Glycemic Control in Acutely Ill
Patients
Martin J. Abrahamson, MD FACP
Associate Professor of Medicine, Harvard Medical
School
Senior 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 %
Mortality Increases with Increases
in Average ICU BG
45
40
35
30
25
20
15
10
5
0
(1826 consecutive ICU patients 10/99 thru 4/02)
80-99
100119
120139
140159
160179
180199
200249
Average ICU glucose (mg/dL)
Krinsley JS: Mayo Clin Proc. 2003;78:1471-1478.
250299
>300
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
Intensive Insulin Therapy and Mortality in
Patients Admitted to SICU
• 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 in Critically Ill
Surgical Patients
Conventional
Treatment
Trigger for
starting iv
insulin
Glucose
achieved
% with glucose
< 40 mg/dL
Glucose in mg/dL
Intensive
Treatment
> 215
> 100
153 + 33
103 + 19
0.7
5
Van den Berghe et al. NEJM 2001; 345:1359-1367
Intensive Insulin Therapy in Surgical
ICU Patients Reduces Mortality
100
Intensive treatment
96
Survival
in ICU (%)
92
4.6% mortality
8% mortality
Conventional treatment
88
84
80
0
0
20
40
60
80
100 120 140 160
Days after Admission
Conventional: insulin when blood glucose > 215 mg/dL
mean BG = 153 mg/dL
Intensive: insulin when glucose > 110 mg/dL and maintained at 80-110 mg/dL
mean BG = 103 mg/dL
Van den Berghe, G. NEJM. 2001;345:1359–1367.
Intensive Insulin Therapy in Surgical ICU
Patients Reduces Morbidity and Mortality
0
Mortality
Sepsis
Dialysis
Blood
Transfusio
n
Polyneuropathy
-10
-20
Percent
Reduction -30
-40
-50
34%
41%
46%
-60
Van den Berghe, G. NEJM. 2001;345:1359–1367.
44%
50%
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
Trigger for
starting iv
insulin
Glucose
achieved
% with glucose
< 40 mg/dL
Glucose in mg/dL
Intensive
Treatment
> 215
> 100
153
111
3.1
18.7
Van den Berghe et al. NEJM 2006; 354:449-460
Intensive Insulin in the MICU Does Not
Decrease Mortality
A. Intention-to-Treat Group (n = 1,200)
– Conventional
Therapy: 40%
– Intensive Insulin
Therapy: 37.3%
In-Hospital Survival (%)
• In-hospital deaths
100
80
Intensive treatment
60
Conventional treatment
100
40
80
60
20
P = 0.33
40
First 30 days
0
0
0
NEJM 354:449, 2006
0
10 20
30
100 200 300 400 500
Days
Subgroup in ICU ≥ 3 days (n = 767)
B. Subgroup in ICU ≥3 Days (n = 767)
– Conventional
Therapy: 52.5%
– Intensive Insulin
Therapy: 43.0%
100
80
In-Hospital Survival (%)
• In-hospital deaths
Intensive treatment
60
100
Conventional treatment
40
80
60
20
P = 0.009
40
First 30 days
0
0
10
20
30
0
NEJM 354:449, 2006
0 50 100150 200250 300 350 500
Days
Effect of Intensive Insulin Therapy on
Morbidity
A
Cumulative Hazard
Weaning from Mechanical
Ventilation
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Discharge from ICU
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
P=0.03
Intensive
treatment
Conventional
treatment
0 10203040506070 8 90
0
Discharge from Hospital
5.0
P=0.04
P=0.05
4.0
3.0
2.0
1.0
0.0
0
20 40 60
8
0
0 010 200300400 50 600
0
100
Days After Admission to ICU
> 3 days in ICU (n = 767)
B
Cumulative Hazard
Weaning from Mechanical
Ventilation
3.5 P<0.001
3.0
Intensive
2.5
treatment
2.0
1.5
1.0
Conventional
0.5
treatment
0.0
0 10203040506070 8 90
0
NEJM 354:449, 2006
Discharge from ICU
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Discharge from Hospital
5.0
P=0.04
P=0.01
4.0
3.0
2.0
1.0
0
20 40 60
8 100
0
Days After Admission to ICU
0.0
0 100 200300400 50 600
0
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 someone
who 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 PAST
AND 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 Algorithm
Decision 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 / 24
For 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