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Emergency and Acute Medicine - Juvenile Diabetes Mellitus
Basics
Description Decrease in effective circulating insulin. Increase in counter regulatory hormones including glucagon, catecholamines, cortisol, and growth hormone. Hyperglycemia owing to: Decreased peripheral glucose utilization. Increased hepatic gluconeogenesis. Hyperosmolality and osmotic diuresis due to hyperglycemia. Ketoacidosis produced by increased lipolysis, with ketone body (β-hydroxybutyrate, acetoacetate) production, causes ketonemia and metabolic acidosis, which is augmented with lactic acidosis from poor tissue perfusion. Potassium deficit: Intracellular shifts into extracellular space owing to hydrogen ion exchange. Loss from osmotic diuresis.
Etiology
Mechanism: Immune-mediated pancreatic islet β-cell destruction. The overall incidence has been increased worldwide by 2–5% over the past 20 yr. Precipitating events leading to diabetic ketoacidosis (DKA): Infection, often minor acute illness such as virus, group A streptococcal pharyngitis, or UTI. Stress. Endocrine: Pregnancy, puberty, hyperthyroidism. Psychiatric disorders, including eating disorders. Medication noncompliance, inappropriate interruption of insulin pump therapy, or treatment error. Risk factors for cerebral edema: Attenuated rise in measured serum sodium during DKA therapy (unrelated to the volume or sodium content of IV fluid or rate of change in serum glucose). Bicarbonate treatment for acidosis correction. Hypocapnia. Increased serum urea nitrogen. No association with degree of hyperglycemia. Demographic factors that have been associated with an increased risk of cerebral edema include younger age, longer duration of symptoms, and new onset diabetes mellitus. These factors are also associated with increased risk of severe DKA.
Diagnosis
Signs and symptoms Polydipsia. Polyuria (may have good urine output despite dehydration). Nocturia. Polyphagia. Malaise, weight loss. DKA: Initial presentation in 20-40% of patients. Often associated with tachypnea (Kussmaul respiration), tachycardia, orthostatic BP changes. Nausea. Vomiting. Abdominal pain, often resolving with reduction in ketosis/acidosis. Hyperpnea. Fruity breath secondary to ketones. Rapid onset of DKA can occur within 7-8 hr with the use of insulin pump therapy if there is an infusion set or insulin delivery malfunction. This is due secondary to lack of long acting insulin to provide a safety net (more commonly seen in female >10 yr of age). Findings with more advanced disease: Dehydration, drowsiness, altered mental status, and ultimately, late stage coma and shock. Cerebral edema: The incidence ranges from 0.87–1.1%. Cerebral edema accounts for 57–87% of all DKA deaths. It typically occurs 4–12 hr after treatment is initiated, but can be presenting (subclinical) before treatment has started. Headache. Change in neurologic status, such as drowsiness, irritability, or specific neurologic deficit, such as pupillary responses or cranial nerve palsies. Inappropriate slowing in pulse rate. Increase in BP. Hyperglycemic hyperosmolar nonketotic coma: Glucose level of 800–1,200 mg/dL. Rare in children; more common in adults.
Essential workup
For DKA: The International Society for Pediatric and Adolescent Diabetes (ISPAD) defines DKA as blood bicarbonate level <15 mmol /> or venous pH <7.3 and hyperglycemia (>200 mg/dL) with related ketonemia or ketonuria. DKA classification: Mild DKA: Venous pH <7.2–7.3 or hco3 <10–15 mmol />. Moderate DKA: Venous pH <7.1–7.2 or hco3 <5–10 mmol />. Severe DKA: Venous pH <7.1 or hco3 <5 mmol />. Hourly vital signs and neurologic checks. Frequent blood chemistries. ECG monitoring (in severe DKA) to assess T-waves for evidence of hyperkalemia or hypokalemia. Accurate fluid input and output. Consider urinary catheterization in patients with impaired level of consciousness.
Diagnosis tests & interpretation
Lab For DKA: Glucose, serum: Hyperglycemia. Urinalysis: Glycosuria. Ketonuria. Exclude UTI. Blood chemistries every 2–4 hr until acidosis has resolved (more frequent as clinically indicated in the more severe cases). Electrolytes and venous pH. Anion gap metabolic acidosis: Potassium—high or normal (artifactual owing to extracellular shift). Serum potassium rises 0.5 mEqL for each 0.1 decrease in pH. Sodium—low or normal (may be artifactual owing to hyperglycemia). Corrected Na (mEq/L) = [measured serum Na (mEqL) + plasma glucose (mg/dL) – 100] × 0.016. Bicarbonate—low. Calculation: Na – (Cl + HCO3). Serum ketones—elevated. β-hydroxybutyrate (BHOB) is a quantitative test that is available to replace the classic nitroprusside test for serum ketones. Serum osmolality. CBC: WBC often elevated owing to stress or infection. Calcium. Phosphate. Cultures as indicated: Group A streptococcal pharyngeal swab, urine, etc. Pregnancy test if indicated. ECG if potassium markedly abnormal. Imaging: CXR if any suggestion of pneumonia. Head CT if there are concerns about cerebral edema.
Differential diagnosis
Infection (may precipitate): UTI. Gastroenteritis. Appendicitis. Sepsis. Ingestion (salicylates, alcohols, glycols). Diabetes insipidus.
Treatment
Pre hospital For DKA: ABCs. Airway protection. Establish IV access and initiate fluid therapy.
Initial stabilization/therapy For DKA: Oxygen. Cardiac monitor. IV access and volume resuscitation.
Ed treatment/procedures For DKA: Fluid replacement: Assume fluid deficit of 10% of body weight. Initial volume expansion with 10-20 mL/kg of 0.9% NaCl or lactated Ringer; may repeat to achieve hemodynamic stability. Correct 50% of fluid deficit over 1st 8 hr, remainder over 24-48 hr. Do not give >3 L/m2 over 1st 24 hr. Begin IV insulin infusion after ketoacidosis confirmed: Initial rate of continuous infusion (regular insulin) 0.1 U/kg/h IV. Adjust rate to drop serum glucose 50–100 mg/dL/h. Add dextrose to infusion fluid when serum glucose <300 mg />L. Change to SC insulin when no longer significantly acidotic and able to eat. Some clinicians prefer IM route, commonly initially using regular insulin at a dose of 0.1–0.2 U/kg/h. Replace potassium and phosphate losses: Verify adequate urine output. Add to fluids as K-acetate (or KCl if acetate not available) and K3PO4 in equal amounts. Large doses of K+ may be necessary; guide therapy by frequent monitoring of K+. Monitor serum sodium: Risk for cerebral edema if Na+ fails to rise as glucose falls. Bicarbonate therapy: Not recommended in most cases since generally it does not alter outcome and it increases risk for cerebral edema with its use. Use it with caution in patients with severe acidosis (pH <6.9) in whom peripheral vasodilation and decreased cardiac contractility may further impair tissue perfusion potentially life-threatening hyperkalemia. cerebral edema: treat edema as soon the condition is suspected due to its high mortality morbidity rates: 21–25% 10–26%, respectively. decrease fluid administration rate. mannitol (0.25–1 g />g over 20 min): No large studies to date demonstrate definitive beneficial or detrimental effects. Consider its use in patients with signs of cerebral edema before impeding respiratory failure. Dose can be repeated in 2 hr if there is no initial response. Endotracheal intubation and ventilation: Avoid aggressive hyperventilation since it has been associated with poor outcome in DKA-related cerebral edema (similar to that found in head trauma).
Medication
Insulin drip: Start regular insulin 0.1 U/kg/h IV (some clinicians prefer the IM dosing and route). Mannitol: 0.25–1 g/kg IV.
Follow-up disposition
Admission criteria For DKA: ICU: Altered mental status. Shock or cardiac dysrhythmia. Initial glucose >700 mg/dL. Initial pH <7. risk factors for cerebral edema (age <5 yr, prolonged symptoms, high bun). inpatient unit: stable new-onset diabetic patients requiring intensive education. with ketoacidosis not meeting requirements icu care. compliance concerns or other social issues. discharge criteria known who respond well to therapy normalization of glucose, ph, and ketosis. tolerating oral fluids. reliable parents. follow-up within 24 hr including appropriate issues referral critically ill. persistent abnormal mental status. poorly controlled diabetes.< />pan>
Follow-up recommendations
Close follow-up with the primary care physician is important even after the resolution of DKA to ensure appropriate management of the patient’s diabetes to prevent further occurrence of DKA. Many children with diabetes are followed at comprehensive diabetes centers in collaboration with primary care physician.
Pearls and pitfalls
Mortality from DKA is predominately related to the occurrence of cerebral edema. Therefore, early and appropriate treatment is of most importance in managing children with DKA. In children, avoid using an insulin bolus since it increase the risk of cerebral edema. Recently, some data suggest that starting insulin drip at 0.05 U/kg/h may reduce the risk for rapid fluid shifts and theoretically for cerebral edema.
Basics
Description Decrease in effective circulating insulin. Increase in counter regulatory hormones including glucagon, catecholamines, cortisol, and growth hormone. Hyperglycemia owing to: Decreased peripheral glucose utilization. Increased hepatic gluconeogenesis. Hyperosmolality and osmotic diuresis due to hyperglycemia. Ketoacidosis produced by increased lipolysis, with ketone body (β-hydroxybutyrate, acetoacetate) production, causes ketonemia and metabolic acidosis, which is augmented with lactic acidosis from poor tissue perfusion. Potassium deficit: Intracellular shifts into extracellular space owing to hydrogen ion exchange. Loss from osmotic diuresis.
Etiology
Mechanism: Immune-mediated pancreatic islet β-cell destruction. The overall incidence has been increased worldwide by 2–5% over the past 20 yr. Precipitating events leading to diabetic ketoacidosis (DKA): Infection, often minor acute illness such as virus, group A streptococcal pharyngitis, or UTI. Stress. Endocrine: Pregnancy, puberty, hyperthyroidism. Psychiatric disorders, including eating disorders. Medication noncompliance, inappropriate interruption of insulin pump therapy, or treatment error. Risk factors for cerebral edema: Attenuated rise in measured serum sodium during DKA therapy (unrelated to the volume or sodium content of IV fluid or rate of change in serum glucose). Bicarbonate treatment for acidosis correction. Hypocapnia. Increased serum urea nitrogen. No association with degree of hyperglycemia. Demographic factors that have been associated with an increased risk of cerebral edema include younger age, longer duration of symptoms, and new onset diabetes mellitus. These factors are also associated with increased risk of severe DKA.
Diagnosis
Signs and symptoms Polydipsia. Polyuria (may have good urine output despite dehydration). Nocturia. Polyphagia. Malaise, weight loss. DKA: Initial presentation in 20-40% of patients. Often associated with tachypnea (Kussmaul respiration), tachycardia, orthostatic BP changes. Nausea. Vomiting. Abdominal pain, often resolving with reduction in ketosis/acidosis. Hyperpnea. Fruity breath secondary to ketones. Rapid onset of DKA can occur within 7-8 hr with the use of insulin pump therapy if there is an infusion set or insulin delivery malfunction. This is due secondary to lack of long acting insulin to provide a safety net (more commonly seen in female >10 yr of age). Findings with more advanced disease: Dehydration, drowsiness, altered mental status, and ultimately, late stage coma and shock. Cerebral edema: The incidence ranges from 0.87–1.1%. Cerebral edema accounts for 57–87% of all DKA deaths. It typically occurs 4–12 hr after treatment is initiated, but can be presenting (subclinical) before treatment has started. Headache. Change in neurologic status, such as drowsiness, irritability, or specific neurologic deficit, such as pupillary responses or cranial nerve palsies. Inappropriate slowing in pulse rate. Increase in BP. Hyperglycemic hyperosmolar nonketotic coma: Glucose level of 800–1,200 mg/dL. Rare in children; more common in adults.
Essential workup
For DKA: The International Society for Pediatric and Adolescent Diabetes (ISPAD) defines DKA as blood bicarbonate level <15 mmol /> or venous pH <7.3 and hyperglycemia (>200 mg/dL) with related ketonemia or ketonuria. DKA classification: Mild DKA: Venous pH <7.2–7.3 or hco3 <10–15 mmol />. Moderate DKA: Venous pH <7.1–7.2 or hco3 <5–10 mmol />. Severe DKA: Venous pH <7.1 or hco3 <5 mmol />. Hourly vital signs and neurologic checks. Frequent blood chemistries. ECG monitoring (in severe DKA) to assess T-waves for evidence of hyperkalemia or hypokalemia. Accurate fluid input and output. Consider urinary catheterization in patients with impaired level of consciousness.
Diagnosis tests & interpretation
Lab For DKA: Glucose, serum: Hyperglycemia. Urinalysis: Glycosuria. Ketonuria. Exclude UTI. Blood chemistries every 2–4 hr until acidosis has resolved (more frequent as clinically indicated in the more severe cases). Electrolytes and venous pH. Anion gap metabolic acidosis: Potassium—high or normal (artifactual owing to extracellular shift). Serum potassium rises 0.5 mEqL for each 0.1 decrease in pH. Sodium—low or normal (may be artifactual owing to hyperglycemia). Corrected Na (mEq/L) = [measured serum Na (mEqL) + plasma glucose (mg/dL) – 100] × 0.016. Bicarbonate—low. Calculation: Na – (Cl + HCO3). Serum ketones—elevated. β-hydroxybutyrate (BHOB) is a quantitative test that is available to replace the classic nitroprusside test for serum ketones. Serum osmolality. CBC: WBC often elevated owing to stress or infection. Calcium. Phosphate. Cultures as indicated: Group A streptococcal pharyngeal swab, urine, etc. Pregnancy test if indicated. ECG if potassium markedly abnormal. Imaging: CXR if any suggestion of pneumonia. Head CT if there are concerns about cerebral edema.
Differential diagnosis
Infection (may precipitate): UTI. Gastroenteritis. Appendicitis. Sepsis. Ingestion (salicylates, alcohols, glycols). Diabetes insipidus.
Treatment
Pre hospital For DKA: ABCs. Airway protection. Establish IV access and initiate fluid therapy.
Initial stabilization/therapy For DKA: Oxygen. Cardiac monitor. IV access and volume resuscitation.
Ed treatment/procedures For DKA: Fluid replacement: Assume fluid deficit of 10% of body weight. Initial volume expansion with 10-20 mL/kg of 0.9% NaCl or lactated Ringer; may repeat to achieve hemodynamic stability. Correct 50% of fluid deficit over 1st 8 hr, remainder over 24-48 hr. Do not give >3 L/m2 over 1st 24 hr. Begin IV insulin infusion after ketoacidosis confirmed: Initial rate of continuous infusion (regular insulin) 0.1 U/kg/h IV. Adjust rate to drop serum glucose 50–100 mg/dL/h. Add dextrose to infusion fluid when serum glucose <300 mg />L. Change to SC insulin when no longer significantly acidotic and able to eat. Some clinicians prefer IM route, commonly initially using regular insulin at a dose of 0.1–0.2 U/kg/h. Replace potassium and phosphate losses: Verify adequate urine output. Add to fluids as K-acetate (or KCl if acetate not available) and K3PO4 in equal amounts. Large doses of K+ may be necessary; guide therapy by frequent monitoring of K+. Monitor serum sodium: Risk for cerebral edema if Na+ fails to rise as glucose falls. Bicarbonate therapy: Not recommended in most cases since generally it does not alter outcome and it increases risk for cerebral edema with its use. Use it with caution in patients with severe acidosis (pH <6.9) in whom peripheral vasodilation and decreased cardiac contractility may further impair tissue perfusion potentially life-threatening hyperkalemia. cerebral edema: treat edema as soon the condition is suspected due to its high mortality morbidity rates: 21–25% 10–26%, respectively. decrease fluid administration rate. mannitol (0.25–1 g />g over 20 min): No large studies to date demonstrate definitive beneficial or detrimental effects. Consider its use in patients with signs of cerebral edema before impeding respiratory failure. Dose can be repeated in 2 hr if there is no initial response. Endotracheal intubation and ventilation: Avoid aggressive hyperventilation since it has been associated with poor outcome in DKA-related cerebral edema (similar to that found in head trauma).
Medication
Insulin drip: Start regular insulin 0.1 U/kg/h IV (some clinicians prefer the IM dosing and route). Mannitol: 0.25–1 g/kg IV.
Follow-up disposition
Admission criteria For DKA: ICU: Altered mental status. Shock or cardiac dysrhythmia. Initial glucose >700 mg/dL. Initial pH <7. risk factors for cerebral edema (age <5 yr, prolonged symptoms, high bun). inpatient unit: stable new-onset diabetic patients requiring intensive education. with ketoacidosis not meeting requirements icu care. compliance concerns or other social issues. discharge criteria known who respond well to therapy normalization of glucose, ph, and ketosis. tolerating oral fluids. reliable parents. follow-up within 24 hr including appropriate issues referral critically ill. persistent abnormal mental status. poorly controlled diabetes.< />pan>
Follow-up recommendations
Close follow-up with the primary care physician is important even after the resolution of DKA to ensure appropriate management of the patient’s diabetes to prevent further occurrence of DKA. Many children with diabetes are followed at comprehensive diabetes centers in collaboration with primary care physician.
Pearls and pitfalls
Mortality from DKA is predominately related to the occurrence of cerebral edema. Therefore, early and appropriate treatment is of most importance in managing children with DKA. In children, avoid using an insulin bolus since it increase the risk of cerebral edema. Recently, some data suggest that starting insulin drip at 0.05 U/kg/h may reduce the risk for rapid fluid shifts and theoretically for cerebral edema.
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