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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
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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.