Olistic Approach to Treatment Adequacy in AKI

Transcription

1 Toronto - Canada, 2014 Olistic Approach to Treatment Adequacy in AKI Claudio Ronco, MD Department of Nephrology, St. Bortolo Hospital, International Renal Research Institute Vicenza - Italy

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6 1) RRT is a cornerstone for the therapy of of AKI in the ICU 2) Indications have changed over the years (replacement vs support) 3) Mortality has changed over the years and so did the case mix 4) We still have a number of unresolved issues or controversies a) Timing for therapy start and stop b) Correct prescription (Dose and Fluid balance) c) Modality and Schedule d) Monitoring and delivery e) Special treatments for special cases

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8 ADEQUACY Let s agree on the meaning of the term AD AEQUATUM = Equal to.. Are we really able to obtain results similar to those achieved by the human kidney? Are we confusing the term Adequate with minimal or sufficient? I personally would define adequate a treatment when further improvements will not result in further benefit. So far adequacy has been identified by the concept of dose (index, marker molecules).

9 Extracorporeal Hemodialysis S u r v i v a l Alwall Kolff and Scribner et Al, 1966 Dose of Dialysis

10 Extracorporeal Hemodialysis THE MECHANISTIC ANALYSIS 70 Gotch & Sargent Av S u r v i v a l Keshaviah Av Kt/V NCDS: Gotch & Sargent 1985 Alwall Kolff and Scribner et Al, 1966 Dose of Dialysis (Urea)

11 Extracorporeal Hemodialysis S u r v i v a l Dose vs Outcome Studies NCDS: Gotch & Sargent 1985 Alwall Kolff and Scribner et Al, 1966 Dose of Dialysis (Urea)

12 Extracorporeal Hemodialysis Hemo Study S u r v i v a l Dose vs Outcome Studies NCDS: Gotch & Sargent 1985 Alwall Kolff and Scribner et Al, 1966 Dose of Dialysis (Urea)

13 Extracorporeal Hemodialysis Hemofiltration Trials S u r v i v a l Dose vs Outcome Studies NCDS: Gotch & Sargent 1985 Alwall Kolff and Scribner et Al, 1966 Dose of Dialysis (Urea)

14 Extracorporeal Hemodialysis Variable HD online HDF p MPO Study Treatment Flux? Time on RRT (years) Membrane Flux Incident Patients? > < Variable HD online - line HDF p Treatment Time (min/s.) HDF < S u r v i v a l Treatment Frequency > 3 s./wk NS (%) Mean Blood Flow ( ml /min) Hemo Study NS Mean Dialysate Flow ( ml /min) < Equil Kt/V < High - Flux Polysulfone (%) Death High - Flux Risk Polysulfone Reduction (%) % 100 Dose of Dialysis (urea and flux)

15 Extracorporeal Hemodialysis Membrane Flux Treatment Flux Incident Patients Body Comp (V) Dialysis duration Tx Time S u r v i v a l Race & Genetics Gender Diabetes & CVD Frequency of Tx Dose of Dialysis (Urea and beyond)

16 Extracorporeal Hemodialysis Correction of Anemia Survival + quality of Life Dose of Dialysis (Urea and Beyond)

17 PERITONEAL DIALYSIS Breaking Point 1.7? 2.0? 1994 S u r v i v a l ADEMEX Study CANUSA Study Dose of Dialysis (urea and flux)

18 AKI and CRRT S u r v i v a l Survival % Stork M, et Al. The Lancet 1991;337: p < 0.05 Stork M, et Al. The Lancet 1991;337: Ronco et Al, The Lancet 356, 1, 26-30, Uf = < 7 l/24h Uf = 7.5 l/24h Uf = 15 l/24h Group 1(n=146) Dose of Dialysis (Urea ( Uf = 20 + ml/h/kg)?) L/h Ronco et Al, The Lancet 356, 1, 26-30, 2000 p < p < Group 2 (n=139) ( Uf = 35 ml/h/kg) p n..s. Group 3 (n=140) ( Uf = 45 ml/h/kg)

19 AKI and CRRT Saudan et Al, KI 2006 Presence of Sepsis Early Intervention Honoré et Al. CCM, 2002 S u r v i v a l Ronco et Al, The Lancet 356, 1, 26-30, 2000 Bellomo et Al, NEJM 2009 Tolwani et Al, JASN 2008 Palewsky et Al, NEJM 2008 Stork M, et Al. The Lancet 1991;337: Dose of Dialysis (ml/kg/hr)

20 CRRT Prescription vs Delivery Venkataraman et al, J Crit Care, ± ± ±3.5 68% of prescribed dose 67% of total hours in day Prescribed Dose (ml/kg/hr) Delivered Dose (ml/kg/hr) Time/Day (hours)

21 DoReMi Database (N=865) Median delivered = 27 ml/kg/h Median prescribed = 34 ml/kg/h Ronco et al, 2009 Patients (%) < >=75 Dose Dose of of CRRT CRRT (ml/kg/hr) (ml/kg/h) Delivered dose Prescribed dose

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23 Renal Replacement Therapy in AKI Practice-Dependent Region S u r v i v a l Dose-Dependent Region Dose of Dialysis (Urea and Beyond)

24 QUESTIONS Adequacy for what? What is the task and target of therapy? Is adequacy target the same for different patients? Is adequacy target constant over time? Are prescription and delivery the same thing? Is it the same to achieve the adequacy target with different modalities Should I consider miltiple parameters to define adequacy?

25 Renal Replacement Therapy Absolute Life Threatening conditions Solute control Homeostatic control Acid-base regulation Relative Renal Support Therapy Volume removal in FO patients Immuno-modulation in sepsis Nutrition support Cancer chemotherapy Attenuate ARDS-induced respiratory acidosis Volume homeostasis in multi-organ dysfunction/failure

26 QUESTIONS Adequacy for what? What is the task and target of therapy? Is adequacy target the same for different patients? Is adequacy target constant over time? Are prescription and delivery the same thing? Is it the same to achieve the adequacy target with different modalities Should I consider miltiple parameters to define adequacy?

27 RRT MORTALITY IN AKI A PROBLEM OF SEVERITY SCORE 100 % Mortality Kidney K + 1 K + 2 K + 3 Number of failing organs

28 CRRT: Impact on Outcomes The Cleveland Clinic Observation Survival % Low Dose (IHD) Severity of Disease High Dose (CRRT)

29 QUESTIONS Adequacy for what? What is the task and target of therapy? Is adequacy target the same for different patients? Are adequacy targets constant over time? Are prescription and delivery the same thing? Is it the same to achieve the adequacy target with different modalities Should I consider miltiple parameters to define adequacy?

30 Azotemia F O % 0 Day 1 Day 3 Day 5 Day 7 Day 1 Day 3 Day 5 Day 7 0 Admission Admission

31 Restrictive Fluid protocols Liberal Fluid protocols Risk of Complications Normal Heart Diseased Heart Hypotension Tachycardia Shock Organ hypoperfusion Oliguria Renal Dysfunction Procedures Drugs R R T Optimal Status Hypertension Peripheral Edema Impaired pulmonary exchanges Organ Congestion Renal Dysfunction Dehydration Fluid Balance Overhydration

32 Bicarbonate levels in CVVH and Daily HD D Short HD HCO3 (meq/l) CVVH D Ext.HD Hours of observation

33 QUESTIONS Adequacy for what? What is the task and target of therapy? Is adequacy target the same for different patients? Are adequacy targets constant over time? Are prescription and delivery the same thing? Is it the same to achieve the adequacy target with different modalities Should I consider miltiple parameters to define adequacy?

34 Treatments for extracorporeal volume removal Technique Frequency Ultrafiltration Hemofiltration Hemodialiysis Hemodiafiltration Isolated Intermittent Daily Continuous

35 D short HD BUN (mg/dl) CVVH 20 D Ext. HD Hours of treatment

36 Composition of fluid removed Continuous Hemofiltration allows for correction of sodium and water disorders by dissociating water and sodium removal Pl. Na + Uf Na + Rem Repl. R Na + Fluid Bal. Na + Bal L Kg mmol L L Kg mmol

37 Blood Volume Variation (%) UF Uf = 3030 ml SCUF Uf = 3050 ml Mean Art. Press. (mmhg) Hours of observation

38 Uf / Refilling rate related hypotension Overall ECFV related hypotension R e l a t i v e Blood Pressure Blood Volume α α 1 C h a n g e s Sequential BNP +BIVA measurements UF beginning UF end

39 CRRT-Associated Mortality in Major RCTs Clinical Trial Comparison APACHE II Endpoint Mortality Ronco et al (2000) CRRT Dose 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 day 66% 3 Vinsonneau et al (2006) IHD vs CRRT day 68% Lins et al (2008) IHD vs CRRT 27 Hospital 58% Tolwani et al (2008) CRRT Dose 26 Hospital 60% 3 ATN Trial (2008) Dialysis Dose day 52.5% 4 RENAL Trial (2009) CRRT Dose ~ day 45% 1: APACHE III score : After CRRT cessation 3: Mortality in low-dose group 4: Overall (CRRT + IHD) mortality

40 Comparison of RENAL with ATN Variable RENAL VA/NIH Mortality day % Mortality day % RRT days (at 28 days) Hospital LOS (days) Dialysis % 45.2% Dialysis % Dialysis %

41 QUESTIONS Adequacy for what? What is the task and target of therapy? Is adequacy target the same for different patients? Are adequacy targets constant over time? Are prescription and delivery the same thing? Is it the same to achieve the adequacy target with different modalities Should I consider miltiple parameters to define adequacy?

42 Adequacy of Extracorporeal Support Urea-based Dosing Control of inflammation Membrane Sieving Timing and Schedule of Tx Spectrum of Solute MV Organ Substitution/Support Restoration of Homeostasis Volume Control Limitation of Oxidant stress Acid-Base Balance

43 Contr. of sepsis Fluid balance Kt/V or ml/h/kg Middle Molecules Cardiovascular Coagulation P & Ca Homeostasis Nutrition Severity scores

44 Contr. of sepsis Fluid balance Kt/V or ml/h/kg Middle Molecules Cardiovascular Coagulation P & Ca Homeostasis Nutrition Severity scores

45 Contr. of sepsis Fluid balance Kt/V or ml/h/kg Middle Molecules Cardiovascular Coagulation P & Ca Homeostasis Nutrition Severity scores

46 Contr. of sepsis Fluid balance Kt/V or ml/h/kg Middle Molecules Cardiovascular Coagulation P & Ca Homeostasis Nutrition Severity scores

47 Contr. of sepsis Fluid balance Kt/V or ml/h/kg Middle Molecules Cardiovascular Coagulation P & Ca Homeostasis Nutrition Severity scores

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