Pulmonary abnormalities after coronary arterial bypass grafting operation: cardiopulmonary bypass versus mechanical stabilization

Pulmonary Abnormalities After Coronary Arterial Bypass Grafting Operation: Cardiopulmonary Bypass Versus Mechanical Stabilization Gary S. Kochamba, MD, Kwok L. Yun, MD, Thomas A. Pfeffer, MD, Colleen F. Sintek, MD, and Siavosh Khonsari, MD Regional Department of Cardiac Surgery, Kaiser Permanente Medical Center, Los Angeles, California

Background. Cardiopulmonary bypass has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting procedures. This randomized prospective study was conducted to determine whether patients undergoing coronary artery bypass grafting operations using cardiac stabilization and thereby avoiding cardiopulmonary bypass will have improved pulmonary function postoperatively. Methods. Fifty-eight patients were randomized to one of two groups: coronary artery bypass grafting operation with stabilization or coronary artery bypass grafting operation with cardiopulmonary bypass. Preoperative and postoperative pulmonary gas exchange measurements were performed on intubated patients, including the arterial partial pressure of oxygen on 100% inspired oxygen, the alveolar–arterial oxygen gradient, and pulmonary shunt. Static and dynamic lung compliance measurements were performed postoperatively. Hemodynamic variables (including creatine kinase-MB and troponin levels), intubation time, postoperative bleeding, and blood transfusions were compared. Results. Both study groups had a large decrease in

arterial partial pressure of oxygen on 100% inspired oxygen (p < 0.0001) and a significant postoperative increase in the alveolar–arterial oxygen gradient (p < 0.0001). There was no statistical difference in the postoperative gas exchange between the two groups; however, the postoperative pulmonary shunt was significantly better in the stabilization group (24% versus 31%, p ⴝ 0.03). The patients were extubated in the intensive care unit earlier in the stabilization group (8.2 hours versus 9.2 hours, not significant). The mean static and dynamic lung compliance postoperatively was lower in the stabilization group, although not statistically significant (p ⴝ 0.06).1 Conclusions. Coronary artery bypass grafting operation using cardiac stabilization technique is safe and avoids the risk of cardiopulmonary bypass. The pulmonary gas exchange postoperatively is comparable to standard cardiopulmonary bypass procedures, but a reduced postoperative pulmonary shunt was seen in the stabilization group.

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nary function in patients undergoing CABG procedures without CPB. The present study was conducted to determine whether patients undergoing CABG using a cardiac stabilization technique, thereby avoiding CPB, will have improved pulmonary function postoperatively.

uch of the postoperative morbidity after coronary artery bypass grafting (CABG) operation has been attributed to a systemic inflammatory response induced by cardiopulmonary bypass (CPB) [1, 2]. The exposure of blood to large areas of synthetic materials in the CPB circuit activates neutrophils, which become trapped in the pulmonary circulation resulting in endothelial and interstitial pulmonary injury [3–5]. Coronary artery bypass grafting procedures performed without CPB result in less inflammatory response [6, 7]. Clinical studies using mechanical stabilization as a technique to perform CABG operation rather than the use of CPB have suggested that the pulmonary function postoperatively is better, allowing earlier extubation [8, 9]. However, no study has rigorously examined the postoperative pulmo-

Accepted for publication Nov 30, 1999. Address reprint requests to Dr Kochamba, Department of Cardiac Surgery, Kaiser Permanente Medical Center, 1526 North Edgemont St, 3rd Floor, Building ‘G’, Los Angeles, CA 90027, e-mail: [email protected].

© 2000 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 2000;69:1466 –70) © 2000 by The Society of Thoracic Surgeons

Material and Methods This prospective randomized study was initiated with the approval of the institutional review board. Patients were included on the basis of the conventional criteria for selection of patients requiring CABG operation. However, inclusion was restricted to patients who required grafts to the left anterior descending coronary artery, diagonal coronary artery, right coronary artery, and posThis article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/section/atsdiscussion/

0003-4975/00/$20.00 PII S0003-4975(00)01142-5

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KOCHAMBA ET AL PULMONARY ABNORMALITIES AFTER CABG OPERATION

terior descending coronary artery to avoid crossover from the stabilization group to the CPB group. Patients who had angiographic anatomy that included calcified or intramyocardial arteries were excluded from participation. Patients who were hemodynamically unstable or required emergent operations were also excluded from the study. Fifty-eight patients were prospectively randomized to two groups. In the CPB group, CABG was performed using the conventional technique. The stabilization group CABG procedure was performed on the beating heart using either an epicardial stabilization retractor (U.S. Surgical, Norwalk, CT) or an epicardial suction device (Medtronic, Minneapolis, MN). All operations were performed by one surgeon using a median sternotomy and the same operative technique as described. In the CPB group, CPB was performed using a membrane oxygenator (Cobe Ultima; Cobe Cardiovascular Inc) primed with 500 mL of Isolyte S, 1000 mL of Hespan, and 50 mL of sodium bicarbonate. The patients received anticoagulation with 3 mg/kg heparin to maintain an activated clotting time greater than 480 seconds. An additional 1 mg/kg heparin was used to treat an activated clotting time less than 450 seconds. The pump flow was 2.2 to 2.4 L 䡠 min⫺1 䡠 m⫺2, and moderate hypothermia was used to lower the patient’s blood temperature to 34°C. Rewarming was continued to 37°C before discontinuation of CPB. In the stabilization group, the US Surgical ring system was used to stabilize target vessels in the left anterior descending and diagonal coronary artery distribution. When the target vessel was located inferiorly involving the right coronary artery or posterior descending coronary artery vessels, the Medtronic Octopus tissue stabilizer was selected. This consists of two malleable arms, each with five suction domes. The stabilization devices were positioned adjacent to the target site. The patients were administered 1 mg/kg of heparin for anticoagulation and 1 mg/kg of lidocaine. Vessel loops were placed proximally and distally around the target vessel, and a 3-minute period of preischemic conditioning was performed by vessel loop occlusion, followed by a 3-minute period of reperfusion. The vessel loops were then resecured, and an arterotomy was performed. Visualization of the anastomotic area was aided with a carbon dioxide mist blower, and the anastomosis was performed in the standard fashion with 7-0 Prolene (Ethicon, Somerville, NJ) suture. A vessel shunt was not used in this study. If a saphenous vein graft was performed, the proximal anastomosis was performed with a partial aortic occlusion clamp. The anesthetic management of these patients included premedication with 2 mg of lorazepam. Induction was performed with a loading dose of fentanyl 10 to 15 ␮g/kg and pancuronium 1 mg/kg; anesthesia was maintained by isoflurane 1% to 1.5%. At the termination of revascularization, both groups received protamine to reverse the circulating heparin by titrating to the activated clotting time. At the completion of the operation, patients were transferred to the intensive care unit, and the postoperative care was standardized by physicians who were blinded to the

Table 1. Patient Demographics Characteristic Age (y) BSA (m2) Sex (% male) EF (%) Diabetes (%) Renal failure (%) Smoking (%) COPD (%)

Stabilization (n ⫽ 29) 55.6 (9.5) 2.00 (0.261) 76% 62.7 (14.7) 41% 10% 66% 3%

CPB (n ⫽ 29)

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p Value

61.6 (10.0) 2.08 (0.268) 79% 64.3 (12.7) 41% 7% 48% 7%

0.05 0.28 0.75 0.87 1.0 1.0 0.29 1.0

Data are presented as percentage or mean ⫾ standard deviation. BSA ⫽ body surface area; COPD ⫽ chronic obstructive pulmonary disease; CPB ⫽ cardiopulmonary bypass; EF ⫽ ejection fraction.

study groups. Pulmonary gas exchange measurements performed after anesthetic induction in the operating room and immediately on arrival to the intensive care unit on intubated patients included the arterial partial pressure of oxygen on 100% inspired oxygen, the alveolar–arterial oxygen gradient, and the pulmonary shunt. Pulmonary mechanics measurements, which included the static and dynamic lung compliance, on the Adult Star 2000 (Infrasonics Inc) ventilator were performed by respiratory therapists. The postoperative cardiac index and the inotropic agents required were recorded. The mechanical ventilation variables were standardized at a respiratory rate of 10 breaths per minute, tidal volume 10 mL/kg, fraction of inspired oxygen 1.0, positive endexpiratory pressure 5 cm H2O, and inspiratory to expiratory ratio 1:3. The criteria for tracheal extubation included an appropriate sensorium, hemodynamic stability, adequate pulmonary function (arterial partial pressure of oxygen greater than 60 mm Hg with fraction of inspired oxygen 0.4), and no active chest-tube bleeding. The intubation times for both groups of patients were recorded. The postoperative complications were recorded until hospital discharge. The creatine kinase-MB levels and troponin I levels were measured in all patients 8 hours postoperatively. An electrocardiogram was performed postoperatively with angiographic documentation of graft patency if there was evidence of perioperative ischemia. The chest-tube blood loss, as well as homologous blood units transfused, was recorded during their hospital stay. The statistical analysis to compare the two groups was performed by the nonparametric Wilcoxon rank-sum test of independent groups. A p value of less than 0.05 was considered statistically significant, and the results are expressed as the mean ⫾ standard deviation unless otherwise indicated.

Results Analysis of the preoperative characteristics of patients in the two study groups (Table 1) shows them to be similar. The sex was predominantly male in both groups, and the

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Table 2. Cardiac Data Variable

Stabilization (n ⫽ 29)

CPB (n ⫽ 29)

p Value

Operative Grafts/patient 1.5 1.6 LIMA/patient 0.97 0.93 Ischemic time (min) 21.8 (9.3) 26.1 (8.9) Postoperative 3.31 (0.66) 3.40 (0.72) Cardiac index (L/min/m2) PCWP (mm Hg) 12.3 (3.7) 12.4 (3.1) CPK-MB (enzyme ng/cc) 5.92 (7.43) 11.34 (5.05) Troponin (enzyme ng/cc) 1.71 (2.52) 4.93 (3.37) A-fib (%) (5/29) (17%) (8/29) (27%)

0.38 0.55 0.03 0.77 0.82 0.0001 0.0001 0.345

Data are presented as mean (⫾ standard deviation). A-fib ⫽ atrial fibrillation; CPB ⫽ cardiopulmonary bypass; CPKMB ⫽ creatine kinase-MB; LIMA ⫽ left internal mammary artery; PCWP ⫽ pulmonary capillary wedge pressure.

average age in the stabilization group was slightly younger than those in the CPB group. There was no difference in the prevalence of renal failure, chronic obstructive pulmonary disease, or history of smoking between groups. The preoperative static lung compliance, preoperative creatine kinase-MB and troponin levels were not significantly different. The operative and postoperative hemodynamic variables are shown in Table 2. The average patient received one internal mammary artery graft, and an average of one and a half bypass grafts were performed per patient. The stabilization group had a 22-minute coronary occlusion time, less than the 26-minute cross-clamp time in the CPB group. The difference was likely related to cardioplegia delivery during the cross-clamp time. The cardiac index measurements when the chest was closed were significantly lower in the stabilization group. The postoperative pulmonary data are presented in Table 3. The preoperative arterial partial pressure of oxygen and alveolar–arterial oxygen gradient on 100% inspired oxygen performed after anesthetic induction were similar in both patient groups. Each group had a significant postoperative decrease in arterial partial pressure of oxygen on 100% inspired oxygen ( p ⬍ 0.0001 for each group) and a significant postoperative increase in the alveolar–arterial oxygen gradient ( p ⬍

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0.0001 for each group). However, there was no statistical difference in the postoperative gas exchange between the two groups. The postoperative pulmonary shunt was elevated in both groups but was significantly lower in the stabilization group ( p ⫽ 0.03) as seen in Figure 1. Figure 2 compares the mean static and dynamic lung compliances between the two groups, and although the stabilization group had a lower lung compliance postoperatively, this did not reach statistical significance ( p ⫽ 0.06). The stabilization group had a 1-hour shorter mean intubation time, which was not statistically significant (Table 3). Postoperative atrial fibrillation occurred in 5 (17%) stabilization patients and 8 (27%) CPB patients. One patient from each group experienced a perioperative myocardial infarction (defined as a postoperative creatine kinase-MB ng/cc greater than 50). No patient in either group had electrocardiographic evidence of a myocardial infarction. The mean creatine kinase-MB and mean troponin levels were elevated in both groups postoperatively and were significantly lower in the stabilization group compared to CPB group ( p ⫽ 0.0001) as seen in Table 2. Four patients in the stabilization group had postoperative angiography for nonspecific changes on electrocardiogram, and all grafts were patent. There were no cerebral infarctions or mortality in either study group. The homologous blood units transfused were recorded in both groups during their total hospital stay. The stabilization patients required fewer units of homologous blood transfused than the CPB patients (0.93 versus 1.31 units per patient; p ⫽ 0.54). Twenty-four percent of stabilization patients required blood products compared with 48% of CPB patients. One patient in the stabilization group returned to the operating room for control of a surgical bleeding site. The 8-hour chest-tube drainage was 315 mL in the stabilization group versus 290 mL in the CPB group. These differences were not statistically significant.

Comment Compared with the CPB group, the stabilization patients in this study exhibited less postoperative shunting, yet they experienced similar increases in alveolar–arterial

Table 3. Pulmonary Data

Preoperative Pao2 (mm Hg) Postoperative Pao2 (mm Hg) Change Pao2 (mm Hg) Preoperative Aa O2 (mm Hg) Postoperative Aa O2 (mm Hg) Change Aa O2 (mm Hg) Intubation time (min) % extubated ⱕ 6 hours

Stabilization (n ⫽ 29)

CPB (n ⫽ 29)

p Value

457.9 (134.6) 268.1 (89.2) ⫺189.8 (139.2) 200.0 (105.3) 397.6 (86.2) 197.6 (99.6) 8.24 (3.59) 55% (16/29)

462.9 (84.7) 246.0 (112.7) ⫺216.8 (129.5) 212.4 (81.8) 396.7 (125.5) 184.3 (156.6) 9.24 (4.20) 38% (11/29)

0.46 0.39 0.0001 0.23 0.93 0.0001 0.30 0.19

Data are presented as mean ⫾ standard deviation or percentage. Aa O2 ⫽ alveolar–arterial oxygen gradient;

CPB ⫽ cardiopulmonary bypass;

Pao2 ⫽ arterial partial pressure of oxygen.

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Fig 1. Postoperative pulmonary shunt. (CPB ⫽ cardiopulmonary bypass group.)

oxygen gradient and trended toward a poorer lung compliance. This indicates that factors other than CPB may hinder postoperative gas exchange and early tracheal extubation. Numerous investigators have documented a decrease in pulmonary gas exchange postoperatively in patients undergoing CABG procedures. Possible causes include decrease in functional residual capacity, decreased lung compliance, increased shunt caused by leukocyte migration to the lungs, and increased permeability of the alveolar capillary barrier [10 –12]. The technique of performing CABG operation with epicardial tissue stabilization has been shown to reduce inflammatory markers, such as tumor necrosis factor-␣, plasma elastase, ␤-thromboglobulins and complement activation (C3a) [13]. Some have suggested that avoiding CPB results in earlier extubation from better lung function [14, 15]; however, studies showing improved pulmonary function are lacking. In fact, in our experience, several patients undergoing CABG using the stabilization technique outside of this study have had poor postoperative gas exchange and unexpected prolonged mechanical ventilation. In this study, patients were prospectively randomized to control for patient selection. Stabilization patients were taken to the intensive care unit intubated to provide measurements of pulmonary gas exchange and pulmonary compliance, although our practice is to extubate many of these patients in the operating room. Patients

Fig 2. Mean postoperative static and dynamic lung compliance. (CPB ⫽ cardiopulmonary bypass group.)

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who required grafting to the circumflex artery territory were excluded for the purpose of the study because of limitations in the stabilization technology. Specifically, many patients with larger hearts do not tolerate the lifting and rotation required for exposure, although deep pericardial elevation sutures and the newer generation stabilization devices are quite helpful. The techniques of grafting the anterior and inferior vessels are technically simpler and can be standardized for a study protocol, thereby avoiding crossover between groups. When our study groups were compared, patients in both groups exhibited equal increases in the alveolar–arterial oxygen gradient. Both groups also had increased pulmonary shunt postoperatively, although shunting was significantly lower in the stabilization group. The decreased lung compliance in the stabilization group suggests that manipulation of the heart may cause pulmonary edema, which in turn may result in ventilation–perfusion mismatch in the absence of the inflammatory effect of CPB. Other intraoperative interventions may contribute to pulmonary congestion, including Trendelenberg positioning and cardiac elevation and rotation to facilitate anastomotic exposure. Early studies found that immobilization of the heart required for vessel stabilization results in a 44% decrease in stroke volume because of direct mechanical compression, which may affect the right ventricle more than the left ventricle [16]. Furthermore, vessel occlusion during coronary anastomosis may induce regional myocardial ischemia, depressing ventricular function. The anesthesiologist may administer agents to induce bradycardia or phenylephrine and fluids to treat hypotension. However, as the stabilization technology evolves, these interventions may be required less often, and better pulmonary function will support earlier tracheal extubation. In our study, the U.S. Surgical stabilization system, which relies on direct mechanical compression, was used to stabilize the anterior vessels. This system was not found to be adequate to stabilize vessels in the right coronary artery distribution; therefore, the Medtronic Octopus system, which uses a suction pod system for vessel stabilization, was used for grafting the inferior vessels. No differences in pulmonary outcome were found between these two devices. Fewer patients in the stabilization group required transfusion of blood products. More importantly, 29% fewer total blood units were transfused in the stabilization group during their hospital stay. The majority of the transfusions were after extubation and did not contribute to the postoperative pulmonary dysfunction in either study group. The postoperative myocardial enzymes were lower in the stabilization group; however, the postoperative cardiac index in the cardiac surgical unit and inotropic requirements were similar in both groups, suggesting that low cardiac output did not contribute to the pulmonary dysfunction postoperatively. Although intuitively it seems reasonable that avoiding CPB may result in improved pulmonary function after CABG operation, this hypothesis may be simplistic, and the effects of mechanical stabilization of the heart on postoperative pulmonary function need to be better defined.

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Several limitations of this study should be discussed. This study was prospectively randomized involving nonemergent patients with two-vessel coronary artery disease (left anterior descending and right coronary artery distributions), and these results may not extrapolate to older or sicker patients with triple-vessel disease. The pump times in the CPB group were relatively short, and a difference in pulmonary function if longer pump times had been accrued could have been missed. In addition, evolving stabilization techniques, possibly including the routine use of intracoronary shunts or more advanced suction devices, may improve outcome from our early experience. In conclusion, off-pump CABG operation is a safe procedure that avoids the potential risks of CPB. No clinical benefit in terms of pulmonary function could be demonstrated by this study, although a reduced postoperative pulmonary shunt was seen in stabilization patients, an effect which may be enhanced by better stabilization techniques.

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We are grateful to Maggie Vargas-Ruiz for preparation of the manuscript and to Raoul Burchette for his statistical analysis.

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