Basic Science applied to medicine

1. Introduction
• Main functions of the kidney:
maintenance of fluid balance
maintenance of acid base balance
elimination of waste products
• 20 –30 % of ICU patients develop AKI
• Many ICU are already on IHD

2. Options for Renal Replacement Thera
• Intermittent Hemo-Dialysis
• Peritoneal Dialysis
• Continuous Renal Replacement Therapy

3. Intermittent Hemodialysis
• The gold standard
• Usually 2 –3 times a week for 3 –4 hours
• Involves a vascular access
• Pump, filter, dialysate& anticoagulation

4. Advantages/Disadvantages
• Very efficient
• Hemodynamic instability in ≤ 30 % of pa
• Causes rapid shifts in osmolarity
– (Disequilibrium syndrome)
• It is “Intermittent”

5. Peritoneal Dialysis
• Simple and cheap, but …….
• Poor solute clearance
• Poor uremic control
• Risk of peritoneal infection
• Mechanical impedance
– Pulmonary and cardiovascular function

6. Continuous Renal Replacement Ther
• Concept-dialyze patients more physiolog
• Avoids the accumulation of waste produc
• Avoids the rapid shifts in volume & osmo
• Avoids disadvantages of Peritoneal Dialy

7. Advantages
• Precise volume control
• Very effective control of uremia and ↑ K⁺
• Rapid control of metabolic acidosis
• Suitable for hemodynamicallyunstable pt
• Improved nutritional support
– (no need for volume restriction)

8. Advantages
• Needs minimal training
• Safer for patients with TBI & CVS disorde
• May have an effect in sepsis
• Probable advantage in terms of renal rec

9. Disadvantages
• Expensive
• Anticoagulation
• Hypothermia
• Severe depletion of electrolytes –K+
and PO4
• Complications of line insertion and sepsis
• Risk of line disconnection

10. Principal
• 2 processes in waste product removal in
1. Diffusion…………Dialysis
2. Convection…….Hemofiltration

11. Diffusion/Dialysis

12. Semipermiable Membrane

13. Semipermiable Membrane

14. Diffusion

15. Ultrafiltration
• The passage of water through a membra
under a pressure gradient.
• Driving pressure can be
+ve(push fluid through the filter)
–ve(pull fluid to other side of filter)
• Pressure gradient is created by effluent p

16. Ultrafiltration

17. Convection
• Movement of solutes through a membran
the force of water.
“solvent drag”
• The water pulls the molecules along with
it flows through the membrane.
• Can remove middle and large molecules,
well as large fluid volumes.
• Maximized by using replacement fluids.

18. Convection

19. Convection

20. Convection

21. Adsorption
• Adsorptionis the removal of solutes from
blood because they cling to the membra
– Think of an air filter. As the air passes throug
impurities cling to the filter itself.
– Eventually the impurities will clog the filter a
will need to be changed.
• The same is true in blood purification. Hi
levels of adsorptioncan cause filters to cl
and become ineffective

22. Adsorption

23. Dialysate
Dialysateis any fluid used on the opposite side of the filte
the blood during blood purification.

24. Replacement Fluids
• Used to increase the amount of convecti
solute removal in CRRT.
• Replacement fluids do not replace a
• Fluid removal rates are calculated
independently of replacement fluid rates
• The common replacement fluid is 0.9% s
• Can be pre or post filter.

25. Replacement Fluids

26. Comparison Pre & Post Dilutio
PRE-FILTER
– Increases filter life
– Increases convective
transport
– Reduced solute clearance
– Some of delivered
replacement fluid lost by
hemofiltration
– Lower anticoagulation
requirements
– Higher UF required given
loss of replacement fluid
through filter
POST-FILTER
– No solute dilution,
improved diffusion and
solute clearance
– Increased
hemoconcentration
– Higher delivered dose
of hemofiltration

27. Indications
• Acidemia(pH <7.1)
• Electrolytes
– Hyperkalemia(K⁺ > 6.5 mEq/L)
– Severe dysnatremia(Na⁺ <115 or >160 mEq/L)
• Ingestions (Toxins, Drugs)
• Overload/ Oliguria(urine output <200 mL/12
• Uremia (urea >30 mg/dL)
– Uremic encephalopathy
– Uremic pericarditis
– Uremic neuro-myopathy
A E I O U

28. Dialysableor Not
Dialysable
Barbiturates
Lithium
Alcohols, Amglcoside
Salicylates
Theophyllin
Penicillins,
Carbapenems, Cephalo
Non-Dialysable
Digoxin
Tricyclic
Antidepressents
Phenytoin
Benzodiazepines
B-blockers
(atenololis removed)
Metformin
PC-B L A S T

29. Timing
• Inadequate data available to answer this
• Observational data suggests better outco
are associated with early RRT initiation
 Getting et al 1999
2
. Urea 15.2 vs33.7 conferred survival benefit.
 Roncoet al 2000
3
and Saudanet al 2006
4
both dose/outcome studies suggested an early
start.
 Liu et al 2006
5
observational PICARD study (Urea 27) suggested an early start
– RENAL study, NEJM 2009, 1508 pts.
– Demirkilic2004, Elahi2004, Piccini2006

30. Early Initiation means…

31. • CRRT includes several treatment modalities
that use a veno-venous access.
• The choice will depend on the needs of the
patient and on the preference of the
physician.
CRRT Modalities

32. • Removal of ultrafiltrateat low rates
• without administration of a substitution solution.
• The purpose is to prevent or treat volume ove
• when waste product removal or pH correction isn’
necessary.
• Primary indication for SCUF -fluid overload
• Mechanism of water transport is Ultrafiltratio
• No dialysate or replacement fluid is used.

33. • Other solutes are removed but are neglig
• The amount of fluid in the effluent bag is
same as the amount removed from the p
• Removal rates are closer to 100 ml/hour

34. Understanding Flow

35. Let’s Revise
• Primary therapeutic goal:
– Safe management of fluid
• Primary indications:
– Fluid overload without metabolic imbalance
• Principle used:
Ultrafiltration
• Therapy characteristics:
– No dialysateor substitution solutions
Fluid removal only

36. • Blood flow:
80 –200 ml/min
• Duration:
(as advised by the physician)
• Ultrafiltration:
20-100 ml/hr (or total volume)
• Anticoagulation…. Acc to physician
• Dialysate…….. NO
• Replacement fluid….. NO

37. • An extremely effective method of solute remov
is indicated for uremia or severe pH or electrol
imbalance with or without fluid overload.
• Particularly good at removal of large molecule
because CVVH removes solutes via convection
• Convective removal of waste products (small a
large molecules) utilizing a substitution solutio
• pH is affected with the buffer contained in the
substitution solution.

38. • Solutes can be removed in large quantiti
while easily maintaining a net zero or ev
positive fluid balance in the patient.
• The amount of fluid in the effluent bag is
equal to the amount of fluid removed fro
the patient plus the volume of replaceme
fluids administered.
• No dialysate is used.

39. Understanding Flow

40. Let’s Revise
• Primary therapeutic goal:
– Solute removal and safe fluid management
• Primary indications:
– Uremia, severe acid/base or electrolyte imbala
– Removal of larger mol wt substances
• Principle used:
convection
• Therapy characteristics:
– Substitution solution to drive
– No dialysatesolution
Effective at removing small and large molecules

41. • Blood flow:
80 –200 ml/min
• Duration:
As advised by physician
• Ultrafiltration:
20-100 ml/hr (or total volume)
• Replacement Fluid:
1000 –2000 ml/hr,preor post filter
• Anticoagulation
• Dialysate…. NO
Dosage:
30ml/kg/hr
70x30=2100ml
Replacement fluid
So
This Replacement can be
divided into pre & post filte
Depending upon physician
Ex, 500 pre and 1500ml po
(All can be pre or post)

42. • Effective for removal of small to medium sized m
• Solute removal occurs primarily due to diffusion
• No replacement fluid is used.
• Dialysateis run on the opposite side of the filter.
• Fluid in the effluent bag is equal to the amount o
removed from the patient plus the dialysate.
• Continuous diffusive removal of waste products
molecules) utilizing a dialysis solution.
• pH is also affected with the buffer contained in t
dialysate.

43. Understanding flow

44. • Blood flow:
80 –200 ml/min
• Duration:
As advised by physician
• Ultrafiltration:
20 -100 ml/hr (or total volume)
• Anticoagulation:
• Dialysate:
600 –1800 ml/hr (up to 3 lit/hr).
• Replacement fluid….NO
Dosage:
45ml/kg/hr
70x45=3150ml
Dialysatefluid
So
Dialysatecan be 3 liters /

45. Let’s Revise
• Primary therapeutic goal:
– Solute removal and safe management of fluid volume
• Primary indications:
– Uremia, severe acid/base or electrolyte imbalance
• Principle used:
Diffusion
• Therapy characteristics:
– Requires dialysatesolution to drive diffusion
– No substitution solution
Effective at removing small to medium molecu

46. • The most flexible of all the therapies, an
combines the benefits of diffusionand
convectionfor solute removal.
• The use of replacement fluid allows adeq
solute removal even with zero or positiv
fluid balance for the patient.

47. • Amount of fluid in the effluent bag equals the fl
removed from the patient plus the dialysate an
replacement fluid.
• Dialysate on the opposite side of the filter and
replacement fluid either before or after the filte
• Continuous diffusive and convective removal o
waste products (small and large molecules)
• Utilizing both dialysate and substitution solutio
• pH is also affected with the buffer contained in
dialysate and substitution solution.

48. Understanding Flow

49. Let’s Revise
• Primary therapeutic goal:
– Solute removal and safe management of fluid volume
• Primary indications:
– Uremia, severe acid/base or electrolyte imbalance
– Removal of large molecular weight substances is required
– Unstable haemodunamics
• Principle used:
diffusion and convection
• Therapy characteristics:
– Requires dialysatefluid and substitution solution
drive diffusion and convection
• Effective at removing small, medium and la
molecules

50. • Blood flow:
80 –200 ml/min
• Duration:
As advised by the physician
• Ultrafiltration:
20-100 ml/hr (or total volume)
• Anticoagulation:
• Dialysate:
600 –1800 ml/hr (up to 3 lit/hr)
• Replacement fluid:
1000-2000 ml/hr, pre or post filter(up to 3 lit/hr)
Dosage:
45ml/kg/hr
70x45=3150ml
½ as Dialysate& ½ as
Replacement fluid
So
1500ml as Dialysate
1500ml as Replacement
be divided into pre & po
filter
Depending upon physicia
Ex, 500 pre and 1000ml p