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1. INSULIN THERAPY IN ICU
2. OUR VISIONTo be a globally-acknowledged centre of excellence for clinical care, education & training, and research in diabetology and endocrinology.
3. EVOLUTION OF INSULINOLOGY 1922 – DISCOVERY OF INSULIN
1993 – tight glycemic control is beneficial in T1DM – DCCT
1998 - tight glycemic control is beneficial in T2DM – UKPDS
1997-99 – GIK infusion in diabetic MI
2001 – insulin in ICU patients
4. EVOLUTION OF CRITICAL CARE 1940 – FIRST COMMERCIAL VENTILATOR [SPIROPULSATOR]
1942 – Penicillin
2001 – INSULIN in ICU patients
5. HYPERGLYCEMIA IN THE CRITICALLY ILL No clear guidelines for defining hyperglycemia in the critically ill
Wide variation in reported incidence: 3 to 71% (Capes, 2000)
6. HYPERGLYCEMIA IN THE CRITICALLY ILL Aim of treatment until recently: lower blood glucose to <220 mg% (Boord, 2001) in fed, critically ill patients
Avoid osmotic diuresis and fluid shift
Avoid infections Moderate hyperglycemia was thought to be beneficial for brain and blood cells, that rely solely on glucose for energy (McCowen, 2001)
7. ‘STRESS DIABETES’ Increase in hepatic gluconeogenesis
Increased levels of
Glucagon (Hill, 1991)
Cortisol (Khani, 2001)
Growth hormone
Cytokines IL-1 (Flores, 1990), IL-6, TNF Increase in hepatic glycogenolysis
Increased levels of
Adrenaline
Noradrenaline (Watt, 2001)
Cytokines IL-1, IL-6, TNF (Sakurai, 1996)
8. ‘STRESS DIABETES’ INSULIN RESISTANCE
Even in previously non-diabetic persons
At receptor, post-receptor level
In liver, skeletal muscle, heart (Mizock, 2001)
9. ACUTE vs. CHRONIC CRITICAL ILLNESS ACUTE PHASE commonly seen
Efficient neuro-endocrine adaptation
Body provides endogenous energy to cover period of temporary starvation by gluconeogenesis, glycogenolysis
10. ACUTE vs. CHRONIC CRITICAL ILLNESS CHRONIC PHASE is a different paradigm (Berghe, 1998); more frequent now
No efficient adaptive response; fall in GH, catecholamine, cytokine, cortisol (van den Berghe, 2001)
Starvation is not a major concern
11. PRESENT SCENARIO 30% of tertiary level ICU patients need >5 days of intensive care (Takala, 1999)
>20% do not survive
Commonest culprit: septic shock (Parrillo, 1993)
Polyneuropathy and skeletal muscle wasting lead to prolonged mechanical ventilation, with reduced survival (Leitjen, 1994)
12. PRESENT SCENARIO Increasing ICU admissions; longer survival in ICU means more costs
Compare the cost of insulin with that of 4th gen antibiotics or ventilatory support
13. IN-HOSPITAL HYPERGLYCEMIA An independent marker of in-hospital mortality in patients with undiagnosed diabetes (Umpierrez, 2002)
Diabetes detected in 38% (12% previously unknown) of 2030 consecutive adult indoor patients. No glycemia measured in 7% patients
Survival least in newly-diagnosed diabetics (18.3x ? mortality vs. 2.7x in known diabetics)
42% new diabetics vs. 77% old diabetics treated with insulin
14. IN-HOSPITAL HYPERGLYCEMIA
15. THE LEUVEN STUDY 1548 mechanically-ventilated patients admitted to ICU after surgery/trauma
INTENSIVE THERAPY GROUP: aim for blood glucose 80-110 mg%
CONVENTIONAL APPROACH: aim for blood glucose 180-200 mg%; begin insulin only if BG > 215 mg% (van den Berghe, 2001, 2003)
Continuous infusion of 50 U insulin in 50 ml 0.9% NaCl given thru’ pump. Whole-blood arterial glucose tested at 1-4 hour intervals
16. RESULTS: MORTALITY Strict glycemic control reduced intensive care mortality by 42% (8.0% to 4.6%, p=0.036)
Best results in prolonged critical illness: mortality reduced from 20.2% to 10.6% (p = 0.005)
Even moderate hyperglycemia (120 – 220 mg%) led to higher mortality. Principal cause of death: Multiple organ failure
Autopsy-proven septic focus less common in intensive group (8 vs. 33 deaths, p=0.02)
17. RESULTS: MORBIDITY Intensive insulin therapy reduced the
Duration of ventilatory support
Duration of intensive care stay
Need for blood transfusions
Incidence of septicemia by 46%
Excessive inflammation (CRP)
Need for >10 days antibiotics by 35%
Critical illness polyneuropathy
Acute renal failure by 42%
18. ? A PANACEA FOR ICU Exact mechanisms remain uncertain
? Due to insulin
? Due to good glycemic control
Both daily dose of insulin and mean glucose level increased mortality
19. DIGAMI TRIAL Diabetics with acute MI randomized to conventional or intensive groups
GIK infusion x 48 hours followed by SC insulin x 3 months
Aim: blood glucose < 220 mg% Insulin led to improvement in (Malmberg 1999)
30-day survival
1 year survival
Reinfarction rates
New cardiac failure
20. INSULIN IN M.I. GIK infusion in previously non-diabetic individuals with acute MI is life-saving: meta-analysis (Fath-Ordoubadi, 1997)
ECLA Study (Diaz, 1998)
21. INSULIN IN STROKE GIST (Glucose-Insulin in Stroke Trial) did not show lower glycemia or mortality with GIK regime in acute stroke (Scott, 1999)
However, this study did not target normoglycemia
Hyperglycemia is predictor of mortality in traumatic head injury and stroke (rovlias, 2000)
22. INSULIN & INFECTION IV insulin infusion reduced post-cardiac surgery deep sternal wounds (0.8% vs. 2% for SC insulin) (Furnary, 1999)
Hyperglycemia leads to failure of skin graft take in burns patients (Gore, 2001)
Relative hyperglycemia, even in non-diabetics, is associated with bacteremia, sepsis (van den Berghe, 2001)
23. RISKS Hypoglycemia
Associated with sedation, ventilation, blunted responses, erratic feed
Brain damage
Arrhythmias
Commonest after 1 week
24. ALGORITHM Measure BG on arrival in ICU
>220: insulin 2-4 U/h
110-220: insulin 1-2 U/h
<110: continue BGM q4h; do not start insulin
25. ALGORITHM Measure BG q1-2h until within normal range
>140: increase dose by 1-2 U/h
110-140: increase by 0.5-1 U/h
<110: adjust by 0.1-0.5 U/h
26. ALGORITHM Measure BG q4h
BG nearing normal: adjust dose by 0.1-0.5 U/h
BG normal: do not change
BG falling steeply: reduce dose by 50%; check BG more frequently
BG 60-80: reduce by 50%; recheck within 1 h
BG 40-60: stop infusion; ensure adequate intake
BG<40: stop insulin; give10g glucose bolus IV
27. IF THERE IS NO PUMP 500 ml NS + 50 U insulin infusion
1 U = 10 ml NS
1 U/hr = 10 microdrops/min
28. ALGORITHM Insulin requirements vary a lot
Consider pre-ICU status, caloric intake, severity & nature of illness, infections, corticosteroids
Anticipate improvement in insulin sensitivity and reduction in dose
Check for renal failure
Coordinate with enteral feeding
29. QUESTIONS UNANSWERED ? medical ICU patients
? children
? surgical patients in general ward
? non-ventilated patients
? how lo do we go
30. BE DYNAMIC: don’t be static Diabetes is a dynamic disease; needs dynamism to manage
Glycemia varies thru’ a diabetic’s life span; so does treatment/insulin requirement
Treatment should be flexible
Be one step ahead of the illness; do not follow its’ complications
32. Who Moved My ? Cheese ?
33. CONCLUSION AIM FOR BETTER GLYCEMIC CONTROL WITH EXOGENOUS INSULIN
ACHIEVE REDUCTION IN MORTALITY & MORBIDITY