Principles of CRRT for AKI - Critical Care Canadacriticalcarecanada.com/.../principles_of_continuous_renal_replacement_therapy_for_aki.pdfPrinciples of CRRT for AKI •Principle: a

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”

• Principle: a fundamental, primary, or general law

or truth from which others are derived








CRRT: - Truths

- Unknowns

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.


• 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)

• Modes of CRRT

CVVHDdialysate


13%

Intensive Care Med (2007) 33:1563–1570

Diffusion

• Modes of CRRT

CVVH (filtration)predilution replacement

ultrafiltrate


1/2 of 53%


Convection

• Modes of CRRT

replacement

ultrafiltrate

CVVH (filtration)postdilution


1/2 of 53%


Convection

• Hemodiafiltration

replacement

ultrafiltrate

CVVHDF


dialysatecitrateCa

gluconate

34%


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


IHD - mortality higher in some studies

- 5 RCT’s: no difference in mortality

- meta-analyses: no differences

SLED- safe, effective, cheaper than CRRT

- limited comparative data

• Comparison with IHD

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


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



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



Fieghen et al. BMC Nephrol 2010; 11:32


• Comparison with SLEDD

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


• Observational study in 11 ICU’s in Canada

• 119 consecutive patients

Clark et al, Can J Anaesth 2012 59:861


• At the initiation of CRRT:



• “Traditional” indications:


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


STARRT-AKI StudyRCT 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?


• Hemodialysis and hemofiltration both “clean” the blood,

but the range of molecules removed is a little different

• Clearance of small molecules is similar

• Better clearance of medium sized molecules by filtration

• Potential benefit in septic patients in removing cytokines

• Mode selection varies significantly across the world

BEST Kidney investigators:

- survey of 54 ICUs in 23 countries

- 1006 patients on CRRT

Uchino et al, Intensive Care Med 2007; 33:1563Friedrich et al, Crit Care 2012; 16:R146


OMAKI study: Optimal mode of clearance in critically ill

patients with acute kidney injury

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

• 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


OMAKI study: Optimal mode of clearance in critically ill

patients with acute kidney injury

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


Meta-analysis (Friedrich et al):

Friedrich et al, Crit Care 2012; 16:R146

• 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


Meta-analysis (Friedrich et al):

Friedrich et al, Crit Care 2012; 16:R146

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


Ronco et al, Lancet 2000; 356:26

45 ml/kg/hr

35 ml.kg/hr

20 ml/kr/hr

• 206 patients randomized

• 60% sepsis

• CVVH versus

CVVH + added D

Saudan et al, Kidney Int 2006; 70:1312

± 42 ml/kg

± 25 ml/kg


• Negative dosing studies


- 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


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.


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.


• 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


Documents

Principles of CRRT for AKI - Critical Care Canadacriticalcarecanada.com/.../principles_of_continuous_renal_replacement_therapy_for_aki.pdfPrinciples of CRRT for AKI •Principle: a