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林口長庚紀念醫院 加護腎臟科/陳永昌
Outline
Introduction
CRRT Nomenclature
Applications for CRRT
Fluid Management in CRRT
Clinical Aspects
Evidence Based Medicine
Conclusions
AKI in ICUs
In ICUs, acute kidney injury (AKI) frequently occurs in
patients with medical or surgical complications and
multiorgan failure
Worse prognosis
Standard intermittent renal replacement (IHD) treatments
are often contraindicated
RIFLE Classification
Risk
Injury
Failure
Loss
ESRD
GFR criteria
Urine output criteria
Increase SCr x 1.5 or
UO < 0.5ml/kg/h x 6 hr
GFR decrease >25%
Increase SCr x 2 or
UO < 0.5ml/kg/h x 12 hr
GFR decrease >50%
Increase SCr x 3 or
UO < 0.3ml/kg/h x 24 hr or
GFR decrease >75% or
anuria x 12 hr
SCr > 4 mg/dl
Complete loss of kidney function > 4 weeks
End stage renal disease (> 3 months)
(Bellomo R et. al. Critcal Care 2004)
Contraindication to Hemodialysis
Hemodynamic instability (hypotension, presence of
significant cardiovascular disease)
Lack of access to circulation
Lack of highly trained staff and/or equipment
Indication and Timing of Dialysis for AKI
Renal Replacement vs. Renal Support
Renal replacement
Purpose
Timing of intervention
Replace renal function
Based on level
biochemical markers
Indications for dialysis Narrow
Dialysis dose
Extrapolated from
ESRD
Renal support
Support other organs
Based on individual
need
Broad
Targeted for overall
support
CRRT vs. IHD
Hemodynamic stability
Fluid removal
Dialysis efficiency
Anticoagulation
Patient mobilization
Specialty personnel
Drug dosing/delivery
Volume restriction
CRRT
IHD
Stable
Slow, gentle, complete
Low efficiency, long time
Frequently necessary
Possible
Perhaps
Easier
Minimal
Unstable
Rapid, harsh, incomplete
High efficiecy, short time
Zero heparin possible
Possible
Definitely
Difficult
Significant
Continuous Renal Replacement Therapy (CRRT)
CAVH: Continuous arteriovenous hemofiltration
CAVHD: Continuous arteriovenous hemodialysis
CAVHDF: Continuous arteriovenous hemodiafiltration
CVVH: Continuous venovenous hemofiltration
CVVHD: Continuous venovenous hemodialysis
CVVHDF: Continuous venovenous hemodiafiltration
AVSCUF: Arteriovenous slow continuous ultralfiltration
VVSCUF: Venovenous slow continuous ultralfiltration
V
X
X
CRRT: AV vs. VV
Arteriovenous therapies (AV)
Technique simplicity
Required large-bore arterial catheter
Blood flow dependent on MAP
Venovenous therapies (VV)
No arterial line
Pump-assisted
Blood flow independent of blood pressure
CGMH CRRT Order
1. Diagnosis
2. CVVH Solution A 3000 cc + 15% KCl __ cc IVF (500~ cc/hr)
3. CVVH Solution B 3000 cc + 7% NaHCO3 240 cc IVF(500~cc/hr)
4. Record I/O Q1h and Keep I/O _____
5. Check: BUN,Cr, Na, K, Cl, Ca, P QD; Mg QW1,4
6. Blood flow 120ml/min
7. Check ACT Q6h and Keep ACT at 200~250 sec
P.S. 15% KCl 6 cc/3L
2.012 meq/L K
7.5 cc/3L
9 cc/3L
10.5 cc/3L
12 cc/3L
2.515 meq/L K
3.018 meq/L K
3.521 meq/L K
4.024 meq/L K
Multi-mode
continuous renal
replacement
machine
Applications for CRRT (1)
Renal application (renal replacement and renal support)
Acute renal failure (specifically complicated ARF with
multiple organ failure)
Oligouric ARF needs large amount of fluid or nutrition
Fluid overloading
An alternative to HD in the mass casualty situation
Electrolytes and acid base disturbance
Applications for CRRT (2)
Non-renal application
Hepatic failure complicated with hepatic coma
Congestive heart failure refractory to diuretics
Overhydration during & after cardiac surgery (CPB & after)
Sepsis
Life-threatening hyperthermia
Hemofiltration for poisoning (lactic acidosis, lithium poisoning)
Cytokine removal: Acute respiratory distress syndrome
Chemofiltration, chemoperfusion
Potential Complications of CRRT
Technical
Vascular access malfunction
Circuit clotting
Circuit explosion
Catheter and circuit kinking
Insufficient blood flow
Line-catheter disconnection
Fluid balance errors
Loss of efficiency
Clinical
Bleeding, Hematomas
Thrombosis
Infection and sepsis
Allergic reactions
Hypothermia
Nutrient losses
Insufficient blood purification
Hypotension, arrhythmia
Fluid Removal vs. Fluid Regulation
Fluid removal Fluid regulation
Normal kidney
IHD
PD
CRRT
+++
+++
++
+++
++++
-
-
+++
Fluid and Solute Removal in CRRT
Fluid
Solute
Back transport
Hemofiltration
Hemodialysis
Hemodiafiltration
(CAVH, CVVH) (CAVHD, CVVHD) (CAVHDF, CVVHDF)
Convection
Convection
Convection
Convection
Diffusion
None
Possible
Convection+Diffusion
Possible
Components of Fluid Regulation
Fluid Balance
Fluid composition
Electrolyte and Acid Base homeostasis
Nutritional balance
Temperature control
Volume Adjustment for Fluid Management
Level 1: Ultrafiltrate volume limited to match anticipated
needs for fluid balance over 8-24 hours. Limited replacement
fluid.
Level 2: Ultrafiltrate volume greater than hourly intake. Net
fluid balance achieved by hourly replacement fluid
administration.
Level 3: Ultrafiltrate volume adjusted greater than hourly
intake. Net fluid balance targeted to achieve specific
hemodynamic parameters eg. CVP, PAWA, MAP.
Sliding Scale for Volume Adjustment
Desired volume change (ml/hr)
PAWP < 6
PAWP 6-8
PAWP 9-11
PAWP 12-14
PAWP 15-17
PAWP 18-20
PAWP 21-22
PAWP >22
+ 175 ml and notify nephrologist
+ 125 ml
+ 75 ml
Zero balance
 50 ml
 75 ml
 100 ml
 125 ml and notify nephrologist
Electrolyte and Acid Base Derangements
Continuous therapies can be used to correct water and
electrolyte imbalances
Hypo-hypernatremia can be corrected not only achieving
a normal plasma sodium concentration, but also by
restoring the normal body sodium content
Hyperkalemia can also be corrected: the efficiency of
continuous arteriovenous and venovenous hemofiltration
in removing potassium is low
AKI in Neonates
Continuous arteriovenous hemofiltration is especially
useful in the treatment of acute renal failure in neonates
and small babies (Ronco et al. 1984, 1986)
CRRT as a successful bridge to liver transplantation
should be considered in children with unrelenting
hyperammonemia not amenable to routine medical
therapy (Chen CY et al. 2000)
Treatment of Multiple Organ Dysfunction
and Sepsis with CRRT
Eicosanoids, cytokines (tumor necrosis factor and
interleukins such as IL-1, IL-6, and IL-8), endothelin, and
platelet-activating factor may all contribute to the reduction
of renal blood flow and GFR during sepsis
ARF cannot be treated effectively unless the underlying
problems are resolved
CVVH using the high-permeability membranes allows
extraction of significant quantities of circulating
macromolecules (MW 30 kDa)
CRRT of AKI in Burns Patients
CRRT may maintain a good uremic control for severely
catabolic burns patients with multiorgan dysfunction
Treatment is possible despite cardiovascular instability and
total parenteral nutrition can be given
CAVHD appears to give somewhat better uremic control,
but the difference in mortality is not significant
Large burns, pulmonary burns and septicemia seems to be
bad prognostic signs (Leblanc et al. 1999)
Advantage of CRRT for Nutritional Support
Fluid restrictions are removed
Electrolyte overload is avoided
Hyperosmolar nutrition solutions are safe
CRRT result in a cumulative Kt/V or small solute removal rate
equivalent or superior to conventional intermittent 4 hours HD
 IHD daily X 4 hr: Kt/V weekly 7.5
 IHD X three sessions /week: Kt/V weekly 3.2
 CAVHD: Kt/V weekly 6.2
 CVVHD: Kt/V weekly 8.0 (Leblanc M. et al. Semin Dial 1995)
CRRT provide adequate clearance of nitrogenous compounds
with the avoidance of repeatedly high peak serum nitrogen
values (Clark WR et al. JASN 1994)
Regional Chemotherapy plus Hemofiltration
vs. Hemoperfusion
Regional intra-arterial chemotherapy: drug delivery 1.5~2 x
systemic dose
Regional chemotherapy plus hemofiltration: drug delivery
3~4 x systemic dose
Regional chemotherapy plus hemoperfusion: drug delivery
5~8 x systemic dose
Ability to overcome drug delivery problems and resistance
Improves survival for HCC, pancreatic cancers, and hepatic
metastasis colorectal cancer (Muchmore et al. 1999)
CRRT in Liver Support
Requirements for liver support
Detoxification
Fluid regulation
Acid-Base and electrolyte homeostasis
Indications of CRRT support
 Combines renal and liver failure
 Liver transplant
 Mx of complications of decompensated liver disease
– Ascites
– Encephalopathy
Post Cardiac Surgery AKI
Intra-operative support and post-operative problems
 Oxygenator membranes and cytokine generation
 Blood tubing and extraction of plasticizers (DEHP)
 Prolonged bypass time and hemodynamic consequences
Application of aggressive ultrafiltration in the cardiac support
of children and outcome improvement
Dialysis variants added to extracorporeal cardiac support
system
 VAD and support
 ECMO and support
 IABP and support
(Lin CY, Chen YC, Fang JT et al. JN 2008)
Evidence Based Medicine (1)
Optimal way to deliver CRRT does not exist
Acute Dialysis Quality Initiative (ADQI) aims at
establishing an evidence-based appraisal and set of
consensus recommendations to standardize care and
direct further research
http://www.ADQI.net
Evidence Based Medicine (2)
Levels of Evidence
Level I: Randomized trials with low false positive () and low
false negative () error (i.e. high power)
Level II: Randomized trials with high  error or low power
Level III: Non-randomized concurrent cohort studies
Level IV: Non-randomized historic cohort studies
Level V: Case series, case reports, expert opinion
Evidence Based Medicine (3)
Grades of Recommendations
Grade A: Supported by at least 2 level I studies
Grade B: Supported by only 1 level I study
Grade C: Supported level II studies
Grade D: Supported by at least 1 level III study
Grade E: Supported by only level IV or V studies
Evidence Based Medicine (4)
CRRT use in a variety of non-ARF conditions including
intoxication with dialyzable/filterable drugs or toxins, cardiac
failure, ARDS, and pediatric cardiac surgery or sepsis and
systemic inflammation
Insufficient evidence to recommend the use of CRRT for nonARF indications outside clinical investigation (Grade E)
CRRT use may be advantageous in the management of ICU
patients with ARF (Grade E)
CRRT is recommended over IHD for patients with AKI who
have, or are at risk for, cerebral edema (Grade C)
CVVH Dose (1)
(Ronco C et al. Lancet 2000)
CVVH Dose (2)
CVVH Dose (3)
Intensive vs. Less-Intensive Strategy (1)
(Palevsky PM et al. NEJM 2008)
Intensive vs. Less-Intensive Strategy (2)
Intensive vs. Less-Intensive Strategy (3)
CVVHDF vs. CVVH (1)
(Saudan P et al. KI 2006)
CVVHDF vs. CVVH (2)
CVVHDF vs. CVVH (3)
p=0.0005
CRRT vs. IHD (1)
(Tonelli M et al. AJKD 2002)
CRRT vs. IHD (2)
(Vinsonneau C et al. Lancet 2006)
CRRT vs. IHD (3)
CRRT vs. IHD (4)
CRRT vs. IHD (5)
B.E.S.T. Kidney Investigators
(Uchino S et al. ICM 2007)
Less Chronic Kidney Disease in CRRT
(Bell M et al. ICM 2007)
Conclusions
CRRT are safe, simple, effective, and well tolerated in the
management of patients with multiple organ failure and
acute renal failure
Maintenance of water, and electrolyte balance
Removal of metabolic waste products
Removal of inflammatory mediators of MOSF
Facilitate full nutrition support
The treatment of choice in critically ill patients with acute
renal failure
No particular form of CRRT has yet shown to be superior of
survival
Scheme for Selection of a Renal Replacement
Therapy in ICUs: Patient-Center Approaching
Renal Failure requiring renal replacement therapy
Uni-organ failure
Intermittent
hemodialysis
Main problems:
biochemical/uremia
Multi-organ failure
Hemodynamically
stable
Main problems:
CRRT
fluid overload or cytokines
Intermittent Hemodialysis
Intolerance
Hemodynamically
unstable
CRRT (EDD, SLED)
IHD