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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.
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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
Severe Hypoglycemia ≤40mg/dL (2.2 mmol/L) 18.7% 17% 16.4% 8.7% 7.8% 6.8% 5.1% 4.1% 3.1% 2.7% 0.8% 0.5% 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.
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