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Ann Thorac Surg 2002;74:S1383-S1389
© 2002 The Society of Thoracic Surgeons

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Supplement: Cardiothoracic Techniques and Technologies

Coronary perfusion methods during off-pump coronary artery bypass: results of a randomized clinical trial

^a Pensacola Heart Institute, Sacred Heart and Baptist Hospitals, Pensacola, Florida, USA

* Address reprint requests to Dr Vassiliades, Cardiothoracic Surgical Associates of Northwest Florida, 5151 North Ninth Avenue, Suite 200, Pensacola, FL 32504 USA
e-mail: vassiliades{at}pol.net

Presented at the Eighth Annual Cardiothoracic Techniques and Technologies Meeting 2002, Miami Beach, FL, Jan 23–26, 2002.

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
BACKGROUND: Several techniques are being used to perform off-pump coronary artery bypass (OPCAB) grafting. This three-armed clinical trial was performed to determine whether one OPCAB method of coronary perfusion was superior over the others with respect to myocardial protection and performance.

METHODS: Over the course of 11 months, 151 consecutive unselected patients underwent elective first-time OPCAB grafting by sternotomy performed by a single surgeon. Patients were prospectively randomized to receive one of three OPCAB coronary perfusion treatments: (1) no coronary perfusion (NCP), ie, OPCAB using no coronary perfusion during the distal anastomosis or graft perfusion after the distal anastomosis until all the proximal anastomoses were completed; (2) passive coronary perfusion (PCP), providing distal coronary perfusion during the anastomosis and immediate graft perfusion after the distal anastomosis by means of a passive cannula from the aorta; or (3) active coronary perfusion (ACP), providing assisted distal coronary perfusion and graft perfusion by means of an in-line pump (perfusion-assisted direct coronary artery bypass. Hemodynamic and biochemical data were recorded to disc continuously throughout the operation and postoperatively.

RESULTS: With no statistically significant differences in the three treatment groups with respect to patient age, left ventricular systolic or diastolic function, and extent and distribution of coronary disease or grafts performed, cardiac performance postoperatively was superior in the active coronary perfusion group compared to the groups receiving either passive coronary perfusion or no coronary perfusion (p < 0.001). In addition, troponin I levels were lower in the coronary perfusion groups (PCP and ACP) (p = 0.023).

CONCLUSIONS: Providing active coronary perfusion during the anastomosis and after each distal anastomosis by using an in-line pump resulted in superior myocardial protection and performance during OPCAB surgery when compared to either no coronary perfusion or passive coronary perfusion.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
With refinement of devices and methods, off-pump coronary artery bypass grafting continues to become less technically demanding. Complete revascularization performed off pump is now fairly routine in many centers throughout the world [1–3]. However, myocardial dysfunction and injury due to transient coronary occlusion continues to be a significant concern [4, 5]. In the past, these concerns have been addressed by the use of ischemic preconditioning of the target coronary bed with variable success [5]. A more recent approach has been to use distal coronary bed perfusion during the distal anastomosis followed by continued perfusion through the completed graft. Distal coronary bed perfusion can be provided either passively, by means of an intracoronary shunt or a shunt from the aorta, or actively, by using a shunt with an in-line pump from the ascending aorta (perfusion assisted direct coronary artery bypass [PADCAB]) [6–9]. Despite reports of success with each of these methods, no study has been performed to assess the effectiveness of these different techniques in a prospective randomized fashion. This three-armed, prospective, randomized trial compared the myocardial protection and performance characteristics of the techniques of off-pump grafting with the following three techniques: (1) no coronary perfusion (NCP); (2) passive coronary perfusion (PCP); and (3) active coronary perfusion (ACP).

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
A total of 151 consecutive, unselected patients were allocated randomly to receive one of the three treatments described above. All operations were performed by the same surgeon (T.A.V.) at Sacred Heart and Baptist Hospitals of Pensacola, FL. Randomization was performed by the method described by Altman and Bland [10]. The institutional review boards of both hospitals approved the study and the patients gave their informed consent. Inclusion criteria included all patients for elective first-time coronary artery bypass grafting except emergency cases, reoperative bypass grafting, or bypass grafting using a nonsternotomy approach. No patients were excluded on the basis of coronary anatomy, left ventricular function, or comorbid risk factors. During the study period (11 months), every elective first-time CABG patient (excluding those undergoing operation with nonsternotomy approaches) was entered into the study, and an OPCAB procedure was performed by this surgeon (T.A.V.). Nonoperative patient care providers were blinded, and management was based on unbiased, criteria-driven protocols.

Patient characteristics
There was no difference in base line characteristics of the three patient groups (Table 1). Patient data were collected and analyzed according to the guidelines and definitions of The Society of Thoracic Surgeons (STS) National Cardiac Surgery Database. All patients were receiving aspirin (81 to 325 mg) preoperatively.

The grafting sequence was similar in all patients. The left anterior descending coronary artery was grafted first; follwed by the anterior, lateral, and posterior vessels. Exceptions to this rule were totally occluded vessels that received collaterals from another coronary artery that also required a bypass graft. In this case, the collaterized vessel was grafted first. Distal anastomoses were performed before the proximal anastomoses. Proximal anastomoses were performed under a partial occlusion clamp. In the presence of an atherosclerotic ascending aorta, the proximal anastomoses were placed to the in situ IMA pedicle and aortic clamping was avoided. Patients were fully reversed with protamine sulfate. The activated clotting time was restored to baseline.

The three treatment arms of the study are outlined below.

NCP group
In the no coronary perfusion (NCP) group, no distal coronary bed perfusion was provided during the distal anastomosis except in cases in which significant ischemic or hemodynamic changes occurred. A shunt was used when grafting the main right coronary artery unless it was totally occluded. Upon completion of the distal anastomosis, distal coronary bed perfusion was reestablished through the stenotic native coronary artery only. The grafts were not perfused until all proximal anastomoses were completed at the conclusion of the operation. Low-dose nitroglycerin (5 to 20 µg/L) was given intravenously throughout the operation as long as the mean arterial pressure remained within the normal range.

PCP group
In the passive coronary perfusion (PCP) group, a DLP aortic root cardioplegia cannula (11F, 9 gauge; Medtronic DLP, Grand Rapids, MI) was placed in a nondiseased portion of the ascending aorta and secured with a pursestring suture. The coronary perfusate was administered passively from the ascending aorta through a multiple perfusion set (Medtronic DLP). A soft 2- or 3-mm olive-tipped catheter (Medtronic DLP) was passed distally through the coronary arterotomy to provide distal coronary perfusion during the anastomosis. After completion of each free graft, the proximal end was connected to an arm of the delivery set so as to provide immediate and continuous coronary blood flow to the myocardial bed. The flow to each coronary bed was directly dependent on the mean arterial pressure in the ascending aorta and the number of grafts connected to the set. Flows ranged from 10 to 50 mL/min per graft. Perfusion to each graft was terminated while the proximal anastomosis was completed. Low-dose nitroglycerin (5 to 20 µg/L) was given intravenously throughout the operation as long as the mean arterial pressure remained within the normal range.

ACP group
In the active coronary perfusion (ACP) group, patients underwent perfusion assisted direct coronary artery bypass (PADCAB) [6]. As in the PCP patients, a DLP aortic root cardioplegia cannula (11F, 9-gauge; Medtronic DLP) was placed in a nondiseased portion of the ascending aorta and secured with a pursestring suture. The cannula was then connected to the Myocardial Protection System (MPS) perfusion delivery system (Quest Medical Inc, Allen, TX). A soft 2- or 3-mm olive-tipped catheter (Medtronic DLP) was passed distally through the coronary arterotomy to provide distal coronary perfusion during the anastomosis. After completion of each free graft, the proximal end of the graft was connected to an arm of the delivery set so as to provide immediate and continuous coronary blood flow to the myocardial bed (Fig 1). Arterial blood was removed from the aorta and actively pumped into the distal coronary bed during and after the anastomosis. The Myocardial Protection System allowed monitoring of delivery line pressure (mm Hg), graft infusion pressure (mm Hg), and flow (cc/min). Unlike the PCP approach, the ACP set-up allows administration of coronary perfusate at suprasystemic pressures, as it is not as dependent on the pressure in the ascending aorta or on the number of grafts being supplied with perfusate at one time. Additionally, low-dose nitroglycerin (5 to 20 µg/L) was used as an additive to the reperfusate in all completed grafts. Flows ranged from 20 to 150 mL/min per graft. Perfusion to each graft was terminated while the proximal anastomosis was completed.

View larger version (54K): [in this window] [in a new window]   Fig 1. Active coronary perfusion using the perfusion-assisted direct coronary artery bypass system. Aortic blood is directed from the aortic cannula (A) through the in-line pump (Quest MPS system) to the multiple perfusion manifold (B), and finally to the grafts (C) or as a shunt during distal anastomosis (D). A feedback line (E) is used to monitor perfusion pressure.

Myocardial performance was assessed in triplicate by a flow-directed thermodilution fiberoptic continuous cardiac output catheter (OPTI-Q Sv02/CCO catheter, Abbott Critical Care Systems, North Chicago, IL). Measurements were taken every 60 seconds and recorded directly to disc. A 12-lead electrocardiogram was obtained in all patients on arrival in the ICU and 24 hours postoperatively.

Statistical analysis
All statistical analyses were performed by an independent group (Array Medical Laboratories, Indiana University, South Bend, IN). The clinical team was kept separate from data handling whenever feasible. Data and results are presented as mean ± standard error of the mean or as median and range. Continuous variables were analyzed using a Student’s t test or a Mann-Whitney rank sum test as appropriate. Categorical variables were analyzed using the ² test or Fisher’s exact test as appropriate. Repeated measures were analyzed using repeated measures analysis of variance (ANOVA). If the ANOVA was significant (p < 0.05), t tests were performed at the individual time points using the Bonferroni correction for multiple testing.

As the study populations failed the underlying assumption of normality, a Kruskal-Wallis analysis of variance on ranks test was used. The results of the ANOVA revealed significant (p < 0.001) differences among the three treatment groups. To isolate the treatment differences, Dunn’s test was used when the samples sizes were unequal, and each treatment was compared against the other in a pairwise manner with appropriate corrections. Significance of Dunn’s test is reported as p less than 0.05. All pairwise multiple comparison procedures were as follows: NCP versus PCP, p less than 0.005 NCP versus ACP, p less than 0.001 PCP versus ACP, p greater than 0.20.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Operative data
There was no significant difference in operating time, fluid requirement, or blood loss. However, a larger volume of blood was autotransfused in the patients receiving active perfusion (ACP) (Table 2). Three patients were converted to cardiopulmonary bypass because of an intramyocardial left anterior descending coronary artery that could not be found, sudden hemodynamic compromise due to global ischemia before cardiac manipulation, and discovery of significant mitral regurgitation. These patients were eliminated from the study. Two patients were randomized to NCP and were allowed to cross over to PCP because of significant ST segment depression during grafting of the proximal left anterior descending coronary artery. These patients were left in the PCP group for the remainder of the study and analysis.

Postoperative results
Postoperative clinical outcome data as collected by the STS National Cardiac Surgery Database was similar in all three groups. Clinical outcome data for the entire study group were as follows: operative mortality 1.3% (2/151), myocardial infarction 1.98% (3/151), stroke 0.6% (1/151), renal failure 0.6% (1/151), sternal infection 0.6% (1/151), reexploration for bleeding 2.6% (4/151), atrial fibrillation 28.4% (43/151), transfusion rate 11.2% (17/151), inotropic support 12.6% (19/151), intraaortic balloon pump use 2.6% (4/151), mean mechanical ventilation time 2.5 hours ± 5.39, mean ICU length of stay 1.0 days ± 0.28, mean hospital length of stay, 4.6 days ± 2.6, 90-day reintervention rate 3.3% (5/151 PTCA only), 90 day readmission rate 11.3% (17/151). Postoperative mediastinal drainage (mean 589 ± 478.8 mL ) was not statistically different among the three groups, but the NCP patients had a statistically significantly higher fluid requirement (p = 0.032). The cardiac indices and mixed venous saturation measurements were statistically higher in the ACP group compared to the NCP group at every 4-hour interval postoperatively (Figs 2 and 3). Comparisons were made controlling for the prevailing central venous pressures. With the exception of the first set of postoperative cardiac index measurements, the PCP group was not significantly different from the NCP group. The difference between the perfusion groups (PCP and ACP) was too small to reach statistical significance, with the exception of the SV02 measurements at time 12 hours. Creatinine phosphokinase–MB and lactic acid levels (measured at 8, 16, and 24 hours postoperatively) were not statistically significantly different among the three groups. However, Troponin I levels measured at 24 hours were lower (p = 0.023) in the ACP group (mean 0.18 ± 0.48 ng/mL) compared to the NCP group (mean 0.51 ± 0.85 ng/mL). The local laboratory reference range for normal at the 99th percentile is less than 0.04 ng/mL, and the cutoff for acute myocardial infarction is 0.5 ng/mL (Sacred Heart Hospital, Pensacola, FL).

View larger version (18K): [in this window] [in a new window]   Fig 2. Cardiac index (CI) (cardiac output/body surface area) as determined at 0, 4, 8, 12, and 16 hrs in the intensive care unit. Pairwise multiple comparisons: NCP vs PCP,p< 0.005; NCP vs ACP,p< 0.001; PCP vs ACP,p< 0.20.Postop= postoperatively.

View larger version (18K): [in this window] [in a new window]   Fig 3. Mixed venous saturation measured at 0, 4, 8, 12, and 16 hrs in the intensive care unit. Pairwise multiple comparisons: NCP vs PCP,p= NS; NCP vs ACP,p< 0.001; PCP vs ACP,p< 0.001.Postop= postoperatively.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

With respect to myocardial injury, the mean total ischemic time for the NCP patients (23 ± 6.6 minutes) was significantly longer (p = 0.01) than in the perfusion groups (PCP 16.6 ± 5.4 minutes, ACP 18.2 ± 7.1 minutes), as shunts were not used during the distal anastomosis and the completed free grafts were not perfused until the proximal anastomosis was completed. As a result, the Troponin I measured at 24 hours was statistically higher (p = 0.023) in the NCP group (0.51 ± 0.85 ng/mL) when compared to that in the PCP (0.26 ± 0.58 ng/mL) and ACP (0.18 ± 0.48 ng/mL) groups. In our laboratory, a Troponin I level of 0.05 ng/mL is the cutoff for acute myocardial infarction. Creatinine phosphokinase–MB levels and lactic acid release were not statistically significantly higher in the NCP group. Troponin I levels have been shown to be the most sensitive and specific in depicting myocardial ischemia and to correlate with subsequent adverse cardiac events [12–14].

In conclusion, this study demonstrates that active coronary perfusion during an OPCAB procedure offers superior myocardial protection over passive or no coronary perfusion. When passive perfusion (involving a cannula with a multidelivery manifold) is used, flow is directly proportional to the prevailing arterial pressure, the quantity of grafts being perfused, and the relative vascular resistance of each of the coronary beds connected to the manifold. The net result is that under situations of hypotension and multiple grafts, the net perfusion to each graft may be less than 20 mL/min. The mechanism behind superior quantity and distribution of assisted flow relates to the simple use of an in-line pump rather than pressure-dependent passive flow. When systemic pressures fall during mechanical manipulation of the heart (as in grafting the posterior wall), coronary blood flow can be maintained at or above systemic levels. By maintaining adequate coronary flow, the negative feedback cycle of decreased systemic pressure causing decreased coronary perfusion pressure and further myocardial dysfunction is interrupted. Another potential strategy that was not used in this study is to perform the proximal anastomosis first. Although the graft flow during the operation will still be determined in part from the aortic root pressure, each graft would be connected individually to the aorta, unlike with the multidelivery manifold. However, we choose to use the multidelivery passive cannula method (PCP) most often in our everyday practice, as it prevents the need to perform the proximal anastomosis first, which we often find inconvenient. Additionally, it is a very reliable blood flow source to use for shunting as well as deairing and providing subsequent blood flow throughout the remainder of the distal anastomosis phase of the operation. However, although the PCP method is very user-friendly and inexpensive, the ACP method provides a significantly greater quantity of coronary blood flow.

We do not believe, however, that this study necessarily justifies the use of the ACP (PADCAB) technique in most OPCAB cases. Many factors can influence the amount of coronary blood flow during the operation, including (but not limited to) the use intravenous or intracoronary nitroglycerin or the maintenance of a higher perfusion pressure. To what degree intra–coronary artery nitroglycerin contributed to the improved outcome was not specifically addressed in this study, which is a potential shortcoming. The capability of infusing intracoronary nitroglycerin aids in decreasing the resistance of the vascular bed and opens collateral circulation [6, 15]. Regardless, we believe that these results provide justification for continued investigation into OPCAB myocardial protection techniques and for further development of new technology to assess the myocardium intraoperatively, such as with coronary sinus metabolites [16], online measurement of myocardial pH [17], and contrast transesophageal echocardiography. Further investigation of myocardial protection during beating heart surgery is currently underway [18].

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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