Renal replacement therapy

1. Renal replacement therapy Dr . Ashish Moderator : Dr. Muralidhar www.anaesthesia.co.inanaesthesia.co.in@gmail.com

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 29269 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;813-818,2005)

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;813-818,2005)

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. 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 :150-300ml/min , Qd:300-500ml/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. 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

38. Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00 100 p < 0.001 90 80 70 p < 0.001 p n..s. 60 Survival (%) 50 40 30 57 % 58 % 41 % 20 10 0 Group 1(n=146) Group 2 (n=139) Group 3 (n=140) ( Uf = 20 ml/h/Kg) ( Uf = 35 ml/h/Kg) ( Uf = 45 ml/h/Kg)

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

40. 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.

41. 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

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 :100-250 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

44. SCUF Return Pressure Air Detector Return Clamp Blood Pump Syringe pump Patient Hemofilter Access Pressure Filter Pressure Effluent Pressure BLD Effluent Pump Pre Blood Pump

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.

47. CVVH Return Pressure Air Detector Syringe Pump Return Clamp Patient Hemofilter Filter Pressure Access Pressure Post Pre Effluent Pressure Post Pre Blood Pump Replacement Pump Effluent Pump Replacement Pump

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 :100-250ml/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.

50. CVVHD Air Detector Return Pressure Return Clamp Syringe Pump Blood Pump Patient Hemofilter Filter Pressure Access Pressure Effluent Pressure BLD Dialysate Pump Pre Blood Pump Effluent Pump