contrÔle perioperatoire de la glycemie jean-charles preiser philippe devos soins intensifs...
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CONTRÔLE PERIOPERATOIRE CONTRÔLE PERIOPERATOIRE DE LA GLYCEMIEDE LA GLYCEMIE
Jean-Charles PreiserJean-Charles PreiserPhilippe DevosPhilippe Devos
Soins Intensifs GénérauxSoins Intensifs GénérauxC.H.U. Sart Tilman – LiègeC.H.U. Sart Tilman – Liège
SAC SAC CharleroiCharleroi
7 novembre 20067 novembre 2006
AU PROGRAMME…AU PROGRAMME…
INSULINO-RESISTANCE POST- INSULINO-RESISTANCE POST- OPERATOIRE OPERATOIRE
PROGRAMME ERASPROGRAMME ERAS EFFETS CLINIQUESEFFETS CLINIQUES CONTRÔLE DE LA GLYCEMIE AUX CONTRÔLE DE LA GLYCEMIE AUX
SOINS INTENSIFSSOINS INTENSIFS
LENGTH OF STAYLENGTH OF STAY
LENGTH OF STAYLENGTH OF STAY
TYPETYPESURGERYSURGERY
BLOODBLOODLOSSESLOSSES
LENGTH OF STAYLENGTH OF STAY
TYPETYPESURGERYSURGERY
BLOODBLOODLOSSESLOSSES
LENGTH OF STAYLENGTH OF STAY
INSULIN INSULIN RESISTANCERESISTANCE
TYPETYPESURGERYSURGERY
LENGTH OF STAYLENGTH OF STAY
INSULIN INSULIN RESISTANCERESISTANCE
AU PROGRAMME…AU PROGRAMME…
INSULINO-RESISTANCE POST- INSULINO-RESISTANCE POST- OPERATOIRE OPERATOIRE
PROGRAMME ERASPROGRAMME ERAS EFFETS CLINIQUESEFFETS CLINIQUES CONTRÔLE DE LA GLYCEMIE AUX CONTRÔLE DE LA GLYCEMIE AUX
SOINS INTENSIFSSOINS INTENSIFS
Stress opératoireStress opératoire
Allongement durée d’hospitalisation (LOS)Allongement durée d’hospitalisation (LOS)
Hormones de stress/Cytokines proinflammatoiresHormones de stress/Cytokines proinflammatoires
Résistance à l’insulineRésistance à l’insuline
RELATIVE INSULIN SENSITIVITY RELATIVE INSULIN SENSITIVITY RELATED TO THE TYPE OF SURGERYRELATED TO THE TYPE OF SURGERY
Thorell A et al, Curr Opin Clin Nutr Metab Care 1999; 2: 69Thorell A et al, Curr Opin Clin Nutr Metab Care 1999; 2: 69
0
50
100
Per
cen
t (%
)
muscles
glucoseglucose
cerveau
acides grasacides gras
érythrocytes
LymphocytesG.Blancs
intestin
glutamine
foiefoie
TissusTissusagressésagressés
lactatelactate
Adaptations métaboliques à l’agression
Insulino-résistance
alaninealanine
adipocytes
glycéroll
Insulino-résistance
InsulinoInsulinoindépendanceindépendance
POSTOP vs DIABETES IIPOSTOP vs DIABETES IICarbohydrate MetabolismCarbohydrate Metabolism
PostopPostop Type II diabetesType II diabetes
HyperglycemiaHyperglycemia ++ ++
Insulin sensitivityInsulin sensitivity -- --
Glucose productionGlucose production ++ ++
GLUT4 translocationGLUT4 translocation -- --
Glycogen formationGlycogen formation -- --
Ljunqgvist Clin Nutr 2001Ljunqgvist Clin Nutr 2001
LIVER gluconeogenesis,from amino acids, lactateand glycerol glycogenolysis
INSULIN-DEPENDENT TISSUES
- SKELETAL MUSCLE, MYOCARDIUM
- ADIPOSE TISSUE
- LIVER
insulin dependentglucose uptake
glycolysis
glycerol synthesis from trigycerides hydrolysis
lactate and alanine synthesis (not in liver)
NON-INSULIN
DEPENDENT TISSUES
(all other tissues including
brain, kidney, immune system, etc.)
glucose uptake
glucose oxidation
plasma glucose
KIDNEY
gluconeogenesis
futilecycles
alanine lactate glycerol
CHO METABOLISM DURING STRESSCHO METABOLISM DURING STRESSBiolo et al Intensive Care Med 2002:28:1512Biolo et al Intensive Care Med 2002:28:1512
TIME COURSE OF INSULIN TIME COURSE OF INSULIN RESISTANCERESISTANCE
Thorell Curr Opin Clin Nutr Metab Care 1999Thorell Curr Opin Clin Nutr Metab Care 1999
0
20
40
60
80
100
120
0 1 6 10 20
Time (days)
Insu
lin s
ensi
tivi
ty (
%)
WHO IS RESPONSIBLE?WHO IS RESPONSIBLE?
Hormones (« counter-regulatory »)Hormones (« counter-regulatory ») GlucagonGlucagon Steroïds Steroïds GHGH Catecholamines Catecholamines
Inflammatory mediatorsInflammatory mediators : : TNF, IL1, IL6,…TNF, IL1, IL6,…
Insulin (receptor)-mediated feedback mechanismsInsulin (receptor)-mediated feedback mechanisms
INSULIN RESISTANCEINSULIN RESISTANCE
Is not beneficialIs not beneficial Should be treated or avoidedShould be treated or avoided Can be decreased by epidural Can be decreased by epidural
analgesia and preoperative CHOanalgesia and preoperative CHO Allows normoglycemia during feedingAllows normoglycemia during feeding Decreases postoperative morbidityDecreases postoperative morbidity
AU PROGRAMME…AU PROGRAMME…
INSULINO-RESISTANCE POST- INSULINO-RESISTANCE POST- OPERATOIRE OPERATOIRE
PROGRAMME ERASPROGRAMME ERAS EFFETS CLINIQUESEFFETS CLINIQUES CONTRÔLE DE LA GLYCEMIE AUX CONTRÔLE DE LA GLYCEMIE AUX
SOINS INTENSIFSSOINS INTENSIFS
ERAS
Enhanced Recovery After colorectal SurgeryEnhanced Recovery After colorectal Surgery
apport oral glucides préopapport oral glucides préop
analgésie épiduraleanalgésie épidurale
mobilisation préopératoire précocemobilisation préopératoire précoce
=> réduction durée d’hospitalisation (LOS)=> réduction durée d’hospitalisation (LOS)
ERAS
Glucides préopGlucides préop
solution orale (12.5%) solution orale (12.5%)
800 ml la veille à minuit et 400 ml 2-3h avant chirurgie800 ml la veille à minuit et 400 ml 2-3h avant chirurgie
Réduction résistance à l’insulineRéduction résistance à l’insulineAmélioration de la balance azotéeAmélioration de la balance azotée
Réduction de l’anxiété préopRéduction de l’anxiété préop
Réduction nausée et vomissements postopRéduction nausée et vomissements postop
Amélioration du bien-être postopAmélioration du bien-être postop
Réduction durée hospitalisationRéduction durée hospitalisationHausel J. et al.Hausel J. et al.
EFFECTS OF PREOP CHOEFFECTS OF PREOP CHONygren Curr Opin Clin Nutr Metab Care 2001Nygren Curr Opin Clin Nutr Metab Care 2001
-60
-50
-40
-30
-20
-10
0
10
20
Insulin resistance (%
change from preop)
Cholecystectomy Colorectal Arthroplasty
Preop CHO
No preop CHO
PREOPERATIVE CHOPREOPERATIVE CHO
20% glucose IV20% glucose IV 12.5 % CARBOHYDRATE DRINK12.5 % CARBOHYDRATE DRINK
800 at midnight + 400 ml 2-3 hrs prior to 800 at midnight + 400 ml 2-3 hrs prior to surgery (295 mOsm/l)surgery (295 mOsm/l)
GASTRIC EMPTYING??GASTRIC EMPTYING??
EFFECTS OF CHO ON GASTRIC EFFECTS OF CHO ON GASTRIC VOLUME AND pHVOLUME AND pH
Hausel Anesth Analg 2001Hausel Anesth Analg 2001
TreatmentTreatment Gastric volume Gastric volume (ml) - IQR(ml) - IQR
Acidity (pH)Acidity (pH)
IQRIQR
Overnight fast Overnight fast (n=89)(n=89)
6-41 6-41 1.6-4.01.6-4.0
Placebo (n=86)Placebo (n=86) 12-3512-35 1.6-2.51.6-2.5
CHO 12.5 % CHO 12.5 % (n=80)(n=80)
7-417-41 1.6-2.71.6-2.7
ERAS
POSTOPERATIVE INSULIN RESISTANCEPOSTOPERATIVE INSULIN RESISTANCE
Is not beneficialIs not beneficial
Should be treated or avoidedShould be treated or avoided
Can be decreased by epidural analgesia and Can be decreased by epidural analgesia and preoperative CHOpreoperative CHO
Allows normoglycemia during Allows normoglycemia during feedingfeeding
Decreases postoperative morbidityDecreases postoperative morbidity
Hausel J. et al.Hausel J. et al.
INSULIN RESISTANCEINSULIN RESISTANCE
Is not beneficialIs not beneficial Should be treated or avoidedShould be treated or avoided Can be decreased by epidural Can be decreased by epidural
analgesia and preoperative CHOanalgesia and preoperative CHO Allows normoglycemia during feedingAllows normoglycemia during feeding Decreases postoperative morbidityDecreases postoperative morbidity
AU PROGRAMME…AU PROGRAMME…
INSULINO-RESISTANCE POST- INSULINO-RESISTANCE POST- OPERATOIRE OPERATOIRE
PROGRAMME ERASPROGRAMME ERAS EFFETS CLINIQUESEFFETS CLINIQUES CONTRÔLE DE LA GLYCEMIE AUX CONTRÔLE DE LA GLYCEMIE AUX
SOINS INTENSIFSSOINS INTENSIFS
AU PROGRAMME…AU PROGRAMME…
INSULINO-RESISTANCE POST- INSULINO-RESISTANCE POST- OPERATOIRE OPERATOIRE
PROGRAMME ERASPROGRAMME ERAS EFFETS CLINIQUESEFFETS CLINIQUES CONTRÔLE DE LA GLYCEMIE AUX CONTRÔLE DE LA GLYCEMIE AUX
SOINS INTENSIFSSOINS INTENSIFS
TIGHT GLYCAEMIA CONTROL:TIGHT GLYCAEMIA CONTROL:The dream comes trueThe dream comes true
BenefitsBenefits•Reduces complication Reduces complication raterate•Reduces mortalityReduces mortality•Decreases LOSDecreases LOS•CheapCheap•Easily accessibleEasily accessible
Risks /constraintsRisks /constraints•HypoglycemiaHypoglycemia•EquipmentEquipment•Human resourcesHuman resources
GLUCOSE CONTROL AND MORTALITY GLUCOSE CONTROL AND MORTALITY IN CRITICALLY ILL PATIENTSIN CRITICALLY ILL PATIENTS
Finney JAMA 2003;290:2041Finney JAMA 2003;290:2041
530 patients : cardiothoracic surgery (90%)530 patients : cardiothoracic surgery (90%) Ranges of glycemia : Ranges of glycemia :
0.8-1.10.8-1.1 1.1-1.41.1-1.4 1.4-1.81.4-1.8 1.8-2.01.8-2.0 >2.0>2.0
Decreased mortality when glycemia < 1.4 g/lDecreased mortality when glycemia < 1.4 g/l « Control of glucose levels rather than of absolute levels « Control of glucose levels rather than of absolute levels
of exogenous insulin appear to account for the mortality of exogenous insulin appear to account for the mortality benefit with intensive insulin therapy » benefit with intensive insulin therapy »
CONSTRAINTS AND RISKS OF CONSTRAINTS AND RISKS OF TIGHT GLUCOSE CONTROLTIGHT GLUCOSE CONTROL
ConstraintsConstraints Frequent checksFrequent checks
CostCost TimeTime
NursesNurses ExamsExams
EquippmentEquippment GlucometersGlucometers Automated syringesAutomated syringes
RisksRisks HypoglycemiaHypoglycemia
Often asymptomatic Often asymptomatic (altered mental status)(altered mental status)
Neurological symptomsNeurological symptoms Adrenergic Adrenergic
manifestationsmanifestations
THE REAL LIFE (2003)THE REAL LIFE (2003)
Glycaemia Threshold IC Units
110 mg/dL 3
120 mg/dL 5
150 mg/dL 19
180 mg/dL 5
200 mg/dL 4
02468
101214161820
# ce
ntr
es
110 120 150 180 200
Glycaemia threshold (mg/dL)Survey on European ICUs in 2003Survey on European ICUs in 2003
GLUCONTROL STUDY - Ph. Devos ESICM 2005GLUCONTROL STUDY - Ph. Devos ESICM 2005
ANZICS survey ANZICS survey 29 hospitals29 hospitals
IssueIssue FrequencyFrequency
IIT protocol for every ptIIT protocol for every pt
IIT protocol in selected ptsIIT protocol in selected pts
10 %10 %
31% (ICU >3d – sepsis - surgery)31% (ICU >3d – sepsis - surgery)
At least Once blood glucose > 6.1 mMAt least Once blood glucose > 6.1 mM
At least once Blood glucose > 11.1 At least once Blood glucose > 11.1 mMmM
91.7 %91.7 %
36.2 %36.2 %
Insulin therapyInsulin therapy 31.1%31.1%
Trigger to start insulinTrigger to start insulin 11.5 mM (9.4-14.0)11.5 mM (9.4-14.0)
Survivors (90%)Survivors (90%)
vs nonsurvivorsvs nonsurvivors
Max BG 9.5 mM Insulin - 8.3%Max BG 9.5 mM Insulin - 8.3%
Max BG 12.0 mM Insulin - 14.3%Max BG 12.0 mM Insulin - 14.3%
D Angus – Ed Abraham AJRCCM 2005 DecD Angus – Ed Abraham AJRCCM 2005 Dec
CURRENT MULTI-CENTRE STUDIES ON CURRENT MULTI-CENTRE STUDIES ON
TIGHT GLUCOSE CONTROL IN ICUSTIGHT GLUCOSE CONTROL IN ICUS DesignDesign PrimPrim
End-ptEnd-pt
Nb ptsNb pts
requiredrequired
Nb hospNb hosp CurrentCurrent
statusstatus
VISEPVISEP 2x22x2
Random Random fluid + BGfluid + BG
MortalityMortality 600600 1717 StoppedStopped
GlucontrolGlucontrol Open labelOpen label
Random/ctrlRandom/ctrl
Stratified Stratified
ICU ICU mortalitymortality
28942894 2424 StoppedStopped
NICE-NICE-SugarSugar
Open labelOpen label
Random/ctrlRandom/ctrl
StratifiedStratified
90-d 90-d mortalitymortality
45004500 2323 OngoingOngoing
TIGHT GLYCAEMIA CONTROL:TIGHT GLYCAEMIA CONTROL:Does the dream come true orDoes the dream come true or
time to wake up? time to wake up?
BenefitsBenefits•Reduces complication Reduces complication rate ?rate ?•Reduces mortality?Reduces mortality?•Decreases LOS?Decreases LOS?•CheapCheap•Easily accessibleEasily accessible
Risks - costsRisks - costs•HypoglycemiaHypoglycemia•EquippmentEquippment•Human resourcesHuman resources
REASONS FOR REASONS FOR DISCONTINUATIONDISCONTINUATION
VISEPVISEP (March 2005 – 488 patients) (March 2005 – 488 patients) Unacceptably high rate of hypoglycemiaUnacceptably high rate of hypoglycemia No beneficial effect on outcomeNo beneficial effect on outcome
VISEP STUDY VISEP STUDY 488 patients in 17 centres488 patients in 17 centres
28-d mort 90-d mort Rate hypo
IIT
CIT
GLUCONTRGLUCONTROLOL
A Multi-Centre Study Comparing the A Multi-Centre Study Comparing the Effects of Two Glucose Control Effects of Two Glucose Control Regimens by Insulin in Intensive Regimens by Insulin in Intensive Care Unit PatientsCare Unit Patients
SAMPLE SIZESAMPLE SIZE
Expected outcomeExpected outcome (considering a baseline (considering a baseline ICU mortality of 20%) ICU mortality of 20%) 4% decrease of absolute ICU mortality (20% 4% decrease of absolute ICU mortality (20%
relative)relative) Power 80%Power 80% 1447 patients /group (total 2894) required (initial 1447 patients /group (total 2894) required (initial
estimate)estimate)
GLUCONTROGLUCONTROLL Prospective, randomised, controlled, Prospective, randomised, controlled,
investigator-blinded and multicentric studyinvestigator-blinded and multicentric study Aimed at comparing the effects of two Aimed at comparing the effects of two
regimens of insulin therapy, respectively regimens of insulin therapy, respectively titrated to achieve a blood sugar level titrated to achieve a blood sugar level between 4.4 and 6.1 mmol/l (80 and 110 mg/dl, between 4.4 and 6.1 mmol/l (80 and 110 mg/dl,
respectively) = respectively) = GROUP AGROUP A and between 7.8 and 10.0 mmol/l (140 and 180 mg/dl, and between 7.8 and 10.0 mmol/l (140 and 180 mg/dl,
respectively) = respectively) = GROUP BGROUP B
GLUCONTROGLUCONTROLL Primary Outcome : absolute intensive care unit Primary Outcome : absolute intensive care unit
(ICU) mortality (target = 4%-decrease).(ICU) mortality (target = 4%-decrease). Secondary outcome variables : Secondary outcome variables :
in-hospital and 28-day mortality, in-hospital and 28-day mortality, lengths of stays in ICU and in the hospital, lengths of stays in ICU and in the hospital, length of ICU stay without life-support therapy, length of ICU stay without life-support therapy,
number and clinical signs of episodes of number and clinical signs of episodes of hypoglycaemia, hypoglycaemia,
rates of infections and organ failures, rates of infections and organ failures, number of red-cells transfusions.number of red-cells transfusions.
Inclusion criteriaInclusion criteria 18 years or older18 years or older admitted in an ICUadmitted in an ICU
Exclusion criterionExclusion criterion Absence of signed informed consentAbsence of signed informed consent
GLUCONTRGLUCONTROLOL
GLUCONTROGLUCONTROLL
Planning :Planning : Interim analysis each 100 ICU deathsInterim analysis each 100 ICU deaths In order to detect a 4% decrease of absolute mortality In order to detect a 4% decrease of absolute mortality
3500 patients to be included3500 patients to be included
GLUCONTROGLUCONTROLL
7 countries7 countries Austria, Belgium, France, Israel, The Austria, Belgium, France, Israel, The
Netherlands, Slovenia and Spain.Netherlands, Slovenia and Spain.
21 units in 19 centres21 units in 19 centres
GLUCONTROGLUCONTROLL
Planning :Planning : Interim analysis each 100 ICU deathsInterim analysis each 100 ICU deaths In order to detect a 4% decrease of absolute mortality In order to detect a 4% decrease of absolute mortality
3500 patients to be included3500 patients to be included
STUDY STOPPED ON MAY 29th, 2006STUDY STOPPED ON MAY 29th, 2006 Safety concernSafety concern High rate of unintended protocol violations High rate of unintended protocol violations
1108 recruited patients1108 recruited patients1099 randomized patients1099 randomized patientsPatients available for the Patients available for the
analysis: analysis: n = 1091 n = 1091 Group A: 538 patientsGroup A: 538 patientsGroup B: 553 patientsGroup B: 553 patients
Length of observation: Length of observation: from 1 to 56 days (median: 5; IQR: 3 – 10)from 1 to 56 days (median: 5; IQR: 3 – 10)
GLUCONTROLGLUCONTROL
0
20
40
60
80
100
120
140
160
180
1 2 3 4 5 6 7 8 9 1011 12 13 14 15 16 17 1819 20 21
Unit
Nu
mb
er
of
pati
en
ts
1091 patients
GLUCONTROGLUCONTROLL
0.69960.69965.0 (3.0 – 10.5)5.0 (3.0 – 10.5)5.0 (3.0 – 10.0)5.0 (3.0 – 10.0)ICU LOS, dayICU LOS, day
0.69590.69594.0 %4.0 %3.5 %3.5 %ReadmissionReadmission
0.99850.998541.3 %41.3 %
32.8 %32.8 %
18.4 %18.4 %
8.1 %8.1 %
41.6 %41.6 %
31.8 %31.8 %
18.6 %18.6 %
8.0 %8.0 %
CategoryCategory
Medical Medical
Scheduled SurgeryScheduled Surgery
Emergency SurgeryEmergency Surgery
Trauma Trauma
0.8320.832342/208342/208336/199336/199Sex ratio, M/FSex ratio, M/F
0.9840.98465 (51 – 74)65 (51 – 74)65 (51-74)65 (51-74)Age, yrAge, yr
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Median (IQR)
GLUCONTROLGLUCONTROL
10 20 30 40 50 60 70 80 90 100
Age, yr
Group A
140
120
100
80
60
40
20
0
Frequency
10 20 30 40 50 60 70 80 90 100
Age, yr
Group B160
140
120
100
80
60
40
20
0
Frequency
GLUCONTROGLUCONTROLL
Group AGroup A
(n = 538)(n = 538)Group BGroup B
(n = 553)(n = 553) PP
SubCategorySubCategory
TraumaTrauma
NeurologicalNeurological
GastroenterologicalGastroenterological
OrthopaedicOrthopaedic
RenalRenal
CardiacCardiac
RespiratoryRespiratory
VascularVascular
HematologicalHematological
OtherOther
5.9 %5.9 %
15.1 %15.1 %
18.1 %18.1 %
1.2 %1.2 %
2.2 %2.2 %
34.0 %34.0 %
18.9 %18.9 %
1.6 %1.6 %
0.4 %0.4 %
2.8 %2.8 %
6.1 %6.1 %
13.3 %13.3 %
14.7 %14.7 %
0.6 %0.6 %
2.7 %2.7 %
34.5 %34.5 %
18.9 %18.9 %
3.4 %3.4 %
0.8 %0.8 %
5.1 %5.1 %
0.23040.2304
GLUCONTROLGLUCONTROL
Group AGroup A
(n = 538)(n = 538)Group BGroup B
(n = 553)(n = 553) PP
APACHE II scoreAPACHE II score 20 (15 - 25)20 (15 - 25) 20 (15 – 26)20 (15 – 26) 0.7280.728
SOFA scoreSOFA score 7 (5 – 9)7 (5 – 9) 7 (5 – 9)7 (5 – 9) 0.6050.605
Preexisting Diabetes:Preexisting Diabetes:
Type of diabetes: Type of diabetes:
Insulin- dependent Insulin- dependent
Non insulin-Non insulin-dependentdependent
HbA1c:HbA1c:
> 6.5 % > 6.5 %
16.4 %16.4 %
34.4 %34.4 %
65.6 %65.6 %
16.3 %16.3 %
23.7 %23.7 %
28.0 %28.0 %
72.0 %72.0 %
25.1 %25.1 %
0.00560.0056
0.39460.3946
0.05350.0535
GCSGCS 15 (8 -15)15 (8 -15) 15 (9 – 15)15 (9 – 15) 0.7740.774
Median (IQR)
GLUCONTROLGLUCONTROL
300
250
200
150
100
50
Group A Group B
p < 0.0001
GLUCONTRGLUCONTROLOL
118 (109-131)118 (109-131) 144 (127-163) 144 (127-163)
Number of glycemia/patients: From 2 to 856 measures (median: 33; IQR: 14 - 85)Number of glycemia/patients: From 2 to 856 measures (median: 33; IQR: 14 - 85)
Blo
od
glu
cose
, m
g/d
l
80
90
100
110
120
130
140
150
160
170
180
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Treatment, days
Group A
Group B
Median with IQR
* * * * * * * * **
* * * * *
* p < 0.001
GLUCONTROGLUCONTROLL
Blo
od
glu
cose
, m
g/d
l
80
90
100
110
120
130
140
150
160
170
180
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Treatment, days
Group A
Group B
Median with IQR
* * * * * * * * **
* * * * *
* p < 0.001
GLUCONTROGLUCONTROLL
Blo
od
glu
cose
, m
g/d
l
80
90
100
110
120
130
140
150
160
170
180
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Treatment, days
Blo
od
glu
cose
, m
g/d
l
Group A
Group B
Median with IQR
* * * * * * * * **
* * * * *
* p < 0.001
GLUCONTROGLUCONTROLL
160
140
120
100
80
60
40
20
0
Variability of blood glucose
Group A Group BSD
of
blo
od
glu
cose
, m
g/d
l
p NS
GLUCONTROGLUCONTROLL
50 100 150 200 250 300
Blood glucose (integrated), mg/dl
300
250
200
150
100
50
Blo
od g
luco
se (
ari
thm
eti
c m
ean),
mg/d
lY = 4.14 + 0.98 X r² = 0.928
GLUCONTROGLUCONTROLL
< 0.0001< 0.00012 (0 – 5)2 (0 – 5)0 (0 – 1)0 (0 – 1)Insulin free days, Insulin free days, daysdays
< 0.0001< 0.00010.4 (0.0 – 0.4 (0.0 – 1.4)1.4)
1.8 (1.0 – 1.8 (1.0 – 2.9)2.9)
Insulin rate, U/hrInsulin rate, U/hr
<0.0001<0.000157.757.784.684.6Patients treated by Patients treated by insulin IV (ITT), %insulin IV (ITT), %
<0.0001<0.000166.966.996.896.8Patients treated by Patients treated by insulin IV (PP), %insulin IV (PP), %
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Median (IQR)
GLUCONTROGLUCONTROLL
Group A
INS
ULI
N F
RE
E D
AYS
, d
ays
Group B
15
10
5
0
p < 0.0001
GLUCONTROGLUCONTROLL
Median with IQR
Median (IQR)
GLUCONTROGLUCONTROLL
< 0.0001< 0.00012.7 %2.7 %9.8 %9.8 %Patients with Patients with hypoglycemia < 40, %hypoglycemia < 40, %
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Multivariable analysis: hypoglycemia < 60 mg/dlMultivariable analysis: hypoglycemia < 60 mg/dl
Adjusted ORAdjusted OR 95 % CI95 % CI pp
Group AGroup A
DeathDeath
Apache IIApache II
7.007.00
2.082.08
1.071.07
4.85 - 10.114.85 - 10.11
1.28 – 3.381.28 – 3.38
1.04 – 1.091.04 – 1.09
0.00010.0001
0.00310.0031
0.00010.0001
Multivariable analysis: hypoglycemia < 40 mg/dlMultivariable analysis: hypoglycemia < 40 mg/dl
Adjusted ORAdjusted OR 95 % CI95 % CI pp
Group AGroup A
DeathDeath
Apache IIApache II
3.683.68
2.592.59
1.071.07
1.95 – 6.951.95 – 6.95
1.34 – 5.031.34 – 5.03
1.03 – 1.111.03 – 1.11
0.00010.0001
0.0480.048
0.00060.0006
GLUCONTROGLUCONTROLL
0.700.705 (3-11)5 (3-11)5 (3-10)5 (3-10)ICU LOS, daysICU LOS, days
0.190.199.769.7612.2712.27Mortality rate, %Mortality rate, %
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Median (IQR)
GLUCONTROGLUCONTROLL
0.190.199.769.7612.2712.27Mortality rate, %Mortality rate, %
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Median (IQR)
GLUCONTROGLUCONTROLL
0
2
4
6
8
10
12
14
16
0 100 200 300 400 500 600 700 800 900 1000 1100 1200
Number of inclusions
Cum
ula
tive D
eath
rate
, %
Group A Group B
GLUCONTROGLUCONTROLL
0.00020.000211.6 %11.6 %18.3 %18.3 %Death among patients Death among patients
with Hypoglycemia < with Hypoglycemia < 40, %40, %
0.1860.1869.769.7612.2712.27Mortality rate, %Mortality rate, %
PPGroup BGroup B
(n = 553)(n = 553)Group AGroup A
(n = 538)(n = 538)
Median (IQR)
GLUCONTROGLUCONTROLL
Univariable analysisUnivariable analysis
Crude ORCrude OR 95 % CI95 % CI pp
Group AGroup A 1.281.28 0.88 - 1.880.88 - 1.88 0.1980.198
Multivariable analysisMultivariable analysis
Adjusted ORAdjusted OR 95 % CI95 % CI pp
Group AGroup A
Gender (male)Gender (male)
Age, yrAge, yr
Apache IIApache II
SOFASOFA
1.311.31
1.781.78
1.021.02
1.041.04
1.081.08
0.88 – 1.950.88 – 1.95
1.15 - 2.751.15 - 2.75
1.01 – 1.041.01 – 1.04
1.02 – 1.071.02 – 1.07
1.01 – 1.161.01 – 1.16
0.1780.178
0.00930.0093
0.00110.0011
0.00030.0003
0.02910.0291
GLUCONTROGLUCONTROLL
RISK OF DEATHRISK OF DEATH
Non diabetic patients: 855Non diabetic patients: 855Diabetic patients: 236Diabetic patients: 236
Type I : 64Type I : 64Type II: 144Type II: 144Unsuspected (HbA1c > 6.5 %): 28Unsuspected (HbA1c > 6.5 %): 28
GLUCONTROGLUCONTROLL
Group AGroup A
(n = 538)(n = 538)Group BGroup B
(n = 553)(n = 553) PP
Previous Diabetes:Previous Diabetes:
Type of diabetes: Type of diabetes:
Insulinodependent Insulinodependent
Non Non InsulinodependentInsulinodependent
Unsuspected prior Unsuspected prior
admission admission
with HbA1c > 6.5 %with HbA1c > 6.5 %
HbA1c:HbA1c:
> 6.5 % > 6.5 %
19.0 %19.0 %
5.8 %5.8 %
11.0 %11.0 %
2.2 %2.2 %
16.3 %16.3 %
24.2 %24.2 %
6.0 %6.0 %
15.4 %15.4 %
2.9 %2.9 %
25.1 %25.1 %
0.04120.0412
0.60410.6041
0.05350.0535
GLUCONTROGLUCONTROLL
Group AGroup A Group BGroup B PP
Non diabetic patients Non diabetic patients
855 patients:855 patients:
Deaths Deaths
Diabetic patientsDiabetic patients
236 patients 236 patients
DeathsDeaths
436436
12.6 %12.6 %
102102
10.8 %10.8 %
419419
10.3 %10.3 %
134134
8.21 %8.21 %
0.2810.281
0.5000.500
GLUCONTROGLUCONTROLL
TIGHT GLYCAEMIA CONTROL:TIGHT GLYCAEMIA CONTROL:
RisksRisks
BenefitsBenefits
TIGHT GLUCOSE CONTROL WITH TIGHT GLUCOSE CONTROL WITH INTENSIVE INSULIN THERAPYINTENSIVE INSULIN THERAPY
Hazards ofhyperglycemia Risks of
hypoglycemia
Being funambulist may not be accessible to everyone