Written By: Kenny Banh, MD & Jason Tsukamaki, MD University of California San Francisco, Fresno, California
Edited By: David A. Wald Temple University School of Medicine Philadelphia, Pennsylvania
The objectives of this module will be to:
- Review the classic presentation of a patient with hyperglycemia, including DKA and HHS.
- Review the diagnostic work up of the hyperglycemic patient.
- Review the principles of managing a patient with hyperglycemia.
Hyperglycemia complicating diabetes ranges from the asymptomatic and benign in patients with mild to moderate uncomplicated hyperglycemia to the life-threatening (i.e. diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). DKA and HHS represent a spectrum of complications from diabetes and differ mainly in the level of hyperglycemia, extent of dehydration and presence and degree of ketoacidosis. Each condition revolves around insulin deficiency, either absolute or relative. DKA and HHS are the most serious, acute metabolic complications of diabetes. Generally DKA occurs in younger patients (<65 y/o) with Type 1 diabetes and usually evolves rapidly over 24 hours. HHS usually occurs in older patients (>65 y/o) with poorly controlled Type 2 diabetes and evolves over several days. Both disease entities originate from a reduction in insulin and an increase in counter-regulatory stress hormones. In the emergency department hyperglycemia is most often seen as a complication of diabetes (both types 1 and 2). Hyperglycemia is defined as:
- Fasting Blood Glucose (for 8 hrs) > 90 - 130 mg/dL
- Postprandial Blood Glucose > 180 mg/dL
Is a state of absolute insulin deficiency, hyperglycemia, anion gap acidosis, and dehydration. It is classically seen in Type 1 diabetics and typically occurs in younger people. The most common causes are infections, disruption of insulin therapy, or as the presentation of new onset diabetes.
Is a state of hyperglycemia, hyperosmolarity, and dehydration without significant ketoacidosis. It is typically seen in Type 2 diabetics, has a higher mortality rate compared to DKA, and occurs in older patients. It most commonly occurs in poorly controlled Type 2 diabetics with an underlying infection.
Initial Actions and Primary Survey
In these patients, a thorough history and physical examination should be performed with a focus on trying to identify a precipitating cause of the hyperglycemia. In patients with an incidental finding of mild to moderate hyperglycemia or those with minor symptoms little else may be necessary beyond anticipatory guidance and proper follow up. In those with blood glucose levels greater than 300 - 350 mg/dL, a urinalysis may help identify the presence of ketones. If present, a basic metabolic profile should be obtained to exclude an increased gap metabolic acidosis. Many of these patients will need intravenous administration of saline. In a patient who is more ill appearing, hemodynamically unstable and those suspected of having DKA or HHS the following should be instituted;
- Close attention should be paid to the ABC's
- 2 large bore intravenous lines should be placed
- Normal saline 1-2 liters (adult), bolus of 20 cc/kg (children), attention should be paid to the volume status of the patient. Be cautious of high volume crystalloid infusion in patients with congestive heart failure or chronic renal failure
- Place the patient on a cardiac monitor
- Dietary indiscretion
- New onset or uncontrolled diabetes
A number of other conditions can affect diabetic patients resulting in an increase in counter regulatory hormones and hyperglycemia, some of which can precipitate DKA or HHS.
- Cocaine use
- Infection / sepsis
- Myocardial ischemia / infarction
Patients with mild hyperglycemia may in fact be asymptomatic. Once the blood glucose level rises above approximately 180 mg/dL (renal threshold), patients will start to develop an osmotic diuresis. At this time, patients may present with a variety of complaints including;
- Weight loss
These symptoms will be highly variable from patient to patient. Some will also develop tachycardia, dizziness, lightheadedness and weakness as a result of dehydration and electrolyte imbalance. As the degree of hyperglycemia progresses leading to marked volume depletion, electrolyte disturbance, acidosis, ketosis, etc. additional symptoms may be seen including;
- Abdominal pain
- Hyperpneic respirations (fast and deep Kaussmaul respirations)
- Ketotic breath (fruity odor in DKA)
- Marked tachycardia
- Neurologic symptoms (seizures, focal weakness, lethargy, coma, death) - more prevalent in HHS
The extent of diagnostic testing will depend on the patients presenting complaints and suspicion for complications related to their diabetes / hyperglycemia. Some patients may need no more than bedside glucose testing +/- urinalysis. In patients suspected of having DKA or HHS, additional tests should be obtained:
- Basic metabolic profile
- Complete blood count (often obtained when suspicious for an infectious etiology, sensitive, not specific)
- Blood gas determination (venous blood gas sample provides accurate information regarding blood pH and closely approximates that of arterial pH)
- Additional electrolytes (phosphorus, magnesium) may be important in patients profoundly dehydrated
- Electrocardiogram (ECG) (In patients with marked acidemia or severe hyperglycemia, extracellular potassium shifts may result in ECG manifestations of hyperkalemia despite total body losses)
- Additional testing based on patient presentation (lipase, hepatic functions, chest radiograph, blood cultures, etc.)
Diagnosing DKA or HHS is done at the bedside with a high clinical suspicion based on the patient history, physical exam, and initial laboratory findings. The following table presents the diagnostic criteria for DKA and HHS. It should be remembered that HHS can present with both an anion gap and ketosis (approximately 50% of patients) but usually will not have a significant acidosis.
|Plasma glucose (mg/dL)||>250||>600|
|Urine ketones||+++||- or faintly +|
|Serum ketones||+++||- or faintly +|
|Serum osmolality (mOsm/kg)||↑||↑↑↑|
|Anion gap||>>>12||Normal (12-16)|
|Mental Status||Variable (from alert to coma)||Stupor/coma|
In patients with an uncomplicated presentation associated with mild - moderate hyperglycemia, often no urgent treatment is required, however in some cases, patients may requires intravenous fluids. Treatment for DKA and HHS is centered around correcting the intravascular volume depletion, management of electrolyte abnormalities, insulin replacement therapy and identification of and treatment of any underlying precipitants. Fluid replacement
- Average fluid loss in DKA 3-6 liters and HHS 8-10 liters
- Start with isotonic saline (0.9%) at 15-20 ml/kg per hour for the first few hours (in the average adult this will be approximately 1 liter/hr)
- Switch to one-half isotonic saline (0.45%) when the serum sodium normalizes
- Add dextrose to the intravenous fluids when serum glucose reaches 250 mg/dL
- Insulin therapy should only be started after adequate fluid resuscitation
- Start with an infusion of regular insulin at 0.1 U/kg/hr. Some authors do not consider an insulin loading dose mandatory, if administering a loading dose use 0.1 U/kg of regular insulin
- Double the dose of insulin if the blood glucose does not fall by 50-70 mg/dL in the first hour
- If the initial potassium is < 3.3 mEq/L then DELAY insulin therapy until fluid and potassium replacement
- Administer potassium with initial fluid replacement if potassium levels are normal or low and maintained between 4 - 5 mEq/L
- Use of bicarbonate is controversial therapy, may cause a paradoxical fall in cerebral pH and neurologic deterioration
- Certain situations may warrant the use of bicarbonate
- Severe acidosis with pH < 6.90
- Severe life-threatening hyperkalemia
- Cardiac or persistently hypotensive patient
Treatment of any other underlying infections or other disease processes. Patients with both DKA and HHS will require serial monitoring of:
- Blood glucose every hour until stable, then every 2 - 4 hours
- Basic metabolic profile and blood pH every 2 - 4 hours during therapy until patient stablizes
One very serious complication of DKA/HHS is cerebral edema. It is mainly seen in children and young adults, occurring 4-12 hours into treatment with a high degree of morbidity and mortality. Clinically it is often preceded by headache, lethargy, and then neurologic deterioration (seizures, coma) with bradycardia and respiratory arrest. Although not completely understood development of cerebral edema is correlated with bicarbonate administration and massive fluid resuscitation.
Patients with uncomplicated hyperglycemia can typically be managed as an outpatient. Some after the administration of intravenous fluids, subcutaneous insulin while others may be discharged without treatment as long as they have proper follow up with a primary care physician. New onset diabetics may at times be discharged on glucophage provided they are adequately hydrated, are not in DKA and have good outpatient follow up.
All patients with DKA and HHS require hospital admission. Depending on disease severity some may require monitoring in the ICU.
Pearls and Pitfalls
- Failure to consider other coexisting illness as a precipitant (infection, myocardial infarction) of DKA and HHS
- Starting insulin therapy prior to administering fluids and checking the potassium level
- Not repleting potassium when the levels drop to normal or low normal range
- Hypoglycemia from failure to start glucose-containing fluids once the blood glucose levels are < 250 mg/dL in DKA / HHS
- In children, failure to recognize and promptly treat signs/symptoms of cerebral edema
- Kitabchi AE, Rose BD. Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults. Uptodate.com. Available at: http://www.uptodate.com/patients/content/topic.do?topicKey=~_wwcvV7HkHijO4w. Accessed June 17, 2010.
- Rucker DW. DKA. Emedicine.com. Available at: http://emedicine.medscape.com/article/766275-overview. Accessed June 17, 2010.
- Sergot PB. HHS. Emedicine.com. Available at: http://emedicine.medscape.com/article/766804-overview. Accessed June 17, 2010.