Endotoxemia and bacteremia in patients with sepsis syndrome in the intensive care unit

Abstract

Study objectives: To study circulatory endotoxin (ET) in patients with sepsis syndrome (SS) in order to answer three questions: (a) How often and at which concentration is ET present in the plasma of patients with SS and is the presence of ET a prognostic marker in this situation? (b) Is detection of ET helpful in predicting Gram-negative bacterial infections with or without bacteremia? (c) What are the kinetics of clearance of ET concentrations in plasma?

Design: Prospective study of consecutive patients fulfilling Bone's criteria for SS.

Setting: Medical ICU in a teaching hospital.

Patients: The study included 93 patients. The simplified acute physiologic score was 19 +/- 6, 49 percent were in shock, and 54 percent were mechanically ventilated. The mortality at day 28 was 53 percent.

Measurements: Endotoxin determinations and blood cultures were performed simultaneously at the onset (day 1) of SS. Samples were collected on several days from 48 patients. Endotoxin concentration was determined using an end point chromogenic Limulus assay. For the first ET determination, the mean circulatory level (mean +/- SEM) was calculated among patients with detectable ET, thus excluding patients with a null value for ET.

Results: On day 1, ET was detected in 44 patients (47 percent; 60.2 +/- 16.5 pg/ml) and was statistically more frequent in patients with shock, elevated plasma lactate, and organ failure. There was no statistical difference for age, gender, ratio of PaO2 to fraction of inspired oxygen. Among patients with proven Gram-negative bacterial infection (n = 46), ET was detected in 67 percent as compared with 28 percent without Gram-negative bacterial infection (p = 0.0001). On day 1, among 19 patients who had positive blood cultures with Gram-negative bacteria (GNB), 15 had detectable ET (79 percent, 61 +/- 22 pg/ml). In 14 other patients whose blood cultures were positive for GNB but became negative on day 1, 9 had detectable ET (64 percent; 36 +/- 6.5 pg/ml). Endotoxin declined linearly between days 1 and 4.

Conclusion: In our study, the plasma ET concentration predicts neither Gram-negative infection, with or without bacteremia, nor the outcome. However, when ET is present in the plasma of patients with SS it remains detectable for a long period of time as compared to its rapid disappearance from plasma of animals or healthy human volunteers receiving ET intravenously. This slow clearance of ET suggests either a continuous release or a defect in its clearance.