Cysteinyl-leukotriene generation as a biomarker for survival in the critically ill

Objective: To evaluate the capacity of cysteinyl-leukotriene generation in the progression of critical illness compared with that in healthy volunteers and to clarify interrelationships between the rate of leukotriene generation, severity of the disease, and clinical outcome. Design: Prospective, observational study. Setting: Surgical intensive care unit (ICU) in a German university hospital. Patients: We studied 14 ICU patients (nine men, five women; aged 42-82 yrs) suffering from systemic inflammatory response syndrome, sepsis, or sepsis syndrome, with a calculated sepsis severity score of 17.7 +/- 4.2 and a Simplified Acute Physiology score of 17.6 +/- 3.0, In addition, five healthy volunteers (three men, two women; aged 34-38 yrs) were included in the study. Interventions: None. Measurements and Main Results: Blood samples were obtained every second day from septic patients until discharge from the ICU or death. Leukotriene C-4 (LTC4) synthesizing capacity was assessed in isolated and stimulated leukocytes (Ca-ionophore) by using combined reversed-phase, high-pressure liquid chromatography and radioimmunoassay methods. Initially, all patients synthesized less LTC4 than the healthy subjects. In patients who did not survive, the low LTC4 generation persisted throughout the observation period, whereas in surviving patients, its formation was normalized during convalescence. In surviving patients, LTC4 concentrations correlated with sepsis severity score. Conclusions: LTC4 generation is impaired in sepsis and may serve as a biomarker for survival in the critical ill.