DIABETIC KETOACIDOSIS

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DIABETIC KETOACIDOSIS Powered By Docstoc
					Diabetic Ketoacidosis
Gary David Goulin, MD

Goals & Objectives
• Understand the action of insulin on the metabolism of carbohydrates, protein, and fat • Understand the pathophysiology of IDDM and DKA • Understand the management approach to the patient with DKA • Appreciate the complications that can occur during treatment of DKA

Introduction
• Diabetes mellitus is a syndrome of disturbed energy homeostasis caused by a deficiency of insulin or of its action resulting in abnormal metabolism of carbohydrate, protein, and fat • Diabetes mellitus is the most common endocrine-metabolic disorder of childhood and adolescence

Introduction
• Individuals affected by insulin-dependent diabetes confront serious burdens that include an absolute daily requirement for exogenous insulin, the need to monitor their own metabolic control, and the need to pay constant attention to dietary intake

Introduction
• Morbidity and mortality stem from metabolic derangements and from longterm complications that affect small and large vessels and result in retinopathy, nephropathy, neuropathy, ischemic heart disease, and arterial obstruction with gangrene of the extremities

Classification
• Type I Diabetes (insulin-dependent diabetes mellitus, IDDM)
– characterized by severe insulinopenia and dependence on exogenous insulin to prevent ketosis and to preserve life – onset occurs predominantly in childhood – probably has some genetic predisposition and is likely autoimmune-mediated

Classification
• Type II Diabetes (non-insulin-dependent diabetes mellitus, NIDDM)
– patients are not insulin dependent and rarely develop ketosis – generally occurs after age 40, and there is a high incidence of associated obesity – As the prevalence of childhood obesity increases, more adolescents are presenting with NIDDM – insulin secretion is generally adequate; insulin resistance is present – no associated genetic predisposition

Classification
• Secondary Diabetes
– occurs in response to other disease processes:
• exocrine pancreatic disease (cystic fibrosis) • Cushing syndrome • poison ingestion (rodenticides)

Type I Diabetes Mellitus: Epidemiology
• Prevalence of IDDM among school-age children in the US is 1.9 per 1000 • The annual incidence in the US is about 12 15 new cases per 100,000 • Male to female ratio is equal • Among African-Americans, the occurrence of IDDM is about 20 - 30% of that seen in Caucasian-Americans

Type I Diabetes Mellitus: Epidemiology
• Peaks of presentation occur at 5 - 7 years of age and at adolescence • Newly recognized cases appear with greater frequency in the autumn and winter • Definite increased incidence of IDDM in children with congenital rubella syndrome

Type I Diabetes Mellitus: Etiology and Pathogenesis
• Basic cause of clinical findings is sharply diminished secretion of insulin • The mechanisms that lead to failure of pancreatic -cell function are likely autoimmune destruction of pancreatic islets • IDDM is more prevalent in persons with Addison’s disease, Hashimoto’s thyroiditis, and pernicious anemia

Type I Diabetes Mellitus: Etiology and Pathogenesis
• 80 - 90% of newly diagnosed patients with IDDM have anti-islet cell antibodies

Type I Diabetes Mellitus: Pathophysiology
High Plasma Insulin (Postprandial State) Liver: Glucose uptake Glycogen synthesis Absence of gluconeogenesis Lipogenesis Absence of ketogenesis Glucose uptake Glucose oxidation Glycogen synthesis Protein synthesis Low Plasma Insulin (Fasted State) Glucose production Glycogenolysis Gluconeogenesis Absence of lipogenesis Ketogenesis Absence of glucose intake Fatty acid and ketone oxidation Glycogenolyss Proteolysis and amino acid release Absence of glucose uptake Lipolysis and fatty acid release Absence of triglyceride uptake

Muscle:

Adipose tissue: Glucose uptake Lipid synthesis Triglyceride uptake

Type I Diabetes Mellitus: Pathophysiology
• Progressive destruction of -cells leads to a progressive deficiency of insulin • As IDDM evolves, it becomes a permanent low-insulin catabolic state which feeding does not reverse • Secondary changes involving stress hormones accelerate the metabolic decompensation

Type I Diabetes Mellitus: Pathophysiology
• With progressive insulin deficiency, excessive glucose production and impairment of utilization result in hyperglycemia, with glucosuria developing when the renal threshold of ~ 180 mg/dL is exceeded • The resultant osmotic diuresis produces polyuria, urinary losses of electrolytes, dehydration, and compensatory polydipsia

Type I Diabetes Mellitus: Pathophysiology
• Hyperosmolality as a result of progressive hyperglycemia contributes to cerebral obtundation in DKA • Serum osmolality:
– {Serum Na+ + K+} x 2 + glucose + BUN 18 3

Type I Diabetes Mellitus: Pathophysiology
• DKA results in altered lipid metabolism
– increased concentrations of total lipids, cholesterol, triglycerides, and free fatty acids – free fatty acids are shunted into ketone body formation due to lack of insulin; the rate of formation exceeds the capacity for their peripheral utilization and renal excretion leading to accumulation of ketoacids, and therefore metabolic acidosis

Type I Diabetes Mellitus: Pathophysiology
• With progressive dehydration, acidosis, hyperosmolality, and diminished cerebral oxygen utilization, consciousness becomes impaired, and the patient ultimately becomes comatose

Type I Diabetes Mellitus: Clinical Manifestations
• Classic presentation of diabetes in children is a history of polyuria, polydipsia, polyphagia, and weight loss, usually for up to one month • Laboratory findings include glucosuria, ketonuria, hyperglycemia, ketonemia, and metabolic acidosis. Serum amylase may be elevated. Leukocytosis is common

Type I Diabetes Mellitus: Clinical Manifestations
• Keotacidosis is responsible for the initial presentation of IDDM in up to 25% of children
– early manifestations are mild and include vomiting, polyuria, and dehydration – More severe cases include Kussmaul respirations, odor of acetone on the breath – abdominal pain or rigidity may be present and mimic acute appendicitis or pancreatitis – cerebral obtundation and coma ultimately ensue

Type I Diabetes Mellitus: Diagnosis
• Diagnosis of IDDM is dependent on the demonstration of hyperglycemia in association with glucosuria with or without ketonuria • DKA must be differentiated from acidosis and coma due to other causes:
– hypoglycemia, uremia, gastroenteritis with metabolic acidosis, lactic acidosis, salicylate intoxication, encephalitis

Type I Diabetes Mellitus: Diagnosis
• DKA exists when there is hyperglycemia (> 300 mg/dL), ketonemia, acidosis, glucosuria, and ketonuria

Type I Diabetes Mellitus: Treatment
• Treatment is divided into 3 phases
– treatment of ketoacidosis – transition period – continuing phase and guidance

Type I Diabetes Mellitus: Treatment
• Goals of treatment of DKA
– intravascular volume expansion – correction of deficits in fluids, electrolytes, and acid-base status – initiation of insulin therapy to correct catabolism, acidosis

Type I Diabetes Mellitus: Treatment
• Intravascular volume expansion
– dehydration is most commonly in the order of 10% – initial hydrating fluid should be isotonic saline • this alone will often slightly lower the blood glucose • rarely is more than 20 cc/kg fluid required to restore hemodynamics • Treatment of electrolyte abnormalities – serum K+ is often elevated, though total body K+ is depleted – K+ is started early as resolution of acidosis and the administration of insulin will cause a decrease in serum K+

Type I Diabetes Mellitus: Treatment
• Phosphate is depleted as well. Phosphate may be added as KPO4 especially if serum chloride becomes elevated • “Pseudohyponatremia” is often present – Expect that the Na+ level will rise during treatment – Corrected Na+ = Measured Na+ + 0.016(measured glucose - 100) – If Na+ does not rise, true hyponatremia may be present (possibly increasing cerebral edema risk) and should be treated

Type I Diabetes Mellitus: Treatment
• BICARBONATE IS ALMOST NEVER ADMINISTERED
– bicarbonate administration leads to increased cerebral acidosis
• HCO3- combines with H+ and dissociated to CO2 and H2O. Whereas bicarbonate passes the bloodbrain barrier slowly, CO2 diffuses freely, thereby exacerbating cerebral acidosis and cerebral depression

Type I Diabetes Mellitus: Treatment
• Indications for bicarbonate administration include severe acidosis leading to cardiorespiratory compromise • Increasing evidence suggests that subclinical cerebral edema occurs in the majority of patients treated with fluids and insulin for DKA

Type I Diabetes Mellitus: Treatment
• Cerebral edema is the major life-threatening complication seen in the treatment of children with DKA
– clinically apparent cerebral edema occurs in ~1% of episodes of DKA – mortality is 40 - 90% – cerebral edema is responsible for 50 - 60% of diabetes deaths in children

Type I Diabetes Mellitus: Treatment
– Cerebral edema usually develops several hours after the institution of therapy – manifestations include headache, alteration in level of consciousness, bradycardia, emesis, diminished responsiveness to painful stimuli, and unequal or fixed, dilated pupils

Type I Diabetes Mellitus: Treatment
• Excessive use of fluids, large doses of insulin, and especially the use of bicarbonate have been linked to the increased formation of cerebral edema – fluids are generally limited to ~ 3 L/m2/24 hours • Children who present with elevated BUN, PaCO2 < 15 torr, or who demonstrate a lack of an increase in serum Na+ during therapy have an increased probability of cerebral edema • Therapy of cerebral edema may include treatment with mannitol, hypertonic saline and hyperventilation

Type I Diabetes Mellitus: Treatment
• Insulin Therapy
– continuous infusion of low-dose insulin IV (~ 0.1 U/kg/hr) is effective, simple, and physiologically sound – goal is to slowly decrease serum glucose (< 100 mg/dL/hr – frequent laboratory and blood gas analyses are obtained to ensure ongoing resolution of metabolic acidosis

Type I Diabetes Mellitus: Treatment
• “Maintenance” IV fluid at a rate of 2000 2400 cc/m2/day consists of 2/3 NS (0.66%) or NS
– 5% Dextrose is added to IVF when blood glucose is ~ 300 mg/dL – 10% Dextrose is added when blood glucose is ~ 200 mg/dL

Type I Diabetes Mellitus: Treatment
• Insulin is used to treat acidosis, not hyperglycemia – insulin should never be stopped if ongoing acidosis persists • When the acidosis is corrected, the continuous insulin infusion may be discontinued and subcutaneous insulin initiated • With this regimen, DKA usually is usually fully corrected in 36 to 48 hours

Type I Diabetes Mellitus: Treatment
• Hypoglycemic Reactions (Insulin Shock)
– symptoms and signs include pallor, sweating, apprehension, trembling, tachycardia, hunger, drowsiness, mental confusion, seizures and coma – management includes administration (if conscious) of carbohydrate-containing snack or drink – glucagon 0.5 mg is administered to an unconscious or vomiting child

Suggested Reading
• Glaser N, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. NEJM 355;4:264-269.
Menon RK, Sperling MA. Diabetic Ketoacidosis. In: Fuhrman BP, Zimmerman JJ, ed. Pediatric Critical Care. Second Edition. St. Louis: Mosby-Year Book, Inc., 1998:84452. Kohane DS, Tobin JR, Kohane IS. Endocrine, Mineral, and Metabolic Disease in Pediatric Intensive Care. In: Rogers, ed. Textbook of Pediatric Intensive Care. Third Edition. Baltimore: Williams & Wilkins, 1996:1261-72. Magee MF, Bhatt BA. Management of Decompensated Diabetes: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome. In: Zaloga GP, Marik P, ed. Critical Care Clinics: Endocrine and Metabolic Dysfunction Syndromes in the Critically Ill. Volume 17:1. Philadelphia: W.B. Saunders Company, 2001: 75-106.

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Case Scenario #1
• A 10 y/o male (~30 kg) presents to the ED with a one-day history of emesis and lethargy. • Vitals show T 37C, HR 110, RR 25 BP 99/65. Patient is lethargic, but oriented x 3. Exam reveals the odor of acetone on the breath, dry lips, but otherwise unremarkable • Labs: pH 7.05 PaCO2 20, PaO2 100, BE -20, Na+ 133, K + 5.2, Cl 96 CO2 8. Urine shows 4+ glucose and large ketones

Case Scenario #1
• How much fluid would you administer as a bolus? • Would you administer bicarbonate? • What is the “true” serum sodium? • How much insulin would you administer? • What IVF would you start? At what rate?

Case Scenario #2
• A 4 y/o female in the PICU is undergoing treatment for new onset IDDM and DKA. She is on an insulin infusion at 0.1 u/kg/hr, and fluids are running at 2400 cc/m2/day. • Over the last hour, she has been complaining about increasing headache. She is now found to be unresponsive with bilateral fixed and dilated pupils, HR is 50 with BP 150/100. • What is your next step in management?


				
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