1. Extracorporális szervpótlás helyzete az intenzív betegellátásban
Prof. Dr. Balla József1
Prof. Dr. Fülesdi Béla2
tanszékvezető egyetemi tanár
tanszékvezető egyetemi tanár
1Debreceni Egyetem OEC Belgyógyászati Intézet Nephrologiai Tanszék,
FMC Extracorporalis Szervpótló Centrum, Debrecen
2Debreceni Egyetem OEC Aneszteziológiai és Intenzív Terápiás tanszék, Debrecen

2. Acute Kidney Injury – Renal Replacement Therapies
József Balla & Béla Fülesdi
University of Debrecen
Hungary

3. Medical and Health Scince Center University of Debrecen

4. Renal Replacement Therapies University of Debrecen
AKI (221) – RRT (112)
Hybrid form
IHD (39) SLED (5) CRRT (72)
CVVHDF (31) + CRRT (41)
HD (15) + HDF (25) CVVHD (29) + CVVH (12)
CVVHD-LMWH/Hirudin (17/3) + CVVHD-CiCa (9)
Alternate (27), Daily (9), Extended (3)
Medical and Health Science Center; March, 2013

6. CVVH, HVHF, CVVHD, CVVHDF
SLED

8. „Prometheus”
Németh Csilla
Palotai Ilona

9. AKI: Acute Kidney Injury/Impairment
The shift of terminology from ARF to AKI has been well received by the research and clinical communities
AKI as defined by the RIFLE criteria is now recognized as an important syndrome
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

10. Renal Replacement Therapies (RRT) Akut vesekárosodás (AVK)
Acute Kidney Injury
(AKI )
Renal Replacement Therapies (RRT)
Intermittent (IHD)
Continuous (CRRT)
Slow Low Efficiancy Dialysis
(SLED)
Akut vesekárosodás (AVK)
Vesepótló kezelés
Intermittáló
Folyamatos vesepótló kezelés
Alacsony hatékonyságú elnyújtott, tartós

11. AKI: Acute Kidney Injury/Impairment
Definition - Stage 1 (RIFLE-Risk)
Serum creatinine increased times baseline
(known or presumed to have occurred within the prior 7 days) or
Serum creatinine increase > 26.5 μmol/l (within 48 hours)
Urine volume < 0.5 ml/kg/h for 6-12 hours
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

12. Hemodialysis

13. Hemofiltration

14. AKI – RRT Modality of renal replacement therapy for patients with AKI
Use continuous and intermittent RRT as complementary
therapies in AKI patients. (Not Graded)
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

15. Modality of renal replacement therapy for patients with AKI
We suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients (2B).
In non-septic AKI, ml/kg/h remains optimal.
We suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. (2B).
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

16. AKI – RRT Modality of renal replacement therapy for patients with AKI
Until the IVOIRE trial becomes available, septic AKI should be treated by continuous veno-venous hemofiltration at 35 ml/kg/h.
Honoré PM, Jacobs R, Boer W, Joannes-Boyau O, De Regt J, De Waele E, Van Gorp V, Collin V, Spapen HD.
New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid therapies in septic acute kidney injury. Blood Purif.
2012;33:44-51
CVVHD-CiCa: BW = 70 kg, 24 x 2,4L = 35 ml/kg/h

17. AKI: Acute Kidney Injury/Impairment
The optimal timing of RRT for AKI is not defined
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

18. Maintaining fluid homeostasis
Fluid overload in critical illness and AKI is associated with adverse outcomes.
Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008;12: R74.
Foland JA, Fortenberry JD, Warshaw BL, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 2004; 32: 1771–1776.
Gillespie RS, Seidel K, Symons JM. Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol 2004; 19:1394–1399.
Goldstein SL, Currier H, Graf C, et al. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001; 107: 1309–1312.
Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multiorgan dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 2005; 67: 653–658.
Hayes LW, Oster RA, Tofil NM, et al. Outcomes of critically ill children requiring continuous renal replacement therapy. J Crit Care 2009; 24:394–400.
Sutherland SM, Zappitelli M, Alexander SR, et al. Fluid overload and mortality in children receiving continuous renal replacement therapy:the prospective pediatric continuous renal replacement therapy registry.Am J Kidney Dis 2010; 55: 316–325.
Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluidmanagement strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575.

19. Maintaining fluid homeostasis
Patients dialyzed for control of both azotemia and volume overload experienced the worst outcome.
Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008;12: R74.
Foland JA, Fortenberry JD, Warshaw BL, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 2004; 32: 1771–1776.
Gillespie RS, Seidel K, Symons JM. Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol 2004; 19:1394–1399.
Goldstein SL, Currier H, Graf C, et al. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001; 107: 1309–1312.
Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multiorgan dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 2005; 67: 653–658.
Hayes LW, Oster RA, Tofil NM, et al. Outcomes of critically ill children requiring continuous renal replacement therapy. J Crit Care 2009; 24:394–400.
Sutherland SM, Zappitelli M, Alexander SR, et al. Fluid overload and mortality in children receiving continuous renal replacement therapy:the prospective pediatric continuous renal replacement therapy registry.Am J Kidney Dis 2010; 55: 316–325.
Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluidmanagement strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575.
Mehta RL, McDonald B, Pahl M, et al. Continuous vs. intermittent dialysis for acute renal failure in the ICU: Results from a randomized multicenter trial (abstract). J Am Soc Nephrol 1996; 7: 1456.

20. Underlying disease When to start RRT
Type and severity of the underlying disease
ANCA vasculitis
Brockmann et al: Proteinase-3 as the major autoantigen
of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis.
Arthritis Res. 2002;4(3):220-5.

21. Timing of initiation of RRT on outcome
early vs. late initiation
Observational studies:
Single-center observational studies that were restricted to AKI after trauma (HD) and coronary artery bypass surgery (CVVHDF, CVVH)
early starters - BUN 15 mM, late starters - BUN 33 mM
early starters – urine output is less than 100 mL/8 hours
time between the operation and the initiation
Conclusion: Suggested a benefit (survival ) to RRT initiation at early start (at lower BUN concentrations)
Gettings LG, Intensive Care Med 1999; 25: 805–813., Demirkilic U, J Card Surg 2004; 19: 17–20.
Elahi MM, Eur J Cardiothorac Surg 2004; 26: 1027–1031.

22. Timing of initiation of RRT on outcome
early vs. late initiation
Observational studies:
A prospective multicenter observational cohort study
Program to Improve Care in Acute Renal Disease (PICARD)
243 patients, adjusted for age, hepatic failure, sepsis, thrombocytopenia, and SCr
Conclusion: initiation of RRT at higher BUN [blood urea > 27.1 mmol/l]
was associated with an increased risk of death (RR 1.85; 95%
CI 1.16–2.96)
Liu KD, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury.
Clin J Am Soc Nephrol 2006; 1:915–919.

23. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery.
Shiao CC, et al. Crit Care 2009; 13: R171.
indications for RRT
Underscore the importance of predicting prognoses of major abdominal surgical patients
with AKI by using RIFLE classification

24. Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis
early vs. late initiation
Meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% confidence interval, 0.40 to 1.05; P = 0.08)
In cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% confidence interval, 0.64 to 0.82; P < 0.001).
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL. Am J Kidney Dis. 2008;52:272–284

25. AKI: Acute Kidney Injury/Impairment
The optimal timing of RRT for AKI is not defined
Urea > 36 mM
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

26. AKI: Acute Kidney Injury/Impairment
The optimal timing of RRT for AKI is not defined
Urea > 36 mM
Potesium > 6 mM
pH < 7.15
etc.
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

27. The optimal timing of dialysis for AKI = Indications for RRT
Initiate RRT emergently when
Life-threatening changes in fluid
electrolyte
acid-base balance
uremic complications: pericarditis, pleuritis, encephalopathy, coagulopathy
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

29. Medical and Health Science Center University of Debrecen Hungary
Thank you
Medical and Health Science Center
University of Debrecen
Hungary

31. The treatment of AKI with RRT has the following goals
to maintain fluid and electrolyte, acid-base, and solute homeostasis
to prevent further insults to the kidney
to permit renal recovery; and iv) to allow other supportive measures (e.g., antibiotics, nutrition support)
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

32. AKI: Acute Kidney Injury/Impairment
Only one RCT has evaluated the effect of timing of initiation of RRT on outcome
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

33. Timing of initiation of RRT on outcome
early vs. late initiation
Bouman et al. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial
Randomized 106 critically ill patients with AKI to early vs. late initiation of RRT
The early initiation group started RRT within 12 hours oliguria (30 ml/h for 6 hours, not responding to diuretics or hemodynamic optimization) or CrCl < 20 ml/min
The late-initiation group started RRT when classic indications were met
Conclusion: did not find differences in ICU or hospital mortality, or in renal recovery among survivors
Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J. Crit Care Med 2002; 30: 2205–2211.
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands

34. Timing of initiation of RRT on outcome
early vs. late initiation
Observational studies:
in the 1960 s and 1970 s
(Conger JD. J Trauma 1975; 15: 1056–1063, Fischer RP. Surg Gynecol Obstet 1966; 123: 1019–1023, Kleinknecht D. Kidney Int 1972; 1: 190–196) blood urea or BUN were used to distinguish early vs. late start of dialysis. However, these studies mostly combined early start with more-intensive dialysis and late start with less-intensive dialysis.
Not conclusive

35. Timing of initiation of RRT on outcome
early vs. late initiation
Observational studies:
A prospective multicenter observational study
(54 ICUs in 23 countries)
Stratified into ‘‘early’’ or ‘‘late’’
by median urea at the time RRT started (24.2 mmol/l)
Also categorized temporally from ICU admission into early (less than 2days), delayed (between 2–5 days), or late (more than 5 days).
Conclusion: - timing by serum urea showed a tendency but no significant difference in mortality
- in relation to ICU admission, late RRT was associated with greater crude mortality
Bagshaw SM, et al. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury. J Crit Care 2009; 24: 129–140.

36. Timing of initiation of RRT on outcome
early vs. late initiation
Observational studies:
A prospective multicenter observational study
Major abdominal surgery AKI
early or late start of renal replacement therapy defined by simplified RIFLE
early start: sRIFLE-0 or Risk; late start: sRIFLE -Injury or Failure
Shiao CC, et al. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care 2009; 13: R171.

37. Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis
Meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival.
calling for an adequately powered randomized controlled trial to address this question
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL. Am J Kidney Dis. 2008;52:272–284

38. Maintaining fluid homeostasis
Patients receiving RRT predominantly for solute control experienced better outcomes than those predominantly treated for volume overload.
Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008;12: R74.
Foland JA, Fortenberry JD, Warshaw BL, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 2004; 32: 1771–1776.
Gillespie RS, Seidel K, Symons JM. Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol 2004; 19:1394–1399.
Goldstein SL, Currier H, Graf C, et al. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001; 107: 1309–1312.
Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multiorgan dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 2005; 67: 653–658.
Hayes LW, Oster RA, Tofil NM, et al. Outcomes of critically ill children requiring continuous renal replacement therapy. J Crit Care 2009; 24:394–400.
Sutherland SM, Zappitelli M, Alexander SR, et al. Fluid overload and mortality in children receiving continuous renal replacement therapy:the prospective pediatric continuous renal replacement therapy registry.Am J Kidney Dis 2010; 55: 316–325.
Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluidmanagement strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575.

39. Maintaining fluid homeostasis
Analysis of a multicenter observational cohort showed that mean daily fluid balance in AKI patients was significantly more positive among nonsurvivors than survivors.
Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008;12: R74.
Survivors had lower fluid accumulation at dialysis initiation compared to nonsurvivors (8.8% vs. 14.2% of baseline body weight; P=0.01 adjusted for dialysis modality and severity score).
PICARD: Liu KD, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2006; 1:915–919.

40. Indications for RRT
fluid homeostasis
Massive volume overload resulting from volume resuscitation may be an indication for RRT even in the absence of significant elevations in BUN or SCr. – not RRT but renal support

41. AKI – RRT Modality of renal replacement therapy for patients with AKI
We suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients (2B).
In non-septic AKI, 25 ml/kg/h remains optimal.
We suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. (2B).
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

42. AKI: Acute Kidney Injury/Impairment
Stage 2 (RIFLE-Injury)
Serum creatinine increased times baseline
Urine volume < 0.5 ml/kg/h for more than 12 hours
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

43. AKI: Acute Kidney Injury/Impairment
Stage 3 (RIFLE-Failure)
Serum creatinine increased > 3.0 times baseline or
Serum creatinine > 354 μmol/l with an abrupt rise of at least 44 mmol/l
Initiation of renal replacement therapy
Urine volume < 0.3 ml/kg/h for more than 24 hours
anuria for more than 12 hours
Kidney Disease: Improving Global Outcomes (KDIGO), 2012