Continuous renal replacement therapies in ICU patients with septic shock: impact on inflammatory mediators removal

ABSTRACT

Continuous renal replacement therapies are widely used for patients with acute renal failure specially in critically ill patients in ICU. It has been suggested that hemofiltration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis. The present study examined whether hemofiltration can eliminate inflammatory mediators in patients with sepsis. A total of 28 consecutive patients with septic shock, as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. All patients had renal affection. Patients were randomly assigned to receive hemofiltration in addition to usual ICU care [n = 17] [group 1], or to usual care plus hemodiafiltration [n =11 [group 2]. We measured the plasma concentrations of complement fraction C3a, IL-6 and TNF -a at baseline, 2 hours and 24 hours after these procedures. C3a showed a fall in concentration between baseline and 2 hrs, which not reached statistical significance during hemofiltration [from median 495.5 to 363 ng/ml, P =.48] and statistical significance during hemodiafiltration [from median 524 to 379.7 ng/ml, P = <0.05]. Furthermore, during HF C3a showed a significant fall in concentration during the interval between 2 hrs and 24hrs [from median, 363 to 274.6 ng/mL, p<0.05], HDF [from median, 379.7 to 215.8 ng/mL, p<0.05]. TNF showed a fall in concentration between baseline and 2 hrs, which reached statistical significance during hemofiltration [from median 397.9 to 332.8 pg/ml, P =0.035] and statistical significance during hemodiaflltration [from median 430.7 to 347.2 pg/ml, P 0.02]. However, during HF TNF showed a non significant change in concentration during the interval between baseline and 24hrs [from median, 397.9 to 410.4 pg/mL, p = 0.6], HDF [from median, 430.7 to 405.6 pg/mL, p = 0.5]. IL-6 showed a fall in concentration between baseline and 2 hrs, which reached statistical significance during hemofiltratio in [from median 1051 to 843.6 pg/ml, P =0.03] and statistical significant during hemodiaflltration [from median 1111.3 to 859 pg/ml, P 0.025]. However, during HFJL-6 showed a non significant change in concentration during the interval between baseline and 24hrs [from median, 1051 to 905 pg/ml, p = 0.13], HDF [from median, 1111.3 to 901.9pg/mL, p = 0.07]. No correlation were detected between inflammatory mediators removal and changing the size of hemofilter [surface area 0.7 and 1.35 square meter] p>0.05. or changing hemofiltration rate [from 1 to 2 liters/hour]. p>0.05. In conclusion, short-term hemofiltration with a highly biocompatible membrane in patients with septic multiple organ dysfunction syndrome and renal failure may even eliminate some of the mediators from septic plasma like C 3a. Filtration of the classic cytokines IL-6 and TNF-a is presumably of minor importance, but clearance of the first few hours may occur so we cannot advocate the use of continuous therapies as a treatment in sepsis for removal of inflammatory mediators only, but in presence of renal affection, these slow renal replacement therapies results in fewer cardiovascular side effects than intermittent techniques, Furthermore, continuous hemofiltration allows better control of fluid balance and simultaneous continuation of total parenteral nutrition in addition to reduction of anaphylatoxin concentrations which could be of clinical importance, since beneficial therapeutic effects in sepsis have been correlated with a fall of anaphylatoxin concentrations