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Perioperative Renal Protection ผศ. นพ. สรพงษ หลอสมฤด Division of Cardiothoracic and Vascular Anesthesia Division Perioperative Renal Protection ผศ. นพ. สรพงษ หลอสมฤด Division of Cardiothoracic and Vascular Anesthesia Division of Transplantation Anesthesia TIVA center Chiangmai University Hospital

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

2547 Acute Dialysis Quality Initiative (ADQI) group แบงระดบความรนแรงของภา 2547 Acute Dialysis Quality Initiative (ADQI) group แบงระดบความรนแรงของภา

Acute Kidney Injury (AKI) Abrupt ↓ kidney function (within 48 hrs) SCr ↑ ≥ 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 นานกวา 6

การแบงระดบความรนแรงของ AKI โดยปรบตาม RIFLE criteria Stage 1 Serum creatinine (SCr) criteria ↑ SCr ≥ การแบงระดบความรนแรงของ AKI โดยปรบตาม RIFLE criteria Stage 1 Serum creatinine (SCr) criteria ↑ SCr ≥ 0. 3 mg/dl (26. 4 μmol/L) ↑ 2 3 ↑ ถง 200% เทาของคาเดม ) ≥ > 150 200 ถง เทาของคาเดม 300% Urine output criteria หรอ (1. 5 (2 - - 2 3 < 0. 5 ml/kg/hr นานกวา ชวโมง ปสสาวะ 6 < 0. 5 ml/kg/hr ) ↑ > 300% (3 เทาของคาเดม ปสสาวะ นานกวา ชวโมง ) ปสสาวะ 12 < 0. 3

Renal Tubule Renal Tubule

Renal Tubule Renal Tubule

Glomerulus Glomerulus

Glomerulus Glomerulus

Constriction of Afferent Arteriole Constriction of Afferent Arteriole

Constriction of Efferent Arteriole Constriction of Efferent Arteriole

Constriction of Mesangial Cell Constriction of Mesangial Cell

Dilation of Afferent Arteriole Dilation of Afferent Arteriole

Dilation of Efferent Arteriole Dilation of Efferent Arteriole

Relaxation of Mesangial Cell Relaxation of Mesangial Cell

Effect of Prostaglandins Effect of Prostaglandins

Effect of Angiotensin II Effect of Angiotensin II

Effect of Increase Sympathetic Input Effect of Increase Sympathetic Input

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

Cystatin C VS Creatinine After Cardiac Surgery Lorsomradee S. , et al. J Cardiothorac 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

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

Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney 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 as a biomarker of acute kidney injury in renal transplant recipients Nature Clinical Practice Nephrology (2008) 4, 362 -363

Causes of AKI • Pre-renal reversible absolute or relative renal hypoperfusion ischemic acute tubular 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

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

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

Euvolemia MAP (mean arterial pressure) > 65 -70 mm. Hg Urine output > 0. Euvolemia MAP (mean arterial pressure) > 65 -70 mm. Hg Urine output > 0. 5 cc/kg/hr CVP 10 -15 mm. Hg PAWP 10 -15 mm. Hg Carmichael P, et al. ANZ Journal of Surgery 2003; 73: 144– 53. Vincent JL, et al. Critical Care Medicine 2004; 32: S 451– 4.

Renal perfusion Autoregulation (MAP 80 -160 mm. Hg) 1 Hypotensive anesthesia contraindicated in CRF Renal perfusion Autoregulation (MAP 80 -160 mm. Hg) 1 Hypotensive anesthesia contraindicated in CRF 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. 2, 3

Perioperative Nephrotoxins • Antihypertensive drugs • Antibiotics • NSAID’s • Contrast dyes • Aprotinin Perioperative Nephrotoxins • Antihypertensive drugs • Antibiotics • NSAID’s • Contrast dyes • Aprotinin

Renal Autoregulation Renal Autoregulation

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

Antibiotics Associated with Acute Interstitial Nephritis : Cephalosporins, Aminoglycosides, Vancomycin 1 Gentamicin accumulate in Antibiotics Associated with Acute Interstitial Nephritis : Cephalosporins, Aminoglycosides, Vancomycin 1 Gentamicin accumulate in renal proximal tubule : 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. 2

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

Cochrane Database of Systematic Reviews 2007; 2: CD 002765. Cochrane Database of Systematic Reviews 2007; 2: CD 002765.

Contrast Induced Nephropathy (CIN) Risk factors CRF, DM, dehydration, poor cardiac performance, contrast volume, 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 Na. HCO 3) N-acetylcysteine Pannu N, et al. The Journal of the American Medical Association 2006; 295: 2765– 79. Bettmann MA. Radiographics 2004; 24: S 3– 10. Pannu N, et al. Current Opinion in Nephrology and Hypertension 2006; 15: 285– 90.

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

Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: 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

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

Dopamine (renal dose) ? Belief : renal arterial vasodilation, ↑ renal blood flow : 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.

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

Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis 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) Increase 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. 60 -8: (1)9; 200

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

Fenoldopam mesylate dopamine-1 receptor agonist 0. 1 mcg/kg/min initiate with the induction of surgery Fenoldopam mesylate dopamine-1 receptor agonist 0. 1 mcg/kg/min initiate with the induction of surgery • • • 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.

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

Systemic Vasodilation 1 • Metabolized by conjugation 1 • No P 450 interaction 1 Systemic Vasodilation 1 • Metabolized by conjugation 1 • No P 450 interaction 1 Does not cross BBB (demonstrated in animals)1 • Coronary Vasodilation (demonstrated in animals) • Reflex tachycardia 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 -63 s 4 Mathur, et al Crit Care Med 1999; 27: 1832 -6

Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: A Meta-Analysis

Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: A Meta-Analysis

The Effects of Levosimendan in Cardiac Surgery Patients with Poor Left Ventricular Function Stefan 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.

A Randomized Trial Evaluating Different Modalities of Levosimendan Administration in Cardiac Surgery Patients With 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

Circulation 2007; 116: 98 -105 Circulation 2007; 116: 98 -105

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