Date post: | 11-Jan-2016 |
Category: |
Documents |
Upload: | blaise-tate |
View: | 218 times |
Download: | 0 times |
• Mr PS• 76 years old• COPD, no DM• Severe CAP• Day 1- intubated, sedated, high o2
requirements, vasopressor dependent• Starting early EN• Glucose 11.1 mmol/L (200 mg/dl)
What would you do?
A.Start insulin infusion and titrate glucose to 4.4- 6.1 mmol/l
B.Start insulin infusion and titrate infusion to 7-9 mmol/l
C.Watchful waiting
D.Don’t Know
E.Don’t care
The Intensive Insulin Therapy Bandwagon
• Endorsed by National and International societies• Recommend by clinical practice guidelines• Standards for hospital accreditation• Part of Institute for Healthcare Improvement and
other quality improvement campaign
What happened?
• Clearly a difference in outcome
• High mortality rate in control group?
• Repeatability?
• Interpretation of findings?
• Generalizability of findings?
TIGHT GLYCEMIC CONTROL
Van den Berge NEJM 2001;345:1359
Canadian Recommendations
Enteral vs. Parenteral Nutrition • Based on one level 1 and 12 level 2 studies, when considering nutrition support for critically ill patients, we strongly recommend the use of Enteral Nutrition over Parenteral Nutrition.
www.criticalcarenutrition.com
Canadian Recommendations
Combined EN and PN • Based on 5 level 2 studies, for critically ill
patients starting on enteral nutrition we recommend that parenteral nutrition not be started at the same time as enteral nutrition.
www.criticalcarenutrition.com
ASPEN/SCCM ICU Nutrition CPGs
• If unable to meet energy requirements after 7-10 days by the enteral route, consider initiating PN.
• Initiating PN prior to this 7-10 day period does not improve outcome and may be detrimental to the patient.
McClave JPEN 2009;33:277
Supplemental PN
• In the patient who was previously healthy prior to critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization (when EN is not available).
PN vs Standard Care
• “If blood glucose is 40-60 mg/dl, stop the insulin infusion, assure adequate baseline glucose intake, and check the blood glucose level within the next hour.”
• “If blood glucose approaches the normal range, reduce insulin by 25-50.”
Reproducibility of the Original Protocol?
• Hypoglycemia rates higher in ITT: 18.7% vs 3.1%Mortality
• Single center• 1200 MICU patients• Same protocol• Control: 180-215 mg/dl• ITT Group: 80-110 mg/dl• Predominantly PN fed
Intensive Insulin Therapy and Pentastarch Resuscitation in Severe
Sepsis
• Hypoglycemia rates higher in ITT: 12.1% vs 2.1%
0
5
10
15
20
25
30
35
40
28 day 90 day
TightControl
Mortality
Brunkhorst NEJM 2008;358:125
• 18 ICUs in Germany (SepNet)
• Control: <180 mg/dl• ITT Group: 80-110 mg/dl• Predominantly enteral fed• 50% surgery• Suspended prematurely
because of higher rate of hypoglycemia
A prospective multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units:
The GLUCONTROL study
Preiser JC Intensive Care Med 2009
Mortality
• Hypoglycemia rates higher in ITT: 8.7% vs 2.7%, p<0.001
• 21 ICUs across Europe• Control: 7.8 -10.0 mmol/L• ITT group: 4.4-6.1 mmol/L• Trials suspended early
because of protocol violations
• 1,101 patients randomized• 60% surgical/40% medical
NICE – SUGAR Study• Aim
– to compare the effects of the two blood glucose targets on 90 day all-cause mortality
• Hypothesis– The hypothesis is that there is no difference in the relative
risk of death between patients assigned a glucose range of 4.5 - 6.0 mmol/L (81 – 108 mg/dl) and those assigned a glucose range of 10.0 mmol/L or less (180mg/dL or less)
Inclusion Criteria
• ICU treatment that extends beyond the calendar day after the day of admission (i.e. on three consecutive days).
• Arterial catheter in situ (or imminent)
• Consent has been / will be obtained
Maximal Generalizability
© The NICE SUGAR Study Investigators 2009
Severe hypoglycaemia(≤2.2mmol/L: ≤40mg/dL)
Intensive Glucose Control
Conventional Glucose Control
Odds ratio
(95% CI)
Patients206/3016
6.8%
15/3014
0.5%
14.7
(9.0 – 25.9)P <0.001
All reported and investigated as SAEsNo long term sequelae reported
© The NICE SUGAR Study Investigators 2009
Outcomes: Mortality
Intensive Glucose Control
Conventional Glucose Control
Odds ratio
(95% CI)
Dead at 28 days670/3010
22.3%
627/3012
20.8%
1.09
(0.96 - 1.23)P = 0.17
Dead at 90 days829/3010
27.5%
751/3012
24.9%
1.14
(1.02 - 1.28)P = 0.02
Adjusted mortality at 90 days
Adjusted for operative admission, geographic region, age, admission source, APACHE II score, mechanical ventilation
1.14
(1.01 - 1.29)P = 0.04
Conclusions of the Trial
• A blood glucose target of 4.5 – 6.0 mmol/L resulted in
increased mortality compared to a target of <10.0mmol/L.
• In comparison with other trials, severe hypoglycaemia was
relatively uncommon but significantly more common in those
assigned to intensive glucose control.
• On the basis of these results we do not recommend targeting
normoglycaemia in critically ill adults.
Severe Hypoglycemia (SH) in Critically Ill Patients: Risk Factors
and Outcomes• Observational study of
>5000 ICU patients• 102 had at least 1 episode
of glucose < 2.2 mmol (40 mg/dL)
• Risk Factors: diabetes, septic shock, renal failure, mechanical ventilation, APACHE score and treatment with ITT.
• SH independently associated with increased mortality
0
10
20
30
40
50
60
ICU
SHControl
Employed Case-control matching
Krinsley CCM 2007;35:2262
0.8
5.1
0
5
10
15
20
25
30
Van den Berghe,2001
Van den Berghe(ITT), 2006
VISEP, 2008 NICE-SUGAR,2009
Conventional
Intensive
3.1
18.7
p<0.001
0.5
6.8
p<0.001
4.5
17.6
p<0.001
p<0.001
%
Intensive Insulin Therapy - Rate of Hypoglycemia (<40 mg/dl) -
3.9
14.5
p<0.001
GluControl, 2006
Canadian RecommendationsIntensive Insulin Therapy
We recommend that hyperglycemia (blood sugars > 10 mmol/L) be avoided in all critically ill patients. Based on the NICE-SUGAR study and a recent meta-analysis, we recommend a blood glucose target of around 8.0 mmol/L (or 7-9 mmol/L), rather than a more stringent target range (4.4 to 6.1 mmol/L) or a more liberal target range (10 to 11.1 mmol/L).
www.criticalcarenutrition.com
Updated May 2009