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Acute Kidney Injury Associated With Cardiac
Surgery
Kenar D. Jhaveri, MD
2015 Update
Hofstra NSLIJ School of Medicine
What’s the connection?
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?
Agenda Introduction
Risk Factors
Treatment
Prevention
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
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 1996JASN 1998
RIFLE Criteria for AKI
Surgical procedures Highest risk of post operative AKI
Cardiac surgery
AAA repair
Surgery to correct obstructive jaundice
The Pre-post and intra-renal kidney injury concept
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 2014Mangano et al Ann Intern Med 1998Gailiunas P et al. J Thorac Card Surg 1980
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 1998Thakar CV KI 2005Lassnigg A et al JASN 2004
Duration of acute kidney injury impactslong-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
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 1994Ishani A et al. Arch Intern Med 2011Leacche M et al. Am J Cardiol 2004
Risk Factors
Rosner M et al. CJASN 2006
Pre-operative Risk Factors Patient related risk factors
Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)
Inflammatory environment
Patient related factors(usually known prior to surgery)
Chronic Kidney Disease (CKD)
LVEF
COPD
DM
Older Age
Women
Emergent surgery
Anderson T Cardi Surg 1993Chertow G Circulation 1997
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 2005Huang TM, JASN 2011
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.
Pre-operative Risk Factors Patient related risk factors
Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)
Inflammatory environment
Nephrotoxins Nephrotoxins ( NSAIDS, ACEI/ARB)
Contrast
IV fluids Choices( Normal Saline, Lactate Ringers, Hetastarch)
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?
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 2008Coca S et al. NDT 2013
Heta-Starch Story
Myburgh JA, NEJM 2012
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
Which Crystalloid?Balanced Solutions vs Saline based
Normal Saline
Lactate Ringers( balanced solutions)
Yunos NM JAMA 2012
Pre-operative Risk Factors Patient related risk factors
Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast)
Inflammatory environment
SP texts SP texts you one day prior to surgery. His text reads…
Off PUMP or ON PUMP?
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
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 1995Urzua J et al. J Cardio Vasc Anes 1992Kanji et al. J Cardio Thora Surg 2010
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 2004Stallwood MI et al. Ann Thorac Surg 2004
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 2004Moller CH et al Cochrane Database Sys Rev 2012
CORONARY TRIAL
Lamy A, NEJM 2012
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 2012Garg A, CORONARY AKI update, JAMA 2014
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 2003Karkouti K J Thorac Cardiovasc Surg 2005Carson JL. NEJM 2011
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 2012Nuis RJ. Circ Cardiovasc Interv 2012Khan UA. J Thorac Cardiovasc Surg 2014Koch CG. NEJM 2008Yu PJ. J Cardiothor And Vasc Anes 2014
Post operative Risk factors
Nephrotoxins
Sepsis
Volume depletion
Hemodynamic instability
Proteinuria
Vaso-active agent choices
ProteinuriaHigher levels of proteinuria after cardiac surgery identify patients at increased risk for AKI during their hospital stay
Molnar AO CJASN 2012
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 2008Morelli A Crit Care 2008Russell JA NEJM 2008
Rosner M et al. CJASN 2006
Summary of Risk Factors
Contrast, NSAIDS,CKD, ACEI/ARB, NPO
CPB, clamp, inflammationhypotension
Sepsis, reduced LV,Nephrotoxins
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)
Predictions?
Thakar CV et alJASN 2005
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.
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 creatininepost 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
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
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 2004van der Voort PH et al Crit Care Med 2009
Anti Inflammatory agents N-acetylcysteine (N-AC , mucomyst)
Steroids
Statins – harm??
Wang G. J Cardiothorac Vasc Aneth 2011Morariu AM Chest 2005Loef BG Br J Anaesth 2004
Bove T JAMA 2014
Fenoldopam
Bove T JAMA 2014
Atrial Natriuretic Peptide(ANP)
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
“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
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
Dialysis Intermittent
hemodialysis(IHD)
CRRT (CVVHD, CVVHDF, CVVH)
Sustained low efficiency dialysis (SLED)
Peritoneal Dialysis(PD)
Indications AEIOU
Acidosis, refractory metabolic
Electrolyte disorders, mainly hyperkalemia
Intoxication ( unusual for CT surgery case)
Overload( fluid related, totally possible)
Uremia( very possible)
IDEAL STUDY
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 withdecreased risk of death.
Bagshaw M et al J Crt Care 2009Shiao CC et al Crit Care 2009
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
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
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
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
Liu Y. J Cardiothorac Vasc Anesth 2014
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.
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
Prevention strategies
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?
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
Increase Renal Blood Flow Dopamine
Fenoldopam
Theophylline
Woo EB et al. Eur J Cardiothor Surg 2002Stone GW et al. JAMA 2003Kramer BK et al. NDT 2002
Induce natriuresis
ANP ( Anaritide)
Diuretics
Mannitol
Allgren RL et al NEJM 1997Lewis J et al. AJKD 2000Lombardi R et al. Ren Fail 2003Rigden SP et al. Clin Nephrol 1984
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 2009Sezai A et al. JACC 2009Sezai A et al. JACC 2010
Block inflammation Steroids
Pentoxifylline
N-AC ( mucomyst)
Cagli K et al. Perfusion 2005Loef BG et al. Br J Anaesth 2004Kshirsagar AV et al. JASN 2004
Steroids in Cardiac Surgery Trial (SiRS)
Randomized 7000 patients undergoing CABG to steroids vsplacebo
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 2014http://solaci.org/es/pdfs/acc2014/6_richard_whitlock_slides.pdf
No BENEFIT
No BENEFIT
Lack of good
randomization
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 2007Li L J of Cardiothorac Surg 2013
Sodium Bicarbonate
Did not reduce in the incidence of AKIProlonged the duration of ventilation and ICU stayIncreased the risk of alkalemia
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
Can we pick up renal disease early?
SP had a successful recovery and was discharged.
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?
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
Thanks