Inpatient Management of Diabetes and Hyperglycemia

Inpatient Management of Diabetes and Hyperglycemia Bin Deng , PharmD, BCACP, BC -ADM, CDCES PHAR 742 | Endocrine West Coast University, School of Pharmacy March 6, 2024 When to perform A1C Test? 2 Glycemic Targets • Initiate insulin therapy for persistent hyperglycemia • • Once insulin therapy is started: • • ay so BG >180 mg/dL checked on two occasions Target BG range 140-180 mg/dL for most critically and non-critically ill patients Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICESUGAR) trial • • Critically ill patients randomized to intensive glycemic management (80-110 mg/dL) vs moderate glycemic management (140-180 mg/dL) Significantly higher mortality (27.5% vs 25%) and 10to 15-fold greater rates of hypoglycemia in the intensive glycemic management group 3 Definitions of Glucose Abnormalities in the Hospital Category Blood Glucose Level (mg/dL) Comments Hyperglycemia >140 Warrants prompt interventions, e.g. alterations in nutrition or changes to medications that cause hyperglycemia Level 1 Hypoglycemia 54-70 Prompt treatment can prevent progression to Levels 2 and 3 hypoglycemia Level 2 Hypoglycemia <54 Typical threshold for neuroglycopenic symptoms Level 3 Hypoglycemia N/A Altered mental and/or physical functioning that requires assistance from another person for recovery so 4 Clinical Presentation Acute Hyperglycemia General • Range from asymptomatic, non-specific, or severe • Severe symptoms include dehydration and acid-base abnormalities DKA • Acute onset (hours to days) • More common in patients with T1DM • Metabolic acidosis, increase in ketone production Hypoglycemia General • Sweating, weakness, tachycardia, tremor, nervousness, hunger Level 1 Hypoglycemia • Mood changes – irritability, confusion Level 2 Hypoglycemia or greater • Severe mental status changes, unresponsiveness HHS • Slower onset (days to weeks) • More common in patients with T2DM • Dehydration, hyperosmolality 5 Etiology and Pathophysiology Hyperglycemic Emergencies: Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic Syndrome (HHS) • Complex metabolic process resulting from absolute and/or relative insulin deficiency • • • • Increased gluconeogenesis and decreased glucose utilization in peripheral tissues Common causes: infection, inadequate insulin therapy (e.g. non-adherence), pancreatitis, myocardial infarction, dehydration, medications (e.g. corticosteroids, thiazide diuretics, atypical antipsychotics) DKA: Due to insufficient insulin to prevent ketoacid (ketone) formation from fat metabolism HHS: Due to longstanding severe hyperglycemic that leads to significant dehydration and loss of electrolytes (urinated out over days/weeks) 6 Etiology and Pathophysiology Multiple mechanisms can lead to hyperglycemia in acutely ill patients • Insufficient antihyperglycemic therapy in patients with diabetes • Increases in insulin resistance in peripheral tissues • “Stress hyperglycemia” due to release of norepinephrine, epinephrine, cortisol, and growth hormone • Increases in hepatic and renal gluconeogenesis • Medications: dextrose-containing IV fluids, glucocorticoids, high carbohydrate tube feedings 7 Management of Diabetes Medications on Admission • Generally, all non-insulin diabetes medications are stopped upon admission to the hospital Medication Insulin Disiontinove Comments • Usually continued; dosing may be different than outpatient regimen • Premixed insulins generally not recommended for inpatient use due to risk of hypoglycemia oral inhospital andcharge after 8 Treatment 16.6 Basal insulin or a basal plus bolus correction insulin regimen is the preferred treatment for noncritically ill hospitalized patients with poor oral intake or those who are taking nothing by mouth. A • • • • • • • 16.7 An insulin regimen with basal, prandial, and correction components is the preferred treatment for most noncritically ill hospitalized patients with adequate nutritional intake. A Scheduled subcutaneous insulin is the inpatient regimen of choice for most nonhospitalized noncritically ill patients Basal insulin (long acting insulin) – manages glucose between meals Nutritional (or prandial or bolus) insulin (short acting or rapid acting) insulin) – for meal-related blood glucose spikes Correctional (or sliding scale) insulin (rapid acting insulin) – for unexpected hyperglycemia not controlled by basal and nutritional insulin Blood glucose checks should precede most insulin doses in the hospital Point-of-care testing (POCT) commonly used due to convenience and fast results Check before every meal if eating; every 4-6 hours if not eating 9 Insulin Regimens • Weight-based dosing (TBW) • • • 0.2-0.7 units/kg/day Begin at 0.5-0.7 units/kg/day for most patients Begin at lower end (0.2-0.4 units/kg/day) for patients at risk of hypoglycemia (e.g. acute end-organ dysfunction) • Total daily dose (TDD) for most patients  50% of TDD as basal; 50% of TDD as nutritional • Insulin drip: Regular insulin IV 0.1 units/kg bolus, then 0.1 units/kg/hr and titrate to goal (DKA: stop ketosis, HHS: target BG). • Do not automatically order the patient’s outpatient insulin regimen upon admission • • Inpatient situations are often unstable Inpatient insulin requirements may differ due to: NPO for a procedure, loss of feeding tube access, emesis, activity level, stress of illness 10 Correctional Insulin 16.8 Use of a correction or supplemental insulin without basal insulin (often referred to as a sliding scale) in the inpatient setting is discouraged. A • Reactive, rather than proactive approach • Different levels of sliding scale (low, moderate, high) based on patient’s level of insulin sensitivity • • Insulin sensitivity may be determined by patient’s daily requirement of insulin or body weight E.g., low sliding scale for insulin-naïve patients or patients at high risk for hypoglycemia 11 Hypoglycemia Management 16.10 Treatment regimens should be reviewed and changed as necessary to prevent further hypoglycemia when a blood glucose value of <70 mg/dL (3.9 mmol/L) is documented. C • All efforts should be made to limit incidence of hypoglycemia • Re-evaluate insulin therapy when blood glucose levels are <100 mg/dL • Hypoglycemia causes include acute kidney injury, sudden steroid dosage reductions, reduced oral intake or vomiting, interruptions of enteral/parenteral feedings • Hypoglycemia protocol allows nurses to treat without waiting for prescriber orders • • Includes route, dose, and form of glucose administration depending on the patient’s level of cognition Common agents used to treat hypoglycemia: glucagon IM, 50% dextrose IVP 13 Discharge Considerations • Diabetes education and follow-up with outpatient prescribers are essential • • Goals: Achieve blood glucose targets and avoid long-term complications of diabetes Medication regimens may change at hospital discharge Discharge Consideration Example Scenario Changes in health status or medication regimens T2DM patient with newly diagnosed heart failure (HF) taking saxagliptin pre-admission Comments • • Saxagliptin may no longer be appropriate to continue (increased risk of HF admissions) If beta-blocker prescribed, counsel on masked symptoms of hypoglycemia Inpatient response to therapy Patient with poor glucose control on admission, T2DM, and coronary artery disease • Consider initiating an SGLT2 inhibitor (CVD benefit and low hypoglycemia risk) Recent HbA1c measurements Patient with an A1c between 7% and 9% at admission • Consider titrating preadmission regimen or add non-insulin diabetes medications 15 Question 4 The initial treatment for cortisol deficiency is hydrocortisone injection via IV route. A. True B. False 16 Adrenal/Addisonian Crisis • Life-threatening acute cortisol insufficiency • Clinical presentation: volume depletion and hypotension (shock) • • Etiology: anything that dramatically increases adrenal requirements • • • • • • Other features may include N/V, fever, fatigue, confusion, loss of consciousness Progression of Addison’s disease HPA-axis suppression via abrupt withdrawal of chronic glucocorticoid use (e.g. >20 mg/day of prednisone equivalent for >2 weeks) Surgery Infection Trauma Requires immediate treatment with parenteral glucocorticoids and isotonic fluid 17 • Surgery • Infection • Trauma • Abrupt withdrawal of chronic glucocorticoid use 18 Acute Treatment Obtain labs Bolus and maintenance fluids Hydrocortisone bolus and continuous infusion • SCr, BUN, electrolytes, glucose, routine measurement of cortisol and ACTH (corticotropin) • Do not wait for lab results; proceed to the next step • 1L NS or D5NS within the first hour; repeat fluid bolus as needed for volume resuscitation • Follow with continuous infusion of maintenance fluids to support blood pressure • Hydrocortisone 100 mg IV bolus followed by 50 mg IV Q6H or 200 mg over 24 hours as a continuous infusion • After 24 hours, reduce dose to 100 mg over 24 hours • Hydrocortisone drug of choice due to combined glucocorticoid and mineralocorticoid activity 19 Treatment after Stabilization of Patient Continue maintenance fluids Resolve underlying cause if possible Taper parenteral glucocorticoid to PO maintenance dose • Slower rate of initial maintenance fluid for 24-48 hours • Adjustment of glucocorticoid if patient is concurrently on medications that may increase cortisol clearance (e.g. carbamazepine, phenytoin, rifampin, St. John’s wort) • Tapered over 1-3 days as tolerated • Hydrocortisone 15-25 mg PO daily in 2-3 divided doses 20 Clinical Presentation (thyroid storm) • High fever (>39.4°C [103°F]), tachycardia, tachypnea, dehydration, delirium, coma, N/V/D • • Average duration of decompensation is 72 hours; symptoms may persist for up to 8 days Physical exam: goiter, ophthalmopathy, hand tremor, warm/moist skin Laboratory Findings TSH Decreased T3 and/or T4 Elevated Glucose Slightly elevated Calcium Slightly elevated LFTs Elevated WBC Decreased or elevated 21 Approach to Therapy Suppress thyroid hormone formation and secretion Antiadrenergic therapy Administer corticosteroids Treat associated complications and precipitating factors 22 Treatment Administer a thionamide (Propylthiouracil or methimazole) • Propylthiouracil (PTU) • • • • Preferred for life-threatening thyroid storm Blocks peripheral conversion of T4 to T3 (T3 levels drop by ~45% within 24 hours) Duration of action 12-24 hours Methimazole • • Suppress thyroid hormone formation and secretion Antiadrenergic therapy Administer corticosteroids Treat associated complications and precipitating factors Longer duration of action compared to PTU (36-72 hours) T3 levels drop by 10-15% within 24 hours Administer iodine one hour after the first dose of thionamide • Blocks release of T4 and T3 from the thyroid gland • If administered prior to thionamide, thyroid may utilize iodine to produce more thyroid hormone • Agents used: sodium iodide, saturated solution of potassium iodide (SSKI), Lugol’s solution 23 Treatment • Beta-adrenergic blockade recommended to control heart rate and blood pressure • Propranolol commonly used • • • • Antiadrenergic therapy Administer corticosteroids Treat associated complications and precipitating factors Esmolol may be used instead of propranolol • • Titrated to achieve control of heart rate Inhibits conversion of T4 to T3 Increased mortality in heart failure patients Suppress thyroid hormone formation and secretion Short duration of action (10-30 minutes) with rapidly reversible effects Beta-1 selective agent or calcium channel blocker may be used with caution in patients with asthma or COPD 24 Treatment • Glucocorticoids reduce conversion of T4 to T3 • May have a direct effect on underlying autoimmune process (e.g. thyroid storm due to Graves’ disease) • May treat impaired adrenal reserve, antipyretic action, and stabilization of BP • No randomized trials comparing management of thyroid storm with or without glucocorticoids • No change in hospital mortality or mortality 30 days after discharge TSATSOULIS A, JOHNSON EO, KALOGERA CH, ET AL. THE EFFECT OF THYROTOXICOSIS ON ADRENOCORTICAL RESERVE. EUR J ENDOCRINOL 2000; 142:231. Suppress thyroid hormone formation and secretion Antiadrenergic therapy Administer corticosteroids Treat associated complications and precipitating factors 25 Treatment Supportive measures given as indicated • Acetaminophen as antipyretic of choice • • • • • • • NSAIDs may displace bound thyroid hormone Fluid and electrolyte replacement Sedatives Antiarrhythmics Insulin Antibiotics Limited efficacy: plasmapheresis, peritoneal dialysis (remove excess thyroid hormone) Suppress thyroid hormone formation and secretion Antiadrenergic therapy Administer corticosteroids Treat associated complications and precipitating factors 26 Subsequent Management • • • If PTU was given for initial management, switch to methimazole upon discharge Better safety profile, higher compliance rates, less hepatotoxicity compared with PTU Initial dose 30-40 mg PO daily, then titrated down to maintain euthyroidism • Discontinue iodine therapy (unless thyroidectomy is planned within 2 weeks) • Discontinue beta blockers after thyroid function tests normalize • Taper and discontinue glucocorticoids • For patients with Graves’ disease: definitive therapy with radioiodine or thyroidectomy • Prevent recurrence of severe thyrotoxicosis 27 Treatment Drug Propylthiouracil Regimen 900-1200 mg PO daily in 4 or 6 divided doses Methimazole 90-120 mg PO daily in 4 or 6 divided doses Sodium iodide Up to 2 g IV daily in single or divided doses Lugol’s solution 5-10 drops PO TID in water or juice Saturated solution of potassium iodide (SSKI) 1-2 drops PO TID in water or juice Propranolol Dexamethasone Prednisone Methylprednisolone Hydrocortisone 40-80 mg PO Q6H 5-20 mg PO or IV daily in divided doses 25-100 mg PO daily in divided doses 20-80 mg IV daily in divided doses 100-400 mg IV daily in divided doses 28 Introduction (Myxedema Coma) • Life-threatening severe hypothyroidism leading to decreased mental status, hypothermia, and other symptoms related to slowing of function in multiple organs • • • High mortality rate  60-70% Other clinical features: bradycardia, hyponatremia, hypoglycemia, hypotension, cessation of gastrointestinal peristalsis Risk factors: • • • Longstanding hypothyroidism Acute events: infection, myocardial infarction, surgery Medications: sedatives (e.g. opioids), lithium, iodinated radiocontrast, amiodarone 29 Treatment (Myxedema Coma) • Draw serum for T4, TSH, and cortisol Obtain labs Levothyroxine IV Hydrocortisone IV • Levothyroxine 200-400 mcg IV, followed by daily doses of 50-100 mcg IV* • Triiodothyronine 5-20 mcg IV, followed by 2.5-10 mcg IV Q8H* • Hydrocortisone 100 mg IV Q8H • Continue until exclusion of adrenal insufficiency *Lower end of dose ranges preferred in lower weight, older patients, or those at risk for cardiac complications 30 Subsequent Management • • • • • • • • • Supportive measures: Mechanical ventilation Fluids and vasopressor drugs to correct hypotension Passive rewarming Intravenous dextrose If indicated: antibiotics and/or antiarrhythmics Switch levothyroxine from IV to PO when tolerated PO dose = IV dose / 0.75 Een Daily monitoring of serum T4 (or free T4) and T3 to determine treatment efficacy 31