AACN Advanced Critical Care Volume 25, Number 3, pp. 197-202 © 2014 AACN
ECG
Earnest Alexander, PharmD, and Gregory M. Susla, PharmD Department Editors
Challenges
Management of Acute Hyperglycemic Emergencies: Focus on Diabetic Ketoacidosis Basirat Sanuth, PharmD, BCPS Andrea Bidlencik, PharmD Andrew Volk, PharmD
D
iabetes mellitus (DM) is a chronic disease diagnosed in 20.9 million Americans; in addition, many people have undiagnosed DM.1 In 2011, the incidence of new diagnoses of DM was approximately 1.7 million and has increased every year since 1995.1 A severe acute metabolic complication of DM is diabetic ketoacidosis (DKA), which is listed as the primary diagnosis in approximately 7 patients with DM per 1000 hospital discharges and is associated with an average hospital length of stay of 3.4 days.1 Diabetic emergencies are twice as common in females.2 The annual expenditure for patients with DKA has been estimated at $2.4 billion.3 Diabetic ketoacidosis is characterized by a decrease in effective insulin concentration and an increase in the concentration of counterregulatory hormones, including catecholamines, cortisol, glucagon, and growth hormone, which leads to the hallmark signs of DKA, such as anion gap metabolic acidosis, hyperglycemia, and elevated levels of ketones in the blood. Undiagnosed or untreated DKA can result in severe metabolic derangements, altered mental status, coma, and death. The causes of DKA include infection, discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and the use of drugs such as corticosteroids, thiazide diuretics, sympathomimetic agents, antipsychotic agents, and pentamidine.3 This column discusses the pharmacological treatment of DKA. Clinical Presentation Diabetic ketoacidosis is a severe medical complication in which ketones build up to dangerous levels in the blood as a result of rapid fatty acid breakdown. Symptoms of DKA include polyuria, polydypsia, nausea, vomiting, abdominal pain, and difficulty breathing. Signs include hypotension, tachycardia, fruity-scented breath, hyperventilation and Kussmaul respirations, dehydration, altered mental status, drowsiness, and coma.
Basirat Sanuth is Critical Care Pharmacy Specialist, Department of Pharmacy Services, Mount Sinai Hospital, 1500 South California Ave, Chicago, IL 60608 ([email protected]). Andrea Bidlencik is PGY-1 Pharmacy Resident, Department of Pharmacy Services, Mount Sinai Hospital, Chicago, Illinois. Andrew Volk is PGY-1 Pharmacy Resident, Department of Pharmacy Services, Mount Sinai Hospital, Chicago, Illinois. The authors declare no conflicts of interest. DOI: 10.1097/NCI.0000000000000045
197 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 197
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Drug Update
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Differentiating DKA From Hyperglycemic Hyperosmolar Syndrome
Hyperglycemic hyperosmolar syndrome (HHS) is an additional acute metabolic complication of DM. Providers must differentiate between DKA and HHS, because each has different treatment. Hyperglycemic hyperosmolar syndrome is associated with significantly worse hyperglycemia compared with DKA, with blood glucose typically up to 600 mg/dL or higher. While present in DKA, significant acidosis is not present in HHS, although low or absent ketone levels in blood serum and urine may be present. In addition, an anion gap commonly is present in DKA, but variable in HHS. In DKA, the serum osmolality is lower than that seen in HHS, in which serum osmolarity is typically greater than 320 mOsm/kg. Symptoms between the 2 conditions vary. Patients with DKA may present with variation in mental status, whereas patients with HHS may present with stupor or coma. The presence of abdominal pain is frequently reported in patients with DKA and is normally absent in HHS.3 Treatment The treatment of DKA includes fluid and electrolyte replacement and insulin administration. The goals of treatment include managing fluid status, correcting and preventing further electrolyte abnormalities, and administering insulin to correct acidosis and treat hyperglycemia. Fluid Replacement
Dehydration and hypovolemia are complications requiring appropriate management in the treatment of DKA. The initial goals of fluid replacement are to expand intravascular volume and increase perfusion to vital organs. Determination of the patient's level of dehydration must be completed using physical assessment and calculating the free water deficit. See Table 1 for an equation that can be used to calculate free water
deficit. Calculating the free water deficit provides a guide for appropriate volume for hydration. Initially, 1 L of 0.9% sodium chloride should be administered. If the patient is experiencing hypovolemic shock, the patient should receive 2 to 4 L of 0.9% sodium chloride within the first hour of presentation, with additional fluid administration based on hemodynamic status thereafter. For dehydrated patients with mild hypotension, assess the corrected serum sodium level to determine the type of fluid to be used (see Table 1). If the corrected sodium level is in normal range or elevated (≥135 mEq/L), use 0.45% sodium chloride for fluid replacement. The infusion rate should be between 250 and 500 mL/h based on hydration status and resolution of fluid deficit. However, if the corrected sodium level is less than normal (2
Every 2-4 h
Phosphorus, mg/dL
>1
Every 2-4 h
Bicarbonate, mEq/L
>18
Every 2-4 h
150-200
Every hour
Serum glucose, mg/dL
to cause life-threatening cardiac arrhythmias in patients with DKA.5 Although incidence of hypokalemia on presentation in DKA is rare, ADA guidelines recommend obtaining a serum potassium level prior to the initiation of insulin.6 If initial potassium levels are less than 3.3 mEq/L, patients should receive potassium replacement before administration of insulin. In addition to supplementation, 20 to 30 mEq of potassium may be added to maintenance fluids to maintain goal levels between 4 and 5.5 mEq/L. Two-thirds of the potassium can be given as potassium chloride and the remaining one-third as potassium phosphate if indicated by the patient’s chloride and phosphate levels. The maximum recommended infusion rate is 10 mEq per hour through a peripheral catheter and 20 mEq per hour through a central catheter to minimize infusion-related pain.7 Potassium given at a rate of 20 mEq per hour also requires continuous electrocardiogram monitoring. Preferred location of intravenous administration, rate of administration, and monitoring of potassium may vary on the basis of hospitalspecific guidelines.
199 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 199
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Drug Update
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Magnesium
Maintaining serum magnesium levels is important for cardiac functionality. Magnesium plays a role in maintaining potassium levels, as hypomagnesemia can result in refractory hypokalemia. The pathophysiology of this response is not fully understood but may be due to impaired potassium transport. According to ADA guidelines, magnesium levels should be maintained higher than 2 mEq/L. For the purpose of electrolyte replacement, the rate of magnesium administration should not exceed 2 g per hour. Phosphorus
Phosphorus is an intracellular anion that may be altered in DKA. Patients initially may have normal or high serum phosphorus levels despite having low total phosphorus levels. During treatment, phosphorus levels fall as the electrolyte shifts back into the intracellular space.5 Acute hypophosphatemia can result in altered mental status, rhabdomyolysis, hemolysis, and cardiomyopathy.8 Randomized trials have shown no additional outcome benefits of phosphorus replacement in patients with DKA.5 Therefore, phosphorus replacement is not indicated unless serum levels are less than 1 mg/ dL. If replacement is necessary, 20 to 30 mmol of phosphate may be administered in maintenance fluids or as a piggyback. Sodium phosphate contains 3 mmol of phosphate and 4 mEq of sodium per milliliter. Potassium phosphate contains 3 mmol of phosphate and 4.4 mEq of potassium per milliliter. Either phosphorus salt can be used on the basis of the patient’s sodium and potassium levels. The usual infusion rate for phosphate is 5 mmol per hour, with maximum rates of 10 to 15 mmol per hour. This rate may vary on the basis of hospital-specific guidelines. Intravenous phosphorus should be used cautiously and serum calcium monitored to avoid hypocalcemia. Sodium Bicarbonate
Sodium bicarbonate administration in DKA remains controversial because of the lack of evidence supporting its use. Metabolic acidosis as a result of DKA can lead to severe, fatal effects in the body. Metabolic acidosis can impair myocardial contractility, reduce cardiac output, and result in organ dysfunction.9 Several studies have failed to prove benefit or harm with the use of sodium bicarbonate therapy in DKA.5 A
review of the use of sodium bicarbonate also showed several deleterious effects of sodium bicarbonate therapy, such as cerebral edema and worsening ketosis.9 The effects of sodium bicarbonate have not been studied in patients with a pH of less than 6.9. In this group of patients, sodium bicarbonate administration is recommended regardless of the lack of available evidence because of the severity of acidosis. Patients may receive 100 mEq sodium bicarbonate in 400-ml sterile water at a rate of 200 ml per hour. After 2 hours, the patient's pH should be checked and administration should continue only if the pH remains less than 7.0.3
Insulin
The administration of regular insulin is the mainstay of treatment for DKA. Randomized trials have shown that regular insulin is equally effective regardless of the route of administration. In clinical practice, intravenous administration is the preferred route in the treatment of DKA. Subcutaneous administration of rapidacting insulin may be acceptable for patients with mild DKA in nonintensive care units.3 Intravenous regular insulin may be administered as a bolus of 0.1 U/kg followed by a maintenance infusion of 0.1 U/kg per hour. Another dosing option is a continuous rate of 0.14 U/ kg per hour of regular insulin without a bolus, which is equivalent to approximately 10 U/h in an average 70-kg patient.3 The goal of insulin therapy is to decrease serum glucose by 50 to 75 mg/dL and assess blood glucose hourly.3 Patients may be at risk for cerebral edema if blood glucose levels decrease too rapidly. If this blood glucose reduction goal is not achieved, the rate of the insulin drip should be doubled every hour until the serum blood glucose declines steadily.3 The insulin infusion rate should be decreased to 0.02 to 0.05 U/kg per hour when the patient’s blood glucose declines to less than 200 mg/dL. When the blood glucose reaches this level, intravenous dextrose should be added to the current maintenance fluid. The patient’s blood glucose level should be maintained between 150 and 200 mg/dL by adjusting the insulin and dextrose infusion rates.3 Patients should be transitioned to subcutaneous insulin after the episode of DKA has resolved and the patient is alert, awake, and able to tolerate oral intake. Criteria for DKA resolution include blood glucose level less
200 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 200
7/18/14 12:18 AM
V O LU ME 25 • N U M BER 3 • JULY–SEPTEM BER 2014
Drug Update
than 200 mg/dL and 2 of the following: serum bicarbonate level of 15 mEq/L or more, pH greater than 7.3, and an anion gap of 12 mEq/L or less. For patients new to insulin therapy, a regimen should be started at 0.5 to 0.8 U/kg per day. The total dose should be divided on the basis of type of insulin used. Intermediate-acting insulin such as neutral protamine Hagedorn or long-acting insulin such as glargine or detemir can be used. For basal-bolus insulin regimens, 40% to 50% of the total dose should be administered as the basal insulin, with the remaining 50% to 60% divided into 3 short-acting insulin boluses. For insulin-experienced patients, their recent insulin regimen should be reevaluated. Intravenous administration of insulin should continue for 1 to 2 hours after the first dose of subcutaneous insulin administration to avoid hyperglycemia.3
Monitoring
During administration of insulin, blood glucose levels should be monitored every hour. Patients with DKA should have electrolyte levels including potassium, magnesium, and phosphorus monitored every 2 to 4 hours. Renal function (serum creatinine and blood urea nitrogen) also should be monitored every 2 to 4 hours. Arterial blood gases should be monitored to determine whether acidosis is resolving with therapy. Laboratory markers for DKA, such as serum ketones, may be monitored for resolution of DKA or worsening clinical status. Assessment of renal function and urine output is especially important in patients with known renal dysfunction or with underlying cardiac dysfunction, such as heart failure, to avoid volume overload.
Patient Education
Prior to hospital discharge, all patients with DKA should be assessed to determine precipitating factors that led to the DKA episode and receive extensive education on the basis of identified gaps in knowledge. For newly diagnosed patients, education may include basic pathophysiology of diabetes. All patients diagnosed with DKA should be educated on signs and symptoms of hyperglycemia and hypoglycemia. A review of insulin administration as well as self-blood glucose monitoring is vital to prevent readmission for DKA. Focus patient educa-
tion on understanding the trigger for the DKA episode to prevent rehospitalization. Common triggers include medication nonadherence, acute illness, dehydration, drug or alcohol abuse, and medications, such as corticosteroids, atypical antipsychotic agents, thiazides, and pentamidine. For example, a discussion on how to manage insulin treatment during sick days would be important for patients admitted as a result of acute illnesses. Patients with substance abuse issues should be referred to social services and drug rehabilitation programs. Once the patient is eligible for discharge, patient-related factors associated with onset of DKA should be evaluated to prevent hospital readmission. All medications should be reviewed with the patient prior to discharge. For each medication, the dose, indication, common or severe adverse effects, and meal requirements should be discussed. Emphasize the importance of medication adherence and encourage patients to contact a health care professional for changes in clinical status. Insulin storage requirements and missed doses are important topics often overlooked during patient education. Finally, patient-specific questions and issues such as costs and procurement of antidiabetic medications and blood glucose monitoring devices should be discussed prior to discharge from the hospital. Conclusion Diabetic ketoacidosis is a medical emergency and requires intense patient monitoring at hospital admission. For the proper management of DKA, the use of algorithms and protocols has been shown to decrease hypoglycemic episodes and mortality rate. Therefore, clinicians should become familiar with their institutions’ DKA protocol. Treatment protocols focus primarily on fluid and electrolyte replacement and regular insulin administration. During treatment of DKA, patients must be monitored closely. Precipitating factors for DKA should be identified, and patient education should be provided to prevent future admissions for DKA. REFERENCES 1. Centers for Diseases Control and Prevention. Diabetes, data, and trends . http://www.cdc.gov/diabetes/ statistics/complications_national.htm#2a. Published 2012. Accessed May 23, 2013. 2. Krentz AJ, Nattrass M. Acute metabolic complications of diabetes: diabetic ketoacidosis, hyperosmolar non-ketotic hyperglycemia and lactic acidosis. In: Pickup JC, Williams
201 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 201
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Drug Update
W W W.A ACNA DVA NCE D CRIT ICA LCA RE .COM
G, eds. Textbook of Diabetes Mellitus. Vol 32. 3rd ed. Oxford, UK: Blackwell Publishing; 2003:1–24. 3. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–1343. 4. Hillier TA, Abbott RD, Barret EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999; 106:399–403. 5. Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 2011;94(3):340–351.
6. Arora S, Cheng D, Wyler B, et al. Prevalence of hypokalemia in ED patients with diabetic ketoacidosis. Am J Emerg Med. 2012;30(3):481–484. 7. Kraft MD, Btaiche IF, Sacks GS, et al. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health-Syst Pharm. 2005;62:1663–1682. 8. Wilson HK, Keuer SP, Lea S, et al. Phosphate therapy in diabetic ketoacidosis. Arch Intern Med. 1982;142:517–520. 9. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis—a systematic review. Ann Intensive Care. 2011;1(1):23.
202 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 202
7/18/14 12:18 AM
ECG
Earnest Alexander, PharmD, and Gregory M. Susla, PharmD Department Editors
Challenges
Management of Acute Hyperglycemic Emergencies: Focus on Diabetic Ketoacidosis Basirat Sanuth, PharmD, BCPS Andrea Bidlencik, PharmD Andrew Volk, PharmD
D
iabetes mellitus (DM) is a chronic disease diagnosed in 20.9 million Americans; in addition, many people have undiagnosed DM.1 In 2011, the incidence of new diagnoses of DM was approximately 1.7 million and has increased every year since 1995.1 A severe acute metabolic complication of DM is diabetic ketoacidosis (DKA), which is listed as the primary diagnosis in approximately 7 patients with DM per 1000 hospital discharges and is associated with an average hospital length of stay of 3.4 days.1 Diabetic emergencies are twice as common in females.2 The annual expenditure for patients with DKA has been estimated at $2.4 billion.3 Diabetic ketoacidosis is characterized by a decrease in effective insulin concentration and an increase in the concentration of counterregulatory hormones, including catecholamines, cortisol, glucagon, and growth hormone, which leads to the hallmark signs of DKA, such as anion gap metabolic acidosis, hyperglycemia, and elevated levels of ketones in the blood. Undiagnosed or untreated DKA can result in severe metabolic derangements, altered mental status, coma, and death. The causes of DKA include infection, discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and the use of drugs such as corticosteroids, thiazide diuretics, sympathomimetic agents, antipsychotic agents, and pentamidine.3 This column discusses the pharmacological treatment of DKA. Clinical Presentation Diabetic ketoacidosis is a severe medical complication in which ketones build up to dangerous levels in the blood as a result of rapid fatty acid breakdown. Symptoms of DKA include polyuria, polydypsia, nausea, vomiting, abdominal pain, and difficulty breathing. Signs include hypotension, tachycardia, fruity-scented breath, hyperventilation and Kussmaul respirations, dehydration, altered mental status, drowsiness, and coma.
Basirat Sanuth is Critical Care Pharmacy Specialist, Department of Pharmacy Services, Mount Sinai Hospital, 1500 South California Ave, Chicago, IL 60608 ([email protected]). Andrea Bidlencik is PGY-1 Pharmacy Resident, Department of Pharmacy Services, Mount Sinai Hospital, Chicago, Illinois. Andrew Volk is PGY-1 Pharmacy Resident, Department of Pharmacy Services, Mount Sinai Hospital, Chicago, Illinois. The authors declare no conflicts of interest. DOI: 10.1097/NCI.0000000000000045
197 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 197
7/18/14 12:18 AM
Drug Update
W W W.A ACNA DVA NCE D CRIT ICA LCA RE .COM
Differentiating DKA From Hyperglycemic Hyperosmolar Syndrome
Hyperglycemic hyperosmolar syndrome (HHS) is an additional acute metabolic complication of DM. Providers must differentiate between DKA and HHS, because each has different treatment. Hyperglycemic hyperosmolar syndrome is associated with significantly worse hyperglycemia compared with DKA, with blood glucose typically up to 600 mg/dL or higher. While present in DKA, significant acidosis is not present in HHS, although low or absent ketone levels in blood serum and urine may be present. In addition, an anion gap commonly is present in DKA, but variable in HHS. In DKA, the serum osmolality is lower than that seen in HHS, in which serum osmolarity is typically greater than 320 mOsm/kg. Symptoms between the 2 conditions vary. Patients with DKA may present with variation in mental status, whereas patients with HHS may present with stupor or coma. The presence of abdominal pain is frequently reported in patients with DKA and is normally absent in HHS.3 Treatment The treatment of DKA includes fluid and electrolyte replacement and insulin administration. The goals of treatment include managing fluid status, correcting and preventing further electrolyte abnormalities, and administering insulin to correct acidosis and treat hyperglycemia. Fluid Replacement
Dehydration and hypovolemia are complications requiring appropriate management in the treatment of DKA. The initial goals of fluid replacement are to expand intravascular volume and increase perfusion to vital organs. Determination of the patient's level of dehydration must be completed using physical assessment and calculating the free water deficit. See Table 1 for an equation that can be used to calculate free water
deficit. Calculating the free water deficit provides a guide for appropriate volume for hydration. Initially, 1 L of 0.9% sodium chloride should be administered. If the patient is experiencing hypovolemic shock, the patient should receive 2 to 4 L of 0.9% sodium chloride within the first hour of presentation, with additional fluid administration based on hemodynamic status thereafter. For dehydrated patients with mild hypotension, assess the corrected serum sodium level to determine the type of fluid to be used (see Table 1). If the corrected sodium level is in normal range or elevated (≥135 mEq/L), use 0.45% sodium chloride for fluid replacement. The infusion rate should be between 250 and 500 mL/h based on hydration status and resolution of fluid deficit. However, if the corrected sodium level is less than normal (2
Every 2-4 h
Phosphorus, mg/dL
>1
Every 2-4 h
Bicarbonate, mEq/L
>18
Every 2-4 h
150-200
Every hour
Serum glucose, mg/dL
to cause life-threatening cardiac arrhythmias in patients with DKA.5 Although incidence of hypokalemia on presentation in DKA is rare, ADA guidelines recommend obtaining a serum potassium level prior to the initiation of insulin.6 If initial potassium levels are less than 3.3 mEq/L, patients should receive potassium replacement before administration of insulin. In addition to supplementation, 20 to 30 mEq of potassium may be added to maintenance fluids to maintain goal levels between 4 and 5.5 mEq/L. Two-thirds of the potassium can be given as potassium chloride and the remaining one-third as potassium phosphate if indicated by the patient’s chloride and phosphate levels. The maximum recommended infusion rate is 10 mEq per hour through a peripheral catheter and 20 mEq per hour through a central catheter to minimize infusion-related pain.7 Potassium given at a rate of 20 mEq per hour also requires continuous electrocardiogram monitoring. Preferred location of intravenous administration, rate of administration, and monitoring of potassium may vary on the basis of hospitalspecific guidelines.
199 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 199
7/18/14 12:18 AM
Drug Update
W W W.A ACNA DVA NCE D CRIT ICA LCA RE .COM
Magnesium
Maintaining serum magnesium levels is important for cardiac functionality. Magnesium plays a role in maintaining potassium levels, as hypomagnesemia can result in refractory hypokalemia. The pathophysiology of this response is not fully understood but may be due to impaired potassium transport. According to ADA guidelines, magnesium levels should be maintained higher than 2 mEq/L. For the purpose of electrolyte replacement, the rate of magnesium administration should not exceed 2 g per hour. Phosphorus
Phosphorus is an intracellular anion that may be altered in DKA. Patients initially may have normal or high serum phosphorus levels despite having low total phosphorus levels. During treatment, phosphorus levels fall as the electrolyte shifts back into the intracellular space.5 Acute hypophosphatemia can result in altered mental status, rhabdomyolysis, hemolysis, and cardiomyopathy.8 Randomized trials have shown no additional outcome benefits of phosphorus replacement in patients with DKA.5 Therefore, phosphorus replacement is not indicated unless serum levels are less than 1 mg/ dL. If replacement is necessary, 20 to 30 mmol of phosphate may be administered in maintenance fluids or as a piggyback. Sodium phosphate contains 3 mmol of phosphate and 4 mEq of sodium per milliliter. Potassium phosphate contains 3 mmol of phosphate and 4.4 mEq of potassium per milliliter. Either phosphorus salt can be used on the basis of the patient’s sodium and potassium levels. The usual infusion rate for phosphate is 5 mmol per hour, with maximum rates of 10 to 15 mmol per hour. This rate may vary on the basis of hospital-specific guidelines. Intravenous phosphorus should be used cautiously and serum calcium monitored to avoid hypocalcemia. Sodium Bicarbonate
Sodium bicarbonate administration in DKA remains controversial because of the lack of evidence supporting its use. Metabolic acidosis as a result of DKA can lead to severe, fatal effects in the body. Metabolic acidosis can impair myocardial contractility, reduce cardiac output, and result in organ dysfunction.9 Several studies have failed to prove benefit or harm with the use of sodium bicarbonate therapy in DKA.5 A
review of the use of sodium bicarbonate also showed several deleterious effects of sodium bicarbonate therapy, such as cerebral edema and worsening ketosis.9 The effects of sodium bicarbonate have not been studied in patients with a pH of less than 6.9. In this group of patients, sodium bicarbonate administration is recommended regardless of the lack of available evidence because of the severity of acidosis. Patients may receive 100 mEq sodium bicarbonate in 400-ml sterile water at a rate of 200 ml per hour. After 2 hours, the patient's pH should be checked and administration should continue only if the pH remains less than 7.0.3
Insulin
The administration of regular insulin is the mainstay of treatment for DKA. Randomized trials have shown that regular insulin is equally effective regardless of the route of administration. In clinical practice, intravenous administration is the preferred route in the treatment of DKA. Subcutaneous administration of rapidacting insulin may be acceptable for patients with mild DKA in nonintensive care units.3 Intravenous regular insulin may be administered as a bolus of 0.1 U/kg followed by a maintenance infusion of 0.1 U/kg per hour. Another dosing option is a continuous rate of 0.14 U/ kg per hour of regular insulin without a bolus, which is equivalent to approximately 10 U/h in an average 70-kg patient.3 The goal of insulin therapy is to decrease serum glucose by 50 to 75 mg/dL and assess blood glucose hourly.3 Patients may be at risk for cerebral edema if blood glucose levels decrease too rapidly. If this blood glucose reduction goal is not achieved, the rate of the insulin drip should be doubled every hour until the serum blood glucose declines steadily.3 The insulin infusion rate should be decreased to 0.02 to 0.05 U/kg per hour when the patient’s blood glucose declines to less than 200 mg/dL. When the blood glucose reaches this level, intravenous dextrose should be added to the current maintenance fluid. The patient’s blood glucose level should be maintained between 150 and 200 mg/dL by adjusting the insulin and dextrose infusion rates.3 Patients should be transitioned to subcutaneous insulin after the episode of DKA has resolved and the patient is alert, awake, and able to tolerate oral intake. Criteria for DKA resolution include blood glucose level less
200 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 200
7/18/14 12:18 AM
V O LU ME 25 • N U M BER 3 • JULY–SEPTEM BER 2014
Drug Update
than 200 mg/dL and 2 of the following: serum bicarbonate level of 15 mEq/L or more, pH greater than 7.3, and an anion gap of 12 mEq/L or less. For patients new to insulin therapy, a regimen should be started at 0.5 to 0.8 U/kg per day. The total dose should be divided on the basis of type of insulin used. Intermediate-acting insulin such as neutral protamine Hagedorn or long-acting insulin such as glargine or detemir can be used. For basal-bolus insulin regimens, 40% to 50% of the total dose should be administered as the basal insulin, with the remaining 50% to 60% divided into 3 short-acting insulin boluses. For insulin-experienced patients, their recent insulin regimen should be reevaluated. Intravenous administration of insulin should continue for 1 to 2 hours after the first dose of subcutaneous insulin administration to avoid hyperglycemia.3
Monitoring
During administration of insulin, blood glucose levels should be monitored every hour. Patients with DKA should have electrolyte levels including potassium, magnesium, and phosphorus monitored every 2 to 4 hours. Renal function (serum creatinine and blood urea nitrogen) also should be monitored every 2 to 4 hours. Arterial blood gases should be monitored to determine whether acidosis is resolving with therapy. Laboratory markers for DKA, such as serum ketones, may be monitored for resolution of DKA or worsening clinical status. Assessment of renal function and urine output is especially important in patients with known renal dysfunction or with underlying cardiac dysfunction, such as heart failure, to avoid volume overload.
Patient Education
Prior to hospital discharge, all patients with DKA should be assessed to determine precipitating factors that led to the DKA episode and receive extensive education on the basis of identified gaps in knowledge. For newly diagnosed patients, education may include basic pathophysiology of diabetes. All patients diagnosed with DKA should be educated on signs and symptoms of hyperglycemia and hypoglycemia. A review of insulin administration as well as self-blood glucose monitoring is vital to prevent readmission for DKA. Focus patient educa-
tion on understanding the trigger for the DKA episode to prevent rehospitalization. Common triggers include medication nonadherence, acute illness, dehydration, drug or alcohol abuse, and medications, such as corticosteroids, atypical antipsychotic agents, thiazides, and pentamidine. For example, a discussion on how to manage insulin treatment during sick days would be important for patients admitted as a result of acute illnesses. Patients with substance abuse issues should be referred to social services and drug rehabilitation programs. Once the patient is eligible for discharge, patient-related factors associated with onset of DKA should be evaluated to prevent hospital readmission. All medications should be reviewed with the patient prior to discharge. For each medication, the dose, indication, common or severe adverse effects, and meal requirements should be discussed. Emphasize the importance of medication adherence and encourage patients to contact a health care professional for changes in clinical status. Insulin storage requirements and missed doses are important topics often overlooked during patient education. Finally, patient-specific questions and issues such as costs and procurement of antidiabetic medications and blood glucose monitoring devices should be discussed prior to discharge from the hospital. Conclusion Diabetic ketoacidosis is a medical emergency and requires intense patient monitoring at hospital admission. For the proper management of DKA, the use of algorithms and protocols has been shown to decrease hypoglycemic episodes and mortality rate. Therefore, clinicians should become familiar with their institutions’ DKA protocol. Treatment protocols focus primarily on fluid and electrolyte replacement and regular insulin administration. During treatment of DKA, patients must be monitored closely. Precipitating factors for DKA should be identified, and patient education should be provided to prevent future admissions for DKA. REFERENCES 1. Centers for Diseases Control and Prevention. Diabetes, data, and trends . http://www.cdc.gov/diabetes/ statistics/complications_national.htm#2a. Published 2012. Accessed May 23, 2013. 2. Krentz AJ, Nattrass M. Acute metabolic complications of diabetes: diabetic ketoacidosis, hyperosmolar non-ketotic hyperglycemia and lactic acidosis. In: Pickup JC, Williams
201 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 201
7/18/14 12:18 AM
Drug Update
W W W.A ACNA DVA NCE D CRIT ICA LCA RE .COM
G, eds. Textbook of Diabetes Mellitus. Vol 32. 3rd ed. Oxford, UK: Blackwell Publishing; 2003:1–24. 3. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–1343. 4. Hillier TA, Abbott RD, Barret EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999; 106:399–403. 5. Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 2011;94(3):340–351.
6. Arora S, Cheng D, Wyler B, et al. Prevalence of hypokalemia in ED patients with diabetic ketoacidosis. Am J Emerg Med. 2012;30(3):481–484. 7. Kraft MD, Btaiche IF, Sacks GS, et al. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health-Syst Pharm. 2005;62:1663–1682. 8. Wilson HK, Keuer SP, Lea S, et al. Phosphate therapy in diabetic ketoacidosis. Arch Intern Med. 1982;142:517–520. 9. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis—a systematic review. Ann Intensive Care. 2011;1(1):23.
202 Copyright © 2014 American Association of Critical-Care Nurses. Unauthorized reproduction of this article is prohibited.
NCI-D-13-00062.indd 202
7/18/14 12:18 AM
