Evaluation of conventional v. intensive blood glucose control

Glycemic Control in Critically
Ill Patients
Hyperglycemia in the ICU
 A common occurrence in both diabetic and non-
diabetic patients
 Defined as a blood glucose > 200 mg/dl
 Etiology
Severe trauma, disease, infection, surgery, etc. result in the
activation of the hypothalamic pituitary adrenal (HPA) axis
Release of glucagon, growth hormone, and cortisol in addition to
norepinephrine and epinephrine
 Blood insulin levels remain normal or low
Insulin resistance, preexisting or not
Fluids (D5W), Medications, TPN, etc.
Treatment of Hyperglycemia
 Insulin infusion
 Titrate every hour
according to protocol
Hypoglycemia in the ICU
 Blood glucose < 70mg/dl
 Result of overcorrection
of hyperglycemia
 Whipple’s triad
Signs and/or symptoms
consistent with
Low plasma glucose
Relief of symptoms after
plasma glucose is increased
 Life threatening
Treatment of Hypoglycemia
 Intravenous glucose (25g) as a 50% solution
 Followed by constant infusion of 5% or 10% dextrose
 If IV access not possible:
 Glucagon (1.0 mg for adults) SC or IM
 Goal glucose: 110-180, but this is a wide range and a
debatable one
Conflicting Findings
 Initial trials suggested that intensive glucose control
could reduce mortality among patients in surgical
ICU and reduce morbidity among those in a medical
Subsequent studies have NOT confirmed this
 NICE-SUGAR trial shows increased risk of death in
patients assigned to intensive glucose control
Van den Berghe G, Wouters P, Week- ers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359-67.
Van den Berghe G, Wilmer A, Her- mans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354:449-61.
 Normoglycemia in Intensive Care Evaluation—
Survival Using Glucose Algorithm Regulation
 A multicenter, randomized, controlled trial
6104 adults in ICUs in 42 hospitals between 2004 & 2008
Intensive blood glucose control group (target BG range 81-108
mg/dl) v. conventional glucose control (target 180 mg/dl or
Intervention continued until patient was eating, discharged
from ICU, or died
Primary outcome: death within 90 days after randomization
Severe hypoglycemia = 40 mg/dl or less
Moderate hypoglycemia = between 41 and 70 mg/dl
 Evidence: Ia
 Recommendation Grade: A
Overall Conclusion:
Although hypoglycemia was significantly more
common among patients assigned to intensive
versus conventional glucose control, the
association of hypoglycemia with death was
similar in the two groups
 Post-hoc analysis
 Whether hypoglycemia leads to death in critically ill patients is unclear
 Findings
Even after adjustment for events occurring after the first episode of
hypoglycemia, moderate hypoglycemia was associated with an
increased risk of death of 40% and severe hypoglycemia with a
doubling of the risk
Causal relationship is plausible because hypoglycemia may increase
mortality by impairment of other systems
 Hypoglycemia may be a marker of severe underlying disease processes
 Autonomic function, alteration of blood flow and composition,
white-cell activation, vasoconstriction, and the release of
inflammatory cytokines
 A wise man once said, “Hyperglycemia in the acute
setting isn’t going to kill you but hypoglycemia will.”
Hal Richards, Pharm.D., BCNSP, Candler Hospital
 Thus, until we have data that says otherwise,
intensive glucose control in the ICU should be
avoided. A target blood glucose of 130-180 mg/dl is a
reasonable goal
 Annetta MG, Ciancia M, Proietti R. Diabetic and nondiabetic
hyperglycemia in the ICU. Current Anaesthesia & Critical Care, 2006
17:6, 385-390.
 LexiComp. Version 1.10.0(159), 2012.
 McDonnell ME, and Umpierrez GE. Insulin therapy for the
management of hyperglycemia in hospitalized patients. Endocrinology
and Metabolism Clinics of North America, March 2012 41:1, 175-201.
 NICE-SUGAR investigators. Hypoglycemia and Risk of Death in
Critically Ill Patients. N Engl J Med 2012;367:1108-18.

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