Endocrine Pre-ICU trainingHyperglycemia care

in the hospital

內分泌暨新陳代謝科 陳偉哲

Patients with hyperglycemia

Medical history of diabetesUnrecognized diabetesHospital-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

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

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 20

01; 32:2426—2432.

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.

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.

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

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

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

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

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

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

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

IndicationsDKA and HHSGeneral preoperative, intraoperative, and postoperative care; Critical care illness

DIABETES CARE, VOLUME 28, SUPPLEMENT 1, JANUARY 2005

60

80

100

120

140

160

180

200

220

240

Non-diabetic Diabetic

Pla

sma

glu

cose

(m

g/d

l)

Meal Snack

Time

Meal-related Plasma Glucose ExcursionsMeal-related Plasma Glucose Excursions

Over 3 months

HbA1C

Blood Glucose Levels Over 24 Hours

Key Pharmacodynamic Properties forDifferent Insulin Preparations

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

Onset30-60min (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

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

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

Onset 6-10hPeak 10-16hDuration 18-24h

Long-action & Mixed type

Insulin aspart / aspart protamin 30/ 70 100IU/ml 3ml cartridgeNovoMix 30 penfill

諾和密斯 30 筆型胰島素類似物

RI/NPH 30/ 70 100IU/ml 10mL/vialMixtard 30 HM

密斯它 30 胰島素注射液

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

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

NEJM 2005; 352: 174-83

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 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

TID- (U) + R / R / R (+U)日常作息不正常者

Continuous HRI IV infusion

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

Continuous Actrapid Infusion Therapy

Actrapid 100U in NS 100ml ivdrip by surestep q4hInitially run 2ml/hrWhen surestep < 100, insulin infusion -1ml/hr, and inform doctor to consider glucose solution supplyWhen surestep 201~250, insulin infusion +0.5ml/hrWhen surestep 251~300, insulin infusion +1ml/hrWhen surestep 301~350, insulin infusion +1.5ml/hrWhen surestep 351~400, insulin infusion +2ml/hrWhen surestep >= 401, insulin infusion +2ml/hr and Actrapid 3U iv bolus stat.

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

Med Clin N Am 88 (2004) 1107–1116

Hyperglycemia Crisis

Management

Hydration

Insulin administration

Monitor and keep electrolyte balance

Correct metabolic acidosis?

★Adrenal insufficiency Crisis

Hypotension 低血壓Hypoglycemia 低血糖Hypothermia 低體溫Hyponatremia 低血鈉

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