Methods: The results of 360 patients who underwent elective CABG surgery between December 2006 and April 2008 were evaluated retrospectively. Two-hundred and sixty-seven of these patients underwent CABG surgery. Finally, we evaluated the results of 55 patients (23 females, 22 males; mean age 66.7±9.4 years; range 45 to 84 years) who had creatinine clearance values lower than 60 mg/kg/m2.
Results: Mortality occurred in two patients (8.6%) with mild glomerular filtration rate (GFR) decrease (0-25% decrease from preoperative GFR), in two patients (11.6%) with moderate decrease (25-50%) and in three patients (75%) with severe decrease (>50%). It was determined that GFR decrease in the postoperative period increased the likelihood of death (p=0.001). The odds ratio of death in the group with mild decrease in GFR increased 12.6 times, that in the group with moderate decrease increased 15.6 times and that in the group with severe decrease increased 35.2 times.
Conclusion: If the renal function in patients with chronic renal disease can be kept at the levels of preoperative values, postoperative early results are affected mildly. However, if acute exacerbation occurs, it increases the risk of mortality. This data also indicates that every effort to save renal function will decrease postoperative mortality.
Chronic kidney disease (CKD) is associated with worse outcomes after CABG surgery. However, there are five different stages of chronic kidney disease according to the National Kidney Foundation.[4] As the stage progresses, mortality increases as well. Mortality rates for stages 1 to 4 are 0, 1.9, 4.3 and 33.3% respectively.[5] Dialysis-dependent CKD (stage 5) is associated with approximately 2.9 and 3.8-fold increases in odds of operative mortality following CABG surgery.[6] Careful perioperative planning and special management are the keys to minimize the risk of the patient as the stage increases.
In this report we would like to investigate short term results of patients who had CKD before CABG surgery.
We performed the study at a tertiary care, teaching University Hospital.
Participants
Adults undergoing elective CABG surgery between
December 2006 and April 2008 were enrolled in the
study. There were 360 patients operated on during this
period. Two hundred and sixty seven patients underwent
CABG surgery. We excluded patients who had off-pump
CABG procedure (n=12). Patients who underwent concomitant
procedures such as valve surgery, ascending
and or arcus aorta surgery, carotid surgery and redo
surgery were also excluded (n=105). Finally, we evaluated
the results of 55 patients (23 females, 22 males;
mean age 66.7±9.4 years; range 45 to 84 years) who had
creatinine clearance values lower than 60 mg/kg/m2.
The study was approved by the ethics committee of our
institution.
Surgical technique
Radial and pulmonary arterial catheters were introduced
under local anesthesia. After standard anesthesia, a median
sternotomy was performed followed by routine aortic
and right atrial two-stage cannulation. The standard
cardiopulmonary bypass (CPB) technique was carried
out using membrane oxygenators and under moderate
systemic hypothermia (30 ºC). Mean arterial blood pressure was kept between 50 and 70 mmHg during CPB.
Myocardial protection was achieved by antegrade and
retrograde cold blood cardioplegia. Heparin was administered
3.0 mg/kg and was neutralized with protamine, in
a ratio of 1:3, within 10 min. after the end of CPB.
Short term mortality was defined as death within 30 days of the operation or during the same hospitalization. Low cardiac output syndrome (LCOS) was defined as the need for postoperative intraaortic baloon support (IABP) and/or inotropic support, for any length of time, in the intensive care unit (ICU).
Renal replacement therapy
We prefer to use continous venovenous hemodiafiltration
(CVVHD) in renal replacement therapy since early
and aggressive use of CVVHD is associated with better
survival in severe acute renal failure (ARF) after cardiac
operations.[8] Patients who were on a hemodialysis
program before surgery had dialysis before and after
surgery. Dialysis the day before was done for potential
beneficial effects.[9] In two patients, hemodialysis was
needed to immediatedly reduce potassium levels following
surgery.
Statistical analysis
We compared baseline patient characteristics and outcome
variables across treatment groups, categorical
variables by using Chi-square or Fisher’s exact tests, and
continuous variables by using T-tests or Wilcoxon ranksum
tests. The variables with a p value less than 0.10 at
univariate analysis were entered in a stepwise multiple
linear regression analysis to identify the independent
predictors of mortality and ICU stay. We estimated odds
ratios according to multivariate logistic regression analyses
and considered two-sided p values less than 0.05
to be statistically significant. We used SPSS (Statistical
Package for the Social Sciences), version 15.0 (SPSS
Inc., Chicago, IL) for analyses.
Age (66.2±9.6 vs. 62.1±17.3 years; p=0.001) was higher, extubation time (8.4±12.6 vs. 6.2±6.6 hours; p=0.01) was longer, ICU stay (64.4±42.5 vs. 44.2±14.2 hours; p=0.02) was longer, and discharge time (9.95±5.56 vs. 7.64±4.3 days; p=0.01) was longer in CKD patients.
Major perioperative morbidities are included in table 2. Five of eight patients who had low cardiac output syndrome (LCOS) received intra-aortic balloon pump (IABP) support and two of them had perioperative myocardial infarction. There was no deep sternal wound infection and no bleeding that required revison as well (Table 2).
Table 1: Perioperative descriptives
Table 2: Perioperative morbidity and mortality
Seven patients died in the early postoperative period. The most common causes of early death were LCOS (5%), multisystem organ failure (MOF) (5%) and perioperative myocardial infarction (3.6%; Table 3). When compared to patients with no CKD (stage 3 and higher), the mortality rate was higher in the CKD group (7% vs 2.5%; p<0.001). All morbidity and mortality parameters were higher in the CKD group, however inotrop usage (p=0.03), prolonged intubation (p=0.02), IABP usage (p=0.03) were statistically higher. According to postoperative GFR, patients were classified in three subgroups: patients who had mild GFR decrease (0-25% decrease from preoperative GFR), moderate (25-50%) and severe (>50%; Table 4). As noted in the table 4, GFR decrease in postoperative period directly increased the likelihood of death. There were two deaths in the mild group which had an odds ratio of 12.6. A moderate decrease in GFR resulted in an odds ratio of 15.6, while a severe decrease increased the likelihood of death 35 times. Three patients died in the severe decrease group which represents 75% of patients in that subcategory.
Table 4: Glomerular filtration rate decrease
Factors that are associated with mortality and ICU stay were identified with logistic regression analysis (Table 5). Preoperative creatinine values were not associated with longer ICU stay and early mortality, however postoperative renal indexes such as increased creatinine and decrease of GFR were associated with longer ICU stay and early mortality. The most significant factor affecting prolonged ICU stay and early mortality was postoperative GFR decrease (p=0.001).
Table 5: Factors for ICU stay (>48 hours) and early mortality
Mild renal disfunction is an important independent predictor of in-hospital and late mortality in adult patients undergoing elective cardiac surgery including CABG and valve operations.[13] The mechanism in by which renal dysfunction contributes to postoperative mortality is unknown. In-hospital deaths were directly secondary to cardiovascular causes in two patients. Decreased GFR may be a marker of a more advanced cardiovascular disease including increased levels of inflammatory mediators and hypercoagulability, endothelial dysfunction, arterial stiffness or calcificatio and left ventricular hypertrophy.[9]
In isolated CABG series, CKD was an important predictor of in-hospital death as well. Zakeri et al.[14] found that the higher the preoperative creatinine levels, the higher the mortality rates were. They found that the mortality rate for GFR 90 mL/min per 1.73 m2 was 1.0% (17 of 1707); GFR 60 to 89 mL/min per 1.73 m2 was 2.1% (40 of 1922); GFR 30 to 59 mL/min per 1.73 m2 was 7.1% (45 of 631) in their large (n=4403) series.
Our postoperative data shows that major complications following CABG such as inotrope usage, LCOS, AF, IABP usage and mortality rates are higher than the elective non-CKD patient population. Mortality rate is 12.7%, which is a very high rate for non-CKD operations, but reasonable for a series of CKD patients.
It was found that the patients had different characteristics based on their decrease in clearance. Mortality rates for the groups were 8.6% for the first group, and 11.1% and 75% for the second and third groups respectively. The odds ratio for mild, moderate and severe decrease in clearence had an odds ration of 12.6, 15.6 and 35.2 respectively. This analysis shows that acute worsening of kidney functions of patients who had chronic kidney disease increases mortality directly related to remaining renal functions. A severe decrease in creatinine clearence increases mortality rates up to 35.2 times, and has a mortality rate of 75%. However, if there is no difference or a minimal change in GFR, mortality rate is significantly lower.
Factors affecting mortality and prolonged ICU stay were related to renal indexes such as postoperative creatinine and postoperative GFR decrease (both p=0.001). The other factor related to early mortality was perioperative myocardial infarction.
Chronic kidney disease is a well known and established risk factor for early complications and death following CABG surgery. If the renal functions would be kept as the levels of preoperative values, the impact of CKD on early results are mild, however if acute exacerbation occurs, it is strongly related to death. This data also indicates that, every effort to save any renal function after surgery has to be done perioperatively in order to reduce postoperative mortality.
Limitations
There was no bleeding which required revision in operating
room, deep sternal wound infection and stroke
in our series. This may be related to small number of
patients in our study. Only one surgical team performed
all the operations; this may also be a very important factor
for reducing bleeding and infectious complications.
Since CKD is a risk factor for all postoperative short term outcomes, this study does not indicate that morbidity and mortality rates are decreased. If the kidney functions remain unchanged like the 0-25% GFR decrease group, the mortality rates is still higher than the normal population at 8.6%.
Fifty-five patients who had GFR lower than 60 mL/min per 1.73 is a small series of patients from a single center. This may under or over estimate the rates of complications and results. More reliable results could be achieved by increasing the number of patients. However all patients were operated on by the same surgeon and team, so we believe this small series can demonstrate a result to show up the effect of renal function on early results.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect
to the authorship and/or publication of this article.
Funding
The authors received no financial support for the
research and/or authorship of this article.
1) Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal
A, Herskowitz A, Mangano DT. Renal dysfunction after
myocardial revascularization: risk factors, adverse outcomes,
and hospital resource utilization. The Multicenter Study of
Perioperative Ischemia Research Group. Ann Intern Med
1998;128:194-203.
2) Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann
LM, Druml W, Bauer P, et al. Minimal changes of serum
creatinine predict prognosis in patients after cardiothoracic
surgery: a prospective cohort study. J Am Soc Nephrol
2004;15:1597-605.
3) Conlon PJ, Stafford-Smith M, White WD, Newman MF,
King S, Winn MP, et al. Acute renal failure following cardiac
surgery. Nephrol Dial Transplant 1999;14:1158-62.
4) National Kidney Foundation. K/DOQI clinical practice
guidelines for chronic kidney disease: evaluation, classification,
and stratification. Am J Kidney Dis 2002;39(2 Suppl
1):S1-266.
5) Kangasniemi OP, Mahar MA, Rasinaho E, Satomaa A,
Tiozzo V, Lepojärvi M, et al. Impact of estimated glomerular
filtration rate on the 15-year outcome after coronary
artery bypass surgery. Eur J Cardiothorac Surg 2008;
33:198-202.
6) Yeo KK, Li Z, Yeun JY, Amsterdam E. Severity of chronic
kidney disease as a risk factor for operative mortality in nonemergent
patients in the California coronary artery bypass
graft surgery outcomes reporting program. Am J Cardiol
2008;101:1269-74.
7) Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth
D. A more accurate method to estimate glomerular filtration
rate from serum creatinine: a new prediction equation.
Modification of Diet in Renal Disease Study Group. Ann
Intern Med 1999;130:461-70.
8) Elahi MM, Lim MY, Joseph RN, Dhannapuneni RR, Spyt
TJ. Early hemofiltration improves survival in post-cardiotomy
patients with acute renal failure. Eur J Cardiothorac Surg
2004;26:1027-31.
9) Haberal C, Keles C, Erdogan HB, Elevli MG, Dağlar B,
Yakut C. Coronary artery surgery in patients with end stage
renal disease receiving hemodialysis treatment. Turkish J
Thorac and Cardiovasc Surg 2000;8:655-7.
10) Rosner MH, Okusa MD. Acute kidney injury associated with
cardiac surgery. Clin J Am Soc Nephrol 2006;1:19-32.
11) Simmons PI, Anderson RJ. Increased serum creatinine: a
marker for adverse outcome before and after cardiac surgery.
Crit Care Med 2002;30:1664-5.
12) Andersson LG, Ekroth R, Bratteby LE, Hallhagen S, Wesslén
O. Acute renal failure after coronary surgery--a study of incidence
and risk factors in 2009 consecutive patients. Thorac
Cardiovasc Surg 1993;41:237-41.