The document discusses the appropriate dose of continuous renal replacement therapy (CRRT) to prescribe. While studies have shown that 20-25 ml/kg/hr of effluent production is as effective as 35 ml/kg/hr, the prescribed dose may not equal the actual delivered dose due to downtime and other factors. Additionally, effluent production is an imperfect surrogate for solute clearance. The document concludes that CRRT dosing should be tailored to the individual patient's clinical situation, guided primarily by their condition, rather than a single number for ml/kg/hr.

1. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
Academic Department of Critical Care
University of Portsmouth & Portsmouth Hospitals NHS Trust
Continuous renal replacement therapy:
What dose to prescribe
Dr Sara Blakeley

2. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
What is dose?
1. an amount of medicine to be taken at one time
2. An amount of radiation received by a person or thing
3. (informal) an amount of flattery or punishment etc
4. (slang) a venereal infection.
- v. to give a dose or doses of medicine to
X X
??

3. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
In the beginning….
• Ronco 2000 study: 425 ICU patients
• “mls/kg/hour” of effluent production as a
surrogate for solute clearance (NB: really
means a surrogate for urea clearance)
• 20 vs 35 vs 45 mls/kg/hour CVVH
– 35mls/kg/hour mortality benefit
• Then came the debate
• Then came the large multi centre trials…..

4. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
Then came the meta-analyses……
Acute Renal Failure Trial Network (ATN) study
20 vs 35 mls/kg/hour
Randomised Evaluation of Normal versus Augmented
Level (RENAL) replacement study
25 vs 40 mls/kg/hour

5. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
Higher dose has no effect on outcome
Higher ≥ 30mls/kg/hr
Lower < 30mls/kg/hr
Higher dose has no effect on outcome
Higher 35-48 mls/kg/hr
Lower 20-25mls/kg/hr
Lies, damned lies and meta analyses?

6. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth

7. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
So what does the evidence tell us to do?
20-25
mls/kg/hour
35
mls/kg/hour

8. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth

9. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
1. Prescribed vs delivered dose
• Continuous is invariably not continuous:
– Many reasons for periods of down time
• Procedures/diagnostic imaging/surgery
• Change in clinical state of the patient
• Filter clotting (multi factorial)
• How good were the studies?
– ATN: low intensity 95% delivered
– RENAL: low intensity 88% delivered
• Should be aiming for 20-25mls/kg/hour delivered dose so realistically need to aim
for 25-30mls/kg/hour prescription
But does the patient really get 20-25mls/kg/hour delivered solute clearance
even with a prescription of 25-30mls/kg/hour?

10. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
2. Actual solute clearance
• Pre vs post dilution
– Varying use in studies (ATN pre, RENAL post)
– Pre dilution reduces solute clearance by 15-20%
• Diffusive vs convective therapy
– Ronco: convective
– ATN/RENAL: diffusive +/- convective
• Other operational characteristics e.g. filter properties, body weight used
• Could do formal clearance studies: but which?
Bottom line: We have no accurate bedside test for how effective filter is at clearing
urea, what we are prescribing may not be what the patient receives

11. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
3. More to life than urea
• ‘mls/kg/hour’ refers mainly to removal of small molecular weight substances
• Recent interest in ‘middle molecules’ (includes inflammatory mediators) – BUT
IVOIRE study not supportive for HVHF in sepsis
• Reasons for starting CRRT may be different
– Severe sepsis with MOF and worsening AKI with metabolic acidosis
– Hyperkalaemia and worsening AKI in rhabdomyolysis
– Severe fluid overload
• Timing of therapy
Bottom line: there are many reasons for starting CRRT and to specify a dose for an
individual in terms of ‘mls/kg/hour’ may be too simplistic

12. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
So what do I do?

13. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth

14. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth

15. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth

16. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
Summary
• Evidence would suggest that 20-25mls/kg/hour of delivered effluent is as good as
35mls/kg/hour of effluent production BUT…
– Prescribed vs delivered
– Pre vs post dilution
– Time/weight indexed effluent vs formal solute clearance
– Low vs middle MW solutes
– CRRT has many benefits which do not fall neatly into ‘mls/kg/hour’
• We should tailor treatment for an individual/situation and be guided mostly by the patients
clinical condition
• ICUs should have a protocol to standardise delivery of therapy
• Mls/kg/hour has many limitations – BUT is a useful starting point

17. Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
For further information
sara.blakeley@porthosp.nhs.uk
http://www.portsmouthicu.com/
@WessexICS/