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7000 patients in Austrialia/Nz randomized to hetastarch vs saline . No diff in mortality. HES more likely to have more non renal side effects and also more likely to receive RRT. There was increased UO in the lower crt arm but overall trend was increasing crt consitently in HES arm
Prospective sequential period design. Austrialia/NZ with initially control period of chloride heavy fluids and in the following year- was intervention arm which had low chloride fluids. As you can see, there was more Renal injury and need for HD in the chloride arm. No diff in length of stay, mortality and need for RRT after discharge.
Acute Kidney Injury in the Cardiac Surgery Patient
Acute Kidney Injury
Associated With Cardiac
Kenar D. Jhaveri, MD
Hofstra NSLIJ School of Medicine
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
What is the percent chance
that I will require dialysis
following the CABG?
Etiology of AKI among Inpatients
ARF on CKD (13%)
Kidney Int: 1996
Natural History of AKI
48% ICU patients require dialysis
58% inpatient mortality among patients who develop AKI in
36% mortality among all inpatients with AKI
20% of survivors received dialysis
Crit Care Med 1996
Highest risk of post operative AKI
Surgery to correct obstructive jaundice
The Pre-post and intra-renal kidney
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
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
Duration of acute kidney injury impacts
long-term survival after cardiac surgery.
1 to 2 days
3 to 6 days
The duration of AKI after cardiac surgery is directly
proportional to long-term mortality.
Brown JR. Ann T Surg 2010
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
Patient related factors
(usually known prior to surgery)
Chronic Kidney Disease (CKD)
Anderson T Cardi Surg 1993
Chertow G Circulation 1997
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
Thakar CV JASN 2005
Huang TM, JASN 2011
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.
Nephrotoxins ( NSAIDS, ACEI/ARB)
IV fluids Choices( Normal Saline, Lactate Ringers, Hetastarch)
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
I am on losartan. Should we
hold it few days prior to
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
Functional AKI likely but not Structural AKI
Raja SG et al. Interact Cardisvasc Thorac Surg 2008
Coca S et al. NDT 2013
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;
Perner A et al NEJM 2012
Balanced Solutions vs Saline based
Lactate Ringers( balanced solutions)
Yunos NM JAMA 2012
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
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
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
With prior CKD, Off pump CABG might be a better option
Decrease in inflammatory markers
Hemo-dilution related injury( decrease viscosity)
Beauford RB et al Heart Surg Forum 2004
Stallwood 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 2004
Moller CH et al Cochrane Database Sys Rev 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
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
Priming leads to hemodilution
Relationship noted with lowest hemoglobin during CPB and
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
Pre and intra-operative PRBCs
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
Higher levels of proteinuria after cardiac surgery identify
patients at increased risk for AKI during their hospital stay
Molnar AO CJASN 2012
Effect on renal blood flow( vasopressin agonist or a pure
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
Morelli A Shock 2008
Morelli A Crit Care 2008
Russell JA NEJM 2008
Rosner M et al. CJASN 2006
Summary of Risk Factors
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
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 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
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
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
Anti Inflammatory agents
N-acetylcysteine (N-AC , mucomyst)
Statins – harm??
Wang G. J Cardiothorac Vasc Aneth 2011
Morariu AM Chest 2005
Loef BG Br J Anaesth 2004
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
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
Indications for and timing of initiation of RRT in
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
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
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
Early starters had increased survival
Hospital mortality 43% in late starters and 22% in
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
Early initiation of RRT for patients with AKI after cardiac
surgery revealed a lower 28 days mortality and shorter ICU
Based on 11 studies with various qualities and very high
heterogeneity of results.
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
*Cerebral perfusion Better Poor
*= data is from non randomized trials
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
dopamine, lasix, mannitol?
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
Woo EB et al. Eur J Cardiothor Surg 2002
Stone GW et al. JAMA 2003
Kramer BK et al. NDT 2002
ANP ( Anaritide)
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
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
N-AC ( mucomyst)
Cagli K et al. Perfusion 2005
Loef BG et al. Br J Anaesth 2004
Kshirsagar AV et al. JASN 2004
Steroids in Cardiac Surgery Trial (SiRS)
Randomized 7000 patients undergoing CABG to steroids vs
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
Lack of good
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
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
Did not reduce in the incidence of AKI
Prolonged the duration of ventilation and ICU stay
Increased 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
SP had a successful recovery and was
What works thus far?
Minimize contrast exposure and time to surgery
Minimize PRBCs transfusions
Avoiding diuretics unless medical indication
Reducing the use of alpha adrenergic agents by adding
Use of ANP?
AKI occurs in 18% of patients with CABG, with 2-6% needing
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