Glycemic Control in Acutely Ill Patients

Martin J. Abrahamson, MD FACPAssociate Professor of Medicine, Harvard Medical

SchoolSenior Vice President for Medical Affairs, Joslin

Diabetes Center

Questions to Ask

• Is hyperglycemia associated with increased morbidity/mortality in acutely ill patients?

• Will lowering glucose improve outcomes for acutely ill patients?

• What glucose levels should be attained in the acutely ill patient?

• How do we best do this?

Mortality Increases with Increases in Average ICU BG

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

(1826 consecutive ICU patients 10/99 thru 4/02)

Intensive Insulin Therapy and Mortality in Patients Admitted to SICU

• 1548 consecutive admissions to SICU

• Randomly assigned (with stratification based on type of critical illness) to conventional vs intensive insulin treatment

Van de Berghe G, et al. NEJM 2001;345:1359-1367

• Conventional treatment– Standardized nutritional therapy and intravenous

insulin therapy if BG >215 mg/dl to maintain blood glucose <200 mg/dl.

• Intensive therapy– Standardized nutritional therapy and intravenous

insulin therapy if BG>110 mg/dl to maintain glucose 80 - 110 mg/dl.

Intensive Insulin Therapy and Mortality in Patients Admitted to SICU

Intensive Insulin Therapy in Critically Ill Surgical Patients

Conventional Treatment

Intensive Treatment

Trigger for starting iv insulin

> 215 > 100

Glucose achieved

153 + 33 103 + 19

% with glucose < 40 mg/dL

0.7 5

Glucose in mg/dL Van den Berghe et al. NEJM 2001; 345:1359-1367

Intensive Insulin Therapy in Surgical ICU Patients Reduces Mortality

Conventional: insulin when blood glucose > 215 mg/dLmean BG = 153 mg/dL

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

mean BG = 103 mg/dL

Survival in ICU (%)

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% mortality

Van den Berghe, G. NEJM. 2001;345:1359–1367.

Intensive Insulin Therapy in Surgical ICU Patients Reduces Morbidity and Mortality

Percent Reduction

Mortality Sepsis Dialysis Polyneuropathy

Blood Transfusio

n

34%

46%41% 44%

50%

Van den Berghe, G. NEJM. 2001;345:1359–1367.

What about Intensive Therapy in the MICU?

♦ 1,200 patients who “were considered to need intensive care for at least 3 days”

♦ Randomized to two groups:♦ IV insulin to achieve glucose 80-110 mg/dl♦ Conventional therapy using insulin for blood

glucose > 215 mg/dl and tapered when < 180 mg/dl

♦ 16.9% of these patients had diabetes

NEJM 354:449, 2006

Intensive Insulin Therapy in Critically Ill Medical Patients

Conventional Treatment

Intensive Treatment

Trigger for starting iv insulin

> 215 > 100

Glucose achieved

153 111

% with glucose < 40 mg/dL

3.1 18.7

Glucose in mg/dL Van den Berghe et al. NEJM 2006; 354:449-460

Intensive Insulin in the MICU Does Not Decrease Mortality

• In-hospital deaths– Conventional

Therapy: 40%– Intensive Insulin

Therapy: 37.3%

NEJM 354:449, 2006

P = 0.33

100

80

60

40

20

A. Intention-to-Treat Group (n = 1,200)

Intensive treatment

Conventional treatment

00 100 200 300 400 500

Days

First 30 days

100

80

60

40

00 10 20 30

In-H

ospi

tal S

urvi

val (

%)

Subgroup in ICU ≥ 3 days (n = 767)

P = 0.009

NEJM 354:449, 2006

100

80

60

40

20

B. Subgroup in ICU ≥3 Days (n = 767)

Intensive treatment

Conventional treatment

00 50 150200250 350

Days

First 30 days

100

80

60

40

00 10 20 30

In-H

ospi

tal S

urvi

val (

%)

100 300 500

• In-hospital deaths– Conventional

Therapy: 52.5%– Intensive Insulin

Therapy: 43.0%

Effect of Intensive Insulin Therapy on Morbidity

NEJM 354:449, 2006

4.0

3.0

2.0

1.0

0.00 10203040506070 8

090

Intensivetreatment

Conventionaltreatment

P=0.03

Weaning from MechanicalVentilation

Cum

ulat

ive

Haz

ard

3.5

2.5

1.5

0.5

5.0

4.0

0.00 010200300400 50

0600

P=0.05

Discharge from Hospital

3.02.01.0

4.5

3.5

2.5

1.00.0

0 20 40 60 80

100

P=0.04

Discharge from ICU

4.0

3.0

2.0

0.5

1.5

A

Days After Admission to ICU

> 3 days in ICU (n = 767)

3.5

2.5

1.5

0.50.0

Intensivetreatment

Conventionaltreatment

P<0.001

Weaning from MechanicalVentilation

B

Cum

ulat

ive

Haz

ard

0 10203040506070 80

90

1.0

2.0

3.05.0

1.00.0

0 100200300400 500

600

Discharge from Hospital

4.03.0

2.0

4.0

3.0

2.0

1.0

0.00 20 40 60 8

0100

P=0.04

Discharge from ICU

3.5

2.5

0.5

1.5

P=0.01

Days After Admission to ICU

Conclusions• Intensive insulin therapy significantly

reduced morbidity but not mortality among all patients in the MICU.

• Although the risk of subsequent death and disease was reduced in patients treated for ≥3 days, these patients could not be identified before therapy.

NEJM 354:449, 2006

Diabetes Care in the Hospital: NICE-SUGAR Study (1)

• Largest randomized controlled trial to date• Tested effect of tight glycemic control

(target 81–108 mg/dL) on outcomes among 6,104 critically ill participants

• Majority (>95%) required mechanical ventilation

ADA. IX. Diabetes Care in Specific Settings. Diabetes Care. 2013;36(suppl 1):S46.

Diabetes Care in the Hospital: NICE-SUGAR Study (2)

• In both surgical/medical patients, 90-day mortality significantly higher in intensively treated vs conventional group (target 144–180 mg/dL)– Severe hypoglycemia more common

(6.8% vs 0.5%; P<0.001)– Findings strongly suggest may not be

necessary to target blood glucose levels<140 mg/dL; highly stringent target of<110 mg/dL may be dangerous

ADA. IX. Diabetes Care in Specific Settings. Diabetes Care. 2013;36(suppl 1):S46.

So what glycemic target should be attempted for acutely ill patients admitted with diabetes?

ADA Recommendations• Critically ill patients:

• 140 – 180 mg/dL • Start iv insulin when glucose exceeds 180

mg/dL• Goal of 110 – 140 mg/dL may be appropriate

for some patients if there is no risk of hypoglycemia

• Non-critically ill• Premeal < 140 mg/dL mg/dL• Random <180 mg/dL

So how do we manage someonewho requires insulin

and is NPO or too ill to eat?

Using Sliding Scale SC Insulin is Like Being on a Roller Coaster!

IT IS A RELIC FROM THE PASTAND SHOULD BE AVOIDED

WHEREVER AND WHENEVER POSSIBLE!!

Estimating Insulin Dose for Infusion

• Infusion of 1.0 - 2.0 units/hr usually maintains blood glucose in 120 - 180mg/dL range

• Insulin requirements depend on – Previous therapy– Degree of control– Use of steroids– Presence of sepsis– Type of surgery

• Increased insulin requirements for renal transplant and open heart surgery

Guidelines for Insulin Infusion

• Decreased insulin needs– Patients requiring diet and/or oral agents– Patients taking less than 50 U of insulin per day

• Increased insulin needs– Obesity, hepatic disease (x 1.5)– Steroid therapy (x2)– Sepsis (x2)– Renal transplant (x 2)– Open heart surgery (x 3-5)

Insulin Infusion AlgorithmDecision to initiate iv insulin

•If BG < 200 mg/dL start with D5 ½ N Saline at 60 – 100 cc/hr• If BG > 300 mg/dL give iv regular insulin 0.1U/kg stat

Initiate at an hourly rate of total daily dose of insulin / 24For patients not usually on insulin start at 0.02 U/kg/hr

Check BG hourly

Adjustment of Insulin is dependent on current glucose,previous glucose

and rate of change of glucose

Transitioning to SC Insulin• Do not stop iv insulin before giving some

short acting insulin sc• Usually continue iv infusion by about 1

hour after administration of short acting sc insulin

• Plan to stop iv after a meal – preferably during the day

• Ensure that there is always intermediate or long acting insulin given to cover basal requirements

Remember – Insulin Requirements..

• Basal

• Prandial/Nutritional

• Correction or Supplemental

Summary

• Hyperglycemia is associated with increased morbidity and mortality in acutely ill patients

• Maintaining glucose levels between 140 and 180 mg/dL in acutely ill patients is associated with the least morbidity and optimal outcomes

• Using iv insulin infusion to achieve this in the ICU is the preferred modality of administering insulin