Managing DKA, HHS, & Hyperglycemia in Acute Care

Transcription

1 Managing DKA, HHS, & Hyperglycemia in Acute Care, Christine Kessler ANP, CNS, BC-ADM, CDTC, FAANP Metabolic Medicine Associates King George, VA My Industry Associations Novo Nordisk advisor and speaker (obesity only) Astra Zeneca T2DM advisor Medtronic Insulin pumps and continuous glucose monitoring (outpatient and inpatient) Case of the Sweetie-Guy 54 year old obese male with DM type II is admitted to MICU for acute nausea, vomiting, epigastric pain and hypotension. Labs and CT of abdomen demonstrates acute pancreatitis. His home diabetes Rx is Janumet 50:1000 mg bid (metformin/sitaglipitin combo), glimperide 4 mg bid. Admission BMP shows a random glucose of 680 and A1C of 9.1. BUN/Cr 30/1.9. How should his hyperglycemia be managed?

2 Patients, % Objectives Discuss how hyperglycemia impacts the patient s morbidities and hospital stay Identify research-supported glycemic goals for patients based on morbidities, Hx of diabetes and age. Develop strategies to safely transition patients off an insulin infusion, out of the acute care unit and out of hospital to home. Compare DKA & HHS with regard to pathogenesis, presentation and treatment priorities Discuss strategies to prevent and treat hypoglycemia. Major Points to Ponder Hyperglycemia is systemic poison causing profound endothelial dysfunction (with increased morbidity, mortality and health care cost) We re not just talking about diabetes You need to identify safe glycemic targets (& get there safely e.g. without hypoglycemia) The greatest risks when transferring patients You can be a hospital star if you help develop/improve inpatient hyperglycemia care Hyperglycemia: Scope of the Problem 50 Diabetes 50 No Diabetes 40 78% 40 26% >200 < < >200 Mean BG, mg/dl Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9): :283A-284A. Courtesy B. Bode MD

3 Mortality (%) Hyperglycemia: An Independent Marker of Inhospital Mortality ICU mortality P < Normoglycemia Known diabetes New hyperglycemia Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87: Why Sweet Pts Go Sour Metabolic changes in response to stress of illness make sugar! insulin secretion stress hormones (cortisol, catecholamines, GH, glucagon) Results in gluconeogenesis, glycogenolysis, lipolysis, proteolysis cytokines (TNFα, IL-1) oxidative stress, inflammation Endothelial damage

4 Other Causes TPN 50% pts. receiving dextrose > 4mg/kg/min develop hyperglycemia Meds in fat emulsions (i.e. Propofol) Dextrose-containing dialysis solutions Immunosuppressants (steroids,tacrolimus, glucocorticoids, catecholamines, tacrolimus, cyclosporine) Vasopressors, dextrose solutions Why patients get too sweet INSULIN RESISTANCE Pressors Corticosteroids Sepsis Uremia Cirrhosis Obesity Bed rest INSULIN DEFICIENCY Advanced age Hypothermia Hypoxemia DM Pancreatitis Why Is Hyperglycemia So Awful for Hospitalized Patients? Cellular injury/apoptosis Inflammation Tissue damage Altered tissue wound repair

5 So what blood sugar levels should we aim at? Insulin In Critically Ill Patients Initiate insulin starting at 180 mg/dl Once insulin started, mg/dl recommended glucose range for most patients More stringent ONLY if closely monitored and less risk of hypoglycemia mg/dl May be better outcomes in surgical ICU patients American Diabetes Association. Standards of medical care in diabetes Diabetes Care. 2015;38(suppl 1):S1-S93. In Non-critically Ill Patients Sub Q insulin basal or basal bolus Premeal target <140 mg/dl with random blood glucose <180 mg/dl Tighter targets may be appropriate Tighter: stable patients with previous tight glycemic control Less tight: severe comorbidities American Diabetes Association. Standards of medical care in diabetes Diabetes Care. 2015;38(suppl 1):S1-S93.

6 AACE/ADA Consensus Statement on Management of Inpatient Hyperglycemia BG goals Avoid Tips MICU <110 If >180, initiate IV short acting insulin General Wards Pre-meal <140 Random <180 <100 In glucocorticoid therapy, initiate accuchecks for 48 hours and then initiate insulin therapy as appropriate Avoid routine use of corrective insulin at bedtime unless continuous nutrition/tpn Minimum Accuracy Criteria for BG Monitors (CLSI standard) 95% of glucose results must be: Glucose < 100 mg/dl within 12 mg/dl of reference Glucose >/= 100 mg/dl within 12.5% of reference And 98% of glucose results must be: Glucose < 75 mg/dl within 15 mg/dl of reference Glucose >/= 75 mg/dl within 20% of reference

7 Mortality Rate, % Sources of BG Reading Error Before testing: site cleaning, proper lancing Strip factors: expired date, heat & humidity, product defects*, handling the strips, Glucometer or sensor malfunction Analytical factors: high altitude, cold, anemia, low oxygen, acetaminophen, L-dopa Severe Hypoglycemia in Critically Ill Patients Associated With Increased Risk of Mortality SH Controls No SH Severe hypoglycemia (<40 mg/dl) was associated with an increased risk of mortality (OR, 2.28; 95% CI, ; P=.0008) Krinsley JS, Grover A. Crit Care Med. 2007;35(10):

8 Events Triggering Hospital Hypoglycemia Transportation off ward, causing meal delay Failure to measure blood glucose before insulin doses Sudden decrease in renal function New NPO status Drugs i.e. tramadol Interruption of IV dextrose therapy or TPN Enteral feedings Continuous venovenous hemodialysis Hughes S. Pain Med Linked to Hypoglycemia. Medscape Medical News [serial online]. Dec ;. Features Increasing the Risk of Hypoglycemia in an Inpatient Setting Advanced age, female gender Renal failure, liver disease Autonomic neuropathy (hypoglycema unawareness) Concurrent illness (cerebral vascular accident, congestive heart failure, shock, sepsis) Ventilator use Concurrent medications ( -blockers, quinolones, epinephrine, tramadol, ETOH) D Hondt NJ. Diabetes Spectrum. 2008;21(4): Symptoms for hypoglycemia Neurogenic or neuroglycopenic symptoms of hypoglycemia: Neurogenic (adrenergic) symptoms: Sweating, shakiness, tachycardia, anxiety, and a sensation of hunger Neuroglycopenic symptoms: Weakness, tiredness, or dizziness; odd behavior, difficulty with concentration; confusion; blurred vision; and, in extreme cases, coma and death

9 Concerns with very low blood sugar If glucose is under 18 mg/dl: Affects white matter (most sensitive tissue) Cerebellum & brainstem less affected can lead to central pontine myelinolysis Shih-Hung T. Hypoglycemia Revisited in the Acute Care Setting.Yonsei Med J Nov 1; 52(6): Hypoglycemia and CV Events Tachycardia and high blood pressure Myocardial ischemia Silent ischemia, angina, infarction Cardiac arrhythmias Transiently prolonged corrected QT interval, Increased QT dispersion Sudden death Wright RJ, Frier BM, Diabetes Metab Res Rev 2008; 24: Treatment of Hypoglycemia Obtain a fingerstick blood glucose immediately If fingerstick glucose not available, begin RX while waiting for the test to be done. Do NOT WAIT for lab serum glucose to confirm hypoglycemia

10 Treatment of Hypoglycemia Treatment based on patient s level of consciousness Conscious patient with no risk of aspiration If glucose mg/dl 6 oz juice 6 oz regular soda One tube glucose gel If glucose below 50 mg/dl 8 oz juice 12 oz regular soda Two tubes glucose gel Hypoglycemia Procedure-Con t Unconscious patients, at risk for aspiration 50 ml 50% dextrose IV over 5 minutes {or D50 = (100-BG) x 0.4 ml IV} Stay with patient until you see patient responding If there is no IV access Glucagon 1 ml (1 mg/ml) IM or SQ Stay with patient until responsive Note: glucagon can cause nausea and vomiting Notify provider and follow protocol

11 There are 13 types of DM Type 1 (autoimmune) Type 2 (insulin resistance) LADA (latent autoimmune DM in adults) Flat bush (ketone-prone T2DM) Atypical DM Iatrogenic type 1 DM Type 3 (bucket dx) MODY type 1, 2, 3, 4, 5, 6 Tips to common Types Type 2 (insulin resistance) High TGs Strong family hx Overweight Acanthosis nigrins Lada (type 1) Pt & family hx of autoimmunity Not too overweight Less family hx (or DM with insulin use) TRUE OR FALSE An A1C is currently the best way to diagnose diabetes?

12 Fast Facts On A1C Normal < 5.7% Prediabetes 5.7 to 6.4% Diabetes >6.7% Ideally should be done on all patients admitted to hospital (if high on DM meds not controlled!) Provides a 3 month average blood sugar (does not show variability!) Not accurate in severe anemia (esp Fe deficiency); or Sickle Cell trait Fast Facts On A1C If not accurate Fructosamine offers 2 week average (not use if low albumin) How Can Diabetes and Hyperglycemia be Controlled in the Hospital? Oral agents or GLP1 agonists = often inappropriate for hospital patients IV insulin = most often used in the intensive care unit setting (or in other defined populations) Subcutaneous insulin = the drug of choice for controlling hyperglycemia in the majority of non-critically ill patients

13 Oral Hypoglycemic Agents Should NEVER be Used in ICU? Non-insulin hyperglycemia agents only okay in patients with normal nutritional intake, stable blood glucose levels, and stable renal and cardiac function. But risks outweigh most benefits: Concern with fluctuating kidney function Volume shifts Delayed onset of action GI upset Need to feed some AACE/ADA Consensus Statement Non-insulin therapies in the hospital? Sulfonylureas are a major cause of hypoglycemia Secreatagogue: Glipizide, glimepiride, glyburide Never in ischemic heart dz caution in CKD Glynides: repaglinide (prandin) or nateglinide (starlix) Prandial, fast, Metformin (insulin sensititzer) contraindicated in setting of renal impairment and with use of iodinated contrast dye Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract AACE/ADA Consensus Statement Non-insulin therapies in the hospital? Thiazolidinediones (insulin sensititizers) associated with fluid retention, edema, weight gain Never in CHF or liver dz α glucosidase inhibitors (starch blockers): Acarbose: prandial glucose lowering agents but Incretins: (prandial) GLP1-agonists: can cause nausea and not use in GFR <45 (Victoza, Byetta, Bydureon) DPP4 antagonist: Januvia, Trajenta, Onglyza SGLT2 (basal/prandial) Invokana, Farxiga, Jordiance Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009

14 Who Needs An Insulin Infusion ALL critically ill with Type 1 diabetes or significant hyperglycemia DKA, hyperglycemic hyperosmolar state Post op cardiac surgical pt with hyperglycemia General perioperative care, intra-abdominal surgery, organ transplantation with hyperglycemia Prolonged NPO, parenteral nutrition (T1DM) Hyperglycemia on high dose steroids Who Needs An Insulin Infusion Uncontrolled hyperglycemia > 180 (2 episodes in 24 hours) If unsure, then monitor qac/qhs glucose monitoring for 24 hours and then continue if BG > 180 Labor & delivery hyperglycemic patient Considerations with the use of IV Insulin Infusion Clarify the concentration from pharmacy Prime tubing (20-50 cc) Determine if a pre-infusion bolus is needed Check glucose hourly and modify drip to protocol Tandem line with potassium!

15 What Needs to be Considered? Type 1 or type (IR or not) Prior insulin use/dose Nutrient intake Exercise Age Kidney function And.. Hmmm? weight Insulin needs are different for this patient than for a thin, type 1 diabetic Insulin Infusion Tips Bolus or no bolus? go with your protocol Modified Yale Protocol: If blood glucose over 180 (or 150) will need a bolus How much to give: divide blood glucose by 70 and round to nearest 0.5 unit Example: blood glucose 210/70 = 3 units If pre-infusion glucose =/> 180 (or 150), give it as bolus and hourly rate

16 DKA Occurs in absence or near-absence of insulin Presenting symptom for ~25% type 1 DM Can be seen in Type 2 variants (Flat Bush or ketoneprone) More common in children esp. under 5 years 40% under 40 20% over 55 Infectious cause most common Mortality 5-10% Increases with age ( > 65 = 20-40%)%)

17 Hyperosmolar Hyperglycemic State (HHS) An acute metabolic complication of type 2 diabetes mellitus characterized by : Profound dehydration elevated plasma osmolality in a patient with hyperglycemia impaired mental status Occurs predominately in Type II Diabetics A few reports of cases in type I diabetics (LADA). The presenting symptom for 30-40% of Type II diabetics. Causes of DKA/HHS Stressful precipitating event that results in increased catecholamines, cortisol, glucagon. Infection (pneumonia, UTI) Alcohol, drugs Stroke Myocardial Infarction Pancreatitis Trauma Medications (steroids, thiazide diuretics) Non-compliance with insulin Diagnostic Criteria for DKA and HHS Mild DKA Moderate DKA Severe DKA HHS Plasma glucose (mg/dl) > 250 > 250 > 250 > 600 Arterial ph < 7.00 > 7.30 Sodium Bicarbonate (meq/l) <15 < 10 > 15 Urine Ketones Positive Positive Positive Small Serum Ketones Positive Positive Positive Small Serum Osmolality (mosm/kg) Variable Variable Variable > 320 Anion Gap > 10 > 12 > 12 variable Mental Status Alert Alert/Drowsy Stupor/Coma Stupor/Coma

18 Common Symptoms of DKA/HHS Polyuria Polydypsia Dehydration Blurred vision Dizziness Nausea/Vomiting Profound Fatigue Physical Examination in DKA/HHS Hypotension, tachycardia Kussmaul breathing (deep, labored breaths)** Fruity odor to breath (due to acetone)** Adominal tenderness more in DKA ** DKA exclusive Obtundation worse in HHS DKA - Associated Abnormalities Sodium variable fall by 1.6 for every 100 increase in glucose (over 100) falsely low with hypertriglyceridemia Chloride hyper in ketoacidosis hypo associated with severe emesis

19 DKA - Associated Abnormalities Potassium high in acidosis (0.6 meq per 0.1 decrease in K+) at high risk for severe hypokalemia when ph is corrected!! Serum acetones Positive in DKA; Possibly small in HHS Urinalysis Ketones (for DKA); leukocyte esterase, WBC (for UTI) Diagnostic Studies in DKA Chemistry Glucose (>250) Bicarbonate (<15) Anion gap = (Na + ) (Cl - + HCO 3- ) ph <7.3 Frequently seen: BUN/creatinine (dehydration) sodium potassium Pseudohypernatremia: to correct, Diagnostic Studies in DKA/HHS CBC Leukocytosis (possible infection) Amylase/Lipase To evaluate for pancreatitis BUT, DKA by itself can also increase them! EKG Evaluate for possible MI

20 DKA Management Fluid resuscitation Normal saline cc/hr with bolus of 1L (LR?) If UOP good and NA > 140, slow IVF and change to 0.45 NS (add KCL 20 meq) Add D5 once BS < 300 (or 250) And add potassium!!!!!!! POC Sugar checks hourly: Every 1 hour initially, then every 2 hours, and so on. (LR?) DKA Insulin (novolog, glulisine or regular)******** 0.4u/kg with 1/2 IV and 1/2 SQ Some say u/kg why not? Or just give 10 to 20 units IV IV infusion better than hourly IV injections continue until ketones in urine resolved, sugars stabilize or pt eating Change to SQ once BS< 200, ph > 7.3, Bicarb > 18 (anion gap closed) DKA Management Potassium K< 3.5 add 40 meq/l K > 3.5 and < 5.0 add 20 meq/l check q 2 hrs Replete hypophosphatemia Give bicarbonate if ph < 7.1 Treat underlying cause

21 Treatment of HHS Hydration!!! Even more important than in DKA Find underlying cause and treat! Insulin drip Should be started only once aggressive hydration has taken place. Switch to subcutaneous regimen once glucose < 200 and patient eating. Serial Electrolytes Potassium replacement. DKA/HHS Complications Hypotension and shock Thrombosis (HHS) Cerebral edema Renal failure Hypoglycemia

22 Glucose (mg/dl) Insulin (µu/ml) Know Your Insulin Needs BASAL vs BOLUS (prandial & correction) Physiologic Insulin Basal Bolus Insulin: Nutritional (Prandial) Insulin Basal Insulin Breakfast Lunch Supper Nutritional Glucose Basal & Prandial Glucose A.M. P.M. Time of Day Suppresses Glucose Production Between Meals & Overnight The 50/50 Rule What Main Insulins Do We Have? BASAL: Glargine (Lantus) Detemir (Levemir) NPH PRANDIAL/CORRECTION: Regular Novolog (Aspart) **** Humalog Glulisine (Apidra) **** OTHERS: combos, concentrated (U500, U300)

23 Insulin Effect Tips & Summary of the Insulin Types Basal insulin: Use non-peaking, longer acting insulins Glargine or detemir are preferred NPH also possible; but mostly used for single day steroid use or PM enteral feedings Prandial/Nutritional insulin: Depends on the type of nutrition Rapid-acting insulin when patients are eating Regular insulin also possible Correctional insulin: Use rapid-acting (or regular) insulin Usually the same as the nutritional insulin to reduce blood glucose Rapid (Prandial, Bolus) Short (Prandial, Bolus) Intermediate (Basal) Long (Basal) Which Insulins are Used? NPH Detemir (Levemir) Glargine (Lantus) Regular Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Inhaled insulin Time (hours)

24 When to Stop Insulin Drip Hourly sugars checks until stable sugars for at least 3 hours at target BG level then q 2 hours If stable for hours may stop the drip. No change expected re: glucose-impacting meds or hemodynamic status Transitioning Off IV Insulin This is where we really hurt our patients!!!!! IMPORTANT!!!!! Must start SC glargine at least 2-3 hours before stopping IV insulin (always for Type 1 DM) Or SC Lispro, Aspart, or Regular mins. before stopping drip May start long-acting insulin on initiation of IV insulin or the night before stopping the drip* NEVER use only boluses for T1DM Bolus-only coverage rarely gets you to target

25 Is SC Insulin (MDI) Required off infusion? YES- DM1 DM 2 or A1c 6 and infusion rate 1 unit / hour On high dose steroids and rate 1 unit / hour NO- Type 2 DM with infusion rate < 1 unit / hour Stress hyperglycemia with HbA1c < 6 Even if high infusion rates So you have to give SQ insulin.how? Converting to SC insulin If more than 0.5 or 1 u/hr IV insulin required with normal BG, start long-acting basal insulin (glargine or detemir). Determine hourly rate IV insulin over past 6-8 hours and multiply x 24 to get TDD Take 80% of that 24 hour dose Give 50% as basal insulin & 50% as bolus divided before each meal Check sugars ac and hs*** Use Correction Bolus and prandial bolus!

26 Example Patient taking ave 2.5 units an hour 2.5 u x 24 hr = 60 80% of 60 = 48 ½ of 48 is 24 so give 24 units of glargine (basal) PM Give other half in divided doses for meals Thus, 8 units bolus with meals tid (adjust for meals eaten and blood glucose) Correction doses of bolus insulin? Determine Insulin Sensitivity Ratio Use this to correct high sugar Take with dose for carb coverage Determine carbohydrate coverage (insulin:carb coverage) For Prandial Insulin Dosing Calculate Insulin Sensitivity Calculate the patient s Insulin Sensitivity* (IS) by compiling their Total Daily Dose (TDD) and dividing this total into 1500 or 1800 Type 2: 1500 / TDI = Insulin Sensitivity Type 1: 1800 /TDI = Insulin Sensitivity (* The IS is the incremental fall in blood sugar that can be expected from each unit of insulin) Use IS to construct a tailored correction

27 What About Dietary Coverage? Type 1 or BMI < 30: give one unit per 15 grams of carbs Type 2 Or BMI > 30: give one unit per 10 grams of carbs Le Menu the diabetes friendly hospital menu Identify the carbohyhdrate amount in full meal portion Marks foods as gms CHO3 Give prandial bolus right AFTER eating Computer Glucose Programs Glucommander Endo Tool GRIP computer program others

28 Pre-operative Medical Management Hold morning oral diabetes medications If on NPH or mixed insulin (70/30) take half in morning If on detemir (Levemir) or glargine (Lantus), take FULL dose in morning.a caveat is.. Encourage pt to check own BG night of and morning of surgery (if <70, contact physician) Use rapid-acting insulin to correct sugar only if needed to keep sugar < 200 prior surgery Tips on EF Glucose Management Continous EF: Check BG at start of EF and every 6 hours Can use basal insulin, i.e., glargine (calculated by CHO loading in continuous feedings (based on BMI) For Nocturnal EF-- NPH is preferable Time action best covers TF duration (10-16hrs) Dose based on weight/bmi BMI <30: 10 units NPH at onset of TF BMI >30: 20 units NPH at onset of TF Give at start of nocturnal tube feeding

29 Intermittent Dosing With Short-acting Insulin Regular Insulin (preferable) every 6h: BMI <30: 1 unit per 15 gm CHO BMI >30: 1 unit per 10 gm CHO Example: 1Cal Tube feeding ( ml/hr:»43.5 gm CHO infused q 6h»BMI <30, 3 units Regular q 6h»BMI >30, 4 units Regular q 6h Tips on EF Glucose Management If TF to be interrupted for > 1 hour: Start IV infusion of 10% dextrose at same rate as EF Continue until EF resumed at former rate Interruptions, clogging, disconnections can cause a major concern for. HYPOGLYCEMIA! TPN considerations Usual Mix is 0.1 unit Regular per gram of dextrose Example: TPN 225 gram dextrose x 0.1units regular = Add 22.5 units regular insulin to TPN bag Trend of BG levels over 24 hours Regular if BG >150 for standard target: Guidelines: Increase by 0.05 units Regular Insulin per gram Dextrose Threshold: 0.3 units regular insulin/gm dextrose, bag/day Check BG on all TPN patients Check BG every 6 hours SQ insulin or an infusion may be added if BG not at target

30 When Your Patient Has an Insulin Pump Allow to stay on pump if non critical units If surgery is planned stop the pump and give glargine or levemir equaling their 24 hr basal rate The pump can provide you lots of information!!! Insulin pumps

31 Glucose (mg/dl) Glucose (mg/dl) Where we are now Fingerstick Blood Glucoses Glucose measurement Insulin bolus Target Range 0 12:00 AM 6:00 AM 12:00 6:00 PM 12:00 AM Continuous Glucose Monitoring Provides More Comprehensive Picture of Glycemic Patterns Glucose measurement Insulin bolus 100 Target Range 0 12:00 AM 6:00 AM 12:00 6:00 PM 12:00 AM

32 Discharge insulin Algorithm Discharge Treatment A1C < 7% Re-start outpatient treatment regimen (OAD and/or insulin) A1C 7%-9% Re-start outpatient oral agents and D/C on glargine once daily at 50-80% of hospital dose A1C >9% D/C on basal bolus at same hospital dose. Alternative: re-start oral agents and D/C on glargine once daily at 50-80% of hospital dose

33 Remember to Consider Exercise