Dr. Kumar presented on renal replacement therapy. The key points are: 1. Approximately 5% of critically ill patients with AKI will require RRT, with a mortality rate as high as 60%. 2. RRT options include intermittent HD, continuous therapies like CVVH/CVVHD/CVVHDF, and SLED. 3. The choice of RRT depends on the patient's cardiovascular status, resources available, and whether fluid removal or solute clearance is required. CRRT is preferred for hemodynamically unstable patients.

1. Presentor : Dr.Kumar
Moderator :Dr.K.Chaitanya
Renal ReplacementTherapy

2. Introduction
It is estimated that a third of patients in the critical care
setting have an AKI and approximately 5% will require
renal replacement therapy .
The hospital mortality in patients with an AKI requiring RRT
is as high as 60%.
no specific treatments have been shown to reverse the
course of AKI, so RRT forms the basis of further
management

3. Definition
Acute kidney injury (AKI), is defined as an abrupt (within
48 hours) reduction in kidney function.
The AKI network defines the reduction in kidney function as
the presence of any one of the following:
1. An absolute increase in serum creatinine of ≥ 0.3 mg.dl -1(≥
26.4 mcmol.l-1)
2. A percentage increase in serum creatinine of ≥ 50% (1.5-fold
from baseline)
3. A reduction in urine output (< 0.5 ml.kg -1 per hour for
more than six hours).

4. Indications of RRT
Acute kidney injury (AKI)with
1. Fluid overload (refractory to diuretics)
2. Hyperkalemia (K+ > 6.5)
3. Severe metabolic acidosis (pH < 7.1)
4. Rapidly climbing urea/creatinine (or urea > 30mmol.l -1)
5. Symptomatic uraemia: encephalopathy, pericarditis,
bleeding, nausea, pruritus
6. Oliguria/anuria

5. Contd..
Overdose with a dialyzable drug or toxin .
drugs are cleared by RRT if they are water-soluble and not highly
protein-bound

6. contd
Severe sepsis
 patients with ARF have severe sepsis, multiorgan
dysfunction and a major systemic inflammatory response.
 to remove or adsorb inflammatory mediators which cause
organ dysfunction may represent yet another reason for its
preferential application

7. Dialyzer unit
 The basic components of the dialyzer unit:
 Dialyzer – cellulose, substituted cellulose, synthetic non cellulose membranes.
 Dialysis solution – dialysate : water must remain free of Al, Cu, chloramines,
bacteria and endotoxin.
 Tubing for transport of blood and dialysis solution.
 Machine to power and mechanically monitor the procedure
 Air monitor
 Proportioning system
 Temperature sensor
 Urea sensror to calculate clearance.
 The basic components of the dialyzer unit:
 Dialyzer – cellulose, substituted cellulose, synthetic non cellulose membranes.
 Dialysis solution – dialysate : water must remain free of Al, Cu, chloramines,
bacteria and endotoxin.
 Tubing for transport of blood and dialysis solution.
 Machine to power and mechanically monitor the procedure
 Air monitor
 Proportioning system
 Temperature sensor
 Urea sensror to calculate clearance.

9. MECHANISM OF SOLUTE REMOVAL
Haemofiltration
involves blood being pumped
through an extracorporeal
system that incorporates a semi-
permeable membrane.
 The hydrostatic pressure that is
created on the blood-side of the
filter drives plasma water across
the filter.
 This process is referred to as
“ULTRAFILTRATION”.

10. Molecules that are small enough to pass through the
membrane (<50,000 Daltons) are dragged across the
membrane with the water by the process of
CONVECTION.
The filtered fluid (ultrafiltrate) is discarded and a
replacement fluid is added in an adjustable fashion according
to the desired fluid balance.

11. Haemodialysis
involves blood being pumped through
an extracorporeal system that
incorporates a dialyzer.
In the dialyzer, blood is separated
from a crystalloid solution (dialysate)
by a semi-permeable membrane.
Solutes move across the membrane
along their concentration gradient
from one compartment to the other
obeying Fick`s laws of diffusion.

12. For example, bicarbonate moves from
dialysate to blood whereas urea and
potassium move from blood to dialysate.
 In order to maintain concentration
gradients and therefore enhance the
efficiency of the system the dialysate flows
countercurrent to the flow of blood.
When removal of water is required the
pressure on the blood-side of the membrane
has to be increased forcing water molecules
to pass into the dialysate.

13. Haemodiafiltration
 as its name suggests, is a combination of filtration and dialysis.
 It has the benefits of both techniques but to a lesser extent than
when the individual techniques are used on their own.
There is no evidence to suggest that CVVDF has a survival benefit
when compared to CVVH but may be a useful way of increasing
clearance of small solutes.

14. Slow continuous ultrafiltration
It is used when the only requirement is water removal.
Effectively, it is CVVH with a low filtration rate.
 It can remove up to 6 litres of fluid a day but solute removal
is minimal.

15. Modes of Renal Replacement Techniques
Intermittent ContinuousHybrid
IHDIHD
Intermittent
haemodialysis
SLEDDSLEDD
Sustained (or slow)
low efficiency daily
dialysis
SLEDD-FSLEDD-F
Sustained (or slow)
low efficiency daily
dialysis with filtration
CVVHCVVH
Continuous veno-venous
haemofiltration
CVVHDCVVHD
Continuous veno-venous
haemodialysis
CVVHDFCVVHDF
Continuous veno-venous
haemodiafiltration
SCUFSCUF
Slow continuous
ultrafiltration

16. Continuous versus intermittent renal
replacement therapy
The typical intensive care patient requiring renal replacement
therapy have some of the following characteristics,
• they are older
• multisystem organ failure consisting of sepsis
• cardiac failure
• adult respiratory distress syndrome
• gastrointestinal bleeding
• liver abnormalities.

17.  They are generally hypercatabolic, hypermetabolic and require
ventilatory support and large amounts of fluid intake to administer
inotropes, medications and nutrition.
This volume of fluid is administered in the context of a low urine
output and increased lung water.
This necessitates the need for fluid removal and when
implemented with intermittent HD, large amounts of fluid are
removed over a small period of time resulting in haemodynamic
instability

18. Intermittent haemodialysis
Intermittent haemodialysis involves dialysing with higher flow
rates than CRRT for defined periods of time.
 A typical regime is 3-5 hours of dialysis 3 times a week.
The high flow rates and rapid fall in plasma osmolality mean that
it is only suitable for patients who are cardiovascularly stable.
It forms the basis of long term RRT for chronic renal failure but
is not often used in the critical care setting.

19. Intermittent Therapies

20. Major complications of IHD
Systemic hypotension
Arrhythmia
Hypoxaemia
Haemorrhage
Infection
Line-related complications(e.g. pneumothorax)
Seizure or dialysis disequilibrium
Pyrogen reaction or haemolysis
?Delay in recovery of renal function

21. Continous Renal replacement therapy

22. SCUF
• High flux membranes
• Up to 24 hrs per day
• Objective VOLUME control
• NotNot suitable for solute clearance
• Blood flow 50-200 ml/min
• UF rate 2-8 ml/min
• High flux membranes
• Up to 24 hrs per day
• Objective VOLUME control
• NotNot suitable for solute clearance
• Blood flow 50-200 ml/min
• UF rate 2-8 ml/min

23. CAVVH
• Extended duration up to weeks
• High flux membranes
• Mainly convectiveconvective clearance
• UF > volume control amount
• Excess UF replacedreplaced
• Replacement pre- or post-filter
• Blood flow 50-200 ml/min
• UF rate 10-60 ml/min
• Extended duration up to weeks
• High flux membranes
• Mainly convectiveconvective clearance
• UF > volume control amount
• Excess UF replacedreplaced
• Replacement pre- or post-filter
• Blood flow 50-200 ml/min
• UF rate 10-60 ml/min

24. CAVVHD
• Mid/high flux membranes
• Extended period up to weeks
• DiffusiveDiffusive solute clearance
• Countercurrent dialysate
• UF for volume control
• Blood flow 50-200 ml/min
• UF rate 1-8 ml/min
• Dialysate flow 15-60 ml/min
• Mid/high flux membranes
• Extended period up to weeks
• DiffusiveDiffusive solute clearance
• Countercurrent dialysate
• UF for volume control
• Blood flow 50-200 ml/min
• UF rate 1-8 ml/min
• Dialysate flow 15-60 ml/min

25. Other Benefits of CRRT
 Its ability to reduce energy expenditure by cooling the
febrile patient,
in the patient with heart failure resistant to diuretics,
continuous ultrafiltration can produce a rise in cardiac
index,while avoiding a fall in arterial pressure.
The haemodynamic improvement is mostlydue to a change
in preload which optimises myocardial contractility onthe
Starlingcurve

26. Sustained low efficiency dialysis
 aims to combine the logistic and cost advantages of IHD
with the relative cardiovascular stability of CRRT.
 Treatments are intermittent but usually daily and with
longer session durations than conventional IHD.
Solute and fluid removal are slower than IHD, but faster than
CRRT.

28. WHICH FORM OF RRT SHOULD WE USE?
What we want to remove from the plasma

29. 2. The patient`s cardiovascular status
• CRRT causes less rapid fluid shifts and is the preferred option if there
is any degree of cardiovascular instability.
3. The availability of resources
• CRRT is more labour intensive and more expensive than IHD
• Availability of equipment may dictate the form of RRT.
4. The clinician`s experience
• It is wise to use a form of RRT that is familiar to all the staff involved.
5. Other specific clinical considerations
• Convective modes of RRT may be beneficial if the patient has septic
shock
• CRRT can aid feeding regimes by improving fluid management
• CRRT may be associated with better cerebral perfusion in patients
with an acute brain injury or fulminant hepatic failure.

30. Vascular access in HD/CRRT
Site Advantages disadvantages
IJV Straight access Swings in flow associated
with respiration.
Subclavian Least association with
infection.
Most comfortable
Swings in flow as above.
Subclavian vein stenosis if
catheter indwelling for a
long time.
Risks of pneumothorax
Femoral Ease of access Infection rates high.

31. Dialysate Fluid
 Bicarbonate buffer solutions is used in IHD to replenish
serum bicarbonate levels and neutralise metabolic acids that are
usually present in patients with renal failure.
Acetate buffer solutions present the body with a large
acetate load to be metabolised by the skeletal muscle.
In critically ill patients the acetate levels rise due to decreased
skeletal muscle metabolism.
Increased acetate levels have been associated with hypotension
and hypoxia due to its negative inotrope effect and vasodilatation
Lactate buffer soulutions

33. Extra corporeal circuit
Most CRRT techniques utilise a pump driven venovenous circuit
as this provides a high constant flow rate

34. Anticoagulation
extracorporeal circuit will activate coagulation pathways and the
premature clotting of a filter is a common problem.
Even a small amount of clot formation will reduce filter
performance.
NON-PHARMACOLOGICAL MEASURES
1. adequate central venous pressure,
2. optimising vascular access
3. adding a proportion of the replacement fluid to the patients
blood before it passes through the haemofilter (this is predilution)

35. GUIDELINES FOR NO
ANTICOAGULATION
There is a already a degree of coagulopathy
INR > 2-2.5
 APTT > 60 seconds
 platelet count < 60 x 10³.mm3
There is a high risk of bleeding
The patient is receiving activated protein C.

36. PHARMACOLOGICAL MEASURES
Unfractionated or low molecular weight heparins
Unfractionated heparin (UFH) [5-30kDa] is the most commonly
used anticoagulant
typical regime involves a 40-70 IU.kg-1 bolus followed by a pre-
filterinfusion at 5-10 IU.kg.-1hr-1
It is the most cost effective anticoagulant and is fully reversible
with protamine.
The APTT should be monitored to avoid excessive anti-
coagulation but there is no evidence that elevating the APTT
prolongs filter life.

37. Low molecular weight heparins (LMWH) [4.5-6kDa]
They are dependant on renal elimination so in this setting
their dosing needs to be guided by anti-factor Xa levels
(aiming for 0.25-0.35 IU.ml-1
 The half life of LMWHs is longer than for UFH (2-6 hrs
versus 1.5-3hrs) and their effect can only be partially
reversed with protamine.
There is not a huge amount of data on the use of LMWH in
CRRT and there is no evidence to suggest that they are
superior to UFH.

38. Prostaglandins
Prostaglandins (prostacyclin or prostaglandin E2) inhibit platelet
function and can either be used on their own or in combination
with heparin they have a synergistic effect.
 short half life (several minutes) so are administered as an infusion
(2.5 – 10 ng/kg/.min). The
anticoagulant effect stops within 2 hours of discontinuing the
infusion
The main side effect is vasodilation which may include a reduction
in HPV leading to hypoxemia.
they are expensive and so are only used as second line therapy

39. Regional citrate anticoagulation
It is an effective therapy especially when there is an increased risk
of bleeding.
It is alternative to heparin
Sodium citrate is infused into the circuit pre-filter which chelates
calcium and inhibits clot formation.
The calcium citrate complex is freely filtered so a calcium infusion
is required post-filter.
This form of anticoagulation is limited by the metabolic
derangements that it can cause: Hypocalcaemia,
hypomagnesaemia , hypernatraemia , metabolic alkalosis (citrate is
metabolised to bicarbonate), metabolic acidosis (caused by the
citrate especially if the body`s citrate handling is impaired e.g.

40. Filters
Filters are either cellulose-based or synthetic.
Synthetic filters such as polysulphone and polyamide are
more biocompatible and are higher-flux membranes so seem
more suitable for CRRT
high-flux membranes with a surface area of 0.6– 1.2m2 and
a pore size allowing the passage of molecules up to 50,000
Daltons

41. Properties
Biocompatibility
o The degree to which the membrane will activate the patient`s
inflammatory and coagulation pathways.
o The greater the biocompatibility of a membrane the less activation
it will cause
Flux
o The permeability of the filter. High flux membranes are
hydrophobic and may have more or larger pores allowing more
water and solute to move across the membrane.

42. Adsorption
o The ability of larger solutes to adhere to the surface of the membrane.
o A highly adsorptive membrane offers the potential benefit of adsorbing
mid sized molecules including inflammatory mediators but only until it
is saturated with them (usually after the first few hours)
Thickness
o Thinner membranes allow greater movement of solute by diffusion and
also favour convective movement
Surface area
o The surface area of the membrane determines the available area for
diffusion and ultrafiltration

43. Complications common to IHD, CRRT,
and hybrid therapies
1. Complications related to the vascath (including line-related
sepsis)
2. Haemodynamic instability
3. Air emboli
4. Platelet consumption
5. Blood loss
6. Electrolyte imbalances
7. Hypothermia
8. Effects of anticoagulation (bleeding or specific side-effects of the
anticoagulant used e.g. heparin induced thrombocytopenia).

44. Adequacy of Dialysis
 Precise standards and goals of dialysis adequacy are based on
the clearance of urea.
 The volume of distribution of urea reflects the total body water.
 Mathematical modeling based on the changing blood
concentrations

45. Dialysis dose
1. Measuring fractional reduction of BUN with each dialysis.
Measured by volume adjusted fractional clearance of urea.
K*t ÷ V urea
Where K – dialyzer urea clearance
t – time on dialysis
V – volume of distribution of urea

46. Dialysis dose
2. Measurement of urea removed through each dialysis.
% of reduction in urea during single hemodialysis treatment –
Urea reduction ratio
[1-(post dialysis BUN concentration) ] x 100
(pre dialysis BUN concentration)

47. Care of patients receiving hemodialysis
Variable Goals
Dialysis dose Urea kinetics model
Fluid balance Individualised. Intradialytic weight gain should be less than 5%
of IBW
Quality Measure endotoxin and bacteria in the dialysate water
Anemia Target a Hb of 10-12gms%. Avoid high dose erythropoietin
Vascular access Monitoring. To establish AV access rather than indwelling
catheters.
Bone & Mineral Calcium levels between 8.4-9.5 and a PO4 3.5-5.5mg/dl
Blood pressure Optimum targets & strategies not well defined
LDL cholesterol <100mg/dl
Quality of life indices Support from the medical social worker