Diabetes MellitusInpatient Management

Surgical Patients2008

Michael T McDermott MDDirector, Endocrinology Practice and Diabetes Program

University of Colorado Hospital

UCH Diabetes Program

Carolee Whitehill RNCarolee Whitehill RNProgram AdministratorProgram Administrator

Bridget Everhart RNPBridget Everhart RNPProgram Nurse ManagerProgram Nurse Manager

Maureen Zaccardi RNMaureen Zaccardi RNDirector of Ambulatory ServicesDirector of Ambulatory Services

Michael McDermott MDMichael McDermott MDProgram DirectorProgram Director

Topics for Discussion Association of Diabetes Mellitus or

Hyperglycemia with Surgical Outcomes

Evidence that Control of Hyperglycemia

Improves Surgical Outcomes

Implementation of Inpatient Glucose Control

at University of Colorado Hospital

Definitions

Diabetes MellitusDiabetes Mellitus

Fasting BG > 125 mg/dlFasting BG > 125 mg/dl

2 hour PPBG > 200 mg/dl2 hour PPBG > 200 mg/dl

Stress HyperglycemiaStress Hyperglycemia

No prior dx of diabetesNo prior dx of diabetes

Hyperglycemia during stressHyperglycemia during stress

GlucoseUtilization

Stress HyperglycemiaPathophysiology

GlucoseProduction

GlucoseUtilization

Insulin

Hyperglycemia

Cortisol Catecholamines Glucagon

Growth Hormone

Association ofDiabetes Mellitus or Hyperglycemia

With Surgical Outcomes

0

5

10

15

20

25

A1C < 7% A1C > 7%

Pre-operative Glucose ControlPost-operative Infection Rate

Dronge AS, Arch Surg 2006; 141:375

RR = 2.13, p < .007

67%

490 patients with DM undergoing major non-cardiac surgery:

Infe

ctio

n R

ate

Ammori J, J Surg Res 2007; 140:227

Retrospective Review: 184 patients undergoing liver transplantationGood intra-operative BG control: mean BG < 150 mg/dl (N=60)Poor intra-operative BG control: mean BG > 150 mg/dl (N=124)

P = .02

605040302010

0

30 Day Infection Rate

Intra-Operative Glucose Control

30%

48%

P = .05

3025201510

50

1 Year Morality Rate

8.8%

21.9%

Intra-operative BG < 150Intra-operative BG > 150

Gandhi G, Ann Intern Med 2007; 146:233

RCT: 400 patients undergoing elective cardiac surgeryConventional (n=201): IV insulin if BG > 200; BG goal < 150 (mean 148)Intensive (n=199): IV insulin infusion to maintain BG of 80-100 (mean 120)Composite Endpoint: death, sternal infection, dysrhythmia, stroke,

prolonged ventilation, acute renal failure

P = NS

Conventional RxIntensive Insulin Rx

605040302010

0

Composite Endpoint

Intra-Operative Glucose Control

46% 44%

P = .06

6

4

2

0

2%

0%

Specific Endpoints

Death Stroke4%

1%

P = .02

0

10

20

30

40

50

60

70

BG < 200 BG > 200

Thomas MC, Transplantation 2001; 72:1321

Acu

te R

ejec

tion

Rat

e %

Post-Operative Glucose ControlAcute Rejection of Renal Transplant

50 patients with DM undergoing renal transplant: Prospective

11%

58%

Mean Blood Glucose in 1st 100 Hours Post-Transplant

5 Fold Increased

Risk

0

0.5

1

1.5

2

2.5

3

Lowest BG Quartile Highest BG Quartile

Post-Operative Glucose ControlCABG Complications StudyC

ompl

icat

ions

Adj

uste

d O

dds R

atio

McAlister FA, Diabetes Care 2003; 26:1518-24

291 Diabetic Patients with CAD undergoing CABGComplications measured: MI, Stroke, Sepsis, Death

2.5

2.5 Fold Increased

Risk

00.20.40.60.8

11.21.41.61.8

Non Diabetic Diabetic

Post-Operative Glucose ControlDeep Sternal Wound Infections

DSW

I Rat

e %

Zerr KJ, Ann Thorac Surg 1997; 63:356-61

0.4%

1.7%

4 Fold Increased

Risk

8,910 Patients having CABG surgery 1987-19931,585 (18%) had Diabetes Mellitus

0

5

10

15

20

25

30

Length of Stay (Days)0

10

20

30

40

50

60

Charges ($1000s)

DSWINo DSWI

Furnary AP, Circulation 1999; 100:11

Post-Operative Glucose ControlDeep Sternal Wound Study

24.8

8.8

54.60

28.20

0123456789

10

< 150 150-175 175-200 200-225 225-250 > 250

Post-Operative Glucose ControlCABG Survival Study

Furnary AP, J Thorac Cardiovasc Surg 2003; 125:1007

Mor

talit

y R

ate

%

Mean Blood Glucose Level

1.4% 1.7% 2.1%

3.8%

5.8%

8.6%

3554 patients undergoing CABG Surgery with elevated BG2612 treated with insulin infusion942 treated with SQ insulin

Gale S, Am Surg 2007; 73:454

Retrospective Review: 103 trauma patients admitted to SICU for > 48 hoursNon-DM: 87%; DM 13%Defined: Controlled BG < 140 mg/dl; Non-Controlled BG > 140 mg/dl

P = .05

Mortality - All

Post-Trauma Glucose Control

9%

22%

P = .05

3025201510

50

Mortality – Non DM

10%

32%

Controlled BG (< 140)Non-Controlled BG (> 140)

3025201510

50

HyperglycemiaRisk Factor for Complications/Mortality

UCH Study (Glasheen, 2006) – Poor BG Control in Elective Knee ReplacementSignificant: Joint Infections and Length of Stay

Renal transplant Cardiovascular surgery Orthopedic surgery Trauma Myocardial infarction Stroke Community acquired pneumonia Mortality in inpatients

Conclusions from these Studies

Hyperglycemia causes poor outcomes

Serious illnesses cause hyperglycemia

Hyperglycemia Causes Poor OutcomesPotential Mechanisms

Increased Infection Risk

Impaired Myocardial Metabolism

Generalized Inflammatory State

One BG > 220 mg/dl risk of nosocomial infection 5.8 fold

Two hours of hyperglycemia WBC function for 2 weeks

Hill, J Parenteral and Enteral Nutr 1998; 22:77-81

Hyperglycemia: Poor OutcomesInfection Risk

Glucose Utilization

ROS MVO2 Cytokines FFA

DysrythmiasNegative Inotropism

Myocardial DysfunctionEndothelial Dysfunction

Hyperglycemia: Poor OutcomesImpaired Myocardial Metabolism

HyperglycemiaGeneralized Inflammatory State

NF-

Glucose Insulin

iNOS

NO

ICAM-1VCAM-1E-selectin

EndothelialCell

AdhesionMolecules Inflammatory

Cytokines

TNF-IL-6 IL-8

MCP-1MMPs

Monocyte/Macrophage

CRP

LiverCell

Acute PhaseProteins

SAA

++

+ -

++

Evidence thatControl of Hyperglycemia

ImprovesSurgical Outcomes

Post-Operative Glucose ControlCABG Survival Study

Furnary AP, J Thorac Cardiovasc Surg 2003; 125:1007

3554 patients undergoing CABG Surgery with elevated BG2612 treated with IV insulin infusion942 treated with SQ insulin prior to IV protocol

MortalityRate%

InsulinInfusionN=2612

2.5%

6543210

SQ InsulinN=942

5.3% 50% Risk Reductionp < .0001

Schmetlz L, Diabetes Care 2007; 30:828

Retrospective Study: 614 consecutive patients undergoing CT surgeryIV Insulin started in ICU when BG > 108 mg/dlSQ Insulin started on wards when BG > 108 mg/dl

ICU admission BG > 198ICU admission BG < 198

P = .02

30

20

10

0

11%

21.4% 21.8%

32.1%

P = .02P = .04

2.3%

6.1%

Death RenalComplication

3.9%

10.7%

P = .02

PulmonaryComplication

CardiacComplication

Post-Operative Glucose Control

Van den Berghe G, NEJM 2001; 345:1359

RCT: 1548 Surgical ICU patients on mechanical ventilationConventional Group: IV insulin if BG > 215; mean BG 153 mg/dlIntensive Group: IV insulin if BG > 115; mean BG 103 mg/dl

In HospitalRisk

ReductionIntensive c/wConventional

0102030405060

Sepsis

46% 50%

DialysisBlood

TransfusionPoly-

neuropathy Mortality

41% 44%34%

Glucose Control Improves SICU OutcomesSICU Study

Brunkhorst F, N Engl J Med 2008; 358:125-39

RCT: 537 patients with severe sepsisIntensive Rx (N=247), mean BG 112; Conventional Rx (n=290), mean BG 151

Intensive Rx, mean BG 112Conventional Rx, mean BG 151

P < .001

40%

30%

20%

10%

04%

17%

5.2%10.9%

P = .01

P = .7426%24.7%

35.4%39.7%

P = .31

Severe Sepsis

Mortality28 Days

Mortality90 Days

Severe BG< 40 mg/dl

SAEs

AACE Position StatementRecommended Inpatient Glucose Targets

ICU: < 110 mg/dl

Non-ICU

Preprandial: < 110 mg/dl

Maximum: < 180 mg/dl

Labor and Delivery: < 100 mg/dlPosition Statement, Endocr Pract 2004; 10:77-82

Sliding ScaleRegularInsulin

Regular Insulin Sliding ScaleDelayed Onset

8 hr

InsulinInjection

4 hr 12 hr 16 hr

2-4 hrBG does not significantly

decrease for 2-4 hours

Regular Insulin Sliding ScaleDelayed Response and Stacking

8 hr

InsulinInjection

4 hr 12 hr 16 hr

InsulinInjection

InsulinInjection

Hypoglycemia

Queale W, Arch Intern Med 1997; 157:545-52Baldwin D, Diabetes Care 2005; 28:1008-11Golightly L, Pharmacotherapy 2006; 26:1421-32Umpierrez G, Diabetes Care 2007; 30:2181-6Datta S, Endocr Pract 2007; 13:225-31

Regular Insulin Sliding ScaleDelayed Response and Stacking

Inability to adequately control hyperglycemia

More frequent hypoglycemia

InsulinInjection

6 hr 12 hr 18 hr

InsulinInjection

InsulinInjection

InsulinInjection

0 hr

Rapid-Acting Correction Insulin for Inpatient HyperglycemiaFaster Acting – better control of hyperglycemiaNo Stacking – less hypoglycemia

InsulinInjection

6 hr 12 hr 18 hr

InsulinInjection

InsulinInjection

InsulinInjection

0 hr

Basal Insulin with Rapid-Acting Correction Insulin for Inpatient

HyperglycemiaSignificantly: Less Hyperglycemia

Less Hypoglycemia

Umpierrez G, Diabetes Care 30:2181-2186, 2007

BBI

SSI

Basal Bolus compared to Sliding Scale InsulinRCT: 130 Insulin naïve Type 2 DM patients, in hospital65 Basal Bolus Insulin (BBI) with Glargine and Glulisine65 Sliding Scale Insulin (SSI) QID

14% of patients, BG > 240 mg/dL

SSI

BBI

SSI

Umpierrez G, Diabetes Care 30:2181-2186, 2007

Basal Bolus compared to Sliding Scale InsulinRCT: 130 Insulin naïve Type 2 DM patients, in hospital65 Basal Bolus Insulin (BBI) with Glargine and Glulisine65 Sliding Scale Insulin (SSI) QID

SSI14% of patients, BG > 240 mg/dL

Implementation of Inpatient

Glucose Control

Inpatient Insulin TherapyPreprinted Order Sets - UCH

Available NowIntravenous Insulin Infusion

SQ Glargine and LisproSQ NPH and Lispro

SQ 70/30 Insulin for Tube FeedsDKA/HHS Treatment

Colorado Insulin Infusion Protocol

Initiation simple

Adjustments based on

Current BG level

Current Insulin infusion rate

Rate of BG change in past hour

Efficacy

Safety

UCH – 65 ICU Patients on IV Insulin Infusion

Subcutaneous Insulin Glargine & Lispro Order Set

Subcutaneous Insulin: Glargine & Lispro

66%

89% 82% 84% 86% 88%

0%20%40%60%80%

100%

Day 1Initial

Insulin

Day 1Prior

Insulin

Day 2 Day 3 Day 4 Day 5

Patient N = 28 on Day 1(total) N = 25 on Day 5

BG 71-179 mg/dL

Subcutaneous Insulin Glargine & Lispro Order Set

Rate of Hypoglycemia (591 BG Values)Rate of Hypoglycemia (591 BG Values)

≤ 70 mg/dL = 1.02%≤ 50 mg/dL = 0%

General Surgery

Blood Glucose Values - General Surgery (GSRG) July - Sept 2007

75% 90%

23% 9%

0%

20%

40%

60%

80%

100%

POC Only Lab

Mean BG 154 Mean BG 131

Total Hypoglycemia Rate = 1.1%

≥ 180 mg/dL

71-179 mg/dL

≤ 70 mg/dl

Surgical ICU

Blood Glucose Values - Surgical ICU (SIA & SIB) July - Sept 2007

85%

13%

0%

20%

40%

60%

80%

100%

Lab & Partial POC

Mean BG = 136

Hypoglycemia Rate = 1.5%

≥ 180 mg/dL

71-179 mg/dL

≤ 70 mg/dl

TransplantBlood Glucose Values - Transplant/Med (TXMS)

July-Sept 2007

70%84%

28% 14%

0%

20%

40%

60%

80%

100%

POC (Partial) LabMean BG 160 Mean BG 134

Total Hypoglycemia Rate = 1.9%

≥ 180 mg/dL71-179 mg/dL≤ 70 mg/dl

Orthopedics

Blood Glucose Values - Orthopedics (BONE) July - Sept 2007

66%86%

31%12%

0%

20%

40%

60%

80%

100%

POC Only Lab

Mean BG 164 Mean BG 137

Total Hypoglycemia Rate = 1.9%

≥ 180 mg/dL

71-179 mg/dL

≤ 70 mg/dl

Conclusions Hyperglycemia causes poor surgical outcomesHyperglycemia causes poor surgical outcomes

PrePre--Operative BG control improves outcomesOperative BG control improves outcomes

IntraIntra--Operative BG control not clearly beneficialOperative BG control not clearly beneficial

PostPost--Operative BG control improves outcomesOperative BG control improves outcomes

SS regular insulin does not control BG SS regular insulin does not control BG

Intravenous insulin orders available ICUsIntravenous insulin orders available ICUs

Subcutaneous insulin orders available on wardsSubcutaneous insulin orders available on wards

UCH insulin orders are safe and effective; UCH insulin orders are safe and effective; continuously monitored and upgradedcontinuously monitored and upgraded

Thank You