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Endocrine Pre-ICU training Hyperglycemia care in the hospital

Endocrine Pre-ICU training Hyperglycemia care in the hospital. 內分泌暨新陳代謝科 陳偉哲. Patients with hyperglycemia. Medical history of diabetes Unrecognized diabetes

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Endocrine Pre-ICU training Hyperglycemia care in the hospital

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  1. Endocrine Pre-ICU trainingHyperglycemia care in the hospital 內分泌暨新陳代謝科 陳偉哲

  2. Patients with hyperglycemia • Medical history of diabetes • Unrecognized diabetes • Hospital-related hyperglycemia: hyperglycemia (fasting blood glucose 126 mg/dl or random blood glucose 200mg/dl) occurring during the hospitalization that reverts to normal after hospital discharge. DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  3. Stress hyperglycemia • Stress-related hormone act as insulin antagonistic hormones: cortisol, epinephrine, nor-epinephrine, glucagon. • Hepatic glucose production is enhanced by an upregulation of both gluconeogenesis and glycogenolysis • Insulin-stimulated glucose uptake by glucose transporter-4 (GLUT-4) is compromised Current Opinion in Critical Care 2005, 11:304—311

  4. Euglycemia in hospital care • A meta-analysis of myocardial infarction revealed an association between stress hyperglycemia and increased risk of in-hospital mortality and congestive heart failure or cardiogenic Lancet 2000; 355:773—778. • Similarly, hyperglycemia predicted a higher risk of death after stroke and a poor functional recovery in patients who survived Stroke 2001; 32:2426—2432.

  5. Euglycemia in hospital care • Elevated glucose levels also predicted increased mortality and length of ICU and hospital stay of trauma patients and were associated with infectious morbidity Conclusions J Trauma 2003; 55:33—38. 2004; 56:1058—1062. • Retrospective analysis of a heterogeneous population of critically ill patients showed that even a modest degree of hyperglycemia was associated with substantially increased hospital mortality contribute to these clinical benefits. Mayo Clin Proc 2003; 78:1471—1478.

  6. Mechanisms explaining the improvedoutcome with intensive insulin therapy • Both glucose control and insulin dose contributed to the reduced inflammation, albeit with a superior effect of lowering glucose levels.

  7. Mechanisms of glucose toxicity in critical illnessand effects of intensive insulin therapy • Prevention of hyperglycemia-induced mitochondrial damage to other cellular systems with passive glucose uptake could theoretically explain some of the protective effects of intensive insulin therapy in severe illness. • Mitochondrial dysfunction with disturbed energy metabolism is indeed a likely cause of organ dysfunction, the most common cause of death in the ICU. • Hyperglycemia has also been linked to the development of increased oxidative stress in diabetes, which is in part accounted for by enhanced mitochondrial

  8. Mechanisms of glucose toxicity in critical illnessand effects of intensive insulin therapy • High glucose levels also negatively affect polymorphonuclear neutrophil function and intracellular bactericidal and opsonic activity, which may play a role in the increased risk of infections observed in patients with hyperglycemia

  9. Treatment Options for inpatients with hyperglycemia Oral diabetes agents. • No large studies have investigated the potential roles of various oral agents on outcomes in hospitalized patients with diabetes. • Each of the major classes of oral agents has significant limitations for inpatient use. • Little flexibility or opportunity for titration in a setting where acute changes demand these characteristics. DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  10. Treatment Options for inpatients with hyperglycemia • Insulin, when used properly, may have many advantages in the hospital setting. • The inpatient insulin regimen must be matched or tailored to the specific clinical circumstance of the individual patient. • A recent meta-analysis concluded that insulin therapy in critically ill patients had a beneficial effect on short-term mortality in different clinical settings DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  11. Insulin Treatment in the hospital care • Subcutaneous insulin therapy may be used in the most hospitalized patients • Programmed or scheduled insulin and supplemental or correction-dose insulin. DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  12. Insulin Treatment in the hospital care • The traditional sliding scale insulin have been shown to be ineffective • Treats hyperglycemia after it has already occurred, rather than preventing the occurrence of hyperglycemia. DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  13. Insulin Treatment in the hospital care • The medical literature supports the use of intravenous insulin infusion in preference to the subcutaneous route for several clinical indications Indications • DKA and HHS • General preoperative, intraoperative, and postoperative care; • Critical care illness DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

  14. 240 220 200 180 160 Plasma glucose (mg/dl) 140 120 100 80 60 Time Non-diabetic Diabetic Meal Snack Blood Glucose Levels Over 24 Hours Meal-related Plasma Glucose Excursions Over 3 months HbA1C

  15. Key Pharmacodynamic Properties forDifferent Insulin Preparations

  16. Short-acting Rapid acting Regular Insulin, Human (Humulin R) 100IU/ml 10ml vial 優泌林常規型胰島素 Regular Insulin, Human (Actrapid HM) 100IU/ml 10ml vial 愛速基因人體胰島素 Insulin aspart,(NovoRapid Penfill) 100IU/ml 3ml/cartridge諾和瑞筆型胰島素

  17. Onset 30-60min (RI), 1-1.5h (Semilente) Peak 2-3h (RI), 5-10h (Semilente) Duration 5-8h (RI), 12-16h (Semilente) Onset 5-15min. (Lispro), 5-10min (Aspart) Peak 0.5-1.5h (Lispro), 1-3h (Aspart) Duration 5h (Lispro), 3-5h (Aspart) 避免形成dimers 及hexamers 經皮下組織吸收迅速

  18. Intermediate-acting Isophane Insulin (NPH Insulin) Humulin N 100IU/ml 10ml vial 優泌林中效型胰島素 Isophane Insulin (NPH Insulin) Insulatard HM Penfill 100IU/ml 3ml 因速來達筆型胰島素 Insulin Zinc (Lente Insulin) Monotard HM 100IU/ml 10ml vial 滿樂達基因人體胰島素

  19. Onset 2-4h (NPH), 2-4h (Lente) Peak 4-10h (NPH), 4-12h (Lente) Duration 10-16h (NPH), 12-18h (Lente) Onset 6-10h Peak 10-16h Duration 18-24h

  20. Long-action & Mixed type Insulin glargine 100IU/ml 10ml/vial Lantus 蘭得仕注射液 Insulin detemir 100U/mL, 3mL/pen Levemir* FlexPen 瑞和密爾諾易筆 RI/NPH 30/ 70 100IU/ml 10mL/vial Mixtard 30 HM 密斯它30胰島素注射液 Insulin aspart / aspart protamin 30/ 70 100IU/ml 3ml cartridge NovoMix 30 penfill 諾和密斯30筆型胰島素類似物

  21. The ideal basal insulin • Mimics normal basal insulin secretion • Smooth and no peak profile • Reduced risk of nocturnal hypoglycemia • Long lasting effect around 24h • Once daily administration

  22. NEJM 2005; 352: 174-83

  23. BID- (R)+N / (R)+N (Split-Mixed) 2/3 AM (2/3 NPH, 1/3 rapid analog or fasting) 1/3 PM (2/3 NPH, 1/3 rapid analogor fasting 1/2 NPH, 1/2 rapid analog or fasting) 由preprandial short acting 改為rapid acting, the basal insulin dose 調上10-15%, rapid acting dose 減 10-15%. 爲免於hypoglycemia, rapid acting dose 依據PC 2h BS調整

  24. TID- (U)+ R/ R / R (+U) 日常作息不正常者

  25. Continuous HRI IV infusion HRI 50U in N/S 100ml ivdrip by SMBG q4h follow up • SMBG <100 Hold insulin IVF 2hours and follow SMBG once stat. • SMBG 101~150 Insulin IVF run 3 ml/hr • SMBG 151~200 Insulin IVF run 5 ml/hr • SMBG 201~250 Insulin IVF run 7 ml/hr • SMBG 251~300 Insulin IVF run 9 ml/hr • SMBG 301~350 Insulin IVF run 10 ml/hr • SMBG 351~400 Insulin IVF run 11 ml/hr • SMBG 401~450 Insulin IVF run 11ml/hr • SMBG >450 Insulin IVF run 12ml/hr and HRI 5U iv bolus once stat.

  26. Continuous Actrapid Infusion Therapy • Actrapid 100U in NS 100ml ivdrip by surestep q4h • Initially run 2ml/hr • When surestep < 100, insulin infusion -1ml/hr, and inform doctor to consider glucose solution supply • When surestep 201~250, insulin infusion +0.5ml/hr • When surestep 251~300, insulin infusion +1ml/hr • When surestep 301~350, insulin infusion +1.5ml/hr • When surestep 351~400, insulin infusion +2ml/hr • When surestep >= 401, insulin infusion +2ml/hr and Actrapid 3U iv bolus stat.

  27. Definition of hypoglycemia • Sometimes define as plasma glucose level <2.8 to 3.9mmol/L (<50 to 70mg/dl) • Whipple triad: (1) symptoms of hypoglycemia (2) low plasma concentration (3) relief of symptoms after the plasma glucose raised From Willians 10th

  28. Med Clin N Am 88 (2004) 1107–1116

  29. Hyperglycemia Crisis Management • Hydration • Insulin administration • Monitor and keep electrolyte balance • Correct metabolic acidosis?

  30. ★Adrenal insufficiency Crisis • Hypotension低血壓 • Hypoglycemia低血糖 • Hypothermia低體溫 • Hyponatremia 低血鈉

  31. Adrenal insufficiency Crisis • Check ACTH/Cortisol immediately • Then given Dexamethsone 4mg q6h(Decardone 1AMp iv q6h) or • Solucortef 1amp ivq 12h* 2 days if condition improved. Then shifted to Prednisolone 1# -0.5# bid

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