INSULIN THERAPY IN ICU Dr SANJAY KALRA, D.M. [AIIMS]
Transcript of INSULIN THERAPY IN ICU Dr SANJAY KALRA, D.M. [AIIMS]
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INSULIN THERAPY IN ICU
• Dr SANJAY KALRA, D.M. [AIIMS]
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OUR VISIONTo be a globally-acknowledged centre of excellence for clinical care, education & training, and research
in diabetology and endocrinology.
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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
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EVOLUTION OF CRITICAL CARE
• 1940 – FIRST COMMERCIAL VENTILATOR [SPIROPULSATOR]
• 1942 – Penicillin
• 2001 – INSULIN in ICU patients
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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)
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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)
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‘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)
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‘STRESS DIABETES’
• INSULIN RESISTANCE
• Even in previously non-diabetic persons
• At receptor, post-receptor level
• In liver, skeletal muscle, heart (Mizock, 2001)
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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
The ‘fight, flight, fright mechanism’: hyperglycemia may help
The ‘fight, flight, fright mechanism’: hyperglycemia may help
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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
Hyperglycemia: deleterious effects enter the arena
Hyperglycemia: deleterious effects enter the arena
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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)
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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
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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
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IN-HOSPITAL HYPERGLYCEMIA
Normo-glycemia
Known diabetes
New hyper-glycemia
Total mortality
1.7% 3.0% 16%
Non-ICU mortality
0.8% 1.7% 10%
ICU mortality
10% 11% 31%
The JURY: stress diabetes is dangerousThe JURY: stress diabetes is dangerous
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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
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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)
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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%
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? 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
?due to both?due to both
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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
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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)
Is it the nurse or the injection which saved me ?
Is it the nurse or the injection which saved me ?
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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)
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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)
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RISKS
• Hypoglycemia– Associated with
sedation, ventilation, blunted responses, erratic feed
– Brain damage– Arrhythmias– Commonest after 1
week
Watch out for low sugars
Watch out for low sugars
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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
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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
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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
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IF THERE IS NO PUMP
• 500 ml NS + 50 U insulin infusion
• 1 U = 10 ml NS
• 1 U/hr = 10 microdrops/min
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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
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QUESTIONS UNANSWERED
• ? medical ICU patients• ? children• ? surgical patients in
general ward• ? non-ventilated
patients• ? how lo do we go
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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
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Who Moved My Cheese ?
WHO KILLED MY ICU PATIENT ?WHO KILLED MY ICU PATIENT ?
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CONCLUSION
• AIM FOR BETTER GLYCEMIC CONTROL WITH EXOGENOUS INSULIN
• ACHIEVE REDUCTION IN MORTALITY & MORBIDITY
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