Download Results

Impact of risk factors in postoperative renal dysfunction in coronary artery bypass
interventions when carried out with and without stopping the heart work. Our
experience
Nikolin Filipi1, Kozeta Filipi2, Adriatik Disani3, Blerim Saraçi4, Arben Kerçiku5
l
European Hospital - Gruppo Villa Maria Tirana, Albania, 2Institute of Public Health, Tirana Albania,
3,4
American Hospital Tirana Albania, 5University Hospital Center “Mother Theresa” Tirana Albania
Correspondence address: Nikolin Filipi, European Hospital - Gruppo Villa Maria, Autostrada Tirane –
Durres tek mbikalimi i Rinasit - Qafe Kashar, Tirana Albania.
Email: [email protected]
The concept of acute renal dysfunction (ARD) has undergone significant re-examination in
recent years. Mounting evidence suggests that acute, relatively mild injury to the kidney or
impairment of kidney function, manifest by changes in urine output and blood chemistries,
portend serious clinical consequences.
Changes in serum creatinine (SCr), urine output and glomerular filtration rate (GFR) could be
reasonably sensitive functional indexes for kidney or tubular injury. Objective: To evaluate
changes in renal parameters in our patient that are intervented with off pump coronary artery
by pass graft (OPCABG G) or coronary artery by pass graft (CABG) type of operation.
Methods: We prospectively collected demographic, intra and postoperative data on renal
function of patients that underwent coronary by pass interventions in a private clinic
"American Hospital" in Tirana, Albania, from January 2007 to February 2010. There were
913 patients operated for coronary by pass interevntions (OPCABG =315; CABG = 598).
Perioperative changes of CrCl, were calculated as difference between these two values:
(DCrCl = PreCrCl - PostCrCl). Results: We support the opinion that isolated analysis of renal
risk should not be taken as a leading indication when selecting the best strategies for our
patients, between OPCABG G or CABG surgery. Conclusions: Our provided data, suggest
that OPCABG neither offers a great risk reduction, nor it provides any protection from renal
damage. However, the different definitions of ARD used in individual trials and
methodological concerns preclude definitive conclusions.
Keywords: acute renal dysfunction, serum creatinine, off pump coronary artery bypass,
coronary bypass interevntion.
Introduction
The concept of acute renal dysfunction (ARD) has undergone significant re-examination in
recent years. Mounting evidence suggests that acute, relatively mild injury to the kidney or
impairment of kidney function, manifest by changes in urine output and blood chemistries,
portend serious clinical consequences [1–5]. It has only been in the past few years that
moderate decreases of kidney function have been recognized as potentially important, in the
critically ill [2] and in studies on contrast-induced nephropathy [4].
It is widely accepted that glomerular filtration rate (GFR) is one of the best overall index of
kidney function in health and disease. However, GFR is difficult to measure and is commonly
estimated from the serum level of endogenous filtration markers, such as creatinie. Chertow
et al. [1] found that an increase of serum creatinine (SCr) of 40.3 mg/dl (426.5mmol/l) was
independently associated with mortality. Similarly, Lassnigg et al.[3] saw, in a cohort of
patients who underwent cardiac surgery, that either an increase of SCr x 0.5 mg/dl
1
(x44.2mmol/l) or a decrease 40.3 mg/dl (426.5mmol/l) was associated with worse survival.
The reasons why small alterations in SCr lead to increases in hospital mortality are not
entirely clear. Possible explanations include the untoward effects of decreased kidney
function such as volume overload, retention of uremic compounds, acidosis, electrolyte
disorders, increased risk for infection, and anemia[6]. Although urine output is both a
reasonably sensitive functional index for the kidney as well as a biomarker of tubular injury.
Indeed a high urine osmolality coupled with a low urine sodium in the face of oliguria and
azotemia is strong evidence of intact tubular function. On the other side in sepsis, the most
common condition associated with ARF in the intensive-care unit (ICU) [7] may alter renal
function without any characteristic changes in urine indices [8,9].
Finally, although severe oliguria and even anuria may result from renal tubular damage, it can
also be caused by urinary tract obstruction and by total arterial or venous occlusion. These
conditions will result in rapid and irreversible damage to the kidney and require prompt
recognition and management as shown in Figure 1.
A number of hospitals, use in their everyday practice the definition of acute renal dysfunction
(ARD) according the following criteria [8] :
 Increase in SCr by 0.3 mg/dl [ 26.5lmol/l] within 48 hours; or
 Increase in SCr to 1.5 times baseline, which is known or presumed to have occurred
within the prior 7 days; or
 Urine volume < 0.5 ml/kg/h for 6 hours. According to its severity, the ARD is staged
to the following criteria as on Table 1.
Background
The incidence of Acute Renal Dysfunction (ARD), varies depending on the adopted
definitions, the mode of detection, and the clinical profile of the analyzed patients [ 1–15]. Its
occurrence, is different across studies, as 1% to 30% of the patients when defined broadly,
whereas frequency of ARD requiring dialysis is generally lower, ranging between less than
1% and 6% [1–15]. Many risk factors for ARD after coronary interventions have been
identified, but only some of them are modifiable [9, 10]. The incidence of ARD is certainly
influenced by the type of cardiac operation [11–14,1 6]. Typically, patients undergoing coronary
artery bypass graft surgery (CABG) present the lowest incidence (2% to 5%), whereas
patients undergoing valvular or combined procedures show a higher rate (as high as 30%)
[17]. Similarly, ARD after transcatheter aortic valve implantation is registered in
approximately 10% of the patients, whereas after complex operations such as aortic surgery
for aneurysm repair or aortic dissection, incidences of ARD have been reported at 10% to
50% [18, 19, 20].
Methodology
Accordingly, we conducted a study aiming to investigate the postoperative renal dysfunction
as an important complication in coronary by pass interevntions that is associated with a
significant increase of morbidity, mortality and much higher healthcare costs.
We hypothesized that, after analyzing relevant covariates, such as demographic data and
renal function tests to put in evidence the hypothesis, whether off pump coronary artery
bypass graft (OPCABG ) is associated with less acute post operatory renal dysfunction
compared to the on pump CABG. Would the presence of risk factors for acute renal failure,
such as age and diabetes mellitus are really independent risk factors for post-operative ARD.
We prospectively collected demographic, intra and postoperative data on renal function of
patients that underwent coronary by pass interevntions in a private hospital “AH" in Tirana
2
Albania, from January 2007 to February 2010. There were 913 patients that underwent
coronary by pass surgeries (OPCABG =315; CABG = 598). During the procedure of Offpump Coronary Artery Bypass grafting (OPCABG ), the patients stays in normothermia, lowdose heparin (150 IU/kg) is given, special myocardial stabilizers (octopus, starfish ..) as well
as partial occluding clamp (POC) technique while introducing proximal grafts in the aorta.
On the other hand, the procedure of coronary artery bypass grafting (CABG) uses full dose of
heparin (300 IU/kg), the use of oxygenator, arterial line filter and sometimes moderate mild
hypothermia (nasopharyngeal temperature to either 32 -34°C).
Inclusive Criteria, include Hannan score: age, sex, obesity, ejection fraction (EF), Acute
Myocardial Infarction(AMI), chronic obstructive pulmonary disease (COPD), diabetes, HTA,
former cardiac operations, history of instable angina, cardiogenic shock and congestive heart
failure. The exclusive Criteria included chronic dialysis and the presence of IABP (intraaortic balloon pump) in the perioperative period.
The preoperative creatinine level, was routinely measured every day in hospital with the
scope to identify its preoperative and postoperative peak values. Preoperative creatinine
value (CrPre), was identified the one more closed to surgery day, but not any longer than 24
hours following the procedure. The highest of all postoperative creatinine figures, was
identified as postoperative creatinine value (CrPost). To calculate the creatinine clearance
(CrCl) of the patients, we based on the Cockcroft and Gault equation, considering it as an
injury marker in the pre and postoperative period.
Perioperative changes of CrCl values, were calculated as difference between these two
values: (DCrCl = PreCrCl - PostCrCl). Univariate comparisons of demographic variables
between two patients’ groups of CABG and OPCABG were estimated using Student’s test.
OPCABG patient’s association with DCrCl was further analyzed using the linear
multivariate regression in SPSS 16.0. Because of abnormal distribution of the CrCl values
and to evaluate the generalization and invariability of the results, these analyses were made
by listing the data. P< 0.05 were considered as significant values.
Results
Demographic and renal function data were collected and analyzed for all the patients,
OPCABG (n =315) and CABG (n=598). Demographic variables among 913 patients were
found to be the same as those reported before among great population. Results were
presented as mean ± SD [Table 2] and [Table 3].
Discussion
We could identify the significant independent associations of renal risk factors (IRA in
preoperative period, advanced age and diabetes [Figure 1]. In our findings, we couldn’t
confirm that OPCABG reduces renal function risk compared to surgery of CABG [Figure 2].
We showed that avoidance of CABG does not reduce the risk of postoperative renal
dysfunction. Avoiding CABG by using instead OPCABG , may submit a comparable risk for
renal insult, as well.
Since most of the interventions of CABG , were performed at an early stage and immediately
after accomplishment of angiography, p < 0.05 (Tab 2), this may alter renal function of the
patients [Graph 3].
As for the duration of the CABG in the cases where stopping heart technique was applied, we
noticed that there is a significant correlation (p < 0.01), between total operation time and the
presence of acute renal dysfunction (Table 3). In our study, we couldn’t find any influence on
the effect that aortic clamping time and cardioplegia amount, have on the manifestation of
acute renal dysfunction among patients (Table 3). In our multivariate analysis, the
3
performance of angiography, didn’t resulted as an independent variable. CrCl is widely
known, as an adequate test of glomerular filtration rate. Definitely, when analyzing that, one
should take into account the other factors of kidney homeostatics as osmolality regulation, the
state of electrolytes and acid alkaline balance, etc. CrCl as an adequate test of glomerular
filtration rate [21].
Our provided data, suggest that OPCABG doesn’t offer a great risk reduction of renal
damage. Anyway, this must be confirmed with a larger study that can examine thoroughly the
way of renal functions and its performance in general. OPCABG surgery compared with
CABG does not provide any protection from renal damage.
Conclusion
While there is everywhere a growing interest in applying new strategies that minimize renal
damage linked to surgery, we support our opinion that isolated analysis of renal risk should
not be taken as a leading indication when selecting the best strategies for our patients,
between OPCABG and CABG surgery. Our analysis didn’t show a statistically significant
benefit with respect to dialysis requirement or mortality. Off pump CABG may sometimes be
associated with a lower incidence of postoperative ARD but it may not affect dialysis
requirement, which is a serious complication of coronary by pass interevntions. However, the
different definitions of ARD used in individual trials and methodological concerns preclude
definitive conclusions. Future studies should apply a standard definition of ARD and target a
high-risk population.
Preoperative
renal insufficiency
Advanced
age
History of
congestive heart
failure
Diabetes
Mellitus
↑ risk of Acute Renal Dysfunction
Recent exposure to
nephrotoxic agents
Intra Aortic
Balloon Pump
Emergency
Surgery
Figure 1. Main risk factors for acute renal dysfunction after
cardiac surgery
4
Cardiopulmonary bypass,
hypothermia, non-pulsatile
flow, renal hypo perfusion,
↑catecholamine levels,
induction of inflammatory
mediators
Stage
1
2
3
Staging of ARD
Serum creatinine
1.5–1.9 times baseline OR 0.3 mg/dl [ 26.5mmol/l] increase
2.0–2.9 times baseline
3.0 times baseline OR Increase in serum creatinine to 4.0 mg/dl [
353.6 mmol/l] OR Initiation of renal replacement therapy OR, In
patients < 18 years, decrease in GFR to < 35 ml/min per 1.73 m2
Urine output
< 0.5 ml/kg/h for 6–12 hours
< 0.5 ml/kg/h for 12 hours
< 0.3 ml/kg/h for 24 hours
OR Anuria for 12 hours
Table 1. Staging of ARD based on Serum creatinine and Urine output [8].
Variables
Number of patients
Age (yrs)
Females (%)
Weight (kg)
HTA (%)
Diabetes (%)
CrPre (mmol/L)
PreCrCl (mL/min)
CrPre ≥ 133 mmol/L (%)
Postoperative peak of Cr serum (mol/L)
Differences in creatinine serum (µmol/L)
Differences in creatinine clearance
(mL/min)
Postoperative renal dysfunction (%)
Use of ACEI (%)
Hannan Score (mean)
Graft Number
Preop. EF (%)
Postop. IABP (%)
Periop. angiography + contrast (%)
Postop. Dialysis (%)
CABG
598
63.3
31.9
84.8
64
34.8
98.1
86.9
9.8
126.4
28.3
16.5
OPCABG
315
60.2
41.6
82.4
61
29.1
94.6
88.1
9.1
123.8
35.7
16.8
P - value
7.7
26.3
0.027
3.10
51.9
3.8
0.31
0.31
8.9
20.9
0.028
1.72
53.9
7.3
25.0
1.8
0.74
0.45
0.87
0.0001
0.31
0.21
0.001
0.10
0.04
0.08
0.36
0.60
0.39
0.57
0.80
0.87
0.78
0.95
0.92
Table 2. Factors affecting acute renal dysfunction (ARD)according to the type of operation performed
Total time of
operation (sec)
Cardioplegia
amount (ml)
Aortic clamp
time (sec)
.451**
.176
-.002
.001
.242
.988
13.213
1921.739
-1.087
.287
42.705
-.024
47
46
46
Pearson Correlation
Sig. (2-tailed)
ARD (acute renal
dysfunction)
Sum of Squares and
Cross-products
Covariance
N
**Correlation is significant at the 0.01 level (2-tailed)
* Correlation is significant at the 0.05 level (2-tailed)
Table 3. Correlation between total operation time and the presence of acute renal dysfunction
5
Figure 1. Correlation of surgery type and possible renal risk factors
Figure 2. Correlation between type of surgery and renal function tests
Figure 3. Correlation between type of surgery and cardiac function
References:
1. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of
stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16:3365–3370.
2. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are
associated with hospital mortality in critically ill patients: a cohort analysis. Crit
Care 2006; 10: R73.
6
3. Lassnigg A, Schmidlin D, Mouhieddine M,et al. Minimal changes of serum creatinine
predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.
J Am Soc Nephrol 2004; 15: 1597–1605.
4. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A
cohort analysis. JAMA 1996; 275: 1489–1494.
5. Uchino S, Bellomo R, Goldsmith D, et al. An assessment of the RIFLE criteria for
acute renal failure in hospitalized patients. Crit Care Med 2006;34: 1913–1917.
6. Hoste EA, Kellum JA. Acute renal failure in the critically ill: impact on morbidity and
mortality. Contrib Nephrol 2004; 144: 1–11.
7. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a
multinational, multicenter study. JAMA 2005; 294: 813–818.
8. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Summary of
Recommendation Statements: Kidney International Supplements [2012] 2, 8–12;
doi:10.1038/kisup.2012.7
9. Rosner M, Okusa M. Acute kidney injury associated with cardiac surgery. Clin J Am
Soc Nephrol 2006; 1: 19–23
10. Stolker JM, McCullough PA, Rao S et al. Pre-procedural glucose levels and the risk
for contrast-induced acute kidney injury in patients undergoing coronary
angiography. J Am Coll Cardiol 2010; 55: 1433–1440
11. Chertow GM, Lazarus JM, Christiansen CL, et al. Preoperative renal risk
stratification. Circulation 1997;95:878–84.
12. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury,
mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol
2005;16:3365–70.
13. Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney injury after cardiac
surgery: focus on modifiable risk factors. Circulation 2009;119:495–502.
14. Wijeysundera DN, Karkouti K, Dupuis JY, et al. Derivation and validation of a
simplified predictive index for renal replacement therapy after cardiac surgery. JAMA
2007;297:1801–9.
15. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clinical score to predict
acute renal failure after cardiac surgery. J Am Soc Nephrol 2005;16:162–8.
16. Mehta RH, Grab JD, O’Brien SM, et al. Bedside tool for predicting the risk of
postoperative dialysis in patients undergoing cardiac surgery. Circulation
2006;114:2208–16.
17. Seabra VF, Alobaidi S, Balk EM, Poon AH, Jaber BL. Offpump coronary artery
bypass surgery and acute kidney injury: a meta-analysis of randomized controlled
trials. Clin J Am Soc Nephrol 2010;5:1734–44.
18. Arnaoutakis GJ, Bihorac A, Martin TD, et al. RIFLE criteria for acute kidney injury
in aortic arch surgery. J Thorac Cardiovasc Surg 2007;134:1554–60.
19. Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased
long-term mortality after cardiothoracic surgery. Circulation 2009;119:2444–53.
20. Bagur R, Webb JG, Nietlispach F, et al. Acute kidney injury following transcatheter
aortic valve implantation: predictive factors, prognostic value, and comparison with
surgical aortic valve replacement. Eur Heart J 2010;31:865–74.
21. Jain AK, McLeod I, Huo C et al. When laboratories report estimated glomerular
filtration rates in addition to serum creatinines, nephrology consults increase. Kidney
Int. 2009 Aug;76(3):318-23. doi: 10.1038/ki.2009.158.
7