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Renal replacement therapy Dr. Ashish Moderator : Dr. Muralidhar

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1 Renal replacement therapy Dr. Ashish Moderator : Dr. Muralidhar

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 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 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 – 1.Thickness and surface of membrane, 2.Temperature of blood 3.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 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, 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

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

39 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 Continuous Renal Replacement Therapy (CRRT)

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

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 Return Clamp Patient Access Pressure Effluent Pump Syringe Pump Filter Pressure Hemofilter Pre Post Replacement Pump Pre Blood Pump Effluent Pressure

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

51 CVVHDF Continuous venovenous hemodiafiltration Blood driven through highly permeable dialyzer via extracorporeal circuit in venovenous mode and countercurrent flow of dialysate is delivered in dialysate compartment UF produced during membrane transit is in excess of pt. desired wt. loss

52 CVVHDF Continuous veno-venous hemodiafiltration –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.

53 CVVHDF Removal of small molecules by diffusion through the addition of dialysate solution. Removal of middle to large molecules by convection through the addition of replacement solution.

54 SLEDD(Slow low efficiency daily dialysis) Hybrid therapy that try to match physiological advantage of CRRT Involves use of blood & dialysate flows less than in IHD Qb : 100-200ml/min & Qd :< 300ml/min T/t time extended to 6-12hr every day

55 SLEDD(Slow low efficiency daily dialysis) Result slower solute clearance & fluid removal & result in hemodynamic stability comparable to CRRT.

56 Removal of sodium & water cannot be dissociated when using diuretic & some RRT Diuretics l/t natriuresis whereas dialysis may result in hypotonia or hypertonia Depending on effect of dialysis on diffusion & on removal of molecules, including urea & other electrolyte

57 Water removal is always a/w removal of other solutes & its amount depend on technique used UF from SCUF is iso-osmotic & and isonatremic because Na elimination is linked to Na conc. in plasma Best evidence to date support RRT dose of 35ml/kg/hr for CVVH, CVVHD, IHD

58 UNLOAD trial(UF versus i.v. diuretics for acute decompensated CHF) First RCT comparing Diuretic versus HF in hypervolemic pt. Principal Findings 1.Ultrafiltration l/t greater wt. & fluid loss 2.Reduction in rate & duration of subsequent hospitiliztions in pt with volume removal by UF 3.Benefits from short term use of UF over 90 days was achieved without significant adverse effects

59 Vascular Access A veno-venous double lumen hemodialysis catheter or two single lumen venous hemodialysis catheters may be used.

60 Access Location Internal Jugular Vein –Primary site of choice due to lower associated risk of complication and simplicity of catheter insertion. Femoral Vein –Patient immobilized, the femoral vein is optimal and constitutes the easiest site for insertion. Subclavin Vein –The least preferred site given its higher risk of pneumo/hemothorax

61 Anticoagulation Blood contact to circuit tubing in CCRT l/t activation of coagulation cascade Result in clotting of filter or circuit Quantity & duration of anticoagulation changes depending on schedule of RRT Anticoagulation necessary for CRRT where blood – artificial surface interaction is maximum

62 Circuit set up optimisation Vascular access adequate size Kinking of circuit tubing avoided Blood flow rate should exceed 100ml/min Plasma filtration fraction < 20% When possible predilution hemofiltration considered

63 Unfractionated heparin Dose 5-10 IU/kg/hr Regional heparinization in 1:1 ratio with protamine ( 150IU Of UFH per mg protamine) Problems : 1.Unpredictable bioavailibility 2.Necessity for AT III levels for optimal use 3.Heparin induced thrombocytopenia

64 LMWH Alternative to UFH Prospective studies hav not shown it superior to UFH in prolonging life of RRT circuit Better bioavailibility Lower incidence of HIT Cost 10% > than UFH

65 Prostacyclin (PGI2) Potent inhibitor of platelet aggregation with short half life Infusion dose 4-8ng/hr with or without addition of low dose UFH Problems: Very short circuit life span Hypotension

66 Citrate Citrate chelates calcium which prevents clot formation Drawbacks : 1.Risk of hypoalcemia 2.Metabolic alkalosis

67 Complications as/w hemodialysis Hypotension – MC d/t osmolar shift & ultrafiltration- induced volume depletion Hypotensive episode may reflect myocardial ischemia,dysarrythmias or pericardial effusion with cardiac tamponade T/t – slowing rate of ultrafitration and/or i.v fluids

68 Hypersensitivity reaction to ethylene oxide used to sterlize dialysis machine d/t specific membrane material polyacrylonitrile MC in pt. receiving ACE inhibitors This reaction d/t bradykinin release which is degraded by kinases but ACE inhibitors block this response

69 Progressive renal failure,catabolism,&anorexia l/t loss of lean body mass but fluid retention mask this may l/t wt. gain Between t/t wt. gain of 3%-4% of body mass is appropriate

70 Increased chances of ischemic heart disease in ESRD pt. on hemodialysis d/t 1.Systemic HTN 2.Anemia 3.Hyperlipidemia 4.Hyperhomocystemia 5.Accelerated atherosclerosis 6.Impaired oxygen delivery to myocardium d/t uremic toxin

71 Pericarditis with pericardial effusion d/t inadequate hemodialysis T/t - Intensive heparin free dialysis Persistent effusion - pericardiocentesis

72 Bleeding tendency d/t altered platelet function, partially correctable by hemodialysis Heparin free dialysis or administration of DDAVP, sufficient to correct bleeding tendency

73 At risk of infection d/t impaired phagocytosis & chemotaxis T.B in pt on hemodialysis is extrapulmonary and atypical symptom mimicing inadequate dialysis Vaccinated against pneumococcal and hepatitis B

74 Summary Mechanism in RRT based on principles of water & solute transport via diffusion & convection These mechanism applied lead to different techniques & modalities Clinical effects on critically ill pt. depend on selected RRT strategy & on severity/ complexity of patients clinical picture


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