Achieving Glycemic Control in the Hospital Setting

143357

(Part 2 of 4)

Trial

    Blood Glucose* Target

Primary Outcome

 

N Setting Intensive Conventional RRR†

Van den Berghe20061

1200 MICU 80-110 180-200Hospital mortality

7.0%¶

Glucontrol20072 1101 ICU 80-110 140-180

ICU mortality

-10%¶

Gandhi20073 399

Operating Room

80-110 <200 Composite 4.3%¶

VISEP20084 537 ICU 80-110 180-200

28-Day mortality

5.0%‡¶

De La Rosa 20085 504

SICUMICU

80-110180-200

28-Day mortality

-13%¶

NICE-SUGAR20096 6104 ICU 81-108 ≤180

90-Day mortality

-10.6§

*Blood glucose in mg/dL; †RRR=Relative risk reduction, intensive group vs conventional group; ‡Personal communication; Dr. Frank Brunkhorst; §P<.05; ¶Not significant (P>.05). 1. Van den Berghe G et al. N Engl J Med. 2006;354(5):449-461; 2. Devos P et al. Intensive Care Med. 2007;33:S189; 3. Gandhi GY et al. Ann Intern Med. 2007;146(4):233-243; 4. Brunkhorst F et al. N Engl J Med. 2008;358(2):125-139; 5. De La Rosa G et al. Crit Care. 2008;12:R120; 6. The NICE-SUGAR Study Investigators et al. N Engl J Med. 2009;360(13):1283-1297.

Selected Randomized Controlled Trials of Intensive Glucose Management in Critical Care Studies Showing No Benefit

Eligibility:Patients expected to require treatment in the ICU for 3 or more consecutive days

NICE-SUGAR Study: Design

• Multicenter, open-label, randomized, controlled trial • Examining the effects of blood glucose management on 90-day, all-cause mortality • The 2 groups had similar baseline characteristics• 42 Centers in Australia, New Zealand, and Canada• Recruitment from December 2004 to November 2008• Last follow-up: November 2008

Conventional control group (target BG: ≤180 mg/dL)

n=3054

n=3050

N=6104

The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360(13):1283-1297.

Intensive control group(target BG: 81-108 mg/dL)

NICE-SUGAR Study Results: Treatment and Glucose Measures

Intensive Control Group

Conventional Control Group P Value

Patients treated with insulin 97.2% 69.0% <.001

Median duration of treatment (IQR), days

4.2(1.9-8.7)

4.3(2.0-9.0)

.69

Mean insulin dose, units/day 50.2±38.1 16.9±29.0 <.001

Morning BG, mg/dL 118±25 145±26 <.001

Time-weighted BG, mg/dL 115±18 144±23 <.001

No. of patients with hypoglycemia (BG ≤40 mg/dL)/ total no. (%)

206/3016 (6.8%)

15/3014(0.5%)

<.001

IQR=interquartile range.The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360(13):1283-1297.

NICE-SUGAR Study: Outcomes

Outcome Measure Intensive

Control GroupConventional Control Group P Value

28-Day mortality 22.3% 20.8% .17

90-Day mortality 27.5% 24.9% .02

Mech. ventilation(Mean days + SD)

96%(6.6±6.6)

95.3%(6.6±6.5)

.17(.56)

Dialysis 15.4% 14.5% .34

Bloodstream infections 12.8% 12.4% .57

The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360(13):1283-1297.

NICE-SUGAR Study: Trial Limitations• Subjects eligible for inclusion were defined by a

subjective rather than an objective criterion, which was the expected time in the ICU

• Medical staff and study personnel were not blinded to treatment arms

• Several patients in the intensive-control group had glucose levels above the target range

• Data regarding potential biological mechanisms underlying the observed outcomes in the intervention groups were not collected

• Data regarding the costs of the trial interventions were not collected

The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360(13):1283-1297.

NICE-SUGAR Study: Conclusions• This large, international, randomized trial found that

intensive glucose control did not offer benefits to critically ill patients1

• Blood glucose target of <180 mg/dL with the achieved target of 144 mg/dL resulted in lower (90-day) mortality than did a target of 81-108 mg/dL1

• Increased hypoglycemic events were observed with lower glucose targets1

• ADA and AACE position: good glucose management, through establishing patient-specific glycemic targets and individualizing care, are important objectives for patients in the hospital setting2

1. The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360(13):1283-1297. 2. Joint statement from the American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) on

the NICE-SUGAR study on intensive versus conventional glucose control in critically ill patients. American Diabetes Association Web site. http://www.diabetes.org/for-media/2009/joint-statement-from-ada-and.html. Accessed December 17, 2009.

How Have These Data Changed Management Paradigms?

Guidelines for Glycemic Control in Hospitalized Patients

• With initiation of insulin therapy, maintain between 140 and 180 mg/dL; potential for better therapeutic outcomes at the lower range1

• Somewhat lower targets might be recommended for selected patients, but targets <110 mg/dL are not recommended1

• Prolonged treatment with sliding-scale insulin as the sole regimen is discouraged1

• Consideration should be given to minimizing the risk of hypogylcemia (a never event), which is associated with adverse short- and long-term outcomes among inpatients1,2

1. Moghissi ES et al. Endocr Pract. 2009;15(4):353-369; 2. Eliminating serious, preventable, and costly medical errors—never events [news release]. Centers for Medicare & Medicaid Services. http://www.cms.hhs.gov/apps/media/press/release.asp?Counter=1863. Accessed December 17, 2009.

Intensive Care Unit

BG≤180 mg/dL

Guidelines for Glycemic Control in Hospitalized Patients (cont’d)

• Reassess treatment regimen if BG <100 mg/dL• Modify treatment if BG <70 mg/dL, unless caused

by other known factors (eg, missed meal)• Stable patients with successful prior history of tight

glycemic control in outpatient setting might be good candidates for lower ranges

• Higher ranges might be appropriate for certain patients*

*Patients who are terminally ill, patients with severe comorbidities, and patients in care settings where frequent BG monitoring is not possible.

Moghissi ES et al. Endocr Pract. 2009;15(4):353-369.

Noncritical Care

Preprandial: <140 mg/dLRandom: <180 mg/dL