Sugar control in Critical care unit

Senior clinical pharmacist : Lihua Fang

Koo Foundation Cancer Center

Glycemic Control in the ICU

A 42-year-old man is admitted to (ICU) with an acute exacerbation of asthma associated with community-acquired pneumonia.

cefotaxime and azithromycin, nebulized albuterol, and intravenous hydrocortisone

No known history of diabetes mellitus Glucose 105 mg/dl-> 195 mg/dl, HbA1c : 5.3% Should this elevated glucose level be treated?

Causes and Effects of Stress Hyperglycemia.

Kavanagh BP, McCowen KC. N Engl J Med 2010;363:2540-2546.

STRATEGIES AND EVIDENCEEvaluation

Acute hyperglycemia : > 200 mg/dl In 2010 the American Diabetes Association : > 140 mg/dl HbA1c > 6.5%

Management Studies of Intensive Insulin Therapy Before 2001, little attention was paid to control of

hyperglycemia in the ICU Targeted is 80 to 110 mg/dl

A single-center trial in Leuven, Belgium

1548 pts, cardiac surgery not blinded The first evidence of a benefit of tight glucose control in the

ICU Intensive insulin therapy (target glucose 80-110 mg/dl) vs

standard care (180-200 mg/dl ) Reduced mortality in ICU (4.6% vs. 8%) Serious hypoglycemia ( <40 mg/dl, 5% ) cause for concern The mortality in the control group was high relative to that

in other cardiac surgical centers.

NEJM 2001;345:1359-1367

A single-center, nonblinded trial from the same group

1200 medical ICU pts :> 3 days Intensive insulin therapy (target glucose 80-110

mg/dl) vs standard care (180-200 mg/dl ) Not reduce overall mortality, serious

hypoglycemia (18.7%) lower rate of acquired renal impairment (5.9% vs. 8.9%) shorter duration of mechanical ventilation shorter stays in the ICU

NEJM 2006;354:449-461

Four additional studies (two multicenter trials and two single-center trials)

2600 pts at 41 centers (medical and surgical) Target glucose levels vs intensive-therapy Intensive insulin therapy :

significant effect on mortality and resulted in a high incidence of hypoglycemia (8 to 28%)

No benefits of secondary outcomes Renal impairment, duration of mechanical

ventilation, length of stay

The largest trial–Survival Using Glucose Algorithm Regulation (NICE-SUGAR)

6104 pts (42 centers) The intensive-therapy group : an absolute in

mortality of 2.6% points (P=0.02) and hypoglycemia (6.8% vs. 0.5%).

Intensive therapy 118±25 mg/dl, the control group : <180 mg/dl.

The mortality rate in the control group :24.9% was lower than that predicted by the APACHE II score (39%)

The nutrition regimen : less aggressive Intensive insulin therapy with glucocorticoids for septic

shock: no reduction in mortality and also a higher hypoglycemia (16.4% vs. 7.8 )

NEJM 2009;360:1283-1297

02468

101214161820

% Intensive insulintherapy

% Control5.1%

0.8%

18.7%

3.1%

17%

4.1%

8.7%

2.7%

16.4%

7.8% 6.8%

0.5%

Severe Hypoglycemia ≤40mg/dL (2.2 mmol/L)

Treatment vs control P<0.001

A meta-analysis of 26 randomized trial

>13,500 pts Intensive insulin therapy

No overall effect on mortality Hypoglycemia that was 6 times higher

A more recent meta-analysis restricted to the seven largest randomized trials ( > 11,000 pts)

Target glucose : 80 to 110 mg/dl no survival benefit and increased morbidity

CMAJ 2009;180:821-827

Glucose Monitoring By intra-arterial, venous catheters or a fingerstick

Point-of-care bedside glucometers (inaccurate, by > 20%)

Laboratory analysis of plasma (slow for use in the ICU)

Blood gas analyzers (highly accurate) : practical New technologies :

Subcutaneous glucose sensors ( every 5 minutes) glucose levels in interstitial fluid, lag behind blood levels.

Continuous intravascular glucose sensors in development, real-time monitoring

Insulin-infusion An insulin-infusion protocol

validated and Algorithm for Monitoring Glucose Levels and Managing Insulin Therapy in the ICU

Computer-directed algorithms Target glucose level : < 180 mg/dl

The risk of hypoglycemia with insulin therapy Subcutaneous insulin

Algorithm for Monitoring Glucose Levels and Managing Insulin Therapy in the ICU.

NEJM 2010;363:2540-2546.

Calculating 24-hour insulin needs

Physical Activity Level

Normal Weight

Obese

High 0.3 U/kg 0.5 U/kg

Moderate 0.4 U/kg 0.6 U/kg

Low 0.5 U/kg 0.8 U/kg

Coexisting Illness (CKD)

Subtract 0.2 U/kg

“Big eater” eating habits

Add 0.1 U/kg

Insulins and Duration of Action

By Sliding scale

Basal and bolus insulin dosing

Based on IV insulin infusion Several models :a threecomponent

basal insulin, nutritional insulin, Basal insulin : Long acting (glargine) or

intermediate-acting insulin every 6–12 hrs ( NPH) At least 2–4 hrs before stopping the insulin infusion rapid-acting insulin ( 10% of the basal dose)

may be given with the basal insulin injection Initial basal dose to 80% of the estimated TDD

Changes in other drug therapy or nutritional regimens

Hypoglycemia An increase in mortality Severe hypoglycemia ( <40 mg/dl)

28% of intensive insulin therapy The neurologic consequences of hypoglycemia

difficult to detect in critically ill patients At 4 years of follow-up, intensive insulin therapy was

found to have impairments in quality of life and social functioning vs conventional treatment.

The long-term sequelae of iatrogenic hypoglycemia in the ICU

difficult to measure

Hypoglycemia BG < 70 mg/dL(<100mg/dL in neurologic injury patients)

Stopping the insulin infusion and administering 10–20g of hypertonic (50%) dextrose

The BG repeated in 15 mins to achieve BG > 70mg/dL

20-50% dextrose dose in grams = [100 − BG] × 0.2g), 10–20g of IV dextrose

Target range in 98% within 30 mins

Crit Care Med 2012 Vol. 40, No. 12

Nutrition A recent meta-analysis in Intensive insulin therapy

with a reduction in mortality only High calories was provided parenterally, to avoid

hypoglycemic complications of intensive insulin therapy and lower the risk of death only when administered in the context of intensive nutritional support

Enteral feeding and parenteral nutrition More beneficial in intensive insulin infusion

Guidelines from Professional Organizations on the Management of Glucose Levels in the ICU.

Kavanagh BP, McCowen KC. N Engl J Med 2010;363:2540-2546.

Glycemic Control in the ICU

A 42-year-old man is admitted to (ICU) with an acute exacerbation of asthma associated with community-acquired pneumonia.

cefotaxime and azithromycin, nebulized albuterol, and intravenous hydrocortisone

No known history of diabetes mellitus Glucose 105 mg/dl-> 195 mg/dl, HbA1c : 5.3% Should this elevated glucose level be treated?

CONCLUSIONS AND RECOMMENDATIONS

With ongoing use of glucocorticoids and the institution of nutritional support

Follow plasma glucose HbA1c : 5.3%, No preexisting diabetes Target : 140 -180 mg/dl Computerized insulin-infusion algorithm and close

monitoring of glucose levels Nutritional support : enteral feeding

Reference Guidelines for the use of an insulin infusion for the management of

hyperglycemia in critically ill patients Crit Care Med 2012 Vol. 40, No. 12