1. Renal replacement therapy
Dr . Ashish
Moderator : Dr. Muralidhar

2. Epidemiology of AKI
Prospective epidemiology survey of AKI was conducted in ICU patient who were either treated with RRT or had ARF(U.O< 200ml /12hr or BUN>30mmol/l)
Of critical ill pts. 5.7% pt. had AKI during ICU stay including 4.3% who were t/t with RRT
BEST study(Beginning and ending supportive therapy for the kidney investigators Acute renal failure in critically ill patients JAMA 294; ,2005)

3. Overall hospital mortality was 60.3%
Most common contributing factor was septic shock in 47.5%
At hospital discharge 86.2% survivors were independent from dialysis
BEST study(Beginning and ending supportive therapy for the kidney investigators Acute renal failure in critically ill patients JAMA 294; ,2005)

4. Introduction
Term RRT is used to describe all the currently available approaches to artificial mechanical support of renal function
Includes traditional intermittent hemodialysis,peritoneal dialysis and variety of other intermittent and continuous therapy, and renal transplant

5. Indications to start and stop RRT
There is no consensus as to indication for initiation of RRT
Common indications are azotemia , anuria, and complications of AKI , including pulmonary edema, severe fluid overload ,hyperkalemia and uncontrolled metabolic acidosis

6. Routine clinical practice is to adequately control fluid balance and to maintain a serum urea <30 mg/dl, creatinine < 2mg/dl and normal electrolyte values

7. Indications of RRT
Anuria – oliguria(diuresis <200 ml in 12 hr)
Severe metabolic acidosis(pH<7.10)
Hyperazotemia(BUN> 80mg/dl) or creatinine >4mg/dl
Hyperkalemia K >6.5mEq/l
Clinical signs of uremic toxicity

8. Indications of RRT
Severe dysnatremia Na<115 or Na>160mEq/l
Hyperthermia (>40 deg.C without response to medical therapy)
Anasarca or severe fluid overload
Multiple organ failure with renal dysfunction and /SIRS, sepsis, or septic shock with renal dysfunction

9. Technique and modalities
All RRT consist of blood purification by having the blood flow through SPM.
Blood flow into hollow fibers composed by porous biocompatible synthetic materials

10. Technique and modalities
Wide range of substances( water , urea,and low, middle and high mol.wt. solutes)allow the blood across such membranes by diffusion (solutes) and by convection(solute and water)

11. Diffusion
Solute move from blood across membrane to reach same concentration on each side of membrane
Leads to passage of solute from compartment with highest conc. to lower compartment with lowest conc.

12. Factors affecting rate of diffusion –
Thickness and surface of membrane,
Temperature of blood
Diffusion coefficient

13. Dialysis occur when solution flows through semi- permeable conduit countercurrent to blood, allowing maximal solute diffusion, because solute conc. is lower in solution than blood

14. Diffusion

15. Diffusion During diffusion , solute flux (Jx) is function of
solute concentration gradient(dc)between two sides of SPM, temp(T), diffusivity coefficient(D), membrane thickness(dx)and surface area(A)
Jx=D.T.A(dc/dt)

16. Convection
During convection , movement of solute across a SPM occurs with significant amount of ultrafiltration( water transferring across the membrane)

17. Convection
As the solvent (water in plasma) is pushed across the SPM in response to TMP(transmembrane pressure) by UF, solutes are carried with it, as long as porosity of membrane allows the molecules to be sieved from blood

18. Convection

19. The process of ultrafiltration is governed by UF rate (Qf), membrane UF coefficient(Km) and TMP gradient generated by pressure on both sides of hollow fiber
Qf= Km.TMP

20. TMP= Pb-Pd-Blood oncotic pressure
Pb: Blood hydrostatic pressure
Pd:Hydrostatic pressure on UF side of SPM

21. Hydrostatic pressure in blood compartment dependent on blood flow(Qb)
Greater the Qb , greater the TMP
Modern RRT machine , UF is maximised by applying a pump, which generates control of UF rate

22. As blood is processed , membrane fiber get soiled and a negative pressure become necessary to maintain a constant Qf
Molecules cleared during convection are physically dragged to UF side , but this function is limited by protein layer that progressively develops and closes fiber pores during convective treatments

23. As UF proceeds over time, plasma water and solutes are filtered from blood, hydrostatic pressure within filter is lost
And oncotic pressure is gained as blood concentrates and Hct rise

24. The fraction of plasma water that is removed from blood during UF is called Filtration Fraction
F.F. is kept ~20-25% to prevent hemoconcentration within filtering membrane

25. Replacing plasma water with a substitution solution completes the hemofiltration(HF) and returns the purified blood to patient
Post dilution HF - Replacement fluid infused after the filter
Pre dilution HF - Replacement fluid infused before the filter

26. Post dilution HF allow urea clearance equivalent to therapy delivery(2L/hr)
While pre dilution l/t prolonged circuit lifespan by reducing hemoconcentration and protein caking effect

27. Conventional HF is performed with highly permeable membrane with surface area of about 1sq.mt, steam sterlized with cutoff point 30kD

28. Difference b/n volume of ultra filtered plasma water and reinfused substitution solution is Net UF
Net UF is fluid finally removed from patient

29. Prescriptions for net UF are based on individual patient need
Range from >1L/hr(pulmonary edema pt. with CHF who is resistant to diuretic)
To zero net UF ( sepsis with catabolic state with increased creatinine levels)

30. Net UF rate must be added to dialysis to achieve fluid balance during diffusion that do not allow water movement

31. Most common techniqe utilised for CRF
IHD
Most common techniqe utilised for CRF
Diffusive t/t in which blood & dialysate are circulated in countercurrent manner & usually low permeability,cellulose membrane is employed
Dialysate must be pyrogen free but not necessarily sterile, as blood contact does not occur

32. IHD
UF rate is equal to scheduled weight loss
This t/t can be typically performed 4 hrs thrice weekly or daily
Qb : ml/min , Qd: ml/min

33. PD
Diffusive t/t in which blood circulating along capillaries of peritoneal membrane , is exposed to a dialysate
Peritoneal catheter allows abdominal instillation of dialysate

34. PD
Solute & water movement achieved by means of variable concentration and tonicity gradients generated by dialysate
Can be done continuously or intermittently

35. Dose and prescription for RRT
During continuous t/t in ICU goal – deliver urea clearance of 2 l/hr
Evaluation of chronic dialysis in ESRD described by fractional clearance of given solute = Kt/v
K: dialysis clearance
t: time for dialysis treatment
v : solute marker volume of distribution
Kt/v urea of 1.2 currently recommended

36. Dose reciept of more dialysis improve patient outcome?

37. Prospective study on 425 patients - 3 groups:
Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00
Prospective study on 425 patients - 3 groups:
Study:
survival after 15 days of HF stop
recovery of renal function
Dr. Ronco set forth to study answer the question “What is the adequate dose for the ARF patient?” thus began the journey to find this dose. The origin of ARF was mostly post surgical with the other causes from medical and trauma related. Sepsis was also prevalent throughout the study participants. Dr. Ronco selected 492 patients for the study, but 67 of those patient were excluded. Some of the 425 patients were actually randomized into the study, and assigned to one of the three doses: 20ml/kg/hr, 35ml/kg/hr, and 45ml/kg/hr. The study was conducted using only convection therapy. All replacement solution was delivered post-filter, and UFR was used to measure dosing.
Why did he use UFR to measure dosing. Well, it is known that solute movement across the membrane is proportional to UFR. For example, Urea has a sieving coefficient of 1 it is then assumed that it is equal to UFR. Therefore, ultrafiltration rate corresponds with clearance, and can be used as a surrogate treatment dose.

38. Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00
100 90 80 70 60 50 40 30 20 10
Group 1(n=146) ( Uf
= 20 ml/h/Kg)
Group 2 (n=139)
= 35 ml/h/Kg)
Group 3 (n=140)
= 45 ml/h/Kg)
41 %
57 %
58 %
p < 0.001
p n..s.
Survival (%)
This is a another way to visually see the outcome from Dr. Ronco’s study. Group 1 is what we consider conventional delivery with poor patient outcome. Group 2 and 3 prove that a higher dose improves patient survival. Group 2 and 3 showed very little difference in survival therefore, the new dosing standard was announced that a dose of 35 mL/hr/kg improved patient outcome.

39. Continuous Renal Replacement Therapy (CRRT)
Is an extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours a day.
* Bellomo R., Ronco C., Mehta R, Nomenclature for Continuous Renal Replacement Therapies, AJKD, Vol 28, No. 5, Suppl 3, November 1996
CRRT is the blanket term which encompasses all continuous therapies. It has been defined as…. Read the slide. Make sure to note the proof source.

40. A central double-lumen veno-venous hemodialysis catheter
Requirements for CRRT
CRRT requires:
A central double-lumen veno-venous hemodialysis catheter
An extracorporeal circuit and a hemofilter
A blood pump and a effluent pump.
With specific CRRT therapies dialysate and/or replacement pumps are required.
In order, to initiate CRRT there are some essential items you will need. CRRT requires a functioning vascular access, which is usually a central double-lumen catheter, and extracorporeal circuit, a hemofilter, a blood pump, and a effluent pump. In some CRRT therapies dialysate and/or replacement pumps are required.

41. SCUF- Slow Continuous Ultrafiltration Ultrafiltration
CRRT Modalities
SCUF- Slow Continuous Ultrafiltration
Ultrafiltration
CVVH- Continuous Veno-Venous Hemofiltration
Convection
CVVHD- Continuous Veno-Venous Hemodialysis
Diffusion
CVVHDF- Continuous Veno-Venous Hemodiafiltration
Diffusion and Convection
CRRT modalities contains four therapies, and we will begin by talking specifically about each therapy. CRRT is well-known by all the acronyms. Each acronym describes the therapy being performed in treating the patient. History has shown us that there are many ways to perform each therapy. However, each therapy does carry is own basic concept.
SCUF- modality is only removing patient plasma water. Does not require replacement or dialysate solution.
CVVH- modality requires replacement solution. This replacement solution drives convection.
CVVHD- is continuous form of hemodialysis and requires dialysate solution to create a concentration gradient for diffusion.
CVVHDF- hemodiafiltration requires the use of dialysate and replacement solution and uses both transport mechanisms of convection and diffusion.
Let’s take a look at the transport mechanisms related to each individual therapy.

42. SCUF
Blood driven through highly permeable filter via extracorporeal circuit in venovenous mode
UF produced during membrane transit is not replaced so it correspond to wt. loss
Used only for fluid control in overloaded pt. (CHF pt not responding to diuretic t/t)
Qb : ml/min &Quf:5-15ml/min

43. SCUF-Ultrafiltration
Slow continuous ultrafiltration:
Requires a blood and an effluent pump.
No dialysate or replacement solution.
Solute control is not goal of this therapy
Fluid removal up to 2 liters/hr can be achieved.
Primary Goal
Safe management of fluid removal
Large fluid removal via ultrafiltration
SCUF (slow continuous ultrafiltration) when using this therapy, significant amounts of fluid are removed from the patient. No dialysate or replacement fluid is used because solute control is not a goal of this therapy. Ultrafiltration can be adjusted to cause dramatic fluid shifts. SCUF treatment utilize UFR’s of up to 2L/hr in some cases. The only pumps needed for this therapy is a blood pump and an effluent pump.

44. SCUF Return Pressure Air Detector Return Clamp Syringe pump Blood Pump
Patient
Hemofilter
Filter Pressure
Access Pressure
Effluent Pressure
BLD
Effluent Pump
Pre Blood Pump
This slide depicts the SCUF (slow continuous ultrafiltration) is a therapy that uses no dialysate or replacement solution.On the right hand side of the screen you see a Pre-blood pump that could deliver anticoagulation solution at the patient access. The there is really only 2 pumps that are required for this therapy: Blood pump, Effluent pump, and if desired the Pre-blood pump. Plasma water is removed by ultrafiltration.

45. CVVH(Continuous venovenous hemofiltration)
Blood driven through highly permeable membrane via extracorporeal circuit in venovenous mode
UF produced during membrane transit is replaced in part or completely to achieve blood purification & volume control
Pre or post dilution hemofiltration based on replacement fluid delivery before or after filter

46. CVVH-Convection Continuous veno-venous hemofiltration
Requires blood, effluent and replacement pumps.
Dialysate is not required.
Plasma water and solutes are removed by convection and ultrafiltration.
CVVH (continuous veno-venous hemofiltration) aims for maximizing convective removal of middle to large molecules. Replacement solutions are used to drive convective transport. When performing CVVH the following pumps are used: The blood pump, replacement pump and the effluent pump.

47. CVVH Return Pressure Air Detector Syringe Pump Return Clamp Patient
Hemofilter
Filter Pressure
Access Pressure
Post
Effluent Pressure
Pre
Post
Replacement Pump
Pre Blood Pump
Effluent Pump
Replacement Pump
This slide depicts the CVVH flowpath for both blood and fluid. As you, can see there are several points that replacement solution can enter the circuit. On the right hand side of the slide the replacement solution is entering pre-blood pump. Delivering the replacement solution Pre-blood pump will allow for greater hemodilution of the access line, and better solute clearance before the blood comes in contact with the filter. The first purple bag from the right hand side delivers the replacement solution Pre-filter, which means that as the blood enters the filter it is mixed with replacement solution. Pre-filter offer greater hemodilution of the filter, which increases filter life. Unfortunately, about 15% of the replacement solution is lost over the filter, thus decreasing solute clearance. The purple bag on the left hand side of the slide is delivering replacement Post-filter, which means as the blood is returning to the patient replacement solution is added. Delivering replacement post-filter allows better solute clearance, but may decrease filter life due to the hemoconcentration of the blood in the filter.

48. CVVHD Continuous venovenous hemodialysis
Blood driven through low permeability dialyzer via extracorporeal circuit in venovenous mode and countercurrent flow of dialysate delivered in dialysis compartment
UF produced during membrane transit correspond to wt. loss
Solute clearance is mainly diffusive & efficiency limited to small solutes only
Qb : ml/min & Qd :15- 60ml/min

49. CVVHD-Diffusion Continuous veno-venous hemodialysis
Requires the use of blood, effluent and dialysis pumps.
Replacement solution is not required.
Plasma water and solutes are removed by diffusion and ultrafiltration.
CVVHD (continuous veno-venous hemodialysis) is a therapy that uses dialysate solution on the fluid side of the filter to increase solute exchange by diffusion. Replacement solution is not required for this therapy. The pumps required for this therapy are as follows: Blood, dialysate and effluent pump. Plasma water and solutes are removed by diffusion and ultrafiltration.

50. CVVHD Return Pressure Air Detector Return Clamp Syringe Pump
Blood Pump
Patient
Hemofilter
Filter Pressure
Access Pressure
Effluent Pressure
BLD
Dialysate Pump
Pre Blood Pump
Effluent Pump
This schematic depicts a CVVHD flowpath. Describe the blood flowpath through the hemofilter and back to the patient. Then show green dialysate entry into the hemofilter (counter-current flow) and effluent removal through the yellow line/bag. Prismaflex allows use of the Pre blood pump fluid/anticoagulant infusion.
The white bag on the right-hand side of the slide can deliver anticoagulation solution. We really want to focus on the green bag on the left hand side of the slide. This is the dialysate solution that is going to be delivered to the fluid side of the filter. The dialysate solution enters at the top of the filter and travels counter-current of the blood. The counter-current flow increases solute removal.

51. CVVHDF Continuous venovenous hemodiafiltration
Blood driven through highly permeable dialyzer via extracorporeal circuit in venovenous mode and countercurrent flow of dialysate is delivered in dialysate compartment
UF produced during membrane transit is in excess of pt. desired wt. loss

52. CVVHDF Continuous veno-venous hemodiafiltration
Requires the use of a blood, effluent, dialysate and replacement pumps.
Both dialysate and replacement solutions are used.
Plasma water and solutes are removed by diffusion, convection and ultrafiltration.
CVVHDF (continuous veno-venous hemodiafiltration) combines the benefits of CVVH and CVVHD using both convective and diffusive transport mechanisms. Replacement and dialysate fluids are both employed. The pumps required for this therapy are as follows: A blood, dialysate, replacement and effluent pumps.

53. CVVHDF
Removal of small molecules by diffusion through the addition of dialysate solution.
Removal of middle to large molecules by convection through the addition of replacement solution.
The use of both diffusion and convection transport mechanism create a therapy called hemodiafiltration. This specific therapy combines dialysate solution to create diffusive clearance of small molecules, and replacement solution to create convective clearance of middle to large molecules.

54. SLEDD(Slow low efficiency daily dialysis)
Hybrid therapy that try to match physiological advantage of CRRT
Involves use of blood & dialysate flows less than in IHD
Qb : ml/min & Qd :< 300ml/min
T/t time extended to 6-12hr every day

55. SLEDD(Slow low efficiency daily dialysis)
Result slower solute clearance & fluid removal & result in hemodynamic stability comparable to CRRT.

56. Removal of sodium & water cannot be dissociated when using diuretic & some RRT
Diuretics l/t natriuresis whereas dialysis may result in hypotonia or hypertonia
Depending on effect of dialysis on diffusion & on removal of molecules , including urea & other electrolyte

57. Water removal is always a/w removal of other solutes & its amount depend on technique used
UF from SCUF is iso-osmotic & and isonatremic because Na elimination is linked to Na conc. in plasma
Best evidence to date support RRT dose of 35ml/kg/hr for CVVH, CVVHD, IHD

58. UNLOAD trial(UF versus i.v. diuretics for acute decompensated CHF)
First RCT comparing Diuretic versus HF in hypervolemic pt.
Principal Findings
Ultrafiltration l/t greater wt. & fluid loss
Reduction in rate & duration of subsequent hospitiliztions in pt with volume removal by UF
Benefits from short term use of UF over 90 days was achieved without significant adverse effects

59. Vascular Access
A veno-venous double lumen hemodialysis catheter or two single lumen venous hemodialysis catheters may be used.
A patient will need a veno-venous double lumen catheter or two single lumen venous hemodialysis catheter. One side of the lumen will deliver blood from the patient to the filter, and the other lumen will return the blood back from the filter to the patient.

60. Access Location Internal Jugular Vein
Primary site of choice due to lower associated risk of complication and simplicity of catheter insertion.
Femoral Vein
Patient immobilized, the femoral vein is optimal and constitutes the easiest site for insertion.
Subclavin Vein
The least preferred site given its higher risk of pneumo/hemothorax
There are three access locations that are used some may be preferred over others. Internal jugular vein is the primary choice due to the simplicity of catheter insertion. Femoral vein is a great access when a patient is immobilized, and is also considered an easy site for insertion. Subclavin is the least preferred and often used if no other sites are available. A Subclavin has a high risk of pnemo/hemothorax and is associated with central stenosis.

61. Result in clotting of filter or circuit
Anticoagulation
Blood contact to circuit tubing in CCRT l/t activation of coagulation cascade
Result in clotting of filter or circuit
Quantity & duration of anticoagulation changes depending on schedule of RRT
Anticoagulation necessary for CRRT where blood – artificial surface interaction is maximum

62. Vascular access adequate size Kinking of circuit tubing avoided
Circuit set up optimisation
Vascular access adequate size
Kinking of circuit tubing avoided
Blood flow rate should exceed 100ml/min
Plasma filtration fraction < 20%
When possible predilution hemofiltration considered

63. Unpredictable bioavailibility
Unfractionated heparin
Dose 5-10 IU/kg/hr
Regional heparinization in 1:1 ratio with protamine ( 150IU Of UFH per mg protamine)
Problems :
Unpredictable bioavailibility
Necessity for AT III levels for optimal use
Heparin induced thrombocytopenia

64. LMWH Alternative to UFH
Prospective studies hav not shown it superior to UFH in prolonging life of RRT circuit
Better bioavailibility
Lower incidence of HIT
Cost 10% > than UFH

65. Prostacyclin (PGI2)
Potent inhibitor of platelet aggregation with short half life
Infusion dose 4-8ng/hr with or without addition of low dose UFH
Problems:
Very short circuit life span
Hypotension

66. Citrate
Citrate chelates calcium which prevents clot formation
Drawbacks :
Risk of hypoalcemia
Metabolic alkalosis

67. Complications as/w hemodialysis
Hypotension – MC d/t osmolar shift & ultrafiltration- induced volume depletion
Hypotensive episode may reflect myocardial ischemia,dysarrythmias or pericardial effusion with cardiac tamponade
T/t – slowing rate of ultrafitration and/or i.v fluids

68. Hypersensitivity reaction to ethylene oxide used to sterlize dialysis machine d/t specific membrane material polyacrylonitrile
MC in pt. receiving ACE inhibitors
This reaction d/t bradykinin release which is degraded by kinases but ACE inhibitors block this response

69. Progressive renal failure,catabolism,&anorexia l/t loss of lean body mass but fluid retention mask this may l/t wt. gain
Between t/t wt. gain of 3%-4% of body mass is appropriate

70. Increased chances of ischemic heart disease in ESRD pt
Increased chances of ischemic heart disease in ESRD pt. on hemodialysis d/t
Systemic HTN
Anemia
Hyperlipidemia
Hyperhomocystemia
Accelerated atherosclerosis
Impaired oxygen delivery to myocardium d/t uremic toxin

71. Pericarditis with pericardial effusion d/t inadequate hemodialysis
T/t - Intensive heparin free dialysis
Persistent effusion - pericardiocentesis

72. Bleeding tendency d/t altered platelet function , partially correctable by hemodialysis
Heparin free dialysis or administration of DDAVP , sufficient to correct bleeding tendency

73. At risk of infection d/t impaired phagocytosis & chemotaxis
T.B in pt on hemodialysis is extrapulmonary and atypical symptom mimicing inadequate dialysis
Vaccinated against pneumococcal and hepatitis B

74. Summary
Mechanism in RRT based on principles of water & solute transport via diffusion & convection
These mechanism applied lead to different techniques & modalities
Clinical effects on critically ill pt. depend on selected RRT strategy & on severity/ complexity of patients clinical picture

75. THANK YOU