Key Point:

There is a significant correlation between the baseline HbA1c and hyperglycemia in MICU patients.

MIAMI—Acute stimuli such as corticosteroids, carbohydrates, and exogenous catecholamines are known to be major determinants of hyperglycemia frequency and severity in the critically ill. However, a recent study has shown that blood glucose regulation in the two to three months prior to critical illness, as measured with the hemoglobin A_1c (HbA_1c)level, is just as strong a predictor of hyperglycemia in those admitted to the medical intensive care unit (MICU).¹

In the study, an elevated baseline HbA_1c was associated with significant increases in the frequency and severity of hyperglycemia among 100 MICU patients; a high-normal baseline HbA_1c showed such a relationship with hyperglycemia, as well. “Surprisingly, severity of illness, as measured by the APACHE II score (or its acute physiology component), was not associated with either the degree or duration of hyperglycemia,” related the study authors.

Hyperglycemia was virtually universal in the study population, occurring in all but four of the patients and typically lasting for most of the ICU stay. “Critically ill patients often have the potential for a fair degree of hyperglycemia before they ever show up in the ICU, and that probably puts the intensivist behind the eight ball right from the start in terms of treatment,” remarked Andrew A. Quartin, MD, one of the study authors, in an interview with Pulmonary Reviews.

Dr. Quartin is Associate Professor in the Division of Pulmonary and Critical Care Medicine at the University of Miami.

PATIENTS WERE SEVERELY ILL

The study subjects were a convenience sample admitted to the MICU primarily for renal or neurologic dysfunction, respiratory insufficiency, an inflammatory state, or sepsis. These patients met the inclusion criteria of no previous treatment in an ICU during their current hospitalization, an anticipated APACHE II score greater than 11, and an estimated ICU stay longer than 48 hours.

Notably, the study did not include any patients who had diabetic ketoacidosis or hemoglobinopathies, who had undergone major surgery, or who were in a hyperglycemic hyperosmolar state before MICU admission. Eight patients were subsequently excluded because their APACHE II scores were lower than 12.

Blood samples for HbA_1c testing were available for 88 of the remaining 92 patients; the samples were taken a median of one day after MICU admission. In 13 of these cases, long-term blood glucose control was considered indeterminate because the patient had received two or more units of red blood cells, lead study author Cynthia M. Cely, MD, told Pulmonary Reviews. Dr. Cely is Voluntary Assistant Professor in the Division of Pulmonary and Critical Care Medicine at the University of Miami.

Of the 75 patients with an interpretable HbA_1c level, 24 showed an abnormally elevated HbA_1c (greater than 6.4%) at baseline; 15 of these patients had a history of diabetes. The baseline HbA_1c was normal—6.4% or less—in 51 patients.

Hyperglycemia (defined as a blood glucose level of greater than 110 mg/dL) developed in 88 patients during the median MICU stay of 7.4 days. It persisted for more than 90% of the MICU stay in the patients with normal and abnormal baseline HbA_1c and for nearly 70% of that stay in the patients with indeterminate long-term blood glucose control. Not surprisingly, however, hyperglycemia was much more severe in the patients with abnormal baseline HbA_1c.

In a univariate analysis of the 51 patients with normal long-term blood glucose control, a strong correlation was found between baseline HbA_1c and the percentage of time spent with hyperglycemia; the latter increased by 19% for every 1% rise in the former. In this analysis, baseline HbA_1c was also significantly associated with the average blood glucose level and the percentage of time with a blood glucose of greater than 150 mg/dL.

In a multiple regression analysis, the baseline HbA_1c and the doses of intravenous dextrose and norepinephrine were independently related to the peak and average blood glucose. In addition, the baseline HbA_1c and the corticosteroid, dextrose, and norepinephrine doses were shown to be independent predictors of the percentage of time with a blood glucose level greater than 150 mg/dL.

WHAT TO DO ABOUT HYPERGLYCEMIA?

The results of this study support “an aggressive approach to the treatment of hyperglycemia during critical illness,” stated Kenneth D. Chinsky, MD, in an accompanying editorial.² However, there is not yet a consensus on the target blood glucose level in critically ill patients, pointed out Dr. Chinsky, who practices pulmonary, critical care, and sleep medicine with Chest Diseases of Northwestern PA in Erie, Pennsylvania.

In 2001, Van den Berghe and colleagues suggested a blood glucose level of 110 mg/dL or less in these patients, while others have endorsed much more conservative blood glucose goals for the critically ill.³ Dellinger et al, for example, recently recommended keeping blood glucose below 150 mg/dL in patients with severe sepsis.⁴ “While any single cutoff value by definition is arbitrary, I believe we should aim for a [blood glucose] level that is as near to normal as is safe and practical,” concluded Dr. Chinsky.

—Timothy Begany

References
1. Cely CM, Arora P, Quartin AA, et al. Relationship of baseline glucose homeostasis to hyperglycemia during medical critical illness. Chest. 2004;126:879-887.
2. Chinsky K. The evolving paradigm of hyperglycemia and critical illness. Chest. 2004;126:674-676.
3. 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.
4. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.

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