Diabetic Emergencies DKA, HHS, Hypoglycemia. Disclosure. Learning Objectives

Transcription

1 Diabetic Emergencies DKA, HHS, Hypoglycemia October 2018 Michael T. McDermott MD Director, Endocrinology and Diabetes Practice University of Colorado Hospital Disclosure Michael McDermott has no conflict of interest or relationships to disclose in relation to this educational activity. Learning Objectives Explain the pathophysiology of diabetic ketoacidosis (DKA) and Hyperosmolar Hyperglycemic Syndrome (HHS). Review the diagnostic approach to DKA and HHS and the distinction between the two conditions. Discuss the treatment of DKA and HHS. Review the treatment of inpatient hypoglycemia. Emphasize strategies to prevent inpatient hypoglycemia.

2 Diabetic Ketoacidosis Clinical Setting Type 1 DM (70-90%) New Onset Poor Compliance Precipitating Event Type 2 DM (10-30%) Precipitating Event Precipitating Events Infection Adrenal Crisis Acute Abdomen Ischemic Extremity Pulmonary Embolus Myocardial Infarction Cerebrovascular Event New Onset Type 1 Diabetes Pathogenesis Insulin Deficiency Absolute h Counterregulatory Hormones Insulin Deficiency Relative h Lipolysis h Ketogenesis h Proteolysis h Gluconeogenesis i Glucose Utilization h Glycogenolysis Minimal Ketogenesis i Alkali Reserve Hyperglycemia Ketoacidosis Dehydration Hyperosmolarity DKA HHS Kitabchi A, Diabetes Care 2009;32:

3 Water and Electrolyte Deficits Plasma Osmolality and Mental Status Plasma Osmolality Mental Status Kitabchi A, JCEM 2008;93: Useful Calculations Anion Gap Na + -(Cl - + HCO3 - ) Normal Range: 7-13 mmol/l Serum Osmolality 2 x (Na + ) + (Glucose/18) + (BUN/2.8) Normal Range: mosm/kg

4 Diabetic Ketoacidosis Diagnosis Glucose > 250 mg/dl HCO3 < 18 meq/l ph < 7.30* Anion Gap > 15 Ketones Positive (Urine, Serum) *Arterial ph best but venous ph OK Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Severity DKA MILD MODERATE SEVERE Glucose: > 250 mg/dl ph: HCO 3: meq/l Ketones: positive Sensorium: alert Glucose: > 250 mg/dl ph: HCO 3: meq/l Ketones: positive Sensorium: alert/drowsy Glucose: > 250 mg/dl ph: < 7.0 HCO 3: < 10 meq/l Ketones: positive Sensorium: stupor/coma HHS Glucose: > 600 mg/dl ph: > 7.30 HCO 3: > 18 meq/l Ketones: small Sensorium: stupor/coma Kitabchi A, Diabetes Care. 2009;32: IV Fluids Rehydrate: Monitor + Correct Hyponatremia Insulin Correct Hyperglycemia Potassium Prevent Hypokalemia Bicarbonate? Correct Severe Acidosis (ph < 6.9) Treat Precipitating Cause

5 IV Fluids 1 st Hour: NS, ml/kg/h ( Liters) Maintenance: ½ NS, ml/h if serum Na h or Normal NS, ml/h if serum Na Low Change to D5 when BG < 200 mg/dl (DKA) or < 300 mg/dl (HHS) Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94: Insulin (Regular) IV Bolus 0.1 U/kg, then Infusion 0.1 U/kg/hr If BG not i by 10% in 1 hour, IV bolus 0.14 U/kg and continue infusion at the previous rate Decrease rate to U/kg/hr when BG < 200 mg/dl (DKA) or < 300 mg/dl (HHS) Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94: Insulin Given by Different Routes Mild-Moderate DKA RCT: IV vs SQ vs IM Insulin Glucose Ketones Conclusion: In Mild-Moderate DKA, Insulin May Be Given IV, SQ or IM Kitabchi A, JCEM 2008;93:

6 Diabetic Ketoacidosis SQ insulin analogs may be used in mild moderate DKA in ED or inpatient Butkiewicz E, Diabetes Care 1995;18: Fisher J, N Engl J Med 1977;297: Nyenwe E, Kitabchi A, Diab Res Clin Pract 2011; 94: Diabetic Ketoacidosis IV Insulin + SQ Glargine RCT: IV Insulin vs IV Insulin + Glargine 0.25 U/Kg within 10 hours of IV Start Open Bars (N=13) No Glargine Closed Bars (N=12) Glargine Average Glucose Percent Rebound h Glucose Conclusion: In DKA, SQ Glargine Given with IV Insulin Reduces the Risk of Future Rebound Hyperglycemia without Increasing Hypoglycemia University of Colorado DKA Study Hsia E, J Clin Endocrinol Metab 2012;97: Potassium (check every 2 hours) Serum K + > 5.2 meq/l: Don t give K + Serum K meq/l: Give K meq/l Serum K + < 3.3 meq/l initially: Delay Insulin Rx. Give K meq/h until serum K + > 3.3 meq/l Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94:340-51

7 Bicarbonate ph < 6.9: Na Bicarbonate, 2 amps (100 mmol) in 400 ml H20 with 20 meq KCL, at rate of 200 ml/h for 2 hr until the venous ph is > 7.0 ph > 6.9: Na Bicarbonate therapy not required Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94: Phosphate Not indicated in most DKA patients Potential hypophosphatemic complications: Add meq/l K Phosphate to IV fluids Monitor serum calcium level Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94: Hypercoagulable State DKA: prophylactic heparin use may be beneficial HHS: full anticoagulation if no contraindications Kitabchi A, Diabetes Care 2009;32: Wilson JF, Ann Intern Med 2010; ITCI-3, Jan 1 Nyenwe E, Diab Res Clin Pract 2011; 94:340-51

8 Glucose < 200 mg/dl HCO3 > 18 meq/l ph > 7.30 Diabetic Ketoacidosis Resolution Anion Gap < 13 Ketones Improving (Urine, Serum) May not become negative for days Diabetic Ketoacidosis Ketone Response to Nitroprusside Measures Acetoacetate B Hydroxybutyrate Predominates Early; Converts to Acetoacetate With Caveat Ketones Measured by NP May Worsen Transiently Before Improving Protocol Use One Kitabchi A, Diabetes Care 2009;32:

9 UCH Protocol Use One Flow Sheet Use One Pitfalls of Precipitating Cause: don t fail to treat Cerebral Edema: don t correct BG too rapidly Relapse: don t turn off the IV insulin too soon Relapse: remember to give SQ long acting insulin before you stop the IV insulin

10 Mortality Mortality DKA: ~ 4% HHS: ~ 15% Adverse Prognostic Factors Coma Hypotension Age Extremes Hypoglycemia Definitions Hypoglycemia Glucose < 70 mg/dl Severe Hypoglycemia Glucose < 55 mg/dl, or Severe Symptoms, or Required IV Glucose or IM Glucagon Most Common Acute Complications Coma Seizures Dysrhythmias Myocardial Infarctions Death Hypoglycemia Complications

11 Hypoglycemia Raise Glucose to > 70 mg/dl ASAP Oral Glucose: 30 gm Recheck BG 20 minutes later Repeat oral glucose if BG still < 70 mg/dl Intravenous Glucose (D50): gm Intramuscular Glucagon: XXXX Recognize Which Medications Cause Hypoglycemia Insulin Sulfonylureas Meglitinides Avoiding Hypoglycemia All Patients Insulin Preparations 2018 Generic Name Peak Duration Inhaled Ins. Afrezza 1-2 hr 2-4 hr Aspart Fiasp 1-2 hr 2-4 hr Aspart Novolog 1-2 hr 3-5 hr Glulisine Apidra 1-2 hr 3-5 hr Lispro Humalog 1-2 hr 3-5 hr Detemir Levemir Minimal hr Glargine Lantus/Basaglar Minimal hr Glarg U300 Toujeo None hr Degludec Tresiba None 36 hr NPH Humulin-N 8-12 hr hr Regular Humulin-R 2-4 hr 6-8 hr U500 Humulin-R U hr hr

12 Basal Insulin Monitor HS to AM BG Trend ( i < 30 mg/dl overnight) Short-Acting Insulin Avoiding Hypoglycemia Insulin Therapy Mealtime Doses: Take Before the Meals Carbohydrate Counting: Learn to Do Accurately Correction Doses: Don t Stack (4 Hour Duration) Avoiding Hypoglycemia Sick Day / NPO Day Rules: Educate Sick Days / Low Intake Days / NPO Days Basal Insulin: i 33-50% (don t stop) Mealtime Insulin NPO: Stop Low Intake: i 50% Correction Insulin: Every 6 Hours for h BG Sulfonylureas/Meglitinides: Stop Avoiding Hypoglycemia Insulin Therapy Adjust Insulin For CKD or AKI egfr ml/min: i total insulin dose 25% egfr < ml/min: i total insulin dose 50%

13 Avoiding Hypoglycemia Insulin Therapy Continuous Glucose Monitoring Professional CGM Every 6 Months, or Personal CGM Continuously Glucose Sensors 2018 Professional Devices Abbott Flash Libre Pro Dexcom G4 Platinum Medtronic ipro 2 BG Data Blinded to the Patient while Wearing Keep Records Downloaded during Visit to MD/DO/CNS/NP/PA/CDE Carlson A. Diabetes Technol Therap 2017; 19(S2), S4-S12 Glucose Sensors 2018 Personal Devices Dexcom G6 Guardian-3 Freestyle Libre Flash BG Data Real-Time to Patient Every 5 Minutes Trend arrows to indicate direction and rate of change Alarms for current or impending Hypo or Hyper Levels Download to provider at next visit

14 Glucose Sensors 2018 Professional Devices Detect Patterns not Seen with SMBG Glucose Sensors Interpretation and Recommendations Interpretation: hypoglycemia occurring most often mid-morning and mid-afternoon. Recommendations: improve fasting glucose so that correction insulin doses are not needed. Use a less aggressive C:I ratio for breakfast and lunch and less aggressive CF during the day. Glucose Sensors Interpretation and Recommendations Interpretation: hypoglycemia occurs most often overnight. Recommendations: improve dinner coverage; change to less aggressive CF after dinner and at bedtime to avoid nighttime hypoglycemia since patients are less aware of hypoglycemic episodes while sleeping.

15 Insulin Pumps Medtronic 670G Guardian Sensor 3 Hybrid Closed Loop Tandem T-Slim X2 +/- DexCom G5 [HCL in Development] OmniPod +/- DexCom G5 [HCL in Development] V-Go Patch Pump Asante Snap Sooil DiabecareIIS Hybrid Closed Loop Insulin Delivery Predictive Glucose Management Medtronic 670G Hybrid Closed Loop Insulin Delivery During Pregnancy Stewart ZA. N Engl J Med 2016; 375:644-54

16 Diabetic Emergencies Summary Find Precipitating Cause of the Event Treat DKA, HHS with Insulin, Fluids, KCl Monitor Closely and Use a Flow Sheet Transition to SQ Insulin before DC IV Insulin Hypoglycemia: Treat with Glucose (PO, IV) or Glucagon (IM) Prevention of Hypoglycemia: Top Priority Thank You