A concise presentation on CRRT dose.

1. Vipin Kauts
MBBS,MD,EDIC
Dose of Renal Replacement Therapy

2. The spectrum of Continuous Renal Replacement
Therapies
SCUF CVVH CVVHD
CVVHDF
Hemofiltration Hemodialysis
CONVECTION DIFFUSION

3. Management Goals of AKI
• Fluid balance.
• Removal of waste products.
• Hemodynamic stabilization.
• Correction of electrolyte abnormalities.
• Restoration of acid-base balance.
• Nutrition support.
Diffusion
Convection

4. Dose adequacy in RRT: The Urea kinetic model
Gotch and Sargent. Kidney Int. 1985;28(3):526-534
t (Time in
minutes)
K(Clearance)
Kt
V
V=Vol of
distribution(BUN)
Dialysis
adequacy
Total body water
(TBW)
Weight x 0.5
or 0.6
Amount of blood
time
Blood flow
(ml/min)
1.2 -1.4
Example
350(flow rate) x180 (time) = 1.3
0.6 x 80(body weight) (x1000)

5. The Kidney Disease: Improving Global Outcomes
(KDIGO) Clinical Practice Guidelines for AKI
Kidney International Supplements.2012; Vol 2 Suppl 1.
Target Kt/V of at least 1.3 , 3 times/week or
3.9/week when delivering IHD in the setting of AKI.

6. Calculation of urea reduction ratio (URR)
Depner TA. Prescribing Hemodialysis: A Guide to Urea Modeling. 1991
URR= ( BUNpre – BUNpost) x 100
BUNpre
URR values of 67%–72 % corresponding to Kt/V values of 1.2-1.4

7. The assumptions of urea kinetic modeling are not valid in
critically ill patients
• Most critically ill patients are hyper catabolic :negative nitrogen balance or variable rates of
urea generation.
• The volume of distribution of urea in patients with AKI may exceed total body water and is
variable due to variations in volume status over time.
• Alterations in regional blood flow (hemodynamically unstable): disequilibrium in urea
distribution between body fluid compartments, invalidating standard single pool models.
Vijayan & Palevsky.Dosing of Renal Replacement Therapy in Acute
Kidney Injury. Am J Kidney Dis. 2012 April ; 59(4): 569–576

8. How is CRRT dose calculated ?
• In all major trials, the delivered dose is considered equivalent to the total effluent volume,
expressed as a weight adjusted hourly effluent rate.
• The effluent rate determines the clearance of small solutes such as urea.
CVVH
Effluent rate= Rate of replacement fluid (ml/hr)
Net Ultrafiltration(ml/hr)
CVVHDF
Effluent rate= Rate of replacement fluid (ml/hr)
Dialysate fluid rate(ml/hr)
Net Ultrafiltration(ml/hr)
+
+
+

9. CVVHDF
CRRT dose( ml/kg/hr)= Effluent(Replacement fluid+ Dialysate+patient net ultrafiltration)
Patient weight
Example:
Dialysate = 1000 ml/hr
Replacement fluid =1000 ml/hr
Patient net ultrafiltration(fluid removal) =200 ml/hr
Patient weight = 70 kg
Prescribed dose= 31.4 ml/kg/hr
2200 ml/hr (Effluent rate)

10. SCUF CVVH CVVHD CVVHDF
Primary
mechanism
Ultrafiltration Convection Diffusion Diffusion and
convection
Blood flow rate 150-180 ml/min 50-300 ml/min 50-300 ml/min 50-300 ml/min
Dialysate No No 500-4000 ml/hr 500-4000 ml/hr
Replacement fluid No 500-4000 ml/hr No 500-4000 ml/hr
CRRT prescription
• Adjust blood flow rate according to hemodynamic status and body size.
• CVVHDF: 1/3rd of total dose as Dialysate,2/3rd as Replacement fluid .
• Replacement fluid: Pre/post filter ratio: 30% pre/70% post.
• If the initial urea is > 39 mmol/l, do not let it fall by > 1/3rd in first 24 hrs of CRRT.

12. Pre vs post filter replacement in CVVH/CVVHDF
Jimenez et al. Nephron 2021;145:91–98
Pre filter replacement
• Dilutes the blood entering the hemofilter.
• This lowers the filtration fraction by
diluting the blood entering the hemofilter.
• Less chance of filter clotting but decrease
in solute clearance.
Post filter replacement
• More concentrated blood in the filter.
• Higher solute clearance but shorter filter life.

13. Dilution factor
• When using pre-filter replacement fluid in CVVH or CVVHDF modes, the blood entering the circuit is
diluted and therefore clearance is decreased by up to 35%.
• In this setting, the total effluent fluid rate should be multiplied (adjusted) by a dilution factor.
Dilution Factor = Plasma Flow Rate (ml/hr)
Plasma Flow Rate (ml/hr) + Pre-Filter Replacement Fluid Rate (ml/hr)
*Plasma Flow Rate (ml/hr) = Blood Flow Rate (ml/min) x (1-HCT) x 60 (min/hr)
Troyanov et al.Nephrol Dial Transplant.2003;18(5):961-6 .

14. Calculation of total effluent fluid rate according to CRRT modality
CVVH: total UF rate(ml/h) + fluid removal rate(ml/h)
Example: CVVH: Effluent rate=1400 ml/hr + 200 ml/hr
Effluent flow rate = 22.9 ml/kg/hr (x 0.86=19.8 ml/kg/hr , adjusted by dilution factor)
Dilution factor for pre filter replacement (predilution):
Plasma flow rate(ml/hr)( =150 x 60 x (1-0.3)=6300)
Plasma flow rate(ml/hr) + Pre-filter replacement fluid rate(ml/hr)
6300
6300+1000
= 0.86
Example : weight 70 kg, HCT = 30%(0.3), blood flow rate = 150 ml/min,
pre-filter replacement = 1000 ml/hr, post-filter replacement =400 ml/hr, dialysate rate = 800 ml/hr,
fluid removal rate = 200 ml/hr
Jimenez et al.Nephron 2021;145:91–98

15. • When using diffusive clearance (CVVHD), dialysate flow rate, concentration gradients,
and filter surface area are the main determinants of clearance.
CVVHD: dialysate rate(ml/hr) + fluid removal rate(ml/hr)
Example: CVVHD: Effluent rate=800 ml/hr + 200 ml/hr
Effluent flow rate = 14.3 ml/kg/hr
CVVHDF: total UF rate(ml/hr) + dialysate rate(ml/hr) + fluid removal rate(ml/hr)
Example: CVVHDF:Effluent rate= 1400 ml/hr + 800 ml/hr + 200 ml/hr
Effluent flow rate = 34.3 ml/kg/hr (x 0.86=29.6 ml/kg/hr adjusted by dilution factor)
Jimenez et al.Nephron 2021;145:91–98

16. Overview of CRRT dose trials

17. Ronco et al. Effects of different doses in continuous veno-venous hemofiltration on
outcomes of acute renal failure: a prospective randomized trial. Lancet. 2000; 356: 26–30.
425 patients
Single center RCT.
CVVH
20 ml/kg/hr
N=146
vs 35 ml/kg/hr
N=139
vs 45 ml/kg/hr
N=140
41 % survival 57 % survival 58 % survival
Ultrafiltration should be at least 35 ml/kg/hr

18. ATN Trial .Palevsky et al.VA/NIH Acute Renal Failure Trial Network; Intensity of renal
support in critically ill patients with acute kidney injury. N Engl J Med. 2008; 359(1): 7–20.
1124 patients
RCT -27 centers in USA
Pre dilution CVVHDF
20 ml/kg/hr vs 35 ml/kg/hr
51.5%
mortality
53.6%
mortality
Intensive renal support did not decrease mortality at 60 days, improve
recovery of kidney function, or reduce the rate of non renal organ failure

19. RENAL Trial. Bellomo et al.The Randomized Evaluation of Normal versus Augmented Level
(RENAL) Replacement Therapy Study .N Engl J Med. 2009;361(17):1627-38.
1508 patients
RCT- 35 centers in Aus/NZ
Post dilution CVVHDF
25 ml/kg/hr vs 40 ml/kg/hr
44.7 %
mortality
44.7 %
mortality
Treatment with higher intensity CRRT did not reduce mortality at 90 days

20. No survival benefit by using a higher dose of CRRT
Vesconi 2009. Critical Care 2009;13:R57
Prospective multicenter observational study:15200 patients.
Compared < 35ml/kg/hr vs >35 ml/kg/hr CVVH.
Van Wert 2010. Systematic review and meta-analysis. CCM.2010;38(5):1360-9
12 trials:3999 patients
Compared ≥30 ml/kg/hr vs ≤30 ml/kg/hr CRRT.
IVOIRE Study 2013.High-volume versus standard-volume haemofiltration for septic shock patients with AKI.
Intensive Care Med 2013;39:1535–1546
Multi center RCT.
140 patients with septic shock and AKI.
Compared 35ml/kg/hr vs 70ml/kg/hr (High Volume Hemofiltration).
Zhang 2012. Nephrol Dial Transplant.2012; 27: 967–973
280 patients with septic shock and AKI
High-volume hemofiltration (50 ml/kg/hr) vs extra high-volume hemofiltration (85 ml/kg/hr)

21. Dose adequacy in CRRT
• Dose adequacy: minimum amount of dose that is needed for clearance to prevent a
negative outcome.
• Optimal dialysis : a dose above which there is no improvement in positive benefit.
Alvarez et al.Can J Anesth/J Can Anesth (2019) 66:593–604

22. Prescribed dose vs delivered dose
The prescribed dose is not always delivered
• Interruptions during CRRT
• Malfunction of alarms.
• Filter clogging/clotting.
• Catheter dysfunction.
• Bag/tubing changes.
• Planned interruptions: surgical or radiological procedures.
• One should account for 10–15% of circuit downtime when prescribing CRRT dose.
Jimenez et al.Nephron 2021;145:91–98

23. Dose requirements of AKI patients treated with CRRT
KDIGO 2012 clinical practice guidelines :
• We recommend delivering an effluent volume of 20 -25 ml/kg/hr for
CRRT in AKI.
• To achieve this, it is necessary to prescribe in the range of 25 -30
ml/kg/hr (10- 15% higher), and to minimize interruptions in CRRT .
Kidney International Supplements 2012; Vol 2: Suppl 1.

24. Extra high dose is required for ammonia clearance
• Hyperammonemia (≥150–200μmol/l ): irreversible neurological damage-cerebral edema and brain
herniation.
• Extracorporeal Ammonia Clearance for Hyperammonemia in Critically Ill Patients: A Scoping Review
Blood Purif 2021;50:453–461
• 13 studies using CVVH: 11 pediatrics, 2 adults.
Ammonia clearance is increased by:
• higher dialysate flow rate.
• higher ultrafiltration rate.
• higher blood flow rate.
• a longer duration of treatment.
• Slack et al.Ammonia clearance with haemofiltration in adults with liver disease Liver Int.2014;34(1):42-8
• Low volume (35 ml/kg/hr) vs high volume (90 ml/kg/hr) CVVH.
• Significantly higher clearance at 1 hr and 24 hr with high volume CVVH.

25. Clotting in the filter
• Premature termination of CRRT is usually due to clotting in the extracorporeal circuit, most commonly
the filter.
• Blood loss.
• Inadequate dialysis due to treatment interruption.
• Increased costs related to set utilization.
• The major causes of short-lived circuits are:
• Inadequate anticoagulation.
• A compromised vascular access: stagnation of blood in the extracorporeal circuit while
frequent machine alarms are managed.
• High filtration fraction (FF).
Karkar and Ronco. Ann. Intensive Care.2020;10:32

26. Filtration fraction in convective clearance( CVVH)
• Proportion of plasma water entering the filter that is removed by ultrafiltration.
• FF= Fluid removed from the filter = Replacement fluid rate( ml/hr)+Net Ultrafiltration(ml/hr)
Fluid entering the filter Plasma flow rate + Pre-filter replacement fluid rate(ml/hr)
*Plasma Flow Rate (ml/hr) = Blood Flow Rate (ml/min) × (1-HCT) × 60 (min/hr)
• FF > 20–25% = higher post-filter hematocrit : clot formation and decreased filter performance.
• FF α 1
Blood flow rate (BFR)
BFR < 100 ml/min= risk of clotting
BFR > 250 ml/min= vascular access issues

27. FUN/BUN ratio: a way to measure delivered CRRT dose
• BUN = BUN concentration entering the circuit (arterial port).
• FUN = BUN concentration in the effluent fluid.
• FUN/BUN should be approximately 1 at the beginning of treatment.
• However, FUN/BUN declines in parallel to a decrease in filter efficiency.
• Multiple factors affect filter efficiency
• solute fouling on the membrane surface (adsorption), and
• filter degradation/clogging.
Jimenez et al.Nephron 2021;145:91–98

28. Quality indicators related to delivered CRRT dose
Jimenez et al.Nephron 2021;145:91–98

29. Quality measures for acute kidney injury and CRRT
Griffin et al.Am J Kidney Dis. 2019; 74(6): 727–35.
Intervention( Quality assurance program):
(1) modification of the electronic medical record (EMR) to automatically calculate average delivered
CRRT dose over 24 hrs.
(2) modification of the CRRT procedure note to include calculated average doses.
(3) modification of the CRRT order to include formulas for dose calculation.
(4) yearly educational sessions on CRRT-specific dosing targets.
• Before the intervention: only 279 of 837 (33%) treatments achieved an average daily delivered
effluent dose of 20–25 ml/kg/hr.
• After the intervention: 631 of 952 (66%) treatments achieved an average daily delivered dose
of 20–25 ml/kg/hr (=KDIGO guidelines).

30. Conclusion
• The success of CRRT depends on the prescribed and achieved doses.
• The dose is a function of:
• Fluid replacement and/or dialysate administration rates.
• Treatment duration.
• Type of dialyzer and method.
• Dose of anticoagulation.
• Delivery and performance of CRRT requires:
• A well-established protocol (e.g.indications for initiation/ cessation, catheter
management ) and
• Well-trained medical and nursing staff.

31. Thank you