NICE-

SUGAR
OVMC
SERIES
LANDMARK TRIALS
NICE-SUGAR: Normoglycemia in Intensive Care
Evaluation–Survival Using Glucose Algorithm
Regulation
BACKGROUND

◾ Hyperglycemia is common in acutely ill patients

◾ Hyperglycemia is associated with increased

morbidity and mortality
◾ Prior to the NICE-SUGAR trial, a study in post-
surgical patients found decreased mortality with sugar
levels between 80-110, but this was a single center
study that could be prone to biases (eg Hawthorne
effect)
CLINICAL QUESTION

◾ In critically ill patients, how does intensive

glycemic control compare to conventional
glycemic control in reducing mortality?
DESIGN

◾ Analysis: Intention-to-treat

◾ Trial Design: Multicenter, non-blinded, parallel group, randomized, controlled trial

◾ Setting: 42 centers

◾ N=6,104
◾ Intensive (n=3,054)

◾ Conventional (n=3,050)

◾ Primary outcome: 90-day mortality (from any cause)

◾ Secondary outcomes: > 90 days survival, cause-specific death, and duration on ventilation, RRT, and
ICU/hospital stays
◾ Tertiary outcomes: mortality within 28 days after randomization, place of death (ICU, hospital ward, or other),
incidence of new organ failure, positive blood culture, transfusion requirement
POPULATION

Inclusion Criteria Exclusion Criteria

◾ Expected to require ICU treatment for ≥3 ◾ Not identified in study
consecutive days
◾ Medical and surgical ICU patients
INTERVENTIONS

◾ Participants randomized to:

◾ Intensive glycemic control (goal 81-108 mg/dL)

◾ Conventional glycemic control (goal ≤180 mg/dL)

◾ Glycemic control occurred with IV insulin infusion

◾ Conventional glycemic control group (goal ≤180 mg/dL) was started on IV insulin infusion for glucose levels >180 and was
discontinued for blood glucose <144, when the patient was eating, or was discharged from the ICU.
Kaplan–Meier Curves Showing
Cumulative Survival of Patients
Who Received Intensive
Insulin Treatment or
Conventional Treatment in the
Intensive Care Unit (ICU).

Patients discharged alive from the ICU

(Panel A) and from the hospital (Panel B)
were considered to have survived. In both
cases, the differences between the
treatment groups were significant
(survival in ICU, nominal P=0.005 and
adjusted P<0.04; in- hospital survival,
nominal P=0.01).

Reference: NEJM Intensive Insulin

Therapy (2001)
CRITICISMS/LIMITATIONS/FUNDING

◾ Inability to blind treating personnel

◾ The intensive insulin therapy arm had more participants that happen to receive corticosteroids. This created
variability in glucose levels
◾ Insulin was given by IV infusion
◾ Study was discontinued prematurely (due to request by patient/surrogate, transition to palliative care) or by physicians
due to adverse events

FUNDING
Australian National Health and Medical Research Council
New Zealand Health Research Council
Vancouver General Hospital Foundation
Canadian Intensive Care Foundation
Canadian Diabetes Association
BOTTOM LINE

◾ Intensive glycemic control (target 81-108

mg/dL) increased deaths compared to
Glucose Goal:140-180 conventional control (target≤180) in ICU
patients: therefore, it can be concluded that a
blood sugar of <180 resulted in lower mortality
than a target 81-108.
DISCUSSION QUESTIONS

◾ In the NICE-TRIAL, what is the optimal target for glucose therapy?

◾ Can this data be extrapolated to inpatient medicine wards (in non-critically ill patients)?
DISCUSSION QUESTIONS

◾ In the NICE-TRIAL, what is the optimal target for glucose therapy?

◾ ANSWER: <180

◾ Can this data be extrapolated to inpatient medicine wards (in non-critically ill patients)?
◾ ANSWER: It depends!

◾ In non-critically ill patients, goal MORNING glucose can be <140 ONLY IF this can be safely achieved
BOARD-LIKE QUESTION

75 yo F is evaluated in the hospital for hip fracture. She has QUESTIO

a history of DM2. N
Which is the most appropriate preoperative diabetic
Patient takes Atorvastatin, Metformin BID, Insulin management for this patient?
Glargine 20 units qHS, Insulin Lispro 5 units qAC.
A. Discontinue Lispro. Start NPH because it is shorter
Her average blood glucose level in the morning is 120 mg/dL. acting than Lantus.
It is Sunday night, and your hospital does not do hip fracture
repairs. Patient is scheduled to be transferred to neighboring B. Stop insulin glargine and insulin lispro, start IV
county hospital on Monday morning. insulin infusion

Laboratory is significant for HgA1c 7.9% and a plasma C. Discontinue Glargine/Lispro. Continue Metformin
glucose of 210 mg/dL. and add sliding scale.
D. Administer insulin glargine, but hold insulin lispro
ADAPTED from MKSAP 17
BOARD-LIKE QUESTION

ANSWE
R
Which is the most appropriate preoperative
Educational Objective:
diabetic management for this patient?
Managing DM2 medications in the preoperative A. Discontinue Lispro. Start NPH because it
setting
is
Key Point: shorter acting than Lantus.
You should continue long-acting insulin while B. Stop insulin glargine and insulin lispro, start IV
withhold shorting acting insulin during fasting insulin infusion
prior to surgical intervention.
C. Discontinue Glargine/Lispro. Continue
Oral hypoglycemic are usually held in the Metformin and add sliding scale.
inpatient
D. lispro
Administer insulin glargine, but hold insulin
setting
REFERENCES

◾ "Intensive versus Conventional Glucose Control in Critically Ill Patients." New England Journal of
Medicine 360.13 (2009): 1283-297
◾ Brain, LLC Peripheral. "NICE-SUGAR." NICE-SUGAR - Wiki Journal Club. N.p.,

◾ n.d.
Cheung, MD Andrew. "The NICE-SUGAR trial: Intensive glycemic control harmful in the ICU [Classics
Series]." 2 Minute Medicine. N.p., 03 Oct. 2014