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Correspondence |

Tight Blood Glucose Control in the ICU Response: How Best To Measure Glucose Control? FREE TO VIEW

Guy W. Soo Hoo, MD
Author and Funding Information

Affiliations: West Los Angeles VA Healthcare Center, Los Angeles, CA,  Catholic University of Leuven, Leuven, Belgium

Correspondence to: Guy W. Soo Hoo, MD, Pulmonary and Critical Care Section (111Q), West Los Angeles VA Healthcare Center, 11301 Wilshire Blvd (111Q), Los Angles, CA 90073; e-mail: guy.soohoo@va.gov



Chest. 2008;133(1):316-317. doi:10.1378/chest.07-2214
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Published online

While Vanhorebeek and colleagues1are to be commended on their comprehensive review of tight glucose control in ICU patients, they have not really addressed the optimal glucose metric in these patients. While hyperglycemia is a risk factor for a host of adverse outcomes, the measure that best characterizes this risk remains to be determined. Indexes such as the ICU admission serum glucose level, mean morning glucose level, and mean or median overall glucose level are all subject to potential inaccuracies. Most values represent time-averaged measures, but this assumes that there are consistent values over the time. Without continuous glucose monitoring, all indexes are subject to distortion by variations in values and an unknown duration of time spent within certain values. There are no measures such as hemoglobin A1C that would provide insight in the hyperglycemic exposure of ICU patients. Some have proposed a hyperglycemic index, which takes the area under the curve for glucose values exceeding an established threshold and eliminates some of the bias that occurs when the time factor is not included in the reporting.2 However, this approach requires validation.

Similarly, while lower serum glucose levels improve patient outcomes, the duration of control within threshold values needed for improvement remains undefined. There is great variability with continuous IV insulin protocols with respect to the time actually within goal ranges. The Leuven studies1 reported that 70% of ICU patients receiving insulin achieve a mean blood glucose level of < 110 mg/dL. But, this is misleading. Time averaging may not provide an accurate reflection of the extent of patient hyperglycemia. For example, Chant and colleagues3reported a mean (± SD) morning blood glucose level of 128 ± 32 mg/dL, but only 52% of glucose measurements were in the target range of 90 to 144 mg/dL. Thomas and colleagues4reported an average glucose level of 6.2 mmol/L (or 111 mg/dL) with their protocol, but only 49% of glucose readings were < 6.1 mmol/L (or < 108 mg/dL). This modest number of readings within the goal range is not unique and is comparable to the reports of other investigators56 who have reported 50 to 70% of glucose readings within the goal range. These are ranges of 80 to 140 mg/dL, which are broader than the range reported in the Leuven study1 of 80 to 110 mg/dL. This raises a question as to what minimally effective glucose control level would be required to positively influence patient outcomes. Would 50 to 70% of values within the range be sufficient? This has important implications for the implementation of protocols, the tolerance of hyperglycemic outliers, and the avoidance of hypoglycemia.

The author has reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Vanhorebeek, I, Langouche, L, Van den Berghe, G (2007) Tight blood glucose control with insulin in the ICU: facts and controversies.Chest132,268-278. [PubMed] [CrossRef]
 
Vogelzang, M, van der Horst, I, Nijsten, MW Hyperglycaemic index as a tool to assess glucose control: a retrospective study.Crit Care2004;8,R122-R127. [PubMed]
 
Chant, C, Wilson, G, Friedrich, JO Validation of an insulin infusion nomogram for intensive glucose control in critically ill patients.Pharmacotherapy2005;25,352-359. [PubMed]
 
Thomas, AN, Marchant, AE, Ogden, MC, et al Implementation of a tight glycaemic control protocol using a web-based insulin dose calculator.Anaesthesia2005;60,1093-1100. [PubMed]
 
Goldberg, PA, Siegel, MD, Sherwin, RS, et al Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care2004;27,461-467. [PubMed]
 
Zimmerman, CR, Mlynarek, ME, Jordan, JA, et al An insulin infusion protocol in critically ill cardiothoracic surgery patients.Ann Pharmacother2004;38,1123-1129. [PubMed]
 
To the Editor:

Strict blood glucose control targeting normoglycemia is being implemented in ICUs, based on results of the two randomized controlled trials14 in Leuven, Belgium, and three implementation studies.57 The Leuven studies14 advocated insulin infusion targeting a blood glucose level between 80 and 110 mg/dL, within the monitoring and feeding environment of these ICUs. In these two ICUs, and in many centers worldwide that attempt to implement this metabolic intervention, nurses and physicians use intermittent blood glucose readings to titrate the insulin dose. The adequacy of the readings is being evaluated by computing the mean morning blood glucose levels, obtained from the entire group or on a per-patient basis, by averaging, for example, all of the available glucose values per patient, the minimum/maximum blood glucose values, the time needed to reach normoglycemia, and the number of hypoglycemic events.

As pointed out by Dr. Soo Hoo,8 such single measurements indeed do not capture the dynamics of blood glucose control, and average values can be biased. The sources of bias include different sampling frequencies, and the concomitant presence of hypoglycemic and hyperglycemic events that may result in “normal” calculated averages, whereas the levels of blood glucose are extremely abnormal. The hyperglycemic index, defined as the area under the glucose curve above the upper limit of the target range, divided by the length of ICU stay, also is prone to bias. Ideally, to capture the dynamics of glucose control in an ICU patient, nearly continuous monitoring with an accurate glucose sensor is required, although it remains unclear which aspect of the dynamics (ie, the time spent within the target range, the variance of the blood glucose reading, or the avoidance of hypoglycemia or overcorrection with hyperglycemia following the hypoglycemia) is important to achieve the full benefit of the intervention. We entirely agree with Dr. Soo Hoo that these aspects remain to be elucidated, and the development of continuous glucose sensors is a prerequisite before these questions can be answered.

References
Vanhorebeek, I, Langouche, L, Van den Berghe, G Tight blood glucose control with insulin in the ICU: facts and controversies.Chest2007;132,268-278. [PubMed] [CrossRef]
 
Van den Berghe, G, Wouters, P, Weekers, F, et al Intensive insulin therapy in critically ill patients.N Engl J Med2001;345,1359-1367. [PubMed]
 
Van den Berghe, G, Wilmer, A, Hermans, G, et al Intensive insulin therapy in medical intensive care patients.N Engl J Med2006;354,449-461. [PubMed]
 
Van den Berghe, G, Wilmer, A, Milants, I, et al Intensive insulin therapy in mixed medical/surgical ICU: benefit vs harm.Diabetes2006;55,3151-3159. [PubMed]
 
Furnary, AP, Gao, G, Grunkemeier, GL, et al Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg2003;125,1007-1021. [PubMed]
 
Krinsley, JS Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc2004;79,992-1000. [PubMed]
 
Reed, CC, Stewart, RM, Sherman, M, et al Intensive insulin protocol improves glucose control and is associated with a reduction in ICUs mortality.J Am Coll Surg2007;204,1048-1054. [PubMed]
 
Soo Hoo, GW Tight blood glucose control in the ICU [letter].Chest2008;133,316-317. [PubMed]
 

Figures

Tables

References

Vanhorebeek, I, Langouche, L, Van den Berghe, G (2007) Tight blood glucose control with insulin in the ICU: facts and controversies.Chest132,268-278. [PubMed] [CrossRef]
 
Vogelzang, M, van der Horst, I, Nijsten, MW Hyperglycaemic index as a tool to assess glucose control: a retrospective study.Crit Care2004;8,R122-R127. [PubMed]
 
Chant, C, Wilson, G, Friedrich, JO Validation of an insulin infusion nomogram for intensive glucose control in critically ill patients.Pharmacotherapy2005;25,352-359. [PubMed]
 
Thomas, AN, Marchant, AE, Ogden, MC, et al Implementation of a tight glycaemic control protocol using a web-based insulin dose calculator.Anaesthesia2005;60,1093-1100. [PubMed]
 
Goldberg, PA, Siegel, MD, Sherwin, RS, et al Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care2004;27,461-467. [PubMed]
 
Zimmerman, CR, Mlynarek, ME, Jordan, JA, et al An insulin infusion protocol in critically ill cardiothoracic surgery patients.Ann Pharmacother2004;38,1123-1129. [PubMed]
 
Vanhorebeek, I, Langouche, L, Van den Berghe, G Tight blood glucose control with insulin in the ICU: facts and controversies.Chest2007;132,268-278. [PubMed] [CrossRef]
 
Van den Berghe, G, Wouters, P, Weekers, F, et al Intensive insulin therapy in critically ill patients.N Engl J Med2001;345,1359-1367. [PubMed]
 
Van den Berghe, G, Wilmer, A, Hermans, G, et al Intensive insulin therapy in medical intensive care patients.N Engl J Med2006;354,449-461. [PubMed]
 
Van den Berghe, G, Wilmer, A, Milants, I, et al Intensive insulin therapy in mixed medical/surgical ICU: benefit vs harm.Diabetes2006;55,3151-3159. [PubMed]
 
Furnary, AP, Gao, G, Grunkemeier, GL, et al Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg2003;125,1007-1021. [PubMed]
 
Krinsley, JS Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc2004;79,992-1000. [PubMed]
 
Reed, CC, Stewart, RM, Sherman, M, et al Intensive insulin protocol improves glucose control and is associated with a reduction in ICUs mortality.J Am Coll Surg2007;204,1048-1054. [PubMed]
 
Soo Hoo, GW Tight blood glucose control in the ICU [letter].Chest2008;133,316-317. [PubMed]
 
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