ENDOTOXEMIA AND INFLAMMATORY MEDIATORS IN FEBRILE PATIENTS WITH HEMATOLOGICAL DISEASE

Objectives. To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactiv e protein (CRP) in febrile neutropenic patients and to assess the pote ntial diagnostic value of these analyses. Design, Consecutive prospect ive study, Setting. Patients treated at the haematology ward at Dander yd Hospital, Sweden, Subjects. Ninety-four patients with fever and hae matological disease entered the study (male/female: 59/35) with 176 fe brle episodes, Interventions. Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF-alpha, IL- 6 and CRP. Results. Infectious aetiology was established in 62.5% of t he febrile episodes. Blood cultures showed significant growth in 71/17 6 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were d iagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF-alpha was dete cted in 61% and IL-6 in 94% of all febrile episodes. The initial TNF-a lpha and IL-6 levels were significantly higher in patients with Gram-n egative bacteraemia than in patients with other causes of fever (P < 0 .001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P < 0.001) decrease in CRP concentrations we re found on day 6 after onset of fever. Conclusions. The sustained, lo w-grade endotoxaemia and persistently elevated levels of TNF-alpha and IL-6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. Th e diagnostic value of endotoxin, TNF-alpha, IL-6 and CRP to discrimina te between bacteraemic and nonbacteraemic febrile episodes was very li mited. The study supports the present policy of broad, empirical antib iotic treatment in patients with haematological disease and fever.