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Similar to Renal replacement therapy in the ICU
Renal replacement therapy in the ICU
- 1. Renal ReplacementRenal Replacement Therapiesin Critical CareTherapies in Critical Care Dr. Andrew FergusonDr. Andrew Ferguson Consultant in Anaesthesia & Intensive Care MedicineConsultant in Anaesthesia & Intensive Care Medicine Craigavon Area HospitalCraigavon Area Hospital
- 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 mmol/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 mmol/L with acute rise > 44 mmol/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 206; 29: 649-659 Cerebral oedemaCerebral oedema
- 45. “You should listento your heart, and not the voices in your head” Marge Simpson
- 46.