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Treating Diabetic Ketoacidosis in Children While Preventing Cerebral Edema: One Hospital's Protocol
PEDIATRIC UPDATE
Treating Diabetic Ketoacidosis in Children While Preventing Cerebral Edema: One Hospital’s Protocol Author: Kathleen Merkley, RN, MS, FNP, ANP, Layton, Utah Section Editors: Deborah Parkman Henderson, RN, PhD, and Donna Ojanen Thomas, RN, MSN
Kathleen Merkley is Nurse Practitioner, Emergency Department, Primary Children’s Medical Center, Salt Lake City, Utah. For reprints, write: Kathleen Merkley, RN, FNP, ANP, 100 North Medical Dr, Salt Lake City, UT 84113; E-mail: Kathleen. [email protected]. J Emerg Nurs 2004;30:569-71. 0099-1767/$30.00 Copyright n 2004 by the Emergency Nurses Association. doi: 10.1016/j.jen.2004.09.005
30:6 December 2004
T
ype I diabetes mellitus is the most common endocrine/metabolic disorder of childhood and adolescence. It is increasing in frequency, with the annual incidence in the United States at 12 to 15 per 100,000 children.1 A complication of this disorder is diabetic ketoacidosis (DKA), which is a state of hyperglycemia (glucose N300 mg/dL), acidosis (pH b7.30 and bicarbonate b15 mEq/L), and ketonemia (ketones strongly positive at greater than 1:2 dilution of serum). Precipitating factors include stress, infections, and gastroenteritis. Cerebral edema is a rare (occurring in 1 of every 1000 cases of DKA) but potentially fatal outcome of DKA during childhood. It is more common in younger children, especially with the initial presentation of diabetes mellitus. Although mortality rates have declined to around 20%, cerebral edema remains the cause of about half of all deaths in children with diabetes mellitus. Morbidity from cerebral edema is also high; about one fourth of survivors may have permanent neurologic sequelae.1 Several theories have been proposed to explain the etiology of cerebral edema in relation to DKA, but no specific cause has been identified. Management focusing on excessive fluid resuscitation and a too-rapid reduction of blood sugar is now being examined as a root cause. Certain laboratory values and physical findings also have been identified as being prognostic in children in whom cerebral edema develops. In a review of medical records of 6977 children hospitalized for DKA during a 15-year period at 10 medical centers, cerebral edema developed in 61 children.2 These patients were compared with 2 control groups of children with DKA whose brains did not swell. The children in whom cerebral edema developed had significantly lower partial pressures of arterial carbon dioxide (Pco2 b18 mm Hg) JOURNAL OF EMERGENCY NURSING
569
PEDIATRIC UPDATE/Merkley
and higher serum urea nitrogen. Failure of serum sodium concentration to increase during therapy also indicated a greater likelihood of cerebral edema.2 In another study, a low Pco2 value was the single most important predictive variable for the development of clinical cerebral edema.3 Neurologic symptoms present an average of 4 hours before the dramatic presentation of cerebral edema occurs.4 These symptoms include drowsiness, headache, agitation, vomiting, papilledema, and progression to coma.1 A relative slowing of heart rate also has been noted as a sign of pending cerebral edema. This is not necessarily a bradycardia—less than 60 beats per minute—but typically a child with a heart rate of 120 who suddenly drops to 80 to 90 beats per minute.4
because of her age, but 20 hours after diagnosis, she was actually doing well. The first patient exhibited confusion, agitation, and a relative bradycardia (heart rate between 60 to 80 beats/minute) at 10 hours after transport. He was taken for a brain computed tomography (CT) scan that showed signs of cerebral edema. Mannitol was administered, and he was admitted to the PICU. The patient died several hours later, after a repeat CT scan showed supra and infratentorial herniation. It appears that a major cause of cerebral edema in children with DKA involves an osmolar shift or dysequilibrium that results in fluid accumulation in the intracellular fluid compartment and brain cell swelling.3,5 This results from a too-rapid correction of hyperglycemia with fluid and insulin.4
Case vignettes
Treatment of DKA
An 8-year-old boy who weighed 29 kg was transferred via fixed-wing transport from an outlying facility to our pediatric ED with a diagnosis of new onset diabetes, strep pharyngitis, DKA, and dehydration. His initial pH was 7.07, with a Pco2 of 13 mm Hg and a glucose value of 596. Pre-arrival treatment included an initial 580 mL f luid bolus that was repeated once. Ten units of regular insulin were given by intravenous push, and an insulin drip at 0.1 units/kg per hour was started. He was placed on maintenance f luids with added potassium and phosphate at 1O times maintenance. On arrival at the tertiary facility the patient had stable vital signs and was tired but was alert and oriented. A 16-month-old girl who weighed 12 kg came to the emergency department with vomiting and dehydration. She was pale, had dry mucus membranes, delayed capillary refill, and bilateral otitis media. A 10 mL/kg f luid bolus of sodium chloride was initiated, and a basic metabolic profile was obtained. Results included a glucose value of 493, an arterial pH of 7.02, and a sodium value of 123 mmol/L. After the fluid bolus, she was placed on 1O times maintenance fluids of O D5NS with 20 mEq potassium and phosphorus per liter and started on an insulin drip at a rate of 0.1 U/kg/hour (1 mL/kg/hour), on an infusion pump. In which of these patients would cerebral edema be expected to develop? The second patient was at greater risk
The objective of treatment should be the gradual reduction in serum osmolality to prevent cerebral edema. This is done with careful fluid resuscitation and avoidance of bolus insulin. Our emergency department and the hospital pediatric endocrinologists developed the following protocol, which is used in our emergency department.6
570
It appears that a major cause of cerebral edema in children with DKA involves an osmolar shift or dysequilibrium that results in fluid accumulation in the intracellular fluid compartment and brain cell swelling. This results from a too-rapid correction of hyperglycemia with fluid and insulin. DKA PROTOCOL FOR ED PATIENTS .
Children with DKA are given one fluid bolus of 10 to 20 mL/kg of normal saline solution over a 20- to 30-minute period. A repeat bolus of 10 mL/kg is only considered if the child is still showing signs of compensated shock (vital sign instability, delayed capillary refill, altered mental status). After completion of the initial bolus, O D5NS with 20 mEq of potassium acetate and 20 mEq potassium
JOURNAL OF EMERGENCY NURSING
30:6 December 2004
PEDIATRIC UPDATE/Merkley
phosphate per liter at 1O times maintenance is administered. This fluid rate should provide maintenance and replacement fluids for 10% dehydration over 48 hours.
Careful monitoring of blood sugar during fluid resuscitation is crucial because of the resultant hypoglycemia and changes in serum osmolality. .
.
.
An insulin drip is started immediately at the completion of the initial f luid bolus. Fifty units of regular insulin is added to 500 mL normal saline solution to make a 0.1 U/mL concentration. Fifty mL of solution should be initially run through the tubing to saturate binding sites. The insulin drip is infused at a rate of 0.1 U/kg/hour (1 mL/kg/hour) on an IVAC pump. No bolus insulin is given. Careful monitoring of blood sugar during fluid resuscitation is crucial because of the resultant hypoglycemia and changes in serum osmolality. Serum glucose is checked every hour. When the blood sugar is below 250 mg%, the maintenance fluid is changed to O D10 NS with 20 mEq potassium acetate and 20 mEq potassium phosphate per liter at 1O times maintenance. If the serum glucose drops below 250 mg% with the O D10 NS infusion running, the insulin infusion is decreased to 0.075 u/kg/hour. Serum electrolytes are monitored every 2 hours. The insulin infusion is stopped when the serum Hco3 is greater than or equal to 18 mEq/L. Bicarbonate therapy is not indicated unless the pH is severely acidotic (pH b6.8 mEq/L).7
Summary
One of the main objectives of treatment of DKA in the pediatric patient is the gradual reduction of serum osmolality. This is achieved by conservative fluid resuscitation and avoidance of bolus insulin or the rapid expansion of the extracellular fluid by the use of high volumes of hypotonic fluids.
30:6 December 2004
The ED nurse must carefully assess the clinical status of patients with risk factors (young age, duration and severity of symptoms before starting treatment, low Pco2, high serum urea nitrogen, lack of increase in serum sodium during therapy, and treatment with bicarbonate) and look for subtle changes in neurologic status. If these neurologic changes occur, immediate intervention is necessary. Prompt control of airway and ventilation as well as initiation of hyperosmolar therapy (intravenous mannitol) to reduce swelling in the brain should be initiated.7 Further studies and new drugs will aid in the treatment of DKA and cerebral edema; however, it will always be important to understand and initiate appropriate treatment for the child and observe for changes in neurologic status. These are the actions that can save a child’s life. REFERENCES 1. Sperling M. Diabetes mellitus. In: Sperling M, editor. Pediatric endocrinology. Philadelphia: Saunders; 2002. p. 341. 2. Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001;344:264-9. 3. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999;21:721-7. 4. American Diabetes Association. Highlights online summary. Causes of cerebral edema-Andrew Muir [online] [2002 June; accessed 2004 May]. Available from: URL: http://www. diabeteshighlights.org/summary 5. Silver SM, Clark EC, Schroeder BM, Sterns RH. Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. Kidney International 1997;51:1237-44. 6. Primary Children’s Medical Center Emergency Department. Guidelines for the treatment of DKA. Salt Lake City: Author; 2004. 7. Marcin JP, Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793-7.
Submissions to this column are welcomed and encouraged. Submissions may be sent to one of the following: Deborah Parkman Henderson, RN, PhD 1117 Heatherside Rd, Pasadena, CA 91105 626 840-9043 . [email protected] Donna Ojanen Thomas, RN, MSN 2822 E Canyon View Dr, Salt Lake City, UT 84109 801 588-2240 . [email protected]
JOURNAL OF EMERGENCY NURSING
571
Treating Diabetic Ketoacidosis in Children While Preventing Cerebral Edema: One Hospital’s Protocol Author: Kathleen Merkley, RN, MS, FNP, ANP, Layton, Utah Section Editors: Deborah Parkman Henderson, RN, PhD, and Donna Ojanen Thomas, RN, MSN
Kathleen Merkley is Nurse Practitioner, Emergency Department, Primary Children’s Medical Center, Salt Lake City, Utah. For reprints, write: Kathleen Merkley, RN, FNP, ANP, 100 North Medical Dr, Salt Lake City, UT 84113; E-mail: Kathleen. [email protected]. J Emerg Nurs 2004;30:569-71. 0099-1767/$30.00 Copyright n 2004 by the Emergency Nurses Association. doi: 10.1016/j.jen.2004.09.005
30:6 December 2004
T
ype I diabetes mellitus is the most common endocrine/metabolic disorder of childhood and adolescence. It is increasing in frequency, with the annual incidence in the United States at 12 to 15 per 100,000 children.1 A complication of this disorder is diabetic ketoacidosis (DKA), which is a state of hyperglycemia (glucose N300 mg/dL), acidosis (pH b7.30 and bicarbonate b15 mEq/L), and ketonemia (ketones strongly positive at greater than 1:2 dilution of serum). Precipitating factors include stress, infections, and gastroenteritis. Cerebral edema is a rare (occurring in 1 of every 1000 cases of DKA) but potentially fatal outcome of DKA during childhood. It is more common in younger children, especially with the initial presentation of diabetes mellitus. Although mortality rates have declined to around 20%, cerebral edema remains the cause of about half of all deaths in children with diabetes mellitus. Morbidity from cerebral edema is also high; about one fourth of survivors may have permanent neurologic sequelae.1 Several theories have been proposed to explain the etiology of cerebral edema in relation to DKA, but no specific cause has been identified. Management focusing on excessive fluid resuscitation and a too-rapid reduction of blood sugar is now being examined as a root cause. Certain laboratory values and physical findings also have been identified as being prognostic in children in whom cerebral edema develops. In a review of medical records of 6977 children hospitalized for DKA during a 15-year period at 10 medical centers, cerebral edema developed in 61 children.2 These patients were compared with 2 control groups of children with DKA whose brains did not swell. The children in whom cerebral edema developed had significantly lower partial pressures of arterial carbon dioxide (Pco2 b18 mm Hg) JOURNAL OF EMERGENCY NURSING
569
PEDIATRIC UPDATE/Merkley
and higher serum urea nitrogen. Failure of serum sodium concentration to increase during therapy also indicated a greater likelihood of cerebral edema.2 In another study, a low Pco2 value was the single most important predictive variable for the development of clinical cerebral edema.3 Neurologic symptoms present an average of 4 hours before the dramatic presentation of cerebral edema occurs.4 These symptoms include drowsiness, headache, agitation, vomiting, papilledema, and progression to coma.1 A relative slowing of heart rate also has been noted as a sign of pending cerebral edema. This is not necessarily a bradycardia—less than 60 beats per minute—but typically a child with a heart rate of 120 who suddenly drops to 80 to 90 beats per minute.4
because of her age, but 20 hours after diagnosis, she was actually doing well. The first patient exhibited confusion, agitation, and a relative bradycardia (heart rate between 60 to 80 beats/minute) at 10 hours after transport. He was taken for a brain computed tomography (CT) scan that showed signs of cerebral edema. Mannitol was administered, and he was admitted to the PICU. The patient died several hours later, after a repeat CT scan showed supra and infratentorial herniation. It appears that a major cause of cerebral edema in children with DKA involves an osmolar shift or dysequilibrium that results in fluid accumulation in the intracellular fluid compartment and brain cell swelling.3,5 This results from a too-rapid correction of hyperglycemia with fluid and insulin.4
Case vignettes
Treatment of DKA
An 8-year-old boy who weighed 29 kg was transferred via fixed-wing transport from an outlying facility to our pediatric ED with a diagnosis of new onset diabetes, strep pharyngitis, DKA, and dehydration. His initial pH was 7.07, with a Pco2 of 13 mm Hg and a glucose value of 596. Pre-arrival treatment included an initial 580 mL f luid bolus that was repeated once. Ten units of regular insulin were given by intravenous push, and an insulin drip at 0.1 units/kg per hour was started. He was placed on maintenance f luids with added potassium and phosphate at 1O times maintenance. On arrival at the tertiary facility the patient had stable vital signs and was tired but was alert and oriented. A 16-month-old girl who weighed 12 kg came to the emergency department with vomiting and dehydration. She was pale, had dry mucus membranes, delayed capillary refill, and bilateral otitis media. A 10 mL/kg f luid bolus of sodium chloride was initiated, and a basic metabolic profile was obtained. Results included a glucose value of 493, an arterial pH of 7.02, and a sodium value of 123 mmol/L. After the fluid bolus, she was placed on 1O times maintenance fluids of O D5NS with 20 mEq potassium and phosphorus per liter and started on an insulin drip at a rate of 0.1 U/kg/hour (1 mL/kg/hour), on an infusion pump. In which of these patients would cerebral edema be expected to develop? The second patient was at greater risk
The objective of treatment should be the gradual reduction in serum osmolality to prevent cerebral edema. This is done with careful fluid resuscitation and avoidance of bolus insulin. Our emergency department and the hospital pediatric endocrinologists developed the following protocol, which is used in our emergency department.6
570
It appears that a major cause of cerebral edema in children with DKA involves an osmolar shift or dysequilibrium that results in fluid accumulation in the intracellular fluid compartment and brain cell swelling. This results from a too-rapid correction of hyperglycemia with fluid and insulin. DKA PROTOCOL FOR ED PATIENTS .
Children with DKA are given one fluid bolus of 10 to 20 mL/kg of normal saline solution over a 20- to 30-minute period. A repeat bolus of 10 mL/kg is only considered if the child is still showing signs of compensated shock (vital sign instability, delayed capillary refill, altered mental status). After completion of the initial bolus, O D5NS with 20 mEq of potassium acetate and 20 mEq potassium
JOURNAL OF EMERGENCY NURSING
30:6 December 2004
PEDIATRIC UPDATE/Merkley
phosphate per liter at 1O times maintenance is administered. This fluid rate should provide maintenance and replacement fluids for 10% dehydration over 48 hours.
Careful monitoring of blood sugar during fluid resuscitation is crucial because of the resultant hypoglycemia and changes in serum osmolality. .
.
.
An insulin drip is started immediately at the completion of the initial f luid bolus. Fifty units of regular insulin is added to 500 mL normal saline solution to make a 0.1 U/mL concentration. Fifty mL of solution should be initially run through the tubing to saturate binding sites. The insulin drip is infused at a rate of 0.1 U/kg/hour (1 mL/kg/hour) on an IVAC pump. No bolus insulin is given. Careful monitoring of blood sugar during fluid resuscitation is crucial because of the resultant hypoglycemia and changes in serum osmolality. Serum glucose is checked every hour. When the blood sugar is below 250 mg%, the maintenance fluid is changed to O D10 NS with 20 mEq potassium acetate and 20 mEq potassium phosphate per liter at 1O times maintenance. If the serum glucose drops below 250 mg% with the O D10 NS infusion running, the insulin infusion is decreased to 0.075 u/kg/hour. Serum electrolytes are monitored every 2 hours. The insulin infusion is stopped when the serum Hco3 is greater than or equal to 18 mEq/L. Bicarbonate therapy is not indicated unless the pH is severely acidotic (pH b6.8 mEq/L).7
Summary
One of the main objectives of treatment of DKA in the pediatric patient is the gradual reduction of serum osmolality. This is achieved by conservative fluid resuscitation and avoidance of bolus insulin or the rapid expansion of the extracellular fluid by the use of high volumes of hypotonic fluids.
30:6 December 2004
The ED nurse must carefully assess the clinical status of patients with risk factors (young age, duration and severity of symptoms before starting treatment, low Pco2, high serum urea nitrogen, lack of increase in serum sodium during therapy, and treatment with bicarbonate) and look for subtle changes in neurologic status. If these neurologic changes occur, immediate intervention is necessary. Prompt control of airway and ventilation as well as initiation of hyperosmolar therapy (intravenous mannitol) to reduce swelling in the brain should be initiated.7 Further studies and new drugs will aid in the treatment of DKA and cerebral edema; however, it will always be important to understand and initiate appropriate treatment for the child and observe for changes in neurologic status. These are the actions that can save a child’s life. REFERENCES 1. Sperling M. Diabetes mellitus. In: Sperling M, editor. Pediatric endocrinology. Philadelphia: Saunders; 2002. p. 341. 2. Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001;344:264-9. 3. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999;21:721-7. 4. American Diabetes Association. Highlights online summary. Causes of cerebral edema-Andrew Muir [online] [2002 June; accessed 2004 May]. Available from: URL: http://www. diabeteshighlights.org/summary 5. Silver SM, Clark EC, Schroeder BM, Sterns RH. Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. Kidney International 1997;51:1237-44. 6. Primary Children’s Medical Center Emergency Department. Guidelines for the treatment of DKA. Salt Lake City: Author; 2004. 7. Marcin JP, Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793-7.
Submissions to this column are welcomed and encouraged. Submissions may be sent to one of the following: Deborah Parkman Henderson, RN, PhD 1117 Heatherside Rd, Pasadena, CA 91105 626 840-9043 . [email protected] Donna Ojanen Thomas, RN, MSN 2822 E Canyon View Dr, Salt Lake City, UT 84109 801 588-2240 . [email protected]
JOURNAL OF EMERGENCY NURSING
571