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

2. Indications of RRT

3. Indications for acute dialysis JT 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 > 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,
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 Citrate 136.
Acid Citrate Dextrose (ACD-A)
Dextrose 2.45%
Citric acid 0.8%. Trisodium Citrate 2.2%,
Na Citrate 113.
ACD-B
Dextrose 1.5%
Na 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 and dose acute RRT to optimize patient outcomes?

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

32. (AKI a mediator of disease)
“Patient are dying of renal failure, rather than with renal 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 , 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, cohort study
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 to

36. Metnitz et al.
Usual predictors of mortality e.g. age, illness severity, septic or cardiogenic shock, etc
Case-control analysis to examine independent association between AKI (defined as requiring RRT) and mortality risk
Exposure group (AKI) versus matched control group by 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 methods to quantify dose have successfully related dose to outcomes in iHD
Studies using effluent (filtration) rate to quantify dose have successfully related dose to outcomes in CRRT

41. Renal Under-Replacement?
Evanson et al, AJKD, Vol 32, pp , 1998
Tapolyai et al, JASN, Vol 5, pp 530A, 1994
Schiffl et al, NEJM, Vol 346, pp , 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: , 2001
Uchino et al, Intensive Care Med 29: , 2000
Kumar et al. IJAO 27: , 2004

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

58. Paganini et al. Blood Purif, Vol 19, pp 239-244, 2001

59. Patient Related Factors
A smaller acute RRT dose than desired is both prescribed and delivered to AKI patients
AKI patients are not in steady state

60. Patient Related Factors
AKI patients generate more uremic toxins than expected (higher G)
AKI patients have a greater pool (higher V) of uremic toxins than expected for unknown reasons, and one should account for this pool by formal UKM rather than anthropometry

61. Patient Related Factors
Solute compartmentalization may be a little (but not a lot) greater in AKI than ESKF
Solute compartmentalization increases with efficiency of solute removal (i.e. important for iHD, not for hybrid or CRRT)
Estimation of eKt/V or dpKt/V for iHD is necessary, utilizing using the Daugirdas, Garred, or Tattersall rate equations
Leblanc et al. Adv Ren Replace Ther, Vol 2, pp , 1995
Paganini et al. Blood Purif, Vol 19, pp , 2001
Marshall et al, Am J Kidney Dis, Vol 35, pp. A19, 2000.

62. Treatment Related Factors
Catheter performance
Dialyzer/filter performance