RINALDO BELLOMOINTENSIVE CARE UNIT

AUSTIN HOSPITAL,MELBOURNE, AUSTRALIA

Defining the correct glucose target in critically ill diabetic

patients?(why intensivists are becoming diabetologists)

Glucose control in ICU and post-op

Hyperglycemia in ICU patients is almost universalGlycaemic 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 physiologyPhysiological reasoning (hyperglycemia induces

glycosuria. Glycosuria may cause dehydration which may be bad. So we should avoid hyperglycemia)

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)

Could we be wrong?

Impossible!

ITT: the new black!

Serious problems

Single centreProtagonist involved in direct patient careOutcome to 28 days onlyGlycaemic control data only in am bloodsP 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

The big trial

IIT increases mortality

The problems with applying belief systems to everyone

As expected

Glycemia in diabetics is different

Hypoglycemia is similar

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

• 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

hypoglycemia per se may be harmful

Chemoreceptors incarotid glomus

Cardiac baroreceptor sensitivity

Heart rate variability

Sympathetic outflow

Cardiovascular instability

Hypoglycemia

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

Hypoglycemia is ”silent” in ICUWhich makes it particularly bad

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• Activation of hormonal counterregulation– Adrenaline– Noradrenaline– Cortisol– Growth hormone– Glucagon

• Neuroglycopenic symptoms– Confusion– Weakness– Drowsiness– etc…

NoDiabetes

invisible

But things may well be even trickier in diabetics! The concept of relative hypoglycemia

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NoDiabetes

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?

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?

Conventionalrange

10-14 mmol/l

Ketones

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

Frequency of relative hypoglycemia and risk of death

Where to from here?Evidence that glucose control in ICU matters (NICE-

SUGAR trial)Evidence that hypoglycaemia is badEvidence that relative hypoglycaemia existsEvidence that it may also be badEvidence 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