Endocrine Pre-ICU training Hyperglycemia care in the hospital

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Endocrine Pre-ICU trainingHyperglycemia care
in the hospital

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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
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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, 11304311
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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 355773778.
• Similarly, hyperglycemia predicted a higher risk
  of death after stroke and a poor functional
  recovery in patients who survived Stroke 2001
  3224262432.

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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 553338. 2004
  5610581062.
• 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 7814711478.

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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.

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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

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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

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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
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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
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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
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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
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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
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Blood Glucose Levels Over 24 Hours
Meal-related Plasma Glucose Excursions
Over 3 months HbA1C
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Key Pharmacodynamic Properties forDifferent
Insulin Preparations
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Short-acting Rapid acting
Regular Insulin, Human (Humulin R) 100IU/ml 10ml
vial ?????????
Regular Insulin, Human (Actrapid HM) 100IU/ml
10ml vial ?????????
Insulin aspart,(NovoRapid Penfill) 100IU/ml
3ml/cartridge????????
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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)
• ????dimers ?hexamers
• ?????????

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Intermediate-acting
Isophane Insulin (NPH Insulin) Humulin N 100IU/ml
10ml vial ?????????
Isophane Insulin (NPH Insulin) Insulatard HM
Penfill 100IU/ml 3ml ?????????
Insulin Zinc (Lente Insulin) Monotard HM 100IU/ml
10ml vial ??????????
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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
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Long-action Mixed type
Insulin glargine 100IU/ml 10ml/vial Lantus
??????
Insulin detemir 100U/mL, 3mL/pen Levemir
FlexPen ???????
RI/NPH 30/ 70 100IU/ml 10mL/vial Mixtard 30 HM
???30??????
Insulin aspart / aspart protamin 30/ 70
100IU/ml 3ml cartridge NovoMix 30 penfill
????30????????
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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

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NEJM 2005 352 174-83
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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)
?preprandial short acting ??rapid acting, the
basal insulin dose ??10-15, rapid acting dose
? 10-15. ???hypoglycemia, rapid acting dose
??PC 2h BS??
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TID- (U) R / R / R (U)
????????
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Continuous HRI IV infusion

• HRI 50U in N/S 100ml ivdrip by SMBG q4h follow up
• SMBG lt100 Hold insulin IVF 2hours and
  follow SMBG once stat.
• SMBG 101150 Insulin IVF run 3 ml/hr
• SMBG 151200 Insulin IVF run 5 ml/hr
• SMBG 201250 Insulin IVF run 7 ml/hr
• SMBG 251300 Insulin IVF run 9 ml/hr
• SMBG 301350 Insulin IVF run 10 ml/hr
• SMBG 351400 Insulin IVF run 11 ml/hr
• SMBG 401450 Insulin IVF run 11ml/hr
• SMBG gt450 Insulin IVF run 12ml/hr and
  HRI 5U iv bolus once stat.

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Continuous Actrapid Infusion Therapy

• Actrapid 100U in NS 100ml ivdrip by surestep q4h
• Initially run 2ml/hr
• When surestep lt 100, insulin infusion -1ml/hr,
  and inform doctor to consider glucose solution
  supply
• When surestep 201250, insulin infusion 0.5ml/hr
• When surestep 251300, insulin infusion 1ml/hr
• When surestep 301350, insulin infusion 1.5ml/hr
• When surestep 351400, insulin infusion 2ml/hr
• When surestep gt 401, insulin infusion 2ml/hr
  and Actrapid 3U iv bolus stat.

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Definition of hypoglycemia

• Sometimes define as plasma glucose level lt2.8 to
  3.9mmol/L (lt50 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
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Med Clin N Am 88 (2004) 11071116
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Hyperglycemia Crisis

• Management
• Hydration
• Insulin administration
• Monitor and keep electrolyte balance
• Correct metabolic acidosis?

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?Adrenal insufficiency Crisis

• Hypotension???
• Hypoglycemia???
• Hypothermia???
• Hyponatremia ???

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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