INTERNAL MEDICINE RESIDENTS NOON CONFERENCE: INPATIENT GLYCEMIC CONTROL Presented by: Leyda Callejas PGY5 Endocrinology, Diabetes and Metabolism Acknowledgements: Dr. P Orlander Dr. V Lavis Dr. N Shah
DEFINITIONS OF GLUCOSE ABNORMALITIES Hypoglycemia is defined a BG level <70 mg/dl Mild to moderate hypoglycemia is when BG levels are between 40 and 69 mg/dl. Severe hypoglycemia is when BG is <40 mg/dl. AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract. 2009;15(No. 4)
DEFINITIONS OF GLUCOSE ABNORMALITIES Hyperglycemia is defined as any blood glucose (BG) value >140 mg/dl. In patients without a previous diagnosis of diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) values of < 6.5% elevated BG may be due to stress hyperglycemia. HbA1c values of >6.5% suggest that DM preceded hospitalization. AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract. 2009;15(No. 4)
HYPERGLYCEMIA IN HOSPITALIZED PATIENTS Irrespective of its cause, hyperglycemia adverse outcomes associated with Hyperglycemia occurs in patients with known or undiagnosed diabetes, or it occurs during acute illness in those with previously normal glucose tolerance ( stress hyperglycemia ) Possible connections between hyperglycemia and complications: Impaired collagen synthesis Impaired WBC function Increased production of free radicals and activation of inflammatory markers Stress Hyperglycemia Dungan et al, Lancet 2009 1789-807
SCOPE OF THE PROBLEM OF HYPERGLYCEMIA IN HOSPITALIZED PATIENTS 12 % admissions previously unrecognized DM or stress hyperglycemia 26 % of admissions known DM 70 % non diabetic patients having cardiac surgery become hyperglycemic( BG > 150) Umpierrez, JCEM 87:978, 2002 Leibowitz ANN Thor Surg 90:1825, 2010
DIABETES DISADVANTAGE Retrospective analysis in 3184 pts admitted to Emory University Hospital for non cardiac surgery A Frisch et al Diabetes Care 33:1783, 2010
RELATION BETWEEN GLUCOSE VALUES AND OUTCOMES
CAUSES OF GLUCOSE INSTABILITY IN HOSPITALIZED PATIENTS Changes in nutrition (NPO, enteral, parenteral feedings) Changes in clinical status/meds (pressors, glucocorticoids) Prolonged use of SSI as monotherapy Failure of clinician to make adjustments Poor coordination of BG testing and administration of insulin Poor communication during times of transfer of care Poor understanding of when insulin can be held and when it should be given (DM-1 vs DM-2, long acting vs short acting) Insulin errors (writing and transcription)
TREATMENT OF HYPERGLYCEMIA IN CRITICALLY ILL PATIENTS
ITH INCREASED MORTALITY IN ICU PATIENTS, INDEP Hyperglycemia is associated with increased mortality in ICU patients, independent of severity of illness Mortality risk increases with mean glucose across the entire cohort (n = 259,040) starting at mild hyperglycemia (p < 0.0001). Odds ratios for mortality after adjustment for severity of illness are Crit Care Med. Dec 2009; 37(12): 3001 3009.
DOES TREATING HYPERGLYCEMIA IMPROVE OUTCOMES? Deep Sternal Wound Infection rate decreased from 3.8% to 0.8% after starting insulin protocol Insulin infusion protocol reduces `rates of wound infections. Furnary AP Starr et al, 1999, ANN Thor Surg 67:352-63
THE NORMOGLYCEMIA IN INTENSIVE CARE EVALUATION AND SURVIVING USING GLUCOSE ALGORITHM REGULATION (NICE- SUGAR) TRIAL Intensive versus Conventional Glucose Control in Critically Ill Patients international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. N Engl J Med 2009; 360:1283-1297
TREATMENT OF HYPERGLYCEMIA IN CRITICALLY ILL PATIENTS Insulin infusion should be used to control hyperglycemia in the majority of critically ill patients in the ICU setting, with a starting threshold of no higher than 180 mg/dl. Once therapy has been initiated, the glucose level should be maintained between 140 and 180 mg/dl. Targets less than 110 mg/dl are not recommended. AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract. 2009;15(No. 4)
ADVANTAGES & DISADVANTAGES OF INSULIN INFUSION Advantages: Easily adjustable Lower risk for hypoglycemia with higher goals Disadvantages: Intensive nursing monitoring Hourly glucose checks Do not address prandial needs
TRANSITION FROM DRIP TO SUBCUTANEOUS (SC) INSULIN Patients with Type 1 and Type 2 DM should receive first dose of scheduled SC insulin 1-2 hrs before discontinuing the insulin drip. Patients with out a diagnosis of DM but who are requiring at least 2 units/ hr on the insulin drip should also be converted to SC insulin
TRANSITION FROM DRIP TO SUBCUTANEOUS (SC) INSULIN In order to calculate insulin requirements you can: Review requirements on insulin drip (75-80%) Use weight based dosing Use home insulin dose as a guide
TREATMENT OF HYPERGLYCEMIA IN NON-CRITICALLY ILL PATIENTS
TREATMENT OF HYPERGLYCEMIA IN NON- CRITICALLY ILL PATIENTS There is no RCT data for establishing specific guidelines in non-critically ill patients. For the majority of patients on insulin, premeal glucose targets should generally be <140 mg/ dl in conjunction with random BG values <180 mg/dl.
TREATMENT OF HYPERGLYCEMIA IN NON- CRITICALLY ILL PATIENTS For avoidance of hypoglycemia, if BG levels decline below 100 mg/dl see if any changes can be done. Modification of the regimen is necessary when BG values are <70 mg/dl, unless the event is easily explained by other factors (such as a missed meal)
TREATMENT OF HYPERGLYCEMIA IN NON- CRITICALLY ILL PATIENTS Scheduled subcutaneous administration of insulin is the preferred method for achieving and maintaining glucose control in non-icu patients with diabetes or stress hyperglycemia. Non-insulin agents are inappropriate in most hospitalized patients. The recommended components of inpatient subcutaneous insulin regimens are a basal, a nutritional, and a supplemental (correction) element Should avoid overuse of sliding scale insulin (SSI) for management of hyperglycemia.
INSULIN THERAPY
PHYSIOLOGIC INSULIN SECRETION Insulin is secreted into portal system Fasting or Basal Low level constantly secreted to decrease hepatic production of glucose from breakdown of muscle Prandial or Bolus Spike in insulin to lower glucose absorbed from food
PHARMACOKINETICS OF SC INSULIN PREPARATIONS Onset Peak Duration Rapid-acting analogs 5-15 min 1-2 h 4 6 h Regular 30-60 min 2-3 h 6-10 h NPH 2-4 h 4-10 h 12-18h Glargine 2 h none 20-24h Detemir 2h none 12-24h
INSULIN PROFILES
COMPONENTS OF MULTIPLE DOSE INSULIN REGIMEN Basal Glargine,NPH, Detemir Circulates between feedings Restrains glucose production, and catabolism of stored fuels Defends against ketoacidosis About 50% of daily insulin requirement Nutritional / Bolus insulin -Aspart, Glulisine, Lispro, Regular) Mimics rapid secretion of insulin in response to feeding Promotes assimilation of ingested nutrients Moderates post-prandial hyperglycemia Correction doses Single doses of short or rapid-acting insulin, for short-term adjustment of the blood sugar over the next few hours Usually given in conjunction with meals, as a positive or negative adjustment of the dose of prandial insulin
ENDOGENOUS INSULIN VERSUS MULTIDOSE INJECTION REGIMEN
ADVANTAGES OF MULTIDOSE INJECTION REGIMEN Mimics physiological insulinemia More opportunities for dosage adjustment Can adjust basal & nutritional insulin independently Reduced risk of hypoglycemia
ERAPY IN THE INPATIENT MANAGEMENT OF P Changes in blood glucose concentrations in patients treated with glargine plus glulisine ( ) and with SSI ( ). *P < 0.01; P < 0.05. Umpierrez G E et al. Dia Care 2007;30:2181-2186
Basal Bolus versus SSRI non-icu
INSULIN REGIMENS Calculate total daily dose of insulin (TDD) 0.4 units / kg if BG concentration is 140-200 mg/dl 0.5 units / kg if BG is between 201-400 mg/dl 0.3 units / kg if elderly / impaired renal function Give one-half of total daily dose as basal and one-half as bolus Umpierrez et al, Diabetes Care 2007; JCEM 2009; Diabetes Care 2011
INSULIN REGIMENS Total daily dose (TDD) 1500 1700 rule ISF ( insulin sensitivity factor) = 1500/TDD ISF/3 =Insulin to Carbohydrate Ratio
INSULIN REGIMENS Give supplemental short acting insulin sliding-scale protocol for blood glucose >150 mg/dl before meals if tolerating PO and if unable to eat, give scale every 6 h (6 12 6 12). Supplemental/sliding scale Low dose for TDD < 40 units/ day Medium dose for TDD 40 80 units/ day High for TDD > 80 units/ day Reassess glucose control daily and adjust basal bolus as indicated (20% change)
BASAL -PLUS INSULIN TRIAL
SPECIAL CONSIDERATIONS
STEROID INDUCED HYPERGLYCEMIA Elevated postprandial BG, which are disproportionate to fasting BG levels NPH given at time of prednisone administration (0.1 units/kg/day for every 10 mg of prednisone) Glargine if using dexamethasone or twice daily prednisone
TPN CONTINUOUS NUTRITION Add regular insulin to TPN 1unit:10 grams of carbs Can administer correctional insulin Q6H (regular) At times the patient might require a basal dose as well Continuous tube feeds NPH Q12H for basal needs & regular insulin Q6H 70/30 insulin every 6 8H with SSI
NPO STATUS FOR PROCEDURES For a type 1 diabetic do not hold evening dose night prior to procedure. The patient needs to receive basal insulin. Can give 1/2 dose prior to procedure and give dextrose containing IVF and administer a correction dose after procedure. For a type 2 diabetic do not hold evening dose night prior to procedure. You can omit AM insulin, give 1/2 dose prior to procedure or full dose after procedure
HYPOGLYCEMIA IN HOSPITALIZED PATIENTS The key predictors of hypoglycemic events in hospitalized patients include older age, greater illness severity (presence of septic shock, mechanical ventilation, renal failure, malignancy, and malnutrition), diabetes, and the use of oral glucose lowering medications and insulin
HYPOGLYCEMIA AND NEGATIVE OUTCOMES Hypoglycemia is associated with an increased risk of mortality. Hypoglycemia is also associated with a prolonged hospital length of stay. Patients with spontaneous hypoglycemia were noted to have higher rates of in-hospital death (18.4 vs. 9.2% in those without hypoglycemia; P < 0.001), mortality was not increased in insulin-treated patients with iatrogenic hypoglycemia (10.4 vs. 10.2% in those without hypoglycemia; P = 0.92).
LOWEST BLOOD GLUCOSE AND PATIENT MORTALITY
STRATEGIES FOR TREATING For treatment of BG HYPOGLYCEMIA below 70 mg/dl in a patient who is alert and able to eat and drink, administer 15 20 g of rapid-acting carbohydrate such as: one 15 30 g tube glucose gel or 4 (4 g) glucose tabs (preferred for patients with ESRD. 4 6 ounces orange or apple juice. 6 ounces regular sugar sweetened soda. 8 ounces skim milk. For treatment of BG below 70 mg/dl in an alert and awake patient who is NPO or unable to swallow, administer 20 ml dextrose 50% solution and consider starting IV dextrose 5% in water
STRATEGIES FOR TREATING HYPOGLYCEMIA For treatment of BG below 70 mg/dl in a patient with an altered level of consciousness, administer 25 ml dextrose 50% (1/2 amp) and consider starting IV dextrose 5% in water In a patient with an altered level of consciousness and no available IV access, give glucagon 1 mg IM Limit, two times. Recheck BG and repeat treatment every 15 min until glucose level is at least 80 mg/dl.
INSULIN SUBQ ORDERS FOR PATIENTS ON PARENTERAL/ENTERAL NUTRITION OR NPO
INSULIN SUBQ ORDERS FOR PATIENTS ON ORAL NUTRITION
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