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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  Childrenโ€™s Healthcare of Atlanta at Egleston Division of Pediatric Critical Care Medicine Emory University School of Medicine, Atlanta, GA USA
Sepsis and CRRT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Sepsis and CRRT: Peak Concentration Hypothesis Adapted from Ronco C, et al, Artif Organs 2003
Controversy in Sepsis and CRRT  ,[object Object],[object Object],[object Object]
Fas/Soluble Fas Ligand (sFasL) System ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hypothesis ,[object Object]
Study Design ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Study Design ,[object Object],[object Object],[object Object],[object Object]
Results ,[object Object],MSSA Toxic Shock 17 yo Multiple Ruptured appendix 7 yo S. viridans T-cell ALL 16 yo S. hominis BMT for AML 14 yo MRSA Septic shock 15 yo S. pneumoniae HUS 14 mo Organism Disease Age
Results ,[object Object],Severe dehydration 14 yo ALL, pancreatitis 15 yo Pulmonary edema 16 yo Disease Age
Results Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH 24 Hours off CVVH
Results Pre-CVVH 12 Hours 24 Hours 48 Hours End of CVVH 24 Hours off CVVH
Absolute cytokine changes in septic shock/ARF patients Log Concentration (pg/ml) p<0.02 * p=0.04 *
Absolute cytokine changes in septic shock/ARF patients Log Concentration (pg/ml) p=0.132 p=0.818
IL-8 Percent Changes From Pre-CVVH Baseline Septic ARF Patients Non-septic ARF Patients * p<0.03 * * * * *
Mean Percent Decrease in Septic Shock/ARF Patients Septic ARF Patients Non-septic ARF Patients * p<0.05 * *
Mean Percent Decrease in Septic Shock/ARF Patients Septic ARF Patients Non-septic ARF Patients * p<0.05 * *
Ultrafiltrate Cytokine Levels Septic ARF Patients Non-septic ARF Patients
Ultrafiltrate Cytokine Levels Septic ARF Patients Non-septic ARF Patients
sFasL Analysis 12 h 24 h 48 h End of CVVH 24 h off CVVH
sFasL Response ,[object Object],[object Object],[object Object]
Conclusions ,[object Object],[object Object],[object Object],[object Object],[object Object]
Implications ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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45 paden pcrrt and cytokine

Editor's Notes

  1. Failure of Anti TNF-alpha , IL-1, and Interferon Gamma monoclonal antibodies. Improve hemodynamics/nutrition/volume overload, Controversy on cardiac output and oxygenation
  2. 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. CRRTโ€™s clearance of everything is its greatest benefit. Restore cytokine levels to a more homeostatic and physiologic level.
  3. Found to play a role in decreased creatinine clearance in CRF. Uremic serum upregulates this pathway.
  4. 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
  5. 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 โ€“ levels at d/c of CVVH in septic patients are more than the highest levels in non-septic patients.
  6. Still see the same overall pattern, the scale is just smaller. Lack a rebound after coming off of CVVH.
  7. IL-6 12704 to 183 IL-10 706 to 45
  8. 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.
  9. 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.
  10. FAKE DATA HERE โ€“ REPLACE BEFORE CONFERENCE
  11. Both absolute decrease and greater relative decrease compared to non-septic ARF patients.
  12. Thank Dr. Pearson and the Emory Transplant Center.