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Maximal Chemiluminescent Intensity in Response to Lipopolysaccharide Assessed by Endotoxin Activity Assay on Admission Day Predicts Mortality in Patients With Sepsis*

Kiguchi, Takeyuki MD1; Nakamori, Yasushi MD, PhD1; Yamakawa, Kazuma MD2; Kitayama, Junichi MD1; Wada, Daiki MD1; Ogawa, Yoshihito MD2; Ogura, Hiroshi MD, PhD2; Kuwagata, Yasuyuki MD, PhD2; Shimazu, Takeshi MD, PhD2; Hamasaki, Toshimitsu PhD3; Fujimi, Satoshi MD, PhD1

doi: 10.1097/CCM.0b013e31827ca960
Clinical Investigations

Objective: Sepsis is the leading cause of death among critically ill patients. There are, however, few appropriate biomarkers to predict mortality in patients with sepsis. We focused on maximal chemiluminescent intensity in response to lipopolysaccharide assessed by endotoxin activity assay and evaluated the diagnostic value of maximal chemiluminescent intensity on admission day as a predictor of mortality in patients with sepsis.

Design: Prospective, observational study.

Setting: ICU.

Patients: One hundred and thirty-two patients with sepsis.

Interventions: None.

Measurements and Main Results: Within 12 hours after admission, a whole-blood sample was collected, and variables assessed by endotoxin activity assay were measured in each patient. Severity of illness was assessed simultaneously by Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score. The primary outcome was 28-day mortality. One hundred and fifteen patients survived and 17 died. maximal chemiluminescent intensity values were significantly lower in the nonsurvivors than in the survivors (p <0.05). We investigated maximal chemiluminescent intensity, APACHE II score, and SOFA score as predictors of 28-day mortality. Receiver operating characteristic analysis showed that area under the curve for maximal chemiluminescent intensity was 0.902, which was superior to the area under the curves for APACHE II score (0.836) and SOFA score (0.807). At the optimal cutoff value for maximal chemiluminescent intensity, 21,000 RLU/s, the sensitivity for correct prediction of 28-day mortality was 82.4% and the specificity was 92.2%. Kaplan-Meier analysis showed that low maximal chemiluminescent intensity (<21,000 RLU/s) closely correlated with poor overall patient survival compared with high maximal chemiluminescent intensity (>21,000 RLU/s) (p <0.001 by log-rank test). After adjusting for APACHE II score by Cox regression analysis, maximal chemiluminescent intensity was identified as an independent predictor for the probability of 28-day mortality.

Conclusion: Maximal chemiluminescent intensity level measured on admission day appears to have high predictive value for mortality in patients with sepsis.

1 Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Japan.

2 Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

3 Department of Biomedical Statistics, Osaka University Graduate School of Medicine, Osaka, Japan.

*See also p. 1575.

The authors have not disclosed any potential conflicts of interest.

Address requests for reprints to: Takeyuki Kiguchi, MD, Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka 558–8558, Japan. E-mail:

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins