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Improving Glycemic Control in the Hospital. Anthony DeSantis, MD Clinical Asst. Professor Division of Metabolism, Endocrinology and Nutrition University of Washington Medical School. Three Types of Hyperglycemic Patient. Known history of diabetes Existing, but unrecognized, diabetes

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Improving glycemic control in the hospital

Improving Glycemic Control in the Hospital

Anthony DeSantis, MD

Clinical Asst. Professor

Division of Metabolism, Endocrinology and Nutrition

University of Washington Medical School


Three types of hyperglycemic patient
Three Types of Hyperglycemic Patient

  • Known history of diabetes

  • Existing, but unrecognized, diabetes

  • Stress hyperglycemia

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


Hyperglycemia adversely affects outcomes
Hyperglycemia Adversely Affects Outcomes

  • Hyperglycemia impacts

    • Mortality

    • Morbidity

    • Rate of infections

    • Length of stay (LOS)


38 of hospital admissions exhibit hyperglycemia
38% of Hospital Admissions Exhibit Hyperglycemia

2030 consecutive adult patients admitted between July and October 1998

38% had hyperglycemia*

*Hyperglycemia defined as admission or FPG ≥126 mg/dL or random BG ≥200 mg/dL

Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982.


New onset hyperglycemia highest mortality rates
New-onset Hyperglycemia: Highest Mortality Rates

Total Inpatient Mortality

ICU Mortality

31%†

*P<0.01

n=1886

†P<0.01

n=243

16%*

11%

10%

3%

1.7%

Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982.


Hyperglycemia impacts rate of infections
Hyperglycemia Impacts Rate of Infections

Note inflection point

Rates of deep sternal wound infection in 4864 patients with diabetes who underwent an open-heart surgical procedure

P=0.001

Rate of infection, %

3-day average postoperative blood glucose, mg/dL

Furnary et al. Endocr Pract. 2004;10(suppl 2):21-33.


Hyperglycemia index of disease severity
HYPERGLYCEMIAIndex of disease severity

14.5%

Mortality %

6.0%

4.1%

2.3%

0.9%

1.3%

Average post-op glucose

Furnary et al J Thorac Cardiovasc Surg 2003;125:1007-21


Hyperglycemia and mortality
Hyperglycemia and Mortality

Inpatient hyperglycemia clearly associated with increased morbidity and mortality

Can interventions, which reduce inpatient hyperglycemia acutely, decrease this increased morbidity and mortality?


Intensive insulin therapy in critically ill surgical patients improves survival
Intensive Insulin Therapy in Critically Ill Surgical Patients Improves Survival

100

Intensive treatment

96

92

Survival in ICU (%)

Conventional treatment

88

84

80

0

0

20

40

60

80

100

120

140

160

Days After Admission

Conventional: insulin when blood glucose > 215 mg/dL.

Intensive: insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dL.

9

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


Intensive insulin therapy in critically ill surgical patients morbidity and mortality benefits
Intensive Insulin Therapy in Critically Ill Surgical Patients: Morbidity and Mortality Benefits

Intensive therapy to achieve blood glucose levels of 80–110 mg/dL reduced mortality (-34%), sepsis (-46%), dialysis (-41%), blood transfusion (-50%), and polyneuropathy (-44%)

Mortality

Sepsis

Dialysis

Blood Transfusion

Polyneuropathy

N = 1,548

Reduction(%)

34%

41%

44%

46%

50%

10

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


The Belgian Study Patients: Morbidity and Mortality BenefitsPost-Hoc Analysis of Various Outcomes by Glucose Levels Achieved in Patients Staying in ICU > 5 Days

11

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


Portland diabetes project mortality
Portland Diabetes Project: Mortality Patients: Morbidity and Mortality Benefits

10

CII

8

Patients with diabetes

6

Mortality(%)

Patients without

4

diabetes

2

0

87

88

89

90

91

92

93

94

95

96

97

98

99

00

01

Year

Reprinted from Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;125:1007–1021 with permission from American Association for Thoracic Surgery.


Inpatient glycemic goals
Inpatient Glycemic Goals Patients: Morbidity and Mortality Benefits

American Diabetes Association. Diabetes Care. 2006;29:S4-S42. Garber et al. Endocr Pract. 2004;10:77-82.


Recent studies suggest that perhaps these targets are too strict
Recent Studies Suggest that Perhaps these Targets Are Too Strict

Frequency of Hypoglycemia (<40mg/dl)

1van den Berghe G, et al. N Engl J Med. 2001;345:1359 4Preiser &Devos, Crit Care Med 2007;35:S503-S507

2van den Berghe G et al. N Engl J Med 2006;354:449 5NICE-SUGAR Invest, N Engl J Med 2009;360:1283 3Brunkhorst et al., N Engl J Med 2008;358:125-139


The belgian micu trial impact of intensive insulin
The Belgian MICU Trial StrictImpact of Intensive Insulin

*

Van den Berghe N Engl J Med 2006;354:449-61

* p= 0.009


The belgian micu trial impact of intensive insulin1
The Belgian MICU Trial StrictImpact of Intensive Insulin

Van den Berghe N Engl J Med 2006;354:449-61


Visep trial
VISEP Trial Strict

Overall Survival

Blood Glucose

100

Conventional therapy (n=290)

80

200

60

150

Probability of Survival (%)

Intensive therapy (n=247)

Mean Blood Glucose (mg/dL)

40

100

Conventional therapy

50

20

Intensive therapy

0

0

10

20

30

40

50

60

70

80

90

100

0

0

1

2

9

10

11

12

13

14

3

4

5

6

7

8

Days

Days

Data from 537 patients:

247 received IIT goal: 80 – 110 mg/dL: mean BG 112 mg/dL

290 received CIT goal: 180 – 200 mg/dL: mean BG 151 mg/dL

IIT, intensive insulin therapy; CIT, conventional insulin therapy.

Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.


Visep trial1
VISEP Trial Strict

*SOFA – sequental organ failure assessment

Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.


The nice sugar study
The NICE-SUGAR Study Strict

IIT goal: 81 – 108 mg/dL (mean BG 118 mg/dL)

CIT goal: <180 mg/dL (mean BG 145 mg/dL)

Nice Sugar, NEJM 2009;360:1283


The nice sugar study1
The NICE-SUGAR Study Strict

Nice Sugar, NEJM 2009;360:1283

90 day mortality: IIT: 829 patients (27.5%), CIT: 751 (24.9%)

Absolute mortality difference: 2.6% (95% CI, 0.4 to 4.8); Odds ratio for death with IIT was 1.14 (95% CI, 1.02 to 1.28; P = 0.02).


Probability of survival and odds ratios for death according to treatment group
Probability of Survival and Odds Ratios for Death, According to Treatment Group

Operative Admission

Diabetes

Severe Sepsis

Trauma

Apache Score

Corticosteroids

All deaths at day 90

Favors Favors

IIT Conventional

Nice Sugar, NEJM 2009;360:1283



Hypoglycemic events to Treatment Group

Favors IIT Favors Control

Griesdale et al., CMAJ 2009;180:821


Favors IIT Favors Control to Treatment Group

All Mixed ICU

0.99 (0.87-1.12)

All Medical ICU

1.00 (0.78-1.28)

All Surgical ICU

0.63 (0.44-0.91)

ALL ICU

0.93 (0.83-1.04)


Mean Glucose & In-Hospital Mortality in 16,871 Patients with AMI

Reference: Mean BG

100-110 mg/dl

Kosiborod M et al. Circulation 2008:117:1018


Relationship between Spontaneous and Iatrogenic Hypoglycemia and Mortality in Patients Hospitalized with Acute MI

Retrospective analysis of 7820 patients hospitalized with acute MI in 40 hospitals in US 1/01 – 12/05, with glucose levels > 140 mg/dl on admission

4775 never received insulin

3045 received insulin

Kosiborod et al., JAMA 2009;301:1556


Hypoglycemia* in Acute MI and Mortality in Patients Hospitalized with Acute MI

*Glucose < 60 m/dL

Kosiborod et al., JAMA 2009;301:1556


Multivariable analysis
Multivariable Analysis and Mortality in Patients Hospitalized with Acute MI

Hypoglycemia in ACS

Kosiborod et al., JAMA 2009;301:1556


Is Hypoglycemia Life- and Mortality in Patients Hospitalized with Acute MIthreatening?

  • Hypoglycemia (BG < 40 mg/dl) has been reported in 5 - 28% of patients on CII

  • Inpatient hypoglycemia is associated with poor clinical outcome

  • No direct evidence indicating insulin-induced hypoglycemia results in increased mortality

  • Similar to hyperglycemia, severe hypoglycemia appears to be a marker of poor ICU outcome


GLYCEMIC TARGETS and Mortality in Patients Hospitalized with Acute MI


Ada aace target glucose levels in icu patients
ADA/AACE Target Glucose Levels in ICU Patients and Mortality in Patients Hospitalized with Acute MI

ICU setting:

Insulin infusion should be used to control hyperglycemia

Starting threshold of no higher than 180 mg/dl

Once IV insulin is started, the glucose level should be maintained between 140 and 180 mg/dl

Lower glucose targets (110-140 mg/dl) may be appropriate in selected patients  

Targets <110 mg/dL are not recommended

Not recommended

< 110

Acceptable

110-140

Recommended

140-180

Not recommended

>180

ADA/AACE Inpatient Task Force

Endocrine Practice 2009;15;1-17


Ada aace target glucose levels in non icu patients
ADA/AACE Target Glucose Levels in non-ICU Patients and Mortality in Patients Hospitalized with Acute MI

Non-ICU setting:

Pre-meal glucose targets <140 mg/dL

Random BG <180 mg/dL

To avoid hypoglycemia, reassess insulin regimen if BG levels fall below 100 mg/dL

Occasional patients may be maintained with a glucose range below or above these cut-points

Hypoglycemia= BG < 70 mg/dl

Severe hypoglycemia= BG < 40 mg/dl

ADA/AACE Inpatient Task Force

Endocrine Practice 2009;15:1-17


Achieving tight glycemic targets
Achieving Tight Glycemic Targets and Mortality in Patients Hospitalized with Acute MI

“Insulin, given either intravenously as a continuous infusion or subcutaneously, is currently the only available agent for effectively controlling glycemia in the hospital.”

Insulin is SEXY Again

Abe DeSantis, MD

ACE Position Statement on Inpatient Diabetes and Metabolic Control, 2004.


Multidisciplinary team extends beyond caregivers

Performance and Mortality in Patients Hospitalized with Acute MI

Improvement/

QI staff

P&T Committee

Critical Care physicians

Other internists

Patient

Safety

Committee

Lab

Multidisciplinary Team Extends Beyond Caregivers

Chief residents/

residency program

directors

Departmental

committees

Biomedical,

medical records,

CPOE expertise

Unit clerks/

secretaries

Surgery,

Trauma,

Orthopedics,

Anesthesiology

leaders

Endocrin-ologists

GLYCEMIC CONTROL COMMITTEE

Patient

Representa-

tives

Hospitalists

  • Pharmacists

OR or

Perioperative

Committees

Forms

Committee

  • Nursing groups

Hospital

Informatics

Nutritionists/

Dietitians

Maynard et al. SHM Glycemic Control Workgroup. Available at: :http://www.hospitalmedicine.org/AM/Template.cfm?Section=Quality_Improvement_Resource_Rooms1&Template=/CM/HTMLDisplay.cfm&ContentID=4337.


Incidence inpatient hyperglycemia nmh
Incidence Inpatient Hyperglycemia and Mortality in Patients Hospitalized with Acute MINMH

  • Documented serum/capillary blood glucose values NMH admits 9/03 - 10/03.

    • 26% of admissions with blood glucose value > 200 mg/dl.

    • Mean BG among those medically treated for DM

      • 213 mg/dl


Post-operative and Mortality in Patients Hospitalized with Acute MI

Check CBG every 4hrs x 48 hours

BG <110 mg/dl

BG >110 mg/dl

BG >200 mg/dl

After initial 48 hours, serum fasting glucose qAM

Repeat CBG 30 minutes from previous

BG <110 mg/dl

BG >110 mg/dl

Start IV insulin protocol

Plans for dietary advance

Continue while NPO/Critically ill

Consult GMS

Monitor glucose; titrate insulin

D/C IV insulin; convert to SQ

DeSantis, et al Endocr Practice 2006;12:491-505

Consider Nutrition consult

Consider Diabetes educator consult


Iv insulin therapy

IV Insulin Therapy and Mortality in Patients Hospitalized with Acute MI


Iv insulin therapy recommended uses
IV Insulin Therapy: and Mortality in Patients Hospitalized with Acute MIRecommended Uses

  • Best method to achieve quick glycemic control

  • IV insulin recommended over SC administration for

    • Hyperglycemic emergencies

    • Critical care illness

    • MI or cardiogenic shock

    • Care following cardiac surgical procedures

    • Type 1 DM NPO

    • Corticosteroid Therapy

SC = subcutaneous; MI = myocardial infarction.

Bode et al. Endocr Pract. 2004;10(suppl 2):71-80.


The ideal iv insulin protocol

and Mortality in Patients Hospitalized with Acute MI

The Ideal IV Insulin Protocol

  • Easily ordered (signature only)

  • Effective (gets to goal safely)

  • 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)

  • Includes nutritional and electrolyte support

  • Easily implemented

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

Moghissi. Cleve Clin J Med. 2004;71:801-808.


Hyperglycemia management initiation of insulin drip therapy
Hyperglycemia Management and Mortality in Patients Hospitalized with Acute MIInitiation of Insulin Drip Therapy

  • 32 yo with Type 1 DM, s/p appendectomy.

  • NPO

  • BS= 278.

  • BG q 1 hour

DeSantis, et al Endocr Practice 2006;12:491-505


Hyperglycemia management titration of insulin drip therapy
Hyperglycemia Management and Mortality in Patients Hospitalized with Acute MITitration of Insulin Drip Therapy

  • Adjust insulin drip based on current BG and rate of BG change

  • One hour later, BG=310. Previous BG 278.

  • An increase of 32.

DeSantis, et al Endocr Practice 2006;12:491-505


Hyperglycemia management titration of insulin drip therapy1
Hyperglycemia Management and Mortality in Patients Hospitalized with Acute MITitration of Insulin Drip Therapy

  • One hour later, BG= 220

  • Previous BG=310, a decrease of 90

DeSantis, et al Endocr Practice 2006;12:491-505


Critical care improvement project glucose control
Critical Care Improvement Project – Glucose Control and Mortality in Patients Hospitalized with Acute MI

Reduce mortality rate by 20% in the ICUs through the implementation of tight glycemic control.

UCL

Spread

LCL

The decrease in the critical care mortality rate is statistical significant.

The Chi Squared Test P-value = 0.03

(Prior 12 months compared to Feb’05 – Apr’05)

  • Baseline Avg Blood glucose 144.3 +/-39 mg/dl

  • May-05 Avg Blood glucose 112.8 +/- 54 mg/dl


Points to consider when transitioning from iv to sc insulin
Points to Consider When Transitioning From IV to SC Insulin and Mortality in Patients Hospitalized with Acute MI

  • What are patients eating? When?

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

    • Continue IV insulin at least 2 hours after first SC injection to cover “gaps” (longer if first injection is basal; consider adding rapid-acting insulin for “gap coverage”)

  • What are the concomitant therapies?

    • Oral insulin secretagogues will lower BG faster than other agents, increasing risk of hypoglycemia

  • Will resolution of the illness alleviate insulin needs?

    • Decrease in TDD of 20%–33% not uncommon


Subcutaneous insulin maintaining physiologic insulin delivery in the hospital
Subcutaneous Insulin and Mortality in Patients Hospitalized with Acute MIMaintaining Physiologic Insulin Delivery in the Hospital

BE THE PANCREAS!


Dark Side and Mortality in Patients Hospitalized with Acute MI

The of Diabetes Management

The Sliding Scale

  • Dose in reaction to a single retrospective blood glucose measurement

  • Does not provide basal insulin coverage

  • Provides supplemental insulin after hyperglycemia occurs

  • Does not consider nutritional changes or diurnal insulin requirements

  • Nonphysiologic dosing places patients at risk of large fluctuations in blood glucose levels

    • Increased incidence of hyperglycemic and hypoglycemic episodes1

1. Queale et al. Arch Intern Med. 1997;157:545-552.


Rabbit 2 trial
RABBIT 2 Trial and Mortality in Patients Hospitalized with Acute MI

  • Prospective randomized trial of 130 insulin naïve T2DM non-ICU inpatients

  • Admission blood glucose b/w 140-400 mg/dl

  • Basal- bolus insulin with glargine and glulisine vs Regular insulin SS


Rabbit 2 trial1
RABBIT 2 Trial and Mortality in Patients Hospitalized with Acute MI

Mean Blood glucose mg/dl

DAYS

Umpierrez, et al Diabetes Care 30;2181-86,2007


Rabbit 2 trial n 9 ssi failures
RABBIT 2 TRIAL and Mortality in Patients Hospitalized with Acute MIn=9 SSI Failures

Mean Blood glucose mg/dl

DAYS


Which insulins are best for basal coverage

NPH and Mortality in Patients Hospitalized with Acute MI

Detemir (Levemir)

Which insulins are best for basal coverage?

Glargine (Lantus)

Regular

Lispro (Humalog)

Aspart (Novolog)

Glulisine (Apidra)

Insulin Effect

Inhaled insulin

0

6

12

18

24

Time (hours)


Which insulins are best for nutritional coverage

NPH and Mortality in Patients Hospitalized with Acute MI

Detemir (Levemir)

Which insulins are best for nutritional coverage?

Glargine (Lantus)

Regular

Lispro (Humalog)

Aspart (Novolog)

Glulisine (Apidra)

Insulin Effect

0

6

12

18

24

Time (hours)


Hyperglycemia management sc insulin calculating basal prandial insulin requirements
Hyperglycemia Management and Mortality in Patients Hospitalized with Acute MISC INSULINCALCULATING BASAL/PRANDIALINSULIN REQUIREMENTS

  • Conversion from IV insulin to SQ

  • Drip rate x 24 = Basal insulin requirements

    • 1u/hr x 24 = 24 units basal insulin

  • Take last stable drip rate (avg of last 6 hours) x 24

  • 60-80% of above as basal insulin

    • 24 x 0.8 = 19.2, 20 units Lantus SQ q 24 hrs

  • 10% of above as prandial insulin at each meal

    • 2 u Novolog with meals

DeSantis, et al Endocr Practice 2006;12:491-505


Calculating initial mdi doses for insulin na ve patients

and Mortality in Patients Hospitalized with Acute MI

Calculating Initial MDI* Doses for Insulin-naïve Patients

*Give after meals as rapid-acting analog if food intake is in doubt

Starting dose = 0.5 × weight in kg

Basal dose = 40%-50% of starting dose at bedtime

Total prandial dose = 50%-60% of starting dose, 1/3 at each meal*

Do not skip correction dose even if no food eaten

Adjust upwards daily by adding 50% of correction doses to basal and bolus doses

*MDI = Multiple daily injection

Thompson et al. Diabetes Spectrum. 2005;18:20-27.


Calculating initial mdi dose example

and Mortality in Patients Hospitalized with Acute MI

Calculating Initial MDI* Dose: Example

Assume 100-kg person with moderate insulin resistance

*Give after meals as rapid-acting analog if food intake is in doubt

Starting dose = 0.5 × 100 kg =50U

Prandial doses =

(0.5–0.6 x 50) = 25-30 U ÷ 3 or 8–10 U at each meal*

Basal dose =

0.4–0.5 x 50 U = 20-25 U at bedtime

Give correction dose

*MDI = Multiple daily injection

Thompson et al. Diabetes Spectrum. 2005;18:20-27.


Bg monitoring during transition periods

and Mortality in Patients Hospitalized with Acute MI

BG Monitoring During Transition Periods

  • Patients who are eating

    • Before meals, 2 hours after meals, and at bedtime

    • Between 2 AM and 3 AM

  • Patients who are not eating

    • Every 4 to 6 hours

BG = blood glucose.

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


80 kg male with Type 2 DM and Mortality in Patients Hospitalized with Acute MI

Basal Insulin

20

X

Prandial Insulin

X

7

7

7

DeSantis, et al Endocr Practice 2006;12:491-505


DETERMINING CORRECTION DOSE and Mortality in Patients Hospitalized with Acute MI

X

X

For pre-meal

BG=220

Pt would receive

7 units + 3 units

=10 units Insulin Aspart

Monitor supplemental insulin

requirements frequently

and adjust standing basal

and prandial doses

The ideal insulin regimen

never requires

supplemental doses

YOU ARE THE PANCREAS


Daily dose revision of sc insulin
Daily Dose Revision of SC Insulin and Mortality in Patients Hospitalized with Acute MI

  • Example: Patient with BG target 180 mg/dL

  • Determine total insulin dose administered the previous day

    Example: 50 U

  • Review corresponding glycemic control for that day

  • Adjust prandial doses by 50-75% of total daily correction dose

Campbell et al. Clin Diabetes. 2004;22:81-88.


Glucose management service subcutaneous protocol
Glucose Management and Mortality in Patients Hospitalized with Acute MIServiceSubcutaneous protocol

% Capillary blood glucose

  • < 60 =1.5 %

  • 400= 0.4%

  • Mean BG = 144 mg/dl

N=1606 6/04-1/06

CBG=32,229

75 % CBG

clinically acceptable range 80-180


Conclusions
Conclusions and Mortality in Patients Hospitalized with Acute MI

  • Inhospital glycemic control is now recognized as a patient safety issue

  • BG target 140 mg/dL-180 mg/dL in some populations

  • Different targets for different populations?

    • 80-110 mg/dl in post CV surgery

  • Safe and Effective Protocols can be implemented institutionally to attain goals with acceptable hypoglycemia

American Diabetes Association. Diabetes Care. 2006;29:S4-S42.


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