Hyperosmolar hyperglycemic state
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious metabolic complications of diabetes
By DeWayne Miller
You arrive in the emergency department of a small hospital where your patient is waiting. Mr Smith is a 64 year old of Portuguese descent with type 2 diabetes, chronic hepatitis B, CVA 2 years ago, CAD, and hypertension. His home medications include metoprolol, aspirin, atorvastatin, lisinopril, furosemide and metformin. His daughter is at the bedside and reports he had been doing well until last week when he appeared depressed and had not been taking his medications on time. When she checked on him today he was difficult to wake and could not sit up in bed. EMS transported to the hospital.
Now he appears weak, and is very slow to respond. His speech is clear. He is able to move all four extremities with no unilateral deficits. B/P 88/56, pulse is 118, respritory rate 22. Oral temp is 37.4 C. His lungs are clear, cardiac exam shows S1, S2 without murmur or gallop. His abdomen is soft and nontender.
Lab results are:
K+ 4.9 mEq/L,
Cl 88 mEq/L,
HCO3 35 mEq/L,
BUN 99 mg/dL
Creatinine 4.3 mg/dL, glucose 1130 mg/dL
Arterial blood gas: pH 7.40
PCO2 35 mmHg
PO2 88 mmHg
WBC 8.4 k
Serum ketones: negative
Urinalysis: 2+ protein, 4+ glucose, no ketones
Is this data complete enough to make a diagnosis? What are the pertinent results to do so?
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious metabolic complications of diabetes. While DKA is more common, HHS has a higher mortality rate. In adult subjects with DKA overall mortality is <1%, mortality figures for HHS range from 5 to 20%.1,2 Death is usually due in part to a comorbid illness so detection and treatment of the underlying illness should be included.
HHS is the result of a sustained osmotic diuresis, typically over several days to weeks. It is characterized by severe hyperglycemia, hyperosmolarity and dehydration without significant ketoacidosis. Patients with a lack of mobility are at a higher risk because of their limited access to water. One of the most common predisposing factors is not recognizing the signs and symptoms of diabetes and then underestimating the fluid requirements of the patient, especially in an assisted living environment.
HHS has been referred to by several names over the years including hyperosmolar nonketotic state, hyperosmolar coma, and hyperglycemic hyperosmolar nonketotic coma.
Pathophysiology and Differential
Biochemical markers comparing HHS to DKA:
neg to slight
+urine & serum
The reason for the absence of ketoacidosis is not completely understood. One theory is that many of these patients still secrete small amounts of insulin, perhaps just enough to block ketogenesis.
The mean onset age is in the early sixth or seventh decade, but it has presented in all age groups.
Hypokalemia should be anticipated and can pose a life threatening risk if missed. Even if serum potassium (K+) levels appear normal, total body stores will be low. Once correction of acidosis and hyperglycemia is started, the serum K+ will drop.
Patients typically present with severe dehydration and some degree of neurological deficits ranging from minimal to frank coma. Assessment should start with the ABC’s, along with a thorough history focused on the precipitating factors. A diagnosis of decompensated diabetes can be made with a bedside glucose test and clinical presentation. Lab studies should include but not be limited to serum pH, K+, glucose, and serum and urine ketones.
Fluid replacement is the first priority in managing HHS. An approximate fluid deficit can be calculated to guide therapy; the fluid deficit for an adult is typically 8 to 12 liters.
The initial fluid of choice is 0.9% sodium chloride (NS). The initial rate of administration depends on the clinical state of the patient and any comorbid conditions limiting volume resuscitation. If the patient is hypotensive and in shock, give 1 to 2 liters of NS until symptoms improve and urine output is established.
For adults that do not present hypotensive initial rates of 15 to 20 mL/kg/hour for the first hour can be used. Then change to 4 to 14 mL/kg/hour and, if the corrected serum sodium is normal to elevated fluid, can be changed to 0.45% sodium chloride. Total fluid volumes should not exceed 50 mL/kg in the first four hours. Fluids should be calculated to replace the deficit over 24 hours for adults or 48 hours for pediatric patients.
All patients with HHS have a total body depletion of K+. Serum levels may still be in the normal range initially. Rehydration and insulin therapy usually results in a rapid decline of serum K+. If initial serum K+ levels are below 3.3 mEq/L replacement should be started immediately. Rates of administration should be 20 to 40 mEq per hour until serum levels are above 3.3 mEq/L. Then add 20 mEq/L of potassium chloride and recheck serum levels every 1 to 2 hours with a goal of 4 to 5 mEq/L. The most rapid change of serum levels occur in the first 5 hours of treatment.
Magnesium replacement need only be initiated outside of the ICU setting if the serum level is low. K+ and magnesium regulation is closely related and hypokalemia correction may be dependant on magnesium.
Insulin therapy should be held until serum K+ is > 3.3mEq/L and fluid replacement has restored perfusion. The recommended dose of regular insulin is 0.1 units/kg per hour IV. A bolus of 0.15 units/kg can be given, however studies have failed to show any benefit to bolus therapy for adults. Bolus therapy is not recommended for pediatric patients. Insulin infusions should not be interrupted once started and serum glucose levels should be checked hourly. Decrease serum glucose levels by no more than 50 to 75 mg/dL per hour to no less than a serum level of 300 mg/dL. Once that level is reached D5W should be added to IV fluids and the insulin rate can be changed to 0.05 U/kg per hour.
If the glucose level does not improve in the first hour ensure the adequacy of fluid volume replacement and increase the insulin dose to 0.2 U/kg per hour.
Searching for and treating the underlying illness that precipitated HHS is crucial in the management of HHS.
It is difficult to predict who is at the greatest risk for complications. Indicators point to overly aggressive volume replacement during the first 4 hours. Cerebral edema is uncommon in adults but is present in >50% of the fatalities in pediatrics with DKA. Little credible data exists on incidence or predisposing factors of cerebral edema in HHS. It is reasonable to assume gradual correction of electrolyte abnormalities and water deficits would place patients at less risk than rapid changes.
Take home points:
- Fluid replacement is the first priority
- Total body K+ stores will be low
- Gradually correct hyperglycemia and hyperosmolarity
- Frequently reassess LOC, hydration and electrolytes
- Find the precipitating illness / cause
1. Ennis ED, Stahl EJVB, Kreisberg RA. The hyperosmolar hyperglycemic syndrome. Diabetes Rev 1994;2:115–126
2. Lorber D. Nonketotic hypertonicity in di- abetes mellitus. Med Clin North Am 1995;79:39 –52
3. American Diabetes Association. Hyperglycemic crises in diabetes. Diabetes Care 2004; 27(Suppl 1):S94–102.
4. Marx J.A., Hockberger R.S., Walls R.M., et al; Rosen’s Emergency Medicine: seventh edition. Philadelphia, Lippincott Williams & Wilkins, 2010. pp 1644-1646.
5. Nugent. Hyperosmolar hyperglycemic state. Emerg Med Clin North Am (2005) vol. 23 (3) pp. 629-48, vii