Objective: To prospectively evaluate the prognostic values of two serum cytokine levels, TNF alpha and IL6 serially measured at predetermined intervals in septic shock patients unresponsive to correction of hypoxaemia and plasma volume expansion and treated according to a strict protocol designed to meet specific therapeutic goals (goal-directed therapy). The evolution of serum lactate levels and oxygen-derived parameters was also investigated.
Design: A prospective case series study. Patients were followed-up until they were discharged from the hospital, or died.
Setting: ICU of a university hospital.
Patients: 30 consecutive patients with septic shock of various origins.
Interventions: The therapy was aimed at achieving and maintaining for at least 24 h supranormal values CI (> or = 4.0 l.min-1.m-2), oxygen delivery (DO2 > or = 550 ml.min-1.m-2) and oxygen uptake (VO2 > or = 150 ml.min-1.m-2) using a combination of fluid loading, norepinephrine, dobutamine and dopamine. A significant decrease in TNF alpha levels was associated with a favourable outcome while TNF alpha levels remained elevated in the patients who died in shock or of multiple organ failure. No prognostic value was associated with changes in IL 6 concentrations. In a stepwise logistic regression analysis, only TNF alpha levels contributed significantly to prediction of patients' outcome. A significant decrease in serum lactate concentrations was observed both in survivors and in patients who survived the episode of septic shock, but subsequently died of multiple organ failure. A positive DO2/VO2 relationship was observed only in survivors but did not contribute significantly to prediction of patient outcome.
Conclusions: TNF alpha is a major mediator involved in the pathogenesis of septic shock and its decrease was significantly associated with a favourable outcome. IL 6 is certainly involved in the pathophysiology of septic shock but further studies are required to determine whether or not it is directly involved in the mediation of late and lethal complications of septic shock. Serum lactate levels and oxygen-derived variables were of less interest as prognostic factors.