1. The 4th CRRT master course (CRRT Initiation, Dose, Stop)
이상헌

2. Potential advantages of Early RRT
CRRT initiation
Potential advantages of Early RRT
Prevention of the deleterious consequences of
Fluid overload
Electrolyte disturbance
Acidosis
Uremia
Prevention of further escalation of harmful medical therapies
 inotropics, fluid loading, diuretics…..
Immunomodulation from RRT
Schetz. 19th International Vicenza Course on Critical Care Nephrology 2010

3. Potential Disadvantages of Early RRT
CRRT initiation
Potential Disadvantages of Early RRT
Early start may expose patients to unnecessary RRT with associated risk
Vascular catheterization
Anticoagulation
Electrolyte disturbances, ex) hypokalemia & hypophosphatemia
Arrhythmias
Hemodynamic instability
Hypothermia
Potential under-dosing of drugs
Delayed recovery of Kidney function
Cost issue
Tolwani A et al., N Eng J Med 367:2505, 2012

4. BUN as a criterion for RRT initiation
CRRT initiation
BUN as a criterion for RRT initiation
Lower BUN level at the time RRT was assiciated with survival benefit
Retrospective study with post-traumatic AKI pts (n=100)
BUN 60mg/dL : early VS late CRRT (mean BUN level 42.6 VS 94.5)
20% absolute reduction in mortality in early CRRT
Rhabdomyolysis was more common in the early group
Multi-organ failure was seen often in the late group
Gettings LG et al., Intensive Care Med 25:805, 1999
PICARD study
large observational study with general ICU population (n=243)
RR for death associated with delayed initiation of dialysis
(BUN > 76 mg/dL) was 1.85 (95% CI:1.16~2.96)
Liu KD et al., Clin J Am Soc Nephrol 1:915, 2006

5. Urine output as a criterion for RRT initiation
CRRT initiation
Urine output as a criterion for RRT initiation
RCT with 28 critically ill patients after cardiac surgery
Early start group : start dialysis if U/O < 30ml/hr for 3 consecutive hours
Delayed group : U/O < 20 ml/hr for 2 consecutive hours
Survival rate after 14 days was significantly higher in early group
(86% VS 14%, p<0.01)
Sugahara S et al., Hemodial Int 8:320, 2004

6. Early VS late initiation of RRT : meta-analysis
CRRT initiation
Early VS late initiation of RRT : meta-analysis
Survival rate after 14 days was significantly higher in early group
(86% VS 14%, p<0.01)
Earlier institution of RRT in critically ill patients with AKI may have a beneficail impact on survival.
Karvellas CJ et al., Crit care 15:R72, 2011

7. Problems with previous studies
CRRT initiation
Problems with previous studies
Variable definition of early RRT
: BUN, Cr, Oliguria, Rifle criteria, Time from ICU admission….
Residual confounding factor
: inotropics, fluid loading, diuretics….
Early group may contain patients who would not receive RRT
because of dead or recovery
Appropriate large scale RCT with more accurate predictors of
persistent and severe AKI  Cystatin C, NGAL, KIM-1….

8. CRRT dose
“Effluent”  End product of filtration and comprises the UF in convection Tx, the spent dialysate in diffusive Tx.
And the SUM of both combined therapies

9. CRRT dose
Prowle et al. Critical Care 15:207, 2011

10. RRT dose : RRT in AKI (multi-center, RCT)
The Veterans Affairs/National Institutes of Health(VA/NIH) Acute Renal Failure
Trial Network (ATN) study
Primary end point : death from any cause by day 60
Palevsky PM et al., N Eng J Med 359:7, 2008
Prowle et al. Critical Care 15:207, 2011
Intensive therapy (n=563)
IHD, SLED 6 times/week (Kt/V 1.2~1.4)
CVVHDF 35mL/kg/hr
Less-Intensive therapy (n=561)
IHD, SLED 3 times/week (Kt/V 1.2~1.4)
CVVHDF 20mL/kg/hr
P = 0.47

11. RRT dose : RRT in AKI (multi-center, RCT)
Palevsky PM et al., N Eng J Med 359:7, 2008

12. RRT dose : RRT in AKI (multi-center, RCT)
Palevsky PM et al., N Eng J Med 359:7, 2008

13. CRRT dose : CRRT in AKI (multi-center, RCT)
Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement
Therapy Study
1508 patients in 35 ICU in Australia and New Zealand
Primary end point : death within 90 days after randomization
Bellomo R et al., N Eng J Med 361:1627, 2009
Prowle et al. Critical Care 15:207, 2011
Higher intensity (n=721)
CVVHDF : 40 mL/kg/hours
Lower intensity (n=743)
CVVHDF : 25 mL/kg/hours

14. CRRT dose : CRRT in AKI (multi-center, RCT)
Bellomo R et al., N Eng J Med 361:1627, 2009

15. CRRT dose : CRRT in AKI (multi-center, RCT)
Bellomo R et al., N Eng J Med 361:1627, 2009

16. Dose of RRT : CRRT in AKI (Meta-analysis)
Jun M et al., Clin J Am Soc Nephrol 5:956, 2010

17. IVORE study
18 ICU in France, Belgium, Netherland, total 140 critically ill patients
HVHF 70ml/kg/hr VS SVHF 35ml/kg/hr
Primary endpoint : 28 day mortality

18. IVORE study

19. Adverse event IVORE study All antibiotics were easily filtered
: Mean sieving coefficients  38.7% ~ 96.7%
Mean elimination half-life of all agent
: HVHF (1.29 ~ 28.54hr) VS SVHF (1.51 ~ 33.85hr)
Electrolyte disturbance
Hypokalemia  HVHF 30% SVHF 20%
Hypophophatemia  HVHF 88% SVHF 38%

20. Debate of high dose CRRT
CRRT dose
Debate of high dose CRRT
Hypophosphatemia / hypokalemia
Higher incidence of hypotension
Effect of pharmacodynamics in antibiotics dosing

21. Dose of CRRT in AKI No evidence for superiority of higher CRRT dose
Dose threshold below which mortality may increase
35ml/kg/hr is a reasonable target for prescription
> 25ml/kg/hr should be effectively delivered
KDIGO 2012
Delivering an effluent volume of 20-25ml/kg/hr for CRRT in AKI (1A)
We recommend frequent assessment of the actual delivered dose
in order to adjust the prescription (1B)

22. CRRT dose
Prowle et al. Critical Care 2011, 15:207

23. Discontinuation of CRRT
Relatively paucity of data about discontinuation of RRT in AKI
BEST kidney (Beginning and Ending Supportive Therapy for the kidney)
(n=1006)
Multi-center, multi-national, prospective, epidemiologic study
Successful discontinuation of CRRT
 being free from dialysis for 7 days after stopping Tx.

24. Discontinuation of CRRT
Uchino S et al., Crit Care Med 37:2576, 2009

25. Discontinuation of CRRT
ROC curve : U/O 436ml/day without diuretics
 highest sensitivity & specificity
 Cutoff U/O 400ml : sensitivity 46.5%
specificity 80.9%, PPV 80.9%, NPV 76.5%
accuracy 78.6%
Uchino S et al., Crit Care Med 37:2576, 2009

26. Prisma

27. PrismaFlex

28. Dialysate flow UF volume Effluent dose PrismaFlex Pre-dilution type
Post 로 나누어줌(Clot 예방)
Pre (800ml) + Post (200ml)
Dialysate flow
UF volume
Effluent dose

29. PrismaFlex Effluent dose : 49ml/kg/hr, Body weight 42kg
국내 도입된 PrismaFlex는 Pre-dilution만 가능. Clot 막기 위해 Post로는 200ml/hr이상으로 주입하는 것을 권함
외국에서는 사전혈액펌프로 Citrate anticoagulation을 사용 중임
국내에서는 사용하지 않아 replacement fluid로 대체함
Effluent dose : 49ml/kg/hr, Body weight 42kg
49 X 42 = effluent solution 2058ml/hr
Dialysate volume 1000ml/hr + replacement 1000ml/hr + Patient removal
= 2058ml/hr, Patients removal 58ml/hr (설정값은 40ml/hr)

30. PrismaFlex Optimal effluent dose 35ml/kg/hr 35 X 42kg = 1470ml/hr
Dialysate : Replacement fluid = 1:1 로 유지한다면
1470ml X ½ = 735ml  Dialysate 735ml, Replacement 735ml
이렇게 setting 한 후에 UF volume을 정해주면 된다.
현재 본원 setting은 Dialysate 1000ml/hr, replacement 1000ml/hr
Fix dose로 간호사들이 setting 중임.