Acute Hemodialysis & CRRT
in AKI
Paweena Susantitaphong,MD,MS1-3
1Physician
Staff , Division of Nephrology, Department of Medicine,
King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok
2 International Society of Nephrology (ISN) fellowship
3Adjunct Instructor of Tufts University School of Medicine, Boston, USA.
Background
DEFINITION

Acute Renal Failure  Acute Kidney Injury
An abrupt (within 48h) reduction in kidney function
Currently defined as an absolute increase in sCr of
either ≥ 0.3 mg/dl or a percentage increase of ≥ 50%
or a reduction in Urine Output (documented oliguria
of < 0.5 cc/kg per h for > 6 h)
Crit Care 2007;11:R31
Stage
Serum creatinine
Urine output
1
1.5–1.9 times baseline OR ≥ 0.3 mg/dl
< 0.5 ml/kg/h for
(≥ 26.5 mmol/l) increase
6–12 hours
2.0–2.9 times baseline
< 0.5 ml/kg/h for
2
≥12 hours
3
3.0 times baseline OR Increase in serum
< 0.3 ml/kg/h for
creatinine to ≥ 4.0 mg/dl (≥353.6 μmol/l)
≥ 24 hours
OR Initiation of renal replacement therapy
OR Anuria for ≥12
OR, In patients < 18 years, decrease in
hours
eGFR to < 35 ml/min per 1.73 m2
World Incidence of Acute Kidney Injury
: A Meta-Analysis
Susantitaphong P, et al. CJASN 2013, June 6
Susantitaphong P, et al. CJASN 2013, June 6
No. studies
No. subjects
154
3,585,911
112
3,303,992
108
3,281,715
108
3,281,715
189
29,400,495
Susantitaphong P, et al. CJASN 2013, June 6
No. studies
No. subjects with AKI
110
429,535
26
8,226
25
42,354
25
42,354
31
6,534
Susantitaphong P, et al. CJASN 2013, June 6
No. studies
No. subjects with AKI
No. subjects without AKI
92
405,616
1,765,574
21
90,048
1,127,070
20
40,631
1,120,523
20
38,914
1,120,523
20
4,427
127,969
Susantitaphong P, et al. CJASN 2013, June 6
Acute Kidney Injury Increases Risk of
ESRD among Elderly
Ishani A ,et al. J Am Soc Nephrol 2009; 20: 223–228
Coca SG, et al. AJKD 2010
Acute Kidney Injury Associates with
Increased Long-Term Mortality
Lafrance JP ,et al. J Am Soc Nephrol 2010;21 :345-52
Renal Replacement Therapy
 Timing of initiation
◦early VS late
Indications in Renal Failure
1. Uremia
 impaired nutrition
N/V
poor appetite
gastritis with UGIB, ileus, colitis
 Altered mental status
 Pericarditis
 Bleeding from platelet dysfunction
(urgent indication)
(urgent indication)
Indications
2. Refractory or progressive fluid overload
3. Uncontrollable hyperkalemia
4. Severe metabolic acidosis esp. oliguria
5. Steady worsening of renal function
BUN > 70-100 mg/dl
Outcome of Early vs. Late RRT in AKI
Authors
Year
Design
N
Pre-RRT BUN
Survival benefit
Early
Late
Early
Late
Mode of
RRT
Parsons et al
1961
Retro
33
120-150
>200
+
HD
Fischer et al
1966
Retro
162
~150
>200
+
HD
Kleinknecht
1972
Retro
500
<93
>163
+
HD
Conger
1975
Pro
18
70
150
+
HD
Gillum et al
1986
Pro
34
60
100
±
Gettings et al
1999
Retro
100
<60
>60
+
Bouman et al
2002
Pro
106
47
105
±
Demirkilic et al
2004
Retro
61
+
CVVHD
Elahi et al
2004
Retro
64
+
CVVH
Liu et al
2006
Retro
243
+
HD and
<76
>76
±
HD
CRRT
±
CVVH
CRRT
Timing of renal replacement therapy initiation in
acute renal failure: a meta-analysis
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL
• We identified 23 studies (5 randomized or quasi-randomized controlled trials,
1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with
a historic control group).
• By using meta-analysis of randomized trials, early RRT was associated with a
nonsignificant 36% mortality risk reduction (RR, 0.64; 95% CI, 0.40 to 1.05; P = 0.08).
• Conversely, in cohort studies, early RRT was associated with a statistically significant
28% mortality risk reduction (RR, 0.72; 95% CI, 0.64 to 0.82; P < 0.001).
• The overall test for heterogeneity among cohort studies was significant (P = 0.005).
• However, early dialysis therapy was associated more strongly with
lower mortality in smaller studies (n < 100) by means of subgroup analysis.
Am J Kidney Dis. 2008 Aug;52(2):272-84.
Effect of early renal replacement therapy (RRT) initiation
on non-recovery of renal function in AKI
Am J Kidney Dis. 2008 Aug;52(2):272-84.
Parameters that were used in studies for classify
early and late renal replacement therapy initiation in AKI
Clinical symptoms
Solute level (Blood urea nitrogen, serum creatinine)
Interval between ICU/hospital admission and renal replacement
therapy initiation
Days between biochemical diagnosis of AKI and renal
replacement therapy initiation
Severity of AKI (AKIN/RIFLE) classification
Prognostic scores
Number of organ failure
Renal Replacement Therapy
 Timing of initiation
◦early VS late
 Modality of RRT
◦Intermittent VS Continuous
Dialysis : Modality
Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)
Dialysis : Modality
Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)
Intermittent Vs Continuous (IHD,SLED vs. CRRT?)
Note IHD Intermittent Hemodialysis
SLED Sustained Low-Efficiency Dialysis
CRRT Continuous Renal Replacement Therapy
RRT Modalities
INTERMITTENT
IHD
CONTINUOUS
SLED/EDD
CRRT
SCUF
CAVHDF
CVVHDF
CAVH
CAVHD
CVVH
CVVHD
Mechanism of clearance
 Hemodialysis = Diffusion
 Hemofiltration = Convection
 Hemodiafiltration = Diffusion + Convection
t=0
Diffusion
t = equilibrium
Concentration gradient
Molecular weight: speed & size
Membrane resistance: membrane & unstir fluid layer
T=0
T = later
Ultrafiltration
(Convection)
Dialysis : Modality
Intermittent Hemodialysis
Dialysis : Modality
Sustained Low-Efficiency Dialysis (SLED)
6-12 hrs
Hemodialysis in ARF patient
-Long duration 6-12 hrs
-Dialysate flow 70-300 ml/min
-Critically-ill patient
Dialysis : Modality
Continuous Renal Replacemet Therapy (CRRT)
Renal Replacement Therapy : Modality
Continuous Renal Replacemet Therapy (CRRT)
Separated system
Automated system
Separated CVVH system
: A one-year prospective observational study , 192 critically ill patients with AKI.
: Separated system CVVH with the pre-dilution. Mean CVVH dose of 34.9±2.7mL/kg/h.
: The APACHEII score was 23.2±8.4 and the SOFA was 12.0±4.3.
: No complications. The survival rate was 32.3%.
Conclusion: Separated system CVVH is simple, safe, and efficient and could provide
cheaper treatments than the integrated system. It could thus be an effective, alternative
treatment for critical acute kidney injury patients when the integrated mode is unavailable
Automated CVVH system
Renal Replacement Therapy : Modality
PD
(24 hrs)
IHD
(4 hrs)
SLED
( 6-12 hrs)
CRRT
(24 hrs)
Solute removal
per day
+
+++
+++
+++
Hemodynamic
stability
best
poor
Fair-good
good
Cost person and ++
time
+
+++
+++
Complication
BP drop
BP drop
- Air
embolism
- BP drop
-Infection
-high
sugar
-visceral
trauma
Slow continuous ultrafiltration (SCUF)
Continuous
arteriovenous
hemofiltration
(CAVH)
Continuous
venovenous
hemofiltration
(CVVH)
Continuous
arteriovenous
hemodialysis
(CAVHD)
Continuous
venovenous
hemodialysis
(CVVHD)
Continuous
arteriovenous
hemodiafiltration
(CAVHDF)
Continuous
venovenous
hemodiafiltration
(CVVHDF)
Vascular access
Slow continuous ultrafiltration (SCUF)
Continuous
venovenous
hemofiltration
(CVVH)
Continuous
venovenous
hemodialysis
(CVVHD)
Continuous
venovenous
hemodiafiltration
(CVVHDF)
Vascular access
Mechanism of Clearance
SCUF
 Slow Continuous UltraFiltration
 Arteriovenous or venovenous
 QUF 100 – 300 mL/day
 Perform to maintain fluid balance, no
significant convective clearance
 No replacement fluid
Measuring
device
Filtrate
CVVH
Replace
-ment
fluid
 Continuous Veno-Venous
HemoFiltration




Veno-venous circuit
High permeable membrane
Typical UF rate 1 – 2 L/h
Requires at least a blood pump
(Flow > 50 ml/min) required
 Replacement fluid
(pre-dilution VS post-dilution)
Measuring
device
Filtrate
CVVHD
 Continuous VenoVenous HemoDialysis
 High permeable membrane
 At least a Blood pump and a pump
for Dialysate (10-30 ml/min or 1-2.5
L/h) required
 No replacement fluid
 UF for volume control, some
convective clearance at high rate
Dialysate
Measuring
device
Filtrate
CVVHDF

Replace
-ment
fluid
Continuous VenoVenous
HemoDiaFiltration
 High permeable membrane
 Ultrafiltration flow > 6 ml/min
(9-12 L/day)
 1 pump for dialysate
(10-30 ml/min or 1-2.5 L/h))
 Replacement fluid
Dialysate
Measuring
device
Filtrate
Continuous Renal Replacement Therapy
Volume
Control
Diffusive
Clearance
Convective
Clearance
Volume
Replacement
SCUF
Yes
-
+
No
CVVH
Yes
-
+++
Yes
CVVHD
Yes
+++
+
No
CVVHDF
Yes
++
++
Yes
IHD
CRRT
Mortality
Study
N
Mode of RRT
ICU hospital mortality P-value
Hospital mortality
P-value Comments
166
CRRT/IHD
59.5% vs 41.5%
65.5% vs 47.6%
< 0.02 Unexplained randomization
RCT
Mehta, 200132
<0.02
problems
Augustine 200433
80
CVVHD/IHD
NA
NA
67.5% vs 70%
NS
Underpowered Inadequate
delivered dose of dialysis
Uelinger 200534
125
CVVHDF/IHD
34% vs 38%
0.71
47% vs 51%
0.72
Vinsonneau 200635
360
CVVHDF/IHD
NA
NA
NA
NA
Enrollment problems
Underpowered
60 day mortality 32.6% vs
31.5% ,p =0.98
Changes in dialysis dose
Underpowered
Lins 200936
316
CRRT/IHD
NA
NA
58.1% vs 62.5%
NS
Meta-analysis (Relative risk)
Tonelli ,200237
>600
CRRT/IHD
NA
NA
0.96
NS
Kellum , 200238
1,400
CRRT/IHD
NA
NA
0.93
NS
Rabindranath, 200739
1,550
CRRT/IHD
1.06
NS
1.01
NS
Used different types of
mortality
After adjustment for study
quality and severity of
illness, mortality was lower in
CRRT patients
Cochrane meta-analysis
Pannu ,200840
6,058
CRRT/IHD
NA
NA
1.1
NS
Systematic review
Renal recovery
Study
N
Mode of RRT
Definition of renal outcome
Outcome
P-value
Comments
Cohort
Jacka , 200541
93
IHD/CRRT
64.3% vs 12.5%
0.0003
,200742
2,202
IHD/CRRT
Dialysis dependence at
discharge
Requirement of chronic
dialysis after 90 days
16.5% vs 8.3%
NA
Higher severity score in
CRRT group
Higher long-term mortality in
IHD vs CRRT ; after 10 yrs
total risk of ESRD almost
the same in both groups
Uchino,200743
1,218
IHD/CRRT
Dialysis dependence at
hospital discharge
33.8% vs 14.5%
<0.0001
Results remained significant
in patients without prior CKD
RCT
Mehta ,200132
166
IHD/CRRT
1) 7% vs 14%
2) 17% vs 4%
1) NS
2) 0.01
Augustine,200433
80
IHD/CRRT
4 pts vs 5 pts
NS
The percentage of CKD in
baseline (≥2mg/dL) was
higher in patients with IHD
(NS)
Small number of patients
Uehlinger,200534
125
IHD/CVVHDF
1) Dialysis dependence at
hospital discharge
2)CKD at hospital discharge
and dealth
Discontinuation of dialysis at
discharge
1) Rate of dialysis
dependence
2) Absence of renal recovery
1) 1pt vs 1pt
2) 58% vs 50%
1) NA
2) 0.61
Similar proportions of
patients with CKD at
baseline
Vinsonneau,200635
360
IHD/CVVHDF
1) Rate of renal recovery at
ICU discharge
2) Rate of renal recovery at
hospital discharge
1)90% vs 93%
2) 100 vs all but
1patient
1) 0.5
2) NA
Not possible to determine
difference in proportion of
patients with CKD in the 2
groups
Meta-analysis
Rabindranath, 200739
1,550
IHD/CRRT
NS
Cochrane meta-analysis
Pannu ,200840
6,058
IHD/CRRT
number of surviving patients RR=0.99
not requiring RRT
RR=0.91
chronic dialysis
NS
Systematic review
Indication for CRRT
• Cardiovascular failure
• Hypercatabolism
• Cerebral edema
• Liver failure
• Sepsis
• Adult respiratory distress syndrome
• Cardiopulmonary bypass
• Crush syndrome
Renal Replacement Therapy
 Timing of initiation
◦early VS late
 Modality of RRT
◦Intermittent VS Continuous
 Dose of RRT
◦Daily vs AD
Dialysis Dose Measurements

The treatment dose of RRT can be defined by
various aspects
◦ Efficiency
◦ Intensity
◦ Frequency
◦ Clinical efficacy
Ricci Z & Ronco C: Crit Care Clin 2005.
Clearance (ml/min)
Efficiency of RRT
(Clearance, K)
Pisitkun et al. Contr Nephrol 2004.
Daily clearance (ml/day)
Intensity of RRT (Kt)
24h
8h
3h
Pisitkun et al. Contr Nephrol 2004.
Weekly Clearance
(ml/week)
Weekly Clearance of RRT
24h
8h
Continuous Alt.days
8h
x7 days
3h
x3 days
3h
x7 days
Pisitkun et al. Contr Nephrol 2004.
Effect of Delivered RRT Dose : CRRT
“Effects of different doses in CVVH on outcomes of ARF”
100
90
80
70
60
50
40
30
20
10
0
Overall
20 ml/kg/hr
35 ml/kg/hr
45 ml/kg/hr
RCT, n=425
Ronco C. , et al. The LANCET 2000
Effect of Delivered RRT Dose : CRRT
“Effects of different doses in CVVH on outcomes of ARF”
100
90
80
70
60
50
40
30
20
10
0
Overall
20 ml/kg/hr
RCT, n=425
Septic patients
35 ml/kg/hr
45 ml/kg/hr
Ronco C. , et al. The LANCET 2000
Effect of Delivered RRT Dose : CRRT
“Effects of different doses in CRRT on outcomes of ARF”
UF/Dialysis 24/18 ml/kg/hr
UF/Dialysis 25/0 ml/kg/hr
RCT, n=206
Saudan P, et al. Kidney Int 2006; 70:1312-7
Effect of Delivered RRT Dose : CRRT
RCT, n=1124
Effect of Delivered RRT Dose : CRRT
RCT, n=1508
NEJM 2009
Effect of Dialysis Dose on Survival in
Critically Ill Patients Requiring RRT
100-
Survival %
90High RRT Dose
807060504030-
Low RRT Dose
20100Severity of Disease
Paganini et al: Blood Purif 2001.
Anticoagulation
Drugs
Advantages
Disadvantages
Heparin
Good anticoagulation
Thrombocytopenia ,
Bleeding
Regional heparin
Reduced bleeding
Complex
management
LMWH
Less thrombocytopenia Bleeding
Citrate
Lower risk for bleeding Metabolic alkalosis,
Hypocalcemia,
Special dialysate
Prostacycline
Reduced bleeding risk
Hypotension
Poor efficacy
Saline flushes
No bleeding risk
Poor efficacy
Dose heparin for CRRT
aPTT (seconds) Bolus dose
Rate change
Repeat aPTT
< 40
40.1-45.0
45.1-55.0
55.1-65.0
1,000 U
Nothing
Nothing
Nothing
+200 U/hr
+100 U/hr
No change
Stop 1/2 hr and
In
In
In
In
Nothing
-100 U/hr
Stop 1 hr and
In 4 hrs
>65.0
6
4
6
4
hrs
hrs
hrs
hrs
-200 U/hr
: Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline for
a heparin concentration of 500U/ml.
: Initial bolus is 25 U/kg followed by an infusion of 5U/kg/hr.
: The goal of treatment is to maintain systemic prefilter aPTT (45 -55 seconds, 1.5 times control)
Common complications for citrate
Derangement
Metabolic acidosis
Cause and signs
Insufficient removal of metabolic acids
Anion gap increases
Loss of buffer substrate is higher than delivery
Citrate metabolism decreases ( decreases, total Ca/iCa increase
[more than 2.1-2.5], and anion gap Increases)
Metabolic alkalosis
Hypocalcemia
Hypercalcemia
Hypernatremia
Increase bicarbonate replacement or Increase bicarbonate dialysate
flow or give additional bicarbonate or increase citrate flow (cave
accumulation)
Decrease citrate delivery or stop Increase dialysate or filtrate flow,
Increase bicarbonate replacement or increase bicarbonate dialysate flow
Delivery of buffer substrate is higher than loss
Decrease bicarbonate replacement or decrease bicarbonate dialysate
flow or stop additional bicarbonate iv or decrease citrate flow (cave
accumulation)
Decrease loss of buffer due to a decline in filtrate flow
Change filter
Increase filtrate flow
Loss of calcium is higher than delivery ( decreases and total
Ca/iCa is normal)
Increase iv calcium dose
Citrate metabolism decrease ( metabolism acidosis , total ca/iCa
increase, and anion gap increases)
Increase iv calcium dose
decrease or stop citrate delivery
increase dialysate or filtrate flow
increase bicarbonate replacement or
increase bicarbonate dialysate flow
Decrease iv calcium dose
Recalculate default settings
Protocol violation
Decrease sodium replacement
Decrease dialysate sodium content
Decrease trisodium citrate flow
Change filter
Delivery of calcium is higher than loss
Delivery of sodium is higher than loss
Decreased loss of sodium due to a decline in filtrate flow
Hyponatremia
Adjustment
Increase CRRT dose (filtrate or dialysate flow) to 35 ml/kg per hr
Loss of sodium is higher than delivery
Recalculate default settings
Protocol violation
Increase sodium replacement
Increase dialysate sodium content
Increase trisodium citrate flow
EXAMPLE
: Rt internal jugular catheter
: CVVH order
BFR 120-150 cc/min, RF (predilution 1,500 cc/hr)
UF -100 cc/hr (2,400 cc/day)
: Dialysate solution
0.45% 900 cc,
3%NaCl 50 cc ,
7.5%HCO3 50 cc
KCl 3 mEq/L
: 10% Calcium gluconate 180
cc/day
: 50% Magnesium sulphate
2 cc iv
Na+, K+, Cl-, HCO3-, Ca2+,
blood sugar q 6-12 hrs
BUN, Cr, Mg2+, PO43-CBC, ,
PT/PTT q 24 hrs
Common complications in CRRT
Vascular access
Bleeding
Thrombosis
Hematoma
Aneurysm
formation
Hemothorax
Pneumothorax
Pericardial
tamponade
Arrthymias
Air embolism
Infection
Extracorporeal circuit
Air embolism
Reduced filter life
Reduced dialysis
dose
Hypothermia
Bioincompatibility
Immunologic
activation
Anaphylaxis
Hematologic
complications
Need for
anticoagulantion
Hypocalcemia
Metabolic alkalosis
Hypernatremia
Citrate intoxication
Bleeding
Thrombocytopenia
Bleeding
Hemolysis
Heparin-induced
thrombocytopenia
Electrolyte
disturbances
Hypophosphatemia
Hypomagnesemia
Hypocalcemia
Hypokalemia
Hyponatremia
Hypernatremia
Hemodynamic
instability
Altered drug
removal
Volume management
errors
Delayed renal
recovery
Nutritional losses
Amino acids &
proteins
Poor glycemic
control
Vitamin deficiencies
Trace minerals
Acid-base
disturbances
Metabolic acidosis
Metabolic alkalosis
Citrate-induced
alkalosis & acidosis
Thank you