Diabetic ketoacidosis

Analyze the clinical and administrative aspects of a fictional hospital case.


Reason for admission: Confusion.

History: A 38-year-old woman with a history of uncontrolled type 1 diabetes, hypertension, and cardiomyopathy was brought into the ED by her sister because she had awakened with an altered mental status. The patient was combative and belligerent and could not provide a history. According to her sister, the patient had reported abdominal pain and vomiting the previous day and woke up that morning at 5 a.m. screaming. She was confused, with hallucinations and moments of drowsiness.

Image by Thinkstock
Image by Thinkstock

According to the patient's sister, the patient had a decrease in appetite and an approximate 6-lb weight loss during the prior few weeks. Her last visit to her primary care physician was four months earlier to renew her insulin prescription. She took insulin 70/30, 14 units with breakfast and 10 units with dinner. The patient was not adherent to her medication due to financial issues. She had a family history of diabetes, renal failure, and hypertension. She had lost her job two years earlier and lived with her sister and three-year-old niece.

Physical examination: Vital signs were as follows: temperature, 98.7°F (37°C); blood pressure, 143/90 mm Hg; heart rate, 108 beats/min; respiratory rate, 26 breaths/min; oxygen saturation, 93% on room air, improving to 98% on 2 L oxygen via nasal cannula; weight, 130 lb. The patient was lying down and appeared drowsy. She appeared to be in mild respiratory distress, using her accessory muscles. She was thin and awake but not oriented. Cardiac examination found tachycardia with regular rate and rhythm and normal S1, S2 heart sounds. On auscultation, the lungs were clear bilaterally with deep respirations. The abdomen was soft with normoactive bowel sounds and no evidence of hepatosplenomegaly. She had 1+ lower-extremity pitting edema bilaterally and dry skin.

Labs: A finger-stick test yielded a glucose level of 477 mg/dL (26.5 mmol/L). A complete blood count (CBC) showed a hemoglobin level of 9.3 g/dL, a hematocrit of 28.9%, a mean corpuscular volume of 77.7 fL, a white blood cell count of 9,500 cells/mm3, and a platelet count of 244,000 U/L. The patient's HbA1c was 8.5%, blood urea nitrogen level was 21.5 mg/dL, creatinine level was 1.6 mg/dL, sodium level was 126 mmol/L, potassium level was 3.3 mmol/L, carbon dioxide level was 11 mmol/L, and chloride level was 99 mmol/L. Prothrombin time, international normalized ratio, and partial thromboplastin time were all normal. Urinalysis was positive for glucose and ketone bodies as well as nitrites and leukocyte esterase. Arterial blood gas was consistent with a pH of 7.12. Partial pressure of carbon dioxide was 12 mm Hg, and bicarbonate level was 8.9 mmol/L. Anion gap was 16.

Imaging: Electrocardiogram revealed sinus tachycardia. Chest X-ray was within normal limits.

Clinical course: In the ED, the patient received an IV bolus of 1 L of 0.9% saline solution and 20 mEq of potassium chloride. She also received a 5-unit bolus of regular insulin and was started on an insulin drip at a rate of 5 U/h. The patient was also prescribed ceftriaxone for a possible urinary tract infection.

The patient was transferred to the ICU for ongoing management with a diagnosis of diabetic ketoacidosis and made NPO. Hourly glucose levels were monitored: 350 mg/dL (19.4 mmol/L) at the first hour, 220 mg/dL (12.2 mmol/L) at the second hour, and 197 mg/dL (10.9 mmol/L) at the third hour. The insulin drip was adjusted accordingly per hospital protocol.

Four hours later, the patient's mental status improved. On reevaluation, the patient was alert and oriented, following directions and making needs known. She reported feeling hungry and asked for food. Her blood glucose level was 145 mg/dL (8.1 mmol/L), and the insulin drip was decreased to 3 U/h. Her sodium level was 133 mmol/L, potassium level was 4.0 mmol/L, chloride level was 100 mmol/L, carbon dioxide level was 20 mmol/L, blood urea nitrogen level was 21.9 mg/dL, and creatinine level was 1.5 mg/dL. The anion gap had closed. A repeat arterial blood gas found normal values. Her blood glucose level was 178 mg/dL (9.9 mmol/L), and she was switched to 5% dextrose in 0.45% sodium chloride, 132 mL/h. She was given 17 units of insulin detemir subcutaneously and was transferred out of the ICU to the medical floor.

A few hours later, the patient reported a headache and received acetaminophen. Her blood glucose level was found to be 224 mg/dL (12.4 mmol/L). Her anion gap was 14. The insulin drip was restarted until her anion gap reclosed and her blood glucose remained under 180 mg/dL (10.0 mmol/L) for several hours.

The patient remained on the general floor, with blood glucose monitored every four hours. She was discharged home on day 3 on her regular home regimen and was told to follow up with her primary care clinician within one week.

Case review

Q: Was our patient diagnosed correctly?

A: Yes. Diabetic ketoacidosis (DKA) is defined as a plasma glucose level above 250 mg/dL (>13.9 mmol/L), a plasma bicarbonate level below 15 mEq/L, a pH below 7.35, ketonuria, and an elevation in the anion gap. This patient clearly met the criteria for DKA.

Q: Was our patient managed and discharged appropriately?

A: No. The patient was transitioned too quickly to subcutaneous (SC) insulin. Ideally, patients should have stable blood glucose values within the goal range (generally 140 to 180 mg/dL [7.8 to 10 mmol/L]) for several hours on the insulin drip prior to transition; some authors suggest a period as long as 24 hours (11. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15:353-69. [PMID: 19454396]).

It is essential to appropriately overlap the first dose of SC basal insulin with the IV drip to prevent hyperglycemia during the transition. In contrast, this patient was immediately transitioned from the drip to SC and discharged from the ICU.

Her home medications should have been reviewed and reconciled before discharge. Influenza and pneumococcal vaccinations should have been given (22. Smith SA, Poland GA; American Diabetes Association. Influenza and pneumococcal immunization in diabetes. Diabetes Care. 2004;27 Suppl 1:S111-3. [PMID: 14693944]).

Q: Were care transitions handled appropriately at discharge?

A: No. Poor coordination of the transition and communication with the patient increased her risk of recurrent DKA. Prior to discharge, the inpatient team should schedule outpatient medical follow-up, preferably within a week, with primary care or endocrinology (33. American Diabetes Association. 14. Diabetes care in the hospital. Diabetes Care. 2017;40:S120-S127. [PMID: 27979901]).

Overview

DKA can be a fatal metabolic complication of uncontrolled diabetes. It is defined by the triad of ketonemia, hyperglycemia, and metabolic acidosis, provoked by an absolute or relative insulin deficiency in the presence increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) (44. Nyenwe EA, Kitabchi AE. The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management. Metabolism. 2016;65:507-21. [PMID: 26975543]). The most frequent causes of DKA in the U.S. and other developed nations are poor adherence to insulin therapy, infection, and newly diagnosed diabetes. In developing countries, infection and poor access to care are the most common causes (55. Umpierrez G, Korytkowski M. Diabetic emergencies-ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016;12:222-32. [PMID: 26893262]).

In times of stress to the body, such as trauma, sepsis, or gastrointestinal illness, a relative deficiency in insulin can occur. The liver and kidneys tend to release more glucose (via glycogenolysis and gluconeogenesis) when the combination of low insulin levels and high counterregulatory hormones is present. This impairs the body's use of glucose and causes the liver to make more ketones. This hyperglycemia, hyperosmolality, ketogenesis, and increased lipolysis lead to ketonemia and acidosis. The elevated blood glucose and elevated ketones lead to osmotic diuresis, dehydration, and electrolyte loss, which worsen the cycle and drive further release of hormones, aggravating insulin resistance, hyperglycemia, and hyperketonemia. Unless this cycle is interrupted, worsening dehydration and metabolic acidosis will occur.

Patients with DKA have dehydration, acidosis, and electrolyte abnormalities that all require correction (55. Umpierrez G, Korytkowski M. Diabetic emergencies-ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016;12:222-32. [PMID: 26893262]). Risk factors associated with the development of DKA include younger age and lower body mass index (66. Butalia S, Johnson JA, Ghali WA, Rabi DM. Clinical and socio-demographic factors associated with diabetic ketoacidosis hospitalization in adults with type 1 diabetes. Diabet Med. 2013;30:567-73. [PMID: 23323955]).

Ketoacidosis alone does not definitively diagnose DKA. Differential diagnoses that should be explored include starvation ketosis and alcoholic ketoacidosis (77. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335-43. [PMID: 19564476]).

Treatment

The treatment of DKA and hyperosmolar hyperglycemic state are similar, including correction of the fluid and electrolyte abnormalities that are typically present (hyperosmolality, hypovolemia, metabolic acidosis [in DKA], and potassium depletion) and the administration of insulin (77. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335-43. [PMID: 19564476], 88. Barrett EJ, DeFronzo RA. Diabetic ketoacidosis: diagnosis and treatment. Hosp Pract (Off Ed). 1984;19:89-95, 99-104. [PMID: 6425326]). Objectives include restoration of circulatory volume and tissue perfusion, cessation of ketogenesis, correction of electrolyte imbalances, and resolution of hyperglycemia (55. Umpierrez G, Korytkowski M. Diabetic emergencies-ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016;12:222-32. [PMID: 26893262]).

Fluids

The first step in the treatment of DKA is infusion of isotonic saline to expand intravascular and interstitial volume and stabilize cardiovascular status. During the first hour, saline should be administered at the rate of 1 L/h, although cautiously in patients with volume overload. The type of fluid replacement used subsequently should be individualized based on the corrected serum sodium level. In patients with normal or high corrected serum sodium levels, the recommended rehydration fluid is 0.45% sodium chloride given at 250 to 500 mL/h (4 to 14 cc/kg per hour). For patients with low corrected serum sodium levels, the recommended rehydration fluid is normal saline, infused at the same rate (77. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335-43. [PMID: 19564476]). When the plasma glucose level falls below 200 to 250 mg/dL (13.9 mmol/L), dextrose-containing fluids should be initiated (99. Corwell B, Knight B, Olivieri L, Willis GC. Current diagnosis and treatment of hyperglycemic emergencies. Emerg Med Clin North Am. 2014;32:437-52. [PMID: 24766942]).

Insulin

Insulin administration is the next essential step in restoring cellular metabolism, reducing hepatic gluconeogenesis, and suppressing lipolysis and ketogenesis (1010. Veitenhansl M, Stegner K, Hierl FX, Dieterle C, Feldmeier H, Gutt B, et al. 40th EASD Annual Meeting of the European Association for the Study of Diabetes: Munich, Germany, 5-9 September 2004. Diabetologia. 2004;47:A1-A464. [PMID: 27770180]). Insulin does not need to be started on initial presentation and should never be started until electrolyte results are available to prevent potentially fatal complications. Regular insulin is preferred over insulin analogs due to their lack of superiority (or noninferiority) and higher cost. Traditional insulin regimens recommend 0.1 U/kg IV bolus and then 0.1 U/kg IV continuous infusion per hour (1111. Tran TTT, Pease A, Wood AJ, Zajac JD, Mårtensson J, Bellomo R, et al. Review of evidence for adult diabetic ketoacidosis management protocols. Front Endocrinol (Lausanne). 2017;8:106. [PMID: 28659865]), but bolus dosing prior to continuous infusion has not shown significant benefit in research (77. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335-43. [PMID: 19564476]). According to a small prospective study, insulin infused at a rate of 0.14 U/kg per hour achieved similar treatment endpoints as the bolus regimen (1212. Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care. 2008;31:2081-5. [PMID: 18694978]). Therefore, initial insulin infusion can be started with either an IV bolus (0.1 U/kg) followed by a continuous hourly infusion (0.1 U/kg per hour) or with a continuous infusion alone (0.14 U/kg per hour). This treatment approach mirrors normal physiology and, in combination with fluid therapy, should clear elevated serum glucose and ketones. The optimal rate of correction of blood glucose is 50 to 70 mg/dL (2.8 to 3.9 mmol/L per hour) and the insulin infusion rate is adjusted according to the hourly point-of-care blood sugar measurements. At a glucose level of around 200 to 250 mg/dL (11.1 mmol/L), the continuous insulin infusion should be decreased by 50% and, to prevent hypoglycemia, 5% dextrose should be added to the IV fluid (1313. Donahey E, Folse S. Management of diabetic ketoacidosis. Adv Emerg Nurs J. 2012;34:209-15. [PMID: 22842963]).

Discontinuation of the insulin infusion can be complex. Because regular insulin has a short half-life, sudden discontinuance of the insulin supply restarts ketogenesis, rebounding patients into hyperglycemia and metabolic acidosis, and DKA recurs. Insulin infusion should be continued until the resolution of ketoacidosis. To prevent recurrence of ketoacidosis or rebound hyperglycemia, the insulin drip should be continued for a minimum of two to four hours after SC basal insulin is given. For patients treated with insulin before admission, restarting the previous insulin regimen may reasonable, with adjustment of the dose as needed. For patients with newly diagnosed diabetes, one could calculate the total daily insulin dose at 0.6 U/kg, then divide the total daily dose into a multidose insulin regimen, given as basal and bolus regimen to mimic natural insulin production.

Electrolytes

During DKA treatment, serum electrolytes should be closely monitored. Insulin administration drives potassium intracellularly, resulting in hypokalemia that may lead to life-threatening arrhythmias. If the serum potassium level decreases below 3.3 mEq/L, insulin should be stopped and IV potassium should be administered. Potassium should be added to IV fluids when the serum potassium level is between 3.3 and 5.3 mmol/L. Potassium replacement is not required for levels above 5.3 mmol/L (1414. Gosmanov AR, Gosmanova EO, Dillard-Cannon E. Management of adult diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2014;7:255-64. [PMID: 25061324]).

Complications

The most frequent complications of DKA treatment are hypoglycemia and hypokalemia, which result from overzealous treatment with insulin. If IV insulin is discontinued without adequate overlap with SC insulin, hyperglycemia may recur. Cerebral edema from uncontrolled diabetes is mostly seen in DKA, with only isolated reports in hyperosmolar hyperglycemic state, and it is more common in children, with the vast majority of affected patients being under 20 years of age (1515. Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:1150-9. [PMID: 16644656]). Symptoms of cerebral edema typically emerge within 12 to 24 hours of the initiation of treatment for DKA, but onset may occur before therapy. Although cerebral edema is rare in adults, it is associated with high rates of morbidity and mortality. Hence, close monitoring for changes in mental or neurologic status is critical for early detection and therapy of cerebral edema.

Discharge

The discharge needs of patients with diabetes should be assessed within 24 hours of admission. Throughout hospitalization, deficits in patients' knowledge regarding their diabetes management should be identified and education should be provided if appropriate. Assessment involves information gathering about patients' knowledge of diabetes, self-management skills, education and social circumstances, expected change in functionality as a consequence of ill health, and barriers to self-care that may affect a safe discharge. Patients should leave the hospital with personalized discharge instructions that include a new list of all medications, with doses, what was added, what was removed, and side effects, as well as follow-up appointments with both an outpatient diabetes care clinician and a diabetes educator whenever possible (1616. Donihi AC. Practical recommendations for transitioning patients with type 2 diabetes from hospital to home. Curr Diab Rep. 2017;17:52. [PMID: 28573408]).

When patients are being discharged on insulin, oral antidiabetic agents, and/or glucose monitoring supplies that they have not previously used at home, an assessment of their ability to afford and use these prescriptions should be performed before discharge. Even patients who have health insurance may be underinsured, have high out-of-pocket costs for prescriptions, or experience difficulty obtaining prescriptions due to lack of formulary coverage for a specific brand or type (vial vs. pen) of insulin (1616. Donihi AC. Practical recommendations for transitioning patients with type 2 diabetes from hospital to home. Curr Diab Rep. 2017;17:52. [PMID: 28573408]).

Documentation

It is very important to specify diabetes and any associated complications when documenting a patient's history. In our case, the primary diagnosis is type 1 diabetes and the secondary diagnosis is diabetic ketoacidosis. This will allow coding that accurately reflects the severity of the patient's medical condition and will ensure appropriate diagnosis-related group classification (Table).

In conclusion, this case demonstrates the importance of following the treatment protocols for DKA that are recommended by experts and supported by the evidence (77. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335-43. [PMID: 19564476]). Physicians should communicate clearly with nursing staff about the need for overlap during the transition from IV insulin to SC basal insulin to prevent any adverse reactions and anion gap reopening.