Cytokine and sFasL Response in Children with Septic ARF on CVVH
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This document summarizes a study examining the cytokine and soluble Fas ligand response in children with septic acute renal failure undergoing continuous venovenous hemofiltration (CVVH). The study found that CVVH significantly removed both pro-inflammatory (IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pediatric patients with septic shock compared to those with non-septic acute renal failure. The decreases in cytokine levels were greater for septic patients. Convective clearance was likely the mechanism of removal. Soluble Fas ligand concentration was not changed by CVVH.
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Cytokine and sFasL Response in Children with Septic ARF on CVVH
- 1. Cytokine and Soluble Fas Ligand Response in Children with Septic Acute Renal Failure (ARF) on CVVH Paden ML, Fortenberry JD, Rigby MR, Trexler AM, Heard ML, Rogers K Children’s Healthcare of Atlanta at Egleston Division of Pediatric Critical Care Medicine Emory University School of Medicine, Atlanta, GA USA
- 3. Sepsis and CRRT: Peak Concentration Hypothesis Adapted from Ronco C, et al, Artif Organs 2003
- 11. Results Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH 24 Hours off CVVH
- 12. Results Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH 24 Hours off CVVH
- 13. Absolute cytokine changes in septic shock/ARF patients Log Concentration (pg/ml) p<0.02 * p=0.04 *
- 14. Absolute cytokine changes in septic shock/ARF patients Log Concentration (pg/ml) p=0.132 p=0.818
- 15. IL-8 Percent Changes From Pre-CVVH Baseline Septic ARF Patients Non-septic ARF Patients * p<0.03 * * * * *
- 16. Mean Percent Decrease in Septic Shock/ARF Patients Septic ARF Patients Non-septic ARF Patients * p<0.05 * *
- 17. Mean Percent Decrease in Septic Shock/ARF Patients Septic ARF Patients Non-septic ARF Patients * p<0.05 * *
- 18. Ultrafiltrate Cytokine Levels Septic ARF Patients Non-septic ARF Patients
- 19. Ultrafiltrate Cytokine Levels Septic ARF Patients Non-septic ARF Patients
- 20. sFasL Analysis 12 h 24 h 48 h End of CVVH 24 h off CVVH
Editor's Notes
- Failure of Anti TNF-alpha , IL-1, and Interferon Gamma monoclonal antibodies. Improve hemodynamics/nutrition/volume overload, Controversy on cardiac output and oxygenation
- SIRS = pro-inflammatory response mediated by IL-1, 6, 8, TNF alpha CARS = coined by Dr. Bone to reflect anti-inflammatory response mediated by IL-10, PGE2 It is the overall overproduction of both pro and anti inflammatory cytokines that is the problem in sepsis. CRRT’s clearance of everything is its greatest benefit. Restore cytokine levels to a more homeostatic and physiologic level.
- Found to play a role in decreased creatinine clearance in CRF. Uremic serum upregulates this pathway.
- Mention IRB approval. Part of a larger study examining the response of urine output to initiation of CVVH. Excluded chronic renal failure. Cytokines measured by cytometric bead array - flow cytometry
- Point 1 is pre-CVVH, point 5 is discontinuation of CVVH. Generally, you see a decrease overtime with institution of CRRT. Is this because the patient is getting CRRT or just because the patient is getting better? Note what happens in septic patients 24 hours after off CVVH (time point 6). Argues that CVVH is at least having some response in clearing these and not just patient improving. Also note scale – levels at d/c of CVVH in septic patients are more than the highest levels in non-septic patients.
- Still see the same overall pattern, the scale is just smaller. Lack a rebound after coming off of CVVH.
- IL-6 12704 to 183 IL-10 706 to 45
- Note scale change. While trend was the same, it was not statistically signifant in this small sample. IL-8 4166 to 384 sFasL 130.5 to 41.1 No signifcant absolute change was seen for any cytokine in non-septic patients.
- Because of such large differences in starting cytokine concentrations, we compared values at the end of CVVH and 24 hours afterwards to baseline (Pre-CVVH) values in both septic and control patients. We found that IL-8,10 concentrations had signficant decreases in septic patients. This same decrease was not seen in the control population.
- FAKE DATA HERE – REPLACE BEFORE CONFERENCE
- Both absolute decrease and greater relative decrease compared to non-septic ARF patients.
- Thank Dr. Pearson and the Emory Transplant Center.