CCM Specialty Board Tutorial RRT in ICU

1. CCM Specialty Board TutorialRRT in ICU Yan Wing Wa Department of Intensive Care PYNEH 22 April 2008

2. Indications of RRT

3. Indications for acute dialysisJT Daugirdas, Handbook of Dialysis 3rd Ed. • Impaired RFT (Creatinine Cl < 20-25ml/min/1.73m2) • Symptoms of Uremia, e.g. GI upset, dec. consciousness, pericarditis or bleeding diathesis • Refractory or progressive fluid overload • Uncontrollable hyperkalemia • Severe metabolic acidosis • Steady worsening of renal function with • Urea > 25-36 mmol/l or • Creatinine Cl < 15-20ml/min

4. R. Bellomo, C. Ronco Kidney International,1998,53,Suppl 66, p106-9

5. Anticoagulation strategies

6. Extracorporeal circuit patency • Systemic anticoagulation • No anticoagulation • Regional anticoagulation

7. Systemic anticoagulation Oudemans-vanStraaten etal, Intensive Care Med 2006,32,188-202 • Unfractionated Heparin (HIT 2.6%) • LMWH (HIT 0.2%) • Heparinoids – Danaparoid (cross react with HIT Abs in ~10%) • Factor Xa inhibitor – Fondaparinux • Direct thrombin inhibitor • r-Hirudin • Argatroban • Dermatan sulfate • Prostacyclin & prostaglandin E1(hypotension) • Protease inhibitors – nafamostat mesilate (anaphylaxis, only a/v in Japan)

8. No anticoagulation • For patients in whom systemic anticoagulation is contraindicated • Frequent circuit clotting

9. Regional anticoagulation • Regional anticoagulation using UFH with protamine • UFH side effect (HIT) and Protamine side effects (platelet and inflammatory mediators activation, hypotension & pulmonary hypertension)

10. Regional citrate anticoagulation (RCA) Indicated in patients with bleeding risk • thrombocytopenia • coagulopathy • pericarditis • recent surgery with bleeding complications • recent surgery after which bleeding would be very dangerous • brain surgery • vascular or cardiac surgery • renal transplant

11. The B.E.S.T. Kidney Study

13. Citrate Metabolism • Half-life 5mins • Metabolized by liver, kidney & muscle • 1 citrate molecule will form 3 HCO3- molecules

14. Citrate Formulations • Trisodium Citrate 4% • Na 408. Citrate 136. • Acid Citrate Dextrose (ACD-A) • Dextrose 2.45% • Citric acid 0.8%. Trisodium Citrate 2.2%, • Na 224. Citrate 113. • ACD-B • Dextrose 1.5% • Na 135. Citrate 68.

16. Longer Filter Life

17. Less Activation

18. Less Transfusion

19. Complications of RCA • Related to calcium chelation/replacement • Hypocalcaemia • Hypercalcaemia • Skin necrosis due to extravasation • Related to citrate metabolism • Metabolic alkalosis • Metabolic acidosis • Related to sodium content • Hypernatraemia • Hyponatraemia • Related to formulation • Electrolytes imbalance • Haemolysis

21. Complications of RCA • Related to calcium chelation/replacement • Hypocalcaemia • Hypercalcaemia • Skin necrosis due to extravasation • Related to citrate metabolism • Metabolic alkalosis • Metabolic acidosis • Related to sodium content • Hypernatraemia • Hyponatraemia • Related to formulation • Electrolytes imbalance • Haemolysis

22. Complications of RCA • Related to calcium chelation/replacement • Hypocalcaemia • Hypercalcaemia • Skin necrosis due to extravasation • Related to citrate metabolism • Metabolic alkalosis • Metabolic acidosis • Related to sodium content • Hypernatraemia • Hyponatraemia • Related to formulation • Electrolytes imbalance • Haemolysis

23. Citrate toxicity

24. Dose of RRT

25. Q. How should one prescribe anddose acute RRT to optimize patientoutcomes?

26. Pesacreta et al. • 27 academic centres involved with the Acute Renal Failure Trial Network (ATN) study • Cross sectional survey of acute RRT prescribing practices circa 2003-2004 • Do practitioners dose acute RRT? Pesacreta etal, J Am Soc Nephrol, Vol 15, pp 350A, 2004

27. Pesacreta et al. iHD • 31% of respondents targeted URR ≥0.65 • 7% of respondents targeted Kt/V≥1.2 • 56% of respondents did not target any specific iHD dose • Fewer than one-quarter of respondents routinely assess delivered iHD dose Pesacreta etal, J Am Soc Nephrol, Vol 15, pp 350A, 2004

28. Pesacreta et al. CRRT • 14% of respondents dosed CRRT indexed to weight (more than three-quarters of these respondents prescribed an effluent rate of ≥35mL/kg/hour) • 66% of remaining respondents prescribed fixed effluent rates of ≤2 L/hour • Remainder did not target any specific dose Pesacreta etal, J Am Soc Nephrol, Vol 15, pp 350A, 2004

29. Overview • Revisiting of dose and outcomes • Patient and treatment related factors affecting dose prescription and delivery • Therapy-specific dose-outcome data • Approach to prescription and quantification of acute RRT dose

30. Overview • Revisiting of dose and outcomes • Patient and treatment related factors affecting dose prescription and delivery • Therapy-specific dose-outcome data • Approach to prescription and quantification of acute RRT dose

31. “Patient are dying withrenal failure, rather than ofrenal failure in the ICU” (AKI an indicator of disease)

32. “Patient are dying ofrenal failure, rather than withrenal failure in the ICU” (AKI a mediator of disease)

33. AKI and Mortality Risk • AKI in critically ill patients still associated with a disappointingly high mortality risk • “Corrected”mortality is that attributable to AKI rather than the underlying illness (Kennedy,1973) • “Corrected” mortality minimal for low illness severity, ~50% at the severe end • Main contributors to “corrected” mortality are haemorrhage, non-resolving shock and infection Uchino et al, JAMA, Vol 294, pp 813-818, 2005 Kennedy et al, QJM, Vol 42, pp 73-86, 1973 Liano et al, Vol 63, S16-S24, 1998

35. Metnitz et al. • Prospective, observational, cohortstudy • Is there as independent association between AKI and patient mortality risk? • 30 medical, surgical, and mixed ICUs in • Austria using a national ICU registry • 17,126 consecutive patients • 01.03.98 to 28.02.00

36. Metnitz et al. • Usual predictors of mortality e.g. age, illness severity, septic or cardiogenic shock, etc • Case-controlanalysis to examine independent association between AKI (defined as requiring RRT) and mortality risk • Exposure group (AKI) versus matched control groupby age, SAPS II, and ICU

37. Metnitz et al.

38. How should one prescribe and dose acute RRT to optimize patient outcomes? Individually, according to the requirements of the patient

39. Overview • Revisiting of dose and outcomes • Patient and treatment related factors affecting dose prescription and delivery • Therapy-specific dose-outcome data • Approach to prescription and quantification of acute RRT dose

40. Expressions of Acute RRT Dose • Studies using urea kinetic methodsto quantify dose have successfully related dose to outcomes in iHD • Studies using effluent (filtration) rateto quantify dose have successfully related dose to outcomes in CRRT

41. Renal Under-Replacement? Evanson et al, AJKD, Vol 32, pp 731-738, 1998 Tapolyai et al, JASN, Vol 5, pp 530A, 1994 Schiffl et al, NEJM, Vol 346, pp 305-310, 2002 Paganini et al, AJKD, Vol 28, pp S81-S89, 1996 Lo et al, JASN, Vol 8, pp173A, 1997

42. Renal Under-Replacement? Venkataraman et al, J Crit Care, 2002 Ronco et al, Lancet 356:26-30, 2000 Mehta et al, Kidney Int 60:1154-1163, 2001 Uchino et al, Intensive Care Med 29:575-578, 2000 Kumar et al. IJAO 27:371-379, 2004

46. Chima et al, JASN, Vol 3, pp 1516-21, 1993 Clark et al, Adv Ren Replace Ther, Vol 4, pp 64-71, 1997