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Diabetic ketoacidosis in the pediatric population
Pediatric Perspective
Stuart A. Bradin, DO, FAAP
Diabetic Ketoacidosis in the Pediatric Population A 14-year-old boy with benign history is found unresponsive in his bedroom by his sister. There is vomit on his shirt. Thinking back, Mom remembers the patient drinking and urinating “a lot” in the past several weeks and thinks “his clothes hang off of him.” He has been home from school the past few days because of fatigue and malaise “and just not feeling well.” They called their doctor when he complained of some abdominal pain and were told, “It's the flu and will get better in a few days.” He has had no fever, rash, injury, or ingestion. His vital signs are as follows: Heart rate: 130 Respiratory rate: 32 Blood pressure: 90/65 Temperature: 37° C Weight: 55 kg General exam: somnolent but arousable, will open eyes on command, fruity odor on breath Airway: patent, no stridor Breathing: tachypneic, Kussmaul respirations Circulation: clammy, cool skin, capillary refill 4 seconds, parched lips, sunken eyes Abdomen: mildly tender diffusely, no distention, BS x 4 quadrants Pupils: 3-4 mm b/l Glasgow Coma Score: 12-13 Chem stix: “high” Emergency personnel give the boy oxygen by face mask, start 2 intravenous lines, and run them wide open as they take him to the emergency department. En route, the patient is responsive to pain, he has a Glasgow Coma Score of only 5, and his pupils are unequal. Upon arrival, his heart rate is 75, his blood pressure is 135/95, and he has agonal respirations. His arterial blood gas is pH 7.02, PCO2 22, and base excess–18.
What happened to this child? Diabetes is second only to asthma as the most prevalent chronic disease of childhood in the United States.1,2 Current data suggest that both insulin- and noninsulin-dependent diabetes mellitus (Types 1 and 2, IDDM and NIDDM, respectively) are increasing globally.2 Almost 13,000 children are newly diagnosed with diabetes each year.1,2 Close to 2 of September-October 2005
every 1000 US children have Type 1 DM, and the figure appears to be rising as rates of pediatric obesity increase. Prevalence among boys and girls is equal.1 Diabetic ketoacidosis (DKA) is one of the most common and dreaded complications of diabetes.1-5 Thought to occur only in Type 1 diabetics, it is now recognized in the Type 2 diabetic patient as well.2,3 Frequently, DKA is the initial presentation of children with new onset Type 1 diabetes; in fact, it occurs in 25 to 40% of children with new onset disease.2,6 It is the most common cause for hospitalization in diabetics under 20 years old.2,4 Incidence of DKA in children with known Type 1 diabetes is 8 per 100 person-years.2,4 DKA remains the leading cause of death in children with diabetes. 1 , 3 , 4 , 7 Mortality is predominantly caused by the occurrence of cerebral edema.4,6-8 Prevention of DKA and early recognition and treatment of its complications should be the primary goal in the management of children with diabetes.1,2,4,7,8 DKA is defined as ketoacidosis that is associated with varying degrees of dehydration.1 Hallmarks include hyperglycemia (blood sugar > 200 mg/dL) and metabolic acidosis (pH < 7.30 and/or HCO3 < 15 meq/L) and accompanied with associated glucosuria, ketonuria, ketonemia, and electrolyte abnormalities.1-4,7 This results in hyperosmolality and volume depletion. In DKA, lack of insulin prohibits use of glucose on a cellular level. Counter-regulatory hormone levels rise, including glucagon, epinephrine, cortisol, and growth hormone. Gluconeogenesis and glycogenolysis in the liver occurs. Lipolysis occurs in fatty acids, creating ketoacids. Lack of insulin prevents tissues from using glucose and ketones. Subsequently, hyperglycemia and ketonemia develop. Glucose in the kidney tubules draws water and electrolytes into the urine, creating an osmotic diuresis that results in volume and electrolyte depletion.1,2,9 DKA is generally classified by the severity of acidosis, from mild (pH < 7.3 and HCO3 < 15 meq/L) to severe (pH < 7.1 and HCO3 < 5 meq/L).7 Clinical manifestations of DKA are related to the degree of dehydration and acidosis.3 Clinical presentation can vary.1-3 Previously undiagnosed patients may have a history of fatigue, weight loss, polyuria, and/or polydipsia for weeks before seeking medical attention.1,3 Often, symptoms mimic other common ailments including gastroenteritis, appendicitis, hyperventilation, or an ingestion.2 Suspect DKA in patients when there is vomiting, dehydration, shortness of breath, abdominal pain, or altered 181
mentation.8 Weight loss, decreased activity, or irritability with signs of dehydration, as well as severe, persistent Candidal diaper rash should heighten suspicion for diabetes in the infant or young child.3 Noncompliance, especially in the adolescent child, is the most common reason that kids with known IDDM go into DKA.2,3 Stress, intercurrent illness, and limited knowledge and understanding about diabetes may precipitate DKA as well.2,3 Any patient with diabetes and vomiting should be presumed to be in DKA until proven otherwise.8 The acute management of DKA in children is different from that of adults; children are at increased risk for developing acute cerebral edema. This complication appears to be unique to the pediatric population. 1 0 One in 100 episodes of pediatric DKA is complicated by clinical cerebral edema. 10,11 The mortality rate of this most dreaded complication of DKA has remained constant for years.5 It is lethal in 20 to 50% of its victims,5 with another third suffering serious neurologic sequelae and disability.10 Classically, symptomatic cerebral edema develops within 4 to 12 hours after therapy has been started, although subclinical brain edema has been described in patients before initiation of any therapy.1 Many factors have been thought to increase the risk for cerebral edema, including rapid intravenous hydration, rapid change in sodium or glucose levels during treatment, and young age of the patient.1,2,12 However, the actual etiology of cerebral edema is unknown,12 and its mechanism is a mystery.10,13 Multiple recent studies have shown no association with previously cited risk factors and occurrence of cerebral edema.5,11,13,14 Though variations in treatment may worsen an ongoing process, cerebral edema is not necessarily caused by therapeutic interventions. 11 Only the use of bicarbonate therapy and increased severity of dehydration upon presentation, as reflected by increased BUN and lower serum PaCO2, have been associated with an increased risk for the development of cerebral edema. 5 , 1 1 , 1 4 Most recent data support the hypothesis that cerebral edema in DKA is related to brain ischemia and children are more affected than adults because of their increased baseline oxygen requirements.11 Patient management should be directed to correction of dehydration, acidosis, and any metabolic derangements while minimizing adverse outcomes.1,2 Much controversy exists regarding optimal fluid therapy. 1,12 Protocols vary among institutions and individuals.1 The greatest controversy remains how best to administer fluids and prevent increased intracranial pressure.2,12 Within this context, how should we treat the child in DKA?1-3,7-9,14 1. Fluid resuscitation
•Assume 10% dehydration4 •deficit 100 cc/kg minimum •Lactated ringer's solution or normal saline solution bolus at 20 cc/kg initially over 1 hour if stable, faster if in shock •If perfusion still poor, 2nd bolus at 10-20 cc/kg •When hemodynamically stable, slow subsequent volume expansion 182
•Change to .45-.9 normal saline solution •Rehydration over 48 hours; volume no more than 2x maintenance in first 24 hours •Calculate maintenance requirements: 1000 cc for first 10 kg + 5 cc for next 10 kg + 20 cc/kg over 20 kg or 100 cc/kg for first 10 kg + 50 cc/kg for next 10 kg + 20 cc/kg for each additional kg 2. Insulin therapy
•No bolus necessary •Start insulin drip within 2 hrs of intravenous fluid •Initial dose 0.1 unit/kg/hr (regular insulin) •Goal is to drop glucose slowly by 75 to 100 mg/dL/hr •When serum glucose is 250 to 300, add D5 to intravenous fluid •Continue drip until pH > 7.3 and/or HC03 > 15 meq/L •Reduce insulin drip only when acidosis is corrected 3. Potassium
•Total body depletion with DKA •Acidosis shifts K out of cells •Initially, K normal or elevated •Will drop with insulin and as acidosis corrects •Replacement therapy once patient voids as follows: 3 to 5 mEq/kg/day < 4, add 30 mEq/L KCl + 30 KPO4 4 to 6, add 20 mEq/L KCl + 20 KPO4; if K < 4, 30 mEq/L KC1 + 30 mEq/L KP04; if K 4 = 6, add 20 mEq/L KC1 + 20 mEq KP04 •Can use K acetate as well 4. Sodium
•Expected 1.6 mEq/L decrease for every 100 mg/dL increase •Serum glucose > 100 mg/dL should rise as glucose corrects 5. Bicarbonate therapy
DO NOT USE! Associated with cerebral edema 6. Labs
•Chem stix, CBC, lytes, VBG, U/A, BUN, creatinine, mag, phos •Monitor chem stix/ vbg q 1 hour for several hours treatment, q2 hr lytes •Space q 2-4 hours as pt corrects •Dip each void for ketones •Severely dry may need Foley •New onset- T3/T4/TSH, HgbA1C •Islet cell antibodies 7. Monitoring
•Cardiac monitor, EKG if high K •Call to Endo •Frequent neuro checks •Diabetic flow sheet 8. Cerebral Edema
•H/A, change in mentation/speech •Incontinence, dizziness, asymmetric pupils •If symptomatic, already advanced edema Air Medical Journal 24:5
•Cushing’s triad (bradycardia, HTN, irregular resp •If intubate, DO NOT aggressively hyperventilate •Mannitol 0.25- 1 g/kg over 20 min potentially can worsen dehydration •3% saline (2, 10) 5-10 cc/kg over 30 min •Fluid restriction •Elevate head bed 30 degrees •Emergent CT •Neurosurgery consult
References 1. Scarfone RJ, Kelly A. The recognition and management of diabetic ketoacidosis in children. Pediatr Emerg Med Reports 2004;9:129-40. 2. Hafeez W, Vuguin P. Managing diabetic ketoacidosis—a delicate balance. Contemp Pediatr 2000;17(6):72-83. 3. Jeha G, Haymond MW. Treatment and complications of diabetic ketoacidosis in children. Available at: uptodate.com 4. Rosenbloom AL, Hanas R. Diabetic ketoacidosis: treatment guidelines. Clin Pediatr 1996;35:261-6. 5. Brown TB. Cerebral edema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J 2004;21:141-4. 6. Quintana EC. Factors associated with adverse outcomes in children with diabetic ketoacidosis-relatedcerebral edema. Ann Emerg Med 2004;43:793-4. 7. Dunger DB, Sperling MA, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004;89:188-94.
September-October 2005
8. Kaufman FR. Type 1 diabetes mellitus. Pediatr Rev 2003;24:291-9. 9. Baumann EE, Thorp F. Endocrine and metabolic emergencies. In: Strange GR, editor. Pediatric emergency medicine: just the facts. New York: McGraw-Hill; 2004. p. 249-50. 10. Levitsky LL. Symptomatic cerebral edema in diabetic ketoacidosis: the mechanism is clarified but still far from clear. J Pediatr 2004;145:149-50. 11. Glaser N, Barnett P, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001;344:264-9. 12. Felner EI, White PC. improving management of diabetic ketoacidosis in children. Pediatrics 2001;108:735-40. 13. Glaser NS, Wooton-Gorges SL, Marcia JP, et al. Mechanism of cerebral edema in children with diabetic ketoacidosis. J Pediatr 2004;145:164-71. 14. Lawrence SE, Cumming EA, et al. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005;146:688-92. 15. Kamat P, Vats A, et al. Use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. Pediatr Crit Care Med 2003;4:239-42.
Stuart A Bradin, DO, FAAP, is a clinical assistant professor of pediatrics and emergency medicine in the division of pediatric emergency medicine at the University of Michigan Health System in Ann Arbor, Mich. 1067-991X/$30.00 Copyright 2005 by Air Medical Journal Associates doi:10.1016/j.amj.2005.06.005
183
Stuart A. Bradin, DO, FAAP
Diabetic Ketoacidosis in the Pediatric Population A 14-year-old boy with benign history is found unresponsive in his bedroom by his sister. There is vomit on his shirt. Thinking back, Mom remembers the patient drinking and urinating “a lot” in the past several weeks and thinks “his clothes hang off of him.” He has been home from school the past few days because of fatigue and malaise “and just not feeling well.” They called their doctor when he complained of some abdominal pain and were told, “It's the flu and will get better in a few days.” He has had no fever, rash, injury, or ingestion. His vital signs are as follows: Heart rate: 130 Respiratory rate: 32 Blood pressure: 90/65 Temperature: 37° C Weight: 55 kg General exam: somnolent but arousable, will open eyes on command, fruity odor on breath Airway: patent, no stridor Breathing: tachypneic, Kussmaul respirations Circulation: clammy, cool skin, capillary refill 4 seconds, parched lips, sunken eyes Abdomen: mildly tender diffusely, no distention, BS x 4 quadrants Pupils: 3-4 mm b/l Glasgow Coma Score: 12-13 Chem stix: “high” Emergency personnel give the boy oxygen by face mask, start 2 intravenous lines, and run them wide open as they take him to the emergency department. En route, the patient is responsive to pain, he has a Glasgow Coma Score of only 5, and his pupils are unequal. Upon arrival, his heart rate is 75, his blood pressure is 135/95, and he has agonal respirations. His arterial blood gas is pH 7.02, PCO2 22, and base excess–18.
What happened to this child? Diabetes is second only to asthma as the most prevalent chronic disease of childhood in the United States.1,2 Current data suggest that both insulin- and noninsulin-dependent diabetes mellitus (Types 1 and 2, IDDM and NIDDM, respectively) are increasing globally.2 Almost 13,000 children are newly diagnosed with diabetes each year.1,2 Close to 2 of September-October 2005
every 1000 US children have Type 1 DM, and the figure appears to be rising as rates of pediatric obesity increase. Prevalence among boys and girls is equal.1 Diabetic ketoacidosis (DKA) is one of the most common and dreaded complications of diabetes.1-5 Thought to occur only in Type 1 diabetics, it is now recognized in the Type 2 diabetic patient as well.2,3 Frequently, DKA is the initial presentation of children with new onset Type 1 diabetes; in fact, it occurs in 25 to 40% of children with new onset disease.2,6 It is the most common cause for hospitalization in diabetics under 20 years old.2,4 Incidence of DKA in children with known Type 1 diabetes is 8 per 100 person-years.2,4 DKA remains the leading cause of death in children with diabetes. 1 , 3 , 4 , 7 Mortality is predominantly caused by the occurrence of cerebral edema.4,6-8 Prevention of DKA and early recognition and treatment of its complications should be the primary goal in the management of children with diabetes.1,2,4,7,8 DKA is defined as ketoacidosis that is associated with varying degrees of dehydration.1 Hallmarks include hyperglycemia (blood sugar > 200 mg/dL) and metabolic acidosis (pH < 7.30 and/or HCO3 < 15 meq/L) and accompanied with associated glucosuria, ketonuria, ketonemia, and electrolyte abnormalities.1-4,7 This results in hyperosmolality and volume depletion. In DKA, lack of insulin prohibits use of glucose on a cellular level. Counter-regulatory hormone levels rise, including glucagon, epinephrine, cortisol, and growth hormone. Gluconeogenesis and glycogenolysis in the liver occurs. Lipolysis occurs in fatty acids, creating ketoacids. Lack of insulin prevents tissues from using glucose and ketones. Subsequently, hyperglycemia and ketonemia develop. Glucose in the kidney tubules draws water and electrolytes into the urine, creating an osmotic diuresis that results in volume and electrolyte depletion.1,2,9 DKA is generally classified by the severity of acidosis, from mild (pH < 7.3 and HCO3 < 15 meq/L) to severe (pH < 7.1 and HCO3 < 5 meq/L).7 Clinical manifestations of DKA are related to the degree of dehydration and acidosis.3 Clinical presentation can vary.1-3 Previously undiagnosed patients may have a history of fatigue, weight loss, polyuria, and/or polydipsia for weeks before seeking medical attention.1,3 Often, symptoms mimic other common ailments including gastroenteritis, appendicitis, hyperventilation, or an ingestion.2 Suspect DKA in patients when there is vomiting, dehydration, shortness of breath, abdominal pain, or altered 181
mentation.8 Weight loss, decreased activity, or irritability with signs of dehydration, as well as severe, persistent Candidal diaper rash should heighten suspicion for diabetes in the infant or young child.3 Noncompliance, especially in the adolescent child, is the most common reason that kids with known IDDM go into DKA.2,3 Stress, intercurrent illness, and limited knowledge and understanding about diabetes may precipitate DKA as well.2,3 Any patient with diabetes and vomiting should be presumed to be in DKA until proven otherwise.8 The acute management of DKA in children is different from that of adults; children are at increased risk for developing acute cerebral edema. This complication appears to be unique to the pediatric population. 1 0 One in 100 episodes of pediatric DKA is complicated by clinical cerebral edema. 10,11 The mortality rate of this most dreaded complication of DKA has remained constant for years.5 It is lethal in 20 to 50% of its victims,5 with another third suffering serious neurologic sequelae and disability.10 Classically, symptomatic cerebral edema develops within 4 to 12 hours after therapy has been started, although subclinical brain edema has been described in patients before initiation of any therapy.1 Many factors have been thought to increase the risk for cerebral edema, including rapid intravenous hydration, rapid change in sodium or glucose levels during treatment, and young age of the patient.1,2,12 However, the actual etiology of cerebral edema is unknown,12 and its mechanism is a mystery.10,13 Multiple recent studies have shown no association with previously cited risk factors and occurrence of cerebral edema.5,11,13,14 Though variations in treatment may worsen an ongoing process, cerebral edema is not necessarily caused by therapeutic interventions. 11 Only the use of bicarbonate therapy and increased severity of dehydration upon presentation, as reflected by increased BUN and lower serum PaCO2, have been associated with an increased risk for the development of cerebral edema. 5 , 1 1 , 1 4 Most recent data support the hypothesis that cerebral edema in DKA is related to brain ischemia and children are more affected than adults because of their increased baseline oxygen requirements.11 Patient management should be directed to correction of dehydration, acidosis, and any metabolic derangements while minimizing adverse outcomes.1,2 Much controversy exists regarding optimal fluid therapy. 1,12 Protocols vary among institutions and individuals.1 The greatest controversy remains how best to administer fluids and prevent increased intracranial pressure.2,12 Within this context, how should we treat the child in DKA?1-3,7-9,14 1. Fluid resuscitation
•Assume 10% dehydration4 •deficit 100 cc/kg minimum •Lactated ringer's solution or normal saline solution bolus at 20 cc/kg initially over 1 hour if stable, faster if in shock •If perfusion still poor, 2nd bolus at 10-20 cc/kg •When hemodynamically stable, slow subsequent volume expansion 182
•Change to .45-.9 normal saline solution •Rehydration over 48 hours; volume no more than 2x maintenance in first 24 hours •Calculate maintenance requirements: 1000 cc for first 10 kg + 5 cc for next 10 kg + 20 cc/kg over 20 kg or 100 cc/kg for first 10 kg + 50 cc/kg for next 10 kg + 20 cc/kg for each additional kg 2. Insulin therapy
•No bolus necessary •Start insulin drip within 2 hrs of intravenous fluid •Initial dose 0.1 unit/kg/hr (regular insulin) •Goal is to drop glucose slowly by 75 to 100 mg/dL/hr •When serum glucose is 250 to 300, add D5 to intravenous fluid •Continue drip until pH > 7.3 and/or HC03 > 15 meq/L •Reduce insulin drip only when acidosis is corrected 3. Potassium
•Total body depletion with DKA •Acidosis shifts K out of cells •Initially, K normal or elevated •Will drop with insulin and as acidosis corrects •Replacement therapy once patient voids as follows: 3 to 5 mEq/kg/day < 4, add 30 mEq/L KCl + 30 KPO4 4 to 6, add 20 mEq/L KCl + 20 KPO4; if K < 4, 30 mEq/L KC1 + 30 mEq/L KP04; if K 4 = 6, add 20 mEq/L KC1 + 20 mEq KP04 •Can use K acetate as well 4. Sodium
•Expected 1.6 mEq/L decrease for every 100 mg/dL increase •Serum glucose > 100 mg/dL should rise as glucose corrects 5. Bicarbonate therapy
DO NOT USE! Associated with cerebral edema 6. Labs
•Chem stix, CBC, lytes, VBG, U/A, BUN, creatinine, mag, phos •Monitor chem stix/ vbg q 1 hour for several hours treatment, q2 hr lytes •Space q 2-4 hours as pt corrects •Dip each void for ketones •Severely dry may need Foley •New onset- T3/T4/TSH, HgbA1C •Islet cell antibodies 7. Monitoring
•Cardiac monitor, EKG if high K •Call to Endo •Frequent neuro checks •Diabetic flow sheet 8. Cerebral Edema
•H/A, change in mentation/speech •Incontinence, dizziness, asymmetric pupils •If symptomatic, already advanced edema Air Medical Journal 24:5
•Cushing’s triad (bradycardia, HTN, irregular resp •If intubate, DO NOT aggressively hyperventilate •Mannitol 0.25- 1 g/kg over 20 min potentially can worsen dehydration •3% saline (2, 10) 5-10 cc/kg over 30 min •Fluid restriction •Elevate head bed 30 degrees •Emergent CT •Neurosurgery consult
References 1. Scarfone RJ, Kelly A. The recognition and management of diabetic ketoacidosis in children. Pediatr Emerg Med Reports 2004;9:129-40. 2. Hafeez W, Vuguin P. Managing diabetic ketoacidosis—a delicate balance. Contemp Pediatr 2000;17(6):72-83. 3. Jeha G, Haymond MW. Treatment and complications of diabetic ketoacidosis in children. Available at: uptodate.com 4. Rosenbloom AL, Hanas R. Diabetic ketoacidosis: treatment guidelines. Clin Pediatr 1996;35:261-6. 5. Brown TB. Cerebral edema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J 2004;21:141-4. 6. Quintana EC. Factors associated with adverse outcomes in children with diabetic ketoacidosis-relatedcerebral edema. Ann Emerg Med 2004;43:793-4. 7. Dunger DB, Sperling MA, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004;89:188-94.
September-October 2005
8. Kaufman FR. Type 1 diabetes mellitus. Pediatr Rev 2003;24:291-9. 9. Baumann EE, Thorp F. Endocrine and metabolic emergencies. In: Strange GR, editor. Pediatric emergency medicine: just the facts. New York: McGraw-Hill; 2004. p. 249-50. 10. Levitsky LL. Symptomatic cerebral edema in diabetic ketoacidosis: the mechanism is clarified but still far from clear. J Pediatr 2004;145:149-50. 11. Glaser N, Barnett P, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001;344:264-9. 12. Felner EI, White PC. improving management of diabetic ketoacidosis in children. Pediatrics 2001;108:735-40. 13. Glaser NS, Wooton-Gorges SL, Marcia JP, et al. Mechanism of cerebral edema in children with diabetic ketoacidosis. J Pediatr 2004;145:164-71. 14. Lawrence SE, Cumming EA, et al. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005;146:688-92. 15. Kamat P, Vats A, et al. Use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. Pediatr Crit Care Med 2003;4:239-42.
Stuart A Bradin, DO, FAAP, is a clinical assistant professor of pediatrics and emergency medicine in the division of pediatric emergency medicine at the University of Michigan Health System in Ann Arbor, Mich. 1067-991X/$30.00 Copyright 2005 by Air Medical Journal Associates doi:10.1016/j.amj.2005.06.005
183