Diabetic ketoacidosis

Diabetic ketoacidosis is a complication of diabetes that occurs when the body cannot use sugar (glucose) as a fuel source because the body has no insulin or not enough insulin, and fat (triglycerides) is used instead. Byproducts of fat breakdown, called ketones, build up in the body. As fats are broken down, acids called ketones build up in the blood and urine. In high levels, ketones are poisonous. This condition is known as ketoacidosis Blood glucose levels rise (usually higher than 300 mg/dL) because the liver produces glucose to try to combat the problem. However the cells cannot pull in that glucose without insulin. Diabetic ketoacidosis usually occurs in people with type 1 (juvenile) diabetes mellitus (T1DM), but diabetic ketoacidosis can develop in any person with diabetes. Since type 1 diabetes typically starts before age 25 years, diabetic ketoacidosis is most common in this age group, but it may occur at any age. Males and females are equally affected.

Diabetic Ketoacidosis Causes

Diabetic ketoacidosis occurs when a person with diabetes becomes dehydrated. As the body produces a stress response, hormones (unopposed by insulin due to the insulin deficiency) begin to break down muscle, fat, and liver cells into glucose (sugar) and fatty acids for use as fuel. These hormones include glucagon, growth hormone, and adrenaline. These fatty acids are converted to ketones by a process called oxidation. The body consumes its own muscle, fat, and liver cells for fuel. In diabetic ketoacidosis, the body shifts from its normal fed metabolism (using carbohydrates for fuel) to a fasting state (using fat for fuel). The resulting increase in blood sugar occurs, because insulin is unavailable to transport sugar into cells for future use. As blood sugar levels rise, the kidneys cannot retain the extra sugar, which is dumped into the urine, thereby increasing urination and causing dehydration. Commonly, about 10% of total body fluids are lost as the patient slips into diabetic ketoacidosis. Significant loss of potassium and other salts in the excessive urination is also common. The most common events that cause a person with diabetes to develop diabetic ketoacidosis are:

infection such as diarrhea, vomiting, and/or high fever (40%),

missed or inadequate insulin (25%), and newly diagnosed or previously unknown diabetes (15%).

Various other causes may include a heart attack, stroke, trauma, stress, alcohol abuse, drug abuse, and surgery. Approximately 5% to 10% of cases have no identifiable cause.

Diabetic Ketoacidosis Symptoms

A person developing diabetic ketoacidosis may have one or more of these symptoms:

excessive thirst or drinking lots of fluid (polydipsia) frequent urination (polyuria) general weakness vomiting loss of appetite confusion abdominal pain shortness of breath (Kussmaul Breathing) a generally ill appearance dry skin and poor skin turgor dry mouth Tachycardia low blood pressure increased rate of breathing (tachypnea) a distinctive fruity odor on the breath.

Possible Complications

Fluid buildup in the brain (cerebral edema) Heart attack and death of bowel tissue due to low blood pressure Renal failure

Exams and Tests

Ketone testing may be used in type 1 diabetes to screen for early ketoacidosis. The ketones test is done using a urine sample. Ketone testing is usually done at the following times:

When the blood sugar is higher than 240 mg/dL During an illness such as pneumonia, heart attack, or stroke When nausea or vomiting occur During pregnancy

Other tests that may be done to diagnose ketoacidosis include:

Arterial blood gas Blood glucose test Blood pressure measurement Amylase blood test Potassium blood test

Medical Treatment

IV 0.9% saline Correction of any hypokalemia IV insulin Some Trade Names HUMULIN NOVOLIN (as long as serum K is 3.3 mEq/L) Rarely IV Na HCO3 (if pH < 7 after 1 h of treatment) The most urgent goals are rapid intravascular volume repletion, correction of hyperglycemia and acidosis, and prevention of hypokalemia. Identification of precipitating factors is also important. Treatment should occur in intensive care settings because clinical and laboratory assessments are initially needed every hour or every other hour with appropriate adjustments in treatment.

Intravascular volume should be restored rapidly to raise BP and ensure glomerular perfusion; once intravascular volume is restored, remaining total body water deficits are corrected more slowly, typically over about 24 h. Initial volume repletion in adults is typically achieved with rapid IV infusion of 1 to 3 L of 0.9% saline solution followed by saline infusions at 1 L/h or faster as needed to raise BP, correct hyperglycemia, and keep urine flow adequate. Adults with DKA typically need a minimum of 3 L of saline over the first 5 h. When BP is stable and urine flow adequate, normal saline is replaced by 0.45% saline. When plasma glucose falls to < 250 mg/dL, IV fluid should be changed to 5% dextrose in 0.45% saline.For children, fluid deficits are estimated at 60 to 100 mL/kg body weight. Maintenance fluids (for ongoing losses) must also be provided. Initial fluid therapy should be 0.9% saline (20 mL/kg) over 1 to 2 h, followed by 0.45% saline once BP is stable and urine output adequate. The remaining fluid deficit should be replaced over 36 h, typically requiring a rate (including maintenance fluids) of about 2 to 4 mL/kg/h, depending on the degree of dehydration. Hyperglycemia is corrected by administering regular insulin 0.15 unit/kg IV bolus initially, followed by continuous IV infusion of 0.1 unit/kg/h in 0.9% saline solution. Insulin should be withheld until serum K is 3.3 mEq/L. Insulin adsorption onto IV tubing can lead to inconsistent effects, which can be minimized by pre-flushing the IV tubing with insulin solution. If plasma glucose does not fall by 50 to 75 mg/dL in the first hour, insulin doses should be doubled. Children should be given a continuous IV insulin infusion of 0.1 unit/kg/h or higher with or without a bolus Ketones should begin to clear within hours if insulin is given in sufficient doses. However, clearance of ketones may appear to lag because of conversion of hydroxybutyrate to acetoacetate (which is the ketone measured in most hospital laboratories) as acidosis resolves. Serum pH and HCO3 levels should also quickly improve, but restoration of a normal serum HCO3 level may take 24 h. Rapid correction of pH by HCO3 administration may be considered if pH remains < 7 after about an hour of initial fluid resuscitation, but HCO3 is associated with development of acute cerebral edema (primarily in children) and should not be used routinely. If used, only modest pH elevation should be attempted (target pH of about 7.1), with doses of 50 to 100 mEq over 30 to 60 min, followed by repeat measurement of arterial pH and serum K. When plasma glucose becomes 250 to 300 mg/dL (13.88 to 16.65 mmol/L) in adults, 5% dextrose should be added to IV fluids to reduce the risk of hypoglycemia. Insulin dosage can then be reduced (minimum 1 to 2 units/h), but the continuous IV infusion of regular insulin should be maintained until the anion gap has narrowed and blood and urine are consistently negative for ketones. Insulin replacement may then be switched to regular insulin (HUMULIN, NOVOLIN) 5 to 10 units sc q 4 to 6 h. When the patient is stable and able to eat, a typical split-mixed or basal-bolus insulin regimen is begun. IV insulin should be continued for 1 to 4 h after the initial dose of sc insulin is given. Children should continue to receive 0.05 unit/kg/h insulin infusion until sc insulin is initiated and pH is > 7.3. Hypokalemia prevention requires replacement of 20 to 30 mEq K in each liter of IV fluid to keep serum K between 4 and 5 mEq/L. If serum K is < 3.3 mEq/L, insulin should be withheld and K given at 40 mEq/h until serum K is 3.3 mEq/L; if serum K is > 5 mEq/L, K

supplementation can be withheld. Initially normal or elevated serum K measurements may reflect shifts from intracellular stores in response to acidemia and belie the true K deficits that almost all DKA patients have. Insulin replacement rapidly shifts K into cells, so levels should be checked hourly or every other hour in the initial stages of treatment. Hypophosphatemia often develops during treatment of DKA, but phosphate repletion is of unclear benefit in most cases. If indicated (eg, if rhabdomyolysis, hemolysis, or neurologic deterioration occurs), K phosphate 1 to 2 mmol/kg of phosphate, can be infused over 6 to 12 h. If K phosphate is given, the serum Ca level usually decreases and should be monitored. Treatment of suspected cerebral edema is hyperventilation, corticosteroids, and mannitol but these are often ineffective after the onset of respiratory arrest.