1. Endocrine Pre-ICU training Hyperglycemia 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— ; 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 improved outcome 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 illness and 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 illness and 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. Blood Glucose Levels Over 24 Hours
Meal-related Plasma Glucose Excursions 60 80
100
120
140
160
180
200
220
240
Non-diabetic
Diabetic
Plasma glucose (mg/dl)
Meal
Snack
Time
Over 3 months
HbA1C
This schematic presentation compares blood glucose excursions in a diabetic person with those of a person without diabetes. Most of the daytime period is occupied by raised prandial and PPG levels (much higher than fasting levels), because of the inadequate amount, and slow rate, of insulin secretion in response to food.
Note the mean increase over fasting levels of 40–50 mg/dl in the diabetic state, compared with approximately 20 mg/dl in the non-diabetic state.
Thus, the primary deficit in insulin secretion in type 2 diabetes is prandial.

16. Key Pharmacodynamic Properties for Different Insulin Preparations

17. 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

18. Onset
30-60min (RI), h (Semilente)
Peak 2-3h (RI), 5-10h (Semilente)
Duration 5-8h (RI), h (Semilente)
Onset 5-15min. (Lispro), 5-10min (Aspart)
Peak h (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

19. 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

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

21. 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/ IU/ml 10mL/vial
Mixtard 30 HM 密斯它30胰島素注射液
Insulin aspart / aspart protamin 30/ IU/ml 3ml cartridge
NovoMix 30 penfill
諾和密斯30筆型胰島素類似物

22. 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

23. NEJM 2005; 352:

24. 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 analog or fasting /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

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

26. CSII is the ONLY therapy that completely separates basic metabolic insulin requirements from the insulin requirements due to the ingestion of food.

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

28. 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.

30. 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

31. Med Clin N Am 88 (2004) 1107–1116

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

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

35. 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