MANAGEMENT AND TREATMENT OF ACUTE KIDNEY INJURY IN CARDIAC SURGERY. CLASSIFICATION OF AKI.

1. By
DR.VIJAYANAND PALANISAMY

3.  “acute or chronic dysfunction in one organ
may induce acute or chronic dysfunction of
the other”

4.  Introduction
 Risk Factors
 Treatment
 Prevention

5. ATN (45%)
Prerenal (21%)
ARF on CKD (13%)
Obstruction (10%)
GN/vasc (4%)
AIN (2%)
Atheroemboli (1%)
Kidney Int: 1996

7.  The RIFLE and AKIN criteria are now well established criteria in
studies of CSA-AKI.
 However, Sampaio et al. declared the KDIGO criteria to be
superior to AKIN and RIFLE with regard to prognostic power.

8.  Highest risk of post operative AKI
◦ Cardiac surgery
◦ AAA repair

10.  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.  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.  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

13. Rosner M et al. CJASN 2006

14.  Nephrotoxins( NSAIDS, ACEI, ARBS, Diuretics, Contrast-
Contrast-induced nephropathy)
 Emergency surgery
 Higher levels of proteinuria pre cardiac surgery identify
patients at increased risk for AKI during their hospital stay.
 IV fluids Choices( Normal Saline, Lactate Ringers,
Hetastarch)

15. Myburgh JA, NEJM 2012

16.  Normal Saline
 Lactate Ringers( balanced solutions)
Yunos NM JAMA 2012

17.  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

18.  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

19.  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

20. Lamy A, NEJM 2012

21. 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

22.  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

23.  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?
 RECEIVING >2 PRBC – GREAT RISK OF AKI
 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

24.  Nephrotoxins
 Sepsis
 Volume depletion
 Hemodynamic instability
 Proteinuria
 Vaso-active agent choices

25.  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

26. Rosner M et al. CJASN 2006
Summary of Risk Factors

27.   
Contrast, NSAIDS,
CKD, ACEI/ARB, NPO
CPB, clamp, inflammation
hypotension
Sepsis, reduced LV,
Nephrotoxins

28. • 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)

29. Thakar CV et al
JASN 2005

31.  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

32.  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

33.  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

34. Bove T JAMA 2014

36.  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

37.  Intermittent
hemodialysis(IHD)
 CRRT (CVVHD,
CVVHDF, CVVH)
 Sustained low
efficiency dialysis
(SLED)
 Peritoneal Dialysis(PD)

38.  AEIOU
 Acidosis, refractory metabolic
 Electrolyte disorders, mainly
hyperkalemia
 Intoxication ( unusual for CT surgery
case)
 Overload( fluid related, totally
possible)
 Uremia( very possible)

42.  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

43.  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

44. 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

45.  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

46.  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.

47. 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

49.  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

50.  Dopamine
 Fenoldopam
 Theophylline
Woo EB et al. Eur J Cardiothor Surg 2002
Stone GW et al. JAMA 2003
Kramer BK et al. NDT 2002

51.  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

52.  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

53.  Preoperative acetylsalicylic acid
 N-Acetylcysteine - antioxidant properties
 Sodium bicarbonate –. Prolonged the duration of ventilation
and ICU stay , Increased the risk of alkalemia
 Steroids in Cardiac Surgery Trial (SiRS) -
Methylprednisolone increases the risk of early post-
operative myocardial infarction
 Preoperative statin therapy - battery of renal biomarkers
were significantly decreased, including urine interleukin-
18, urine and plasma NGAL, and urine kidney injury
molecule-1.

54.  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

56.  The two biomarkers that have shown to be most
promising are human NGAL(neutrophil
gelatinase-associated lipocalin) and cystatin C.
 NGAL, also known as lipocalin 2, is secreted by
injured distal tubule epithelial cells, and enters
the urine via tubular back leak.
 Cystatin C is a low-molecular-weight protein
that is rapidly filtered by the glomerulus. When
GFR decreases, serum cystatin C levels increase
before elevations in SCr.


58.  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?

59.  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