1. 台大醫院雲林分院 黃道民 Tao-Min Huang NTUH Yun-Lin Branch taominhuang@gmail.com Acute Cardio-renal Syndrome.

2. A clinical scenario. A 62-year-old man PHx: DM, type 2 CKD, stage III ICMP, NYHA Fc II CC: 1 week of progressive dyspnea and weight gain. PE: BP: 118/70mmHg; HR = 82 bpm Basilar rales Bilateral pitting edema.

3. A clinical scenario. ECG: NSR N-Terminal pro-BNP = 16,500 pg/mL (0-450 pg/mL) CK, CK-MB, Tr. I: WNL UN = 38mg/dL; Cre = 2.0mg/dL (Baseline 1.7-1.8mg/dL) U/A, renal sonography: unremarkable CXR

4. Chest film.

5. Treatment. IV bolus Furosemide 20mg q6h U/o = 500ml/day Continous Furosemide U/O = 300ml/day Cre = 2.2mg/dL Spironolactone and lisinopril were held. U/O = 100ml/day Orthopnea aggravated. Nephrologist consultation for RRT

6. A Common scenario in Critical Care.

7. Epidemiology

8. Severity of WRF. Gottlieb et al., J Card Fail. 2002;8(3):136

9. How to define WRF Gottlieb et al., J Card Fail. 2002;8(3):136

10. Worsening Renal Function Forman et al. J Am Coll Cardiol. 2004;43(1):61 1. WRF: defined with ≥0.3mg/dL elevation of SCr. 2. 1004 patients admitted to hospital.

11. Mid-Term Survival Am Heart J. 2005 Aug;150(2):330

12. Adjusted HR for ESRD: 147,007 AMI Elderly. Arch Intern Med. 2008 May 12;168(9):987

13. Adjusted HR for All Cause Death: 147,007 AMI Elderly. Arch Intern Med. 2008 May 12;168(9):987

14. Cox’ Proportional Survival Function: 147,007 AMI Elderly Arch Intern Med. 2008 May 12;168(9):987

15. WRF: a meta-analysis J Card Fail. 2007 Oct;13(8):599 All Cause Mortality HR = 1.62

16. J Card Fail. 2007 Oct;13(8):599

17. WRF in ADHF Incidence: 19-45% Negative outcome predictor in: Short- and long-term all-cause and cardiovascular mortality Prolonged duration of hospitalization Increased readmission rates Accelerated progression to ESRD Higher healthcare costs Eur Heart J. 2010 Mar;31(6):703

18. Pathophysiology. (a) Adequacy of arterial filling and renal perfusion (b) Degree of venous congestion (c) Raised intra-abdominal pressure.

19. Pathophysiology: Low cardiac output. Heart 2010;96:255

20. Not all CRS are equal. J Am Coll Cardiol. 2006 Jan 3;47(1):76

21. Mortality between preserved/reduced Renal Function. J Am Coll Cardiol. 2006 Jan 3;47(1):76 O.R. = 2.45 (Diastolic) vs. 2.72 (Systolic)

22. Congestion and WRF: not novel findings J Physiol. 1931 Jun 6;72(1):49

23. CVP is better predictive. J Am Coll Cardiol 2009;53:589

24. Which is more important? Congestion or WRF? (+) WRF (+) Congestion (-) WRF (+) Congestion (-) WRF (-) Congestion (-) WRF (-) Congestion (+) WRF (-) Congestion 1 year Death or reTx. Circ Heart Fail. 2012 Jan 1;5(1):54

25. Which is more important? Congestion or WRF? (+) WRF (+) Congestion (-) WRF (+) Congestion (-) WRF (-) Congestion (-) WRF (-) Congestion (+) WRF (-) Congestion 1 year Death, HF readmission, or reTx. Circ Heart Fail. 2012 Jan 1;5(1):54

26. Intra-Abdominal Pressure David J.J. Muckart, MD, University of Natal Medical School

27. IAP and Mortality Crit Care Med 2005; 33:315

28. IAP and Mortality Crit Care Med 2005; 33:315

29. IAP and Change of Cre. J Am Coll Cardiol. 2008 Jan 22;51(3):300

30. Congestion? Kidney Injury? WRF (or CRS type 1) is bad. Congestion (high filling pressure, fluid overload) is bad. But WRF is not associated with (so much) hazard, after adjustment of “Congestion.”

31. De-congestive therapy.

32. Diuretics Patients admitted with evidence of significant fluid overload should initially be treated with loop diuretics, usually given intravenously. Early intervention has been associated with better outcomes for patients hospitalized with decompensated HF. ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

33. Diuretics and BNP: AEHERE registry 58,465 ADHF episodes. J Am Coll Cardiol. 2008 Aug 12;52(7):534

34. Factors predicting in-hospital death: Early Diuretics is Important. J Am Coll Cardiol. 2008 Aug 12;52(7):534

35. Sub-clinical fluid retention. Adamson et al. J Am Coll Cardiol. 2003;41(4):565

36. Sub-clinical fluid retention. Adamson et al. J Am Coll Cardiol. 2003;41(4):565

37. Benefit of De-congestion therapy. Symptom improvement Cardiopulmonary function Myocardial structure Re-hospitalization rates Am J Kidney Dis. 2011;58(6):1005

38. Loop Diuretics: Continuous or Intermittent? J Am Coll Cardiol. 1996 Aug;28(2):376

39. Loop Diuretics: Continuous or Intermittent? J Am Coll Cardiol. 1996 Aug;28(2):376

40. Loop Diuretics: Cont. or Bolus? 24hrs’ urine Cochrane Database Syst Rev. 2005:20;(3):CD003178.

41. Loop Diuretics: Cont. or Bolus? All Cause Mortality Cochrane Database Syst Rev. 2005:20;(3):CD003178.

42. Loop Diuretics: Cont. or Bolus? Significant e- change Cochrane Database Syst Rev. 2005:20;(3):CD003178.

43. Loop Diuretics: Cont. or Bolus? Hearing Loss Cochrane Database Syst Rev. 2005:20;(3):CD003178.

44. Loop Diuretics: Cont. or Bolus? Increased SCr. Cochrane Database Syst Rev. 2005:20;(3):CD003178.

45. How to Prescribe Diuretics in ADHF: DOSE Study Dose: High dose: total daily intravenous furosemide dose 2.5 times their total daily oral loop diuretic dose in furosemide equivalents Standard Dose: total intravenous furosemide dose equal to their total daily oral loop diuretic dose in furosemide equivalents Route: Bolus Every 12 hours. (Q12H) Continuous Randomized to 4 groups (1:1:1:1) Felker et a. N Engl J Med. 2011;364(9):797

46. Loop Diuretics: Dose? Continuous? Global VAS Score Felker et a. N Engl J Med. 2011;364(9):797

47. Loop Diuretics: Dose? Continuous? Composite Outcomes Felker et a. N Engl J Med. 2011;364(9):797

48. Complications: DOSE Felker et a. N Engl J Med. 2011;364(9):797

49. Limitations of DOSE. Primary endpoint: Global assessment of symptoms. Underpowered to detect other clinical outcomes. In addition, bolus group tended to receive a higher total dose Supine position may promote diuresis Felker et a. N Engl J Med. 2011;364(9):797

50. Diuretics Resistance When diuresis is inadequate to relieve congestion, as evidenced by clinical evaluation, the diuretic regimen should be intensified using either: Higher doses of loop diuretics; Addition of a second diuretic (such as metolazone, spironolactone or intravenous chlorothiazide); or Continuous infusion of a loop diuretic. (Level of Evidence: C) ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

51. Ultrafiltration

52. Concept of Ultrafiltration.

53. Removal of Fluids with UF. RAPID-CHF. J Am Coll Cardiol. 2005 Dec 6;46(11):2043

54. Fluid removal and Weight. RAPID-CHF. J Am Coll Cardiol. 2005 Dec 6;46(11):2043

55. UNLOAD UNLOAD. J Am Coll Cardiol. 2007;49(6):675

56. Loop Diuretics: Neurohormon activation. After single bolus injection of fursemide in 15 patients with chronic heart failure: 20 mins later: SVI LV filling Heart rate MAP SVRI PRA Plasma norepinephrine Plasma arginine vasopressin 3.5 hrs later: Rreturned toward the control levels. Ann Intern Med. 1985 Jul;103(1):1-6

57. Loop Diuretics and Vasodilators: Neurohormon activation. J Am Coll Cardiol. 2002 May 15;39(10):1623

58. Loop Diuretics and Vasodilators: Neurohormon activation. J Am Coll Cardiol. 2002 May 15;39(10):1623 Fig. Effect of therapy on plasma aldosterone levels (left) and plasma renin activity (right) before intervention (A), after intravenous vasodilators and diuretics (B) and after transition to an oral regimen, including captopril (C). *p 0.05 compared to A.

59. Ultrafiltration: Less neurohormon activation. Am J Med. 1994 Mar;96(3):191-9.

60. Composition of Urine: Sodium (Na) Congest Heart Fail. 2009;15(1):1-4.

61. Composition of Urine: Potassium (K) Congest Heart Fail. 2009;15(1):1-4.

62. Composition of Urine: Magnesium (Mg) Congest Heart Fail. 2009;15(1):1-4.

63. Symptom control: RAPID-CHF Trial. RAPID-CHF. J Am Coll Cardiol. 2005;46(11):2043

64. Symptom Control: UNLOAD Study UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

65. Electrolyte disturbance UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

66. Hypotension. UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

67. J Card Fail. 2006 Dec;12(9):707

68. Clinical adverse events. J Card Fail. 2006 Dec;12(9):707

69. Elevated Creatinine (AKI?) J Card Fail. 2006 Dec;12(9):707

70. AKI (SCr change) in UNLOAD UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

71. Ultrafiltration improves renal function? J Card Fail. 2008 Aug;14(6):531-2

72. Reduction of IAP J Card Fail. 2008 Aug;14(6):508

73. Reduction of IAP J Card Fail. 2008 Aug;14(6):508

74. Congestion Inadequate Venous filling Abdominal Pressure

75. Cost. Circ Cardiovasc Qual Outcomes. 2009 Nov;2(6):566

76. Commercialized UF machine http://www.gambro.com

77. Aquapheresis Summary.

78. Current Setting in YL branch. Machine: HF 440 Indication: CHF and diuretics resistance (Bumetanide > 1mg/hr) UF: 1000cc/hr Net UF: 200-400cc/hr Pre dilution: 70% No anticoagulation

79. Summary of UF vs. Diuretics. Neurohormonal activation. Efficient Na removal. K/Mg wasting. Cost Mechanical complication Easy to apply. Bleeding issue. Unknown. Survival Re-admission rate Length of stay Symptom control Hypotension

80. Ultrafiltration “Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy” ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

81. A clinical scenario. UF with HF440 was done for 2 days with heparinization. A total of 4000cc water was removed using CVVH. Patients symptom improved and u/o increased to baseline. At discharge, UN = 32mg/dL Cre = 1.8mg/dL BW: comparable to basline

82. Thanks for your attention.