Hyperlactatemia affects the association of hyperglycemia with mortality in nondiabetic adults with sepsis

Abstract

Background: Admission hyperglycemia has been reported as a mortality risk factor for septic nondiabetic patients; however, hyperglycemia's known association with hyperlactatemia was not addressed in these analyses.

Objectives: The objective was to determine whether the association of hyperglycemia with mortality remains significant when adjusted for concurrent hyperlactatemia.

Methods: This was a post hoc, nested analysis of a retrospective cohort study performed at a single center. Providers had identified study subjects during their emergency department (ED) encounters; all data were collected from the electronic medical record (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous lactate and glucose testing in the ED were enrolled. The setting was the ED of an urban teaching hospital from 2007 to 2009. To evaluate the association of hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate ≥ 4.0 mmol/L), a logistic regression model was created. The outcome was a diagnosis of hyperlactatemia, and the primary variable of interest was hyperglycemia. A second model was created to determine if coexisting hyperlactatemia affects hyperglycemia's association with mortality; the main outcome was 28-day mortality, and the primary risk variable was hyperglycemia with an interaction term for simultaneous hyperlactatemia. Both models were adjusted for demographics; comorbidities; presenting infectious source; and objective evidence of renal, respiratory, hematologic, or cardiovascular dysfunction.

Results: A total of 1,236 ED patients were included, and the median age was 77 years (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days of their initial ED visits. After adjustment, hyperglycemia was significantly associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95% confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia was not (OR = 0.78, 95% CI = 0.39 to 1.57).

Conclusions: In this cohort of septic adult nondiabetic patients, mortality risk did not increase with hyperglycemia unless associated with simultaneous hyperlactatemia. The previously reported association of hyperglycemia with mortality in nondiabetic sepsis may be due to the association of hyperglycemia with hyperlactatemia.

Figure 1

Adjusted 28-day mortality risk by lactate and glucose stratum. Glucose measured in mg/dL. The model was adjusted for patient age (AOR = 1.04 for every year older than 21 years; p< 0.01), Charlson score (AOR = 1.15 for every one-point increase in scoring system; p < 0.01), renal dysfunction (AOR = 1.11 for serum blood urea nitrogen > 20 mg/dL; p < 0.01), respiratory dysfunction (AOR = 1.15, p=0.01), and cardiovascular dysfunction (AOR = 1.29, p < 0.01). Hosmer-Lemeshow goodness-of-fit test χ² = 11.22 (DF = 8), p = 0.19, which indicates statistically significant “fit.” Reference group: 21-year-old subject with a serum lactate level < 4.0 mmol/L and serum glucose level ≤ 200 mg/dL. AOR = adjusted odds ratio.