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Eur J Cardiothorac Surg 2002;22:552-558
© 2002 Elsevier Science NL

Off-pump coronary artery bypass grafting: a case-matched comparison of hemodynamic outcome

Yves Louagiea*, Jacques Jamartb, Serge Brokac, Edith Collardc, Vincent Scavéea, Manuel Gonzalezd

a Cardiovascular and Thoracic Surgery, University Clinics of Mont Godinne, Université Catholique de Louvain, Mont Yvoir, Belgium
b Biostatistics, University Clinics of Mont Godinne, Université Catholique de Louvain, Mont Yvoir, Belgium
c Anesthesiology, University Clinics of Mont Godinne, Université Catholique de Louvain, Mont Yvoir, Belgium
d Intensive Care Unit, University Clinics of Mont Godinne, Université Catholique de Louvain, Mont Yvoir, Belgium

Received 3 April 2002; received in revised form 18 June 2002; accepted 26 June 2002.

* Corresponding author. Tel.: +32-81-423151; fax: +32-81-423158
e-mail: louagie{at}chir.ucl.ac.be


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Objective: The objective of this study was to assess improved myocardial protection by performing coronary artery bypass grafting (CABG) on the beating heart. A case-matched study was conducted among patients who underwent CABG either on-pump (group 1), or off-pump (group 2). Methods: Forty-five pairs of patients, having a similar clinical profile, were selected on the basis of five variables: age, gender, body surface area, ejection fraction, extent of coronary disease. Operative risk predicted by the The Society of Thoracic Surgeons national database was 1.80±0.35% in group 1, and 1.89±0.37% in group 2 (NS). Cold blood cardioplegia and 28°C cardiopulmonary bypass were used in group 1. In group 2, beating heart coronary grafting was achieved with the OctopusTM 1 and 2 stabilizers. The average number of distal anastomoses was 2.8±0.1 in group 1 and 2.3±0.1 in group 2 (P=0.015). Results: There was no significant difference among the groups regarding the trend in cardiac index, left and right ventricular stroke work indexes, and systemic and pulmonary vascular resistance indexes. However, heart rate trend was slower in group 2 (P=0.05). Pharmacological support was required in 65% of the patients in group 1, and in 33% in group 2 (P<0.001). The total amount of Dobutamine and/or Dopamine administered during the first 48 h was 3914±1306 {gamma}/kg in group 1 and 1645±697 {gamma}/kg in group 2 (P=0.049). Release of creatine kinase MB mass isoenzyme (CK-MB mass) was markedly reduced in group 2 (P<10-4). Conclusions: Hemodynamic outcome following off-pump CABG is similar to on-pump CABG but the need for inotropic support is significantly reduced and CPK-MB mass release is markedly lower.

Key Words: Myocardial revascularization • Beating heart surgery • Myocardial protection


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 References
 
Off-pump coronary artery bypass grafting (OPCAB) was presented as an attractive alternative in high-risk patients [1–3]. However, better preservation of cardiac function after beating heart CABG was rarely demonstrated. Ascione et al. showed in a prospective randomized study excluding patients having ejection fraction of <30% and disease involving the distal circumflex [4], that heart-rate (HR) was superior in the on-pump group, but that the other hemodynamic variables studied (mean arterial pressure, central venous pressure) did not differ. Dopamine inotropic support was higher in the on-pump group, although it did not reach statistical significance.

The present study was carried out to compare the hemodynamic outcome of patients undergoing CABG on-pump or off-pump, including three-vessel disease patients, and high-risk patients. The primary end-point was cardiac function, including the amount of pharmacologic support required to obtain the hemodynamic performance. The secondary end-points were myocardial enzyme release and clinical outcome.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 References
 
2.1. Patients
Patients were selected from a database and rigorously matched for demographic factors and angiographic variables. Patients undergoing associated valvular surgery, carotid surgery, emergency procedures (within 24 h of catheterization) and those who required preoperative intra-aortic balloon counterpulsation were excluded. Likewise, ten patients undergoing beating heart surgery with cardiopulmonary bypass support were excluded from this study: in six cases, this solution was deliberately chosen because of severe left ventricular dysfunction and cardiomegaly, in four cases, the procedure started without cardiopulmonary bypass (CPB), but CPB support was later required because of hemodynamic instability and/or ischemia.

All the patients were operated on by the same surgeon using the same technique of myocardial protection and strategy for bypass grafts. The matching process used the following variables: age, gender, body surface area, coronary lesions, left ventricular ejection fraction. Forty-five pairs of patients were matched. The patients undergoing cardioplegic arrest (group 1) were operated upon between April 1, 1997 and August 7, 2000, whereas the patients undergoing beating heart surgery (group 2) were operated upon between April 1, 1998 and August 8, 2000.

The clinical profiles of the matched patients were comparable and are described in Table 1. Operative risk predicted according to the The Society of Thoracic Surgeons [5] was 1.80±0.35% (range 0.3–15.6) in group 1 and 1.89±0.37% (range 0.4–15.2) in group 2 (NS).


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  		Table 1. Clinical profile of matched patientsa

 
2.2. Operative methods
Monitoring was performed with an arterial pressure line, a Swan-Ganz catheter, and transesophageal echocardiography. The anesthesia protocol included propofol, sufentanil and cisatracurium, administered intravenously. All procedures were realized by median sternotomy.

In the group operated upon under cardioplegic arrest, myocardial protection was obtained using 8°C blood cardioplegic solution (8:1 dilution ratio) administered continuously antegradely and retrogradely. The method of continuous blood cardioplegia used was described previously [6]. The procedure was realized under 28°C hypothermia.

In the beating heart group, systemic anticoagulation with heparin was established using half of the CPB loading dose and was periodically supplemented, to maintain an activated clotting time between 200 and 300 s. Temperature homeostasis (>35.5°C) was achieved throughout the procedure using room temperature (>20°C), warm circulating water mattresses, and warm infusion solutions. Traction sutures were applied to the margins of the pericardium, displacing the heart superiorly. To realize the anastomoses on the marginal arteries, deep pericardial stitches were used; the patient was placed in the Trendelenburg position and tilted to the right. In all cases, suction-based tissue stabilizers Octopus 1 and 2 (Medtronic OctopusTM system, Medtronic, Inc., Minneapolis, MN, USA), designed by Borst and colleagues in Utrecht, were applied [7,8]. A Prolene 4/0 (Ethicon, Somerville, NJ) suture was applied around the coronary artery, proximal and distal to the site selected for the arteriotomy. The proximal suture was snared with a thin silicone tube and the distal part suture was simply lifted. A microblower was used (Visuflo, Research Medical Inc, Midvale, UT). Before the anastomosis was performed, the vessels were occluded for 5 min and reperfused for 2 min to achieve ischemic preconditioning. All anastomoses were realized by the same surgeon (Y.L.) using 8/0 monofilament sutures and 6x magnification with headlight illumination.

Graft flow assessment was realized systematically in all cases using intraoperatively an 8 MHz pulsed-wave Doppler ultrasound flowmeter (Scimed OPDOP 130, Bristol, UK) [9]. This system allows the simultaneous measurement of flow, velocity, resistance and pulsatility index in association with analysis of phasic flow pattern. It provides the criteria required to detect technical errors or flow limitations.

2.3. Hemodynamic data
Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were monitored. Thermodilution cardiac output was measured in triplicate using a Hellige CO computer. The hemodynamic measurements were repeated before pericardial incision, after reversal of heparin, and at regular intervals after surgery. Derived cardiovascular variables, including cardiac index (CI), left ventricular stroke work index (LVSWI), right ventricular stroke work index (RVSWI), systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were calculated using standard formulas.

Pharmacologic therapy with inotropic agents was used to keep the CI greater than 2.0 l/min/m2; that therapy was not interrupted when hemodynamic data were measured. A minimum preload, using as a guideline a left ventricular end diastolic area over 6 cm2 at transesophageal echography, was required before the administration of an inotropic agent. Dobutamine was used as the first-choice inotropic agent.

2.4. Myocardial enzymes
Levels of creatine kinase isoenzymes (CPK and CPK-MB mass) were measured upon arrival in the intensive care unit (ICU), and at regular intervals. They were expressed as a total value. According to our laboratory limits, a CPK-MB mass concentration exceeding 9.4 ng/ml indicated myocardial injury.

2.5. Data analysis
Perioperative data were collected and entered prospectively into the cardiovascular database by the surgeon. Postoperative data were collected by a data manager (B.M.). Values are presented as the mean± the standard error of the mean. The amount of pharmacologic support was quantified by multiplying the drug dose by its duration of administration, expressed in minutes. Each change of dose was recomputed for the duration of administration and was added to the previous amount. This allowed us to compute a volume of inotropic drug administered per patient.

Numerical and categorical variables were compared between both matched groups by Wilcoxon signed rank and binomial tests, respectively. Data obtained repeatedly, such as hemodynamic and enzymatic determinations, were compared by regression analysis of repeated measures using generalized estimating equations (GEE) as described by Liang and Zeger [10]. The statistical analyses were performed using the SPSS for Windows (SPSS Inc, Chicago, IL) software package, except regression analysis of repeated measures for which the RMGEE program was used [11].


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 References
 
3.1. Perioperative course
The operative data are described in Table 2. The off-pump group differs only by a smaller number of vessels grafted (2.3 vs. 2.8 grafts, P=0.015). Use of arterial grafts is the same in the two groups.


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  		Table 2. Perioperative dataa

 
Technical errors (anastomotic stricture, internal mammary or right gastroepiploic pedicle torsion) were identified by Doppler flowmeter assessment in 1.6 and in 4.8% of the distal anastomoses in group 1 and in group 2 patients, respectively (NS). These were corrected by graft reposition (n=3), redo of anastomosis (n=2), additional anastomosis (n=1), or section of adhesion (n=1).

The following drugs were administered intraoperatively: dobutamine at <5 {gamma}/kg/min in eight cases in group 1 and in five cases in group 2 (NS), dobutamine at >=5 {gamma}/kg/min in one case in group 1, dopamine at <5 {gamma}/kg/min in one case in each group.

The core temperature outcome in the two groups during the first 24 h was identical. Upon admission to the ICU, core temperature was 36°C and it increased rapidly to 37.6°C within 6 h.

3.2. Hemodynamic data
There was no significant difference among the groups regarding the trend in CI, LVSWI, SVRI, RVSWI and PVRI (Figs. 1 and 2 ). However, HR trend was significantly slower in group 2 (P=0.05).



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  		Fig. 1. Serial determinations of cardiac index, left ventricular stroke work index, and systemic vascular resistance index, before and after surgery in patients undergoing coronary artery bypass grafting through median sternotomy on the beating or cardioplegically arrested heart. Results are expressed as mean±SEM. There was no significant difference among the two groups.

 


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  		Fig. 2. Serial determinations of heart rate, right ventricular stroke work index, and pulmonary vascular resistance index, before and after surgery in patients undergoing coronary artery bypass grafting through median sternotomy on the beating or cardioplegically arrested heart. Results are expressed as mean±SEM. Heart rate trend was slower in the off-pump group (P=0.05).

 
During the stay in the ICU, pharmacological support (levorenine, dobutamine, dopamine and/or adrenaline) was required in 65% of the patients in group 1, and in 33% in group 2 (P<0.001). Group 1 patients required more dobutamine (P=0.013). The total amount of dobutamine and/or dopamine administered during the first 48 h was 3914±1306 {gamma}/kg in group 1 and 1645±697 {gamma}/kg in group 2 (P=0.049). A detailed description of the drugs administered is shown in Fig. 3 .



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  		Fig. 3. Comparison of the proportion of patients receiving inotropic support: the group of patients operated on off-pump required significantly less vasoactive drug support (P<0.001) and dobutamin administration (P=0.013). The volume of dobutamin/dopamin infused during the first 48 h stay in the intensive care unit is significantly lower in the off-pump group (insert).

 
3.3. Creatine kinase-MB mass
Plasma levels of the creatine kinase isoenzymes (CPK tot) and of the MB mass isoenzyme of creatine kinase (CPK-MB mass) were markedly lower (P<10-5 and P<10-4, respectively) in patients undergoing OPCAB (Fig. 4 ).



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  		Fig. 4. Plasma levels of the creatine kinase isoenzymes (CPK tot) and of the MB mass isoenzyme of creatine kinase (CPK-MB mass) were markedly lower (P<10-5 and P<10-4, respectively) in patients undergoing off-pump coronary artery bypass grafting.

 
3.4. Postoperative care
The duration of mechanical ventilation and the length of stay in the ICU were significantly shorter in group 2 (P=0.0025 and P=0.0023, respectively) (Table 3). The complications rate, including the advent of a new supraventricular arrhythmia, was similar in both groups as shown in Table 4. There was no perioperative myocardial infarction and no need for intra-aortic balloon counterpulsation.


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  		Table 3. Postoperative carea

 

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  		Table 4. Postoperative complicationsa

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
References
 
OPCAB is presented as a viable alternative to conventional CABG, particularly for patients with extreme left ventricular dysfunction [1], in the elderly [3], or in reoperations [2].

Several investigators studied the hemodynamic tolerance during multivessel grafting, particularly in the circumflex territory [12–14]: the resultant impairment of cardiac output during Octopus OPCAB could be generally corrected with fluid redistribution. However, little attention has been paid to the postoperative hemodynamic outcome and a clear superiority of OPCAB surgery regarding cardiac performance was not demonstrated yet. Indeed the only prospective randomized study available was completed by Ascione et al. [4]: they showed that heart rate was higher in the on-pump group, but that the other hemodynamic variables studied (mean arterial pressure, central venous pressure) did not differ. In addition, the patients operated off-pump required significantly less dopamine, at a minimal dose of 3–5 {gamma}/kg/min. It should be mentioned that only a small proportion of the patients had grafts implanted onto the circumflex territory and that the study included mainly two-vessel disease patients scheduled for elective surgery.

By contrast, the present study includes all patient risk categories and a large proportion of three-vessel disease. The study is not randomized, but the patients were matched according to relevant risk factors. In order to avoid any bias related to postoperative hypothermia, the core temperature trend was carefully studied in both groups. The similar rewarming outcome in the two groups shows that the potential for heat loss in the OPCAB group was well counteracted by the measures taken (room temperature >20°C, warm circulating water mattresses, and warm infusion solutions). This confirms the validity of the hemodynamic data comparison.

OPCAB patients underwent fewer bypass grafts per patient compared with the on-pump group. This finding is common in studies comparing OPCAB surgery with their conventional CABG counterparts [3,15–17]. This suggests that intraoperative considerations may cause a surgeon to perform fewer bypasses compared with patients undergoing on-pump CABG. In the present study, this difference did not result in an increased myocardial infarction rate (which was nil in both groups). Whether this will result in increased future reinterventions or cardiac events for OPCAB patients remains to be determined. However, the recent availability of suction-based devices allowing better exposure of the left ventricular wall should reduce this technique-related bias in the future.

The hemodynamic trend, including SVR, was similar in both groups. However, there was a marked and significant difference regarding the use of inotropes and particularly dobutamine. This corroborates an early study made by Pfister et al. [18] who matched for left ventricular function, 220 off-pump-patients, with controls operated on-pump. They found that the low output state occurred statistically less frequently off-pump. In addition, Bergsland et al. showed that the need for postoperative mechanical assistance was reduced in patients operated off-pump [2].

The present study demonstrated a slower HR trend in group 2 which is in accordance with the prospective randomized study of Ascione [4]. The reduced release of CK-MB mass enzymes confirms the superior myocardial protection obtained by the off-pump method. This corroborates previous studies assessing CK-MB and troponin I release [4,19–21].

The hemodynamic and biochemical differences observed between the two groups in this study were not translated into clinical benefits for the patients. Indeed, the small number of patients precludes from demonstrating a difference in clinical outcome given a lack in statistical power. In addition, this report represents an initial experience of beating heart surgery including a learning curve. Nevertheless, there was a markedly reduced duration of mechanical ventilation and of stay in the intensive care unit in the off-pump group. Other studies including a similar number of patients were unable to demonstrate a difference [22]. However, studies including a larger number of patients [2,18] or dealing with specific subgroups of high-risk patients [3] demonstrated a reduced complications rate associated with off-pump surgery.

We conclude, on the basis of this case-matched comparison, that off-pump CABG provides superior myocardial protection, since the need for postoperative inotropic support is markedly lower and CPK-MB mass release is reduced. However, given the limits of this study, further prospective randomized investigations are needed to confirm these early results.


   Acknowledgments
 
We wish to thank Brigitte Malhomme for her excellent data management work.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

  1. Moshkovitz Y., Sternik L., Paz M.A., Gurevitch J., Feinberg M.S., Smolinsky A.K., Mohr R. Primary coronary artery bypass grafting without cardiopulmonary bypass in impaired left ventricular function. Ann Thorac Surg 1997;63:S44-S47.
  2. Bergsland J., Hasnan S., Lewin A.N., Bhayana J., Lajos T.Z., Salerno T.A. Coronary artery bypass grafting without cardiopulmonary bypass – an attractive alternative in high risk patients. Eur J Cardio-thorac Surg 1997;11:876-880.[Abstract]
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