Renal replacement therapy

1. Renal Replacement Therapy

2.  AKI affects 5% of hospitalized patients
 Leads to increased mortality and morbidity
 NEED OF THE HOUR

3. Principles
 All forms : movement of solute or water or both across semipermeable membrane
 Fluid removal : Ultrafiltration
 Solute removal : diffusion and convection

4. Ultrafiltration
 Process of fluid removal across SP membrane
 Removal by application of hydrostatic pressure or osmotic pressure
 Most machines use : hydrostatic pressure

5. Solute clearance
 Removal of solute across semipermeable membrane
 By Diffussion : movement of solute from High conc to Low Conc
 By Convection : SOLVENT DRAG : Solute swept via SP Membrane by moving stream
of UF

6. Hemodialysis : Removal of water and solutes by diffusion across conc. Gradient
 Adequate clearance of small molecules : Urea(60) & Creatinine (113)
Hemofiltration : NO DIFFUSSION … NO DIALYSATE USED … ONLY CONVECTIVE
TRANSPORT
 Insufficient for solute removal
 Better for MIDDLE SIZED MOLECULES : cleared by convective transport

8.  Adsorption
1. Molecular adherence to the surface or interior of the membrane
2. This mechanism is used in:
 SCUF
 CVVH
 CVVHD or CVVHD with ultrafiltration
 CVVHDF

9.  Small molecules easily pass through a membrane driven by diffusion and
convection.
 Middle and large size molecules are cleared primarily by convection.
 Semi-permeable membrane remove solutes with a molecular weight of up to
50,000 Daltons.
 Plasma proteins or substances highly protein—bound will not be cleared.

10. Sieving Cofficient
 Ability of a substance to pass from the blood compartment of hemofilter to fluid
compartment across SP membrane
 Depends upon MW and protein binding of a substance
 1: free passage of substance
 0 : Unable to pass

11. Substance Sieving Coeff
Na 0.97-1
K 0.92
Ca 0.7
Albumin <0.01
Urea 0.7-1.06
Creat 0.7-1.04
Myoglobin 0.55

12. KT/V
 A number used to quantify hemodialysis and peritoneal dialysis treatment
adequacy.
K - dialyzer clearance of urea
t - dialysis time
V - volume of distribution of urea, approximately equal to patient's total body water
Kt/V target is ≥ 1.3 HD
In peritoneal dialysis the target is ≥ 1.7/week.

13. Example,
Infusing four 2 liter exchanges a day, and drains out a total of 9 liters per day, then
they drain 9 × 7 = 63 liters per week.
If the patient has an estimated total body water volume V of about 35 liters,
then the weekly Kt/V would be 63/35, or about 1.8.

14. Requisites of Ideal RRT
1. Control Volume overload
2. Control Electrolyte disturbances
3. Control acid base disturbances
4. Provides clearance of solutes
5. Associated with minimal complications : Hypotension Bleeding

15. Types of RRT : Basis of Duration
Intermittent
3-4 hrs
IHD PD IUF
Continuous
24 hrs
CVVH CVVHD CVVHDF SCUF PD
Hybrid
Few to 24
hrs
SLED

16. Choice of Modality
 Based on four factors
1. Patient’s age & size
2. Cardiovascular status
3. Vascular access is available / Conditon of peritoneal membrane
4. Available expertise

18. Indications of RRT
 Fluid overload
 Uremic encephalopathy
 Hyperkalemia persistent
 Severe metabolic acidosis
 Hyper or hyponatremia

19. Peritoneal dialysis
 Simple & safe
 Vascular access not required
 Advantage for small children
 No anticoagulation
CONS:
Excessive ultrafiltration lead to significant hemodyanamic instability
Insertion of catheter : expertise
Infections : catheter related

20. Cathetors
 Non Cuffed Rigid acute cathetor : max upto 72 hours : Infection
 Tenkckhoff catheter – Single cuffed(Bedside) , double cuffed(Surgically)

21.  Proximal Cuff : Implanted in Pre peritoneal space , Holds catheter in place
 Distal Cuff : In SC tissue , Acts as barrier to infection

22.  Blockage by the omentum is always a risk with PD catheters.
 If the catheter is to be placed surgically then consideration should be given to
partial omentectomy
 In patients who are having a PD catheter inserted under general anesthetic a
cephalosporin antibiotic (20 mg/kg) should be given as a single intravenous dose
up to 1 h prior to implantation of the catheter .
 Any subsequent accidental contamination should result in the use of prophylactic
antibiotics, e.g., cefuroxime 125 mg/l in the dialysate for 48 h.

23. PD solutions
PH 5.8
Dextrose 1.5-4.25
Na 130
K 0
Cl 100
Buffer Lactate : 35-40Meq/l
HCO3 : 25 or 34Meq/l
Mg 1.5
Ca 3.0

24. Practical Considerations
 Dialysis fill volumes of 10–20 ml/kg (300–600 ml/m2) should be used initially,
depending on the body size and cycle in and out, until the dialysate becomes clear.
 PD with 1-h (10-30-20) should be used during the first 24 h.
 Shorter cycles can be considered initially if hyperkalemia needs urgent treatment.

25.  To be adjusted with increasing dwell times and cycle fill volume (if no leakage
problems) until desired fill volume (800–1,200 ml/m2) achieved
 Adequate ultrafiltration and biochemical control to be achieved

26.  Commence with the lowest concentration of glucose solution possible (1.36%),
with stepwise increments.
 Care is needed if 3.86% glucose solution is required as
(1) rapid ultrafiltration can occur (especially in infants)
(2) hyperglycemia may develop (especially in septic and multi-organ failure patients)
leading to hyperosmolarity and loss of effective ultrafiltration

27.  Heparin (500 units/l) should be added to the dialysis fluid to prevent fibrin
deposition and to improve peritoneal solute permeability
 HCO3 :to be used in :
Lactic acidosis
Asepsis required
Part A : 60 ml Na HCO3 plus 440 ml 5% Dx
Part B : 500 ml NS
Mix Part 1 part of A and 2 parts of B
Contains 40 meq/l of HCO3

28.  Use Y transfer sets : Prevents Peritonitis
 Fluid Overload : 1. rapid cycles 2. increase glucose Conc (Inc UF)
 Increase Solute Removal : Increase Dwell time
 Target : Not more than 5-10% of wt loss

29. Additives in PD
Heparin 500U /L
K Hypokalemia
2-4 meq/l
Insulin 3-4U/L for 1.5 % Dx
5-6U/L for 2.5% Dx
7-10U/l for 4.25% Dx

30.  Most slutions use glucose : Hyperinsulinemia , Hyperlipidemia , Peritoneal damage
 Long term PD : Dx Solutions can cause cellular and morphological changes in PM –
angioneogenesis or Submeothelial fibrosis
 Alternatively icodextrin can be used : absorbed in lymphatic channels at slow rate and
allows sustained UF over a longer dwell , Prolonged UF profile (Baxter)
 Equivalent to 3.86% Dx , metabolised to amylase .
 Biocomatible as iso osmolar , lacks Glucose

31. Osmotic agents
Icodextrin Prolonged UF profile but slow , less
effects
Glucose Rapid UF
More damage to PM
Amino acids Less acidity , more biocompatible , no
glucose . Also lits protein loss

32. Methods to increase dialysis adequacy
 Continuous equilibrated PD : Larger fill volume – 40-45ml/kg , long dwell times 2-6
hours
 Tidal PD : maintain atleast 30 % of fill volume (15ml/kg) throughout the dialysis
session . Increases solute clearance
 Automated PD : One time connection , less infection , warming , keeps record

33. Maintanenace PD : types
Types Advantages Disadvantages Patient
selection
Issues
NIPD : Short
Nocturnal Cycle
with daytime
dwell
Preservation of
membrane
No day time
glucose
Decreased
Middle
molecule
clearance
High Urine
output
Anuria
CCPD : Short
Nocturnal
Cycles with day
time dwells
Inc UF and
solute
clearance
May require
daytime
exchange
Low Urine
output
High glucose
absorption
CAPD : Daytime
and night time
cycles
Complete
equilibration
Risk of
peritonitis ,
high glucose
absorption
Cost effective Recurrent
peritonitis

34. Three types of UF failures
 Type 1 : Rapid solute transport : shorten dwell time , more frequent excahnges
 Type 2 : Impaired Solute Transport : increases Dwell time
 Type 3 : decreased lymphatic absorption : avoid large volume of dialysate

35. Complications and limitations
 Leakage : use tenckhoff catheter
 Hypothermia : warm PD solutions
 Malposition , kinking , omental wrapping , fibrin clot : Heparin , urokinase
 Sick infant : vasoconstriction of mesenteric vessels , poor UF
 Inadequate solute removal
 Peritonitis : Cloudy effluent , pain and fever
An effluent count of >100 leuco/ml (after 2 hours of dwell) with 50% neutrophils
Stiff catheter 48-72 hours affair !!

36. Hemodialysis

37. Equipment
 Water system: An extensive purification system is absolutely critical for hemodialysis.
 Dialysis patients are exposed to vast quantities of water, which is mixed with dialysate
concentrate to form the dialysate, even trace mineral contaminants or bacterial
endotoxins can filter into the patient's blood.
 Filtered and temperature-adjusted and its pH is corrected by adding an acid or base.
 Softened. Next the water is run through a tank containing activated charcoal to adsorb
organic contaminants.
 Primary purification is then done by forcing water through a membrane with very tiny
pores, a so-called reverse osmosis membrane

38. Dialyzer
 The dialyzer is the piece of equipment that actually filters the blood.
 Almost all dialyzers in use today are of the hollow-fiber variety.
 A cylindrical bundle of hollow fibers, whose walls are composed of semi-permeable
membrane, is anchored at each end into potting compound (glue).
 blood compartment & dialysate compartment

39. Membrane and flux
 Dialyzer membranes come with different pore sizes.
 Smaller pore size are called "low-flux" and those with larger pore sizes are called "high-flux."
 Some larger molecules, such as beta-2-microglobulin, are not removed at all with low-flux dialyzers;
the trend has been to use high-flux dialyzers
 cellulose or synthetic materials, using polymers such as polyarylethersulfone, polyamide,
polyvinylpyrrolidone, polycarbonate, and polyacrylonitrile
 Synthetic membranes can be made in either low- or high-flux configuration, but most are high-flux
 Less proinflammatory cytokines

40. Dialyzer size and efficiency
 K0A - the product of permeability coefficient and area
 Larger membrane area (A) will usually remove more solutes than a smaller dialyzer,
especially at high blood flow rates
 However slow blood flow in children will take lot of time to fill larger membrane
area dialyzer
 Surface area of dialyzer should be equal to surface area of the child

41.  Hemodialysis utilizes counter current flow, the dialysate is flowing in the opposite
direction to blood flow in the extracorporeal circuit.
 Counter-current flow maintains the concentration gradient across the membrane at
a maximum and increases the efficiency of the dialysis.
 Fluid removal (ultrafiltration) is achieved by altering the hydrostatic pressure of the
dialysate compartment, causing free water and some dissolved solutes to move
across the membrane along a created pressure gradient.

42. HD dialysate
PH 7.1-7.3
Dextrose 0.1
Na 135-140
K 0-3
Cl 108
Buffer Lactate 35-40
Mg 0.5-1.5
Ca 2.5-3.2

43. Anticoagulation
 Heparin : loading dose of 20u/kg followed by infusion of 10u/kg/hr
ACT to be monitored , kept between 140-170 sec
 LMWH : cleared via kidney , longer half life in AKI patients
 Citrate : Chelates Calcium leads to regional anticoagulation , less systemic SE
Solutions:
1. Trisodium citrate (Na 440meq/l )
2. ACD A : (Na 220) – more commonly used to prevent Hyper Na
Rate is 1.5 X BFL(ml/min)
Cal. Chloride continuos infusion : citrate flow rate X 0.4
Maintain circuit ionized calcium between 0.2-0.4 & patient’s 1.1-1.3

44.  Others
1. No anticoagulation – thrombocytopenia , coagulopathies , liver failure
2. Periodic saline slushes to prevent clotting
3. Danaproid : LMW heparinoid
4. Argatroban : direct thrombin inhibitor
5. Fondaparinux : anto factor Xa inhibitor

45. Tubing
 Short as possible
 Extracorporeal blood volume <10% blood volume otherwise priming
 Arterial segment : ports for sampling , anticoagulation , predilution
 Venous segment : port for post dilution
 Monitors for pressure monitoring
 Air trapping and removal
 Pumps
 Available in 3 sizes : neonatal 25 ml , Pediatric 75 ml , adult 127 ml

46. Hemodialysis
 Highly effective in acute settings
 Can accomplish Isolted UF also
 Vascular Acess
1. Permanent : Arteriovenous Fistula or Arteriovenous graft
2. Acute : IJV or femoral vein
3. Subclavian to be avoided : risk of venous stenosis

47. Neonate 7F
3-6 kg 7F DL
6-15 Kg 8F DL
15-30 kg 9F DL
>30 Kg 10-12.5 F DL

48. Blood flow rates
 5-7 ml /kg of body wt per minute

49. Dialysate flow rate
 500 ml / min
 Upto 800 ml/min , clearance increases as increase in flow rate
 Twice the blood flow rate !!

50. Ultrafiltration
 Depends upon transmembrane pressure
 Max UF rate : 0.2ml/kg/min
 Depends upon UF coeff.

51.  The first session should not exceed 2–3 h, but the standard time is usually 4 h.
 Longer sessions are advisable to avoid too-rapid ultrafiltration and disequilibrium
syndrome

52. Complications
 Thrombosis , stenosis and infection : Cathetor related
 Hypotension : Smaller BV in children : Slower UF rate , Saline / Albumin infusion
 Hypothermia
 Dialysis Disequilibrium syndrome : Acute cerebral oedema
Can be prevented by decreasing dialysis time , reducing blood flow rates
Patients where UREA is high : administer mannitol at start of HD

53.  Target Urea reduction around 30-40% to prevent acute shift of osmoles
 After 3-4 HD , Full HD prescription to be started
Ist Cycle 30% Urea
clearance
KT/V – 0.7 Low Surface are
& shorter time
dialysis
2nd cycle 70% 1.0
Later on 100% 1.2

54. Drug removal
 > 25% of administered drug removal is considered significant
 Leads theraupetic compromise
 Extra dose can be given

55. CRRT
 IHD not well tolerated in hemodyanamically unstable patients .
 CRRT allows slow rate of fluid removal and solute exchange
 Pros :
1. Less HD instability
2. Better tolerance to UF
3. Removal of Immunomodulatory substances as in sepsis
4. Less effect on ICT
 Cons
1. Expensive
2. Requires expertise

56. Types
 CAVH
 CVVH
 CVVHD
 CVVHDF
 SLED : Slow low efficiency diffusion HD
 SCUF : slow conyinuous UF

57. CVVH
 CAVH can have complications : Hemorrhage , Embolisation , Infection
 So CVVH is preffered CRRT
 Dialysate is not required in hemofiltration
 BFR : 0-10 kg – 50ml/min , 11-20 kg – 80-100 ml /min , 21-50 kg – 150ml/min
4-5ml/kg/min
 Only Convective clearance across membrane

58.  Initial net UF rate to be 1-3% of patients Blood volume /hour
 Replacement fluid rates to be determined by desired net fluid loss
 Actual fluid removal rate – desired net hourly fluid removal + IV /oral intake – all
outputs

59. Replacement fluids
 Bicarbonate(preffered) and lactate based solutions
Na 140
HCO3 25-35
Ca 0.3-0.5
Mg 1.5-2

60. Site of replacement of fluid
 Predilution : prior to hemofilter .
1. Useful if large volume of ultrafiltrate to be removed , increased hydrostatic
pressure
2. Prevents hemoconcentration
3. Improves life of the filter
 Post dilution : Post filter , more solute clearance , less life of the filter

61. © 306100135
CVVH
Return Pressure Air Detector
Return Clamp
Patient
Access Pressure
Effluent Pump
Syringe Pump
Filter Pressure
Hemofilter
Pre
Post
Post
Replacement PumpReplacement Pump Pre Blood Pump
Effluent Pressure

62. CVVHD
 Dialysate runs through membrane
 Diffusion is primary method of solute clearance
 Total amt of fluid removed less than the CVVH
 Clearance is directly proptionate to dialysate flow rate (2l/m2/hr)
 BFR – 4-5 ml/kg/min
 No replacement fluid in this modality

63. 306100135
CVVHD
Return Pressure Air Detector
Return Clamp
Access Pressure
Blood PumpSyringe Pump
Filter Pressure
Hemofilter
Patient
Effluent PumpDialysate Pump Pre Blood Pump
BLD
Effluent Pressure

64. CVVHDF
 CVVH is not adequate for solute clearance
 Dialysate used for diffusive solute clearance
 Diffusion plus convection clearance
 BFR : 4-5ml/kg/min
 Dialysate Flow rate : 2L /m2/hr

65.  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.

67. SLEDD : Slow low efficiency diffusion HD
 Uses HD machine to offer CRRT
 BFR : 100-200ml/min
 Dialysate flow rates : 100-300ml/min
 Pros : avoids expense of CRRT , less HD instability , avoids disequilibrium , less need
of anticoagulation
 Cons : poorer clearance of small and middle molecules as compared to CRRT

68. HD SLED
Access CVC CVC
Dialyser Hgh Flux , High efficiency Low flux , low efficiency
Tubings Appropriate size Appropriate size
BFR 5-7ml/kg/min 3-5ml/kg/min
Dilysate Flow rate 2X BFR 2X BFR
Treatment time 4 hrs 6-8 hrs
UF rate 10ml/kg/hr 10ml/kg/hr

69. SCUF
 Mainly to manage fluid overload without diffusive process
 Better tolerated Hemodyanamcally
 No dialysate
 No replacement fluid
 Used where fluid removal is priority !!

70. Complications
 Hypotension
 Hypothermia
 Electrolyte imbalances
 Clotting of filter Cathetor malfunction

71. Prescription
 Case 12 yr old boy with snake envenomation . Received 20 vials of ASV and
Clotting time has normalized . Puffy & edematous . UO is 50 ml in 36 hrs
BP – 100/70 mm hg , wt at admission is 30 kg Ht : 140cm .. BSA 1m2
Urea 170 , creat : 3.1 , Na : 128 , K 6.5
Modality of choice ???

72.  Access ??
 Dialyzer ??depends on surface area : ist hemodialysis – low surface area , shorter
time (2hrs ) !! Synthetic dialyser !!
15 kg F3
15-30kg F4
30-45 kg F5
45-60kg F6
>60Kg F8

73.  Tubing : calculate total blood volume , Size depends on age !!
Extracorporeal BV <10% … otherwise needs priming ??
Priming solution :saline , 5% albumin , PRC
 Dialysate composition – Bicarbonate buffered , glucose conc at physiological value
 BFR : 5-7ml/kg/min

74.  Dialysate Flow : 300-500ml/min or 2X BFR
 UF : 10ml/kg/hr
 Anticoagulation
 Duration of dialysis

75. Prescription looks like !!
1st dialysis Full dose Dialysis
Access CVC CVC
Tubings 78ml 78ml
Dialyser Avoid high efficiency High flux high efficient
Dialysate High Na Conc 2-3 meq
higher than plasma
Standard dialysate
BFR 5-7 5-7 ml.kg/min
UF rate 10ml/kg/hr 10ml/kg/hr
Anticoagulation Heparin Heparin
Time 2 hrs 4hrs