Hyperglycemia and the Hyperglycemia and the Critically Ill PatientCritically Ill Patient

Tony Gerlach, PharmD, BCPSTony Gerlach, PharmD, BCPSThe Ohio State University The Ohio State University

Medical CenterMedical Center

ObjectivesObjectives

Review the consequences of Review the consequences of hyperglycemia in ICU patientshyperglycemia in ICU patients

Summarize the pathophysiology of Summarize the pathophysiology of hyperglycemia in ICU patientshyperglycemia in ICU patients

Review the effects of intensive insulin Review the effects of intensive insulin therapy on outcomestherapy on outcomes

Effects of InsulinEffects of Insulin

Decrease glucoseDecrease glucose Anabolic effectsAnabolic effects

– Increase protein, glycogen synthesisIncrease protein, glycogen synthesis– Inhibits lipolysisInhibits lipolysis

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

Glucose control in Healthy Glucose control in Healthy People with out DiabetesPeople with out Diabetes

Insulin Release

GlucagonDecrease

Glucose Intake

Causes of Hyperglycemia: Causes of Hyperglycemia: Glucose IntakeGlucose Intake

Excess CaloriesExcess Calories

– Enteral/Parenteral NutritionEnteral/Parenteral Nutrition

– Drugs diluents (e.g., D5W)Drugs diluents (e.g., D5W)

– PropofolPropofol

– Peritoneal dialysis with high dextrose Peritoneal dialysis with high dextrose formulasformulas

Causes of Hyperglycemia: Stress Causes of Hyperglycemia: Stress ResponseResponse

Shock and SIRSShock and SIRS– Increased stress hormonesIncreased stress hormones

Endogenous catecholaminesEndogenous catecholamines ACTHACTH GlucagonGlucagon CortisolCortisol Growth HormoneGrowth Hormone Pro-inflammatory CytokinesPro-inflammatory Cytokines

Causes of Hyperglycemia: Causes of Hyperglycemia: Medications And DiseaseMedications And Disease

CorticosteroidsCorticosteroids Catecholamines Catecholamines

Epi, NE, Dopamine, DobutamineEpi, NE, Dopamine, Dobutamine SympathomimeticsSympathomimetics ImmunosupressantsImmunosupressants

– CyclosporinCyclosporin– TacrolimusTacrolimus

DiabetesDiabetes PancreatitisPancreatitis

Epidemiology of Epidemiology of Hypoglycemia in the ICUHypoglycemia in the ICU

Variable Variable – Patient typesPatient types– Different definitionsDifferent definitions– Under diagnosis of DMUnder diagnosis of DM

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

One study in MICU 50 % where hyperglycemic One study in MICU 50 % where hyperglycemic when those w/ DM excludedwhen those w/ DM excluded– Mean glucose 194 +/- 66 mg/dL Mean glucose 194 +/- 66 mg/dL

Long-term Glycemic Control and Long-term Glycemic Control and Postoperative Infection ComplicationsPostoperative Infection Complications

0

2

4

6

8

10

12

14

16

18

20

Mortality**

Hb A1C < 7

HB A1C >7

%

Arch Surg 2006;141:375-80.** Statistically Significant

Hyperglycemia and MortalityHyperglycemia and Mortality

05

1015202530354045

80-99

100-199

120-139

140-159

160-179

180-199

200-249

250-299

>300

Mortality

Mayo Clin Proc. 2003;78:1471-8.

%

Hyperglycemia, Infectious Complication Hyperglycemia, Infectious Complication and Mortality in Trauma Patientsand Mortality in Trauma Patients

0

5

10

15

20

25

30

35

< 110 mg/dL 110-200 mg/dl > 200 mg/dL

Infection

Mortality

J Trauma 2004;56:1058-62.

%

Effects of HyperglycemiaEffects of Hyperglycemia

Intravascular fluid balanceIntravascular fluid balance– DehydrationDehydration– GlucosuriaGlucosuria

Immune FunctionImmune Function– Abnormal WBC functionAbnormal WBC function

Granulocyte adhesion, chemotaxis, phagocytosis, Granulocyte adhesion, chemotaxis, phagocytosis, intracellular killingintracellular killing

– Impaired complement activityImpaired complement activity

Sternal Wound Infections in Diabetics Sternal Wound Infections in Diabetics undergoing Cardiac Surgeryundergoing Cardiac Surgery

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Sternal wound infections**

SQ Insulin

Insulin Drip

Ann Thorac Surg 1999;67:352-62

%

** Statistically Significant

Intensive Insulin Therapy and Intensive Insulin Therapy and Outcomes in SICU PatientsOutcomes in SICU Patients

0

5

10

15

20

25

Mortality** ICU LOS > 5 days**

Intensive Therapy Conventional Therapy

N Engl J Med 2001;345:1359-67.

%

** Statistically Significant

Intensive Insulin Therapy and Intensive Insulin Therapy and Outcomes in Mixed ICU PatientsOutcomes in Mixed ICU Patients

0

5

10

15

20

25

30

Mortality* (%) Infections* (N) Transfusions*(%)

ARF* (n)

Intensive Therapy Conventional Therapy

Mayo Clin Proc 2004;79:992-1000* Statistically Significant

Intensive Insulin Therapy and Intensive Insulin Therapy and Outcomes in MICU PatientsOutcomes in MICU Patients

0

10

20

30

40

50

60

In-hospitalMortality

Mortailty if ICULOS > 3 Days*

Newly acquiredkidney injury*

Bacteremia

Intensive Therapy Conventional Therapy

N Engl J Med 2006;354:449-61

%

* Statistically Significant

Blood Glucose and Insulin Blood Glucose and Insulin Requirements during ICU StayRequirements during ICU Stay

0

20

40

60

80

100

120

140

160

180

200

Day 0 Day 1 Day 3 Day 4 Day 5 Day 6 Day 7

0

0.1

0.2

0.3

0.4

0.5

0.6

Mean Glucose Insulin

Crit Care Med 2003;31:359-66

mg/dL Units/h per cal/kg

0

10

20

30

40

50

60

70

80

ICU LOS** Hosp LOS** ICU Mortality** HospMortality**

Early < 48 H Late > 48 H** Statistically Significant Inten Care Med 2008;34:881-7

Early versus Late Intensive Early versus Late Intensive Insulin Therapy in ICU PatientsInsulin Therapy in ICU Patients

Hyperglycemia and mortality Hyperglycemia and mortality in VA ICU patientsin VA ICU patients

Analysis of over 216,000 admissionAnalysis of over 216,000 admission Mortality increased by 40 % in those with mild Mortality increased by 40 % in those with mild

hyperglycemia (111-145 mg/dl)hyperglycemia (111-145 mg/dl) In 154,000 without DM mortality did not increase In 154,000 without DM mortality did not increase

until glucose > 146 mg/dLuntil glucose > 146 mg/dL Greatest risk for patients admitted for Greatest risk for patients admitted for

cardiovascular disorders (MI, USA, Stroke)cardiovascular disorders (MI, USA, Stroke) Diagnosis with no relationship include: COPD, Diagnosis with no relationship include: COPD,

hepatic failure, GI neoplasm, and orthopedic hepatic failure, GI neoplasm, and orthopedic disordersdisorders

ADA 2006 Scientific SessionsMedscape July 23, 2006

GluControl StudyGluControl Study

0

2

4

6

8

10

12

14

16

18

Hypoglecmia Mortality

Goal 80-100 mg/dl Goal 140-180 mg/dL

Mean Age 65 yrsMean Age 65 yrs 40 % MICU pts40 % MICU pts Mean GlucoseMean Glucose

– 118 low range118 low range– 144 high range144 high range

No difference in No difference in length of staylength of stay

SCCM 2007 Scientific SessionsMedscape February 2007

What is the Optimal Glucose What is the Optimal Glucose Range?Range?

Waiting for results of Waiting for results of NICE-SUGARNICE-SUGAR

Goal is to recruit 6100 Goal is to recruit 6100 pts pts

Comparing low rangeComparing low range 80-110 mg/dl80-110 mg/dl 140-180 mg/dl140-180 mg/dl

Optimal Glucose TargetOptimal Glucose Target

Target ranges differ between studyTarget ranges differ between study Appears upper threshold to be 145-150 Appears upper threshold to be 145-150

mg/dLmg/dL Normal glucose (< 110 to 120 mg/dL) is Normal glucose (< 110 to 120 mg/dL) is

associated with better outcomes during associated with better outcomes during post hoc analysis post hoc analysis (Crit Care Med 2003;31;359-66)(Crit Care Med 2003;31;359-66)

OSUMC Insulin Infusion ProtocolOSUMC Insulin Infusion Protocol

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

Insulin SolutionInsulin Solution:: IV regular insulin 100 units per IV regular insulin 100 units per 100 mL 0.9% NaCL100 mL 0.9% NaCL

Serum Glucose Goal Range: 110 - 150 mg/dLSerum Glucose Goal Range: 110 - 150 mg/dL Assessment: Serum or capillary glucose q1 hour Assessment: Serum or capillary glucose q1 hour Patient must receive dextrose Patient must receive dextrose CONTINUOUSLYCONTINUOUSLY

during insulin infusion (e.g. D5W atduring insulin infusion (e.g. D5W at10 mL/hour, TPN, or enteral nutrition) 10 mL/hour, TPN, or enteral nutrition)

OSUMC Insulin Infusion ProtocolOSUMC Insulin Infusion Protocol

Initiate insulin infusion at 2 units/hour Initiate insulin infusion at 2 units/hour Monitor ABG q1 hour and adjust the insulin Monitor ABG q1 hour and adjust the insulin

infusion rate as directed in the following table.infusion rate as directed in the following table. Frequency of glucose checks can be reduced to Frequency of glucose checks can be reduced to

q2 hours if patient is medically stable and insulin q2 hours if patient is medically stable and insulin infusion rate has not changed for 3 hours.infusion rate has not changed for 3 hours.

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

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

OSUMC Experience

024681012141618

Hypoglycemicevents**

Pts w/hypoglycemia**

Amps of D50Used

BaselineProtocol

** Statistically Significant

%

Source of DextroseSource of Dextrose

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

Acceptable sources are:Acceptable sources are: Tube FeedsTube Feeds TPNTPN Dextrose 5% at 10-40 ml/hr for most patientsDextrose 5% at 10-40 ml/hr for most patients

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

OSUMC Nursing Hypoglyecmia OSUMC Nursing Hypoglyecmia PolicyPolicy

Repeat Glucose < 55 or > 400 mg/dLRepeat Glucose < 55 or > 400 mg/dL Glucose < 40 mg/dL is considered critical Glucose < 40 mg/dL is considered critical

valuevalue SymptomsSymptoms

Autonomic: Tremble, shaking, diaphoresis, Autonomic: Tremble, shaking, diaphoresis, tachycardia, tachycardia,

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

Final ThoughtsFinal Thoughts

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

Decrease insulin or start D5 when Decrease insulin or start D5 when stopping Tube feeds stopping Tube feeds

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

When patient travels verify glucoseWhen patient travels verify glucose When in doubt stop drip and get glucoseWhen in doubt stop drip and get glucose