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Management of Hyperglycemic Crises in Adults with DiabetesHyperglycemic crisis and metabolic acidosis -
On one end of the spectrum lie absolute insulin deficiency and profound ketosis and acidosis, which is DKA. DKA tends to occur in patients with type 1 diabetes, who, because of destruction of β-cells, exhibit absolute insulin deficiency. On the other end of the spectrum is extreme hyperglycemia without ketosis and acidosis.
As the analogy implies, patients may present with various manifestations of both disorders. For example, a patient with DKA may have used enough insulin to partially suppress ketosis but still manifest profound hyperglycemia. Patients with HHS may also have varying degrees of ketosis and mild acidosis, depending on the degree to which they have been able to produce insulin and the extent of associated factors such as dehydration.
Insulin deficiency causes a lack of glucose utilization in insulin-dependent tissues such as muscle and adipose and therefore leads to hyperglycemia. Lack of insulin also stimulates hyperglycemia by increasing hepatic gluconeogenesis.
This is a common mechanism in both DKA and HHS. Deprived of glucose utilization, the body must look elsewhere for fuel to survive. In addition to hyperglycemia, lack of insulin increases degradation of triglycerides into free fatty acids in adipose tissue, which travel to the liver and are converted to the ketoacids β-hydroxybutyric acid, acetone, and acetoacetate.
Unopposed conterregulatory hormone effect causes further increases in glucose production from the liver and degradation of triglycerides. The surge of ketoacid formation from unrestrained ketone body formation can be profound. DKA develops when the surge of ketoacid production is so powerful that a metabolic acidosis results.
In HHS, there remains sufficient insulin presence to suppress ketosis enough to prevent the development of metabolic acidosis. Dehydration is another common finding in DKA and HHS. Because of osmotic pressure, unregulated diuresis follows.
Patients frequently complain of preceding polyuria and polydipsia. Considerable electrolyte loss may result, especially potassium depletion. Further dehydration and volume contraction can lead to worsening of hyperglycemia.
Patients presenting in HHS and DKA typically exhibit a history of polyuria and polydipsia. Frequently, one can identify a precipitating factor leading to DKA.
Such factors can include inappropriate use of insulin non-compliance , cardiovascular disease, or infection, which may be the most common causes of DKA. Patients with DKA may also manifest leukocytosis simply due to DKA.
It is important to not overlook other possible causes of DKA and HHS, however. Myocardial infarction may precipitate hyperglycemia and DKA via an increase in counterregulatory hormones, such as epinephrine. Drugs such as thiazides, sympathomimetics, second-generation antipsychotics, and corticosteroids may also precipitate HHS and DKA.
Other disorders that may precipitate diabetes include pancreatitis and illicit drug use. Additionally, and especially in patients with type 1 diabetes, decline in diabetes control and hyperglycemia may indicate the onset of an autoimmune thyroid disease, such as Grave's disease or Hashitoxicosis.
Patients may develop progressive hyperglycemia over weeks or days, although patients with DKA may experience more rapid onset than those with HHS. Symptoms of both HHS and DKA include polyuria and polydipsia due to hyperglycemia and signs of dehydration, including lack of skin turgor, hypotension, dry oral mucosae, tachycardia, weakness, and altered sensorium.
Patients with DKA typically exhibit signs of acidosis, such as abdominal pain sometimes severe , nausea, vomiting, and Kussmaul respirations, and may also exhibit guaiac-positive vomitus. Hypothermia, should it be present, is a poor prognostic indicator. Laboratory findings in patients with DKA include hyperglycemia, ketosis, and metabolic acidosis.
Patients who are suspected of DKA or HHS should undergo measurement of electrolytes with anion gap, glucose serological , creatinine and blood urea nitrogen, serum ketones, urinalysis with ketones, complete blood count, A1C, and arterial blood gas testing.
Additionally, electrocardiogram, chest X-ray, and urine, sputum, and blood cultures may be warranted. If children are otherwise healthy and there are no signs of infection, it may be acceptable to omit an infection workup. Significant ketosis has been shown in up to one-third of patients with HHS, again indicative of the continuum of pathology between DKA and HHS.
Buildup of ketoacids is responsible for anion gap metabolic acidosis in DKA. It is important, however, to remember other causes of anion gap metabolic acidoses, including starvation, lactic acidosis especially in patients using metformin , salicylates, ethanol, methanol, ethylene glycol, paraldehyde, renal insufficiency, and isopropyl alcohol intoxication.
Serum potassium levels are typically elevated in response to the presence of acidosis and insulin deficiency, but total body potassium is depleted. Patients presenting with hypokalemia in the setting of DKA are particularly potassium-depleted and require aggressive monitoring and potassium repletion.
Both amylase and lipase may be elevated in the setting of DKA and are not necessarily indicative of pancreatitis. The cornerstones of treatment of DKA and HHS are fluids, insulin, correction of electrolyte abnormalities, and close monitoring.
In the absence of underlying renal and cardiac disease, initial fluid resuscitation should consist of isotonic fluids to restore renal perfusion. Subsequently, fluids may be altered or titrated based on degree of dehydration and electrolyte abnormalities.
Titration of fluids is based on hemodynamic improvement, urine output, laboratory improvement, and clinical response. Patients with underlying cardiac and renal disease may require lower initial fluid resuscitation rates and more frequent monitoring of clinical status to avoid fluid overload.
Insulin therapy for DKA and HHS is typically administered intravenously, although uncomplicated mild to moderate DKA may be managed with subcutaneous insulin therapy.
Typically, in the absence of hypokalemia, patients receive a bolus of intravenous regular insulin at 0. Doses may be titrated based on clinical response, which will vary based on the degree of insulin resistance. For example, patients with type 2 diabetes who present in DKA will typically require a higher dose of insulin than those with type 1 diabetes because of higher insulin resistance.
If subcutaneous insulin is to be used to treat uncomplicated DKA, patients typically receive an initial dose of 0. Such approaches may be associated with a lower cost of hospitalization by avoiding intensive care unit placement. Electrolytes, glucose, blood urea nitrogen, osmolality, creatinine, and pH arterial or venous should be drawn every hours to monitor patients' responses to therapy and to allow titration of insulin and fluids.
It is important to note that hyperglycemia typically resolves before ketosis; therefore, dextrose should be added to fluids as glucose declines as described above. Ketosis should be measured via β-hydroxybutyric acid whenever possible because that is the prevalent ketone body produced in DKA.
The nitroprusside reaction, which is still used in many laboratories to detect ketone formation, does not detect β-hyrdoxybutyric acid and therefore may yield false-negative results.
Most patients presenting in DKA exhibit hyperkalemia as a result of insulin deficiency and acidosis despite total body potassium depletion. Treatment with insulin, restoration of normal circulatory volume, and resolution of acidosis allow total body potassium depletion to manifest itself as hypokalemia during treatment of DKA.
Including mEq of potassium in each liter of fluid is usually sufficient to maintain a potassium concentration within normal limits. This will help to avoid cardiac arrhythmia and skeletal muscle dysfunction because insulin initiation can cause an acute decline in serum potassium concentration.
Use of bicarbonate to raise pH is controversial. Patients also frequently exhibit hypophosphatemia at presentation in DKA, but phosphate repletion has not demonstrated a beneficial effect on clinical outcomes in DKA. Patients receiving phosphate therapy should be monitored closely for hypocalcemia, which can result from phosphate administration.
Patients should resume rapid-acting insulin at meals and intermediate- or long-acting insulin when they are able to eat substantial carbohydrate. It is important to continue intravenous insulin for several hours after resumption of subcutaneous insulin to avoid recurrent hyperglycemia and a possible return to ketosis.
The most common complications that occur when treating adults with ketoacidosis are hypokalemia and hypoglycemia.
Potassium depletion is the most life-threatening electrolyte abnormality in the treatment of DKA. As previously described, total body potassium at presentation in DKA is low despite hyperkalemia because of metabolic acidosis. Delayed potassium supplementation can lead to considerable hypokalemia as the serum potassium concentration drops precipitously in the presence of insulin and resolution of ketoacidosis.
In the setting of normal renal function, patients should receive potassium supplementation in their fluids when the potassium level approaches normal values. Hypoglycemia is also a potential complication of DKA. The threat of hypokalemia and hypoglycemia both also illustrate the importance of frequent reassessment of patients treated for DKA.
Care must also be taken in intravenous fluid administration. Patients with underlying medical conditions such as renal insufficiency or congestive heart failure are susceptible to fluid overload. Patients should be assessed for such disorders before initiation of fluid resuscitation.
Cerebral edema is yet another potential complication of DKA and HHS. It occurs more frequently in pediatric patients than in adults. Signs of cerebral edema include mental status changes, vomiting, headache, lethargy, elevated diastolic blood pressure, decorticate or decerebrate posturing, cranial nerve palsies, or Cheyne-Stokes respiration.
Treatment options include use of mannitol or hypertonic saline to decrease cerebral edema, although there have been no large controlled trials clearly demonstrating benefit. Hyperchloremic nonanion gap metabolic acidosis is a very frequent finding after resolution of DKA.
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Download references. Department of Medicine, Division of Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, GA, USA.
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