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Ann Thorac Surg 2001;72:768-774
© 2001 The Society of Thoracic Surgeons

Original article: cardiovascular

One-stage coronary and abdominal aortic operation with or without cardiopulmonary bypass: early and midterm follow-up

Raimondo Ascione, MDa, Gabriele Iannelli, MDa, Kelvin H.H. Lim, FRCSa, Hajime Imura, PhDa, Nicola Spampinato, MDa

a Department of Cardiovascular Surgery, University "Federico II" of Naples, Naples, Italy

Accepted for publication April 25, 2001.

Address reprint requests to Dr Ascione, Bristol Heart Institute, Bristol Royal Infirmary, Marlborough St, Bristol BS2 8HW, UK
e-mail: r.ascione{at}bristol.ac.uk


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
Background. The aim of this study was to compare hospital, early, and late clinical outcomes for patients undergoing one-stage, coronary and abdominal aortic surgical intervention with and without cardiopulmonary bypass.

Methods. From March 1990 to September 1999, 42 consecutive patients underwent combined operations at a single institution. Cardiopulmonary bypass and cardioplegic arrest were used during coronary revascularization in the first 20 patients (on-pump group), and the next 22 patients received the one-stage operations on the beating heart (off-pump group).

Results. Baseline characteristics were similar between groups. Three cardiac-related hospital deaths occurred in the on-pump group and one such death in the off-pump group (p = 0.25). Cardiac-related events, pulmonary complications, inotropic support, blood loss and transfusion requirements, intensive care unit stay, and hospital stay were significantly reduced in the off-pump group (all, p < 0.05). The actuarial survival rates in the on-pump and off-pump groups were 80% and 95%, respectively, at 1 year (p = 0.13) and 75% and 89%, respectively, at 3 years (p = 0.22). Freedom from cardiac-related events at 1-year follow-up was 91% in the off-pump group and 65% in the on-pump group (p < 0.05). No difference in cardiac-related events between groups was observed at 3 years.

Conclusions. Off-pump coronary surgical procedures decrease postoperative complications in high-risk patients undergoing simultaneous coronary and abdominal aortic operations compared with the conventional one-stage procedure. The early benefits achieved with off-pump surgical intervention are not at the expense of the long-term clinical outcome.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
The management of patients who require operation for both severe coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) represents a therapeutic challenge. One therapeutic strategy consists of simultaneous coronary artery bypass grafting (CABG) and abdominal aortic surgical intervention (AAS) [1–7] to prevent the risk of complications arising from the untreated vascular territory [4–11]. Perioperative myocardial infarction (MI) remains a leading cause of early death in patients undergoing AAA repair [3], whereas coronary artery revascularization before AAS causes a risk of perioperative AAA rupture [2, 9]. Blackbourne and associates [2] reported that 3 of 9 patients scheduled to undergo AAA repair more than 2 weeks after coronary artery revascularization died of aneurysmal rupture. However, critics of the one-stage approach of combined surgical intervention for CAD and AAA argue against the longer operating and anesthesia time requirements, the need to coordinate surgical teams and timing of the operation, the increased risks of bleeding and other overlapping complications that may be attributable to either procedure, and the current limited experience level because of the relatively small case loads reported in the literature [12].

Off-pump coronary artery bypass grafting (OPCAB) has become increasingly popular [13–17]. Reports [18–24] show reduced postoperative morbidity and costs and early angiographic results comparable to those achieved with conventional CABG.

This retrospective review compares the early and midterm clinical outcomes for high-risk patients undergoing a one-stage surgical approach for CAD and AAA with or without cardiopulmonary bypass (CPB).


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Our unit accepts patients referred from the southwest region of Italy. Routine practice includes cardiac and major vascular operation. Therefore, in the presence of concomitant symptoms in different vascular territories, patients undergo complete investigation, which includes cardiac catheterization, abdominal computed tomographic scanning, and aortic and peripheral angiography, where appropriate. The combined approach was used for patients with CAD (Canadian Cardiovascular Society class III to IV or poor left ventricular ejection fraction) and symptomatic AAA or asymptomatic AAA greater than 7 cm in diameter or severe aortic occlusive disease associated with severe peripheral claudication.

This 9-year study includes 42 consecutive patients (37 men and 5 women with a mean age of 65.4 ± 5.9 years) who underwent simultaneous CABG and AAS at our institution. The first 20 patients had operation using moderately hypothermic CPB and intermittent antegrade cold blood cardioplegia (on-pump group) between March 1990 and January 1995, and the following 22 patients underwent OPCAB (off-pump group) between February 1995 and September 1999. Allocation of patients to off-pump surgical procedures started early in 1995 when there was enough experience with the OPCAB technique at our institution to make it safe. In 28 patients (67%), coronary artery revascularization was the primary indication for operation.

Anesthesia technique
Anesthesia technique consisted of intravenous administration of propofol (3 mg · kg-1 · h-1) combined with fentanyl (10 to 15 µg · kg-1 · h-1). Pancuronium bromide (0.10 to 0.15 mg/kg) was used to achieve neuromuscular blockade. Mean arterial blood pressure was maintained at 60 mm Hg or higher. In the off-pump group, propranolol hydrochloride (1 mg) was used to maintain a heart rate of less than 70 beats per minute. Postoperative anesthesia management did not differ between groups.

Surgical technique
On-pump group
A routine median sternotomy was performed. Heparin sodium was given at a dose of 300 IU/kg to achieve a target activated clotting time greater than 450 seconds before commencement of CPB. Cardiopulmonary bypass was instituted using ascending aortic cannulation and two-stage venous cannulation of the right atrium. A standard extracorporeal circuit comprising a Bard tubing set and a hollow-fiber membrane oxygenator was used with a Sarns roller pump. Priming solution consisted of Ringer’s solution (1 L), Emagel (500 mL), mannitol (0.5 g/kg), 10% calcium gluconate (7 mL), and heparin (6,000 IU). During CPB, nonpulsatile flow of 2.4 L · m-2 · min-1 was used with systemic temperature maintained at 32°C. Myocardial protection was achieved with intermittent antegrade hyperkalemic cold blood cardioplegia. After the patient was weaned from CPB, the heart was decannulated, and protamine sulfate was administered to achieve an activated clotting time of 250 to 300 seconds. The chest was closed in the usual manner.

A xiphopubic incision was made, the abdominal viscera were mobilized, and the abdominal aorta was exposed down to the iliac arteries. For aorta–bifemoral bypass, the femoral arteries were also exposed through separate groin incisions. A standard graft inclusion technique was used with a collagen-coated Dacron tube or bifurcated graft (Hemashield; Meadox Medicals, Inc, Oakland, NJ). Protamine was given to achieve the preoperative value of the activated clotting time, and the abdomen was closed in a standard fashion.

Off-pump group
The surgical technique used in the off-pump group has been described previously [25]. Briefly, a routine median sternotomy was performed. The heart was exposed and stabilized with the aid of a retractor and stabilizer (CardioThoracic Systems, Inc, Cupertino, CA) [26]. Heparin (100 IU/kg) was administered prior to the start of the first anastomosis to achieve an activated clotting time of 250 to 300 seconds. The target coronary vessel was exposed and snared above the anastomotic site using a Gore-Tex suture with a soft plastic snugger to prevent coronary artery injury. The artery was opened, and the distal anastomosis was fashioned. An intracoronary shunt was used with release of the snare to allow distal perfusion. On completion, the proximal anastomoses of vein grafts were performed with partial aortic clamping. After standard closure of the sternotomy, the AAS was carried out as described for the on-pump group. On completion of that operation, protamine was given to restore the preoperative value of the activated clotting time.

Perioperative clinical recording and definitions
Cardiovascular monitoring included the use of Swan-Ganz pulmonary artery catheter and continuous electrocardiographic monitoring during the first 72 hours. Routine standard biochemical and hematological profiles and repeat chest radiographs were also made. Complete perioperative subsystem clinical outcome was recorded. Clinical diagnosis of perioperative MI was confirmed by fulfillment of electrocardiographic and biochemical criteria, which included new Q waves greater than 0.04 ms, a reduction in R waves greater than 25% in at least two leads, or both of these, and a significant elevation of levels of the myocardial-specific isoenzyme of creatine kinase over 24 to 48 hours. Chest infection was defined as the presence of fever with purulent sputum requiring antibiotic therapy according to the sputum cultures grown.

The methods of patient follow-up included questionnaires and telephone interviews when outpatient clinic attendance was not possible.

Statistical analysis
Data are presented as the mean ± the standard deviation unless otherwise specified. Statistical analysis of categorical variables was performed using the {chi}2 or Fisher’s exact tests, and continuous data were analyzed with two-sample t test where appropriate. Serial hemodynamic data were analyzed using analysis of variance for repeated measurements and post hoc comparisons were performed using the Bonferroni/Dunn test. Kaplan-Meier survival curves were plotted for the two groups. Cumulative survival rates were estimated by the actuarial method, and differences between groups were analyzed using Mantel-Cox log-rank test. All statistical analyses mentioned were performed with the aid of the software package Statview for Windows (SAS Institute Inc, Cary, NC).


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
Baseline and operative characteristics are shown in Tables 1 and 2, respectively. Twenty-eight patients (13 on-pump group, 15 off-pump group) were seen with a history of previous MI. Of the 11 patients with AOD, only one patient in each group presented with signs of lower limb ischemia, whereas the remnant had intermittent claudication. No differences were observed between groups in regard to mean number of grafts placed and distribution of grafts. One patient (aged 58 years) in the off-pump group underwent one-stage triple surgical procedures—left carotid endoarterectomy, CABG, and AAS (Fig 1).


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  		Table 1. Preoperative Demographic Dataa

 

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  		Table 2. Surgical Dataa,b

 


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  		Fig 1. Patient who underwent one-stage triple surgical procedures: left carotid endoarterectomy, coronary artery bypass grafting, and abdominal aortic surgical procedure without cardiopulmonary bypass. Third postoperative day.

 
In the on-pump group, there were three hospital deaths. One patient with a preoperative left ventricular ejection fraction lower than 0.30 died of postoperative low cardiac output syndrome on day 6. Two patients died as result of multiorgan failure on days 12 and 18. In the off-pump group, 1 patient died of multiorgan failure and low cardiac output after a postoperative MI. The 30-day mortality rate was 15% and 5% for the on-pump and off-pump groups, respectively (p = 0.25).

Hemodynamic measurements show a depressed cardiac index soon after operation in both groups compared with baseline (p < 0.001) (Fig 2). However, within 12 hours, the cardiac index had improved to baseline in the off-pump group but not in the on-pump group. Furthermore, cardiac index levels in the off-pump group were significantly higher than those in the on-pump group at 1 hour, 4 hours, and 12 hours after operation (all, p < 0.05) (see Fig 2).



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  		Fig 2. Cardiac index measurements made at various times before and after operation. Data are plotted as the mean ± the standard error. By analysis of variance, F value = 22.6 and p < 0.0001. (*p < 0.05, on-pump group versus off-pump group.)

 
Postoperative complications are shown in Table 3. The on-pump group had a significantly higher incidence of cardiac-related events, inotropic support requirement, longer intubation time, and chest infection episodes (all, p < 0.05 versus off-pump group). Total blood loss and transfusion requirements were significantly lower in the off-pump group (p < 0.001) along with a shorter duration of intensive care unit and hospital stays (p < 0.001).


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  		Table 3. Perioperative Clinical Outcomesa

 
One patient (on-pump group) was lost to follow-up after 46 months. The mean interval of follow-up was 67.7 ± 40.4 months, in the on-pump group 30.9 ± 18.7 months in the off-pump group. There were five late deaths in the on-pump group, two of which occurred within the first 3 years after operation, compared with one death in the off-pump group during a similar period of follow-up (p = 0.22). The causes of late death in the on-pump group were MI in 2 patients at 21 and 80 months, stroke-related complications in 1 patient at 8 months, and malignancies in 2 patients at 65 and 93 months. In the off-pump group, the only death occurred after an MI at 19 months postoperatively.

The estimated actuarial 1-year survival rates were 80% ± 9% and 95% ± 5% for the on-pump and off-pump groups, respectively (p = 0.13) (Fig 3). The 3-year survival rates were 75% ± 10% and 89% ± 8% for the on-pump group and off-pump group, respectively (p = 0.22), and the 9-year survival rate for the on-pump group was 55% ± 12%.



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  		Fig 3. Kaplan-Meier plot showing cumulative survival data of patients undergoing single-stage approach for abdominal aortic disease and coronary artery disease, with coronary revascularization performed either on or off pump. Data are shown as cumulative survival ± the survival standard error.

 
Details of late-onset complications in both groups are listed in Table 4. One patient in each group required coronary reintervention with percutaneous transluminal coronary angioplasty at 48 months (off-pump group) and 75 months (on-pump group) because of ischemia in untreated coronary territories. Figure 4 shows the Kaplan-Meier plot of freedom from all cardiac-related events, fatal and nonfatal, during and after operation. Because of the high incidence of early cardiac-related complications experienced in the on-pump group, the difference in freedom rates between groups at the 1-year follow-up remained significant: 91% ± 6% versus 65% ± 11%, off-pump and on-pump groups, respectively (p < 0.05).


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  		Table 4. Follow-up Dataa,b

 


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  		Fig 4. Kaplan-Meier plot showing freedom from cardiac-related events in off-pump and on-pump groups undergoing single-stage approach for abdominal aortic disease and coronary artery disease. Data are expressed as freedom from events ± the standard error.

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
Severe correctable CAD is identified in a third of patients with abdominal aortic disease [9, 27]. The mortality rate is reported to be 10% ± 20% in elderly high-risk patients undergoing conventional CABG and in elderly high-risk patients seen with poor left ventricular function, a heavily calcified aorta, or associated cerebral, pulmonary, renal, hepatic, and vascular comorbid diseases [28, 29]. Conversely, OPCAB avoids exposure to the detrimental effects of CPB and cardioplegic arrest on subsystem function [15, 16, 30, 31] while allowing multiple CABG.

To our knowledge, this is the first reported comparison of a rather large number of patients undergoing one-stage CABG and AAS either on or off pump (Table 5). The first observation from this study is the significant reduction in postoperative morbidity in the off-pump group. Fewer patients in the OPCAB group sustained perioperative major cardiac-related events and the off-pump group had better preservation of postoperative hemodynamic status and reduced inotropic support requirements. This might be due to a reduced intraoperative myocardial injury achieved with OPCAB procedures because of the absence of ischemic arrest. This is consistent with previous findings of reduced myocardial injury observed with beating heart surgery as indicated by the lower release of troponin I [16, 32]. Another mechanism might be related to the sharp rise in systemic vascular resistance when the abdominal aorta is cross-clamped. In this situation, the resulting increased afterload and left ventricular wall stress may lead to subendocardial ischemia of the heart, which is still recovering from the previous ischemic arrest [9].


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  		Table 5. Published Results of Simultaneous Coronary Artery Bypass Grafting and Operation for Abdominal Aortic Aneurysm

 
Pulmonary complications were also reduced in the off-pump group. This likely is related to the greater systemic inflammatory response observed when CPB is used [30]. This response leads to intrapulmonary sequestration of white cells, generation of free radicals and protease enzymes, and interstitial edema, all of which are generally implicated in the requirement of longer postoperative ventilation [31].

King and associates [1] speculated that the inflammatory response caused by CPB might have a direct impact on AAA dilatation, causing further wall weakening and decreased tensile strength. Collagen is believed to be a primary constituent of the aneurysm wall. Thus, factors that decrease collagen production, such as perioperative malnutrition, and those that increase collagenase activity, which has been reported to occur after major surgical procedures, could both contribute to early aneurysmal rupture. Busuttil and coauthors [33] compared aortic specimens obtained from patients who underwent AAA repair or operation for aortic occlusive disease. Collagenase activity was detectable in the AAAs and correlated with aneurysm size, but it was not found in atherosclerotic aorta or fascia, results suggesting that endogenous collagenolytic activity may be responsible for aneurysmal expansion and rupture. Therefore, the authors advised that a combined rather than a staged surgical procedure be performed.

Critics of the one-stage on-pump approach suggest that there may be an increased risk of bleeding and other overlapping complications that may be attributable to either procedure [12]. In contrast, the present study shows a significant reduction in blood loss and transfusion requirements in the off-pump group, and this finding indicates that in these high-risk patients, OPCAB reduces the risks of transfusion-related and bleeding-related complications [34].

The economic impact related to the duration of intensive care unit and hospital stays is an important variable in modern health-care assessment of efficiency. In this study, there was a significant reduction in both intensive care unit stay and hospital stay in the off-pump group. This together with reduced transfusion requirements and postoperative morbidity has important beneficial cost-saving implications.

Midterm survival and freedom from cardiac-related events after CABG and AAS are influenced by several factors. These include preoperative status, completeness of revascularization, progression of native vessel disease, late attrition of bypass conduits in both the coronary and abdominal aortic vascular territories, the surgical accuracy of the performing surgeon, and the quality of the anastomoses. The present study showed a significantly lower incidence of cardiac-related events at 1-year follow-up in the off-pump group. This was associated with a trend toward fewer cardiac-related events and better survival at 3 years in the off-pump group. These results suggest that the early benefits of OPCAB are not at the expense of late outcome.

The rationale for performing the abdominal part of the one-stage procedure after closure of the chest was based on considerations aimed at minimizing the potential risk of mediastinal infection from protracted exposure of the thoracic cavity and open communication with the abdominal cavity. With the partial reversal of heparin after the thoracic procedure, the risk of excessive bleeding during the abdominal procedure is also reduced. In patients undergoing off-pump coronary surgical procedures, this strategy may decrease the potential for higher body-heat loss.

One limitation of this study is the sequential nature of the patient series that was spread over a long period. This needs to be considered in the interpretation of the results because during this time, confounding factors might have been in effect to make the comparison difficult. However, the conventional technique of CABG remained strictly the same over the entire study period in all its components of anesthesia, operation, and perfusion, and all the patients were operated on by the same surgeon.

Patient selection to the one-stage procedure in this series was not limited by age or body mass index. Although in principle, the abdominal operation might have been safely deferred in patients with aortic occlusive disease, such patients were offered the one-stage approach because of the severity of the peripheral claudication.

In conclusion, this study suggests that the use of OPCAB for high-risk patients undergoing a one-stage surgical approach for CAD and AAA results in a significant reduction in hospital morbidity. These benefits are not at the expense of late clinical outcome. A prospective, randomized study is needed to support these conclusions.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

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