes.

Generally, no consultation is absolutely required to manage HHS in the ED; however, in occasional cases, consultations may be useful.

A consultation with an endocrinologist is suggested for patients with HHS. Consider a consultation with a neurologist for most patients with altered mental status. A neurologist should monitor the cases of any patients with underlying neurologic disease (eg, cerebrovascular accident or a history of seizures). A pulmonologist or critical care specialist should monitor the cases of patients requiring intubation and mechanical ventilation. Other consultations (eg, with infectious disease or psychiatry) may be obtained as appropriate.

Primary care follow-up is necessary for additional diabetic teaching and any appropriate immunizations. Visiting home nurse referral may be necessary to enhance compliance.

After any episode of HHS, enroll patients in a program of routine diabetes care. Adhere to American Diabetes Association guidelines for the care of people with diabetes. For patients with diabetes that was unrecognized before HHS, perform a routine diabetic care exam. This includes a routine eye exam and foot exam, as well as lab work to check for nephropathy and evaluation for signs of macrovascular disease. Advise patients treated with insulin to wear a bracelet or chain identifying them as having diabetes.