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Eur J Cardiothorac Surg 2006;30:431-435
© 2006 Elsevier Science NL

Risk factors of postoperative nephropathy in patients undergoing innovative CABG and intraoperative graft angiography

Thomas Schachnera,*, Johannes Bonattia, Nikolaos Bonarosa, Ruth Poeltla, Gudrun Feuchtnerc, Günther Laufera, Otmar Pachingerb, Guy Friedrichb

a Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria
b Department of Cardiology, Innsbruck Medical University, Innsbruck, Austria
c Department of Radiology II, Innsbruck Medical University, Innsbruck, Austria

Received 13 March 2006; received in revised form 15 May 2006; accepted 2 June 2006.

* Corresponding author. Tel.: +43 512 504 80820; fax: +43 512 504 22528. (Email: Thomas.Schachner{at}uibk.ac.at).


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
Introduction: Intraoperative graft angiography is considered gold standard in quality control of innovative CABG techniques. Iodixanol, an iso-osmolar, non-ionic contrast agent has been safely applied in patients with impaired renal function. We aimed to quantify postoperative nephropathy in CABG patients undergoing intraoperative angiography and to define associated risk factors. Methods: One hundred and thirty-five patients, aged 61 years (range: 43–83), underwent intraoperative angiography following CABG (36 robotically assisted CABG via sternotomy, 41 OPCAB and MIDCAB, 51 AHTECAB, 7 BHTECAB). In all patients iodixanol (VisipaqueTM) was used, median amount: 150 ml (range: 20–500). Nephropathy was defined as an increase in serum creatinine concentration ≥0.5 mg/dl compared with preoperative values. Results: Nephropathy occured in 19/135 (14%) patients, and was correlated with the following variables: preoperative serum creatinine (p = 0.015, r = 0.208), age (p = 0.008, r = 0.229), postoperative peak troponin T levels (p < 0.001, r = 0.545), postoperative CK-MB peak levels (p = 0.028, r = 0.189), and presence of peripheral vascular disease (p = 0.011). No correlation was found for the contrast agent amount, diabetes mellitus, hypertension, preoperative urea level, cardiopulmonary bypass time, aortic cross clamp time, postoperative CK peak levels. Multivariate analysis showed that postoperative peak troponin T levels (p < 0.001), preoperative serum creatinine (p = 0.031), and patient age (p = 0.043) were independently associated with a postoperative increase of serum creatinine. In all 19 patients with postoperative nephropathy serum creatinine levels returned to preoperative levels. Conclusion: Patients with older age and elevated serum creatinine levels undergoing innovative CABG and intraoperative angiography were at increased risk of postoperative nephropathy. However, no correlation was found between the amount of contrast agent (iodixanol) applied and the nephropathy rate and none of the nephropathy cases persisted.

Key Words: Coronary surgery • CABG • Angiography • Nephropathy • Iso-osmolar contrast agent


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
Intraoperative graft angiography is an important tool for quality control after coronary artery bypass grafting (CABG). It is indicated when new surgical techniques such as robotically enhanced CABG are used or when difficult anastomoses are sutured on the beating heart. Since the control is performed intraoperatively, the surgeon is able to immediately revise the patient. Thus it is guaranteed, even after longer operating times or conversions to sternotomy, that the patient leaves the operating room with patent bypass grafts [1–5]. Furthermore, the availability of a coronary angiography facility is a prerequisite for simultaneous hybrid revascularisation procedures [6–8]. An important point of discussion, however, is the risk of postoperative nephropathy in those patients. Two major risk factors for hospital-acquired nephropathy (i.e. surgery and contrast agent exposure) come together in the group we observed. It was the aim of our study to quantify the risk of postoperative nephropathy and its further course in patients undergoing both coronary surgery, and intraoperative angiography. Furthermore, we aimed to define risk factors for postoperative nephropathy in this special patient population.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
Between 2001 and 2005, 135 patients underwent intraoperative angiography following coronary artery bypass grafting (CABG). The operations performed were 36 robotically assisted CABG via sternotomy, 41 off pump coronary artery bypass grafting (OPCAB) and minimally invasive direct coronary artery bypass grafting (MIDCAB), 51 arrested heart totally endoscopic coronary artery bypass grafting (AHTECAB), and 7 beating heart totally endoscopic coronary artery bypass grafting (BHTECAB). The mean number of distal coronary anastomoses was 1.5 ± 0.7. None of the patients had undergone previous cardiac operations. Four patients underwent urgent surgery due to rest angina. Patient characteristics and operative data are listed in Table 1 .


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  		Table 1. Patient characteristics and operative data of 135 patients who underwent intraoperative angiography after CABG
 
Intraoperative graft angiography was performed via a 7-F femoral access in the left or right groin using the Judkins technique. Fluoroscopy was carried out with a GE OEC9800 mobile C-arm at 25 frames/s, which was covered with sterile plastic sheets. The sequences were transferred to a computer workstation and visualized using the OEC CRS-PC Software. Two to four projections (anterior posterior, LAO 20°, RAO 20°, or LAO 90°) were used to visualize the grafts. Depending on individual anatomical features, standard Judkins right and left or bypass catheters (Boston Scientific) were used. The operating table was a Maquet 1150.10D0 (Maquet, Rastatt, Germany).

In all patients iodixanol (VisipaqueTM) was used for angiography. Nephropathy was defined as increase in serum creatinine concentration of ≥0.5 mg/dl compared with preoperative values.

Serum creatinine levels were measured at the day of operation and on postoperative days 1,2, and 5 in all patients and daily in patients with raising creatinine levels.


   3. Statistical analysis
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Statistical analysis
4. Results
 5. Discussion
 6. Conclusions
 References
 
Statistical analysis was carried out with SPSS 12.0 software. Continuous variables are presented as median (minimum–maximum). Categoric variables are given as percentages. Pearson's correlation coefficients (r) were calculated for continuous variables. Associations between categorical variables were analyzed using chi-square tests. Multivariate analysis for the independent effect was performed using a general linear model. The criterion for a variable entry into multivariate analysis was a univariate probability level of p < 0.05. p-Values of less than 0.05 were considered significant.


   4. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Statistical analysis
 4. Results
5. Discussion
 6. Conclusions
 References
 
In all 135 patients intraoperative graft angiography could be performed adequately. The examination time was 23 min (range: 8–110), and 150 ml (range: 20–500) of the contrast agent iodixanol (VisipaqueTM) were used.

The median creatinine levels increased from 1.02 mg/dl (range: 0.58–1.84) preoperatively to a median maximum postoperative values of 1.16 mg/dl (range: 0.62–3.90), which was a median difference of 0.14 mg/dl (range: –0.33–2.41). The time points at which the maximum postoperative serum creatinine levels were found are displayed in Fig. 1 .


Figure 1
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  		Fig. 1. The time points at which the maximum postoperative serum creatinine values where found. The vast majority of maximum serum creatinine levels is found during the first 2 days after operation (Day 0 = day of operation).

 
In 19/135 (14%) patients a postoperative nephropathy occurred with an increase of serum creatinine of 0.5 mg/dl or more compared with preoperative values. The median increase of serum creatinine in these 19 patients was 0.75 mg/dl (range: 0.51–2.41). In all 19 patients the postoperative serum creatinine levels returned to preoperative values (Fig. 2 ). None of the patients required hemodialysis.


Figure 2
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  		Fig. 2. The preoperative (preop), maximum postoperative (max postop), and late serum creatinine levels of 19 patients with postoperative nephropathy following CABG with intraoperative graft angiography. Note that none of the patients suffered from persistent nephropathy. In 16 patients late SCr values were measured within 10 days after CABG, in 1 patient at 1 month, and in 2 patients at 3 months postoperatively.

 
The increase of serum creatinine levels compared with preoperative values was correlated with the following variables: preoperative serum creatinine level (p = 0.015, r = 0.208, Fig. 3 ), patient's age (p = 0.008, r = 0.229, Fig. 4 ), postoperative peak troponin T level (p < 0.001, r = 0.545), postoperative peak level of CK-MB (p = 0.028, r = 0.189). There was a trend found for an association between the EuroSCORE and the postoperative increase of serum creatinine levels (p = 0.079, r = 0.175, Fig. 5 ). No correlation was found between the increase of serum creatinine level and the amount of contrast agent administered (Fig. 6 ), preoperative urea level, cardiopulmonary bypass time, aortic cross clamp time, and postoperative peak level of creatinekinase.


Figure 3
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  		Fig. 3. The correlation between preoperative serum creatinine levels and the postoperative increase of serum creatinine values in 135 CABG patients who underwent intraoperative graft angiography.

 

Figure 4
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  		Fig. 4. The correlation between age and the postoperative increase of serum creatinine values in 135 CABG patients who underwent intraoperative graft angiography.

 

Figure 5
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  		Fig. 5. The correlation between EuroSCORE and the postoperative increase of serum creatinine values in 135 CABG patients who underwent intraoperative graft angiography.

 

Figure 6
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  		Fig. 6. There is no correlation between the amount of contrast agent used and the postoperative increase of serum creatinine levels.

 
The occurrence of postoperative nephropathy was associated with the presence of peripheral vascular disease (p = 0.011), whereas it was not associated with the presence of diabetes mellitus (p = n.s.) or hypertension (p = n.s.).

Multivariate analysis considering all factors that were significantly associated with a postoperative increase of serum creatinine in the univariate analysis, showed that postoperative peak troponin T levels (p < 0.001), preoperative serum creatinine (p = 0.031), and patient age (p = 0.043) were independently associated with a postoperative increase of serum creatinine.

Four patients underwent simultaneous hybrid revascularisation with totally endoscopic LIMA to LAD bypass grafting and PTCA and stenting of another coronary artery (right coronary artery in two cases, posterolateral branch in one case, marginal branch in one case). The amount of contrast agent used was 363 ml (range: 250–500) in this group, and the postoperative increase of serum creatinine was 0.19 mg/dl (range: 0.01–0.24). None of the four patients showed a contrast nephropathy.

Postoperatively, the length of stay on the intensive care unit was 21 h (range: 7–432). No in-hospital death was observed in this series.


   5. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Statistical analysis
 4. Results
 5. Discussion
6. Conclusions
 References
 
The rate of nephropathy following examinations using contrast agent is found to be 2% in a healthy population, 9–40% in patients with diabetes mellitus, and raises up to 50–90% in patients with chronic renal insufficiency [9]. In patients who were exposed to two of the most common risk factors of hospital-acquired nephropathy (i.e. exposure to contrast agent and surgery) we found a postoperative nephropathy in 14%. With an increase of serum creatinine levels of 0.5 mg/dl or more we chose a quite low value. In literature creatinine increases of 0.5–1.0 mg/dl have been most commonly suggested to define contrast-induced nephropathy [9]. In our series 4/135 (3%) had an increase of serum creatinine levels of 1.0 mg/dl or more.

In patients with contrast-induced nephropathy serum creatinine levels usually peak within 3–5 days after the procedure [9]. In agreement with this we found the vast majority of serum creatinine peaks within 2 days postoperatively.

Contrast-induced nephropathy is associated with an increased mortality [9,10]. In our series, however, none of the patients died during the hospital stay. One may speculate that despite the risk of contrast-induced nephropathy and longer operative times after revisions due to angiographic findings it is beneficial that all patients leave the operating room with patent bypass grafts.

Renal dysfunction has been reported to interfere with elevated troponin T levels, mostly in studies including chronic renal failure patients. Patients with chronic renal impairment are often affected with coronary artery disease and therefore belong to a patient subgroup with higher risk for cardiac events [11–13]. The possible relationship of elevated CK-MB and troponin T levels to postoperative higher serum creatinine levels may be explained by this constellation, and making renal insufficient patients more vulnerable for minor cardiac ischemic events. Another possible explanation may be the fact that a more intense elevation of troponin T and CK-MB levels in these patients, caused by larger microinfarctions and myocyte damage during CABG, leads to a more complicated and prolonged peri- and postoperative course causing an additive renal stress.

Goldenberg and Matetzky found in the literature a strong association between preprocedural serum creatinine levels and contrast-induced nephropathy [14]. In accordance we saw in our patients a significant correlation between preoperative serum creatinine levels and postoperative nephropathy. Interestingly there was no association between preoperative blood urea and postoperative nephropathy in our series.

Advanced age is a known risk factor of nephropathy in patients who receive contrast agents [9,14]. The reason for this could be a general decrease of renal parenchyme and renal function in elderly patients. In our current study, a clear correlation between increasing age and postoperative increase of serum creatinine levels was present.

Several groups report that the amount of contrast agent is a risk factor for contrast-induced nephropathy [9,14]. For the intraoperative angiography we used a median amount of 150 ml iodixanol. This is comparable to the amount used for a computed tomography scan. Approximately 100 ml of contrast agent are used for a cardiac CT scan, and 170 ml for an aortoiliacal CT angiography or a whole body CT scan. Interestingly we found no correlation between the amount of contrast agent used and the postoperative increase of serum creatinine. The safe application of the iso-osmolar, non-ionic contrast medium, iodixanol in high-risk patients and its superiority to low-osmolar contrast agents was demonstrated in the NEPHRIC study [15]. In four patients, we used amounts of >400 ml of contrast agent. In one patient two graft angiographies were performed due to a diagnosis of a partial anastomotic stenosis, which was revised and controlled by a second intraoperative angiography. The second patient received a totally endoscopic double vessel CABG with a LIMA and a RIMA graft. Since the RIMA was difficult to intubate a total amount of 500 ml of iodixanol was used. The third patient underwent emergency hybrid revascularisation with PTCA and stenting of the right coronary artery after acute occlusion. In the fourth patient a planned simultaneous hybrid revascularisation with PTCA and stenting of the right coronary artery was performed in addition to the graft angiography. Nevertheless, the postoperative increase of serum creatinine was only 0.07, 0.2, 0.2, and 0.17 mg/dl, respectively in these four patients.

The EuroSCORE is a composite parameter that includes all of the three patient related risk factors of postoperative nephropathy in our study. This may explain the trend of association between higher EuroSCOREs and postoperative increase of serum creatinine. However the association did not reach statistical significance.

Limitations of the study: it is a retrospective cohort analysis. For new technologies there was of course a patient selection that led to a relatively low-risk population.

Both, hypertension and diabetes mellitus are reported risk factors of contrast-induced nephropathy in the general patient population [9,14]. Interestingly these two diseases did not emerge as risk factors in our study. One reason for this might be the good control of hypertension and diabetes in patients with coronary artery disease by the internist. Thereby, a parenchymal damage of the kidneys would be prevented.


   6. Conclusions
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
References
 
In older patients with potential risk to nephropathy due to their underlying disease and the necessarily indicated cardiac operation, the isosmolar iodixanol seemed to be a safe contrast agent with regard to longer lasting deteroriation of kidney function, also when higher amounts of iodixanol have to be applied intraoperatively.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 

  1. Bonatti J, Danzmayr M, Schachner T, Friedrich G. Intraoperative angiography for quality control in MIDCAB and OPCAB. Eur J Cardio Thorac Surg 2003;24:647-649.[Abstract/Free Full Text]
  2. Mack MJ, Magovern JA, Acuff TA, Landreneau RJ, Tennison DM, Tinnerman EJ, Osborne JA. Results of graft patency by immediate angiography in minimally invasive coronary artery surgery. Ann Thorac Surg 1999;68:383-389.[Abstract/Free Full Text]
  3. Izzat MB, Khaw KS, Atassi W, Yim AP, Wan S, El-Zufari MH. Routine intraoperative angiography improves the early patency of coronary grafts performed on the beating heart. Chest 1999;115:987-990.[Abstract/Free Full Text]
  4. Bonatti J, Schachner T, Bernecker O, Chevtchik O, Bonaros N, Ott H, Friedrich G, Weidinger F, Laufer G. Robotic totally endoscopic coronary artery bypass: Program development and learning curve issues. J Thorac Cardiovasc Surg 2004;127:504-510.[Abstract/Free Full Text]
  5. Bonatti J, Schachner T, Bonaros N, Oehlinger A, Danzmayr M, Rutzler E, Bernecker O, Margreiter J, Velik-Salchner C, Friedrich G, Jonetzko P, Laufer G. Ongoing procedure development in robotically assisted totally endoscopic coronary artery bypass grafting (TECAB). Heart Surg Forum 2005;8(4):E287-E291.[CrossRef][Medline]
  6. Friedrich GJ, Jonetzko P, Bonaros N, Schachner T, Danzmayr M, Bonatti J, Laufer G, Pachinger O, Bonatti J. Hybrid coronary artery revascularization: logistics and program development. Heart Surg Forum 2005;8(4):E258-E261.[CrossRef][Medline]
  7. Bonatti J, Schachner T, Bonaros N, Laufer G, Kolbitsch C, Margreiter J, Jonetzko P, Pachinger O, Friedrich G. Robotic totally endoscopic coronary artery bypass and catheter based coronary intervention in one operative session. Ann Thorac Surg 2005;79:2138-2141.[Abstract/Free Full Text]
  8. Bonatti J, Schachner T, Bonaros N, Jonetzko P, Ohlinger A, Lockinger A, Stalzer B, Eschetzhuber S, Friedrich G. Treatment of double vessel coronary artery disease by totally endoscopic bypass surgery and drug-eluting stent placement in one simultaneous hybrid session. Heart Surg Forum 2005;8(4):E284-E286.[CrossRef][Medline]
  9. Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy. AJR 2004;183:1673-1689.[Free Full Text]
  10. Cox CD, Tsikouris JP. Preventing contrast nephropathy: What is the best strategy? a review of the literature. J Clin Pharmacol 2004;44:327-337.[Abstract/Free Full Text]
  11. Frankel WL, Herold DA, Ziegler TW, Fitzgerald RL. Cardiac troponin T is elevated in asymptomatic patients with chronic renal failure. Am J Clin Pathol 1996;106:118-123.[Medline]
  12. Musso P, Cox I, Vidano E, Zambon D, Panteghini M. Cardiac troponin elevations in chronic renal failure: prevalence and clinical significance. Clin Biochem 1999;32:125-130.[CrossRef][Medline]
  13. Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM, Mahaffey KW, Newby K, Califf RM, Simoons ML, Topol EJ, Lauer MS. Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 2002;346:2047-2052.[Abstract/Free Full Text]
  14. Goldenberg I, Matetzky S. Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies. CMAJ 2005;172(11):1461-1471.[Abstract/Free Full Text]
  15. Aspelin P, Aubry P, Fransson S, Strasser R, Willenbrock R, Berg KJ, for the NEPHRIC Study Investigators Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.[Abstract/Free Full Text]
  16. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9-13.[Abstract/Free Full Text]



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