2. Perioperative Renal Protection ผศ. นพ. สุรพงษ์ หล่อสมฤดี Division of Cardiothoracic and Vascular Anesthesia Division of Transplantation Anesthesia TIVA center Chiangmai University Hospital

3. Small Reductions in Renal Function Following CABG Predict Prolonged Hospitalization ADAPTED FROM:Mora-Mangano, et al. Anesth Analg 2000; 90, SCA 35

4. 2547 Acute Dialysis Quality Initiative (ADQI) group แบ่งระดับความรุนแรงของภาวะ ARF

5. Acute Kidney Injury (AKI) Abrupt ↓ kidney function (within 48 hrs) SCr ↑ ≥ 0.3 mg/dl ↑ 1.5 fold from baseline Oliguria < 0.5 ml/kg/hr นานกว่า 6 hr

6. การแบ่งระดับความรุนแรงของ AKI โดยปรับตาม RIFLE criteria StageSerum creatinine (SCr) criteria Urine output criteria 1 ↑ SCr ≥ 0.3 mg/dl (26.4 μmol/L) หรือ ↑ ≥ 150 ถึง 200% (1.5 - 2 เท่าของ ค่าเดิม ) ปัสสาวะ < 0.5 ml/kg/hr นานกว่า 6 ชั่วโมง 2 ↑ > 200 ถึง 300% (2 - 3 เท่าของค่า เดิม ) ปัสสาวะ < 0.5 ml/kg/hr นานกว่า 12 ชั่วโมง 3 ↑ > 300% (3 เท่าของค่าเดิม ) หรือ SCr ≥ 4.0 mg/dl (354 μmol/L) ร่วมกับ ↑SCr ≥ 0.5 mg/dl (44 μmol/L) ปัสสาวะ < 0.3 ml/kg/hr นานกว่า 24 ชั่วโมง หรือ Anuria นานกว่า 12 ชั่วโมง

7. Renal Tubule

8. Renal Tubule

17. Glomerulus

19. Constriction of Afferent Arteriole

20. Constriction of Efferent Arteriole

21. Constriction of Mesangial Cell

22. Dilation of Afferent Arteriole

23. Dilation of Efferent Arteriole

24. Relaxation of Mesangial Cell

25. Effect of Prostaglandins

26. Effect of Angiotensin II

27. Effect of Increase Sympathetic Input

28. # Suraphong Lorsomradee, et al Asian Cardiovasc Thorac Ann June 2008;16:256-264. Cardiac surgery with CPB # Thoracoabdominal aortic surgery with supraceliac artery clamping Liver transplantation Perioperative AKI Patients at Risk Mortality > 50% Pre-op Risk ↑ SCr/BUN ↓ cardiac performance Past history renal dysfunction Other Advance age Active bacterial endocarditis ↓ serum albumin Malignancy Emergency Vascualr disease

29. Cystatin C VS Creatinine After Cardiac Surgery Lorsomradee S., et al. J Cardiothorac Vasc Anesth. 2006 ;20(5):684-90 Julier K. Anesthesiology, 98(6).2003.1315-1327

31. Biomarker Cystatin C KIM-1 (kidney injury molecule 1) IL-18 (interleukin 18) NGAL (neutrophil gelatinase associated lipocalin)

32. Kidney injury molecule-1 as a biomarker of acute kidney injury in renal transplant recipients Nature Clinical Practice Nephrology (2008) 4, 362-363 Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney International 2002; 62: 237–44. Kidney Injury Molecule-1 (KIM-1)

35. Causes of AKI Pre-renal reversible absolute or relative renal hypoperfusion ischemic acute tubular necrosis (ATN) Intrinsic renal glomerular tubular vascular interstitial Post-renal obstruction Lameire N, et al. Lancet 2005; 365: 417-30

36. Perioperative Renal Protection Euvolemia Adequate renal perfusion Avoid nephrotoxins Pharmacotherapeutic intervention

37. Hypovolemia & ↓ O 2 delivery : renal medulla ischemic ATN Volume status monitoring Hypervolemia Debating: Crystalloids vs Colloids Debating: Hydroxyethyl starch (HES) Volume Status

38. Euvolemia MAP (mean arterial pressure) > 65-70mmHg Urine output> 0.5cc/kg/hr CVP10-15mmHg PAWP10-15mmHg Carmichael P, et al. ANZ Journal of Surgery 2003; 73: 144–53. Vincent JL, et al. Critical Care Medicine 2004; 32: S451–4.

39. Renal perfusion Autoregulation (MAP 80-160 mmHg) 1 Hypotensive anesthesia contraindicated in CRF 2,3 Laparoscopic surgery 4-10 1. Palmer BF. The New England Journal of Medicine 2002; 347: 1256–61. 2. Hara T, et al. Journal of Clinical Anesthesia 1998; 10: 539–45. 3. Sharrock NE, et al. British Journal of Anaesthesia 2006; 96: 207–12. 4. Demyttenaere S, et al. Surgical Endoscopy 2007; 21: 152–60. 5. Nguyen NT, et al. Annals of Surgery 2005; 241: 219–26. 6. Pastor CM, et al. Critical Care Medicine 2001; 29: 1017–22. 7. Nakache R, et al. Transplantation Proceedings 2000; 32: 683. 8. Troppmann C, et al. American Journal of Transplantation 2005; 5: 175–82. 9. Derweesh IH, et al. Urology 2005; 65: 862–6. 10. Koivusalo AM, et al. Anesthesia & Analgesia 1997; 85: 886–91.

41. Perioperative Nephrotoxins Antihypertensive drugs Antibiotics NSAID’s Contrast dyes Aprotinin

42. Renal Autoregulation

43. Palmer BF. Renal dysfunction complicating the treatment of hypertension. The New England Journal of Medicine 2002; 347: 1256–61. ACEI Angiotensin-receptor blockers Dilation of Efferent Arteriole

44. Antibiotics Associated with Acute Interstitial Nephritis 1 : Cephalosporins, Aminoglycosides, Vancomycin Gentamicin accumulate in renal proximal tubule 2 : cause ATN Dosing should be based on creatinine clearance Peak & trough drug levels 1. Rossert J. et al. Kidney International 2001; 60: 804–17. 2. Nagai J, et al. Drug Metabolism and Pharmacokinetics 2004; 19: 159–70.

45. NSAID’s Efrati S, et al. Nephrology Dialysis Transplantation 2007;22:1873-81

46. Cochrane Database of Systematic Reviews 2007; 2: CD002765.

47. Contrast Induced Nephropathy (CIN) Risk factors CRF, DM, dehydration, poor cardiac performance, contrast volume, and high osmolar contrast Prophylactic strategies Pre- and Post procedure hydration (NSS or NaHCO3) N-acetylcysteine Pannu N,et al. The Journal of the American Medical Association 2006; 295: 2765–79. Bettmann MA. Radiographics 2004; 24: S3–10. Pannu N, et al. Current Opinion in Nephrology and Hypertension 2006; 15: 285–90.

48. Risk of postoperative renal dysfunction Vol 371, 475-82, 2008

49. Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study Vol 371, 475-82, 2008

50. Pharmacotherapeutic intervention Dopamine (renal dose) ? Loop diuretics Anaritide Fenoldopam mesylate

51. Dopamine (renal dose) ? Belief :renal arterial vasodilation, ↑ renal blood flow :renal parenchymal oxygen homeostasis (no guarantee) proximal tubular diuretic :↑ Na(+) delivery to tubular cells, ↑ oxygen demands : Not prevent renal dysfunction and death Routine use is not recommended Jones D, Bellomo R. Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition? Journal of Intensive Care Medicine 2005; 20: 199–211. Friedrich JO, Adhikari N, Herridge MS, Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Annals of Internal Medicine 2005; 142: 510–24. Kellum JA, Decker M. Use of dopamine in acute renal failure: a meta-analysis. Critical Care Medicine 2001; 29: 1526–31. Marik PE. Low-dose dopamine: a systematic review. Intensive Care Medicine 2002; 28: 877–83.

52. Juste, et al Intensive Care Med 1998 (24): 1217-20 Dosing of Dopamine: Lack of Predictable Plasma Concentrations

53. Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis Shorter duration of RRT (weighted mean difference, 1.4 days; 95% CI, 0.2 to 2.3 days; P=0.02), shorter time to spontaneous decline in serum creatinine level (weighted mean difference, 2.1 days; 95% CI, ?0.4 to 3.7 days; P=0.01) I ncrease in urine output (OR, 2.6; 95% CI, 1.4-4.9; P=0.004). No statistical difference in mortality or renal recovery (odds ratio [OR], 1.28; 95% CI, 0.89-1.84; P=0.18) (OR, 0.88; 95% CI, 0.59-1.31; P=0.5) Crit Care Resusc. 2007;9(1):60-8

54. Anaritide Recombinant Human Atrial Natriuretic Peptide Critical Care Medicine 2004; 32: 1310–5

55. Fenoldopam mesylate dopamine-1 receptor agonist Murphy MB, et al. Fenoldopam: a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. The New England Journal of Medicine 2001; 345: 1548–57. Morelli A, et al. Prophylactic fenoldopam for renal protection in sepsis: a randomized, double-blind, placebo-controlled pilot trial. Critical Care Medicine 2005; 33: 2451–6. Caimmi PP, et al. Fenoldopam for renal protection in patients undergoing cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia 2003; 17: 491–4. Landoni G, et al. Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. American Journal of Kidney Diseases 2007; 49: 56–68. Halpenny M, et al. The effects of fenoldopam on renal function in patients undergoing elective aortic surgery. European Journal of Anaesthesiology 2002; 19: 32–9. Sward K, et al. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Critical Care Medicine 2004; 32: 1310–5. 0.1 mcg/kg/min initiate with the induction of surgery

56. DA 1 ( vasodilation) ++++++ DA 2 (vasodilation, emesis +++ - inhibits prolactin) α (vasoconstriction) ++ - β 1 (inotropic, chronotropic) +++ - β 2 (vasodilation) + - Adrenergic Receptor Agonism: Dopamine vs. Fenoldopam DopamineFenoldopam ADAPTED FROM:Frishman WH and Hotchkiss H, Am Heart J, 1996, 132(4):861-70

57. Systemic Vasodilation 1 Does not cross BBB (demonstrated in animals) 1 Coronary Vasodilation (demonstrated in animals) Reflex tachycardia 1 Metabolized by conjugation 1 No P450 interaction 1  RBF 1  Na excretion 2,3  Diuresis 2,3 Maintains GFR 3,4 during BP lowering 1 CORLOPAM®(fenoldopam mesylate) Package Insert, 2000. Abbott Laboratories. North Chicago, Illinois 2 Elliott, et al Circulation 1990; 49: 285-93 3 Carey, et al, Am J Hypertens 1990; 3:59-63s 4 Mathur, et al Crit Care Med 1999; 27: 1832-6 1 CORLOPAM®(fenoldopam mesylate) Package Insert, 2000. Abbott Laboratories. North Chicago, Illinois 2 Elliott, et al Circulation 1990; 49: 285-93 3 Carey, et al, Am J Hypertens 1990; 3:59-63s 4 Mathur, et al Crit Care Med 1999; 27: 1832-6

58. Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: A Meta-Analysis J Cardiothoracic Anesth 2008; 22:27-33

59. Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: A Meta-Analysis J Cardiothoracic Anesth 2008; 22:27-33

60. The Effects of Levosimendan in Cardiac Surgery Patients with Poor Left Ventricular Function Stefan G. De Hert, Suraphong Lorsomradee, Stefanie Cromheecke. Anesth Analg. 2007 Apr;104(4):766-73.

61. A Randomized Trial Evaluating Different Modalities of Levosimendan Administration in Cardiac Surgery Patients With Myocardial Dysfunction Journal of Cardiothoracic and Vascular Anesthesia, In Press, Corrected Proof, Available online 14 May 2008 Stefan G. De Hert, Suraphong Lorsomradee, Hervé vanden Eede, Stefanie Cromheecke, Philippe J. Van der Linden

64. Circulation 2007; 116:98-105

65. The End Thank you for your attention