Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis

Abstract

Objectives: Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among specific patient populations. The purpose of the study was to determine the association between hyperglycemia and risk- adjusted mortality in critically ill patients and in separate groups stratified by admission diagnosis. A secondary purpose was to determine whether mortality risk from hyperglycemia varies with intensive care unit type, length of stay, or diagnosed diabetes.

Design: Retrospective cohort study.

Setting: One hundred seventy-three U.S. medical, surgical, and cardiac intensive care units.

Patients: Two hundred fifty-nine thousand and forty admissions from October 2002 to September 2005; unadjusted mortality rate, 11.2%.

Interventions: None.

Measurements and main results: A two-level logistic regression model determined the relationship between glycemia and mortality. Age, diagnosis, comorbidities, and laboratory variables were used to calculate a predicted mortality rate, which was then analyzed with mean glucose to determine the association of hyperglycemia with hospital mortality. Hyperglycemia was associated with increased mortality independent of illness severity. Compared with normoglycemic individuals (70-110 mg/dL), adjusted odds of mortality (odds ratio, [95% confidence interval]) for mean glucose 111-145, 146-199, 200-300, and >300 mg/dL was 1.31 (1.26-1.36), 1.82 (1.74-1.90), 2.13 (2.03-2.25), and 2.85 (2.58-3.14), respectively. Furthermore, the adjusted odds of mortality related to hyperglycemia varied with admission diagnosis, demonstrating a clear association in some patients (acute myocardial infarction, arrhythmia, unstable angina, pulmonary embolism) and little or no association in others. Hyperglycemia was associated with increased mortality independent of intensive care unit type, length of stay, and diabetes.

Conclusions: The association between hyperglycemia and mortality implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients. The finding that hyperglycemia-related risk varied with admission diagnosis suggests differences in the interaction between specific medical conditions and injury from hyperglycemia. The design and interpretation of future trials should consider the primary disease states of patients and the balance of medical conditions in the intensive care unit studied.

Figure 1. Hyperglycemia is associated with increased mortality in ICU patients, independent of severity of illness

Mortality risk increases with mean glucose across the entire cohort (n = 259,040) starting at mild hyperglycemia (p < 0.0001). A) Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association. B) Cubic splines depict this relationship using mean glucose as a continuous variable.

Figure 1. Hyperglycemia is associated with increased mortality in ICU patients, independent of severity of illness

Mortality risk increases with mean glucose across the entire cohort (n = 259,040) starting at mild hyperglycemia (p < 0.0001). A) Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association. B) Cubic splines depict this relationship using mean glucose as a continuous variable.

Figure 2. Mortality risk from hyperglycemia is greater in patients without a diagnosis of diabetes

Hyperglycemia is significantly associated with increased adjusted mortality in patients with (n = 78,142) and without (n =180,898) diagnosed diabetes, but the mortality risk is greater in those without diabetes (P < 0.01). A) Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association. B) Cubic splines depict this relationship using mean glucose as a continuous variable.

Figure 2. Mortality risk from hyperglycemia is greater in patients without a diagnosis of diabetes

Hyperglycemia is significantly associated with increased adjusted mortality in patients with (n = 78,142) and without (n =180,898) diagnosed diabetes, but the mortality risk is greater in those without diabetes (P < 0.01). A) Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association. B) Cubic splines depict this relationship using mean glucose as a continuous variable.

Figure 3. The association between hyperglycemia and mortality varies with admission diagnosis

There is a significant association between hyperglycemia and increased mortality for aggregate groups of significant and non-significant diagnostic categories (p < 0.0001). However, the magnitude of mortality risk remains greater for the aggregate group of significant diagnoses (n = 156,119) vs. aggregate group of non-significant diagnoses (n = 102,921). Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association.