IMPACT OF CONTINUOUS HEMOFILTRATION ON CYTOKINES AND CYTOKINE INHIBITORS IN OLIGURIC PATIENTS SUFFERING FROM SYSTEMIC INFLAMMATORY RESPONSESYNDROME

The impact of continuous hemofiltration (CHF) using a polyacrylonitril e membrane on the kinetics of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and their inhibitors (soluble TNF rec eptors [sTNFrI, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflamm atory response syndrome. Blood and plasma flow (Q(b), Q(p)), sieving c oefficient (SC), plasma and ultrafiltrate clearances (K-p, K-uf), and plasma extraction rates (ERp) were calculated at different time points using standard formulas. No significant improvement of hemodynamics o r gas exchange was noted following HF but a significant increase in se rum bicarbonate occurred after 24 h (P < 0.05). TNF alpha was detected in plasma from all patients (153 +/- 2.3 pg/mL [mean +/- SEM]). None of the patients had detectable IL-1 beta levels. High levels of the TN F receptors (sTNFrI 20.338 +/- 2.431 pg/mL; sTNFrII 17.839 +/- 2.630 p g/mL) and IL-1Ra (19.775 +/- 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrI/TNF alpha ratio amounted to 269 +/- 84.6 and the sTNFrII/TNF alpha ratio to 249 +/- 91.8. Mean ultrafiltrate volume (V-uf) was 11.8 +/- 0.4 L/d ay. Appreciable sieving of IL-1Ra (SC 0.45 +/- 0.10), but not of the o ther cytokines, was noted (SCTNF alpha, sTNFrI, sTNFrII < 0.09). Despi te minimal K-uf of TNF alpha, sTNFrI, and STNFrII (K-uf < 0.8 mL/min), appreciable K-p was noted, suggesting that membrane adsorption occurs (K-p approximate to 8 mL/min). There as a nonsignificant increase of the ratios between both TNF receptors and TNF alpha across the filter (sTNFrI/TNF alpha ratio [pre] 231 +/- 37.9 versus [post] 312 +/- 75.3) ; sTNFrII/TNF alpha ratio [pre] 211 +/- 42.1 versus [post] 291 +/- 79. 3). Appreciable K-p of IL-1Ra was noted (K-p 17.3 +/- 1.61 mL/min), wh ich was only in part due to K-uf (4.0 +/- 0.86 mL/min). There was a si gnificant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 +/- 2.282 versus [post] 16.637 +/- 2.039 pg/mL; P < 0.01 ) and at different time points (P < 0.01). Only for IL-1Ra was signifi cant extraction from plasma noted (ERp 26 +/- 6.0%). Plasma levels of TNF alpha, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF . In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane a bsorption. Using low-volume HF (V-uf approximate to 12 L/day), no impa ct on cytokine plasma levels nor the patients hemodynamics or gas exch ange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (> 50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to b e investigated.