DKA

1. DKA Mark Vanderwel, MD Pediatric Endocrinology and Diabetes Specialists 704.512.3636

2. INADEQUATE INSULIN  glucose utilization  extracellular glucose  intracellular glucose  Glucagon  Cortisol, Epi Osmotic diuresis DEHYDRATION  glycogenolysis  gluconeogenesis Vomiting  lipolysis ACIDOSIS  ketogenesis

3. HISTORY • Prodrome is usually of a more gradual onset in newly diagnosed diabetes than in an established patient presenting in DKA • Polyuria, Polydipsia, Nocturnal Enuresis • Polyphagia/Anorexia • Weight Loss • Abdominal pain, nausea, vomiting • Concurrent illness

4. OTHER HISTORY TO OBTAIN • Family history of DM • Overall incidence of T1DM is between 1:300 and 1:400 • Children of a mother with T1DM or sibs of T1DM have a 3% incidence • Children of a father with T1DM have a 6% risk • This also helps to gauge the family’s familiarity with diabetes care, but DOES NOT mean that they will do it well or do not have to learn more

5. Social history • Who cares for the child? (i.e. Who must learn about the disease?) • Psychosocial stressors (especially in established patients)

6. Compliance (in established patients) • Missed insulin • Frequency of blood sugar testing • Dietary excursions • Possibility of alcohol or drug use • Do they know their typical HgbA1C? (If not, this is probably a bad sign) • History of prior DKA? (80-90% of our patients with DM never need to be rehospitalized after diagnosis – the other 10% you get to know very well.)

7. Medicines? • Especially glucocorticoids

8. PHYSICAL • Dehydration • Prolonged capillary refill • Sunken eyes • Dry mucosa • Tachycardia • Shock • Ketoacidosis • Kussmaul breathing • Fruity odor to breath • Abdominal tenderness • Lethargy/altered Mental status

9. PHYSICAL • Fungal infections • Acanthosis • (children with Type 2 DM can also present in ketosis, although the acidosis is generally less severe)

10. INITIAL STAT LABS • Fingerstick blood glucose • Basic Metabolic Panel • Urine for ketones and glucose

11. WORKING THROUGH THE ORDERS • ADMIT to Dr. Parker/Houchin/Vanderwel/Mieszczak/ICU • Housestaff are encouraged to follow and be involved

12. Mandatory ICU: • Altered mental status • Shock • Initial glucose > 800 • pH < 7.10 or HCO3- < 10 • HCO3- < 14 in a patient younger than 5 • Significant intercurrent illness

13. Possible Progressive Care • Patients requiring insulin drip but none of the above Floor Bed • Ketosis with mild acidosis, even brief insulin drips • New onset DM without ketosis

14. VITALS: • Include mental status checks to monitor cerebral edema • Cushing’s Triad: Hypertension, bradycardia, irregular respirations

15. ACTIVITY: • Restricted in DKA; encouraged once acidosis is resolved • DIET: • NPO if HCO3- <18 • Patients with HCO3- above 14 may drink clears if they’re not nauseated. • Constant Carb Diet

16. IV FLUIDS: • If the patient is in shock, give 20 cc/kg NS, repeat as necessary. • Remember that if blood sugar is greater than 180, the patient is exceeding their renal threshold for glucose, and may require additional correction fluid. • Because of this, calculations of fluid deficit and replacement that you learned in medical school might be thrown off.

17. INSULIN: IV or SQ? • In a patient with a bicarbonate < 14 or a pH < 7.20, an insulin drip is generally preferred. • If HCO3 > 20 or pH > 7.30, most patients can start on shots. • The middle ground is attending and patient specific. • However, if insulin is to be administered IV, it should be given as part of an insulin drip, not as “IV push.” The half-life of IV insulin is measured in minutes, and IV push insulin has very little relevance in the pediatric world.

18. THE THREE BAG SYSTEM: • INSULIN DRIP: • Mix 50 units of regular insulin in 50 cc NS. Run at 0.1 units/kg/hr. Order this to be prepared STAT. Children in DKA should not go without insulin waiting for a drip to be sent up from pharmacy. • “SUGAR-FREE FLUID”: • Most patients will require ½ NS. • Serum potassium will plummet with insulin administration, and most patients require at least 20 mEq/L of KCL and 20 mmol/L of K phos. • DEXTROSE-CONTAINING FLUID: • The exact fluid you’ve chosen for #2 with D10.

19. POTASSIUM CONTENT: • Give half of potassium as KCl and half as KPhos unless conditions warrant otherwise • If K<3.0, give 30 and 30 • If K between 3 and 5, give 20 and 20 • If K between 5 and 5.5, give 20 mEq/L KCl only • If K > 5.5, no potassium, but continue to monitor

20. The Three Bag System • Run total fluids at 1.5 to 2x maintenance. • Add the D10 fluid if BG drops by more than 50 points per hour or if patient becomes hypoglycemic. • Once euglycemia is achieved, here’s a sample order set for a patient on an insulin drip: • D10 ½ NS with 20 mEq KCl and 20 mmol/L KPhos @ 75 cc/hr • ½ NS with 20 mEq KCl and 20 mmol/L KPhos @ 75 cc/hr. • If blood sugar < 60 or > 300, call house officer (and/or attending) • If blood sugar < 100, increase D10 and decrease non-dextrose fluid by 25 cc/hr • If blood sugar > 150, increase non-dextrose fluid and decrease D10 by 25 cc/hr

21. Notes on the 3 bag system • These orders might save you a phone call or two, but are not meant to allow you to abandon care of the patient to a protocol! • Hyperglycemia almost always corrects before acidosis. • If the patient is “maxed out” on dextrose-containing fluid and is still hypoglycemic, call one of us BEFORE you decrease the insulin drip. • (Caveat – for significant hypoglycemia, you can put the drip on hold until we respond; just don’t leave it off for too long.)

22. LABS: • Blood sugars q hour • (if glucose has plateaued in the normal range, these may be decreased to every 2 hours, especially for patients on progressive care) • Dip voids for ketones until negative (?) • I’ve changed my tune on this recently; others of my partners still like it • (Don’t forget to look at the other urinalysis parameters. It’s embarrassing to miss a UTI.) • BMP q 4 to 6 hours until HCO3- > 18

23. Case dependent repeating labs: • Beta-hydroxybutyrate (measurement of serum ketones) and acetoacetate • Blood Gas • CBC (if infection suspected)

24. Initial labs for all patients • Hemoglobin A1C • TSH/Free T4

25. Initial labs for new diagnosis patients • Antibodies – if questioning diagnosis of Type 1 vs. Type 2 • Anti-Islet Cell • Anti-Insulin • Anti-GAD 65 • Anti-TPO (20% incidence of autoimmune thyroiditis in patients with type 1 DM) • TTG

26. Labs to consider • Amylase/Lipase (for patients with severe abdominal pain or nausea/vomiting out of context with acidosis) • Cultures

27. NOTES on labs: • Remember to correct serum sodium for hyperglycemia • Corrected Na = measured Na + 1.6* (glucose – 100)/100 • Anion Gap: (Na + K) – (Cl + HCO3)An anion gap > 16 is typical of DKA • Elevated White Counts are very common, often secondary to stress response • An elevated BUN may reflect a decrease in extracellular volume or may be secondary to increased protein breakdown

28. OTHER CRITICAL CONSIDERATIONS: • Bicarbonate • Infection • Cerebral Edema

29. BICARBONATE • Very controversial, and everyone is likely to have a different opinion • (always discuss with either/both PICU attending and Endo attending) • Usually only consider if pH<7 AND patient in poor clinical condition • If chosen, give 1 mEq/kg IV (max dose 50 mEq) over 30 minutes

30. Do NOT give bicarbonate: • As an IV push • If patient is hypokalemic • (bicarbonate makes it worse) • If unable to adequately ventilate patient • (if there is a component of respiratory acidosis, you might not be able to eliminate the CO2 produced, and serum pH will actually decrease)

31. Arguments for Bicarb • A rapid, slight improvement in acidosis may improve myocardial contractility and mental status, stabilizing the patient until a definitive treatment takes effect

32. Arguments against Bicarb • Paradoxical CNS acidosis caused by the CO2 produced, crossing the blood-brain barrier more readily and resulting in a lower CNS pH • Bicarb shifts the oxy-hemoglobin dissociation curve to the left, leading to impaired oxygen release to tissues and an increased production of lactate. • However, this usually is only a concern if there is a problem with oxygenation • There has not been shown to be a difference in the rate of recovery between patients treated with Bicarb and those not

33. INFECTIONS • Infections are frequent precipitants of DKA in established patients • Patients with poorly controlled DM are prone to infections • Urine • Sinuses • Skin and subcutaneous tissue • Lungs • Fever may be absent in a patient with DKA, particularly if poorly perfused • CXR is unreliable for diagnosing pneumonia in dehydrated patients • CBC’s are of little diagnostic value

34. CEREBRAL EDEMA • Most patients in DKA have some degree of asymptomatic cerebral edema. • Symptomatic cerebral edema occurs in less than 1% of patients, but they’re the most critical 1%. • Symptoms from cerebral edema usually occur within the first 16 hours of therapy for DKA

35. Time of onset of cerebral edema after start of therapy NEJM 2001; 344: 264-9

36. Signs and Symptomsof Cerebral Edema • Severe headache • Mental Status Changes • Cushing’s Triad • (bradycardia, hypertension, irregular respirations) • Vomiting • Fixed/Dilated pupils • Papilledema

37. Risk Factorsfor Cerebral Edema • New Onset DM • Prolonged DKA prior to admission • Chronic poor diabetic control leading to chronic hyperosmolality. • Age < 5 • Severe acidosis • Provision of more than 4 L/Meter Squared/Day of fluids • Excessive swings of glucose, plasma osmolality and pH • Variable rate of fluid replacement • Rate of decrease of serum glucose > 100 mg/dL/hr • Failure of sodium to increase as glucose decreases

38. Therapy for Cerebral Edema • (PICU and Endo attendings must know this is happening immediately) • ABC • Raise head of bed 30 degrees, head in midline position • Decrease IVF to < maintenance • Mannitol • 0.5 g/kg IV over 5 minutes, • may repeat up to 2.5 g/kg q 5-10 minutes x 2 until a response is obtained • Little consensus about dose, but speed is critical • Hyperventilation • Head CT if stable • Neurosurg consult for ICP monitoring • Steroids have not been shown to be of benefit, and will only worsen hyperglycemia

39. NON-CRITICAL CONSIDERATIONS • (Once the acidosis is resolving) • Education • Eating • Conversion to shots

40. Education • Patients should have been given a Pink Panther book on admission (excellent diabetes review book) • Please write to consult diabetes educator (Amy Magid)

41. Eating • OK to drink sugar-free fluids while on drip • If patient still needs insulin drip, but we decide it’s time to eat, we can cover with subcutaneous shot of Novolog for the carbs while the insulin drip continues. • Generally, eating happens when we convert to subcutaneous insulin dosing. • Again, kids don’t eat an ADA diet – “consistant carb” is how we order it

42. Conversion to shots • Almost all of our patients are on a “basal/bolus” insulin regimen. • The insulin pump is the optimal way to provide basal-bolus insulin for most patients, but our new diabetics usually start on shots. • For established patients, typically convert to home regimen once HCO3 is > 18. • If they get their basal insulin at night, but they are ready to convert in the morning, half of the basal dose can be given, or we can use extra bolus insulin until it’s time for their basal insulin. • (This decision will be attending and patient dependent.)

43. New Patient Insulin Dosing • Approximately half of insulin to be administered will be basal • Half will be bolus for carbohydrate coverage and hyperglycemia correction. • Decision-making will be at the discretion of the attending based on the individual patient, but might initially approximate this chart:

44. New Patient Insulin Dosing

45. Types of Insulin • Basal/Intermediate • Lantus (Insulin Glargine) • Levemir (Insulin Detemir) • NPH (that’s so 1945…) • Rapid Acting (used for carbohydrate coverage and correction of hyperglycemia) • Novolog (Insulin Aspart) • Humalog (Insulin Lispro) • Apidra (Insulin Glulisine) • Regular (that’s so 1923…) • Pre-Mixed • Multiple combinations that we generally only use in patients that can only handle 2 shots a day, and we sacrifice precise control to limit DKA admissions

46. Pen vs. Syringe • Many patients prefer insulin dosing using a pen rather than the syringe method. • Discuss with us or Amy Magid (diabetes educator) • The NovoPen Jr. can administer half-unit doses, as can the Humalog Luxura Pen • The Humalog KwikPen and Novolog FlexPen can only administer in whole unit doses.

47. Further Considerations on fluids • Once we convert to shots and are off the drip, the dextrose-containing fluid should be discontinued. • Non-dextrose fluid should be continued at 1.5 x maintenance until urine ketones are negative. • The IV can generally be removed once the patient is off IV fluids.

48. Further Considerations on labs • Unless there’s an electrolyte (or other) concern, venipuncture should end once the patient is off the insulin drip. • Fingerstick blood sugars should be obtained qAC, qHS, midnight and 0300. • Once voids are negative for ketones, we don’t need to send further urine for analysis unless blood sugar is greater than 250.

49. Insulin dose adjustment • (to be done only in conjunction with endocrine attending) • The stress and inactivity of the hospitalization typically makes inpatient blood sugars 25-100 mg/dL higher than they’d be at home. • Therefore, in the hospital, we typically target a blood sugar range between 125 and 200. • Typically, if the majority of blood sugars are running high, increase basal insulin by 10% • Adjust carbohydrate coverage if patient goes from a normal blood sugar to hyperglycemia after eating. • Adjust correction factor if the patient doesn’t come down from a high blood sugar appropriately enough.

50. Low blood sugar management • Write for the Hypoglycemia protocol • Only use 15 carbohydrates for lows between 50 and 80. Too many carbs, and you’re dealing with rebound hyperglycemia. • Severe/symptomatic lows should also initially be treated with 15 carbs, but follow-up blood sugar in 15 minutes should confirm improvement. • If patient seizures or is unable to take carbs, 25 cc of D50 can be given IV (or 50 cc of D25). This is 12.5 g of carbs. • If no IV access, give glucagon: • Under 20 kg, give 0.5 mg (0.5 cc or half of the syringe) • Over 20 kg, give 1 mg (1 cc or the entire glucagon syringe)