Towards Understanding Tight Glycemic Control in the ICU: A Systematic Review and Meta-analysis.
Chest. 2009 Dec 16;
Authors: Marik PE, Preiser JC
BACKGROUND: Following publication of the "Leuven Intensive Insulin Therapy Trial" in 2001, tight glycemic control became the standard of care in ICU's around the world. Recent studies suggest that this approach may be flawed OBJECTIVE: The goal of this systematic review was to determine the benefits and risks of tight glycemic control in ICU patients and to explain the differences in outcomes between reported trials. Data Sources: MEDLINE, Embase, the Cochrane Database of Systematic Reviews and citation review of relevant primary and review articles. Study Selection: Prospective, randomized, controlled clinical trials (RCT's) that studied the impact of tight glycemic control (blood glucose 80-110 mg/dl) on mortality in ICU patients. Data Extraction and analysis: Data were abstracted on study design, study size, patient characteristics as well as the mean (or median) and standard deviation of the ICU blood glucose level, mean daily dose of insulin administered, average daily caloric intake, percentage of calories given intravenously (parenteral nutrition), incidence of hypoglycemia, need for dialysis and 28 day/hospital mortality. Meta-analytic techniques were used to analyze the data; sub-group analysis and meta-regression were used to explain differences in the treatment effect. Data Synthesis: We identified 7 RCT's studies that included 11 425 patients. Overall, tight glycemic control did not reduce the 28 day mortality (OR 0.95; 95% CI 0.87-1.05), the incidence of blood stream infections (OR 1.04; 95% CI 0.93-1.17) nor the requirement for renal replacement therapy (OR 1.01; 95% CI 0.89-1.13). The incidence of hypoglycemia was significantly higher in patients randomized to tight glycemic control (OR 7.7; 95% CI 6.0-9.9, p< 0.001). Meta-regression demonstrated a significant relationship between the treatment effect (28 day mortality) and the proportion of calories provided parenterally (p=0.005). This suggests that difference in outcome between the two "Leuven Intensive Insulin Therapy Trials" and the subsequent trials could be related to the use of parenteral nutrition. When the two "Leuven Intensive Insulin Therapy Trials" are excluded from the meta-analysis, mortality was lower in the control patients (OR 0.90; 95% CI 0.81-0.99, p=0.04, I(2) =0%). CONCLUSIONS: There is no evidence to support the use of intensive insulin therapy in general medical-surgical ICU patients who are fed according to current guidelines. Tight glycemic control is associated with a high incidence of hypoglycemia and an increased risk of death in patients not receiving parenteral nutrition.
PMID: 20018803 [PubMed - as supplied by publisher]