Document

Report
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

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