PROTECTING THE KIDNEYS FROM PERIOPERATIVE ISCHEMIA. Connie Lynne Lorette, PhD, CRNA Northeastern University Boston MA

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1 PROTECTING THE KIDNEYS FROM PERIOPERATIVE ISCHEMIA Connie Lynne Lorette, PhD, CRNA Northeastern University Boston MA

2 Key Points Pathophysiology and diagnostic criteria for perioperative renal failure Risk factors for development of perioperative renal failure Are any specific measures know to protect renal function during the perioperative period Of measures used to protect renal function in the perioperative period, does any one method appear to be more effective than the others Of measures used to protect renal function in the perioperative period, does any one method appear to be safer than the others

3 Kidney Injury Direct and indirect insult Changes in physiology (surgery and anesthesia) Significant morbidity and mortality Interventions Pharmacological Dopamine Diuretics - Calcium channel blockers - ACE inhibitors N-acetyl cysteine ANP NaHCO3 Antioxidants Hydration fluids How interventions might work Maintain CO Maintain renal vasodilation Maintaining renal tubular flow

4 Contrast Induced Nephropathy Risk factors CRF DM Dehydration Low EF Contrast volume High osmolar contrast Prophylactic strategies Pre and Post procedure hydration (NS or NaHCO3) N-acetylcysteine

5 Review of literature Primary outcome Acute renal failure or death Secondary outcome UOP Creatinine clearance or GFR Renal blood flow Free water clearance Fractional excretion of sodium Urinary NAG/creatinine ratio Urinary RBP/creatinine ratio Urinary NGAL/creatinine ratio Plasma cystatin C.

6 Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network:report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007 Mar 1;11(2):R31.

7 Plasma Creatinine Plasma creatinine is an indirect determinant of GFR > 50% reduction in GFR before changes in plasma creatinine are seen Plasma creatinine also reflects muscle mass, which does not reflect changes in GFR Severe renal impairment tubular secretion of creatinine has a greater role GFR is determined by clearance of an inert substance freely filtered at glomerulus no tubular secretion or reabsorption Creatinine clearance correlates well with GFR Collection of urine and plasma creatinine determination

8 Other Markers UOP Non-specific measure of renal function Renal blood flow Fick Free water clearance Urinary concentrating ability Fractional excretion of sodium Renal tubular reabsorption of sodium

9 New Markers Urinary NAG/creatinine ratio Urinary RBP/creatinine ratio Urinary NGAL/creatinine ratio Plasma cystatin C.

10 Prevalence of Perioperative Renal Injury Cardiac surgery AKI: /4% CRRT: 1 5% Gastric Bypass AKI: 8.5% Non-cardiac surgery GFR < 50mL/min = 0.8% Vascular surgery AKI: 15 46% Liver transplant AKI: 48 94% CRRT 8 17%

11 Evidence AKI, ARF and RF in the Perioperative Period Changes Outcome 7-10 fold increase in risk-adjusted odds of death over patients without AKI Mortality rates at 30 days, 60 days and 1 year was increased amongst the 15,000 patients followed after non-cardiac surgery amongst those with AKI 2.7% to 15%, %, 15%-31% Similar numbers for Liver Transplant and Vascular surgery Cardiac Surgery: Mortality rate 0.8% without renal dysfunction 9.5% with AKI 44.4% with renal failure and RRT need

12 Preoperative Risk Factors Age Emergency Surgery BMI > 33 Peripheral vascular occlusive disease COPD requiring bronchodilator therapy

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14 Other Issues Maintenance of adequate intravascular volume Uncorrected hypovolemia can lead to pre-renal AKI and in the context of further perioperative stress can lead to ischemic ATN Thus an important part of the perioperative consultation Particularly in emergent setting, elderly, and Hip Fractures Volume best determinant History Physical exam CVP/PA line? NPO? Diuretics what to do the day of OR NSAIDS All neprhotoxins Crystalloid/colloid debate

15 Optimizing Renal Perfusion Renal autoregulation = MAP Unclear what ideal MAP is to protect kidneys Optimal perfusion pressure in chronic hypertension? Pharmacologic management Diuretics ACE/ARB Alters renal regulation Associated with post-induction hypotension No clear renal outcome data Individualized perioperative RAAS agent management

16 Specific Surgical Issues Cardiac Surgery Duration of CPB Risk increases over 100 minutes Lack of pulsatile flow Off pump CABG Decreased incidence of AKI Questionable cardiac outcomes Vascular surgery Duration of cross-clamp Direct renal artery injury Improved outcome with endovascular procedures Dependent upon contrast utilization

17 Specific Surgical Issues Laparoscopy RBF and function are reduced during pneumoperitoneum Increased intra-abdominal pressure is associated with decreases in UOP Bowel preps Role of hypovolemia Blood transfusion Independent associated risk of AKI

18 Renal Protection??? Identification of patients at risk Mitigate all that is controllable Are there therapies that will decrease the risk of perioperative AKI

19 Dopamine Low dose (or renal dose) Renal vasodilation Dose dependent increase in RBF High dose Increase RBF through increase CO Net sum Increase RBF Increase GFr Diuresis Natriuresis Numerous side effects Does NOT protect from AKI

20 Mannitol Maintenance of glomerular filtration pressure Prevention of tubular obstruction by cellular casts Scavenging of hydroxyl free radicals and prevention of cellular swelling.

21 Furosemide Enhances tubular oxygen balance Inhibits renal tubular oxygen consumption Renal cortical vasodilation Has NOT been shown to decrease AKI Will increase UOP But now change in outcome

22 Calcium channel blockers Protection against intracellular calcium injury

23 ACE Inhibitors Alter the balance between the vasoconstrictive and saltretentive properties of angiotensin Alter the balance between vasodilatory and natriuretic properties of bradykinin Kidneys Decrease glomerular capillary pressure Decreasing arterial pressure Selectively dilating efferent arterioles

24 N-acetyl Cysteine Antioxidant Stimulates endothelium-derived relaxing factor Improving microvascular flow Increases cyclic guanosine monophosphate levels Vasodilator Inhibitor of platelet aggregation

25 ANP/Anaritide CV renal endocrine homeostasis Renal hemodynamic Increases GFR by increasing glomerular capillary pressure Direct tubular actions Inhibits angiotensin II stimulated Sodium and water transport Inhibits vasopressin stimulated water transport in collecting tubules Inhibits sodium absorption in the inner medullary collecting duct Combined effect Natriuresis and diuresis

26 Fenoldopam Dopamine receptor agonist Systemic vasodilation Coronary vasodilation Increase RBF Increase Na excretion Increase diuresis Maintains GFR

27 Erythropoietin Pleiotropic (tissue protective) effect Inhibition of apoptotic cell death Stimulation of cellular regeneration Inhibition of deleterious pathways Promotion of recovery

28 Prophylactic Dialysis Extremely high risk surgeries and in patients at high risk Liver Transplant Cardiac surgery Did not decrease rates of perioperative AKI But useful to manage complications Hypervolemia Acidosis Hyperkalemia

29 Conclusion Perioperative AKI is common and serious No reliable evidence from the available literature suggests that interventions during anesthesia and surgery can protect the kidneys from damage Recent methods of detecting renal damage (e.g. biomarkers) and better defined criteria for identifying renal damage may have to be explored further to determine any possible benefit derived from interventions used to protect the kidneys during the perioperative period Judicious management of volume and blood pressure is paramount Be cognizant of patients at risk

30 References Cogliati AA, Vellutini R, Nardini A, Urovi S, Hamdan M, Landoni G, et al.fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. Journal of Cardiothoracic and Vascular Anesthesia 2007;21(6): HaaseM, Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, et al.sodium bicarbonate to prevent increases in serum creatinine afte cardiac surgery: a pilot doubleblind, randomized controlled trial. Critica Care Medicine 2009;37(1):39 47 Mitaka C, Kudo T, Jibiki M, Sugano N, Inoue Y, Makita K, et al.effects of huma atrial natriuretic peptide on renal function in patients undergoing abdominal aortic aneurysm repair. Critical Care Medicine 2008;36(3): \ Lassnigg A, Donner E, Grubhofer G, Presterl E, Druml W, & Heismayr M. Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. Thakar CV, Arrigain S, Worley S, et al. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16: Zacharia M, Mugawar M, Herbison GP, Walker RJ, Hovhannisyan K, Sivalingam P, Conlon NP. Interventions for protecting renal function in the perioperative period (Review). Cochrane Collaboration June 2013, Issue 9