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Right arrow Minimally invasive surgery

Ann Thorac Surg 2002;74:1537-1543
© 2002 The Society of Thoracic Surgeons


Original article: cardiovascular

How safe is the port access technique in minimally invasive coronary artery bypass grafting?

Selami Dogan, MDa*, Kai Graubitz, MDa, Tayfun Aybek, MDa, Mohammad Fawad Khan, MDa, Paul Kessler, MD, PhDb, Anton Moritz, MD, PhDa, Gerhard Wimmer-Greinecker, MD, PhDa

a Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt, Germany
b Department of Anesthesiology, Intensive Care, and Pain Therapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany

Accepted for publication June 20, 2002.

* Address reprint requests to Dr Dogan, Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany.
e-mail: s.dogan{at}em.uni-frankfurt.de


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
BACKGROUND: This study compares conventional coronary artery bypass grafting (CABG) with port access CABG via a left anterior small thoracotomy in patients requiring surgical multivessel revascularization. Clinical, neuropsychological, and angiographic outcomes were studied, as well as parameters of myocardial and cerebral protection. Pathogenicity of cardiopulmonary bypass (CPB) was further evaluated by measuring parameters of peripheral limb ischemia and inflammatory whole-body response.

METHODS: In a prospective randomized study, 40 patients who required multivessel CABG were assigned to either conventional CABG via complete median sternotomy (group A) or port access CABG via minithoracotomy (group B). Control angiograms were performed in group B only. In addition, patients underwent neuropsychological testing after the operation. CK, CK-MB, and Troponin T levels were documented. S-100B protein and neuron-specific enolase (NSE) served to quantify cerebral injury. The terminal complement complex (C5b-9) and myeloperoxidase concentrations were determined to analyze inflammatory whole-body response after CPB.

RESULTS: There was no mortality. One patient suffered a retrograde aortic dissection immediately after onset of CPB, but had an uneventful postoperative course after surgical repair. Troponin T and CK-MB showed no difference between groups. CK and myoglobin were significantly higher in the minimally invasive cohort. Changes in complement activation (C5b-9) and myeloperoxidase during CPB markers of the whole-body inflammatory response were similar in both groups. S-100B concentrations in the port access group were significantly higher, whereas NSE levels were similar in both groups. Both groups did not display any significant difference in neuropsychological testing.

CONCLUSIONS: Minimally invasive multivessel CABG via minithoracotomy using port access technology is feasible and safe. Though prolonged operating and CPB times with significantly higher S-100B concentrations were observed in group B, equivalent myocardial and cerebral protection and similar whole-body inflammatory response were documented.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
The port access technique using femoral cannulation for cardiopulmonary bypass (CPB) and an intraaortic balloon clamp for occlusion of the aorta was introduced into clinical practice in 1997 with the primary intent to facilitate totally endoscopic surgery [13]. Intravascular or intracardiac placement of all cannulas and catheters provides free access to the operative field. This idea failed at the beginning due to lack of advanced endoscopic instruments specially designed for cardiac operations. A variety of small access cardiac procedures (mainly coronary revascularizations and mitral valve surgery) emerged out of the initial experience [4, 5]. However, most of these small access operations were abandoned due to complexity of the port access system. Clinical benefits of port access surgery are still in controversial discussion [610].

The use of the port access technique became indispensable for totally endoscopic cardiac operations because computer-enhanced telemanipulation systems finally facilitated totally endoscopic cardiac surgery [1114].

This study compares conventional coronary artery bypass grafting (CABG) with port access CABG via a left anterior small thoracotomy in patients requiring surgical multivessel revascularization. Clinical, neuropsychological, and angiographic outcomes were studied, as well as parameters of myocardial and cerebral protection and parameters of inflammatory response to evaluate potential differences in pathogenicity of CPB.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
In a prospective randomized study, 40 patients who required surgical multivessel coronary artery revascularization were assigned to either conventional CABG via complete median sternotomy (group A) or port access CABG via a left anterior small thoracotomy (LAST) approach (group B). All patients had the intention to be completely revascularized. Each patient gave informed written consent. The study underwent institutional review and was approved by the local Ethical Committee. Exclusion criteria are listed in Table 1. The last three exclusion criteria are requirements for port access surgery [15]. Mean age in group A (17 men, 3 women) was 61.6 ± 7.7 years, and in group B (18 men, 2 women) was 65.2 ± 7.1 years. Comorbidity and preoperative data are listed in Table 2. Before randomization for this study, port access CABG was performed in selected low-risk patients to overcome the initial learning curve in handling the port access system. After completion of 14 such cases with good clinical outcome, this study was started.


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Table 1. Exclusion Criteria

 

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Table 2. Comorbidity and Preoperative Data

 
Conventional CABG
After median sternotomy and harvesting of the grafts, the aorta and the right atrium were cannulated for CPB. After cross-clamping the aorta and application of antegrade cold-blood cardioplegia, the distal anastomoses were sutured on the arrested heart. Proximal anastomoses were performed in partial aortic clamping. The procedure was finished in standard fashion.

Port access CABG
The Heartport Port Access system (Redwood City, CA) was used for this procedure [1]. All patients had Doppler ultrasound of femoral vessels before randomization to rule out relevant calcification of the femoral artery cannulation site. Duplex sonography was conducted to detect potential stenoses of peripheral arteries. Transthoracic echocardiography was performed to evaluate the ascending aorta. Only after exclusion of relevant peripheral and central vascular disease, randomization for the study was carried out. Intraoperatively, the femoral artery was reassessed by palpation as well as the thoracic aorta by transesophageal echocardiography (TEE). Before skin incision, a pulmonary vent as well as a coronary sinus catheter were introduced through the jugular vein and advanced into their proper position under echocardiographic guidance. In single lung ventilation, the left internal thoracic artery (ITA) was dissected after a minithoracotomy approach in the fourth intercostal space. Meanwhile, the vein grafts were harvested. After dissection of the left groin, the femoral vessels were cannulated. A long venous drainage cannula was advanced into the right atrium. For the endoarterial return, the left femoral artery was cannulated in open technique and a guide wire was advanced into the descending aorta. The distal femoral artery was occluded during CPB. After onset of CPB, the endoaortic balloon clamp was guided into the ascending aorta. All intravascular maneuvers were performed under echocardiographic control. Proximal anastomoses were performed first through the minithoracotomy incision on the beating but decompressed heart after partial clamping of the aorta [15, 16]. Then, the intraaortic balloon was insufflated and antegrade as well as retrograde cold blood cardioplegia was administered. Distal anastomoses were performed on the arrested heart by exposing the target anastomotic site with sponges. After weaning from CPB, the femoral cannulas were removed and the thoracotomy was closed. Before transfer to the intensive care unit (ICU), the ventilation tube was changed.

Heparin (300 U/kg) was administered for systemic anticoagulation in both groups. CPB was instituted with a Jostra Quadrox capillary membrane oxygenator and tubing set (Jostra Medizintechnik AG, Hirrlingen, Germany). All patients were cooled to a rectal temperature of 32°C.

Intraoperative and clinical assessment
Bypass time, aortic cross-clamp time, and time of the operation were documented. The latter one is defined as total time in the operating room including induction of anesthesia. Further times of mechanical ventilation, postoperative blood drainage (24 hours), ICU stay, and hospital stay were analyzed. Patients in group B received invasive coronary angiograms before discharge to assess anastomotic quality and graft function. In group A, anastomotic quality and graft function were not specifically examined, because open sternotomy and arrested heart cases are considered to be the gold standard for coronary anastomoses.

Biochemical parameters
In addition to CK and CK-MB, troponin T levels were documented to quantify myocardial damage (Enzymun-Test Troponin T; Boehringer Mannheim Immundiagnostica, Mannheim, Germany). Myoglobin was analyzed to determine the quantity of limb ischemia and reperfusion damage after femoral cannulation with an immunoassay (Beckmann, Essen, Germany).

S-100B protein and neuron-specific enolase (NSE) served to quantify cerebral injury. Protein S-100B was determined in serum specimens using a sensitive luminometric assay (Byk-Sangtec, Lund, Sweden), which selectively measures the beta subunits (present in glial and Swann cells) [17]. NSE is a sensitive indicator of neuronal cell destruction clinically evident as stroke [18] and was determined with an enzyme-linked immunosorbent assay (ELISA) (Boehringer Mannheim Immundiagnostica).

The terminal complement complex (C5b-9) and myeloperoxidase (MPO) concentrations were determined to quantify the inflammatory whole-body response of CPB [19]. C5b-9 was analyzed with an ELISA (Gambro, Hechingen, Germany) and MPO with an ELISA (Calbiochem-Navibiochem, San Diego, CA).

Neuropsychological testing
Patients underwent neuropsychological testing 1 day before, 5 days after, and 2 months after the operation. Testing required about 1 hour and was performed on the ward or the outpatient clinic, respectively.

The test battery used was in accordance with the "Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac Surgery" [20]. This includes the Block Design Test (problem-solving strategies and recognition and analysis of forms), the Trail Making Test (cognitive achievement at speed), and the Digit Span Test (short-term memory and memory of figures). In addition, the Benton Test (visual constructive abilities), the d2 Test (concentration and care at speed), and the Beck’s Depression Inventory (quantifying state of mood, motivation, self esteem, and vitality) were employed. Testing was carried out by the same two physicians.

Statistical analysis
Statistical analysis was carried out using the StatView software package (Abacus Concepts, Berkeley, CA) for repeated assessment of neuropsychological test scores and biochemical values. Data are presented as means ± standard deviation of means. Comparison between groups was performed using the Mann-Whitney U test. Differences were considered significant when the p value was below 0.05. Spearman-Rank-Test was used to correlate neuropsychological testing results with laboratory results, and CPB time with S-100B concentrations.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
The data of only 19 patients were evaluated in group B. One patient suffered a retrograde aortic dissection immediately after onset of CPB. After complete sternotomy and replacement of the ascending aorta in deep hypothermic arrest, the patient was extubated on the day of surgery and recovered well. This patient had no further complication and was discharged from the hospital on postoperative day 9. Examination of the histologic findings of a specimen of the resected aorta showed severe medionecrosis. This patient was excluded from the port access group. In another patient, both groins were dissected due to heavy calcification at the initial cannulation site. Results of postoperative angiography in group B revealed good anastomotic quality with normal graft function in all cases (patency = 100%). There was no mortality. Intra- and postoperative data are shown in Table 3.


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Table 3. Perioperative Data

 
Markers of myocardial ischemia such as troponin T (peak 0.53 µg/L in group B vs 0.64 µg/L in group A) and CK-MB (peak 17 U/L in group B vs 15 U/L in group A) showed no difference between groups. CK levels rose to about 600 U/L in the port access group, in contrast to about 200 U/L in the conventional group. Myoglobin levels were significantly higher in the port access group (1500 µg/L vs 300 µg/L; Figs 1, 2). Changes in complement activation (C5b-9) (peak 1,352.83 µg/L in group B vs 946.21 µg/L in group A) and MPO (peak 33.01 µg/L in group B vs 34.99 µg/L in group A) during CPB expressing inflammatory whole-body response were similar in both groups.



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Fig 1. Creatine kinase concentration graph. Sampling time: 1 = before induction of anesthesia; 2 = after induction of anesthesia; 3 = after onset of cardiopulmonary bypass; 4 = immediately before release of the aortic cross-clamp. Squares = minimally invasive group; X = conventional group. p < 0.0001.

 


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Fig 2. Myoglobin graph. Sampling times: 1 = before induction of anesthesia; 2 = after induction of anesthesia; 3 = after onset of cardiopulmonary bypass; 4 = immediately before release of the aortic cross-clamp; 5 = 5 minutes after release of the aortic cross-clamp; 6 = 1 hour after surgery; 7 = 24 hours after surgery; 8 = 5 days after surgery. Squares = minimally invasive group; X = conventional group. p < 0.0001.

 
Biochemical parameters of cerebral damage such as S-100B and NSE yielded different results. S-100B concentrations in the port access group were significantly higher (p < 0.001; Fig 3), whereas NSE levels were similar in both groups (Fig 4). Correlation analysis between S-100B and CPB time yielded a coefficient of r = 0.2117. In neuropsychological testing, a postoperative decrease was only observed in scores of d2 and BDI tests. This was shown in both groups. All other neuropsychological tests showed no difference between preoperative and any time postoperative. Comparison between both groups did not display any significant difference. The detailed results of neuropsychological testing are displayed in Table 4 .



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Fig 3. Protein S-100B graph. Sampling times: 1 = before induction of anesthesia; 2 = after induction of anesthesia; 3 = after onset of cardiopulmonary bypass; 4 = immediately before release of the aortic cross-clamp; 5 = 5 minutes after release of the aortic cross-clamp; 6 = 1 hour after surgery; 7 = 24 hours after surgery; 8 = 5 days after surgery. Squares = minimally invasive group; X = conventional group. p < 0.0001.

 


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Fig 4. Neuron specific enolase graph. Sampling times: 1 = before induction of anesthesia; 2 = after induction of anesthesia; 3 = after onset of cardiopulmonary bypass; 4 = immediately before release of the aortic cross-clamp; 5 = 5 minutes after release of the aortic cross-clamp; 6 = 1 hour after surgery; 7 = 24 hours after surgery. Squares = minimally invasive group; X = conventional group. p = NS.

 

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Table 4. Neuropsychological Data

 

    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Minimally invasive techniques were introduced into cardiac surgery with the goal towards smaller incisions to reduce surgical trauma, improve cosmesis, reduce the risk of wound infection to a minimum, and reduce postoperative pain. With the development of port access technology for peripheral CPB induction, venous and aortic cannulas are removed from the operative field so that the skin incision may be further reduced [1, 16, 21]. The ultimate goal to avoid any thoracotomy was finally achieved by using robotic telemanipulators enabling totally endoscopic CABG [22, 23]. Totally endoscopic coronary artery bypass grafting (TECAB) on the arrested heart is completely dependent on port access technology.

This leads to an increasing interest in reevaluation of this technique. Testing of biochemical parameters such as parameters for myocardial tissue damage, skeletal muscle damage, brain damage, and inflammatory response [19] were conducted by our group to justify further application of the port access technique.

CPB using the port access cannulation system is a complex method in which venous and arterial cannulation and handling of the endoaortic balloon may be difficult in regards to placement and migration [24, 25]. The risk of retrograde aortic dissection constitutes a serious threat for the patient [26]. In our overall institutional experience of more than 150 port access cases, the aortic dissection cited in group B was the only dissection that occurred. In these cases of aortic dissection, a high mortality is reported [21]. Therefore, careful preoperative evaluation of femoral vessels (size, quality of vessel wall at cannulation site) by doppler and duplex ultrasound along with pre- and intraoperative assessment by transthoracic and transesophageal echocardiography, respectively, is necessary to identify candidates who are at risk for dissection and thus not suitable for port access surgery. Of course, a patient displaying severe medionecrosis will always stay undetected. In addition, the perfusionist has to monitor the arterial line pressure carefully. Early detection is crucial; therefore, constant TEE control during and after port access system placement is mandatory. Immediate weaning from CPB, instant implementation of antegrade perfusion, and immediate surgical repair is essential to master such a complication.

Even though suturing for proximal and distal anastomoses was performed under technically demanding circumstances in the minithoracotomy group, postoperative angiography did not show any compromise in surgical quality. Except for longer operating times in group B, which are due to the small-access approach, all patients had a good clinical outcome, including the 1 with the aortic dissection.

Postoperative treatment on the ICU was similar for both groups of patients. Applying the same extubation criteria to both cohorts, patients in group B had significantly longer ventilation times. This may be due to single-lung ventilation and a prolonged CPB time in this group. It also has to be considered that 1 patient of group B suffered a severe pneumonia and had to be mechanically ventilated for 127 hours.

A mild increase in troponin T (peak 0.53 µg/L in group B vs 0.64 µg/L in group A) and CK-MB (peak 17 U/L in group B vs 15 U/L in group A) concentrations after cardiac arrest were documented in the conventional as well as in the minimally invasive cohort. In our study, cross-clamp time has been comparable in both groups. No significant differences in troponin T and CK-MB levels were found between groups. This shows that myocardial protection is sufficient in using port access technology.

Significantly higher CK and myoglobin concentrations after CPB were documented in the minimal invasive cohort and were interpreted as consequences of partial lower limb ischemia due to femoral cannulation. Whether additional musculoskeletal trauma caused by the thoracotomy adds to elevated CK and myoglobin levels remains open. Because the length of incision was only 7 cm on average and the muscle was mainly divided parallel to the fibers, we believe that the amount of muscle trauma from the thoracotomy is of minor relevance. Clinically, no serious reperfusion syndromes were detected in hypoperfused limbs.

Levels of C5b-9 and MPO were elevated in both groups without a significant difference. This indicates a similar reaction of these mediators between groups, although CPB time was markedly prolonged in the minimally invasive cohort. Higher numbers of intravascular cannulas and catheters necessary using port access technology did not cause a difference in inflammatory markers.

Longer CPB times, the potential risks of balloon placement, and retrograde blood flow are making this technique especially prone to cerebrovascular incidents [25, 27]. S-100B was found to be four times higher in the port access group. This protein is a marker of blood-brain barrier damage [18, 27]. Thus, cerebral swelling can be detected after use of CPB [28], and is part of the inflammatory whole-body response due to blood-surface and blood-air contact. The longer CPB times certainly contribute to this findings [29], but cannot explain this pronounced increase of S-100B levels after release of the aortic cross-clamp. We could not find any correlation between CPB time and peak S-100B levels in either group.

We believe that higher S-100B levels in the port access group are mainly caused by retrograde aortic blood flow. As a further potential cause, endoaortic balloon placement seems to be an unlikely source for microemboli, because none of the patients in the port access group displayed aortic plaques on echocardiography. Recently, publications showed a dependency of S-100B levels on different methods of intraoperative blood processing [29, 30]. Because this was handled completely equally between groups and even the postoperative amount of chest tube drainage did not differ, no influence by this matter should have occurred.

As a very sensitive, CPB-independent marker for neuronal cell lesions, NSE concentrations were measured [31]. Although there is a theoretical risk for focal neurologic injury due to retrograde perfusion in port access technique, NSE levels did not differ between groups. The isolated increase of S-100B underlines our assumption that increased blood-brain barrier damage in group B is due to microemboli generated by retrograde blood flow in the abdominal and descending thoracic aorta.

No clinically detectable neurologic deficit occurred. Though two neuropsychological tests showed significant differences before and after CPB within groups A and B, neither of the neuropsychological tests yielded significant results between the port access and the conventional group. These biochemical and neuropsychological results demonstrate that damage of the blood-brain barrier is reversible and elevation of biochemical markers of neurologic injury only expresses a subclinical deficit.

The present study has the shortcoming of a small sample size. Because multivessel revascularization via the LAST approach using port access technology is a demanding procedure, also necessitating a great amount of personal resources, large numbers cannot be achieved easily. We do believe, though, that tendencies shown by randomized trials with small patient numbers are still of scientific value, taking these issues into account.

Safety and feasibility of port access technology supporting minimally invasive bypass grafting via a minithoracotomy are shown in this preliminary study. Though prolonged operating and CPB times as well as significantly higher S-100B concentrations are evident in the port access group, no differences in myocardial and cerebral protection and similar inflammatory whole-body response were found. This advocates for the use of port access technology for a totally endoscopic cardiac surgery program.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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