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Acute Kidney Injury in the Cardiac Surgery Patient

A recent review on risk factors, treatment and prevention of acute kidney injury in cardiac surgery unit.

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Acute Kidney Injury in the Cardiac Surgery Patient

  1. 1. Acute Kidney Injury Associated With Cardiac Surgery Kenar D. Jhaveri, MD 2015 Update Hofstra NSLIJ School of Medicine
  2. 2. What’s the connection?
  3. 3. CASE SP is a 57 year old male with DMII, HTN and hyperlipidemia. He has a routine stress test and is referred to get a cardiac cath. After demonstration of triple vessel disease, patient is offered to get a CABG. The patient is a nephrologist. All he cares about is the risk to the kidneys. His pre-op serum creatinine is 1.6mg/dl. His serum creatinine prior to cardiac cath was 1.2mg/dl. He has two questions? Is this CABG urgent, can we wait till the crt is back to 1.2mg/dl ? What is the percent chance that I will require dialysis following the CABG?
  4. 4. Agenda  Introduction  Risk Factors  Treatment  Prevention
  5. 5. Etiology of AKI among Inpatients ATN (45%) Prerenal (21%) ARF on CKD (13%) Obstruction (10%) GN/vasc (4%) AIN (2%) Atheroemboli (1%) Kidney Int: 1996
  6. 6. Natural History of AKI  48% ICU patients require dialysis  58% inpatient mortality among patients who develop AKI in the ICU  36% mortality among all inpatients with AKI  20% of survivors received dialysis Crit Care Med 1996 JASN 1998
  7. 7. RIFLE Criteria for AKI
  8. 8. Surgical procedures  Highest risk of post operative AKI  Cardiac surgery  AAA repair  Surgery to correct obstructive jaundice
  9. 9. The Pre-post and intra-renal kidney injury concept
  10. 10. Incidence After bypass surgery  Incidence of AKI ranges from 1-30% in patients with cardiac surgery ( most recent being 18%)  Typical CABG 2.5%  Valvular surgery 2.8%  Valvular surgery with CABG 4.6%  Requiring ECMO 80%  Incidence of AKI requiring dialysis is around  Typical CABG 1%  Valvular surgery 1.7%  Valvular surgery with CABG 3.3% Dardhasti A J Thorac Cardiovasc Surg 2014 Mangano et al Ann Intern Med 1998 Gailiunas P et al. J Thorac Card Surg 1980
  11. 11. Mortality  15-30% if there is AKI  As high as 60% if on dialysis  Higher risk of infections for those who develop AKI and started on dialysis  Even small rises in serum creatinine were noted to have 3 fold to 18 fold higher mortality. Chertow G. AJM 1998 Thakar CV KI 2005 Lassnigg A et al JASN 2004
  12. 12. Duration of acute kidney injury impacts long-term survival after cardiac surgery.  1 to 2 days  3 to 6 days  ≥7 days  The duration of AKI after cardiac surgery is directly proportional to long-term mortality. Brown JR. Ann T Surg 2010
  13. 13. Implications  AKI associated with prolonged ICU stay  Higher risk of chronic kidney disease  For those that require dialysis in CTICU, 64% require HD permanently. Zanardo G et al J Thorac Cardi Surg 1994 Ishani A et al. Arch Intern Med 2011 Leacche M et al. Am J Cardiol 2004
  14. 14. Risk Factors Rosner M et al. CJASN 2006
  15. 15. Pre-operative Risk Factors  Patient related risk factors  Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)  Inflammatory environment
  16. 16. Patient related factors (usually known prior to surgery)  Chronic Kidney Disease (CKD)  LVEF  COPD  DM  Older Age  Women  Emergent surgery Anderson T Cardi Surg 1993 Chertow G Circulation 1997
  17. 17. Proteinuria??  Higher levels of proteinuria pre cardiac surgery identify patients at increased risk for AKI during their hospital stay.  Mild and heavy proteinuria each associated with an increased odds of cardiac surgery associated AKI , independent of CKD stage  Heavy proteinuria also associated with increased odds of postoperative RRT Thakar CV JASN 2005 Huang TM, JASN 2011
  18. 18. Bottom Line  Most predictive factor is pre operative serum creatinine. 2-4mg/dl ( risk of dialysis prone AKI is 10-20%) >4mg/dl ( risk of dialysis prone AKI is 25-28%)  All of the defined risk factors – somehow lead to decrease renal perfusion or decreased renal reserve.
  19. 19. Pre-operative Risk Factors  Patient related risk factors  Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)  Inflammatory environment
  20. 20. Nephrotoxins  Nephrotoxins ( NSAIDS, ACEI/ARB)  Contrast  IV fluids Choices( Normal Saline, Lactate Ringers, Hetastarch)
  21. 21. SP Calls SP was glad you waited till the creatinine came back to1.2mg/dl. The CABG is now planned in 3 days. He calls your office cell phone and asks you a question again? I am on losartan. Should we hold it few days prior to surgery?
  22. 22. ACEI/ARB prior to surgery? Systematic review has been performed of 421 articles concerning use of ACEI/ARB in CT surgery 3 randomized studies, other observational Low quality evidence supporting holding ACEI/ARB before surgery Functional AKI likely but not Structural AKI Individualize therapy. Raja SG et al. Interact Cardisvasc Thorac Surg 2008 Coca S et al. NDT 2013
  23. 23. Heta-Starch Story Myburgh JA, NEJM 2012
  24. 24. Fluids  Colloid versus Crystalloid battle  NEJM 2012: randomized controlled trial in sepsis patients showed that patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.  In CCU and CTICU, no data to support either way.  Renal injury is evident with HES more than Ringer’s lactate or Normal Saline (In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal- replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04) Perner A et al NEJM 2012
  25. 25. Which Crystalloid? Balanced Solutions vs Saline based  Normal Saline  Lactate Ringers( balanced solutions) Yunos NM JAMA 2012
  26. 26. Pre-operative Risk Factors  Patient related risk factors  Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)  Inflammatory environment
  27. 27. SP texts  SP texts you one day prior to surgery. His text reads… Off PUMP or ON PUMP?
  28. 28. Intra-operative Risk Factors  Regional Hypoxia  Atherosclerotic Emboli  Inflammation( free radicals, cytokines)  Hemodynamic State  Mechanical Blood Trauma( centrifugal vs. roller pumps)  The Cardiopulmonary Bypass  Hematocrit  Peri-operative PRBCs transfusions
  29. 29. Intra operative events  Systemic Perfusion Pressures  Animal data supports renal blood flow(RBF) dependence on renal perfusion pressures(PP) in CPB  Small clinical studies have shown that increasing MAP and adding pressors increased renal PP during CPB.  No head to head higher vs. lower PP has been done for renal outcomes . Mackay JH et al Crt Care Med 1995 Urzua J et al. J Cardio Vasc Anes 1992 Kanji et al. J Cardio Thora Surg 2010
  30. 30. Surgical risks  Cross clamp time ( blood flow to renal vessels)  Traditional On-pump CABG versus Off -pump CAB surgery( most controversial topic)  Non randomized studies showed AKI was less frequent in Off Pump CABG  With prior CKD, Off pump CABG might be a better option  Decrease in inflammatory markers  No hemolysis  Hemo-dilution related injury( decrease viscosity) Beauford RB et al Heart Surg Forum 2004 Stallwood MI et al. Ann Thorac Surg 2004
  31. 31. Off pump versus On pump  The complications of on-pump CABG, especially stroke and decrease in higher mental function, spurred the development of the Off pump technique  Largest meta-analysis showed: “Eighty-six trials (10,716 participants) were included. Pooled analysis of all trials showed that off-pump CABG increased all-cause mortality compared with on-pump CABG (189/5,180 (3.7%) versus 160/5144 (3.1%); RR 1.24, 95% CI 1.01 to 1.53; P =.04). No significant differences in myocardial infarction, stroke, renal insufficiency, or coronary re- intervention were observed.  No circulatory support of CPB, hypotension, vasopressor requirements- Perhaps the AKI risk stays the same Puskas JD et al JAMA 2004 Moller CH et al Cochrane Database Sys Rev 2012
  32. 32. CORONARY TRIAL Lamy A, NEJM 2012
  33. 33. Off Pump vs. On Pump No difference in new renal injury requiring dialysis Less risk of mild-moderate AKI, not requiring dialysis in the off-pump group Use of off-pump compared to on-pump CABG reduced risk of post operative AKI by 17%( 95% CI, 5-28%) There is no change in kidney function 1 year out with off pump CABG compared to on pump The absolute risk reduction of acute kidney injury with off-pump vs on- pump CABG surgery was greater in those with CKD compared with those without CKD. In a subgroup analysis, preoperative CKD did not alter overall 1year kidney function results. Lamy A, CORONARY, NEJM 2012 Garg A, CORONARY AKI update, JAMA 2014
  34. 34. Hematocrit  Priming leads to hemodilution  Relationship noted with lowest hemoglobin during CPB and AKI  Is there an optimum hemoglobin that balances risk of hemodilution( and less release of free hemoglobin) with risks of inadequate oxygen delivery with CPB? 8.5g/dl?? Swaminathan M. Ann Thorac Surg 2003 Karkouti K J Thorac Cardiovasc Surg 2005 Carson JL. NEJM 2011
  35. 35. Pre and intra-operative PRBCs transfusion  Anemia and number of PRBCs transfusion are independent risk factors for development of AKI post CABG  Catalytic iron can produce oxidative stress  Surrogate for hypotension and a “sick patient”  Age of PRBCs maybe the culprit?  16% increase risk of mortality post CABG  Risk of sepsis and pneumonia  Risk of increased length of intubation Karkouti K. Br J Anesth 2012 Nuis RJ. Circ Cardiovasc Interv 2012 Khan UA. J Thorac Cardiovasc Surg 2014 Koch CG. NEJM 2008 Yu PJ. J Cardiothor And Vasc Anes 2014
  36. 36. Post operative Risk factors  Nephrotoxins  Sepsis  Volume depletion  Hemodynamic instability  Proteinuria  Vaso-active agent choices
  37. 37. Proteinuria Higher levels of proteinuria after cardiac surgery identify patients at increased risk for AKI during their hospital stay Molnar AO CJASN 2012
  38. 38. Vasopressor selection  Effect on renal blood flow( vasopressin agonist or a pure alpha agonists)  Norepinephrine vs Phenylephrine in septic shock ( more urine output in norepinephrine arm)  Vasopressin vs Norepinephrine ( 2 trials)  It is reasonable to use either norepinephrine or vasopressin for hemodynamic support in patients with high risk for AKI post CABG Morelli A Shock 2008 Morelli A Crit Care 2008 Russell JA NEJM 2008
  39. 39. Rosner M et al. CJASN 2006 Summary of Risk Factors
  40. 40.    Contrast, NSAIDS, CKD, ACEI/ARB, NPO CPB, clamp, inflammation hypotension Sepsis, reduced LV, Nephrotoxins
  41. 41. Can we predict the risk via a calculator? • CICSS (Continuing Improvement in Cardiac Surgery Study) • Cleveland Clinic • STS Bedside Risk • MCSPI (Multicenter study of perioperative ischemia) • AKICS (AKI after Cardiac Surgery) • NNECDSG (Northern New England Cardiovascular Disease Study Group)
  42. 42. Predictions? Thakar CV et al JASN 2005
  43. 43. Your response  Dr. SP, your risk of needing dialysis after CABG is only 1.8% given your risk factors. I think we can proceed with on- pump CABG… And let’s hold your losartan now.
  44. 44. Post Op Day 1  SP is hypotensive and you decide to start IV fluids. His baseline serum creatinine is 1.2mg/dl pre op. His creatinine post op has been stable and urine output is starting to diminish… What fluids would you consider starting now?  A. 0.9% normal saline  B. Lactate Ringers  C. Hetastarch (HES)  D. 25% Salt poor albumin
  45. 45. Supportive  Maintenance of hemodynamic status  Assessment of etiology for any acute cause for AKI  Fluids management ( avoid HES)  Start renal replacement therapy ( CRRT or HD ) for severe AKI and when indicated
  46. 46. Diuretics  Make patients non oliguric from oliguric/anuric  Does it help?- increases urine output  Two randomized trials have been conducted and no improvement in renal outcomes or mortality benefit.  Suggest against the use of it as long term therapy and use should not postpone need for initiation of dialysis  Short term use of it is preferred for volume management Cantarovich F et al AJKD 2004 van der Voort PH et al Crit Care Med 2009
  47. 47. Anti Inflammatory agents  N-acetylcysteine (N-AC , mucomyst)  Steroids  Statins – harm?? Wang G. J Cardiothorac Vasc Aneth 2011 Morariu AM Chest 2005 Loef BG Br J Anaesth 2004
  48. 48. Bove T JAMA 2014
  49. 49. Fenoldopam Bove T JAMA 2014
  50. 50. Atrial Natriuretic Peptide(ANP)
  51. 51. ANP  Re combinant ANP(rhANP) used in AKI post cardiac surgery for heart failure  Patients who received it had a significant reduction in incidence of dialysis at day 21 after start of treatment  ANP was infused at lower rate in the above study compared to prior studies Sward K Crit Care Med 2004
  52. 52. “Cocktail “  Mannitol + Furosemide+ Dopamine  Postoperative oliguric/anuric patients randomly assigned to above regimen or intermittent doses of loop diuretics  90% vs. 6.7% requirement of dialysis  Early restoration of renal function. Sirivella S et al. Ann Thor Surg 2003
  53. 53. Mesenchymal Stem Cells  Pre clinical studies have shown that mesenchymal stem cells (MSC) both prevent and facilitate recovery of renal failure.  Allogenic human MSC was used in a phase 2 trial that was RCT in CABG patients who developed AKI. ( intra arterial dose of MSC or placebo)  21 centers in north America, 156 patients randomized  This phase 2 trial with early AKI following CABG, treatment with MSC did not improve the time to complete kidney recovery, need for dialysis or mortality within 30 and 90 days. Swaminathan M. ASN Oral Abstract, Philadelphia, 2014
  54. 54. Dialysis  Intermittent hemodialysis(IHD)  CRRT (CVVHD, CVVHDF, CVVH)  Sustained low efficiency dialysis (SLED)  Peritoneal Dialysis(PD)
  55. 55. Indications  AEIOU  Acidosis, refractory metabolic  Electrolyte disorders, mainly hyperkalemia  Intoxication ( unusual for CT surgery case)  Overload( fluid related, totally possible)  Uremia( very possible)
  56. 56. IDEAL STUDY
  57. 57. Indications for and timing of initiation of RRT in the ICU  Bagshaw et al showed that early initiation of dialysis by creatinine criteria was associated with an increased risk of death.  Shiao et al showed that early initiation of dialysis by BUN criteria was associated with decreased risk of death. Bagshaw M et al J Crt Care 2009 Shiao CC et al Crit Care 2009
  58. 58. Cardiac surgery patients?  CVVHDF was performed on Group 1 when creatinine level exceeded 5 mg/dL, or potassium level exceeded 5.5 mEq/L irrespective of the urine output. CVVHDF was performed on Group 2 when urine output was less than 100 mL within consecutive 8 hours, with no response to 50 mg furosemide with the supplementary criterion that urine sodium concentration should be >40 mEq/L before the administration of furosemide.  The mean intensive care unit (ICU) stay for Group 1 was 12 ± 3.44 days and 7.85 ± 1.26 days for Group 2 (p = 0.0001). ICU mortality rate was 48.1% for Group 1 and 17.6% for Group 2 (p = 0.014). The overall hospital mortality rate was 55.5% for Group 1 and 23.5% for Group 2 (p = 0.016).  Conclusion: Recognition of ARF and early beginning of the CVVHDF are extremely important. The sooner the ARF after surgery is recognized and CVVHDF is performed, the higher the likelihood of the reduction of the hospital mortality. Demirkiliç et al. J Card Surg 2004
  59. 59. Early and aggressive CRRT is associated with better predicted survival. Early starters had increased survival benefit. Hospital mortality 43% in late starters and 22% in early starters Elahi et al. Eur J of cardio thora surg 2009
  60. 60. International survey of Nephrologists  Analysis of survey of nephrologists found that severity of illness in ICU patients with AKI influences the timing of dialysis initiation. So, survey respondents were more likely to initiate early dialysis in case scenarios portraying higher severity of illness. Also, the study found that decision to initiate dialysis in ICU patients with AKI is still largely driven by imminent indications of dialysis (e.g. hyperkalemia, or hypoxemia) rather than a proactive decision based on degree of severity of kidney injury.  Until we have prospective clinical trials, timing of dialysis will remain a subjective decision, one that is dependent on several factors including severity of illness. Thakar CV , Crit Care 2012
  61. 61. But here comes a meta analysis in CT ICU patients  Early initiation of RRT for patients with AKI after cardiac surgery revealed a lower 28 days mortality and shorter ICU stay.  Based on 11 studies with various qualities and very high heterogeneity of results. Liu Y. J Cardiothorac Vasc Anesth 2014
  62. 62. Liu Y. J Cardiothorac Vasc Anesth 2014
  63. 63. Modality of choice  CRRT versus Intermittent hemodialysis: A paucity of evidence exists that have examined these issues. However, current data suggest that survival and recovery of renal function are similar with both CRRT and IHD.
  64. 64. In the hemodynamic unstable patient Modality CRRT IHD Mortality Poor Poor Recovery or renal function Poor Poor *Hemodynamic stability Better Poor *Volume management Better Poor *Inflammatory markers removal Better Poor *Cerebral perfusion Better Poor *= data is from non randomized trials
  65. 65. Prevention strategies
  66. 66. SP’s recovery  SP responded well to LR and his renal function never got worse. He did not require dialysis and he is now transferred to step down. You are making rounds and he asks you? Is there anything you can give your patients to prevent renal failure following CABG? Mucomyst, dopamine, lasix, mannitol?
  67. 67. Overall prevention  Identify HIGH risk patients early to prevent AKI  Optimize renal perfusion and avoid nephrotoxins (NSAIDS and contrast if possible)  Delay time between contrast and surgery  Pharmacologic interventions???- all are failures  Cardiac surgery induced ATN is too complex  Too late usually given  Most studied had been low risk patients. Del Duca D. Ann Thorac Surg 2007
  68. 68. Increase Renal Blood Flow  Dopamine  Fenoldopam  Theophylline Woo EB et al. Eur J Cardiothor Surg 2002 Stone GW et al. JAMA 2003 Kramer BK et al. NDT 2002
  69. 69. Induce natriuresis  ANP ( Anaritide)  Diuretics  Mannitol Allgren RL et al NEJM 1997 Lewis J et al. AJKD 2000 Lombardi R et al. Ren Fail 2003 Rigden SP et al. Clin Nephrol 1984
  70. 70. ANP  Systematic review ( 19 studies) and another meta-analysis of 11 studies showed no significant benefit. However, low dosage ANP was associated with significant reduction of need for dialysis.  Two randomized trials ( small) each of around 500 patients to ANP at 0.02ug/kg per min or placebo found that the incidence of AKI was much lower in ANP arm. No mortality difference. Post operative complications less in ANP arm. No patients in ANP arm required dialysis. The second study was 130 patients or so with low EF ( <35%)- similar findings. Nigwekar U et al. J Cardiothor Vasc Anes 2009 Sezai A et al. JACC 2009 Sezai A et al. JACC 2010
  71. 71. Block inflammation  Steroids  Pentoxifylline  N-AC ( mucomyst) Cagli K et al. Perfusion 2005 Loef BG et al. Br J Anaesth 2004 Kshirsagar AV et al. JASN 2004
  72. 72. Steroids in Cardiac Surgery Trial (SiRS)  Randomized 7000 patients undergoing CABG to steroids vs placebo  Methylprednisolone does not reduce death or major morbidity at 30 days for high-risk patients undergoing cardiac surgery with the use of cardiopulmonary bypass.  Methylprednisolone increases the risk of early post- operative myocardial infarction  Methylprednisolone did not have any impact on development of new renal failure in 30 days. Whitlock R. Am H Journal 2014 http://solaci.org/es/pdfs/acc2014/6_richard_whitlock_slides.pdf
  73. 73. No BENEFIT No BENEFIT Lack of good randomization
  74. 74. Remote Ischemic Preconditioning  Brief ischemia and reperfusion in distant tissues protects a critical target organ or tissue from lethal ischemia and reperfusion through neuronal or humoral pathway.  Results in cardiovascular surgery related use in AKI remain controversial.  Meta-analysis showed no evidence in using such strategy in renal protection. There was no significant difference for incidence of AKI, renal biomarkers or hemodialysis requirements and mortality. Hausenloy DJ Lancet 2007 Li L J of Cardiothorac Surg 2013
  75. 75. Sodium Bicarbonate Did not reduce in the incidence of AKI Prolonged the duration of ventilation and ICU stay Increased the risk of alkalemia
  76. 76. Dialysis before surgery?  Durmaz et al looked at prophylactic dialysis for 42 CKD patients to improve renal outcomes- showed decreased mortality and ICU stay.  One arm was prophylactic dialysis pre CABG , other arm was dialysis as needed post CABG as the control.  Mortality was higher in control arm of 30.4% compared to 5% in prophylactic arm.  These results need to be repeated in randomized control trials before considering it in practice. Durmaz et al. Ann Thorac Surg 2003
  77. 77. Can we pick up renal disease early?
  78. 78. SP had a successful recovery and was discharged.
  79. 79. What works thus far?  Minimize contrast exposure and time to surgery  Avoid HES  Minimize PRBCs transfusions  Avoiding diuretics unless medical indication  Reducing the use of alpha adrenergic agents by adding vasopressin  Use of ANP?
  80. 80. Summary  AKI occurs in 18% of patients with CABG, with 2-6% needing dialysis.  Mortality is high when you have AKI  There are NO active treatments that work for cardiac surgery associated AKI  Prevention strategies are needed.  Dialysis may be needed in patients with severe AKI  Early CRRT may improve renal outcomes and mortality

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