Principles of CRRT for AKI

Stephen Lapinsky
Mount Sinai Hospital
Toronto
 Objectives

Review the principles of CRRT, relevant

to the practice of critical care

Highlight work produced by the

Toronto Acute Kidney Injury (TAKI) group
 Principles of CRRT for AKI

Principle: a fundamental, primary, or general law

or truth from which others are derived
 Principles of CRRT for AKI

Principle: a fundamental, primary, or general law

or truth from which others are derived
 Principles of CRRT for AKI

Principle: a fundamental, primary, or general law

or truth from which others are derived

CRRT: - Truths
- Unknowns
Truths regarding CRRT for AKI
Truths regarding CRRT for AKI
It is commonly used for AKI in the ICU (BEST Kidney)1
Suitable for use in hemodynamically unstable patients2
Allows precise, adaptable, volume control
Very effective control of uremia, PO4, K
Available 24 hours a day

1. Int J Artif Organs. 2007;30:281-92.

2. BMC Nephrol. 2010 Nov 25;11:32.
Truths regarding CRRT for AKI
It is commonly used for AKI in the ICU (BEST Kidney)
Suitable for use in hemodynamically unstable patients.
Allows precise, adaptable, volume control
Very effective control of uremia, PO4, K
Available 24 hours a day
It is more expensive than other modalities of RRT
Usually requires continuous anticoagulation
Can cause severe depletion of electolytes (and
potentially other substances)
Truths regarding CRRT for AKI
Modes of CRRT
CVVHD dialysate

Diffusion

13%
Intensive Care Med (2007) 33:15631570
Truths regarding CRRT for AKI
Modes of CRRT
CVVH (filtration)
predilution replacement

Convection

ultrafiltrate
1/2 of 53%
Intensive Care Med (2007) 33:15631570
Truths regarding CRRT for AKI
Modes of CRRT
CVVH (filtration)
postdilution
replacement

Convection

ultrafiltrate
1/2 of 53%
Intensive Care Med (2007) 33:15631570
Truths regarding CRRT for AKI
Hemodiafiltration
CVVHDF
dialysate
Ca citrate replacement
gluconate

ultrafiltrate
34%
Intensive Care Med (2007) 33:15631570
Unknowns regarding CRRT for AKI
Unknowns regarding CRRT for AKI

Is it better than IHD or SLEDD ?

When to initiate CRRT ?
What mode to use CVVHD or CVVH ?
What dose of dialysis to use ?
Is it better than IHD or SLEDD?

Few direct comparative data

Is it better than IHD or SLEDD?

IHD - mortality higher in some studies

- 5 RCTs: no difference in mortality
- meta-analyses: no differences

SLED
- safe, effective, cheaper than CRRT
- limited comparative data
Is it better than IHD or SLEDD?
Comparison with IHD

Kellum et al. Intensive Care Med 2002; 28:29

Is it better than IHD or SLEDD?
Comparison with IHD

Bagshaw et al, Crit Care Med 2008; 36:610

Is it better than IHD or SLEDD?
Comparison with IHD

Bagshaw et al, Crit Care Med 2008; 36:610

Is it better than IHD or SLEDD?
Comparison with SLEDD

Fieghen et al. BMC Nephrol 2010; 11:32

When to initiate CRRT?
When to initiate CRRT?
Optimal timing unknown
Heterogeneity across centres and physicians
Early:
Avoid complications and organ damage ?
Non-renal benefits ?
Waiting for traditional indication:
Volume overload
Metabolic acidosis
Hyperkalemia
Uremic complications
When to initiate CRRT?
Observational study in 11 ICUs in Canada
119 consecutive patients

Clark et al, Can J Anaesth 2012 59:861

When to initiate CRRT?
At the initiation of CRRT:

Clark et al, Can J Anaesth 2012 59:861

When to initiate CRRT?
Traditional indications:

Clark et al, Can J Anaesth 2012 59:861

 When to initiate CRRT?
Survey of Nephrologists and Intensivists in Canada:
Wide variation in the severity of indications and timing

Clark et al, Nephrol Dial Tranplant 2012 27:2761

When to initiate CRRT?
STARRT-AKI Study
RCT comparing:
accelerated arm: CRRT within 12 hr
standard arm - traditional criteria
Inclusion criteria
AKI based on 2 out of 3 of:
creatinine, oligura, NGAL
PI: Dr. Ron Wald
4 sites enrolling, 6 almost ready
What mode to use CVVHD or CVVH?
What mode to use CVVHD or CVVH?
Hemodialysis and hemofiltration both clean the blood,
but the range of molecules removed is a little different
Clearance of small molecules is similar
BEST Kidney investigators:
Better clearance of medium sized molecules by filtration
- survey of 54 ICUs in 23 countries
Potential benefit in septic patients in removing cytokines
- 1006 patients on CRRT
Mode selection varies significantly across the world

Uchino etet
Friedrich al,al,
Intensive
Crit Care
Care
2012;
Med16:R146
2007; 33:1563
What mode to use CVVHD or CVVH?
OMAKI study: Optimal mode of clearance in critically ill
patients with acute kidney injury

Multicentre pilot study of CVVH v CVVHD at 35 ml/kg

78 patients enrolled
SOFA score decreased more rapidly in CCVH group,
due to decreased vasopressor requirements
No difference in mortality

Wald et al. Crit Care 2012, online Oct 25th

What mode to use CVVHD or CVVH?
OMAKI study: Optimal mode of clearance in critically ill
patients with acute kidney injury

Wald et al. Crit Care 2012, online Oct 25th

What mode to use CVVHD or CVVH?
Meta-analysis (Friedrich et al):
19 RCTs met inclusion criteria
3 trials compared CVVHD with CVVH at
similar small molecule clearance dose.
Other studies used CVVHDF or variation in
dosing
No difference in outcome
Hemofiltration may reduce filter life
Friedrich et al, Crit Care 2012; 16:R146
What mode to use CVVHD or CVVH?
Meta-analysis (Friedrich et al):

Friedrich et al, Crit Care 2012; 16:R146

What dose of dialysis to use ?
What dose of dialysis to use ?
Dose
Clearance in terms of volume cleared per hour
eg. replacement fluid (or dialysate) at 2000ml/h
in 70kg patient = 2000/70 = 28 ml/kg/h

Some refinements:
- loss of efficiency with predilution
- volume of citrate anticoagulation
What dose of dialysis to use ?

45 ml/kg/hr
35 ml.kg/hr
20 ml/kr/hr

Ronco et al, Lancet 2000; 356:26

 What dose of dialysis to use ?

206 patients randomized

60% sepsis
42 ml/kg
CVVH versus
CVVH + added D
25 ml/kg

Saudan et al, Kidney Int 2006; 70:1312

What dose of dialysis to use ?
Negative dosing studies
What dose of dialysis to use ?
- 200 ICU patients with acute renal failure
CVVHDF 20 v 35 ml/kg/hr
No difference

Tolwani et al J Am Soc Nephrol 2008; 19:1233

What dose of dialysis to use ?
NIH ATN study:
1124 patients, multicentred
Intensified (35ml/kg, 6x/wk IHD) versus
Standard (20ml/kg, 3x/wk IHD)
No difference in mortality

Palevsky et al. N Engl J Med 2008; 359:7.

What dose of dialysis to use ?
RENAL study (Australia)
1508 patients, approx 50% sepsis
Prescribed dose achieved: 84 88%
CVVHDF, postdilution (1:1 dialysate:filtration)
Low intensity: 25 ml/kg/hr
High intensity: 40 ml/kg/hr
No difference in mortality

N Engl J Med 2009; 361:1627-1638.

What dose of dialysis to use ?
25ml/kg seems adequate
Some criticisms/comments:
Delayed initiation of RRT in Tolwani and ATN studies: 6 to 8
days; RENAL: 48-54 hr in ICU before randomisation
No clear separation of dose delivered when combining CRRT
and IHD dosing (ATN study)
Majority (65%) enrolled after initial dialysis
Dosing was not actually achieved in the ATN study
Timing of the higher dose may be important