Professor Rinaldo Bellomo is an Intensivist at the Austin Hospital in Melbourne. He is Professor of Medicine at Melbourne University, and Honorary Professor of Medicine at Monash University, Melbourne and The University of Sydney. He is one of the most eminent researchers in Intensive Care Medicine today and has been named one of the most influential scientific minds of our time. In this thought-provoking talk Professor Bellomo discusses glycemic control of critically ill diabetic patients in the ICU.

1. RINALDO BELLOMO
INTENSIVE CARE UNIT
AUSTIN HOSPITAL,
MELBOURNE, AUSTRALIA
Defining the correct glucose target
in critically ill diabetic patients?
(why intensivists are becoming diabetologists)

2. Glucose control in ICU and post-op
 Hyperglycemia in ICU patients is almost universal
 Glycaemic control in ICU and post-operatively is an
article of faith.
The reasons we apply it are:
 We are intensivists and we are secretly sworn
upon a sacred oath to normalize all physiology
 Physiological reasoning (hyperglycemia induces
glycosuria. Glycosuria may cause dehydration which
may be bad. So we should avoid hyperglycemia)

3. Why treat hyperglycemia in ICU II
 2. Association with specific risk (some diabetics
with poor glucose control develop diabetic
keotacidosis or hyperomolar non-ketotic diabetic
coma. So we should avoid hyperglycemia )
 3. Association with general risk (hyperlycemia in
ICU is independently associated with mortality and
maybe even with infection [which came first
hyperglycemia or infection?]. So we should avoid
hyperglycemia)

4. Could we be wrong?

5. Impossible!

6. ITT: the new black!

7. Serious problems
 Single centre
 Protagonist involved in direct patient care
 Outcome to 28 days only
 Glycaemic control data only in am bloods
 P level low (0.04)
 Most of the effect in cardiac surgery patients but
with controls carrying a mortality of 5.1%!
 High mortality in other controls for a given mean
APACHE score

8. The big trial

9. IIT increases mortality

10. The problems with applying
belief systems to everyone

12. As expected

13. Glycemia in diabetics is different

15. Hypoglycemia is similar

18. Despite higher overall glucose levels diabetics develop
hypoglycaemia three times as often (which must
mostly be iatrogenic)

19. • High rate of hypoglycemia and 3% excess
mortality in intensive control group
• Cardiovascular cause of death more
common in the intensive control group
• Hypo independently associated with
increased mortality
• Association strongest among patients with
distributive shock

20. hypoglycemia per se may be harmful
Chemoreceptors in
carotid glomus
Cardiac baroreceptor sensitivity
Heart rate variability
Sympathetic outflow
Cardiovascular instability
Hypoglycemia

21. Previous hypoglycaemia increases hypothalamic activation
during subsequent hypoglycaemia (which inhibits sympathetic
activation – the so-called habituation response to stress)

23. Hypoglycemia is ”silent” in ICU
Which makes it particularly bad
3
4
5
6
7
9
8
10
BloodGlucoseLevel(mmol/L)
3.9
• Activation of hormonal counterregulation
– Adrenaline
– Noradrenaline
– Cortisol
– Growth hormone
– Glucagon
• Neuroglycopenic symptoms
– Confusion
– Weakness
– Drowsiness
– etc…
No
Diabetes
invisible

24. But things may well be even trickier in diabetics!
The concept of relative hypoglycemia
3
4
5
6
7
9
8
10
BloodGlucoseLevel(mmol/L)
No
Diabetes
30%
30%
Diabetes
• Evidence from ’clamp studies’
• 30% drop from baseline triggers
hormonal/neuroglycopenic
responses (relative hypoglycemia)
• Hypoglycemia counter-regulation
can occur within a normal blood
glucose range in patients with
chronic poor glucose control
The adverse effects of hypoglycemia may happen
at a normal glucose level in diabetics
Do we have reasons to believe this is true?

25. Questions
 How does chronic glycaemic control
influence the relationship between
acute glycaemia and outcome
 What is hypoglycaemia in a diabetic
patient?
 Is it the same as in a non-diabetic?
 Is there a different response?
 If so what does it mean?

26. Conventional
range
10-14 mmol/l

39. Ketones

45. MIMIC database (Harvard)
Mortality and relative hypoglycemia (>30% fall b/w 2 consecutive blood gases)

46. Frequency of relative hypoglycemia and risk of death

47. Where to from here?
 Evidence that glucose control in ICU matters (NICE-
SUGAR trial)
 Evidence that hypoglycaemia is bad
 Evidence that relative hypoglycaemia exists
 Evidence that it may also be bad
 Evidence that diabetics (esp. bad ones) are different and
at particular risk of relative and absolute hypoglycaemia
 Evidence we can assess chronic glycaemic control on
admission by HbA1c
 Evidence we can decrease relative hypoglycaemia with
liberal glycaemic control in diabetics
 RCTs applied for and likely to start soon