1 / 45

Renal Replacement Therapies in Critical Care

Renal Replacement Therapies in Critical Care. Dr. Andrew Ferguson Consultant in Intensive Care Medicine & Anaesthesia Craigavon Area Hospital, United Kingdom. Where are we - too many questions?. What therapy should we use? When should we start it? What are we trying to achieve?

wells
Download Presentation

Renal Replacement Therapies in Critical Care

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Renal Replacement Therapies in Critical Care Dr. Andrew Ferguson Consultant in Intensive Care Medicine & Anaesthesia Craigavon Area Hospital, United Kingdom

  2. Where are we - too many questions? • What therapy should we use? • When should we start it? • What are we trying to achieve? • How much therapy is enough? • When do we stop/switch? • Can we improve outcomes? Does the literature help us?

  3. Overview • Impact of Acute Kidney Injury in the ICU • Dose-outcome relationships & IRRT v CRRT • Mechanisms of solute clearance • Therapies in brief • IRRT, CRRT & Hybrid therapies e.g. SLEDD • Solute clearance with IRRT v CRRT v SLEDD • Extracorporeal blood purification in sepsis • Putting it together – making a rational choice

  4. AKI classification systems 1: RIFLE

  5. AKI classification systems 2: AKIN Patients receiving RRT are Stage 3 regardless of creatinine or urine output

  6. Acute Kidney Injury in 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 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 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 • There 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 nodefinitive evidence forsuperiority of one therapy over another, and wide practice variation exists*** • Accepted indications for RTT vary • No 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 in IRRT p = 0.01 p = 0.001 Schiffl, H et al. NEJM 2002; 346: 305-310

  11. Therapy Dose in CVVH 45 ml/kg/hr 35 ml/kg/hr 25 ml/kg/hr Ronco, C et al. Lancet 2000; 355: 26-30

  12. Outcome with IRRT vs 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 “there is insufficient evidence to establish whether CRRT is associated with improved survival in critically ill patients with ARF when compared with IRRT” Kellum, J et al. Intensive Care Med 2002; 28: 29-37

  13. Outcome with IRRT vs CRRT (2) • No mortality difference between therapies • No renal recovery difference between therapies • Unselected patient populations • Majority of studies were unpublished Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885

  14. Outcome with IRRT vs CRRT (3) Vinsonneau, S et al. Lancet 2006; 368: 379-385

  15. Proposed Indications for RRT • 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 the available data

  17. The Ideal Renal Replacement 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 (?)

  18. Solute Clearance - Diffusion • 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 Replacement Techniques Intermittent Hybrid Continuous IHD Intermittent haemodialysis SLEDD Sustained (or slow) low efficiency daily dialysis CVVH Continuous veno-venous haemofiltration IUF Isolated Ultrafiltration CVVHD Continuous veno-venous haemodialysis SLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVHDF Continuous veno-venous haemodiafiltration SCUF Slow continuous ultrafiltration

  21. Intermittent Therapies - PRO

  22. Intermittent Therapies - CON

  23. Intradialytic Hypotension: Risk Factors • LVH with diastolic dysfunction or 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) 2005 National Kidney Foundation K/DOQI GUIDELINES

  25. Continuous Therapies - PRO

  26. Continuous Therapies - CON

  27. SCUF • High flux membranes • Up to 24 hrs per day • Objective VOLUME control • Not suitable for solute clearance • Blood flow 50-200 ml/min • UF rate 2-8 ml/min

  28. CA/VVH • Extended duration up to weeks • High flux membranes • Mainly convective clearance • UF > volume control amount • Excess UF replaced • Replacement pre- or post-filter • Blood flow 50-200 ml/min • UF rate 10-60 ml/min

  29. CA/VVHD • Mid/high flux membranes • Extended period up to weeks • Diffusive 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 flux membranes • Extended period up to weeks • Diffusive& convective solute • clearance • Countercurrent dialysate • UF exceeds volume control • Replacement 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 • Excellent 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 of Solute Clearance TAC = time-averaged concentration (from area under concentration-time curve) EKR = equivalent renal clearance Inulin represents middle molecule and b2 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, 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 & 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) Continuous Intermittent 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 • Removes cytokines from blood compartment during pro-inflammatory phase of sepsis • Assumes 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 unknown 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 blood level 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 Di Carlo, JV & Alexander, SR. Int J Artif Organs 2005; 28: 777-786

  41. High Volume Hemofiltration • May reduce unbound fraction of cytokines • Removes • endothelin-I (causes early pulm hypertension in sepsis) • endogenous cannabinoids (vasoplegic in sepsis) • myodepressant factor • PAI-I so may eventually reduce DIC • Reduces post-sepsis immunoparalysis (CARS) • Reduces inflammatory cell apoptosis • Human trials probably using too 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 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 IHD? HVHF 60-120 ml/kg/hour for 96 hours Daily SLEDD Daily SLEDD? CVVHD/F ? dose EBT PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH > 35 ml/kg/hour CVVH @ 35ml/kg/hour CVVH > 35ml/kg/hour ? 50-70 ml/kg/hour Cerebral oedema Honore, PM et al. Int J Artif Organs 2006; 29: 649-659

  45. “You should listen to your heart, and not the voices in your head” Marge Simpson

More Related