CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what

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1 Cardiac surgery induced acute kidney injury and the perfusionist M. Ranucci Director of Clinical Research Dept of Cardiothoracic and Vascular Anesthesia and Intensive Care IRCCS Policlinico S.Donato Ranuuci, M et al Outline CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what (probably) bl can do

2 Outline CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what (probably) bl can do Things we really, honestly know about AKI after cardiac surgery It happens! Recurrent clinical observation Multiple (>200) human case series, case reports and epidemiological papers It severely deteriorates the outcome Courtesy of R. Belloma

3 Things we really, honestly know about AKI after cardiac surgery As many as 50% of the patients who require new-onset RRT early after cardiac surgery will die CSI-AKI may irreversibly deteriorate kidney function Even small rises in serum creatinine are associated with a worse outcome RIFLE criteria The definition of AKI AKIN criteria Should be applied within 48 hours from surgery

4 Things we really know about ARF after cardiac surgery It is the second most common type of severe ARF in Australian ICUs Estimate:1/100,000/year 20 (10,000 in developed countries) % 5 0 Sepsis Cardiac Sx Cardiac shock AAA Sx Silvester W, Bellomo R, Cole L. Crit Care Med 2001; 29: Courtesy of R. Belloma Risk RIFLE Criteria for Acute Renal Dysfunction GFR Criteria* Urine Output Criteria Abrupt (1-7 days) Increase creat 50% or GFR decrease > 25% UO <.5ml/kg/h x 3 hr High Sensitivity Injury Increase creat x2 Or GFR decrease > 50% UO <.5ml/kg/h x 12 hr Failure Increase creat x3 Or GFR decrease > 75% UO <.3ml/kg/h x 24 hr Anuria x 12 hrs High Specificity Loss ESRD Courtesy of R. Belloma Persistent ARF** = complete loss of renal function > 2 weeks End Stage Renal Disease Bellomo et al. Critical Care 2004; 8: R

5 AKIN Criteria for Acute Renal Dysfunction AKI stage 1: serum creatinine increase +50% x baseline AKI stage 2: serum creatinine increase 2 x baseline AKI stage 3: serum creatinine ne increase 3 x baseline or RRT

6 What do we mean by AKI? Typically we actually only measure very few aspects of renal function By AKI we actually clinically mean loss of small solute clearance (urea/creatinine) This implies loss of GFR (GFR could be preserved but there might be solute backleak) So..clinically we actually mean probable acute decrease in GFR Courtesy of R. Belloma What happens with cardiac surgery which might decrease GFR? Low cardiac output Low BP Pulsatility is lost Major biological changes with CPB Hemolysis Hemodilution (too little/too much) Other factors Courtesy of R. Belloma

7 Circumstantial evidence Low cardiac output syndrome (LCOS) is typically associated with ARF Makes physiological sense (decreased blood flow to kidneys and glomeruli) Other states of LCOS (AMI, cardiac arrest, CCF) also lead to ARF Ischemia (decreased flow to glomeruli) seems a resonable explanation Courtesy of R. Belloma Perfusion Pressure and Organ Flow RPP = MAP - Tissue pressure CPP = DAP - LVEDP % Blood flow Kidney Heart Hypertrophic heart Renovascular disease Courtesy of R. Belloma MAP in mmhg

8 Outline CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what (probably) bl can do Predicting AKI after Cardiac Surgery Need to define AKI first Variable definitions iti in the literaturet If AKI = need for renal replacement therapy (clinically relevant) - incidence: 2-5% If >50% decrease in GFR (still clinically relevant) using formulae- then 4-8% If lesser changes variable incidence but unclear clinical relevance Courtesy of R. Belloma

9 Risk Factors on MVLRA 4 OR 3,5 3 2,5 2 1,5 1 0,5 0 Age (y) Sex Preop Creat (mg/dl) Preop IABP Complex Sx Emergency Sx Left main PVD n=24,660 from Cleveland Clinic (Am J Kidney Dis 2003) Courtesy of R. Belloma Predicting ARF Recursive partitioning algorithm (Kidney Int 2000) If Creat Cl <60 ml/min, IABP, LVEF<35%, PVD, valve Sx = 7.1% incidence of dialysis If Cr Cl >60 ml/min, no previous heart Sx, no valve = 0.7% incidence of dialysis Courtesy of R. Belloma

10 The biggest risk factor: CRF 35 3,5 % risk of ARF 3 2,5 2 1,5 1 0,5 0 Courtesy of R. Belloma > <40 Estimated creatinine clearance in ml/min Odds Ratios for ARF Cr Cl<40 Cr Cl Cr Cl IABP preop EF<35% 1 0 Fortescue et al. Kidney Int 2000; 57: Courtesy of R. Belloma

11 Other independent predictors of need for RRT diabetes cardiogenic shock urgent Sx NYHA 3 or 4 CPB > 2 hours LCOS Need for post op transfusion Courtesy of R. Belloma Limitations Most data from single centres No standard criteria for RRT No agreed definition of ARF No multinational database Limited information on area under the curve for ROC Limited information on calibration Courtesy of R. Belloma

12 Clinical Score from Cleveland Clinic n=15,838 to develop it and n=>17,000 to validate it One point each for: female, CHF, LVEF<35%, COPD, IDDM, Re-do Sx, Valve only Sx. Two points each for: Pre-op IABP, Emergency Sx, CABG+valve, Other Sx, Creat 1.2 to <2.1mg/dL Five points if creat 2.1 mg/dl Courtesy of R. Belloma Am J Kidney Dis Cleveland Score AUC for ROC = % needing dialysis Development cohort Validation cohort 5 Courtesy of R. Belloma 0 0 to 2 3 to 5 6 to 8 9 to 13 Score

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17 Outline CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what (probably) bl can do Possible perfusion-related risk factors CPB itself Perfusion pressure Perfusion flow Loss of pulsatility Severe hemodilution Poor oxygen delivery Hemolysis

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20 2 Audience Response Questions

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23 Pressure on CPB may be important Flow on CPB is extremely important

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25 Audience Response Question

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27 Inappropriate transfusions induce AKI!!!!

28 Possible perfusion-related risk factors CPB itself Perfusion pressure Perfusion flow Loss of pulsatility Severe hemodilution Poor oxygen delivery Hemolysis The Renal Corpuscle Composed of Glomerulus and Bowman s capsule

29 STRUCTURE OF THE KIDNEY(after A.Despopoulos & S.Silbernagl, Color Atlas of Physiology, 2003) Vesa Recta

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32 Kidney and oxygen supply Renal medulla is chronically hypoxemic A low oxygen content (hemodilution) further worsen kidney hypoxia Low blood flow is a major determinant of reduced d oxygen supply : A CHANGE IN PARADYGM

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35 % < > 28 Total N/100 Lowest HCT on CPB % ARF-D Cut off Karkouti et al, Ann Thorac Surg te (%) Mortality rat < > 24 MEN WOMEN Lowest HCT on CPB DeFOE et al, Ann Thorac Surg 2001

36 Habib et al, JTCVS 2003 Lowest HCT on CPB is associated to: Reopening Bleeding Perioperative MI Cardiac arrest Stroke Coma Prolonged ventilation IABP Renal failure MOF

37 RBC transfusion rate CRUDE RBC transfusion rate ADJUSTED 2 2 RBCunitstransfusionrate transfusion rate CRUDE 2 RBC units transfusion rate ADJUSTED AKI rate CRUDE AKI rate ADJUSTED FAVOURS LPVO Inspire FAVOURS CONVENTIONAL Figure Nadir HCT 24% AKI rate (% with 95 % CI) Conventional: 15% P < 0.05 Inspire: 9.7% Nadir HCT on CPB (%)

38 0.25 Nadir HCT 24% AKI rate (% with 95 % CI) Conventional: 15% 20 years later Data confirmed! P < 0.05 Inspire: 9.7% Nadir HCT on CPB (%) Audience Response Question

39 Why severe hemodilution on CPB is so bad? Viscosity, cp; OD DI Oxygen Delivery Index vs.viscosity Hematocrit, % Viscosity ODI

40 Running CPB below the critical DO2 means pushing the patient into the anaerobic zone a bad place to stay

41 AUC: 0.76 AUC: 0.73 nal failure rate (%) p < 0.01 p < % 6.2 % Low hematocrit n = 242 Rena al replacement -Acute re % High hematocrit n = 640 A 1.9 % Low hematocrit n = 53 B High hematocrit n = 113 High oxygen delivery Low oxygen delivery Group If we increase the pump flow and restore an adequate DO2,the ARF rate stays low; conversely, a low DO2 is associated to a high ARF even in presence of a high HCT C D

42 THE GOAL-DIRECTED PERFUSION CONCEPT 3,0 ak Arterial Blood Lactate (mmol/l) Pea 2,5 2,0 1,5 Critical DO2 GDP: KEEP THE PATIENT HERE 1, Lowest Oxygen Delivery (ml/min/mq)

43 nal failure rate (%) p < 0.01 p < % 6.2 % Low hematocrit n = 242 Rena al replacement -Acute re % High hematocrit n = 640 A 1.9 % Low hematocrit n = 53 B High hematocrit n = 113 High oxygen delivery Low oxygen delivery Group If we increase the pump flow and restore an adequate DO2,the ARF rate stays low; conversely, a low DO2 is associated to a high ARF even in presence of a high HCT C D Crit Care 2011

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46 Outline CSI-AKI: the magnitude of the phenomenon Risk factors for CSI-AKI Perfusion-related risk factors What the perfusionist should avoid and what (probably) bl can do : ten golden rules 1. Limit hemodilution on CPB 0.25 AK KI rate (% with 95% CI) Nadir HCT on CPB (%)

47 2. Always stay at a DO2 > 270 ml/min/m2 3. Increase the DO2 by acting on pump flow, PaO2

48 4. Transfuse RBC based on SvO2 and O2ER, avoid inappropriate transfusions 5. Avoid hemolysis 6. Avoid hypotension 7. Do not exceed with cell-saving 8. UF, MUF, ZB-UF are not magic bullets

49 9. Hypothermia is not bad to the kidney, but rewarming may be. Rewarming phase is the most critical for DO2 10. Do not rely on pharmacological agents /fenoldopam, sodium bicarbonate, statines..