林口長庚紀念醫院 加護腎臟科 / 陳永昌

1. 連續性腎臟替代療法 --沿革、技術與臨床應用 林口長庚紀念醫院 加護腎臟科/陳永昌

2. Outline • Introduction • CRRT Nomenclature • Applications for CRRT • Fluid Management in CRRT • Clinical Aspects • Evidence Based Medicine • Conclusions

3. Introduction

4. AKI in ICUs • In ICUs, acute kidney injury (AKI) frequently occurs in patients with medical or surgical complications and multiorgan failure • Worse prognosis • Standard intermittent renal replacement (IHD) treatments are often contraindicated

5. RIFLE Classification (Bellomo R et. al. Critcal Care 2004)

6. Contraindication to Hemodialysis • Hemodynamic instability (hypotension, presence of significant cardiovascular disease) • Lack of access to circulation • Lack of highly trained staff and/or equipment

7. Indication and Timing of Dialysis for AKI Renal Replacement vs. Renal Support

8. CRRT vs. IHD

9. CRRT Nomenclature

10. Continuous Renal Replacement Therapy (CRRT) • CAVH: Continuous arteriovenous hemofiltration • CAVHD: Continuous arteriovenous hemodialysis • CAVHDF: Continuous arteriovenous hemodiafiltration • CVVH: Continuous venovenous hemofiltration • CVVHD: Continuous venovenous hemodialysis • CVVHDF: Continuous venovenous hemodiafiltration • AVSCUF: Arteriovenous slow continuous ultralfiltration • VVSCUF: Venovenous slow continuous ultralfiltration

11. V X X

13. CRRT: AV vs. VV • Arteriovenous therapies (AV) • Technique simplicity • Required large-bore arterial catheter • Blood flow dependent on MAP • Venovenous therapies (VV) • No arterial line • Pump-assisted • Blood flow independent of blood pressure

14. CGMH CRRT Order • Diagnosis • CVVH Solution A 3000 cc + 15% KCl __ cc IVF (500~ cc/hr) • CVVH Solution B 3000 cc + 7% NaHCO3 240 cc IVF(500~cc/hr) • Record I/O Q1h and Keep I/O _____ • Check: BUN,Cr, Na, K, Cl, Ca, P QD; Mg QW1,4 • Blood flow 120ml/min • Check ACT Q6h and Keep ACT at 200~250 sec • P.S. 15% KCl

15. Multi-mode continuous renal replacement machine

16. Applications for CRRT

17. Applications for CRRT (1) Renal application (renal replacement and renal support) • Acute renal failure (specifically complicated ARF with multiple organ failure) • Oligouric ARF needs large amount of fluid or nutrition • Fluid overloading • An alternative to HD in the mass casualty situation • Electrolytes and acid base disturbance

18. Applications for CRRT(2) Non-renal application • Hepatic failure complicated with hepatic coma • Congestive heart failure refractory to diuretics • Overhydration during & after cardiac surgery (CPB & after) • Sepsis • Life-threatening hyperthermia • Hemofiltration for poisoning (lactic acidosis, lithium poisoning) • Cytokine removal: Acute respiratory distress syndrome • Chemofiltration, chemoperfusion

19. Potential Complications of CRRT

20. Fluid Management in CRRT

21. Fluid Removal vs. Fluid Regulation

22. Fluid and Solute Removal in CRRT

23. Components of Fluid Regulation • Fluid Balance • Fluid composition • Electrolyte and Acid Base homeostasis • Nutritional balance • Temperature control

24. Volume Adjustment for Fluid Management • Level 1: Ultrafiltrate volume limited to match anticipated needs for fluid balance over 8-24 hours. Limited replacement fluid. • Level 2: Ultrafiltrate volume greater than hourly intake. Net fluid balance achieved by hourly replacement fluid administration. • Level 3: Ultrafiltrate volume adjusted greater than hourly intake. Net fluid balance targeted to achieve specific hemodynamic parameters eg. CVP, PAWA, MAP.

25. Sliding Scale for Volume Adjustment

26. Clinical Aspects

28. Electrolyte and Acid Base Derangements • Continuous therapies can be used to correct water and electrolyte imbalances • Hypo-hypernatremia can be corrected not only achieving a normal plasma sodium concentration, but also by restoring the normal body sodium content • Hyperkalemia can also be corrected: the efficiency of continuous arteriovenous and venovenous hemofiltration in removing potassium is low

29. AKI in Neonates • Continuous arteriovenous hemofiltration is especially useful in the treatment of acute renal failure in neonates and small babies (Ronco et al. 1984, 1986) • CRRT as a successful bridge to liver transplantation should be considered in children with unrelenting hyperammonemia not amenable to routine medical therapy (Chen CY et al. 2000)

31. Treatment of Multiple Organ Dysfunction and Sepsis with CRRT • Eicosanoids, cytokines (tumor necrosis factor and interleukins such as IL-1, IL-6, and IL-8), endothelin, and platelet-activating factor may all contribute to the reduction of renal blood flow and GFR during sepsis • ARF cannot be treated effectively unless the underlying problems are resolved • CVVH using the high-permeability membranes allows extraction of significant quantities of circulating macromolecules (MW 30 kDa)

34. CRRT of AKI in Burns Patients • CRRT may maintain a good uremic control for severely catabolic burns patients with multiorgan dysfunction • Treatment is possible despite cardiovascular instability and total parenteral nutrition can be given • CAVHD appears to give somewhat better uremic control, but the difference in mortality is not significant • Large burns, pulmonary burns and septicemia seems to be bad prognostic signs (Leblanc et al. 1999)

35. Advantage of CRRT for Nutritional Support • Fluid restrictions are removed • Electrolyte overload is avoided • Hyperosmolar nutrition solutions are safe • CRRT result in a cumulative Kt/V or small solute removal rate equivalent or superior to conventional intermittent 4 hours HD • IHD daily X 4 hr: Kt/V weekly 7.5 • IHD X three sessions /week: Kt/V weekly 3.2 • CAVHD: Kt/V weekly 6.2 • CVVHD: Kt/V weekly 8.0 (Leblanc M. et al. Semin Dial 1995) • CRRT provide adequate clearance of nitrogenous compounds with the avoidance of repeatedly high peak serum nitrogen values (Clark WR et al. JASN 1994)

36. Regional Chemotherapy plus Hemofiltration vs. Hemoperfusion • Regional intra-arterial chemotherapy: drug delivery 1.5~2 x systemic dose • Regional chemotherapy plus hemofiltration: drug delivery 3~4 x systemic dose • Regional chemotherapy plus hemoperfusion: drug delivery 5~8 x systemic dose • Ability to overcome drug delivery problems and resistance • Improves survival for HCC, pancreatic cancers, and hepatic metastasis colorectal cancer (Muchmore et al. 1999)

37. Requirements for liver support Detoxification Fluid regulation Acid-Base and electrolyte homeostasis Indications of CRRT support Combines renal and liver failure Liver transplant Mx of complications of decompensated liver disease Ascites Encephalopathy CRRT in Liver Support

38. Intra-operative support and post-operative problems Oxygenator membranes and cytokine generation Blood tubing and extraction of plasticizers (DEHP) Prolongedbypass time and hemodynamic consequences Application of aggressive ultrafiltration in the cardiac support of children and outcome improvement Dialysis variants added to extracorporeal cardiac support system VAD and support ECMO and support IABP and support Post Cardiac Surgery AKI

40. (Lin CY, Chen YC, Fang JT et al. JN 2008)

41. Evidence Based Medicine

42. Evidence Based Medicine (1) • Optimal way to deliver CRRT does not exist • Acute Dialysis Quality Initiative (ADQI) aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research • http://www.ADQI.net

43. Evidence Based Medicine (2) Levels of Evidence • Level I: Randomized trials with low false positive () and low false negative () error (i.e. high power) • Level II: Randomized trials with high  error or low power • Level III: Non-randomized concurrent cohort studies • Level IV: Non-randomized historic cohort studies • Level V: Case series, case reports, expert opinion

44. Evidence Based Medicine (3) Grades of Recommendations • Grade A: Supported by at least 2 level I studies • Grade B: Supported by only 1 level I study • Grade C: Supported level II studies • Grade D: Supported by at least 1 level III study • Grade E: Supported by only level IV or V studies

45. Evidence Based Medicine (4) • CRRT use in a variety of non-ARF conditions including intoxication with dialyzable/filterable drugs or toxins, cardiac failure, ARDS, and pediatric cardiac surgery or sepsis and systemic inflammation • Insufficient evidence to recommend the use of CRRT for non-ARF indications outside clinical investigation (Grade E) • CRRT use may be advantageous in the management of ICU patients with ARF (Grade E) • CRRT is recommended over IHD for patients with AKI who have, or are at risk for, cerebral edema (Grade C)

46. CVVH Dose (1) (Ronco C et al. Lancet 2000)

47. CVVH Dose (2)

48. CVVH Dose (3)

49. Intensive vs. Less-Intensive Strategy (1) (Palevsky PM et al. NEJM 2008)

50. Intensive vs. Less-Intensive Strategy (2)