Hyperglycemia and the Critically Ill Patient Tony Gerlach, PharmD, BCPS The Ohio State University Medical Center

Objectives Review the consequences of hyperglycemia in ICU patients Summarize the pathophysiology of hyperglycemia in ICU patients Review the effects of intensive insulin therapy on outcomes

Review the consequences of hyperglycemia in ICU patients

Summarize the pathophysiology of hyperglycemia in ICU patients

Review the effects of intensive insulin therapy on outcomes

Effects of Insulin Decrease glucose Anabolic effects Increase protein, glycogen synthesis Inhibits lipolysis Decreases Hypertriglyceridemia, TNF, prostaglandins, Plasminogen activator inhibitor, & free radicals

Decrease glucose

Anabolic effects

Increase protein, glycogen synthesis

Inhibits lipolysis

Decreases Hypertriglyceridemia, TNF, prostaglandins, Plasminogen activator inhibitor, & free radicals

Glucose control in Healthy People with out Diabetes Insulin Release Glucagon Decrease Glucose Intake

Causes of Hyperglycemia: Glucose Intake Excess Calories Enteral/Parenteral Nutrition Drugs diluents (e.g., D5W) Propofol Peritoneal dialysis with high dextrose formulas

Excess Calories

Enteral/Parenteral Nutrition

Drugs diluents (e.g., D5W)

Propofol

Peritoneal dialysis with high dextrose formulas

Causes of Hyperglycemia: Stress Response Shock and SIRS Increased stress hormones Endogenous catecholamines ACTH Glucagon Cortisol Growth Hormone Pro-inflammatory Cytokines

Shock and SIRS

Increased stress hormones

Endogenous catecholamines

ACTH

Glucagon

Cortisol

Growth Hormone

Pro-inflammatory Cytokines

Causes of Hyperglycemia: Medications And Disease Corticosteroids Catecholamines Epi, NE, Dopamine, Dobutamine Sympathomimetics Immunosupressants Cyclosporin Tacrolimus Diabetes Pancreatitis

Corticosteroids

Catecholamines

Epi, NE, Dopamine, Dobutamine

Sympathomimetics

Immunosupressants

Cyclosporin

Tacrolimus

Diabetes

Pancreatitis

Epidemiology of Hypoglycemia in the ICU Variable Patient types Different definitions Under diagnosis of DM In one study in a SICU 74.5 % were hyperglycemic when only 13 % had a DM One study in MICU 50 % where hyperglycemic when those w/ DM excluded Mean glucose 194 +/- 66 mg/dL

Variable

Patient types

Different definitions

Under diagnosis of DM

In one study in a SICU 74.5 % were hyperglycemic when only 13 % had a DM

One study in MICU 50 % where hyperglycemic when those w/ DM excluded

Mean glucose 194 +/- 66 mg/dL

Long-term Glycemic Control and Postoperative Infection Complications % Arch Surg 2006;141:375-80. ** Statistically Significant

Hyperglycemia and Mortality Mayo Clin Proc. 2003;78:1471-8 . %

Hyperglycemia, Infectious Complication and Mortality in Trauma Patients J Trauma 2004;56:1058-62. %

Effects of Hyperglycemia Intravascular fluid balance Dehydration Glucosuria Immune Function Abnormal WBC function Granulocyte adhesion, chemotaxis, phagocytosis, intracellular killing Impaired complement activity

Intravascular fluid balance

Dehydration

Glucosuria

Immune Function

Abnormal WBC function

Granulocyte adhesion, chemotaxis, phagocytosis, intracellular killing

Impaired complement activity

Sternal Wound Infections in Diabetics undergoing Cardiac Surgery Ann Thorac Surg 1999;67:352-62 % ** Statistically Significant

Intensive Insulin Therapy and Outcomes in SICU Patients N Engl J Med 2001;345:1359-67. % ** Statistically Significant

Intensive Insulin Therapy and Outcomes in Mixed ICU Patients Mayo Clin Proc 2004;79:992-1000 * Statistically Significant

Intensive Insulin Therapy and Outcomes in MICU Patients N Engl J Med 2006;354:449-61 % * Statistically Significant

Blood Glucose and Insulin Requirements during ICU Stay Crit Care Med 2003;31:359-66 mg/dL Units/h per cal/kg

Early versus Late Intensive Insulin Therapy in ICU Patients ** Statistically Significant Inten Care Med 2008;34:881-7

Hyperglycemia and mortality in VA ICU patients Analysis of over 216,000 admission Mortality increased by 40 % in those with mild hyperglycemia (111-145 mg/dl) In 154,000 without DM mortality did not increase until glucose > 146 mg/dL Greatest risk for patients admitted for cardiovascular disorders (MI, USA, Stroke) Diagnosis with no relationship include: COPD, hepatic failure, GI neoplasm, and orthopedic disorders ADA 2006 Scientific Sessions Medscape July 23, 2006

Analysis of over 216,000 admission

Mortality increased by 40 % in those with mild hyperglycemia (111-145 mg/dl)

In 154,000 without DM mortality did not increase until glucose > 146 mg/dL

Greatest risk for patients admitted for cardiovascular disorders (MI, USA, Stroke)

Diagnosis with no relationship include: COPD, hepatic failure, GI neoplasm, and orthopedic disorders

GluControl Study Mean Age 65 yrs 40 % MICU pts Mean Glucose 118 low range 144 high range No difference in length of stay SCCM 2007 Scientific Sessions Medscape February 2007

Mean Age 65 yrs

40 % MICU pts

Mean Glucose

118 low range

144 high range

No difference in length of stay

What is the Optimal Glucose Range? Waiting for results of NICE-SUGAR Goal is to recruit 6100 pts Comparing low range 80-110 mg/dl 140-180 mg/dl

Waiting for results of NICE-SUGAR

Goal is to recruit 6100 pts

Comparing low range

80-110 mg/dl

140-180 mg/dl

Optimal Glucose Target Target ranges differ between study Appears upper threshold to be 145-150 mg/dL Normal glucose (< 110 to 120 mg/dL) is associated with better outcomes during post hoc analysis (Crit Care Med 2003;31;359-66)

Target ranges differ between study

Appears upper threshold to be 145-150 mg/dL

Normal glucose (< 110 to 120 mg/dL) is associated with better outcomes during post hoc analysis (Crit Care Med 2003;31;359-66)

OSUMC Insulin Infusion Protocol Consider initiating if 3 consecutive blood glucose values > 200 mg/dL Insulin Solution : IV regular insulin 100 units per 100 mL 0.9% NaCL Serum Glucose Goal Range: 110 - 150 mg/dL Assessment: Serum or capillary glucose q1 hour Patient must receive dextrose CONTINUOUSLY during insulin infusion (e.g. D5W at 10 mL/hour, TPN, or enteral nutrition)

Consider initiating if 3 consecutive blood glucose values > 200 mg/dL

Insulin Solution : IV regular insulin 100 units per 100 mL 0.9% NaCL

Serum Glucose Goal Range: 110 - 150 mg/dL

Assessment: Serum or capillary glucose q1 hour

Patient must receive dextrose CONTINUOUSLY during insulin infusion (e.g. D5W at 10 mL/hour, TPN, or enteral nutrition)

OSUMC Insulin Infusion Protocol Initiate insulin infusion at 2 units/hour Monitor ABG q1 hour and adjust the insulin infusion rate as directed in the following table. Frequency of glucose checks can be reduced to q2 hours if patient is medically stable and insulin infusion rate has not changed for 3 hours. Resume q1 hour glucose checks if there is a major change in clinical condition or if the glucose concentration is out of the goal range. Rate of decline in glucose concentration should be less than 100 mg/dL/hour

Initiate insulin infusion at 2 units/hour

Monitor ABG q1 hour and adjust the insulin infusion rate as directed in the following table.

Frequency of glucose checks can be reduced to q2 hours if patient is medically stable and insulin infusion rate has not changed for 3 hours.

Resume q1 hour glucose checks if there is a major change in clinical condition or if the glucose concentration is out of the goal range.

Rate of decline in glucose concentration should be less than 100 mg/dL/hour

OSUMC Experience ** Statistically Significant %

Source of Dextrose Remember to give patient a source of carbohydrates (dextrose) to prevent hypoglycemia Acceptable sources are: Tube Feeds TPN Dextrose 5% at 10-40 ml/hr for most patients Considered decreasing insulin infusion if stop tube feeds, TPN< or Dextrose in MIV and increase monitoring

Remember to give patient a source of carbohydrates (dextrose) to prevent hypoglycemia

Acceptable sources are:

Tube Feeds

TPN

Dextrose 5% at 10-40 ml/hr for most patients

Considered decreasing insulin infusion if stop tube feeds, TPN< or Dextrose in MIV and increase monitoring

OSUMC Nursing Hypoglyecmia Policy Repeat Glucose < 55 or > 400 mg/dL Glucose < 40 mg/dL is considered critical value Symptoms Autonomic: Tremble, shaking, diaphoresis, tachycardia, Neuro: Dizziness, change in consciousness, Fatigue, blurred vision, slow thinking

Repeat Glucose < 55 or > 400 mg/dL

Glucose < 40 mg/dL is considered critical value

Symptoms

Autonomic: Tremble, shaking, diaphoresis, tachycardia,

Neuro: Dizziness, change in consciousness, Fatigue, blurred vision, slow thinking

Final Thoughts Small amount of continuous IV dextrose (D5W at 10-40 ml/hr) decreases hypoglycemia Decrease insulin or start D5 when stopping Tube feeds Need to transition to scheduled insulin if insulin > 2 units/hr When patient travels verify glucose When in doubt stop drip and get glucose

Small amount of continuous IV dextrose (D5W at 10-40 ml/hr) decreases hypoglycemia

Decrease insulin or start D5 when stopping Tube feeds

Need to transition to scheduled insulin if insulin > 2 units/hr

When patient travels verify glucose

When in doubt stop drip and get glucose