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Renal Replacement Therapy IN ICCU
This document discusses renal replacement therapies in critical care. It begins with several questions about what therapy to use, when to start and stop it, how much therapy is needed, and whether outcomes can be improved. It then provides an overview of AKI classification systems and discusses the relationship between AKI severity and mortality. The document reviews evidence on initiating RRT, compares intermittent therapies to continuous therapies, and discusses solute clearance methods, major RRT techniques, and managing risks like hypotension. It also explores RRT as extracorporeal blood purification therapy and hypotheses about cytokine removal.
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Renal Replacement Therapy IN ICCU
- 1. Renal ReplacementRenal Replacement Therapiesin Critical CareTherapies in Critical Care Dr. Andrew FergusonDr. Andrew Ferguson Consultant in Intensive Care Medicine & AnaesthesiaConsultant in Intensive Care Medicine & Anaesthesia Craigavon Area Hospital, United KingdomCraigavon Area Hospital, United Kingdom
- 2. Where are we- too many questions? • What therapy should we use?What therapy should we use? • When should we start it?When should we start it? • What are we trying to achieve?What are we trying to achieve? • How much therapy is enough?How much therapy is enough? • When do we stop/switch?When do we stop/switch? • Can we improve outcomes?Can we improve outcomes? Does the literature help us?Does the literature help us?
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- 4. AKI classification systems1: RIFLE
- 5. AKI classification systems2: AKIN Stage Creatinine criteria Urine output criteria 1 1.5 - 2 x baseline (or rise > 26.4 µmol/L) < 0.5 ml/kg/hour for > 6 hours 2 >2 - 3 x baseline < 0.5 ml/kg/hour for > 12 hours 3 > 3 x baseline (or > 354 µmol/L with acute rise > 44 µmol/L) < 0.3 ml/kg/hour for 24 hours or anuria for 12 hours Patients receiving RRT are Stage 3 regardless of creatinine or urine output
- 6. Acute Kidney Injuryin the ICU • AKIis common: 3-35%* of admissions • AKI is associated with increased mortality • “Minor” rises in Cr associated with worse outcome • AKI developing after ICU admission (late) is associated with worse outcome than AKI at admission (APACHE underestimates RODAPACHE underestimates ROD) • AKI requiring RRT occurs in about 4-5% of ICU admissions and is associated with worst mortality risk ** * Brivet, FG et al. Crit Care Med 1996; 24: 192-198 ** Metnitz, PG et al. Crit Care Med 2002; 30: 2051-2058
- 7. Mortality by AKISeverity (1) Clermont, G et al. Kidney International 2002; 62: 986-996
- 8. Mortality by AKISeverity (2) Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409
- 9. RRT for AcuteRenal Failure • There is some evidenceThere is some evidence for a relationship between higher therapy dose and better outcome, at least up to a point • This is true for IHD* and for CVVH** • There is nono definitive evidencedefinitive evidence for superiority of one therapy over another, and wide practice variation exists*** • Accepted indications for RTT vary • No definitive evidenceNo definitive evidence on timing of RRT *Schiffl, H et al. NEJM 2002; 346: 305-310 ** Ronco, C et al. Lancet 2000; 355: 26-30 *** Uchino, S. Curr Opin Crit Care 2006; 12: 538-543
- 10. Therapy Dose inIRRT p = 0.01 p = 0.001 Schiffl, H et al. NEJM 2002; 346: 305-310
- 11. Therapy Dose inCVVH 25 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr Ronco, C et al. Lancet 2000; 355: 26-30
- 12. Outcome with IRRTvs CRRT (1) • Trial quality low: many non-randomized • Therapy dosing variable • Illness severity variable or details missing • Small numbers • Uncontrolled technique, membrane • Definitive trial would require 660 patients in each arm! • Unvalidated instrument for sensitivity analysis Kellum, J et al. Intensive Care Med 2002; 28: 29-37 “there is insufficient evidence to establish whether CRRT is associated with improved survival in critically ill patients with ARF when compared with IRRT”
- 13. Outcome with IRRTvs CRRT (2) Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885 • No mortality difference between therapies • No renal recovery difference between therapies • Unselected patient populations • Majority of studies were unpublished
- 14. Outcome with IRRTvs CRRT (3) Vinsonneau, S et al. Lancet 2006; 368: 379-385
- 15. Proposed Indications forRRT • Oliguria < 200ml/12 hours • Anuria < 50 ml/12 hours • Hyperkalaemia > 6.5 mmol/L • Severe acidaemia pH < 7.0 • Uraemia > 30 mmol/L • Uraemic complications • Dysnatraemias > 155 or < 120 mmol/L • Hyper/(hypo)thermia • Drug overdose with dialysable drug Lameire, N et al. Lancet 2005; 365: 417-430
- 16. Implications of theavailable data
- 17. The Ideal RenalReplacement Therapy • Allows control of intra/extravascular volume • Corrects acid-base disturbances • Corrects uraemia & effectively clears “toxins” • Promotes renal recovery • Improves survival • Is free of complications • Clears drugs effectively (?) • Allows control of intra/extravascular volume • Corrects acid-base disturbances • Corrects uraemia & effectively clears “toxins” • Promotes renal recovery • Improves survival • Is free of complications • Clears drugs effectively (?)
- 18. Solute Clearance -Diffusion • Small (< 500d) molecules cleared efficiently • Concentration gradient critical • Gradient achieved by countercurrent flow • Principal clearance mode of dialysis techniques • Small (< 500d) molecules cleared efficiently • Concentration gradient critical • Gradient achieved by countercurrent flow • Principal clearance mode of dialysis techniques
- 19. Solute Clearance –Ultrafiltration & Convection (Haemofiltration) • Water movement “drags” solute across membrane • At high UF rates (> 1L/hour) enough solute is dragged to produce significant clearance • Convective clearance dehydrates the blood passing through the filter • If filtration fraction > 30% there is high risk of filter clotting* • Also clears larger molecular weight substances (e.g. B12, TNF, inulin) * In post-dilution haemofiltration
- 20. Major Renal ReplacementTechniques Intermittent ContinuousHybrid IHDIHD Intermittent haemodialysis IUFIUF Isolated Ultrafiltration 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
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- 23. Intradialytic Hypotension: RiskFactors • LVH with diastolic dysfunction oror LV systolic dysfunction / CHF • Valvular heart disease • Pericardial disease • Poor nutritional status / hypoalbuminaemia • Uraemic neuropathy or autonomic dysfunction • Severe anaemia • High volume ultrafiltration requirements • Predialysis SBP of <100 mm Hg • Age 65 years + • Pressor requirement • LVH with diastolic dysfunction oror LV systolic dysfunction / CHF • Valvular heart disease • Pericardial disease • Poor nutritional status / hypoalbuminaemia • Uraemic neuropathy or autonomic dysfunction • Severe anaemia • High volume ultrafiltration requirements • Predialysis SBP of <100 mm Hg • Age 65 years + • Pressor requirement
- 24. Managing Intra-dialytic Hypotension •Dialysate temperature modelling • Low temperature dialysate • Dialysate sodium profiling • Hypertonic Na at start decreasing to 135 by end • Prevents plasma volume decrease • Midodrine if not on pressors • UF profiling • Colloid/crystalloid boluses • Sertraline (longer term HD) • Dialysate temperature modelling • Low temperature dialysate • Dialysate sodium profiling • Hypertonic Na at start decreasing to 135 by end • Prevents plasma volume decrease • Midodrine if not on pressors • UF profiling • Colloid/crystalloid boluses • Sertraline (longer term HD) 2005 National Kidney Foundation K/DOQI GUIDELINES
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- 27. SCUF • High fluxmembranes • 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
- 28. CA/VVH • Extended durationup 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
- 29. CA/VVHD • Mid/high fluxmembranes • 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
- 30. CVVHDF • High fluxmembranes • Extended period up to weeks • DiffusiveDiffusive & convective& convective solute clearance • Countercurrent dialysate • UF exceeds volume control • ReplacementReplacement fluid as required • Blood flow 50-200 ml/min • UF rate 10-60 ml/min • Dialysate flow 15-30 ml/min • Replacement 10-30 ml/min • High flux membranes • Extended period up to weeks • DiffusiveDiffusive & convective& convective solute clearance • Countercurrent dialysate • UF exceeds volume control • ReplacementReplacement fluid as required • Blood flow 50-200 ml/min • UF rate 10-60 ml/min • Dialysate flow 15-30 ml/min • Replacement 10-30 ml/min
- 31. SLED(D) & SLED(D)-F: Hybrid therapy • Conventional dialysis equipment • Online dialysis fluid preparation • ExcellentExcellent small molecule detoxification • Cardiovascular stability as good as CRRT • Reduced anticoagulation requirement • 11 hrs SLED comparable to 23 hrs CVVH • Decreased costs compared to CRRT • Phosphate supplementation required Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39 Berbece, AN & Richardson, RMA. Kidney International 2006; 70: 963-968
- 32. Kinetic Modelling ofSolute Clearance CVVH (predilution) Daily IHD SLED Urea TAC (mg/ml) 40.3 64.6 43.4 Urea EKR (ml/min) 33.8 21.1 31.3 Inulin TAC (mg/L) 25.4 55.5 99.4 Inulin EKR (ml/min) 11.8 5.4 3.0 β2 microglobulin TAC (mg/L) 9.4 24.2 40.3 β2 microglobulin EKR (ml/min) 18.2 7.0 4.2 TAC = time-averaged concentration (from area under concentration-time curve) EKR = equivalent renal clearanceEKR = equivalent renal clearance Inulin represents middle molecule and β2 microglobulin large molecule. CVVH has marked effects on middle and large molecule clearance not seen with IHD/SLED SLED and CVVH have equivalent small molecule clearance Daily IHD has acceptable small molecule clearance Liao, Z et al. Artificial Organs 2003; 27: 802-807
- 33. Uraemia Control Liao, Zet al. Artificial Organs 2003; 27: 802-807
- 34. Large molecule clearance Liao,Z et al. Artificial Organs 2003; 27: 802-807
- 35. Comparison of IHDand CVVH John, S & Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464
- 36. Beyond renalrenal replacement… RRTas blood purificationblood purification therapytherapy Beyond renalrenal replacement… RRT as blood purificationblood purification therapytherapy
- 37. Extracorporeal Blood Purification Therapy(EBT) Intermittent Continuous TPETPE Therapeutic plasma exchange HVHF High volume haemofiltration UHVHFUHVHF Ultra-high volume haemofiltration PHVHFPHVHF Pulsed high volume haemofiltration CPFACPFA Coupled plasma filtration and adsorption
- 38. Peak Concentration Hypothesis •Removes cytokines from blood compartment during pro-inflammatory phase of sepsis • Assumes blood cytokine level needs to fallAssumes blood cytokine level needs to fall • Assumes reduced “free” cytokine levels leads to decreased tissue effects and organ failure • Favours therapy such as HVHF, UHVHF, CPFA • But tissue/interstitial cytokine levels unknownunknown • Removes cytokines from blood compartment during pro-inflammatory phase of sepsis • Assumes blood cytokine level needs to fallAssumes blood cytokine level needs to fall • Assumes reduced “free” cytokine levels leads to decreased tissue effects and organ failure • Favours therapy such as HVHF, UHVHF, CPFA • But tissue/interstitial cytokine levels unknownunknown Ronco, C & Bellomo, R. Artificial Organs 2003; 27: 792-801
- 39. Threshold Immunomodulation Hypothesis •More dynamic view of cytokine system • Mediators and pro-mediators removed from blood to alter tissue cytokine levels but bloodbut blood level does not need to falllevel does not need to fall • ? pro-inflammatory processes halted when cytokines fall to “threshold” level • We don’t know when such a point is reached • More dynamic view of cytokine system • Mediators and pro-mediators removed from blood to alter tissue cytokine levels but bloodbut blood level does not need to falllevel does not need to fall • ? pro-inflammatory processes halted when cytokines fall to “threshold” level • We don’t know when such a point is reached Honore, PM & Matson, JR. Critical Care Medicine 2004; 32: 896-897
- 40. Mediator Delivery Hypothesis •HVHF with high incoming fluid volumes (3-6 L/hour) increases lymph flow 20-40 times • “Drag” of mediators and cytokines with lymph • Pulls cytokines from tissues to blood for removal and tissue levels fall • High fluid exchange is key • HVHF with high incoming fluid volumes (3-6 L/hour) increases lymph flow 20-40 times • “Drag” of mediators and cytokines with lymph • Pulls cytokines from tissues to blood for removal and tissue levels fall • High fluid exchange is key Di Carlo, JV & Alexander, SR. Int J Artif Organs 2005; 28: 777-786
- 41. High Volume Hemofiltration •May reduce unboundunbound fraction of cytokines • Removes – endothelinendothelin-II (causes early pulm hypertension in sepsis) – endogenous cannabinoidsendogenous cannabinoids (vasoplegic in sepsis) – myodepressant factormyodepressant factor – PAI-IPAI-I so may eventually reduce DIC • Reduces post-sepsis immunoparalysis (CARS) • Reduces inflammatory cell apoptosis • Human trials probably using too low a dosetoo low a dose (40 ml/kg/hour vs 100+ ml/kg/hour in animals) • May reduce unboundunbound fraction of cytokines • Removes – endothelinendothelin-II (causes early pulm hypertension in sepsis) – endogenous cannabinoidsendogenous cannabinoids (vasoplegic in sepsis) – myodepressant factormyodepressant factor – PAI-IPAI-I so may eventually reduce DIC • Reduces post-sepsis immunoparalysis (CARS) • Reduces inflammatory cell apoptosis • Human trials probably using too low a dosetoo low a dose (40 ml/kg/hour vs 100+ ml/kg/hour in animals)
- 42. CRRT, Haemodynamics &Outcome • 114 unstable (pressors or MAP < 60) patients • 55 stable (no pressors or MAP > 60) patients • Responders = 20% fall in NA requirement or 20% rise in MAP (without change in NA) • Overall responder mortality 30%, non-responder mortality 74.7% (p < 0.001) • In unstable patients responder mortality 30% vs non-responder mortality 87% (p < 0.001) • Haemodynamic improvement after 24 hours CRRT is a strong predictor of outcome • 114 unstable (pressors or MAP < 60) patients • 55 stable (no pressors or MAP > 60) patients • Responders = 20% fall in NA requirement or 20% rise in MAP (without change in NA) • Overall responder mortality 30%, non-responder mortality 74.7% (p < 0.001) • In unstable patients responder mortality 30% vs non-responder mortality 87% (p < 0.001) • Haemodynamic improvement after 24 hours CRRT is a strong predictor of outcome Herrera-Gutierrez, ME et al. ASAIO Journal 2006; 52: 670-676
- 43. Common Antibiotics andCRRT These effects will be even more dramatic with HVHF Honore, PM et al. Int J Artif Organs 2006; 29: 649-659
- 44. Towards Targeted Therapy? Non-septicARFNon-septic ARF Septic ARFSeptic ARF Cathecholamine resistant septic shock Cathecholamine resistant septic shock Daily IHDDaily IHD Daily SLEDDDaily SLEDD CVVHD/F ? doseCVVHD/F ? dose CVVH >> 35ml/kg/hour ? 50-70 ml/kg/hour CVVH >> 35ml/kg/hour ? 50-70 ml/kg/hour CVVH @ 35ml/kg/hour CVVH @ 35ml/kg/hour Daily IHD?Daily IHD? Daily SLEDD?Daily SLEDD? HVHF 60-120 ml/kg/hour for 96 hours HVHF 60-120 ml/kg/hour for 96 hours PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH >> 35 ml/kg/hour PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH >> 35 ml/kg/hour EBTEBTEBTEBT Honore, PM et al. Int J Artif Organs 2006; 29: 649-659 Cerebral oedemaCerebral oedema
- 45. “You should listento your heart, and not the voices in your head” Marge Simpson