CORRESPONDENCE: LETTER TO THE EDITOR
Strict Glucose Control in the Cardiac Intensive Care UnitPoised for Real Time?
John R. Kapoor, MD, PhD* and
Roger Kapoor, MD, MBA
* Division of Cardiology, Stanford University, 300 Pasteur Drive, Stanford, California 94305 (Email: jkapoor{at}stanford.edu).
Strict glucose control has been promoted in many intensive care unit (ICU) settings, including the cardiac ICU, because of the notion that this will "lower the risk of mortality in critically ill patients" (1). However, enthusiasm should be tempered by a realization that the landmark trial showing benefit is wrought with significant flaws and other studies show either no benefit or harm from such a strategy. Ceriello et al. (1) assert that "strong evidence for tight glycemic control as a key strategy for improving prognosis after acute coronary syndromes comes from the study by Van den Berghe et al." (2). However, this study was done on surgical patients, and the greatest decrease in mortality occurred in patients with sepsis. Additionally, concerns have been raised regarding uncharacteristically high mortality rates in the control group and for the concomitant use of a high-dose glucose infusion and parenteral nutrition (3), which is not a standard practice strategy (4). Ceriello et al. (1) also cite beneficial findings of strict glucose control in the medical ICU (5), without noting that comparisons in this trial were made with historical controls, making it difficult to tease out what, if any, benefit accrued from strict glucose control as opposed to other changes in ICU management over time.
In contrast, recent studies have demonstrated no mortality benefit and more adverse outcomes with strict glucose control (6,7). One multicenter, randomized controlled trial conducted in 18 centers using treatment protocols based on the trial by Van den Berghe (2) was stopped early, because there was no significant mortality difference and the intensive-therapy group experienced higher rates of severe hypoglycemia than the conventional-therapy group (17.0% vs. 4.1%, p < 0.001), higher rates of serious adverse events (10.9% vs. 5.2%, p = 0.01), and a trend to longer ICU stays (6). Another multicenter, randomized controlled study conducted in 7 countries and in 21 ICUs was halted prematurely, because of safety concerns and an increased rate of hypoglycemia and a trend toward higher mortality in the intensive-therapy group (7). In another cohort study of 10,456 ICU patients, there was also a trend toward higher mortality with strict glucose control (8). Finally, a meta-analysis of 29 randomized controlled trials of 8,432 ICU patients demonstrated no hospital mortality benefit of strict glucose control and no significant difference in mortality when stratified by glucose goal, but there was a 5-fold increased risk of hypoglycemia, leading the authors to conclude, "tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia" (3). Taken together, one is left to question the purported "beneficial" effects of strict glucose control in the ICU setting over the potential for significant harm incurred by hypoglycemia.
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1. Ceriello A, Zarich SW, Testa R. Lowering glucose to prevent adverse cardiovascular outcomes in a critical care setting J Am Coll Cardiol 2009;53(Suppl):S9-S13.[Abstract/Free Full Text]2. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients N Engl J Med 2001;345:1359-1367.[CrossRef][Web of Science][Medline] 3. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis JAMA 2008;300:933-944.[Abstract/Free Full Text] 4. Kreymann KG, Berger MM, Deutz NE, et al. ESPEN guidelines on enteral nutrition: intensive care Clin Nutr 2006;25:210-223.[CrossRef][Web of Science][Medline] 5. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients Mayo Clin Proc 2004;79:992-1000.[Abstract/Free Full Text] 6. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis N Engl J Med 2008;358:125-139.[CrossRef][Medline] 7. Devos P, Preiser J, Melot C. Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the glucontrol study Intensive Care Med 2007;33(Suppl 2):S189. 8. Treggiari MM, Karir V, Yanez ND, Weiss NS, Daniel S, Deem SA. Intensive insulin therapy and mortality in critically ill patients Crit Care 2008;12:R29.[CrossRef][Medline]
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- Antonio Ceriello
J. Am. Coll. Cardiol. 2009 54: 374.
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