Diabetic Ketoacidosis Diabetic Ketoacidosis An anion gap acidosis

Diabetic Ketoacidosis

Diabetic Ketoacidosis · An anion gap acidosis due to severe insulin deficiency and excess of counterregulatory hormones

Insulin Deficiency · · · Insulin is required for efficient transport of glucose into muscle, adipose, and liver cells Proper utilization of glucose within liver cells is also dependent on insulin In the absence of insulin glucose cannot be effectively transported into cells and it accumulates in the blood The liver begins to manufacture glucose from amino acids (gluconeogenesis) Additional glucose is thus secreted into the bloodstream

Insulin Deficiency: Effects on the Kidney · When the degree of hyperglycemia exceeds the · · kidney’s capacity for tubular reabsorption glucose appears in the urine Osmotic diuresis ensues and the patient develops polyuria Severe dehydration may result

Insulin Deficiency: Effects on Lipolysis · Under normal circumstances insulin inhibits lipolysis · In the absense of insulin adipose cells degrade their · · stores of triglycerides into fatty acids Fatty acids are converted by the liver into ketone bodies (acetoacetate and b-hydroxybutyrate) A metabolic acidosis develops

Actions of Glucagon · Glucagon when unopposed by normal insulin is · · · responsible for the hepatic components of diabetic decompensation Increased glycogenolysis Increased gluconeogenesis Increased ketogenesis

· Insulin deficiency causes augmented delivery to the · liver of substrates for glucose and ketone production Glucagon is the switch that activates the hepatic production machinery for glucose and ketones

Precipitating Factors in DKA · · · Failure to take insulin Failure to increase insulin during acute illness, infection Other intercurrent illness such as myocardial infarction, pancreatitis, stroke, trauma or severe emotional stress · The counterregulatory hormones released during medical stress oppose insulin and stimulate glucagon release · Hypovolemia increases the secretion of glucagon, catecholamines by decreasing renal blood flow and this further reduces glucagon degradation by the kidney

Signs and Symptoms of DKA · Polyuria and polydipsia · Kussmaul hyperventiation · Vomiting and abdominal pain · An acetone odor to breath · Dehydration · Stupor and coma

Initial Lab Findings · Hyperglycemia · Anion gap acidosis · Positive urine and serum ketones · Hyperosmolarity

Differential Diagnosis · Anion gap acidosis: (Na + K) - (Cl +Bicarb) >16 · Alcoholic ketoacidosis · Lactic acidosis · Renal failure · Ethylene glycol or methyl alcohol poisoning · Starvation in late pregnancy or lactation (rare)

Initial Lab Findings in DKA Glucose 475 Sodium 132 Potassium 4. 8 Bicarbonate <10 BUN 25 Acetoacetate 4. 8 B-hydroxybutyrate 13. 7 Free Fatty acids 2. 1 Lactate 4. 6 Osmolarity 310

Treatment of DKA · Replacement of fluid and electrolytes · Insulin therapy · Glucose administration

Replacement of Fluid and Electrolytes · · · · Restores perfusion of tissues to normal and lowers levels of counterregulatory hormones Average fluid deficit is 3 -5 liters 1 -2 liters of normal saline administered rapidly in the first 2 hours If hypernatremia develops 1/2 NS can be substituted Hyperkalemia usually present on admission recedes when insulin action begins; potassium replacement is then required Phosphate deficit becomes apparent after insulin administration but is usually clinically silent Bicarbonate is usually not given unless p. H is below 7 or bicarb less than 5 mmol/l

Insulin Therapy · IV bolus of 10 -20 units regular insulin · Follow by hourly insulin infusion · Insulin should be given intravenously until the urine is free of ketones

Glucose Administration · Once insulin has restored glucose uptake and · · suppressed hyperglucagonemia, hypoglycemia will occur unless exogenous glucose is provided Glucose levels always fall before ketone levels decrease therefore exogenous glucose must be provided to cover the insulin needed to reverse ketosis Glucose is usually started when plasma glucose reaches 250 -300 mg/dl

Insulin-Glucose Infusion for DKA Blood glucose Insulin infusion D 5 W infusion <70 0. 5 units per hour 150 cc/hour 70 -100 1. 0 125 101 -150 2. 0 100 151 -200 3. 0 100 201 -250 4. 0 75 251 -300 6. 0 50 301 -350 8. 0 0 351 -400 10. 0 0 401 -450 12. 0 0 451 -500 15. 0 0 >500 20. 0 0

Following Resolution of DKA · · · Most patients require 0. 5 -0. 6 units of insulin per kg body weight 1/2 - 2/3 requirement is given as long-acting insulin - NPH, Lente, Ultralente or Lantus 1/3 -1/2 is given as short-acting meal time insulin - regular, Humalog or Novolog Give both long and short acting insulin subcutaneously about 2 hours prior to tapering insulin infusion Patient education key to avoiding future episodes

Clinical Errors · · · Administration of hypertonic glucose solutions at the outset Giving insulin in patients with severe volume deficit without sufficient fluids can cause fluid shift into cells can precipitate shock Premature administration of potassium before insulin has begun to act can cause fatal hyperkalemia Failure to administer potassium after insulin has begun to act can lead to fatal hypokalemia Recurrent ketoacidosis caused by failure to maintain IV insulin and glucose until ketones have cleared or by failure to administer subcutaneous insulin before stopping IV infusion Hypoglycemia caused by insufficient glucose administration

DKA and Pregnancy · · · Pregnancy is a state of relative insulin resistance marked by enhanced lipolysis and ketogenesis High serum ketones may be teratogenic DKA represents a substantial risk for the fetal compromise

Complications of DKA · Death is usually due to precipitating or complicating · · illness such as MI, pancreatitis or sepsis Infection Vascular thrombosis Cerebral edema Respiratory distress syndrome

Hyperosmolar Nonketotic Coma · · · Extreme hyperglycemia and dehydration which results when the ability to excrete glucose as rapidly as it enters the extracellular space Maximum hepatic glucose output results in a plateau of plasma glucose no higher than 300 -500 mg/dl When sum of glucose excretion plus metabolism is less than the rate at which glucose enters extracellular space

Hyperosmolar Nonketotic Coma · · · Older patients with intercurrent illness with impaired ability to ingest fluids When urine volume falls the ability to excrete glucose falls As glucose rises CNS dysfunction occurs and water intake is additionally impaired The result is extreme hyperglycemia and hyperosmolarity with high mortality Either enough insulin is present to prevent ketosis or the extreme hyperglycemia inhibits lipolysis

Admission Findings: Hyperosmolar Nonketotic Coma · Extreme dehydration · Supine or orthostatic hypotension · Confusion to coma · Seizures or other neurological findings

Admission Findings: Hyperosmolar Nonketotic Coma · Average glucose 1200 · Na 144 ·K 5 · Bicarb 17 · Osm 384

Treatment of HONK · Fluid repletion: give first 2 -3 liters rapidly · Total deficit may be 10 liters: replete 1/2 the deficit in the first 6 hours · Insulin 10 unit bolus followed by sliding scale hourly · Treat underlying precipitating illness