Treatment Related Factors Catheter performance QB tends be roughly comparable for FE and R) sided SC and IJ lines Maximum achievable QB tends to be lower by ~100 mL/min in L) sided SC and IJ lines AR tends to be highest in short FE lines, intermediate in long FE lines, and lowest in SC and IJ lines Dialyzer and filter performance Oliver et al, Semin Dial, Vol 14, pp 432-435, 2001 Little et al, AJKD, Vol 36, pp 1135-1139, 2000 Margetts et al, JASN, Vol 10, pp 211A, 1999

Little et al, AJKD, Vol 36, pp 1135-1139, 2000

A- IJ catheter with no recirculation; B- 20 cm FE catheter assumed to have AR of 0% at 150 mL/min, 8.5% at 250 mL/min and 17% at 350 mL/min; C- 15 cm FE catheter assumed to have AR of 5% at 150 mL/min, 20% at 250 mL/min and 30% at 350 mL/min (iHD treatments are modelled under the following conditions; duration 240 mins, dialysate flow 500 mL/min, hemodialyzer mass transfer coefficient 911 mL/min, V 40 L, nPCR 0.8 g/kg/day)

Treatment Related Factors Catheter performance Dialyzer (iHD and Hybrid) performance Heparin-free iHD is associated with significant fibre bundle clotting, and also with reduced delivered iHD dose K decreases by 10-20% during in the hour before dialyzer clotting during Hybrid Therapy Low-flux dialyzers are associated with lower iHD dose (KoA, QD) Sakiewicz et al,JASN, Vol 10, pp 196A, 1999 Evanson et al, AJKD, Vol 32, pp 731-738, 1998 Marshall et al, UpToDate, “Sustained Low-Efficiency Dialysis” Paganini et al, Am J Kidney Dis, Vol 28 (Suppl), ppS81-S89, 1996

Marshall and Golper, UpToDate, “Sustained Low-Efficiency Dialysis”

Treatment Related Factors Catheter performance Filter (CRRT) performance Down time due to filter clotting is the major reason for reduced CRRT dose

Treatment Related Factors Catheter performance Filter (CRRT) performance Down time due to filter clotting is the major reason for reduced CRRT dose Concentration polarization reduces filtration rate and the filtrate concentrations of various medium / large sized proteins High filtration fraction (high UF + low QB or post dilution) is associated with both of above Pre-dilution versus post-dilution

Treatment Related Factors

Treatment Related Factors For iHD, long catheters should be used for femoral angioaccess, and adjust dose prescription in anticipation of increased AR For iHD, can adjust for solute compartmentalization using the Daugirdas, Garred, or Tattersall rate equations For both iHD and CRRT, optimize anticoagulation and adjust dose prescription in the advent of dialyzer and filter clotting

Treatment Related Factors For CRRT, avoid high filtration fraction by higher blood flow rates and pre-dilution to minimize concentration polarization and hemoconcentration Except using Regional Citrate Anticoagulation with post-dilution replacement For CRRT, adjust prescription for predilution with either a FUN/BUN ratio or an empirical 15% for lower-dose prescriptions (~2L/hr) and 30-40% for higher-dose prescriptions (>4L/hr)

Overview Revisiting of dose and outcomes Patient and treatment related factors affecting dose prescription and delivery Therapy-specific dose-outcome data Approach to prescription and quantification of acute RRT dose

Dose-Outcome Data CRRT

Table I – Clinical Diagnosis of study patients No of Patients Multiple injury 12 Aortic rupture 2 Osteomyelitis 1 Abdominal aortic aneurysm repair 22* Thoracic aortic aneurysm repair 4 Other vascular procedures 11 Bronchial carcinoma 3 Other thoracic procedures Necrotising pancreatitis 10 Gastric cancer 9 Peritonitis / intestinal perforation 7 Diseases of gallbladder 6 Ileus 5 Perforated ulcer Other abdominal operations 17 *Emergency in 18, elective in 4

* Not Randomized

Dose-Outcome Data (CRRT) Dose is quantified as effluent (filtration) rate indexed to body size A dose of 35 mL/kg/hr in post-dilution mode is reported as giving the best results Starting acute RRT earlier rather than later is suggested as giving the best results

Dose-Outcome Data iHD

Dose-Outcome Data (iHD) Dose is quantified as clearance indexed to solute pool size (single pool Kt/V) A dose of >1.0 is reported as giving the best results Daily iHD is reported as giving better results that alternate day iHD

Phu et al. 70 patients with sepsis randomized to CVVH or CAPD Average weight 53 kg Most common diagnosis falciparum malaria CVVH 25L/day pre-dilution lactate based substitution fluid rate, Ku 25L/day CAPD 70L/day dialysate exchanged, Ku 28L/day

CAPD provided unsatisfactory control of cidosis, longer duration of ARF, poorer survival

Overview Revisiting of dose and outcomes Patient and treatment related factors affecting dose prescription and delivery Therapy-specific dose-outcome data Approach to prescription and quantification of acute RRT dose

CRRT Prescription For all CRRT, aim for >85% delivery of prescribed dose For all CRRT, aim for effluent rate of >35 mL/kg/hr, with appropriate adjustments for the effect of pre-dilution, and accounting for patient and treatment related barriers

CRRT Prescription It is unlikely CVVH can achieve an effluent rate of 35mL/kg/hr without high blood flow rate +/- pre-dilution Except the patient is small/pediatric, or not particularly sick or Using Regional Citrate Anticoagulation + post-dilution The adequacy of an effluent rate of 35mL/kg/hr is unclear for CVVHD(F) since this dose applies to dialysate generated by diffusion rather than filtrate generated by convection

iHD Prescription It is unlikely that iHD can deliver an adequate dose outside of a daily or near –daily regimen unless the patient is unless the patient is small/pediatric, or not particularly sick For daily iHD, aim for a delivered single pool Kt/V of at least >1.0, accounting for patient and treatment related barriers (? prescribe 1.3)

iHD Prescription The most practical expression of iHD dose is single pool Kt/V, and is most accurately achieved by formal UKM The most realistic expression iHD dose is equilibrated Kt/V, and is most accurately achieved by adjusting single pool Kt/V using the Daugirdas, Garred, or Tattersall rate equations

PD Prescription It is even less likely that PD can deliver an adequate dose outside of continuous flow PD unless the patient is small/pediatric, or not particularly sick

Dose and Therapy Choice If iHD is not delivering adequate dose despite optimizing all factors, try Hybrid Therapy or CRRT If CRRT is not delivering adequate dose despite optimizing all factors, try Hybrid Therapy or iHD There are increasing data suggesting that delaying acute renal replacement therapy in critically ill patients is unwise

Is there an expression of acute RRT dose that will allow us to reconcile these different recommendations for iHD and CRRT?

Standard Kt/V (stdKt/V) Units: week-1

stdKt/V Requires a solute steady state for calculation Expresses acute RRT dose as a new less intuitive parameter Based on peak-concentration hypothesis, which can reconcile Kt/V standards forCAPD and iHD dose in the outpatient setting, but is arbitrary and difficult to define in the critically ill

Corrected Equivalent Renal Urea Clearance (EKRc) Units: mL/min

= G/TAC or J/TAC

A comparison of BUN time-concentration profiles between two intermittent hemodialysis regimens delivering a cEKR of 24 ml/min. The solid line reflects solute removal over 3 treatments per week, the dotted solute removal over 7 treatments per week.

EKRc (1st Generation) Analogous to GFR, conceptually simple since it expresses acute RRT dose as mL/min Is corrected for body size (a 70 kg person with a V of 40L or BSA of 1.73m2) Is based on time-averaged BUN, which is easier to define and less arbitrary than peak BUN

EKRjc (2nd Generation)

EKRjc (2nd Generation) Is valid during solute non-steady state, and is insensitive to variation in V and G Does not require precise knowledge of V, G of Kd Can be calculated on a simple Excel spreadsheet with input of patients’ estimated V and BUN both pre and post iHD for sequential dialysis cycles Can use post-iHD Ceq (Tattersall)

Dialysis Dose and Prescription

http://www.atnstudy.org/

Augmented vs Normal Renal Replacement Therapy in Acute Renal Failure http://www.clinicaltrials.gov/ct/show/NCT00221013 Augmented vs Normal Renal Replacement Therapy in Acute Renal Failure

How should one prescribe and dose acute RRT to optimize patient outcomes? Individually, according to the requirements of the patient