Introduction of Continuous Renal Replacement Therapy

(CRRT)

Yohanes WH George

Acute Renal Failure in Critical Ill Patients

A) Mortality rate of acute renal failure

A) Mortality rate over 80% before intermittent hemodialysis (HD)

B) Drop of mortality to 50% after HD

C) Mortality rate over 70% since 1980

B) Reasons for high mortality rate of ARF

A) Progressive in intensive care: antibiotics, hemodynamic monitor, cardiovascular & respiratory support

B) Old age

C) Multiple organ failure

Acute Renal Failure in ICU

Intensivist Nephrologist

Maintain tissue O2 delivery Fluid management

Increased cardiac output

Enhance ventilation

Maintain blood pressure Solute control

Prevent hypermetabolism

Provide adequate nutrition

Treat primary process Electrolyte balance

Acid -Base balance

Goals for treatment

Proposed Criteria for the Initiation of Renal Replacement Therapy in Adult Critically Ill Patients

  1. Oliguria (urine output<200 ml/12 hr)2. Anuria/extreme oliguria (urine output<50 ml/12 hr)3. Hyperkalemia ([K+]>6.5 mmol/liter)4. Severe academia (pH<7.1)5. Azotemia ([urea]>30 mmol/liter)6. Clinically significant organ (especially lung) edema7. Uremic encephalopathy8. Uremic pericarditis9. Uremic neuropathy/myopathy10.Severe dysnatremia ([Na]>160 or<115 mmol/liter)11.Hyperthermia12.Drug overdose with dialyzable toxin

( KI 1998, R. Belloma and C. Ronco)

Renal Replacement Therapy for Acute Renal Failure in Intensive Care Units

Intermittent therapies: Intermittent hemodialysis (IHD), extended daily dialysis (EDD), slow low-efficiency dialysis (SLED)

Peritoneal dialysis (PD)

Continuous renal replacement therapy (CRRT): SCUF, CAVH, CAVHD, CAVHDF, CVVH, CVVHD, CVVHDF

Advantages of CRRT Compared with IHD

1. CRRT maintains consistent homeostasis through slow, gradual shifts in volume status and serum osmolality

2. CRRT avoids hypotensive or dysequilibrium episode

3. CRRT permits continuous control of fluid balance and reduces the need to restrict fluid administration

4. CRRT requires a lower volume of blood to be circulating outside the body

5. CRRT has less effect on complement or leukocytes

6. CRRT does not require expensive equipment or extensive training of personnel

7. CRRT has greater clearance of mid-molecular weight solute

History of CRRT (1)

1960 Scriber et al: The technique of continuous hemodialysis

1967 Henderson et al: Blood purification by ultrafiltration and fluid replacement1974 Silverstein et al: Treatment of severe fluid overloading by ultrafiltration1977 Peter Kramber et al: Continuous arteriovenous

hemofiltration (CAVH)1979 CVVH was employed in Cologne

1979 Paganini et al: Slow continuous ultrafiltration (SCUF)

1982 FDA approval: CAVH in ICU patients

1984 October 7, Peter Kramber sudden death

1984 Geronemus et al: Continuous arteriovenous hemodialysis (CAVHD)

1988 Tam et al: Continuous venovenous hemodialysis (CVVHD)

Definitions of CRRT

Any extracorporeal blood purification therapy intended to substitute for impaired renal function over the extended period of time and applied for, or aimed at being applied for 24 hours/day.

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

SCUF: Slow continuous ultralfiltration

CRRT: AV v.s 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

Further Definitions (1)

Ultrafiltration:

In the field of renal replacement therapy, this is a term describing the process by which plasma water and ultrafiltrate solutes are separated from whole blood, across a semipermeable membrane in response to transmembrane pressue.

Ultrafiltrate:

The plasma water and ultrafiltered solutes produced during ultrafiltration or hemofiltration of blood.

Dialysate:

The synthetic, uremic solute-free solution administered into the ultrafiltrate-dialysate compartment of the hemofilter or hemodialyzer in order to achieve diffusive solute clearance.

Further Definitions (2)

Arterio-venous (A-V) circuit :

A term describing the arterial and venous vascular access cannulae or shunt and the associated tubing necessary to carry blood into and out of the hemofilter, and back into the circulation.

Veno-venous (V-V) circuit:

A term describing the venous vascular access and associated tubing carrying blood into and out of the hemofilter, and back into the circulation.

Pre-dilution:

The administration of replacement fluid into the patient’s blood prior to its entry into the hemofilter (pre-filter delivery).

Further Definitions (3)

Post-dilution:

The administration of replacement fluid into the patient’s blood after its exit from the hemofilter (post-filter delivery).

Suction:

A technique whereby ultrafiltrate production is augmented by applying negative pressure to the ultrafiltrate port of the hemofilter.

Ultrafiltration control system:

A technique whereby ultrafiltrate production is controlled by a volumetric pumps applied to the ultrafiltrate outflow tubing.

Circuit: CAVH – CVVH with Post-dilution

Artery Vein

Vein Vein

Mechanisms of function

Membrane Reinfusion Diffusion Convection

High flux Yes Low High

P

UF UF

R R

CAVHQb= 50-100 ml/min

Qf: 8-12 ml/min

CVVHQb= 50-200 ml/min

Qf: 8-12 ml/min

Circuit: CAVH – CVVH with Pre-dilution

Artery Vein

Vein Vein

Mechanisms of function

Membrane Reinfusion Diffusion Convection

High flux Yes Low High

P

UF UF

R RCAVH

Qb= 50-100 ml/minQf: 8-12 ml/min

CVVHQb= 50-200 ml/min

Qf: 8-12 ml/min

Circuit: CAVHD - CVVHD

CAVHD CVVHD

Artery Vein Vein Vein

Dial out Dial in Dial out Dial in

Mechanisms of functionMembrane Reinfusion Diffusion Convection

Low flux No High Low

P

Qb=50-100 ml/minQf = 1-3 ml/minQd 10-20 ml/min

Qb=50-200 ml/minQf = 1-5 ml/minQd 10-30 ml/min

Circuit: CAVHDF -CVVHDF

CAVHDF CVVHDF

Artery V Vein Vein

Dial out +Uf Dial in Dial out +Uf Dial in

Mechanisms of functionMembrane Reinfusion Diffusion Convection

High flux Yes High High

P

RR

Qb 50-100 ml/minQd 10-20 ml/minQf 8-12 ml/min

Qb 50-200 ml/minQd 20-40 ml/minQf 8-15 ml/min

Circuit: SCUF

A-V SCUF V-V SCUF

A V V V

UF UF

Mechanisms of functionMembrane Reinfusion Diffusion Convection

High flux No Low Low

P

VC

Qb 50-100 ml/minQf 2-6 ml/min

Qb 50-200 ml/minQf 2-8 ml/min

Vascular Access for CRRT

* CAVH, CAVHD, CAVHDF: Femoral artery and vein

Advantages : simplest system to assemble and operate

Disadvantage: Required arterial puncture and cannulation

Required a second catheter

Risk of arterial embolization

Unreliable blood flow

* CVVH, CVVHD, CVVHDF: Femoral vein, internal jugular vein, subclavian vein with double lumen catheter

Advantages : No arterial puncture or cannulation

Less systemic anticoagulation required

Only one puncture , Faster blood flow

More reliable blood flow

Disadvantage: Required extracorporeal blood pump

Commercially available filter for CRRT

Company Name Membrane Surface (m2 )

Amicon Diafilter 30 Polysulphone 0.60

Diafilter 20 Polysulphone 0.25

Diafilter 10 Polysulphone 0.20

Minifilter Polysulphone 0.015

Minifilter Plus Polysulphone 0.08

Asahi Med. Ultrafilter GS Polyacrylonitrile 0.50

Bellco BL 650 Polysulphone 0.20

Fresenius AV-400 Polysulphone 0.70

AV-600 Polysulphone 1.35

Gambro FH 66 Polyamide 0.60

FH22 Polyamide 0.15

Hospal Multiflow 60 AN69S 0.60

PLATE AN 69S 0.50

Renal Syst. HF 500 Polysulphone 0.50

HF 250 Polysulphone 0.25

Sorin HFT 04 Polysulphone 0.45

HFT 02 Polysulphone 0.24

Factors Affecting Drug Removal During CRRT

* Drug properties

Protein binding

Molecular weight

Hydration radius

Molecular charge

* Ultrafilter membrane properties

Pore size

Membrane charge

Length and width of fiber

Filter surface area

Applications for CRRTRenal Application vs Non-renal Application

Renal Application ( Renal replacement and Renal support)

* Acute renal failure ( specifically complicated ARF with multiple organ failure and cardiovascular failure)

* Oligouric ARF needs large amount of fluid or nutrition

* Acute renal failure with cerebral edema

* Acute renal failure with hypercatabolism

* An alternative to HD in the mass casualty situation

* Electrolytes and acid base disturbance

Applications for CRRTRenal Application vs Non-renal Application

Non-renal Application

* Hepatic failure complicated with hepatic coma

* Congestive heart failure refractory to diuretics

* Overhydration during & after cardiac surgery ( CPB )

* Sepsis

* Life-threatening hyperthermia

* Lactic acidosis

* Cytokine removal: Acute respiratory distress syndrome

* Tumor lysis syndrome

* Crush injury

* Inborn errors of metabolism: maple syrup disease, urea cycle disorder

Scheme for Selection of a Renal Replacement Therapy in Intensive Care Units

Renal Failure requiring renal replacement therapy

Uni-Organ failure Multi-Organ failure

Intermittent hemodialysis Hemodynamically stable

Hemodynamically unstable

Main problems: biochemical/uremia

Main problems: fluid overload or cytokines

CRRT

CRRTIntermittent Hemodialysis

Untolerant

Conclusions

* CRRT provide good supportive treatment 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* Mortality of CRRT is non-significant difference as

compared with IHD, but severity of illness is more in CRRT

* No particular form of CRRT has yet shown to be superior of survival