Influence of Pleurotomy on Pulmonary Function After Off-Pump Coronary Artery Bypass Grafting

Influence of Pleurotomy on Pulmonary Function After Off-Pump Coronary Artery Bypass Grafting CARDIOVASCULAR Solange Guizilini, PhD, Walter J. Gomes, MD, PhD, Sonia M. Faresin, MD, PhD, Douglas W. Bolzan, BScPT, Enio Buffolo, MD, PhD, Antonio C. Carvalho, MD, PhD, and Angelo A. V. De Paola, MD, PhD Cardiology and Cardiovascular Surgery Disciplines, Pirajussara and São Paulo Hospitals, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil Background. This study evaluated the influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting (CABG) using the left internal thoracic artery (LITA). Methods. Thirty patients were prospectively allocated into two groups: 15 patients with an opened left pleural cavity (OP group) and 15 patients with an intact pleural cavity (IP group). Bedside pulmonary function tests were recorded preoperatively and on postoperative days 1, 3, and 5. Arterial blood gas analyses and ratio of partial pressure of arterial oxygen (PaO 2 )/fraction of inspired oxygen (FIO 2 ) ratio were evaluated preoperatively and on postoperative day 1. Results. A significant decrease of pulmonary function was observed in both groups until postoperative day 5. When compared with the percentage of the preoperative value, the forced vital capacity was significantly lower in the OP group than in the IP group on postoperative days 1 (33.3% 8.3% versus 49.1% 8.4%, p < 0.001), 3 (45.4% 7.0% versus 62.1% 8.6%, p < 0.001), and 5 (56.1% 8.7% versus 77.5% 11.6%, p < 0.001). Similar results were found for forced expiratory volume in 1 second on postoperative days 1 (35.7% 8.6% versus 50.0% 9.8%, p < 0.001), 3 (48.4% 7.0% versus 61.5% 9.02%, p < 0.001) and 5 (58.8% 8.5% versus 75.9% 10.2%, p < 0.001). The PaO 2 value and the PaO 2 /FIO 2 ratio dropped on postoperative day 1 in both groups (p < 0.05), with a higher fall in the OP group (p < 0.05). Orotracheal intubation time (p 0.012) and hospital stay (p 0.002) were lower in the IP group. Conclusions. Off-pump CABG using the LITA, independently of pleural opening, induced a significant reduction in early postoperative pulmonary function. However, the patients undergoing pleurotomy demonstrated more pronounced pulmonary dysfunction. (Ann Thorac Surg 2007;84:817 22) 2007 by The Society of Thoracic Surgeons The left internal thoracic artery (LITA) has long been established as the graft of choice for coronary artery bypass grafting (CABG) surgery [1]. Superior long-term graft patency leads to improved survival, better quality of life, and lower incidence of cardiac events compared with vein grafts [1, 2]. However, evidence suggests that LITA harvesting is associated with a greater decrease in postoperative pulmonary function, therefore increasing the risk of pleuropulmonary complications [3 7]. This has largely been attributed to pleurotomy, the further need for placement of a chest tube [4, 8, 9], and likely additional trauma to the chest wall during dissection of the graft [3, 5]. Beyond LITA mobilization, several other factors can influence pulmonary dysfunction after CABG, including the combined effects of the general anesthesia, sternotomy, and cardiopulmonary bypass (CPB) [3, 10]. Despite the evidences of pulmonary function impairment in the CABG postoperative period [3 5, 8, 9], the role of pleural opening is still debated. Previous studies demonstrated that on-pump CABG using the LITA graft Accepted for publication April 16, 2007. Address correspondence to Dr Guizilini, Rua Pedro Inácio de Araujo, 201/13-A, São Paulo, SP, 05386-330, Brazil; e-mail: s_guizilini@yahoo. com.br. and maintaining pleural integrity has beneficial effects on pulmonary function [8, 11], which could reduce respiratory morbidity [11 14]. Therefore, the objective of this study was to evaluate the influence of pleurotomy on pulmonary function in patients undergoing off-pump CABG using the LITA. Patients and Methods This study was performed in the Pirajussara and Sao Paulo Hospitals of the Federal University of Sao Paulo, Sao Paulo, Brazil. The Institutional Ethics Committee for Clinical Research approved the protocol, and written informed consent was obtained from all participants of the study. Patients This prospective study enrolled 30 patients undergoing elective first-time off-pump CABG where the LITA graft was anastomosed to the left anterior descending coronary artery in all patients and harvested according to the skeletonized technique. Excluded from the study were patients undergoing emergency surgery or reoperation, patients with a left ventricular ejection fraction of less 2007 by The Society of Thoracic Surgeons 0003-4975/07/$32.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2007.04.062

CARDIOVASCULAR 818 GUIZILINI ET AL Ann Thorac Surg PLEUROTOMY AND PULMONARY FUNCTION AFTER OPCAB 2007;84:817 22 than 0.50, and those with acute or chronic pulmonary disease. The patients were prospectively allocated into two groups of 15 patients each: those with the pleural cavity being open (OP group) and those with an intact left pleural cavity (IP group). proximal soft silicone snare. The distal anastomosis was done with a 7-0 running polypropylene suture. The vein top ends were then attached to the ascending aorta using side-bite clamping. An Octopus 3 (Medtronic, Inc, Minneapolis, MN) suction stabilizer was used in all cases. Pulmonary Function Assessment The lung function indicators of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV 1 ) were evaluated at the bedside on the day before the operation and repeated on postoperative days (PODs) 1, 3, and 5 by the same respiratory physiotherapist, using a portable spirometer (Spirobank G, MIR, Rome, Italy), according to the standards of The American Thoracic Society [15]. Each test was done in triplicate, and the best result was selected for analyses. Arterial blood samples for gas analyses (partial pressure of arterial oxygen [Pao 2 ] and partial pressure of carbon dioxide [Paco 2 ]) and evaluation of gas exchange (ratio between the partial arterial oxygen pressure and the inspired oxygen fraction [Pao 2 /Fio 2 ]) were determined in the preoperative period and on POD 1 with the patient breathing room air, always before performing spirometry. After the preoperative evaluation, the patients received guidance about the operation, the immediate postoperative period, and the importance of respiratory exercises and the necessity to resume walking as soon as possible. Anesthesia and Operative Technique All patients received the same anesthetic regimen. Anesthesia was induced in a routine fashion with etomidate and midazolam and maintained with sufentanil and isoflurane (0.5% to 1%). The patients were ventilated to maintain normocapnia without positive end-expiratory pressure (PEEP) and Fio 2 between 50% and 60%. During the operation, the temperature and preload were continuously monitored. The operation was done through a midline sternotomy and using the LITA, with and without left pleurotomy, complemented with additional saphenous vein grafts. The LITA was harvested in a skeletonized fashion, separating it from the chest wall and isolating it from the fascia, the veins, and adipose tissue. Skeletonization was done from the origin down to the bifurcation. Side branches were ligated with small-sized hemostatic clips only on the LITA side. Routinely, in our service, meticulous care is taken to preserve the integrity of the pleura during LITA harvesting. In all cases where the pleural cavity was incidentally opened (disregarding the hole size), a pleural drain was inserted and exteriorized at the intersection of the sixth left intercostal space in the midaxillary line. In all patients, a mediastinal tubular drain was also left at the subxiphoid region. A heated water mattress was used to keep all patients normothermic throughout the operation. Off-pump CABG has followed the pattern at our service [16]. Briefly, with systemic heparinization to achieve an activated clotting time exceeding 250 seconds, occlusion of the coronary artery was accomplished by using a Postoperative Management After the operation, the patients were transferred to the postoperative cardiac surgical unit. The lungs were initially ventilated in synchronized intermittent mandatory ventilation at 12 to 14 breaths/min, an inspiratory/ expiratory ratio of 1:2, PEEP of 5 cm H 2 O, tidal volume of 8 ml/kg of body weight, pressure support to maintain this volume and Fio 2 for keeping arterial oxygen saturation above 90%. Extubation was performed when the patient was hemodynamically stable and alert to maintain self-ventilation and good blood gas values. All patients received the same analgesic protocol administered during the first 5 postoperative days and were given daily physiotherapy until discharge. The chest drains were routinely removed on the second postoperative day in all patients. No signs of perioperative myocardial infarction were detected in either group, as assessed by electrocardiographic changes or enzyme elevation. Statistical Analysis Data are expressed as means standard deviation. The FVC, FEV 1, and Pao 2 were analyzed, and values are expressed as a percentage of the preoperative value. Within-group variables comparing preoperative versus postoperative values were evaluated by paired Student t tests and analysis of variance for repeated measures with Table 1. Preoperative and Intraoperative Clinical and Demographic Characteristics Variables Group OP Group IP p (n 15) a (n 15) a Value Age (years) 57.5 10.3 62.1 6.6 0.15 Gender (n, %) Male/female 14/01 13/02 0.54 BMI (kg/m 2 ) 26.1 3.0 27.2 3.5 0.37 Pulmonary function FVC (L) 3.7 0.6 3.6 0.6 0.98 % Predicted 102.2 16.6 102.5 11.5 0.95 FEV 1 (L) 2.8 0.4 2.9 0.6 0.41 % Predicted 98.9 14.4 105.5 13 0.20 Pao 2 (mm Hg) 74.4 6.8 77.6 4.6 0.13 Paco 2 (mm Hg) 38.2 3.6 39.2 3.5 0.48 Pao 2 /Fio 2 360.5 44.5 370.0 22.8 0.46 Surgery time (min) 309.3 19.3 295.6 22.6 0.08 Grafts per patient 2.2 0.8 2.4 0.6 0.52 a Data are shown as mean standard deviation. BMI body mass index; FEV 1 Forced expiratory volume in 1 second; FVC forced vital capacity; IP intact pleura; OP opened pleura; Paco 2 partial arterial carbon dioxide pressure; Pao 2 partial arterial oxygen pressure; Pao 2 /Fio 2 ratio between the partial arterial oxygen pressure and the inspired oxygen fraction.

Ann Thorac Surg GUIZILINI ET AL 2007;84:817 22 PLEUROTOMY AND PULMONARY FUNCTION AFTER OPCAB 819 CARDIOVASCULAR Fig 1. Pulmonary function test values are presented for postoperative days (PODs) 1, 3, and 5 as the percentage of the preoperative values for the groups with opened pleura (clear bar) and intact pleura (solid bar). The p values refer to the difference of the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV 1 ) between the groups. Data are shown as mean standard deviation. p 0.05. the Newman-Keuls posttest. Differences between groups were analyzed by unpaired Student t test or the Mann- Whitney test, when necessary. The categoric data were analyzed by the Pearson 2 test. Statistical analysis was performed with GraphPad Prism 3.0 software (GraphPad Software Inc, San Diego, CA). A value of p 0.05 was considered statistically significant. Fig 2. Partial arterial oxygen pressure (Pao 2 ) values on postoperative day (POD) 1 are presented as a percentage of the preoperative value for the groups with opened pleura (clear bar) and intact pleura (solid bar). The p values refer to the difference between the groups. Data are shown as mean standard deviation. p 0.05. Fig 3. The ratio between the partial arterial oxygen pressure and the inspired oxygen fraction (Pao 2 /Fio 2 ) ratio values are presented for postoperative day (POD) 1 for the groups with opened pleura (clear bar) and intact pleura (solid bar). The p values refer to the difference between the groups. Data are shown as mean standard deviation. p 0.05. Results Preoperative and intraoperative patient characteristics are summarized in Table 1. No statistical difference was found in terms of age, gender, body mass index (BMI), preoperative pulmonary function, operative time, and number of grafts per patient. A significant decrease in pulmonary function tests was observed in both groups until POD 5 (p 0.05). The FVC mean, expressed as a percentage of the preoperative value, was significantly lower in the OP group than in the IP group on PODs 1 (33.3% 8.3% versus 49.1% 8.4%, p 0.001), 3 (45.4% 7.0% versus 62.1% 8.6%, p 0.001), and 5 (56.1% 8.7% versus 77.5% 11.6%, p 0.001). Similar results were found for FEV 1 (POD 1: 35.7% 8.6% versus 50.0% 9.8%, p 0.001; POD 3: 48.4% 7.0% versus 61.5% 9.0%, p 0.001, and POD 5: 58.8% 8.5% versus 75.9% 10.2%, p 0.001; Fig 1). There was a significant drop in Pao 2 on POD 1 for both groups (p 0.001), but the IP group maintained higher values than the OP group (76.5 9.1% versus 85.3 5.8%, p 0.001; Fig 2). The Paco 2 values increased in both groups (p 0.05), but no significant difference was found when they were compared (42.9 7.8 versus 42.9 4.6, p 1.000). The Pao 2 /Fio 2 ratio also decreased in both groups (p 0.001), but the IP group showed significantly higher values than the OP group (275.4 32.0 versus 314.6 26.3, p 0.001; Fig 3). Orotracheal intubation time (10.4 1.2 versus 8.8 1.2 hours; p 0.012) and hospital stay (7.0 2.0 versus 5.3 1.1 days, p 0.002) were lower in the IP group.

CARDIOVASCULAR 820 GUIZILINI ET AL Ann Thorac Surg PLEUROTOMY AND PULMONARY FUNCTION AFTER OPCAB 2007;84:817 22 Comment The present study demonstrates that an evident impairment of pulmonary function occurs in the early postoperative period of off-pump CABG independent of the pleurotomy, an effect already reported by other authors studying the same subject in on-pump CABG [3 6, 17, 18]. The cause of the significant reduction on pulmonary function after CABG surgery is multifactorial [10]: The general anesthesia results in reduction of the diaphragmatic tonus with an upward shift, relaxation of the chest wall, and a shift in blood volume to the abdomen from the thorax [19]. The median sternotomy can impair chest stability and decrease chest wall compliance [3]. The use of the LITA for CABG surgery may be an adjunctive factor for postoperative lung dysfunction [3 6]. Possible causes involve the technique for LITA preparation and the high incidence of pleurotomy, which typically necessitates the insertion of a pleural drain [4, 9]. Furthermore, LITA removal may reduce blood supply to intercostal muscles and phrenic nerve, resulting in postoperative respiratory dysfunction [3, 5]. Different methods for LITA preparation have been used. Usually, the grafts are harvested as a pedicle. The skeletonized technique, however, involves meticulous dissection of the artery, with minimal injury to the surrounding tissues and better preservation of the pleural integrity [20, 21] and the blood supply to the sternum and [20, 22, 23] intercostal nerves compared with the conventional technique [24]. Improved postoperative pulmonary function has also been reported with the use of skeletonized technique [25, 26]. In addition, CPB apparently further impairs pulmonary function compared with off-pump CABG [27, 28], and this has been attributed to the systemic inflammatory response syndrome [29, 30, 31]. It is well accepted that on-pump CABG induces a higher release of inflammatory mediators than does off-pump CABG [32, 33]. The inflammatory cells are activated in various organs, particularly in the lungs, causing tissue injury, increasing the permeability of the alveolar-capillary membrane [30], and reducing the production of alveolar surfactant and diffusion by the blood-gas membrane. This causes harm to the pulmonary complacency and consequently to the pulmonary volume and the gas exchange [28 31]. This prospective study reports the influence of pleurotomy on the pulmonary function after off-pump CABG using the LITA, hence avoiding the systemic inflammatory response syndrome and pulmonary injury associated with CPB. Despite the evidence showing a decrease of pulmonary function in the CABG postoperative period [3 6, 17, 18], there is no agreement that opening the pleural cavity influences this impairment. Clinical studies demonstrated that the opening of the pleural space further decreased postoperative pulmonary function tests compared with closed pleural cavity in on-pump CABG using the LITA [8, 11, 34]. Our study showed significant reduction of the FVC and FEV 1 in both groups until POD 5; however, the patients undergoing pleurotomy presented a significant decrease in these indicators compared with IP patients. Postsurgical data analysis showed a gradual improvement of FVC and FEV 1 values until POD 5; however, the values for these variables did not returned to normal and remained far below the preoperative values. Others studies reported that the pleurotomy does not affect postoperative FEV 1 and FVC [25, 35]. Possible explanations for the interference of pleurotomy on pulmonary function are a higher incidence of pleural effusion and atelectasis [8, 11], increased intrapulmonary shunting [4], and increased postoperative pain due to more extensive trauma to the chest wall [8]; however, the greater decline in FVC and FEV 1 seems to result from the association of pleural changes and increased thoracic trauma [9]. The conventional pleural opening and placement of the chest tube certainly involves trauma. The drain causes damage to the parietal pleura and intercostal muscles, both very sensitive structures. The friction of the drain between ribs during breathing increases pain due to the ongoing irritation of the intercostal nerves and costal periosteum [8, 36]. As a consequence, the patient usually reacts with superficial breathing, and deep breathing may be restricted until the drain is removed [36, 37]. The capacity to cough decreases, and this could induce mucus retention, atelectasis, and aggravate hypoxemia. Major incidences of respiratory complications during the postoperative course may occur and delay recovery of pulmonary function [13, 17, 38]. Some authors have reported a negative influence of pleurotomy in pulmonary oxygenation during on-pump CABG with the LITA [4, 34, 38]. In the present study, the decrease in the Pao 2 occurred in both groups on POD 1; however, the decline in the OP group (23.4%) was significantly greater than in the IP group (14.7%). A more pronounced impairment of the Pao 2 /Fio 2 ratio was also seen in the OP group. This demonstrates that pleural opening during LITA dissection and placement of pleural drain further aggravate the impairment of oxygenation and postoperative gas exchange, likely secondary to the greater reduction in the lung volumes observed in the OP group. Alveolar hypoventilation might, at least in part, have contributed to postoperative hypoxemia observed in two groups because the values of the Paco 2 on POD 1 were significantly higher than the preoperative values. However, certainly it was not responsible in aggravating hypoxemia on the OP group patients because the two groups had similar Paco 2 values. The larger decrease of the FVC, FEV 1, oxygenation, and gas exchange observed in this study likely reflects the patients that were subjected to a greater degree of chest wall trauma. To minimize the chest wall injury after CABG, it has been reported that a change in the insertion site of pleural drain may influence the degree of pulmonary function compromise. Two studies showed that during CABG with pleurotomy, the placement of a subxiphoid drain results in reduced pain and lower pulmo-

Ann Thorac Surg GUIZILINI ET AL 2007;84:817 22 PLEUROTOMY AND PULMONARY FUNCTION AFTER OPCAB nary function impairment in the early postoperative compared with an intercostal drain [39, 40]. These data may be of special interest when CABG requires opening and drainage of both pleural cavities. Some studies reported advantages in preserving pleural integrity during LITA harvesting, including a shorter orotracheal intubation time [7], a decrease in respiratory complications [12 14, 17] and, consequently, a shorter hospital stay [34]. In our study, the opening of the pleural space was associated with a significantly longer orotracheal intubation time and hospital length of stay compared with the IP group, confirming previous reports [7, 34]. Our findings therefore suggest that the enhanced preservation of the pulmonary function and lower intubation time seem to be, at least in part, responsible for the shorter hospital stay found in patients with intact pleura. 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