In this episode I’ll discuss diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).

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Definition

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious acute complications of diabetes. These diabetic crises cause thousands of deaths annually in the US.

DKA and HHS differ clinically according to the presence of ketoacidosis and the degree of hyperglycemia.

In DKA metabolic acidosis is often the major finding. The serum glucose is below 800 mg/dL and usually in the 350-500 mg/dL range. DKA usually evolves rapidly.

In HHS, there is little or no ketoacidosis and the serum glucose concentration frequently exceeds 1000 mg/dL. HHS usually evolves over a period of several days.

Overlap between DKA and HHS occurs in more than one-third of patients.

Pathogenesis

Insulin deficiency/resistance and glucagon excess are responsible for the development of DKA and HHS.

The deficiency in insulin (either absolute or relative deficiency) is more severe in DKA compared with HHS.

In HHS the residual insulin secretion and its systemic activity minimizes the development of ketoacidosis but is not adequate to control hyperglycemia.

In patients with absolute or relative insulin deficiency, DKA and HHS are usually precipitated by a stressor such as infection or discontinuation of / inadequate insulin therapy.

Treatment

The treatment of DKA and HHS involves the correction of fluid and electrolyte abnormalities, followed by the administration of insulin.

Specific treatment protocols include: ADA guidelines, Joslin protocol, and Yale New Haven.

The order of treatment is essential. A patient in DKA or HHS is already volume-depleted. Insulin forces glucose as well as potassium and water into cells. Therefore giving insulin before correcting fluid and electrolyte abnormalities can result in cardiovascular collapse and death.

Fluid replacement

Fluid replacement should begin in most patients with isotonic saline at a rate of 1000 mL/hr for several hours. If the patient has hypovolemic shock IV fluids may need to be infused even faster.

Potassium replacement

Unless the serum potassium is above normal, potassium replacement should be initiated immediately. It is important to get ahead of potassium levels since fluid replacement and insulin administration will lower the serum potassium.

If the initial serum potassium is below 3.3 mEq/L, and especially if the patient was hypokalemic prior to therapy, very aggressive replacement of potassium at rates of 20-40 mEq/hr will be necessary.

Caution is necessary if renal function remains depressed and/or urine output does not increase to a level >50 mL/hour. Careful monitoring of the serum potassium is essential for the management of both DKA and HHS.

Insulin

IV insulin can be started as long as the serum potassium is above 3.3 mEq/L and aggressive fluid resuscitation has been started.

Insulin lowers the serum glucose concentration and diminishes ketone production.

ADA treatment guidelines for DKA and HHS suggest starting IV regular insulin with a 0.1 unit/kg bolus and 0.1 unit/kg/hr infusion. Alternatively, the bolus dose can be omitted and a continuous infusion of 0.14 units/kg/hr can be used.

Serum glucose should decrease by about 50 to 70 mg/dL per hour. If the serum glucose does not fall by at least 50 to 70 mg/dL from the initial value in the first hour, the insulin infusion rate should be doubled every hour until a steady decline in serum glucose is achieved.

When the serum glucose reaches 200 mg/dL in DKA or 250 to 300 mg/dL in HHS, the IV saline solution is switched to dextrose in saline, and it may be possible to decrease the insulin infusion rate to 0.02 to 0.05 units/kg/hr. The reason the lowering of glucose is held to this level is that further lowering may promote the development of cerebral edema.

Bicarbonate

Bicarbonate use is controversial because there is a lack of evidence of benefit and there are several potential serious side effects:

1. Reduced cerebral pH

2. Slower recovery of ketosis

3. Post treatment metabolic alkylosis

In addition bicarbonate administration can contribute to further lowering of serum potassium. If the arterial pH is less than 6.9, consider giving 50 mEq of sodium bicarbonate per hour for 2 hours.

Phosphate

Phosphate replacement should be used if severe hypophosphatemia occurs (serum phosphate concentration below 1.0 mg/dL), especially in the setting of cardiac dysfunction, hemolytic anemia, and/or respiratory depression.

Resolution of ketoacidosis in DKA

The hyperglycemic crisis is considered to be resolved when the following goals are reached:

1. The anion gap has ‘closed’ to less than 12 mEq/L

2. The patient is mentally alert (if they had HHS)

3. The patient is able to eat

Once these goals are met, the patient can be converted to subcutaneous insulin.

Patients with preexisting insulin regimens may have their home insulin dose resumed.

In insulin-naive patients, an insulin regimen totaling 0.5 to 0.8 units/kg per day, including bolus and basal insulin should be initiated.

If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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