Glycemic Control in Critically
Ill Patients
EVALUATION OF CONVENTIONAL V.
INTENSIVE BLOOD GLUCOSE CONTROL
DANELLE BLUME
UNIVERSITY OF GEORGIA
COLLEGE OF PHARMACY
2013 PHARM.D. CANDIDATE
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
hypoglycemia
Low plasma glucose
Relief of symptoms after
plasma glucose is increased
 Life threatening
http://diabeticradio.com/?page_id=685
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
ICU*

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.
NICE-SUGAR
 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
less)
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
NICE-SUGAR
 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
NICE-SUGAR
 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

Relevance
 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
References
 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.