DOSE DIALITICA E OUTCOME: UN PROBLEMA ANCORA APERTO Angelo F. Perego Nefrologia e Dialisi Ospedale Vittorio Emanuele III Monselice (PD) ULSS 17 Veneto GDS SIN TRATTAMENTI DEPURATIVI IN AREA CRITICA STAMPA A COLORI 0ANTONE 0ANTONE GRIGIO ARGENTO
Status of issues concerning RRT use in the ICU Continuous renal replacement therapy: recent advances and future research John R. Prowle & Rinaldo Bellomo Nature Reviews Nephrology 6, 521-529 (September 2010) CRRT dose A resolved issue in favor of conventional dosing (target effluent flow rate 20 25 ml/kg per h)????!!!!! = 42 L/die??? CRRT versus IHD Consensus in favor of CRRT in hemodynamically unstable critically ill patients, but without formal evidence Timing of CRRT Unresolved issue that requires further research CRRT outcomes Unresolved issue; studies to date may have been too focused on mortality over renal recovery and other patient-centered outcomes CRRT modality Unresolved issue CRRT modalities might be equivalent
GFR = 130-180 L/die
Figure 1 Relationship between delivered RRT intensity and survival in critically ill patients with acute kidney injury (AKI) John A. Kellum & Claudio Ronco (2010) Results of RENAL what is the optimal CRRT target dose? Nat. Rev. Nephrol. doi:10.1038/nrneph.2010.15
CRRT cosa? SCUF CVVH CVVHD CVVHDF EDD; SLED SLEDD SLEDD-f CPFA NO REINFUSIONE POST-DILUIZIONE PRE-DILUIZIONE PRE+POST- DILUIZIONE
Effluente COSA? Ultrafiltrato puro di plasma ( post-dil)? Ultrafiltrato da pre-diluizione? Ultrafiltrato da pre+post-diluizione? Bagno di dialisi?
Effluent Volume in Continuous Renal Replacement Therapy Overestimates the Delivered Dose of Dialysis R. Claure-Del Granado*,Etienne Macedo*,Glenn M. Chertow,Sharon Soroko*,Jonathan Himmelfarb,T. Alp Ikizler, Emil P. Paganini,Ravindra L. Mehta* Conclusions: Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume. CJASN March 2011 vol. 6 no. 3 467-475
Percent Decrease in Solute Clearance During High-Dose Pre-Dilution CVVH #,* Troyanov et al, Nephrol Dial Transplant 2003 Filter (m 2 ) Urea Creatinine Phosphate β 2 M M-100 33.8 ± (0.9) a 2.6 38.2 ± 2.2 38.8 ± 1.6 39.0 ± 3.1 HF1000 (1.1) b 9 34.4 ± 2.3 39.4 ± 1.5 41.4 ± 4.0 44.0 ± 2.4 # : Results expressed as % decrease relative to postdilution *: Q B = 125-150 ml/min; Q F = 4.5 L/hr a : mean Hct = 0.26 ± 0.04 b : mean Hct = 0.30 ± 0.05
Table 1 Randomized trials comparing CRRT with IHD in the ICU Prowle, J. R. & Bellomo, R. (2010) Continuous renal replacement therapy: recent advances and future research Nat. Rev. Nephrol. doi:10.1038/nrneph.2010.100
CRRT-Associated Mortality in Major RCT s Clinical Trial Comparison APACHE II Endpoint Mortality Ronco et al (2000) CRRT Dose 22 15-day 2 59% 3 Mehta et al (2001) IHD vs CRRT 25.5 Hospital 66% Augustine et al (2004) IHD vs CRRT - Hospital 68% Saudan et al (2006) CRRT Dose 25 90-day 66% 3 Vinsonneau et al (2006) IHD vs CRRT 25 60-day 68% Lins et al (2008) IHD vs CRR 27 Hospital 58% Tolwani et al (2008) CRRT Dose 26 Hospital 60% 3 ATN Trial (2008) Dialysis Dose 26.3 60-day 52.3 4 RENAL Trial (2009) CRRT Dose ~26 1 90-day 45% 1: APACHE III score 102-103 2: After CRRT cessation 3: Mortality in low-dose group 4: Overall (CRRT + IHD) mortality
Table 2 Randomized controlled trials comparing CRRT dose in the ICU Prowle, J. R. & Bellomo, R. (2010) Continuous renal replacement therapy: recent advances and future research Nat. Rev. Nephrol. doi:10.1038/nrneph.2010.100
Comparison of Major CRRT Dose Trials Ronco Saudan Tolwani ATN Number of patients 425 206 200 1124 Multi-center RCT No No No Yes CKD (%) NA 33 42 Exclusion Predominant AKI cause Surgical Sepsis Sepsis Ischemia APACHE II ~23 25 26 ~29 Initiation BUN (mg/dl) 53 83 75 65 Modality post CVVH pre CVVHDF pre CVVHDF pre CVVHDF % Convective 100 ~60 43-44 50 Prescribed dose (ml/kg/h) 20/35/45 25/42 20/35 20/35 Effective dose (ml/kg/h) 20/35/45 ~20/37 ~17/29 ~17/27 ICU wait (days) NA NA 8 6.9
ATN Study
Interpretation of ATN Results: A Cautionary Note for Physicians The National Cooperative Dialysis Study (NCDS) should give pause to those who favor an immediate reduction in CRRT dose NCDS was performed in US chronic HD patients during the late 1970 s First large-scale trial to study the relationship between dose and survival A flawed analysis of the data resulted in a misinterpretation of the results and a downward trend in dose prescription for 15 years in the US The results were disastrous, with residual effects still influencing clinical practice in the US The NCDS debacle argues strongly against a rush to judgment with regard to the ATN Trial results 18
Molecular Transport Mechanisms Ultrafiltration Diffusion Convection Adsorption } Solute Fluid Transport Transport
Sieving Characteristics caratteristiche di SETACCIO che identificano il CUT-OFF point 100.0 80.0 Percent Permeated 60.0 40.0 20.0 MWCO MWCO = Molecular Weight Cut-Off 0.0 1 10 100 1000 S = C permeate C Feed Molecular Weight (kda( kda)
CONSIDERAZIONE FINALE Tutta la letteratura, ad oggi, non mostra differenze, in termini di sopravvivenza, tra trattamenti intermittenti; continui; diffusivi, convettivi o combinati; ad alta o bassa dose QUALE IPOTESI UNIFICANTE PER SPIEGARE QUESTA ANGOSCIANTE ASSENZA DI RISULTATI?
BERNARDINO DI BETTO detto il PINTURICCHIO 1495 Perugia, Galleria Naz.Umbra
RIFLESSIONI INTORNO ALLA DOSE MODALITA SPETTRO RIMOZIONE QB QF QD PRE, POST, PRE+POST FILTRO: TIPO di MEMBRANA, CUT-OFF, SUPERFICIE ANTICOAGULAZIONE TIPI DI ACCESSO VASCOLARE
Original Paper Long-Term Clinical Results with High-Efficiency Hemofiltration G. Civati, C. Guastoni, A. Perego, U. Teatini, M. Giachetti, F. Zoppi, L. Minetti Renal Unit and Department of Biochemistry, Niguarda Ca' Granda Hospital, Milano, Italy Uremic toxicity is widely thought to be caused by the retention of a large spectrum of solutes, ranging from small to large molecular weight. Hemodialysis (HD), although achievinga high clearance of small molecules, does not permit a satisfactory removal of middleand large molecules. Conventional hemofiltration (CHF) improves the removal of middleand large molecules, but removes less small molecules compared to HD. A really satisfactory removal of small, middle and larger solutes can only be achieved by post-dilution high-efficiency hemofiltration (HEHF), surpassing the performances of both HD and CHF. On this basis the authors formulate a prescription about hemofiltration dose (2 L/KG/week). The artificial GFR given to each patient must be comparable to that of a symptom-free patient with a residual GFR of 8-10 ml/min. Vol. 1, No. 3, 1983