renal replacement therapy

1. RENAL REPLACEMENT
THERAPY
BY : Dr Nalluru Likhitha (MD Anaesthesia)
Moderator : Dr Guru Charan , MD Anaesthesia
NRIIMS
Sanghivalasa

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
20XX Presentation title 2

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)
20XX Presentation title 3

4. Classification of AKI
R- RISK Increase in serum creatn>1.5times
baseline
Urine output < 0.5ml/kg/hr for 6hrs
I – INJURY Increase in sereum creat >2 times
baseline
Decrease in GFR > 50%
Urine output <0.5ml/kg/hr for >12hrs
F-Failure Increase in serum creat >3 times
baseline
Decrease in GFR<75%
Urine output <0.3ml/kg/hr for >24hrs
Or anuria for >12hrs
L-loss of function Persistent loss of kidney function for
>4weeks
ESRD Persistent loss of kidney function for >3
months
20XX Presentation title 4

5. Indications of RRT
20XX Presentation title 5

6. Indications of RRT
➢ drugs are cleared by RRT if they are water-soluble and not highly protein-bound.
20XX Presentation title 6
Removed by RRT Not removed by RRT
Lithium
Methanol
Ethylene glycol
Salicylates
Barbiturates
Metformin
Aminoglycosides ,metronidazole,
carbapenems.cephalosporins and most
pencillins.
Digoxin
Tricyclics
Phenytoins
Beta blockers
Benzodiazepines
Macrolide and quinolone antibiotiocs
Warfarin

7. Dialyser 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.
20XX Presentation title 7

8. 20XX Presentation title 8

9. 20XX Presentation title 9
DIFFUSION CONVECTION
ADSORPTION ULTRAFILTRATION
principles

10. Mechanism of Solute Removal
ULTRAFILTERATION :
• Movement of fluid through a semipermeable membrane.
• Along a pressure gradient.
• Net removal of fluid from patient.
20XX Presentation title 10

11. Mechanism of Solute Removal
CONVECTION:
• Convection is one way movement of solute through a semipermeable membrane with a water flow.
• Efficient for both larger and smaller molecules.
• It requires pressure gradient.
• It can be provided by adding extra fluid to create pressure difference an drag the solutes to other side.
• The extra fluid been given is called replacement fluid.
20XX Presentation title 11

12. Mechanism of Solute Removal
DIFFUSION
• Movement of solutes from area of higher concentration to lower concentration.
• This works by a difference in concentration gradient.
• We need to have a solution that is of lower concentration than blood called as DIALYSATE .
• Efficient in clearing smaller molecules.
20XX Presentation title 12

13. • Concentration difference can be created by two means : cocurrent flow and countercurrent flow.
20XX Presentation title 13

14. Convection –Filtration (HF) Diffusion –Dialysis (HD)
20XX Presentation title 14
SCUF
CVVH
CVVHD
CVVHDF

15. Modes of renal replacement techniques
20XX Presentation title 15
Peritoneal dialysis

16. Peritoneal Dialysis
• Procedure using peritoneum as a membrane for fluid exchange therapy in azotemic patients.
• It is performed using peritoneum as a semipermeable membrane.
• This allows water and solute transport from vascular system to peritoneal cavity.
• The peritoneal cavity holds upto 3litres of fluid.
• Uses diffusion and ultrafiltration as principles.
20XX Presentation title 16

17. Peritoneal Dialysis
Indications : Contraindications:
Renal : CKD/AKI with Absolute : severe IBD ,ischemic bowel disease ,
Vascular access failure acute active diverticulosis
Intolerance to hemodialysis peritoneal fibrosis and adhesions
Children 0-5years. abdominal abscess
Chronic infections
Non renal indications : Relative :severe malnutrition
Refractory congestive cardiac failure obesity
Hepatic failure hernias
Pancreatitis colostomy
20XX Presentation title 17

18. 20XX Presentation title 18

19. Peritoneal dialysate solution
• pH-5.2
• Omolarity : 363mOsm/L
• Sodium 130mmol/L
• Calcium – 1.5mmol/L
• Magnesium – 0.75mmol/l
• Chloride – 100mmol/L
• Bicarbonate : 35mmol/l
• Glucose : 1.36-4.25mh/gl
20XX Presentation title 19

20. Complications :
Due to catheter placement :
• Bowel perforation
• Bleeding
• Wound infection
• Peritonitis
• Hernias
Due to procedure :
• Protein loss
• Hyperglycemia
• Hypertriglyceredimia
• Weight gain
• Shoulder pain
• Raised ICP
20XX Presentation title 20

21. Intermittent hemodialysis
• 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.
20XX Presentation title 21

22. Intermittent therapies
Relatively inexpensive
Flexible timing allows for mobility and transport
Rapid correction of fluid overload
Rapid removal of dialysable drugs
Rapid correction of acidosis and electrolyte abnormality
Minimises anticoagulant exposure
20XX Presentation title 22

23. 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
20XX Presentation title 23

24. Continuos Renal Replacement
Therapy
• It 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 24hours a day.
• The concept behind continuos renal replacement techniques is to dialyse patients in a more physiologic way
slowly over 24 hours just like kidney.
20XX Presentation title 24

25. Continuos renal replacement therapy
Hemodynamic stability
Stable and predictive volume control
Stable intracranial pressure
Disease modification by cytokine removal as in sepsis
20XX Presentation title 25

26. IHD VERSUS CRRT
IHD CRRT
Mainly diffusive
High flow (50-0-800l/min)
On line dialysis production
Usually 4hr per dialysis session.
Technically demanding .
Usually used in patients who are hemodynamically stable
Mainly convenctive (CVVH),diffusive (CVVHD) or
both(CVVHDF)
Low flow(1-2L/hr) or no dialysate flow in CVVH
Use commercial fluid
continuos
Technically less demanding
Usually used in patients with hemodynamic instability or
increased ICP
20XX Presentation title 26

27. SCUF
• High flux membranes
• Up to 24 hrs per day
• Objective VOLUME control
• Not suitable for solute clearance
• Blood flow 50-200 ml/min
• UF rate 2-8 ml/min
20XX Presentation title 27

28. CVVH
• Extended duration up to weeks
• High flux membranes
• Mainly convective clearance
• UF > volume control amount
• Excess UF replaced
• Replacement pre- or post-filter
• Blood flow 50-200 ml/min
• UF rate 20-25ml/hr
• Use convection principle .
20XX Presentation title 28

29. CVVHD
• Mid/high flux membranes
• Extended period up to weeks
• Diffusive 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
• By Diffusion principle.
20XX Presentation title 29

30. CVVHDF
20XX Presentation title 30
• Use diffusive and convective principles.
• Require dialysate as well as
replacement fluid.
• Rate of filtration 8-12ml/min

31. 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
20XX Presentation title 31

32. 20XX Presentation title 32

33. WHICH FORM OF RRT TO BE USED?
20XX Presentation title 33

34. WHICH FORM OF RRT TO BE USED?
20XX Presentation title 34
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

35. NEED FOR RRT
IHD/SLED
20XX Presentation title 35
AKI/ESRD
ON PRESSORS??
NO YES
BP
STABLE
??
NO
CRRT
YES
Severe
hyperkalemia
Severe fluid overload Acidosis with untreated cause
Yes
IHD/
CRRT
NO
SLED
YES
CRRT
NO
SLED
YES
CRRT
NO
SLED

36. Vascular access :
• Venovenous RRT requires a double lumen vascular catheter placed in central vein.
• The tip should be sited in IVC for femoral lines or SVC for internal jugular and subclavian veins.
• The catheters are usually made of polyurethrane or silicone and need to be stiff enough to prevent kinking.
20XX Presentation title 36

37. VASCULAR ACCESS
20XX Presentation title 37

38. 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 solutions
20XX Presentation title 38

39. DIALYSATE FLUID
• Electrolyte concentration of a commonly available dialysate solution
20XX Presentation title 39
Electrolyte Concentration
Sodium
Potassium
Lactate
Chloride
Calcium
Magnesium
Glucose
Osmolality
140mmol/L
1mmol/L
45.5mmol/l
102mmol/l
1.6mmol/l
0.82mmol/l
10.9mmol/l
285mmol/l

40. Parameters
Dose :
• Defined by effluent rate .( recommended I 25ml/kg/hr)
• Higher rates used for metabolic acidosis ( 40-70ml/kg/hr ) until corrected..
Filtration fraction :
• Defined as proportion of plasma water entering the dialyser which is filtered.
• Usually maintained below 20%
• FF=ultrafiltration flow rate / plasma water flow rate .
Blood flow rate :
• For patients on anticoagulation : 200ml/min
• No anticoagulation : 300l/min
• Lower flow rates cause blood stasis and clotting.
20XX Presentation title 40

41. 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)
20XX Presentation title 41

42. 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
• Anticoagulants should be considered in all other situations and aim is to anticoagulated the filter and not the
patient.
20XX Presentation title 42

43. Anticoagulation
The forms of anticoagulation available are :
• Unfractionated heparin (UFH) [5-30kDa] is the most commonly used anticoagulant in the UK and atypical
regime involves a 40-70 IU.kg-1 bolus followed by a pre-filter infusion 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.
20XX Presentation title 43

44. Anticoagulation
• Low molecular weight heparins (LMWH) [4.5-6kDa] are only used for RRT in 4% of intensive care
units in the UK.
• 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.
20XX Presentation title 44

45. Anticoagulation
Prostaglandins :
• Prostaglandins (prostacyclin or prostaglandin E2) inhibit platelet function and can either be used on their own
or in combination with heparin whereby they have a synergistic effect.
• Prostaglandins have a short half life (several minutes) so are administered as an infusion (2.5 – 10
ng.kg1.min-1).
• Theanticoagulant effect stops within 2 hours of discontinuing the infusion making them a useful alternativeto
heparin in patients at high risk of bleeding.
• The main side effect is vasodilation which may include a reduction in hypoxic pulmonary vasoconstriction
leading to hypoxemia.
• The other downside is that they are expensive and so are only used as second line therapy
20XX Presentation title 45

46. Anticoagulation
Regional citrate anticoagulation :
• Regional citrate anticoagulation is an effective therapy especially when there is an increased risk of
bleeding.
• 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 ofanticoagulation is limited by the metabolic derangements that it can cause: Hypocalcaemia,
hypomagnesaemia (Mg2+ is also chelated), hypernatraemia (sodium load in sodium citrate), metabolic
alkalosis (citrate is metabolised to bicarbonate), metabolic acidosis (caused by the citrate especially if
the body`s citrate handling is impaired e.g. liver failure).
20XX Presentation title 46

47. Filters
The properties of a filter that have an impact on its function are:
Biocompatibility
• The degree to which the membrane will activate the patient`s inflammatory and coagulation pathways. The greater the
biocompatibility of a membrane less activation it will cause.
Flux
• 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.
Adsorption
• The ability of larger solutes to adhere to the surface of the membrane. 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
• Thinner membranes allow greater movement of solute by diffusion and also favour convective movement
Surface area
• The surface area of the membrane determines the available area for diffusion and ultrafiltration
20XX Presentation title 47

48. Replacement fluids
Replacement fluids vary slightly in their composition but are all are balanced salt solutions with either a lactate
or bicarbonate buffer.
• Lactate-based solutions are stable and hence the cheaper and more practical option, however, their buffering
capacity depends on the conversion of lactate into bicarbonate.
• Under normal physiological conditions the body converts lactate into bicarbonate on an equimolar basis.
• This is not always the case in critically ill patients, particularly if they have impaired liver function or already
have a lactic acidosis.
• In these situations, RRT using a lactate-based replacement fluid can worsen the patient’s acidosis so a
bicarbonate-based replacement solution should be used.
• If, however, this is not possible and serum lactate levels are not excessive then an alternative option is to
continue with the lactate based replacement solution and commence an intravenous infusion of bicarbonate
20XX Presentation title 48

49. Replacement fluids
• Bicarbonate-based replacement solutions have a more reliable buffering capacity but need to be prepared
just prior to use.
• At present, there is no evidence to suggest that the choice of replacement fluid has an impact on survival or
renal recovery.
• Replacement fluid can be added pre- or post-filter in varying ratios.
• The benefit of adding some of the replacement fluid pre-filter is that it lowers the haematocrit of the blood
which reduces the likelihood of the filter clotting.
20XX Presentation title 49

50. Complications common to
IHD,CRRT,Hybrid therapies
• Complications related to the cath (including line-related sepsis)
• Haemodynamic instability
• Air emboli
• Platelet consumption
• Blood loss
• Electrolyte imbalances
• Hypothermia
• Effects of anticoagulation (bleeding or specific side-effects of the anticoagulant used e.g. heparin induced
thrombocytopenia).
20XX Presentation title 50

51. Summary
• AKI is common and 5% of the critical care population receive RRT.
• There are various forms of RRT but they all remove unwanted solutes using the processes of diffusion
(dialysis) and/or convection (filtration).
• RRT can be administered continuously or intermittently.
• No single form of RRT has been shown to offer a survival benefit over the others but there are often other
reasons why a particular technique may be preferable in a given situation.
• There is some evidence that high volume haemofiltration may improve survival in patients with septic shock
but there have been no large randomised controlled trials in this area.
• Lifespan of the circuit is dependant on good quality vascular access and appropriate anticoagulation.
• 60% of people receiving RRT for AKI will die during that admission but 80% of the survivors will be free from
RRT one year later.
20XX Presentation title 51

52. References
1. Morgan and Mickhail’s clinical anesthesiology 5 edition
2. Stoelting’s physiopharmacology
3. Millers Anaesthesia 8 edition
4. Renal replacemenent therapy in crtitical care by Dr Andrew Baker , et all.
5. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294: 813
6. Liu, KD, Himmelfarb, J, Paganini, E, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol
2006; 1: 915-9
20XX Presentation title 52

53. 20XX Presentation title 53
Thank you