Introduction Coronary artery bypass grafting (CABG) is a highly successful surgical treatment for the relief of angina and prolongs life in patients with coronary artery disease (CAD). Preoperative renal dysfunction is a significant risk factor that influences the outcome in patients undergoing CABG surgery. Mild renal dysfunction is an adverse prognostic indicator in patients with coronary artery disease. Several studies showed that patients with mild renal dysfunction have an increased risk of dying within 30 days after coronary surgery. Patients with renal dysfunction who require CABG represent a complex group of patients with accelerated atherosclerosis and advanced cardiovascular disease. Methods And Materials This is a prospective study was conducted in the Department of Cardiothoracic and vascular surgery, Yashoda Hospital, Secunderabad. OPCAB was performed with the Octopus-Evolution tissue stabilizer system device for target coronary artery stabilization. A mean systemic arterial pressure was maintained around 65 to 70 mmHg throughout the procedure. An intracoronary shunt was used in all target coronaries greater than 1.25mm in diameter during construction of distal anastomosis. Humidified carbon dioxide blower /mister was used to disperse the blood from the anastomotic site while constructing the distal anastomoses Results The mean age in mild group was 59.05±7.60 and 56.37±9.06 in normal group, p=0.15. In mild group 16 (40.00) were females and 24 (60.00) were males whereas 10(25.00) were females and 30 (75.00) were males in normal group, p=0.15(figure 2). Preoperative variables such as BMI>30 (p=0.30), Smoking (p=1.00), Hypertension (p=0.33), Diabetes mellitus (p=0.57), Hyperlipidaemia (p=0.63), COPD (p=0.80), preoperative MI (p=0.81) were compared between the mild and normal groups and none of the baseline variables were significant between the groups Conclusions There was no significant difference in the patients undergoing off-pump CABG with normal renal function and mild renal dysfunction in terms of short-term mortality, myocardial infarction, stroke, or renal failure requiring dialysis. Off-pump CABG is more reno-protective for patients with normal renal function but for patients with mild renal dysfunction may need preoperative assessment of renal function by GFR in addition to serum creatinine levels to stratify the risk for postoperative renal dysfunction and to optimize measures for renal preservation during surgical myocardial revascularization
Coronary artery bypass grafting (CABG) is a highly successful surgical treatment for the relief of angina and prolongs life in patients with coronary artery disease (CAD). Preoperative renal dysfunction is a significant risk factor that influences the outcome in patients undergoing CABG surgery [1-4].
Mild renal dysfunction is an adverse prognostic indicator in patients with coronary artery disease [5]. Several studies showed that patients with mild renal dysfunction have an increased risk of dying within 30 days after coronary surgery [6,7,8]. Patients with renal dysfunction who require CABG represent a complex group of patients with accelerated atherosclerosis and advanced cardiovascular disease [9-11].
Patients with decreased renal function (serum creatinine ≥2.0 mg/dL) carry significant operative risks, require prolonged hospital stays, and have a higher risk of dying within 3 years after coronary surgery [8]. In addition, severe preoperative renal disease is associated with a higher incidence of morbidity, need for dialysis, and length of hospital stay after CABG [12].
Coronary artery bypass grafting performed with the aid of cardiopulmonary bypass adversely affects renal function, causing varying degrees of post-operative renal impairment. Off-pump coronary artery bypass grafting (OPCAB), eliminates the need for cardiopulmonary bypass (CPB), has been reported to be associated with better outcomes and is expected to have less negative impact on the postoperative renal function than conventional CABG in patients with renal dysfunction [12–15]. Though off-pump coronary artery bypass surgery technique avoids cardiopulmonary bypass circuit induced adverse effects on renal function, multiple other factors cause postoperative renal dysfunction in these group of patients.
Elevated preoperative serum creatinine (SCr) is considered an independent risk factor for postoperative morbidity and mortality in patients undergoing cardiac surgery [16,17,18]. The overall mortality for the patients with preoperative serum creatinine more than 1.5mg/dL, ranges from 5%-30% with the rise in the probability of death [17-20]. So, it is crucial to accurately assess the preoperative renal function.
Report from the Society of Thoracic Surgeons National Database on patients undergoing CABG showed that preoperative renal disease is common in patients undergoing CABG and that early mortality and morbidity after CABG rise inversely with declining preoperative renal function. Preoperative renal dysfunction is thus a powerful, independent predictor of postoperative acute kidney injury. Hence, the assessment of preoperative renal function should be incorporated into clinical risk assessment and prediction models. Furthermore, the EUROSCORE II includes renal impairment, as measured by creatinine clearance, as one of the risk factors for adverse outcomes after surgery. [21]
This is a prospective and randomized study was conducted in the Department of Cardiothoracic and vascular surgery, Yashoda Hospital, Secunderabad.
Study sample Inclusion criteria
Exclusion criteria
Off- pump CABG technique (OPCAB)
OPCAB was performed with the Octopus-Evolution tissue stabilizer system device (MEDTRONIC, Cardiovascular, Minneapolis, Minnesota, US) for target coronary artery stabilization. A mean systemic arterial pressure was maintained around 65 to 70 mmHg throughout the procedure. An intracoronary shunt (Medtronic, Inc, Minneapolis, MN, USA) was used in all target coronaries greater than 1.25mm in diameter during construction of distal anastomosis. Humidified carbon dioxide blower /mister (Medtronic, Inc, Grand Rapids, MI) was used to disperse the blood from the anastomotic site while constructing the distal anastomoses
Data collection and definitions
Demographic and procedural data will be collected from patients who are willing to take part in the study. At the time of admission to the operation baseline clinical characteristics such as age, sex, obesity, smoking, New York Heart Association (NYHA) class, previous myocardial infarction (MI), percutaneous coronary intervention (PCI), diabetes mellitus (DM), hypertension, hyperlipidaemia, chronic obstructive pulmonary disease (COPD), Left ventricular ejection fraction (LVEF), prior CVA , eGFR, anatomical severity of coronary artery disease (CAD). Operative data like number of grafts, type of conduit, target artery and postoperative details such as major adverse cardiac cerebrovascular events were collected.
Definitions
The serum creatinine was measured before surgery and the GFR was calculated by using Cockcroft- Gault formula [6]. Normal renal function was defined as eGFR of 90 ml/min/1.73 m2 or more and mild RI was defined as eGFR of 60 to 89 ml/min/1.73 m2.
Estimation of GFR by MDRD Equation
With reference to Clinical Practice Guidelines of National Kidney Foundation, normal renal function was defined as eGFR of 90 ml/min/1.73 m2 or more, and mild, moderate and severe renal insufficiency were defined as eGFR of 60 to 89, 30 to 59, and less than 30 ml/min/ 1.73 m2, respectively. This study focused on patients with mild preoperative renal insufficiency (eGFR of 60–89 ml/ min/1.73 m2) and patients with normal preoperative renal function (eGFR of 90 ml/min/1.73 m2 or more).
Surgical mortality was defined as death occurring during the same hospitalization or within 30 days of the operation. Postoperative myocardial infarction was defined by either the appearance of new Q waves in 2 or more contiguous leads on the electrocardiogram or an increase in the creatinine kinase MB isoenzyme fraction of more than 50U, in concert with an excess of 7% of the total creatinine kinase level. After OPCAB surgery, any episode of atrial fibrillation that was registered by the monitoring system on a rhythm strip or the 12-lead ECG and lasting for more than 5 min with or without symptoms, was defined as postoperative atrial fibrillation.
Intra-aortic balloon pump (IABP) support, postoperative respiratory failure (duration of mechanical ventilation more than 72 h or re-intubation following OPCAB surgery), postoperative pneumonia (a positive result in a sputum culture requiring anti-infective treatment, or chest X-ray diagnosis of pneumonia following cardiac surgery), stroke (new permanent neurological event; early stroke: within 24 h and delayed stroke greater than 24 h postoperatively), redo for bleeding (re-operation to control bleeding within 36 h following initial surgery), red blood cell (RBC) transfusion, acute kidney injury requiring dialysis, and deep sternal wound infection (DSWI) (bone related; any drainage of purulent material from the sternotomy wound and instability of the sternum) will be recorded
Statistical methods
Data will be presented as absolute numbers, mean, and standard deviation, or percentages. Values of continuous variables will be expressed as a mean ± standard deviation (SD). Categorical variables are represented as frequency distributions and single percentages. Normally distributed continuous variables will be compared using a student t-test, non-normally distributed continuous variables using the Mann-Whitney U test, and categorical variables will be compared by χ2 and Fisher's exact test where appropriate. Estimations of risk and potential independent predictors of outcome will be identified by logistic regression analyses. All statistical tests will be two-sided. Results will be considered statistically significant at a level of p less than 0.05. All analysis will be performed using SAS version 9.2 (SAS institute, Cary, NC) software
Of 80 patients, 40 patients had normal renal function and 40 patents had preoperative mild renal dysfunction
Analysis of baseline characteristics between mild and normal groups
The mean age in mild group was 59.05±7.60 and 56.37±9.06 in normal group, p=0.15. In mild group 16 (40.00) were females and 24 (60.00) were males whereas 10(25.00) were females and 30 (75.00) were males in normal group, p=0.15(figure 2). Preoperative variables such as BMI>30 (p=0.30), Smoking (p=1.00), Hypertension (p=0.33), Diabetes mellitus (p=0.57), Hyperlipidaemia (p=0.63), COPD (p=0.80), preoperative MI (p=0.81) were compared between the mild and normal groups and none of the baseline variables were significant between the groups (table 1).
Table 1: Baseline characteristics between mild and normal groups
Variable |
Unit |
Mild (n=40) |
Normal(n=40) |
p value |
Age |
mean±SD |
59.05±7.60 |
56.37±9.06 |
0.15 |
Sex |
Female |
16 (40.00) |
10(25.00) |
0.15 |
Male |
24(60.00) |
30(75.00) |
||
BMI>30 |
No |
28(70.00) |
32(82.00) |
0.30 |
Yes |
12(30.00) |
8(20.00) |
||
Smoking |
No |
22(55.00) |
22(55.00) |
1.00 |
Yes |
18(45.00) |
18(45.00) |
||
Hypertension |
No |
11(27.50) |
15(37.00) |
0.33 |
Yes |
29(72.50) |
25(62.50) |
||
Diabetes mellitus |
No |
7(17.50) |
9(22.50) |
0.57 |
Yes |
33(82.50) |
31(77.50) |
||
Hyperlipidemia |
No |
26(62.00) |
28(70.00) |
0.63 |
Yes |
14(35.00) |
12(30.00) |
||
COPD |
No |
28(70.00) |
29(72.50) |
0.80 |
Yes |
12(30.00) |
11(27.50) |
||
NYHA |
1 |
2(5.00) |
4(10.00) |
0.51 |
2 |
34(85.00) |
34(85.00) |
||
3 |
4(10.00) |
2(5.00) |
||
NYHA |
mean±SD |
2.05±0.38 |
1.95±0.38 |
0.10 |
Preoperative CVA |
No |
40(100.00) |
40(100.00) |
- |
Yes |
0(0.00) |
0(0.00) |
||
Preoperative MI |
No |
16(40.00) |
15(37.50) |
0.81 |
Yes |
24(60.00) |
25(62.50) |
||
Prior PTCA |
No |
29(72.50) |
30(75.00) |
0.79 |
Yes |
11(27.50) |
10(25.00) |
||
LV dysfunction |
No |
0(0.00) |
0(0.00) |
- |
Yes |
40(100.00) |
40(100.00) |
||
Extent of CAD |
SVD |
0(0.00) |
1(2.50) |
0.12 |
DVD |
0(0.00) |
3(7.50) |
||
TVD |
40(100.00) |
36(90.00) |
||
Surgery |
Elective |
40(100.00) |
40(100.00) |
- |
COPD: chronic obstructive pulmonary disease; NYHA: New York heart association; CVA: cerebrovascular accident; MI: myocardial infarction; PTCA: percutaneous transluminal coronary angioplasty; LV: left ventricle; SVD: single vessel disease; DVD: double vessel disease; TVD: triple vessel disease
Intraoperative and postoperative characteristics
Distribution of various territories and conduits shown in figure 3 and figure 4. Mean number of grafts were equal between the groups (mild 3.5±0.90 vs 3.57±0.95), p=0.72. means of ventilation requirement 12.17±9.32 was slightly high in mild group compared to means of normal group 11.9±12.01 but did not show any significance between the groups (p=0.90). Highly significant difference was observed in terms of chest drain between the groups (p=<.0001). Higher amounts of drain was observed in mild group 561.75±276.02 compared to normal group 336.25±129.11. IABP usage was observed more in mild group 6 patients (15.00%) where as it was used in 3 patients in normal group (7.50%), p=0.28 (Table 2).
Table 2: Intraoperative and postoperative characteristics
Variable |
Unit |
Mild (n=40) |
Normal(n=40) |
P value |
Type of territories |
LAD |
0(0.00) |
1(2.50) |
0.46 |
LAD, LCx |
5(12.50) |
3(7.50) |
||
LAD, LCx, RCA |
28(70.00) |
32(80.00) |
||
LAD, RCA |
7(17.50) |
4(10.00) |
||
Type of conduit |
LIMA |
0(0.00) |
1(2.50) |
0.57 |
LIMA+SVG |
34(85.00) |
34(85.00) |
||
SVG |
6(15.00) |
5(12.50) |
||
Number of grafts |
mean±SD |
3.5±0.90 |
3.57±0.95 |
0.72 |
Ventilation |
mean±SD |
12.17±9.32 |
11.9±12.01 |
0.90 |
Chest drain |
mean±SD |
561.75±276.02 |
336.25±129.11 |
<.0001 |
IABP |
No |
34(85.00) |
37(92.50) |
0.28 |
Yes |
6(15.00) |
3(7.50) |
LAD: left anterior descending artery; LCx: left circumflex artery; RCA: right coronary artery; LIMA: left internal mammary artery; SVG: saphenous vein graft, IABP: intra- aortic balloon pump
Postoperative outcomes
Postoperative outcomes were recorded and the outcomes were similar between the groups. One mortality (2.50%) occurred in mild group and none in normal group (p=0.31). In mild group postoperative renal dysfunction was observed in 2 patients (5.00%) and none in normal group, (p=0.15). Even though the difference between the groups is not statistically significant, postoperative CVA (p=0.61), postoperative MI (p=1.00), deep sternal wound infection (p=0.53) and means of ICU stay (p=0.72) were more in mild group compared to normal group. Means of hospital stay showed slightly high values in mild group 9.22±5.19 versus normal group 7.37±3.39, (p=0.06) and showed an inclining trend towards mild group (Table 3 & Table 4).
Table 3: Postoperative outcomes
Variable |
Unit |
Mild (n=40) |
Normal(n=40) |
P value |
GI complications |
No |
38(95.00) |
39(97.50) |
0.55 |
Yes |
2(5.00) |
1(2.50) |
||
Pulmonary complications |
No |
27(67.50) |
31(77.50) |
0.31 |
Yes |
13(32.50) |
9(22.50) |
||
LCOS |
No |
28(70.00) |
34(85.00) |
|
|
Yes |
12(30.00) |
6(15.00) |
0.10 |
Postoperative AF |
No |
29(72.50) |
35(87.50) |
0.09 |
|
Yes |
11(27.50) |
5(12.50) |
|
Postoperative renal dysfunction |
No |
38(95.00) |
40(100.00) |
0.15 |
|
Yes |
2(5.00) |
0(0.00) |
|
DSWI |
No |
33(82.50) |
35(87.50) |
0.53 |
|
Yes |
7(17.50) |
5(12.50) |
|
ICU stay |
mean±SD |
3.62±1.70 |
3.57±0.95 |
0.72 |
Hospital stay |
mean±SD |
9.22±5.19 |
7.37±3.39 |
0.06 |
GI: gastrointestinal; LCOS: low cardiac output syndrome; AF: atrial fibrillation; DSWI: deep sternal wound infection, ICU: intensive care unit;
Table 4: Postoperative MACCE
Variable |
Unit |
Mild (n=40) |
Normal(n=40) |
P value |
Postoperative MI |
No |
38(95.00) |
38(95.00) |
1.00 |
Yes |
2(5.00) |
2(5.00) |
||
Mortality |
No |
39(97.50) |
40(100.00) |
0.31 |
Yes |
1(2.50) |
0(000) |
||
CVA |
No |
37(92.50) |
39(97.50) |
0.61 |
Yes |
3(7.50) |
1(2.50) |
||
Re-exploration |
No |
34(85.00) |
36(90.00) |
0.49 |
Yes |
6(15.00) |
4(10.00) |
MACCE: major adverse cardiac and cerebrovascular events; MI: myocardial infarction CVA: cerebrovascular accident
Table 5. Analysis of Maximum Likelihood Estimates effecting hospital stay with in-hospital variables
|
Estimate |
Standard error |
Odds ratio |
95% Confidence interval |
p value |
|
Number of grafts |
0.026 |
0.72 |
1.027 |
0.24 |
4.25 |
0.97 |
Chest drain |
0.0058 |
0.004 |
1.006 |
0.99 |
1.01 |
0.21 |
Sr CrDay-1 |
-10.99 |
3.51 |
<0.001 |
<0.001 |
0.01 |
0.001 |
GFR Day-1 |
-0.21 |
0.08 |
0.804 |
0.68 |
0.94 |
0.007 |
Sr Cr Day-5 |
-368 |
6.55 |
0.025 |
<0.001 |
>999.9 |
0.57 |
GFR Day -5 |
-0.22 |
0.11 |
0.801 |
0.64 |
0.99 |
0.04 |
Ventilation |
-032 |
0.21 |
0.724 |
0.47 |
1.11 |
0.14 |
IABP usage |
-1.76 |
3.09 |
0.029 |
<0.001 |
>999.9 |
0.56 |
Low cardiac output syndrome |
-0.51 |
1.65 |
0.355 |
<0.001 |
237.66 |
0.75 |
Postoperative atrial fibrillation |
-1.74 |
1.57 |
0.03 |
<0.001 |
14.71 |
0.26 |
Postoperative Renal dysfunction |
-8.74 |
223.8 |
<0.001 |
<0.001 |
>999.9 |
0.96 |
Re-exploration |
1.62 |
3.81 |
25.98 |
<0.001 |
>999.9 |
0.66 |
Deep sternal wound infection |
-0.52 |
0.35 |
0.35 |
0.004 |
32.13 |
0.64 |
Preoperative renal dysfunction has been designated as an important risk factor for postoperative outcomes in isolated CABG. Mild renal dysfunction is associated with higher incidence of major adverse cardiovascular and cerebral event (MACCE) as compared to normal population undergoing CABG
The strong association between renal function and outcome after cardiac surgery has been demonstrated in previous studies. Durmaz et al. [22] reported increased in-hospital mortality rates of 11.8%, 33.0% and 12.5% in patients who had creatinine levels between
1.6 and 2.5 mg/dl, 2.5 mg/dl and end-stage renal disease on haemodialysis, respectively.
Weerasinghe et al. [20] demonstrated that a mild elevation (1.31–1.5 mg/dl) in preoperative serum creatinine level significantly increased the need for renal replacement therapy, the duration of special care, total postoperative stay and in-hospital mortality. In alignment with previous studies the current study also demonstrated increased hospital mortality, postoperative stay in mild renal dysfunction group with rise in serum creatinine levels on 5th postoperative day.
Various studies have determined the comparison between normal and mild renal dysfunction. Hirose et al studied 1725 patients undergoing CABG and concluded that mild renal dysfunction was associated with prolonged postoperative course and higher incidence of major complications (28.8% vs 10.7%; p< 0.001) and mortalities (6.8% vs 0.5%; p< 0.0005) [8]. Zaker and colleagues [1] studied 4403 patients undergoing primary isolated CABG with baseline serum creatinine greater than 200umol/l and found significant in hospital mortality (2.1% vs. 6.1%; p< 0.001), new dialysis (0.8% vs 5.2%; p< 0.001), arrhythmias (29% vs 39%) among the mild renal dysfunction group. Current study is in concurrence with these studies where the major adverse cardiac and cerebrovascular events are associated in patients with mild renal dysfunction.
Ueki and colleagues [23] filtration rate (eGFR). The clinical outcomes were compared between patients undergoing off-pump (n= 23,634) and on-pump CABG in each stratum. The study demonstrated that in patients with mildly reduced renal function (eGFR of 60- 89 mL/min/1.73 m2), there was no significant risk reduction effect of off-pump CABG for operative mortality. Conversely, in patients with moderate or severe renal disease (eGFR of<60 mL/min/1.73 m 2), off-pump CABG was associated with a significantly lower incidence of operative death. In addition, in patients with severe renal disease (eGFR of <30 mL/min/1.73 m2), off-pump CABG was associated with a significantly lower incidence of de novo dialysis.
Ueki and colleagues concluded that off-pump CABG significantly reduced operative mortality in patients with moderate or severe preoperative renal dysfunction but not in those with mild preoperative renal dysfunction. The present study was conducted in patients who underwent only off-pump CABG and compared mild preoperative renal dysfunction with and normal renal function. Even though the current study was not in alignment with the study design of Ueki et al, the results of this study are similar in terms of less outcomes postoperatively may be due to usage of off- pump CABG technique.
Prolonged mechanical ventilation and greater risk of reintubation in patients with renal dysfunction are attributed to impaired ability of the kidneys to eliminate fluid from the interstitium thereby predisposing these patients to fluid retention and excessive lung water. Studies have shown that a need for more than 48hrs ventilation and reintubation is higher in patients with significant renal dysfunction undergoing CABG relative to those with normal or mild renal [24] dysfunction. The authors [25] found greater requirement for ventilation in their study.
Charitan et al showed progressive increase in ventilation duration in the patients with various stages of CKD [26]. In concurrence with these authors the current study also showed slightly high requirement of ventilation in mild group compared to normal group.
Incidence of post-operative atrial fibrillation (AF) has been seen to increase with progression of CKD. The mechanism behind the myocardial electrical disturbance can be attributed to electrolyte imbalance frequently observed in this subset of patients when compared to patients with normal renal function undergoing CABG. The high incidence of stroke in CKD patients has been shown by studies in plenty [27]. Similarly increase in incidence of postoperative AF and CVA was observed in this study.
There was no significant difference in the patients undergoing off-pump CABG with normal renal function and mild renal dysfunction in terms of short-term mortality, myocardial infarction, stroke, or renal failure requiring dialysis. Off-pump CABG is more reno-protective for patients with normal renal function but for patients with mild renal dysfunction may need preoperative assessment of renal function by GFR in addition to serum creatinine levels to stratify the risk for postoperative renal dysfunction and to optimize measures for renal preservation during surgical myocardial revascularization.