1. Renal Replacement Therapy in Critical Illness Silverstar 2005 Jim Kutsogiannis Terry Paul Zoheir Bshouty

2. Grades of Recommendations Gyatt G. Chest 2004;126:179S-187S Grade: Clarity Risk/Benefit Methodological Strength of Supporting Evidence Implications 1A Clear RCTs without important limitations.Strong recommendations; can apply to most patients in most circumstances without reservation. 1C+ Clear No RCTs but strong RCT results can be unequivocally extrapolated, or overwhelming evidence from observational studies. Strong recommendation; can apply to most patients in most circumstances. 1B Clear RCTs with important limitations.(inconsistent results, methodological flaws: unblinded, subjective outcomes, bias) Strong recommendations; likely to apply to most patients. 1C Clear Observational studies.Intermediate strength recommendations; may change when stronger evidence is available.

3. Grades of Recommendations Gyatt G. Chest 2004;126:179S-187S Grade : Clarity Risk/Benefit Methodological Strength of Supporting Evidence Implications 2A Unclear RCTs without important limitations.Intermediate-strength recommendation; best action may differ depending on circumstances or patients’ or societal values. 2C+ Unclear No RCTs but strong RCT results can be unequivocally extrapolated, or overwhelming evidence from observational studies. Weak recommendation; best action may differ depending on circumstances or patients’ or societal values. 2B UnclearRCTs with important limitations (inconsistent results, methodological flaws) Weak recommendation; alternative approaches likely to be better for some patients under some circumstances. 2C UnclearObservational studies. Very weak recommendations; other alternatives may be equally reasonable.

4. Overview Use of diuretics in acute renal failure Dosing of renal replacement therapy –Intermittent hemodialysis –Continuous renal replacement therapy (CRRT) High volume hemofiltration in sepsis Intermittent vs. continuous renal replacement Anticoagulation in CRRT Nutritional considerations in acute renal failure

5. Use of diuretics in acute renal failure The literature on the use of diuretics in acute renal failure is conflicting. –One large cohort study demonstrated an association with the use of diuretics in ARF and mortality –A second larger cohort study did not demonstrate a significant association between the use of diuretics and the development of ARF No suggestion can be made for or against the use of diuretics in ARF LEVEL 2C SUGGESTION that the effect of diuretics on mortality in acute renal failure is unclear.

6. Dosing of Renal Replacement Therapy in ARF One randomized trial without significant limitations comparing daily intermittent hemodialysis (IHD) vs alternate day IHD demonstrated a significant survival advantage of daily IHD (Kt/V averaged 5.8 per week) LEVEL 1A RECOMMENDATION for the use of daily IHD or the equivalent dose of Kt/V=5.8 per week. One randomized trial without significant limitations comparing CRRT (CVVH) at 35 or 45 ml/kg/hr vs. CVVH at 25 ml/kg/hr demonstrated a significant survival advantage of 35 over 25 ml/kg/hr. LEVEL 1A RECOMMENDATION for 35 ml/kg/hr dose of CVVH.

7. High Volume Hemofiltration (HVHF) in Sepsis Defined as CVVH at rates > 35 ml/kg/hr Two randomized trials and one cohort study with limitations demonstrated a reduction in dose of norepinephrine vs. controls. LEVEL 1B RECOMMENDATION for the use of HVHF for the end-point of reducing dose of vasopressors in sepsis. Small observational studies with historic controls demonstrated improved survival. LEVEL 2C SUGGESTION for the use of HVHF for improving survival in sepsis.

8. IHD vs. CRRT Randomized trial, observational studies unclear and limited because of patient populations and significant cross-over to CRRT. Meta-analysis unclear because of limitation of original studies. LEVEL 2B SUGGESTION of no difference between the use of IHD vs. CRRT as therapy for acute renal failure.

9. Anticoagulation in CRRT Two randomized trials and one observational study demonstrating improved hemofilter survival and reduced bleeding risk of regional citrate anticoagulation vs. unfractionated heparin in CRRT. The effect is seen in those not at a high risk for bleeding. LEVEL 1A RECOMMENDATION for the use of regional citrate anticoagulation in patients with ARF with or without a high risk for bleeding including those with HITT. Requires a learning curve to use.

10. Anticoagulation in CRRT 3 observational studies comparing no anticoagulation with low-dose heparin LEVEL 2C SUGGESTION of the equivalence of no anticoagulation vs low-dose heparin in terms of hemofilter survival. Improved bleeding risk with no anticoagulation. 1 randomized trial of LMWH (Dalteperin) vs. UFH. Prolongation of t1/2 of LMWH in renal failure. LEVEL 1B RECOMMENDATION of no advantage of LMWH over UFH in terms of hemofilter survival. Increase in cost of LMWH. No difference in bleeding risk using LMWH.

11. Anticoagulation in CRRT Use of danaparoid for circuit anticoagulation in HITT. LEVEL 2C SUGGESTION of no benefit of danaparoid for anticoagulation in HITT. Separate from its therapeutic use. Use of Lipirudin for circuit anticoagulation. 2 randomized trials against UFH (no HITT) and 2 case series (patients with HITT). LEVEL 1B RECOMMENNDATION of no advantage of the use of Lipirudin over UFH. May be considered as a therapeutic option in HITT although t ½ of Lipirudin prolonged in renal failure and no improvement in circuit survival over no anticoagulation.

12. Anticoagulation in CRRT Regional heparin anticoagulation with heparin and protamine. 1 RCT an 2 observational studies. LEVEL 1B RECOMMENDATION of no advantage of hemofilter survival or bleeding risk with the use of “regional heparin” with protamine as compared with low- dose heparin or no anticoagulation. Prostaglandins. 2 RCTs with limitations and 1 observational study. LEVEL 2B SUGGESTION of improvement in hemofilter survival using PGE1+ UFH over UFH alone. Higher risk of hypotension using PG’s.

13. Nutrition in ARF One randomized trial and one cohort study demonstrating significantly improved nitrogen balance in ARF patients on CRRT when 2.5 gm/kg/day of protein vs. lower doses administered. Improved nitrogen balance associated with a significantly improved survival. However higher protein intake has yet to be shown to improve survival. LEVEL 1B RECOMMENDATION for the use of 2.5 gm/kg/day of protein to improve nitrogen balance in patients with ARF on CRRT.

14. Nutrition in ARF Observational studies have demonstrated increased t1/2 of lipids in ARF with no renal clearance or removal using CRRT. LEVEL 2C SUGGESTION to limit the use of lipids in patients with ARF. Observational studies have demonstrated loss of water soluble vitamins and minerals in CRRT. LEVEL 2C SUGGESTION to supplement patients with ARF on CRRT with 2 x RDA of Selenium, 2 x RDA of Folate, 1.5 x RDA Thiamine, 400 mg/day Vitamin C.