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Ann Thorac Surg 2000;70:1656-1661
© 2000 The Society of Thoracic Surgeons

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Original articles: general thoracic

Pulmonary function after thoracoscopic thymectomy versus median sternotomy for myasthenia gravis

^a Department of Surgery, Humboldt University Medical School (Charité), Campus Mitte, Berlin, Germany

Address reprint requests to Dr Rückert, Klinik für Allgemein-, Thorax-, Gefäß- und Visceralchirurgie, Universitätsklinikum Charité der Humboldt-Universität zu Berlin, Campus Mitte, Schumannstr 20/21, D-10117 Berlin, Germany
e-mail: jens-c.rueckert{at}charite.de

Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Impaired pulmonary function due to myasthenia gravis (MG) is further compromised by thymectomy, which is necessary in most cases. Thoracoscopic thymectomy (tThx) can achieve the same resection and functional improvement of MG as median sternotomy (sThx). The possible advantage of tThx in maintaining better perioperative lung function was quantified.

Methods. In a prospective trial, 20 patients with MG were randomly allocated to undergo tThx (n = 10) by three-trocar left-sided approach or sThx (n = 10) performed as an extended procedure. Complete pulmonary function was measured at 12-hour intervals, beginning 6 hours postoperatively. Effective postoperative pain control in both groups was achieved by patient-controlled analgesia with morphine sulfate assessed by a visual analogue scale. Statistical analysis for comparison of tThx and sThx was performed using the Mann-Whitney U test.

Results. Postoperative vital capacity, forced vital capacity, forced expiratory volume per second, and peak expiratory flow, measured as a percentage of the individual preoperative capacity, were significantly better with tThx compared with sThx. Immediate postoperative lung function was reduced to 35% and 65% after tThx and sThx, respectively. By the third postoperative day, recovery of pulmonary function was complete after tThx but only 55% after sThx.

Conclusions. Less pronounced impairment and faster recovery of pulmonary function after tThx characterize this new approach for thymectomy as minimally invasive. These results could make tThx the preferred surgical treatment of MG, which was improved to the same extent as after sThx.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
While thymectomy (Thx) has been established as the procedure of first choice for most cases of myasthenia gravis (MG), the optimal surgical approach for Thx remains a matter of discussion [1–9]. The necessity of complete radical Thx to achieve maximal improvement of MG has been repeatedly emphasized [2, 4, 6]. However, no data are available from a prospective randomized comparison of several surgical approaches for Thx, which aim either at minimal impairment of the myasthenic patient [1, 5, 9–11] or at adequate radicality through a wide surgical access [2, 4, 6]. The new approach of thoracoscopic thymectomy (tThx) can achieve the same radicality and functional improvement of MG as median sternotomy (sThx) [5, 9, 11].

Apart from the fact that adequate functional improvement of MG by tThx has not yet been demonstrated prospectively, there is also a lack of prospective studies addressing the postoperative recovery of pulmonary function as well as pain relief after thoracoscopic techniques in general as compared with conventional approaches of thoracic surgery [12, 13]. There is hardly any other disease requiring a minimally invasive surgical approach more than MG because pulmonary function that is already impaired by MG is compromised even further by Thx. We therefore performed a study to quantify the possible advantage of tThx in maintaining better perioperative lung function.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Hypothesis, end points, and sample size calculation
The hypothesis was that pulmonary function is less markedly diminished and recovers faster after tThx than sThx. This hypothesis was tested by analyzing the postoperative course of vital capacity (VC), functional vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and peak expiratory flow (PEF). The sample size required to test the hypothesis was calculated according to the methods described by Altman [14]. The FVC and FEV₁ served as major criteria for calculating the sample size. The assumed decrease of FVC and FEV₁ after conventional sThx was 50% ± 35%. A difference of 45% in the postoperative FVC and FEV₁ values between tThx and sThx groups can be detected by a two-tailed test with an alpha level of 0.05, a beta level of 0.20 (power 80%), and 10 patients in each group.

Study design
In a prospective trial, 20 patients with MG were randomly allocated to undergo tThx (n = 10) by three-trocar left-sided approach or sThx (n = 10) performed as an extended procedure. Patients with the established diagnosis of MG, aged between 15 and 69 years, who were scheduled for thymectomy with stages I, IIa, or IIb according to the classification of Ossermann and Genkins [15], were included in the study. Patients with a preoperatively suspected thymoma were excluded from the study. The study was approved by the local ethics committee, and informed consent was obtained from each patient. Medical treatment of MG was optimized before surgery. Anesthesia prepared for single-lung ventilation was performed by the same anesthesiological team in a standardized manner and was comparable in both groups.

Operative technique
Refinements of the operative technique resulted in a standardized thoracoscopic approach for Thx, which has been described before [11]. With the patient in a 30-degree elevated lateral decubitus position, the trocar sites were defined between the third and sixth intercostal spaces and medioclavicular and anterior axillary lines following the submammary line.

Each operation was documented by video. Preparation started at the lower ends of the main thymic lobes with the incision of the mediastinal pleura along the phrenic nerve, which had to be carefully preserved. The incision of the mediastinal pleura was continued at the upper edge to open the connection to the neck tissue. During further mobilization of the anterior mediastinal tissue portion by retrosternal incision down to the diaphragm, the arterial thymic supply had to be divided. Retrosternal branches from the internal mammarian artery required clip ligature before dissection. The most effective technique to avoid bleeding during preparation was dissection by ultrasound energy using the harmonic scalpel (UltraCision; Ethicon Endo Surgery Inc, Cincinnati, OH). The whole tissue portion was then easy to mobilize from the pericardial surface by blunt dissection in the proper layer. After full exposure of the innominate vein, complete preparation and dissection of the thymic veins was carried out. The specimen was removed in a retrieval bag.

Complete median sternotomy was performed as an extended conventional approach for Thx, as described by other authors [2, 4, 6]. Briefly, with the patient in the supine position, a longitudinal incision was made. After sternal splitting, all mediastinal soft tissue from the thyroid gland to the diaphragm and between both phrenic nerves, including the thymus, was removed. Both pleural cavities were opened for resection of cardiophrenic fatty tissue and hilar inspection. The sternum was closed by single stitches with resorbable sutures. All patients were extubated immediately after the operation.

Postoperative pulmonary function and analgesia
Bedside spirometry (Flow Screen Version 2.1; Firma Erich Jaeger, Würzburg, Germany) was carried out with the patient in the supine position and the upper part of the body elevated 45 degrees. Each test was repeated three times, and the best of the three results was taken for analysis. Spirometry was performed preoperatively, two times per day until the third postoperative day, and once a day from the fourth until the sixth day. The best of the two results, measured on the first three postoperative days, was used for analysis. All values were recorded as percentages of the individual preoperative function tests. Spirometry was validated by body plethysmography performed preoperatively and on the sixth postoperative day.

All patients received patient-controlled analgesia (PCA) by intravenous morphine sulfate without continuous infusion as long as required. The dosage of a single bolus was individually adjusted to the patient’s body weight in all cases. The amounts of morphine sulfate were calculated from the PCA mode of application. The patient’s subjective pain perception was assessed by visual analog scale (VAS) every 12 hours, using a scale from 1 to 10, and doses were adjusted accordingly. For thorough evaluation of pain, the VAS score was determined with the patient at rest and, additionally, during inspiration, mobilization, and coughing. Postoperative morbidity was completely recorded. Clinical improvement of MG after Thx was assessed according to the classification of Viets and Schwab [16].

Statistical analysis
Continuous data with normal distribution are given as mean ± SD and were compared between the groups using the Student’s t test. To compare categorical data, Fisher’s exact test was employed. The data of pulmonary function and VAS are given as median with range and were compared between the groups using the Mann-Whitney U test and the Kolmogorov-Smirnov test for unpaired nonparametric data. If appropriate, the Wilcoxon rank sum test was employed. A p value of 0.05 was considered significant. Statistical analysis of all data was performed using commercial software (SPSS for Windows, Version 9.0.1; SPSS Inc, Chicago, IL).

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
From January 1, 1998 to August 30, 1999, 20 patients were randomly assigned to tThx (n = 10) or sThx (n = 10) for MG. Demographic data of the patients are shown in Table 1. There were no significant differences in these characteristics. The distribution of operative risk class (ASA) was similar for the tThx group (I-4, II-6) and the sThx group (I-3, II-7). In the tThx group, 2 patients had rheumatoid arthritis associated with MG and 1 patient had thyroid disease. There was one case of colitis ulcerosa and one case of thyroid disease in the sThx group. Particularly, staging of MG according to Ossermann and Genkins [17] revealed all patients in stage II (a/b), with no difference between tThx (5/5) and sThx (4/6) groups. The preoperative duration of MG was slightly longer in the tThx group (11.9 months; SD 21.3) than in the sThx group (5.3 months; SD 4.0) but the difference was not significant. Preoperatively, all patients were on cholinesterase inhibitors, and 50% of the patients in each group received immunosuppressive medication.

In neither group were there any major complications after surgery. Postoperative morbidity (one abnormal wound healing with sThx; one pleural effusion and one atelectasis in each group) did not require special treatment and had only a minor influence on recovery.

Except for the time point 12 hours postoperatively, the sThx patients required significantly higher doses of morphine sulfate compared with the tThx group on the first 2 postoperative days (Table 2). None of the tThx patients required PCA for more than 2 days postoperatively, whereas it was continued until the sixth postoperative day in the sThx group. The results of complex VAS evaluation showed pain relief to be sufficient in all patients to effectively compare sThx and tThx with respect to pulmonary function tests. Except for the time points of 12 hours postoperatively, with mobilization, and 3 days postoperatively, at rest, there were no significant differences of subjective postoperative pain perception (VAS) between both groups.

View larger version (31K): [in this window] [in a new window]   Fig 1. Box-and-whisker plots of the median values and range of: (A) VC; (B) FVC; (C) FEV1; and (D) PEF after tThx and sThx over the study period. *p < 0.05, **p < 0.001 (tThx vs sThx, Mann-Whitney U test); °p < 0.05 (postoperative vs preoperative values, Wilcoxon rank sum test). The preoperative data are percentages of the normal values. All postoperative data are percentages of the individual preoperative function tests.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
The thoracoscopic approach for Thx has been developed in our clinic according to the rules of good clinical practice since 1994 [17]. Therefore, the comprehensive evaluation of this new approach comprised an experimental anatomical demonstration of the adequate radicality, a prospective clinical study [11], and a prospective comparison of tThx with one of the most widely accepted techniques for Thx [2, 4, 6]. Both partial and simple complete sternotomy are used for Thx, as well as the extended transcervical technique [1, 3, 10]. However, neither a limited sternotomy nor the transcervical approach are suitable as a gold standard concerning radicality of Thx and functional improvement of MG [6, 7]. Though some investigators consider a limited "J" sternotomy to allow full access from the neck to the diaphragm, others point out that there is even a remarkable difference in completeness between extended and simple complete median sternotomy [7]. One of the most important advantages of tThx in the complex regimen for treating MG could be its minimally invasive character. In the present study, tThx achieved the resection of similar amounts of mediastinal tissue as compared with sThx, and these data are in accordance with the results of extended Thx [8]. The current mean follow-up time of 12 months for the patients included in our study is by far not long enough to assess definitely the role of tThx for MG, but the preliminary results demonstrate equal improvement rates of MG after tThx and sThx (Table 1). Moreover, these results are encouraging as compared with the results published so far [3, 4, 7–12]. This is considered a fundamental prerequisite for the evaluation of pulmonary function as related to different operative techniques. Part of our latest clinical investigations of tThx was to compare this procedure with the conventional approach of sThx with respect to perioperative impairment of pulmonary function.

Both thoracotomy and median sternotomy potentially produce a marked reduction in postoperative pulmonary function [18]. Hence, analgesia after thoracic surgery is of particular significance, for several reasons. Thoracotomy has been reported to be among the most intense clinical postoperative pain experiences known, whereas median sternotomy produces less pain. Successful pain therapy is therefore one of the most important prerequisites for analyzing pulmonary function after thoracic surgery [19].

Impairment of pulmonary function in MG can be attributed to weakness of the diaphragm and thoracic chest wall muscles. Furthermore, upper airway obstruction is suggested to be much more common in patients with MG than previously recognized [20]. The effect of pyridostigmine and plasma exchange on lung volumes, respiratory muscle strength, and ventilatory control system indirectly demonstrates impaired pulmonary function in MG patients [21]. These patients are therefore especially prone to develop pulmonary complications after any kind of surgery, and in particular after Thx.

The severe and prolonged alteration in pulmonary mechanics caused by a thoracotomy or median sternotomy has a multifactorial etiology, and pain is one of the most relevant factors [22]. The adequate method to determine the postoperative analgetic requirement in both groups was difficult to find because different aspects had to be taken into consideration. The most effective mode of analgetic administration in conventional thoracic surgery seems to be a combination with local application of analgetics [19, 23]. Thus, the gold standard for postthoracotomy pain control is continuous epidural analgesia or, potentially even better, continuous paravertebral extrapleural infusion [18, 23]. However, for a sternotomy, neither epidural nor intraspinal morphine is now used in many centers because sternotomy pain can be managed by PCA or oral narcotics. Though median sternotomy is less painful compared with a standard lateral thoracotomy, especially in median sternotomy for MG, intraspinal morphine provided effective postoperative analgesia resulting in improved initial ventilatory function [24, 25]. For thoracoscopy, however, regional analgesia did not lead to a reduction in analgetic consumption [13]. Given that patients are expected to be impaired only little by a thoracoscopic operation in general and tThx in particular, intraspinal analgesia would appear to represent overtreatment. Moreover, possible complications of epidural analgesia include improper placement, pulmonary complications, pruritus, nausea and vomiting, respiratory depression, mental status changes, postural hypotension, paresthesias, and urinary retention [23]. Nilsson and associates found a 40% rate of postpuncture headache after intrathecal morphine application for sThx [25].

PCA was continued until the second postoperative day, and the intravenous application was discontinued on the third postoperative day in the tThx group because it was no longer required in any of the patients. In contrast, the patients of the sThx group needed PCA, though with declining doses, 4 days longer.

The postoperative decrease of pulmonary function (VC, FVC, FEV₁, PEF) after sThx in our study to approximately 30% of the preoperative values is in accordance with the findings of Kirsch and associates and Nilsson and associates [24, 25]. Also, the recovery rate of pulmonary function after sThx until the third postoperative day is comparable with the data published earlier [25]. It cannot definitely be ruled out that the diminished pulmonary function after sThx was partially due to the higher doses of analgetics in this group because analgesia-related central depression of respiration has to be considered as an additional cause [18]. Nevertheless, because there was only a small difference in analgetic requirement between both groups, the pronounced difference in the postoperative depression of pulmonary function between sThx and tThx can only be explained by the different operative approach itself. Other investigations confirm that the rather slow postoperative recovery of lung function parameters cannot be attributed to pain alone [13].

Less pronounced impairment and faster recovery of pulmonary function after tThx characterize this new approach for thymectomy as minimally invasive. These results could make tThx the preferred surgical treatment of MG, which was improved to the same extent as after sThx.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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