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1

Learning Objectives

! Identify patient populations at risk for adverse outcomes related to hyperglycemia in the hospital setting

! State recommended target blood glucose levels for critically ill patients and patients in nonintensive care units

! Describe available intravenous insulin infusion protocols and reflect on how these might be modified to suit different institutional practices

! Implement rational therapeutic approaches using subcutaneous insulin in noncritically ill hospitalized patients

! Provide appropriate recommendations for transition to outpatient care

Hyperglycemia in Hospitalized Patients

" A common finding in hospitalized patients, even those without a previous history of diabetes

" Associated with increased mortality among patients

" Contributes to longer lengths of stay and other complications

American College of Endocrinology Position Statement. Endocr Pract. 2004;10:77-82. Bhattacharyya A et al. Diabet Med 2002;19:412-416.

Frequency of Uncontrolled Glucose Levels in the Hospital

Target = preprandial BG 72–162 mg/dL.

Perc

ent

(%)

0

10

20

30

40

50

60

Good Control Suboptimal Control Poor Control

IV Insulin: Medical

IV Insulin: Surgical

SC Insulin: Medical

SC Insulin: Surgical

Glycemic control while on:

Mortality Increases With Increases in Average BG

Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478.

0

5

10

15

20

25

30

35

40

45

80–99 100–119 120–139 140–159 160–179 180–199 200–249 250–299 > 300

Mor

talit

y Rat

e (%

)

Mean Glucose Value (mg/dL)

(N = 1826)ICU

0

2

4

6

8

10

12

14

16

< 150 150–175 175–200 200–225 225–250 > 250

Average Postoperative Glucose (mg/dL)

Mor

talit

y %

Furnary AP et al. J Thorac Cardiovasc Surg. 2003;125:1007-1021.

Mortality Increases With Increasesin Average BG Levels

Cardiac-related mortalityNoncardiac-related mortality

Post-CABG

2

Postoperative Hyperglycemia Is aPredictor of Serious Infectious Complications

13 1625

67

0

10

20

30

40

50

60

70

100–150 150–200 200–250 250–300

Zerr KJ et al. Ann Thorac Surg. 1997;63:356-361.

Day 1 BG (mg/dL)

P = 0.002

Dee

p in

fect

ion

rate

(%

)

Increasing BG Concentrations Are Associated With Adverse Clinical Outcomes

in Non-ICU Patients

0

5

10

15

20

25

30

35

< 108 mg/dL 108–124 mg/dL 126–160 mg/dL > 162 mg/dL

Baker EH et al. Thorax. 2006;61:284-289.

Patients with COPD exacerbations

Mor

talit

y (%

)

Highest BG During Hospital Stay

N = 284

Admission Hyperglycemia Is Associated With Adverse Outcomes in Patients

Admitted to Non-ICU Settings

0%

5%

10%

15%

20%

25%

30%

35%

< 200 mg/dL > 200 mg/dL

N = 2471

Non-ICU patients with community acquired pneumonia%

of

Patie

nts

McAlister FA et al. Diabetes Care. 2005;28:810-815.

*P = 0.03; †P = 0.01.

Mortality

Complications

*

*

†

†

Admission BG Level

Hyperglycemia Affects Mortality Regardless of Diabetes Status

0

10

20

30

40

50

60

180-Day Mortality in Patients Admitted for MI

Euglycemicpatients withoutdiabetes

Euglycemicpatients withdiabetes

Hyperglycemicpatients withdiabetes

Hyperglycemicpatients withoutdiabetes

*! 200 mg/dL

% o

f Pa

tient

s

Rady MY et al. Mayo Clin Proc. 2005;80:1558-1567. Ainla MIT et al. Diabet. Med. 2005;22:1321-1325.

*

*

Intensive Insulin Therapy in SurgicalICU Patients Improves Survival

Intensive: Insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dLmean BG = 103 mg/d

Conventional: Insulin when BG > 215 mg/dLmean BG = 153 mg/dL

van den Berghe G et al. N Engl J Med. 2001;345:1359-1367.

Surv

ival

in I

CU (

%)

100

96

92

88

800

84

0 20 40 60 80 100 120 140 160

Intensive treatment

Conventional treatment

Days After Admission

4.6% mortality

8.0% mortality

P = 0.005

2006 Leuven Medical ICU Study

! Randomized control trial, N = 1200

! Goal: 80–110 vs 180–200 mg/dL

! Analysis separated outcomes at 3 days

• Improved mortality among patients with ICU stay > 3 days

• No significant difference in mortality among short-stay patients

! Improved morbidity: renal insufficiency, duration of mechanical ventilation, shortened ICU stay

Van den Berghe G et al. N Engl J Med. 2006;354:449-461.

3

Glucose Control with IV Insulin Lowers Mortality Risk After Cardiac Surgery

Furnary AP et al. J Thorac Cardiovasc Surg. 2003;125:1007-1021.

10

8

6

4

0

Mor

talit

y (%

)

87 88 89 90 91 92 93 94 98 99 00

Year

Patients with diabetes

Patients without diabetes

2

95 96 97 01

IV Insulin Protocol

Intensive Insulin Managementin Medical-Surgical ICU

Krinsley JS. Mayo Clin Proc. 2004;79:992-1000.

130

152

0

20

40

60

80

100

120

140

160

Mean BG Levels(mg/dL)

P < 0.001

0

2

4

6

8

10

12

14

Nursing Requirements(h/patient day)

P = NS

0%

5%

10%

15%

20%

25%

Hospital Mortality (%)

P < 0.002

29.3% Reduction

Baseline group (n = 800) Glucose management protocol group (n = 800)

Glucose Control in the Hospital

! Tight glycemic control reduces mortality, morbidity, and costs in critically ill patients

! Hospitalization is an opportunity to assess glycemic control and intensify the outpatient therapy

American College of Endocrinology Position Statement. Endocr Pract. 2004;10:77-82.Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement.Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.

Managing Hyperglycemiain Hospitalized Patients

Treatment Targets and OvercomingBarriers to Implementation

Glycemic Targets in Hospitalized Patients

! ICU

• " 110 mg/dL

! Medical/surgical floors

• " 110 mg/dL preprandial

• " 180 mg/dL maximal glucose

American College of Endocrinology Position Statement. Diabetes Care. 2006;29(8):1955-1962.

Methods for Managing Hospitalized Persons With Diabetes

! Continuous variable-rate IV insulin drip

• Regular insulin

! Basal-bolus therapy (MDI)

• Long-acting insulin and rapid-acting insulin

! Premixed insulin

• For patients transitioning to outpatient care

4

Barriers to Good Glycemic Controlin the Hospital

! Reliance on sliding scale insulin regimens! Fear of hypoglycemia ! Inadequate knowledge/understanding of diabetes,

hyperglycemia, and their management among health care providers

! Lack of integrated information systems that allow tracking and trending of glycemic control and hypoglycemia

! Poor communication during patient transfers• A lack of ownership for hyperglycemia • Most patients are admitted for reasons other than

hyperglycemiaInpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement.Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.Cook CB et al. Endocr Pract. 2007; Mar-Apr;13(2):117-124.Cook CB et al. J Hosp Med. 2007;Aug;7;2(4):203-211.

Successful Strategies for Implementation

! Champion

! Support from administration

! Multidisciplinary steering committee to drive the development/implementation of initiatives

• Medical staff, nursing and case management, pharmacy, nutrition services, dietary services, laboratory, quality improvement, information systems, and administration

! Assessment of current processes, quality of care, and barriers to practice change

Adapted from Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement. Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.

Successful Strategies for Implementation

! Standardized order sets! Protocols, algorithms ! Policies! Educational programs (physicians/nurses, etc)! Glycemic management clinical team ! Metrics for evaluation

• System to track hospital glucose data on anongoing basis

• Assess the quality of care delivered• Continuous improvement of processes and protocols

Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement. Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.

The Ideal IV Insulin Protocol

! Easily ordered (signature only)

! Effective (gets to goal quickly)

! Maintains BG within a defined target range

! Includes an algorithm for making temporary corrective increments or decrements of insulin infusion rate

! Safe (minimal risk of hypoglycemia)

! Easily implemented

! Can be executed by nursing staff in response to a single physician order

Cost-Effectiveness of Inpatient IV Insulin Therapy

Annualized cost savings = $1,340,000

Savings per patient = $1580

! Reduced LOS (mean = 3.4 days; median = 1.7 days)

! Number of ICU hours: 17.2% reduction

! Number of ventilator hours: 19.0% reduction

! Lab costs: 24.3% reduction

! Pharmacy costs: 16.7% reduction

! Imaging costs: 5.0% reduction

Krinsley JS et al. Chest. 2006;129:644-650.


IV Insulin Strategies

5

Some Indications for IV Insulin Therapy in the Hospital

" Critical illness (surgical, medical)

" Prolonged NPO status in patients who are insulin deficient

" Elevated glucose exacerbated by high-dose glucocorticoid therapy

" Perioperative period

" Stroke

" Post organ transplant

" Total parenteral nutrition therapy

" Other illnesses requiring prompt glucose control (eg, nonketotic hyperosmolar state, diabetic ketoacidosis)

American College of Endocrinology Position Statement. Endocr Pract. 2004;10:77-82.

Successful Protocols for IV Insulin Infusion

" Executed by nursing staff in response to a single physician order

" Correct hyperglycemia over several hours

" Maintain BG within a defined target range

" Include algorithms for making temporary corrective increments or decrements of insulin infusion rate

" Adjustments to rate of maintenance as insulin resistance changes

" Directions for adjusting insulin infusion for any rapid change in BG

" Directions for treatment of hypoglycemia

" Guidelines for timing and selection of doses for transition to SC insulin

Goldberg PA et al. Diabetes Care. 2004;27:461-467. Markovitz LJ et al. Endocr Pract. 2002;8:10-18. van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. Malmberg K et al. Circulation. 1999;99:2626-2632. Malmberg K et al. Eur Heart J. 2005;26:650-661. Krinsley J. Mayo Clin Proc. 2004;79:992-1000. Ku SY et al. Jt Comm J Qual Patient Saf. 2005;31:141-147.Donaldson S et al. Diabetes Educ. 2006;32(6):954-62. DeSantis AJ et al. Endocr Pract. 2006;12(5):491-505.

IV Insulin Protocols

! Yale

! Markovitz

! Leuven

! Portland

!DIGAMI

!University of Washington

!Luther Midelfort Mayo Health System

!Rush University Protocol

!Northwestern University

Goldberg PA et al. Diabetes Care. 2004;27:461-467.

Yale Insulin Infusion Protocol

Initiating An Insulin DripInsulin infusion: 1 U regular human insulin/1 mL 0.9 % NaCl

! Administer via infusion pump (in increments of 0.5 U/h)

! Target BG levels: 100-139 mg/dL

! Bolus and initial insulin drip rate: divide initial BG level (mg/dL) by 100, then round to nearest 0.5 U for bolus and initial drip rate

Fingerstick (FS) BG monitoring! Check FS hourly until stable (3 consecutive values in target range)

! Then check FS every 2 hours; once stable x 12–24 hours

Factors Increasing Risk of Hypoglycemia in an Inpatient Setting

! Factors related to carbohydrate intake

• Mistiming of insulin dosage with respect to food

• Transportation off ward causing meal delay

• New NPO status

! Interruption of any of the following:

• IV dextrose, TPN, enteral feedings, continuousrenal replacement therapy

! Indecipherable orders

! Inadequate glucose monitoring

! Medication and medication changes

! Liver or renal dysfunction, advanced age

Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement.Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.


Converting to Subcutaneous Insulin Therapy inthe Hospital and Transition to Outpatient Care

6

SC Insulin: General Points

! Effective insulin therapy must provide both basal and nutritional coverage to achieve target goals

! Hospitalized patients often require high insulin doses to achieve desired target glucose levels

! In addition to basal and nutritional insulin requirements, patients often require supplemental or correction insulin for treatment of unexpected hyperglycemia

Clement S et al. Diabetes Care. 2004;27:553-591.

Transition from IV to SC Insulin

! Continue IV insulin until patient is able to tolerate solid food intake

! Continue IV insulin at least 2 hours after the first SC insulin injection is given (longer if starting basal insulin)

! Arrange for outpatient follow-up of patients placed on insulin in the hospital

Therapeutic Options to ConsiderWhen Converting to SC Insulin

! Resumption of prior insulin regimens

! Initiation of basal insulin

! Initiation of basal/bolus MDI

! Initiation of premixed insulin

Use of “Sliding Scale” Insulin Aloneis Discouraged

! Evidence does not support this technique without basal insulin because it has resulted in unacceptably high rates of:

• Hyperglycemia

• Hypoglycemia

• Iatrogenic diabetic ketoacidosis in hospitalized patients with type 1 diabetes

Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement.Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.Umpierrez, GE et al. The American Journal of Medicine. 2007;120(7);563-567.Umpierrez GE et al. Diabetes Care. 2007; May 18; [Epub ahead of print].

Premeal Algorithm forCorrection Dose Insulin

To be administered in addition to scheduled insulinto correct premeal hyperglycemia

12 Units8 Units5 Units>349

10 Units7 Units4 Units300–349



2 Units1 Unit1 Unit150–199

IndividualizedHighDose

MediumDose

Low Dose

Premeal BGmg/dL

Additional Insulin

Hyperglycemia in Hospitalized Patients

Discharge Planning

7

Knowndiabetes

Hyperglycemia inHospitalized Patients

Previously unknown/undiagnosed diabetes

Transient (stress) hyperglycemia

3 possibleetiologies

Opportunity toassess efficacyof preadmissionglycemic control

regimen

“Unrecognized”(diabetes or prediabetes)

Confirm at discharge, monitor later

Mayrevert

tonormal after

discharge

Norhammar A et al. Lancet. 2002;359:2140-2442.Improving Inpatient Diabetes Care: A Call to Action Conference, AACE, 2006. Available at:http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed June 5, 2006.

Discharge Planning

! Starts at admission

! Be proactive!

• Inpatient education—survival skills

• Outpatient education

– Clinic

– ADA-recognized education programs (www.diabetes.org)

! Prepare for outpatient follow-up

Inpatient Diabetes and Glycemic Control: A Call to Action Conference. Position statement.Available at: http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed May 16, 2006.

Patients Newly Diagnosed With Diabetes During Hospitalization

! Newly diagnosed inpatients represent an opportunity to institute a convenient plan for long-term glycemic control, which if initiated early, may lead to prevention of complications

• Unfortunately, patients with newly noted hyperglycemia are frequently ignored in the hospital

Improving Inpatient Diabetes Care: A Call to Action Conference, AACE, 2006. Available at:http://www.aace.com/meetings/consensus/IIDC/IDGC0207.pdf. Accessed June 5, 2005.

Patients Newly Diagnosed With Diabetes During Hospitalization

! Treatment options for patients with mild hyperglycemia on discharge• Insulin

– Basal insulin– Premixed insulin

• Other Injectable Agents– GLP-1 agonists and mimetrics

• OADs– Metformin– TZDs– Insulin secretagogues– DPP-4 inhibitors

AgentsHuman regular

Insulin analogs: aspart, glulisine, lispro

NPH

Insulin analogs: detemir, glargine

Human 70/30, 50/50

Insulin lispro 75/25, 50/50Insulin aspart 70/30

ClassShort-acting

Rapid-acting

Intermediate-acting

Long-acting

Basal/Bolus:Human premixed insulin

Premixed insulinanalogs

Insulin PreparationsExamples of Typical Starting Insulin Regimens for the Outpatient Setting

! 1 injection

• Intermediate-acting insulin or long-acting analogat bedtime

• Premixed formulation before dinner

! 2 injections

• Premixed formulation before breakfast and dinner

8

Options When Not at Goal WithOne Injection of Basal Insulin

! Add rapid-acting analog before meals if eating

• Or after meals if intake uncertain

• Or every 4 hours if NPO (parenteral feeding)

• 6 U or 0.1U/kg

OR

! Switch to a premixed insulin analog

• Divide dose in half and give bid (breakfast and dinner) after meals if feeding uncertain

Connecting Inpatient Careto Outpatient Support

! Multidisciplinary team: case manager, clinical pharmacist, registered dietitian, bedside nurse

! High-risk patients identified at admission

! Bedside nurse does assessment using Admission Database form and adds 5 questions related to diabetes

! If need identified, bedside nurse contacts appropriate team member

Pollom RK et al. Crit Care Nurs Q. 2004;27:185-188.

Key Points

! Hyperglycemia is highly prevalent among hospitalized patients and is associated with morbidity and mortality

! Glycemic control in the hospital is critical

! Hospitals must implement effective insulin protocols (IV and SC)

! Insulin therapy can be tailored to meet physiologic requirements and targeted glucose levels

• Sliding scale alone is ineffective and shouldnot be used

Key Points

! Hyperglycemia in critical care units should be managed to goals with the use of IV insulin protocols

! Cost analyses have documented substantial cost savings with this therapy

! Transition to SC insulin therapy can be accomplished on medical/surgical floors

! Patient follow-up postdischarge should evaluate ongoing need for glycemic control

AACE INPATIENT GLYCEMIC CONTROL RESOURCE CENTER (GC-RC)

# Basic Science# Clinical Evidence# Health Economics

& Administration

# Inpatient ICU# Inpatient Non-ICU# Labor & Delivery

# Glucometrics# Pharmacy &

Medications# Dietary/Nutrition# Nursing# Models of

Implementation

# Transition from Inpatientto Outpatient

AACE INPATIENT GC-RC

• Slide Presentations• Protocols/Order Sets• Articles

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AACE Inpatient Glycemic Task ForceCochairs:

Alan J. Garber, MD and Etie S. Moghissi, MD

Advisory Members

Linda Haas, PhD, RN, CDESilvio Inzucchi, MDJanet L. Kelly, PharmDLanell Olson, MSM, RD/LD, CDEJaqui Thompson, MAS, RN, CDE

Task Force Members

Mercedes Falciglia, MDIrl B. Hirsch, MDLois Jovanovic, MDMary Korytkowski, MDD. Harold Lebovitz, MDChristopher A. Newton, MD

AACE INPATIENT GC-RC

http://www.aace.com/Resources

Inpatient GC-RC

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