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Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
Renal replacement therapy in intensive care
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Renal replacement therapy in intensive care

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  • 1. Dr. Andrew Ferguson Consultant in Anaesthesia & Intensive Care Medicine Craigavon Area Hospital Renal Replacement Therapies in Critical Care
  • 2. Where are we - too many questions? Does the literature help us? <ul><li>What therapy should we use? </li></ul><ul><li>When should we start it? </li></ul><ul><li>What are we trying to achieve? </li></ul><ul><li>How much therapy is enough? </li></ul><ul><li>When do we stop/switch? </li></ul><ul><li>Can we improve outcomes? </li></ul>
  • 3. Overview
  • 4. AKI classification systems 1: RIFLE
  • 5. AKI classification systems 2: AKIN Patients receiving RRT are Stage 3 regardless of creatinine or urine output Stage Creatinine criteria Urine output criteria 1 1.5 - 2 x baseline (or rise &gt; 26.4 mmol/L) &lt; 0.5 ml/kg/hour for &gt; 6 hours 2 &gt;2 - 3 x baseline &lt; 0.5 ml/kg/hour for &gt; 12 hours 3 &gt; 3 x baseline (or &gt; 354 mmol/L with acute rise &gt; 44 mmol/L) &lt; 0.3 ml/kg/hour for 24 hours or anuria for 12 hours
  • 6. Acute Kidney Injury in the ICU * Brivet, FG et al . Crit Care Med 1996; 24: 192-198 ** Metnitz, PG et al . Crit Care Med 2002; 30: 2051-2058 <ul><li>AKIis common: 3-35%* of admissions </li></ul><ul><li>AKI is associated with increased mortality </li></ul><ul><li>“ Minor” rises in Cr associated with worse outcome </li></ul><ul><li>AKI developing after ICU admission (late) is associated with worse outcome than AKI at admission ( APACHE underestimates ROD ) </li></ul><ul><li>AKI requiring RRT occurs in about 4-5% of ICU admissions and is associated with worst mortality risk ** </li></ul>
  • 7. Mortality by AKI Severity (1) Clermont, G et al . Kidney International 2002; 62: 986-996
  • 8. Mortality by AKI Severity (2) Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409
  • 9. RRT for Acute Renal Failure *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 <ul><li>There is some evidence for a relationship between higher therapy dose and better outcome, at least up to a point </li></ul><ul><li>This is true for IHD* and for CVVH** </li></ul><ul><li>There is no definitive evidence for superiority of one therapy over another, and wide practice variation exists*** </li></ul><ul><li>Accepted indications for RTT vary </li></ul><ul><li>No definitive evidence on timing of RRT </li></ul>
  • 10. Therapy Dose in IRRT p = 0.01 p = 0.001 Schiffl, H et al . NEJM 2002; 346: 305-310
  • 11. Therapy Dose in CVVH 25 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr Ronco, C et al . Lancet 2000; 355: 26-30
  • 12. Outcome with IRRT vs CRRT (1) <ul><li>Trial quality low : many non-randomized </li></ul><ul><li>Therapy dosing variable </li></ul><ul><li>Illness severity variable or details missing </li></ul><ul><li>Small numbers </li></ul><ul><li>Uncontrolled technique, membrane </li></ul><ul><li>Definitive trial would require 660 patients in each arm! </li></ul><ul><li>Unvalidated instrument for sensitivity analysis </li></ul>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 IRRT vs CRRT (2) Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885 <ul><li>No mortality difference between therapies </li></ul><ul><li>No renal recovery difference between therapies </li></ul><ul><li>Unselected patient populations </li></ul><ul><li>Majority of studies were unpublished </li></ul>
  • 14. Outcome with IRRT vs CRRT (3) Vinsonneau, S et al . Lancet 2006; 368: 379-385
  • 15. Proposed Indications for RRT Lameire, N et al . Lancet 2005; 365: 417-430 <ul><li>Oliguria &lt; 200ml/12 hours </li></ul><ul><li>Anuria &lt; 50 ml/12 hours </li></ul><ul><li>Hyperkalaemia &gt; 6.5 mmol/L </li></ul><ul><li>Severe acidaemia pH &lt; 7.0 </li></ul><ul><li>Uraemia &gt; 30 mmol/L </li></ul><ul><li>Uraemic complications </li></ul><ul><li>Dysnatraemias &gt; 155 or &lt; 120 mmol/L </li></ul><ul><li>Hyper/(hypo)thermia </li></ul><ul><li>Drug overdose with dialysable drug </li></ul>
  • 16. Implications of the available data
  • 17. The Ideal Renal Replacement Therapy <ul><li>Allows control of intra/extravascular volume </li></ul><ul><li>Corrects acid-base disturbances </li></ul><ul><li>Corrects uraemia &amp; effectively clears “toxins” </li></ul><ul><li>Promotes renal recovery </li></ul><ul><li>Improves survival </li></ul><ul><li>Is free of complications </li></ul><ul><li>Clears drugs effectively (?) </li></ul>
  • 18. Solute Clearance - Diffusion <ul><li>Small (&lt; 500d) molecules cleared efficiently </li></ul><ul><li>Concentration gradient critical </li></ul><ul><li>Gradient achieved by countercurrent flow </li></ul><ul><li>Principal clearance mode of dialysis techniques </li></ul>
  • 19. Solute Clearance – Ultrafiltration &amp; Convection (Haemofiltration) * In post-dilution haemofiltration <ul><li>Water movement “drags” solute across membrane </li></ul><ul><li>At high UF rates (&gt; 1L/hour) enough solute is dragged to produce significant clearance </li></ul><ul><li>Convective clearance dehydrates the blood passing through the filter </li></ul><ul><li>If filtration fraction &gt; 30% there is high risk of filter clotting* </li></ul><ul><li>Also clears larger molecular weight substances (e.g. B12, TNF, inulin) </li></ul>
  • 20. Major Renal Replacement Techniques Intermittent Continuous Hybrid IHD Intermittent haemodialysis IUF Isolated Ultrafiltration SLEDD Sustained (or slow) low efficiency daily dialysis SLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVH Continuous veno-venous haemofiltration CVVHD Continuous veno-venous haemodialysis CVVHDF Continuous veno-venous haemodiafiltration SCUF Slow continuous ultrafiltration
  • 21. Intermittent Therapies - PRO
  • 22. Intermittent Therapies - CON
  • 23. Intradialytic Hypotension: Risk Factors <ul><li>LVH with diastolic dysfunction or LV systolic dysfunction / CHF </li></ul><ul><li>Valvular heart disease </li></ul><ul><li>Pericardial disease </li></ul><ul><li>Poor nutritional status / hypoalbuminaemia </li></ul><ul><li>Uraemic neuropathy or autonomic dysfunction </li></ul><ul><li>Severe anaemia </li></ul><ul><li>High volume ultrafiltration requirements </li></ul><ul><li>Predialysis SBP of &lt;100 mm Hg </li></ul><ul><li>Age 65 years + </li></ul><ul><li>Pressor requirement </li></ul>
  • 24. Managing Intra-dialytic Hypotension <ul><li>Dialysate temperature modelling </li></ul><ul><ul><ul><li>Low temperature dialysate </li></ul></ul></ul><ul><li>Dialysate sodium profiling </li></ul><ul><ul><ul><li>Hypertonic Na at start decreasing to 135 by end </li></ul></ul></ul><ul><ul><ul><li>Prevents plasma volume decrease </li></ul></ul></ul><ul><li>Midodrine if not on pressors </li></ul><ul><li>UF profiling </li></ul><ul><li>Colloid/crystalloid boluses </li></ul><ul><li>Sertraline (longer term HD) </li></ul>2005 National Kidney Foundation K/DOQI GUIDELINES
  • 25. Continuous Therapies - PRO
  • 26. Continuous Therapies - CON
  • 27. SCUF <ul><li>High flux membranes </li></ul><ul><li>Up to 24 hrs per day </li></ul><ul><li>Objective VOLUME control </li></ul><ul><li>Not suitable for solute clearance </li></ul><ul><li>Blood flow 50-200 ml/min </li></ul><ul><li>UF rate 2-8 ml/min </li></ul>
  • 28. CA/VVH <ul><li>Extended duration up to weeks </li></ul><ul><li>High flux membranes </li></ul><ul><li>Mainly convective clearance </li></ul><ul><li>UF &gt; volume control amount </li></ul><ul><li>Excess UF replaced </li></ul><ul><li>Replacement pre- or post-filter </li></ul><ul><li>Blood flow 50-200 ml/min </li></ul><ul><li>UF rate 10-60 ml/min </li></ul>
  • 29. CA/VVHD <ul><li>Mid/high flux membranes </li></ul><ul><li>Extended period up to weeks </li></ul><ul><li>Diffusive solute clearance </li></ul><ul><li>Countercurrent dialysate </li></ul><ul><li>UF for volume control </li></ul><ul><li>Blood flow 50-200 ml/min </li></ul><ul><li>UF rate 1-8 ml/min </li></ul><ul><li>Dialysate flow 15-60 ml/min </li></ul>
  • 30. CVVHDF <ul><li>High flux membranes </li></ul><ul><li>Extended period up to weeks </li></ul><ul><li>Diffusive &amp; convective solute </li></ul><ul><li>clearance </li></ul><ul><li>Countercurrent dialysate </li></ul><ul><li>UF exceeds volume control </li></ul><ul><li>Replacement fluid as required </li></ul><ul><li>Blood flow 50-200 ml/min </li></ul><ul><li>UF rate 10-60 ml/min </li></ul><ul><li>Dialysate flow 15-30 ml/min </li></ul><ul><li>Replacement 10-30 ml/min </li></ul>
  • 31. SLED(D) &amp; SLED(D)-F : Hybrid therapy Fliser, T &amp; Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39 Berbece, AN &amp; Richardson, RMA. Kidney International 2006; 70: 963-968 <ul><li>Conventional dialysis equipment </li></ul><ul><li>Online dialysis fluid preparation </li></ul><ul><li>Excellent small molecule detoxification </li></ul><ul><li>Cardiovascular stability as good as CRRT </li></ul><ul><li>Reduced anticoagulation requirement </li></ul><ul><li>11 hrs SLED comparable to 23 hrs CVVH </li></ul><ul><li>Decreased costs compared to CRRT </li></ul><ul><li>Phosphate supplementation required </li></ul>
  • 32. Kinetic Modelling of Solute Clearance TAC = time-averaged concentration (from area under concentration-time curve) EKR = equivalent renal clearance Inulin represents middle molecule and  2 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 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  2 microglobulin TAC (mg/L) 9.4 24.2 40.3  2 microglobulin EKR (ml/min) 18.2 7.0 4.2
  • 33. Uraemia Control Liao, Z et al . Artificial Organs 2003; 27: 802-807
  • 34. Large molecule clearance Liao, Z et al . Artificial Organs 2003; 27: 802-807
  • 35. Comparison of IHD and CVVH John, S &amp; Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464
  • 36. Beyond renal replacement… RRT as blood purification therapy
  • 37. Extracorporeal Blood Purification Therapy (EBT) Intermittent Continuous TPE Therapeutic plasma exchange HVHF High volume haemofiltration UHVHF Ultra-high volume haemofiltration PHVHF Pulsed high volume haemofiltration CPFA Coupled plasma filtration and adsorption
  • 38. Peak Concentration Hypothesis <ul><li>Removes cytokines from blood compartment during pro-inflammatory phase of sepsis </li></ul><ul><li>Assumes blood cytokine level needs to fall </li></ul><ul><li>Assumes reduced “free” cytokine levels leads to decreased tissue effects and organ failure </li></ul><ul><li>Favours therapy such as HVHF, UHVHF, CPFA </li></ul><ul><li>But tissue/interstitial cytokine levels unknown </li></ul>Ronco, C &amp; Bellomo, R. Artificial Organs 2003; 27: 792-801
  • 39. Threshold Immunomodulation Hypothesis <ul><li>More dynamic view of cytokine system </li></ul><ul><li>Mediators and pro-mediators removed from blood to alter tissue cytokine levels but blood level does not need to fall </li></ul><ul><li>? pro-inflammatory processes halted when cytokines fall to “threshold” level </li></ul><ul><li>We don’t know when such a point is reached </li></ul>Honore, PM &amp; Matson, JR. Critical Care Medicine 2004; 32: 896-897
  • 40. Mediator Delivery Hypothesis <ul><li>HVHF with high incoming fluid volumes (3-6 L/hour) increases lymph flow 20-40 times </li></ul><ul><li>“ Drag” of mediators and cytokines with lymph </li></ul><ul><li>Pulls cytokines from tissues to blood for removal and tissue levels fall </li></ul><ul><li>High fluid exchange is key </li></ul>Di Carlo, JV &amp; Alexander, SR. Int J Artif Organs 2005; 28: 777-786
  • 41. High Volume Hemofiltration <ul><li>May reduce unbound fraction of cytokines </li></ul><ul><li>Removes </li></ul><ul><ul><li>endothelin - I (causes early pulm hypertension in sepsis) </li></ul></ul><ul><ul><li>endogenous cannabinoids (vasoplegic in sepsis) </li></ul></ul><ul><ul><li>myodepressant factor </li></ul></ul><ul><ul><li>PAI-I so may eventually reduce DIC </li></ul></ul><ul><li>Reduces post-sepsis immunoparalysis (CARS) </li></ul><ul><li>Reduces inflammatory cell apoptosis </li></ul><ul><li>Human trials probably using too low a dose (40 ml/kg/hour vs 100+ ml/kg/hour in animals) </li></ul>
  • 42. CRRT, Haemodynamics &amp; Outcome <ul><li>114 unstable (pressors or MAP &lt; 60) patients </li></ul><ul><li>55 stable (no pressors or MAP &gt; 60) patients </li></ul><ul><li>Responders = 20% fall in NA requirement or 20% rise in MAP (without change in NA) </li></ul><ul><li>Overall responder mortality 30%, non-responder mortality 74.7% (p &lt; 0.001) </li></ul><ul><li>In unstable patients responder mortality 30% vs non-responder mortality 87% (p &lt; 0.001) </li></ul><ul><li>Haemodynamic improvement after 24 hours CRRT is a strong predictor of outcome </li></ul>Herrera-Gutierrez, ME et al. ASAIO Journal 2006; 52: 670-676
  • 43. Common Antibiotics and CRRT 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-septic ARF Septic ARF Cathecholamine resistant septic shock Daily IHD Daily SLEDD CVVHD/F ? dose CVVH &gt; 35ml/kg/hour ? 50-70 ml/kg/hour CVVH @ 35ml/kg/hour Daily IHD? Daily SLEDD? HVHF 60-120 ml/kg/hour for 96 hours PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH &gt; 35 ml/kg/hour EBT Honore, PM et al . Int J Artif Organs 206; 29: 649-659 Cerebral oedema
  • 45. Marge Simpson “ You should listen to your heart, and not the voices in your head”
  • 46. Questions?

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