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

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

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

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

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

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

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….

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

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

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

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

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

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

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

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

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

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

IVORE study

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%

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

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)

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

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.

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

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

Prisma

PrismaFlex

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

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)

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.