CRRT Principles (Thai).pdf

Changing Paradigm of AKI
Management: CRRT
Principles, Patient Selection, and Prescription
Nattachai Srisawat, MD, MS, EDIC
Excellence Center for Critical Care Nephrology,
King Chulalongkorn Memorial Hospital,
Thai Red Cross Society,

Outlines
CRRT Principles
· What is CRRT
· Timing of initiation: How early initiation of CRRT might help mitigate AKI and its
complications
· Modalities (CVVH/CVVHD/CVVHDF) of CRRT-When to use which modalities and
their benefits.
Patient selection
· Clinical criteria for initiation of CRRT (Hemodynamic instability, Azotemia etc.)
· Definition of hemodynamically unstable patient
· CRRT in comparison to SLED in Hemodynamically unstable patient
Prescription
· Dose calculation for CVVH/CVVHD/CVVHDF
· Details of dosing

1. Patients is admitted in ICU
2. Patients’s volume, perfusion pressure, and tissue oxygenation were optimized
3. Suspected or proven AKI (KDIGO criteria)
Start AKI monitoring, using IT
Patients data
Severity assessment
- APACHE, SAP, SOFA
Patients data + Risk factor + severity + RIFLE (AKIN) + ….. = Patient score
4. Start RRT

5. Prescription
Choose mode of therapy
Machine type
Choose therapy setting
Filter type
Intermittent CRRT
Dialysate/
replacement solution
Dose Vascular access
Prescription done
Applied therapy data collection (24 hr)
Evaluation of criteria for stopping or continuing therapy
End of treatment

40 Years of CRRT
Int J Artif Organs 2017; 40(6): 257-264

Clinical outcome
• Mortality
• Clearance waste product
• Improve fluid balance (fluid control)
• Improve acidosis
• Improve renal recovery
• Impact beyond renal support

RRT ideal method
• Good clinical outcome
• Adaptable to the patients status
• Excellence hemodynamic status
• No need for anticoagulation
• Allowing patient mobility
• Low nurse work load

Clin J Am Soc Nephrol 2008;; 3: 887
Top research priority of AKI

Seminars in Dialysis. 2003; 675–681

Kidney International (2017) 91, 1022–1032
Life-threatening complication

CONCEPTUAL TIMELINE
Increased
Risk
Stressor Damage
Decrease
GFR/AKI
Kidney
failure
Death
RRT
? ? ? ?

How to define “Early”
• BUN based à we do not use this alone in
clinical practice
• Creatinine based à CKD ?
• Admission to hospital based
• Admission to ICU based
• RIFLE, AKIN based
• Fluid overload based
• Biomarker directed

RIFLE critieria
BUN/creatinine
based
AKIN critieria
• Hospital admission time
Fluid overload
based
• ICU admission time

Benefit of early RRT
- Better solute and fluid control
- Fast acid-base disorder correction
- Prevent uremia
- Reduce distant organ dysfunction
Risk of early RRT
- Risk of vascular access
- Oxidative stress
- Hemodynamic instability
- Delay renal recovery
- Inadequate hemodynamic optimization
- Cost

Author Year Mode of
RRT
Study
design
N Criteria for initiation of RRT Survival (%)
Early Late Early Late
Parsons
Fischer
Kleinknecht
Conger
Gillum
Gettings
Bouman
Demirkilic
Elahi
Piccinni
Liu
1961
1966
1972
1975
1986
1999
2002
2003
2003
2006
2006
IHD
IHD
IHD
IHD
IHD
CRRT
CRRT
CRRT
CRRT
CRRT
IHD&CRRT
Retro
Retro
Retro
RCT
RCT
Retro
RCT
Retro
Retro
Retro
Retro
33
162
500
18
34
100
106
61
64
80
243
BUN120-150 mg/dl
BUN ~ 150 mg/dl
BUN < 93 mg/dl
BUN < 70 mg/dl or sCr <
5 mg/dl
sCr 8 mg/dl
BUN < 60 mg/dl
< 12 hrs after AKI
diagnosis
UOP < 100 ml/8hr
UOP < 100 ml/8hr
< 12 hrs after ICU
admission
BUN ≤ 76 mg/dl
BUN >200 mg/dl
BUN > 200 mg/dl
BUN > 163 mg/dl
BUN ~150 mg/dl, sCr
~10 mg/dl
BUN ~ 100 mg/dl or sCr
~ 9 mg/dl
BUN > 60 mg/dl
BUN > 112 mg/dl, K >
6.5 mEq/L, or PE
sCr > 5mg/dl or K > 5.5
BUN ≥ 4 mg/dl, sCr > 2.8
mg/dl, or K > 6
BUN > 76 mg/dl
75
43
73
64
41
39
LV:69,
HV:74
77
78
55
65
12
26
58
20
53
20
LV:7
5
45
57
28
59
BUN-based timing

Cr-based timing: NSARF
Early: RIFLE “R”
Late: RIFLE “I, or F”
Indication for start RRT:
Conventional indication
Shiao et al. Crit Care 2009;; 13:R171

Shiao et al. Crit Care 2009;; 13:R171
Early better

Creatinine has a lag time effect
• Half life 4 hours
• 50% reduction in GFR
= 8 hours
• Require 3-5 half life
Before reach a new
steady state
24-40 hours
Filtration marker

Bilateral nephrectomy model

• Timing from hospital admission
• Timing from ICU admission
• Timing from AKI diagnosis
Admission date-based timing
What is the right timing ?

Bagshaw J, et al. J Crit Care 2009;; 24:129-40
Early better

Fluid overload is a risk factor for
mortality in AKI patients
Bouchard J, et al. Kidney Int 2009;;76:422-7

N Engl J Med 2016;375:122-33.
620 patients enrolled in ICU
on MV +/- vasopressor
with KDIGO stage 3

• 231 ICU patients with KDIGO stage 2 AKI and exhibiting a NGAL level
above 150 ng/ml.
• Compared with delayed treatment, an early strategy resulted in
lower 90 day mortality,
more rapid recovery of renal function, and
significantly shorter duration of hospital stay.
JAMA. 2016;315(20):2190-2199.

SUMMARY STUDY TIMING TO START RRT
Features ELAIN AKIKI STARRT-AKI pilot
Country Germany France Canada
Number of sites 1 31 12
Number of participants 231 (604) 620 (5528) 100
Population 94.8% surgical
patients
79.7% medical
patients
Mixed medical/surgical ICU
Enrollment criteria KDIGO at least
stage 2 and
uNGAL > 150
ng/mL
KDIGO stage 3 2/3 of i) 2 times increased sCr from basline, ii)
UOP < 6 ml/kg in 12 hours, iii) pNGAL > 400
ng/mL
pNGAL level, early vs
standard (delayed) group,
ng/mL
490 vs 618.5 - >1300 vs >1300
Time difference 25.5 hours 57 hours 41.6 hours
RRT modality CVVHDF CRRT and IHD,
(Initial IHD 55(%
Initial IHD 31-34 %in both groups
Baseline SOFA score 16 10.9 13
Serum creatinine at RRT
initiation, mg/dL
1.9 vs 2.4,
p<0.001
3.27 vs 5.33,
p<0.001
3.68 vs 4.57
Received RRT in standard
(delayed) group, %
90.8 51 75
Mortality, early vs standard
(delayed) group, %
28 day
60 day
90 day
30.4 vs 40.3,
p=0.11
38.4 vs 50.4,
p=0.07
39.3 vs 54.7,
41.6 vs 43.5
48.5 vs 49.7, p=0.79
-
-
-
38 vs 37, p=0.92

ELAIN study
AKIKI study
Shiao et al. Critical Care (2017) 21:146
25 hours
57 hours

Kidney International (2017) 91, 1022–1032

Demand and Capacity Paradigm
Risk stratification is the key !!!
Identify high risk patient who will receive the most benefit from early RRT

Potential role of biomarkers AFTER developed AKI
Increased
Risk
Stressor Damage
Decrease
GFR/AKI
Kidney
failure/
RRT
Death
Predict renal recovery, outcome
Predict AKI early,
outcome, severity, RRT

Nature and source of NGAL
- PMN mainly release the dimeric form, and
some of monomeric form
- Tubular cells mainly produce the monomeric
form and to some extent NGAL conjugated
with MMP-9 (heterodimeric NGAL). Blood Purif 2014;;37:304–310
25-40 ng/mL

Acta Physiol 2017, 219, 556–574
NGAL

Summary studies using NGAL to predict AKI
Blood Purif 2014;;37:304–310

NGAL: meta-analysis
• N = 19 studies
• 2,538 patients
• 487 with AKI (19.2%)
• AUC for predict AKI = 0.82
• AUC for predict RRT = 0.78
• AUC for predict death = 0.71
Haase et al. Am J Kidney Dis 2009; 6:1012

Therapeutic Apheresis and Dialysis 2013;; 17(3):332–338
pNGAL > 1000 ng/ml
uNGAL > 2000 ng/ml

pNGAL: Systemic (distant organ, inflammatory cell), Renal pool (decrease GFR)

Srisawat N, et al, Kidney Int 2011

Propose cut point for NGAL
Dx AKI DX severe AKI Consideration
RRT
Urine NGAL
(ng/mlL)
100-150 1000 2000
Plasma NGAL
(ng/mL)
100-150 400 1000
Tiranathanagul K et al. Ther Apher Dial 2013;; 17(3):332–338
Srisawat N, et al. Clin J Am Soc Nephrol 2011;; 6: 1815-23
Srisawat et al. Kidney Int 2011;;80:545-52.

Acta Physiol 2017, 219, 556–574
L-FABP

Marker of inflammation
Marker of ischemia

Cell cycle arrest biomarkers
SAPPHIRE study

FDA approved Nephrocheck
September 5, 2014

Biomarkers NGAL TIMP-2/IGFBP-7 L-FABP
Site of production Distal tubule unknown Distal tubule
Biology Bacteriostatic
function in the
innate immune
response, iron
delivery to
mammalian cells
Cell cycle arrest Regulation of fatty
acid uptake and the
intracellular
transport
Cut off point 100 ng/mL 0.3 Yes
Prediction/
Diagnosis
Yes Yes Yes
Predict prognosis Yes No Yes
Predictt progression
to ESRD
Yes Yes No

Furosemide stress test (FST):
A novel AKI biomarker
• Definition: Urine output
(UOP) in 2 hours after
standardized iv
furosemide load
• Low UOP after FST
(< 200 mL/2 h) could
predict progression to
severe AKI, need for RRT,
and death
Chawla et al. Crit Care 2013;;17:1-9
Koyner et al. J Am Soc Nephrol 2015;;26:1-9.
Need for RRT
Biomarker AUC ± SEM
FST (2-hr
UOP)
0.86 ± 0.08
Urine NGAL 0.50 ± 0.08
Urine IL-18 0.61 ± 0.07
Urine KIM-1 0.61 ± 0.10
Urine IGFBP-7
x TIMP-2
0.61 ± 0.13
Urine ACR 0.67 ± 0.09
FeNa 0.64 ± 0.09
Plasma NGAL 0.52 ± 0.13

Biomarkers guided RRT initiation

Case example
• 47 year-old male
• Developed severe ARDS
from pneumonia, admitted
to ICU
• On admission; BP drop to
79/38 mmHg and a rise in
Body Temperature 39 c
• Septic work up was done,
start ABX
Treatment
- Central line, A-line,
Norepinephrine at 0.4
mcg/kg/min
-Fluid: Normal saline 4 litre
Lab: WBC 24,000 (N 90%)
- Baseline BUN and Cr were
20/1.0
- Now serum creatinine 1.4 mg/dl
- No acidosis, no hyperkalemia
- UOP 15 ml/hr for 6 hours
- Shall we start RRT ?
If urine NGAL 5680 ng/mL
No absolute indication

Lumlertgul et al. Critical Care (2018) 22:101

13.6%
75.0%
Lumlertgul et al. Critical Care (2018) 22:101

• SCUF: Ultrafiltration
•
• CVVH: convection
• CVVHD: diffusion
• CVVHDF: convection + diffusion
Mode of CRRT

Ultrafiltrate
Replacement fluid
Pump
CVVH
(Predilution)
Limitation factors : UF rate (adequate BF, ↑ Hct)
Cost of infusion fluid

Dialysate out Dialysate in
CVVHD
Pump

Dialysate out
+
Ultrafiltration
Dialysate in
CVVHDF
Pump Replacement fluid
(Postdilution)

Chapter 5.6: Modality of RRT
for patients with AKI
• Use continuous and intermittent RRT as
complementary therapies in AKI patients. (Not
Graded)
• We suggest using CRRT, rather than standard
intermittent RRT, for hemodynamically unstable
patients. (2B)
• We suggest using CRRT, rather than intermittent
RRT, for AKI patients with acute brain injury or
other causes of increased intracranial pressure
or generalized brain edema. (2B)

CRRT can be applied in any setting
Hemodynamic instabilities
Hemodynamic stable
CRRT
IHD, PD Hybrid therapy
SLED/EDD
SLEDf
CRRT
CRRT
CRRT
CVS SOFA score 3,4
CVS SOFA score 0,1,2

Intermittent hemodialysis
• Disadvantages
o Hypotension
• Related to rapid
solute removal not
blood flow
• Fluid shift
o Dysequilibrium
syndrome
• Dose: daily
• Not good for larger
molecules
• Advantages
o Rapid solute
correction: K +
o Cost
o Convenience: day time
treatment
o Safety
o Patient mobility

Dialysate Na concentration
Dheena et al, KI 2001

Role of hypothermia
Rokyta Jr., NDT 2004

Optimization of IHD
• Simultaneous line connection
• High dialysate Na (145)
• Cool temperature 35 c
• Low ultrafiltration rate
Shortgen F et al, AJRCCM 2000

Better volume control with CRRT
Bouchard J, et al. Kidney Int 2009;;76:422-7

Srisawat et al, Crit Care 2010

What dose ?
1. HOW TO CALCULATE
SOLUTE CLEARANCE

— How to calculation ?
— Principle
— Solute clearance for
¡ CVVH: pre and post dilution
¡ CVVHD
¡ CVVHDF; pre and post dilution
Solute clearance

CVVH: post-dilution
— BFR 100 ml/min
— Uf 1.5 L/hr
— BUN = 60 mg/dl
— Effluent BUN = 60
mg/dl
— BW 60 kg
— Filtration fraction =
Quf/Qplasma flow
K = 60 x 1500
60
1500
100 x 60 x (1-0.30)
35.7%
25 ml/min

CVVH: pre-dilution
— Uf 1.5 L/hr
mg/dl
— BW 60 kg
Quf/Qplasma flow
K = 60 x 1500
60
1500
{100 x 60 x (1-0.30)}
26%
20 ml/min
X
6000
1500 + 6000
+ 1500

Pre-dilution VS Post-dilution
48 patients were studied (33 in pre-dilution and 15 in post-dilution).

Filter run time
The median creatinine clearance during pre-dilution
was 33 vs. 45 ml/min in post-dilution (p = 0.001).

CVVHD
— Dialysate inflow rate
= 1.5 L/hr
— Net Uf = 0
mg/dl
— BW 60 kg
K = 60 x 1500
60
25 ml/min

Diffusion VS Convection
Crit Care 2006;10:R67
P = 0.03
Filter life time

CVVHDF: post-dilution
— Dialysate inflow rate =
1.5 L/hr
— Replacement fluid rate
= 1. 5L/hr
— Net Uf = 0
mg/dl
— BW 60 kg
K = 60 x 3000
60
50 ml/min

CVVHDF: pre-dilution
BFR 100 ml/min
Dialysate inflow rate = 1.5 L/hr
Replacement fluid rate = 1. 5L/hr
Net Uf = 0
BUN = 60 mg/dl
Effluent BUN = 60 mg/dl
BW 60 kg
K = 60 x 3000
60
40 ml/min
6000
1500 + 6000
x
Quf/Qplasma flow
1500
{100 x 60 x (1-0.30)}
26%
+ 1500

Current evidence
35 vs 20 ml/kg/hr
40 vs 25 ml/kg/hr
ATN trial, USA
RENAL trial, ANZIC

Proposed relationship between RRT
intensity and survival
Kellum J, Ronco C. Nat Rev Nephrol 2010;;6:191

Conclusions
CRRT Principles
· Timing of initiation: Early might be better
· Modalities (CVVH/CVVHD/CVVHDF) of CRRT-
Patient selection
• Clinical criteria for initiation of CRRT (Hemodynamic instability, Azotemia etc.)
· Definition of hemodynamically unstable patient
· CRRT in comparison to SLED in Hemodynamically unstable patient
Prescription
· Dose calculation for CVVH/CVVHD/CVVHDF
· Details of dosing

CRRT Principles (Thai).pdf

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