CJA
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chevalley, C.
Right arrow Articles by Licker, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chevalley, C.
Right arrow Articles by Licker, M.
Canadian Journal of Anesthesia 48:446-451 (2001)
© Canadian Anesthesiologists' Society, 2001
General Anesthesia

Perioperative medical management and outcome following thymectomy for myasthenia gravis

Catherine Chevalley, MD*, Anastase Spiliopoulos, MD{dagger}, Marc de Perrot, MD{dagger}, Jean-Marie Tschopp, MD{ddagger} and Marc Licker, MD*

* From the Division of Anesthesiology and
{dagger} Unit of Thoracic Surgery, University Hospital of Geneva, and
{ddagger} Thorax Medical Center of Montana, Switzerland.

Address correspondence to: Dr. Marc Licker, Division d'Anesthésiologie, Hôpital Cantonal Universitaire, CH- 1211 GENEVA 14, Switzerland. Phone: 00-41-22-3827402; Fax: 00-41-22-3727690; E-mail: marc-joseph.licker{at}hcuge.ch


   Abstract
TOP
 Abstract
Methods
 Results
 Discussion
 APPENDIX
 References
 
Purpose: To describe the evolution of the perioperative management of myasthenia gravis (MG) patients undergoing thymectomy and to question the need for systematic postoperative ventilation.

Clinical features: We collected data retrospectively from 36 consecutive MG patients who underwent thymectomy over a 21-yr period, via transthoracic, -cervical or -sternal incisions (n=5, n=7, n=24, respectively). From 1980 to 1993, a balanced anesthetic technique (n=24) included various inhalational agents with opiates and myorelaxants (in eight cases); 22 patients were admitted to the intensive care unit (ICU). Since 1994, iv propofol was combined with epidural bupivacaine and sufentanil (n=12); all patients were admitted to the postanesthesia care unit.

Short-term postoperative ventilation (median time four hours, range from three to 48 hr) was required in eight patients who had longer hospital stay (median stay=12 days, range (8–28) vs five days (4–15) for patients with early extubation, P <0.05) but similar clinical improvement six months after thymectomy.

Postoperative ventilatory support was required more frequently when a balanced anesthetic technique was used (odds ratio=4.2 (1.1–9.7), P=0.03) and particularly when myorelaxants were given (odds ratio=13.9 (2.1–89.8), P=0.009). Leventhal's scoring system had low sensitivity (22.2%) and positive predictive values (25%).

Conclusions: Our data show that the severity of MG failed to predict the need for postoperative ventilation. A combined anesthetic technique was a safe and cost-effective alternative to balanced anesthesia as it provided optimal operating conditions and resulted in fewer admissions in ICU and shorter hospital stays.

MYASTHENIA gravis (MG) is a rare auto-immune disease characterized by fluctuating muscle weakness and fatigability due to a reduction in available acetylcholine receptors at the neuromuscular junction.1 The role of the thymus has been suggested by the presence of tumours and germinal centres in a majority of patients with MG and by the beneficial effects of thymectomy in about 40–90% of patients.2,3 Besides thymectomy, therapy with anticholinesterase drugs, - providing an increase in acetylcholine - is of partial clinical benefit whereas the use of corticosteroids, immunosuppressive drugs and plasmapheresis often improve the prognosis of those patients resistant to anticholinesterase drugs or with life-threatening symptoms.4,5

Clinicians are well aware of the risk of postoperative respiratory failure6,7 that may result from stress-induced exacerbation of MG (myasthenic crisis), an overdose of anticholinesterases (cholinergic crisis), the residual effects of myorelaxants or other adverse drug interactions (with antibiotics or antiarrhythmics). Therefore, routine postoperative ventilatory support and planned extubation in the intensive care unit (ICU) have been recommended in high-risk patients. To predict the need for postoperative ventilation, Leventhal et al. proposed a scoring system which takes into account the duration of MG, the dosage of pyridostigmine, lung functional volumes and the presence of concomitant respiratory diseases.8

Various anesthetic approaches have been reported in MG patients.7,9,10 In our institution, thoracic epidural anesthesia in combination with propofol anesthesia has been routinely performed since 1994. The purpose of this retrospective study was to determine if a combined technique could be safely substituted to balanced anesthesia in MG patients undergoing thymectomy and to question whether the need for postoperative ventilation could be accurately predicted.


   Methods
TOP
 Abstract
 Methods
Results
 Discussion
 APPENDIX
 References
 
From January 1980 to March 2000, 36 consecutive patients with MG underwent thymectomy and were managed by the same medical team at the University Hospital of Geneva. The medical and nursing charts of patients with MG were reviewed retrospectively. All patients had MG proven by an anticholinesterase test and by electroneuro-myographic assessment. According to the classification by Osserman and Genkins,11 the clinical severity of MG was graded in five stages (I, ocular signs only; IIA, generalized mild muscle weakness; IIB, generalized moderate weakness and/or bulbar dysfunction; III, acute fulminating presentation and/or respiratory dysfunction; IV, late generalized weakness). Besides routine examinations, preoperative investigations included chest computed tomography scan, lung volume spirometry and detection of various circulating auto-antibodies (anti-acetylcholine receptor, anti-smooth muscle cell, anti-nuclear factor). Patients' preoperative characteristics are summarized in Table IGo. For each patient, the preoperative risk score was calculated according to Leventhal et al.(see appendix).


View this table:
[in this window]
[in a new window]
  		TABLE I Demographic, clinical and histological characteristics of 36 patients with myasthenia gravis (n patients, median (range))
 
The operations were performed by three experienced thoracic surgeons either through thoracic incision, transcervical approach (n=5; n=7), or via sternotomy (n=24). An arterial line was inserted in all patients with respiratory symptoms (n=19). Tracheal extubation was performed in the operating room ("early" extubation) or in the intensive care unit (ICU) ("delayed" extubation) when the patient appeared fully responsive and could generate an inspiratory force greater than -20 cm H2O. The usual dose of pyridostigmine was administered prior to surgery. Pyridostigmine was resumed within six hours after surgery at a lower dose; neostigmine (2.5–5 mg) was given intravenously in those patients who were unable to swallow.

Data were collected concerning anesthetic variables and any perioperative complications. In the immediate postoperative period, difficulties with weaning and the duration of mechanical ventilatory support were evaluated. At regular follow-up visits, neurologists adjusted the medical treatment and assessed the time course of the disease.

Data are expressed as median and range or absolute numbers. When appropriate, statistical evaluation was performed using Mann-Whitney U-test, Wilcoxon test, power analysis and chi-square analysis (2) with Fisher' exact test. The sensitivity, specificity and predictability of Leventhal's scoring system were also determined.


   Results
TOP
 Abstract
 Methods
 Results
Discussion
 APPENDIX
 References
 
Over a 21-yr period, thymectomy for MG was performed under two different types of anesthesia (Table IIGo): 1) from 1980 to 1993, a balanced technique included various inhalational agents with small doses of opiates (n=24) and myorelaxants in eight cases; 2) since 1994, iv propofol was combined with epidural administration of bupivacaine and sufentanil (n=12).


View this table:
[in this window]
[in a new window]
  		TABLE II Anesthetic management of 36 patients with myasthenia gravis
 
Successful tracheal extubation was achieved in 28 patients in the operating room ("early" extubation) whereas five patients required three to four hours of ventilatory support and three others remained intubated for eight, 19 and 48 hr after the end of surgery ("delayed" extubation). Patients managed with a combined general and epidural anesthesia were all extubated immediately after surgery (Figure 1Go) and were electively admitted in the postanesthesia care unit, after balanced anesthesia, a majority (22 of 24) were admitted in the ICU.



View larger version (20K):
[in this window]
[in a new window]
  		FIGURE 1 Delayed or early extubation after thymectomy under balanced or combined anesthesia, with ({blacksquare}) or without ({square}) muscle relaxants.

 
There were no differences between the "delayed" and "early" extubation groups with regard to preoperative clinical staging, body mass index, anticholinesterase dosage, duration of the disease, histological diagnosis, lung function, duration of surgery, infusion of intraoperative fluid and surgical technique (Table IIIGo). Postoperative ventilatory support was more frequently required when a balanced anesthetic technique was performed (odds ratio=4.2 (1.1–9.7), P=0.03) and particularly in patients who were given myorelaxants (odds ratio=13.9 (2.1–89.8), P=0.009).


View this table:
[in this window]
[in a new window]
  		TABLE III Characteristics of patients with immediate vs delayed extubation
 
No patient required re-intubation for myasthenic or cholinergic crisis. Compared with the "early" extubation group, patients with delayed extubation had a more prolonged hospital stay (median stay=12 days, range (8–28) vs five days (4–15), P <0.05) but had similar clinical improvement six months after thymectomy (Figure 2Go). Bronchopneumonia was diagnosed on the 5th postoperative day in one patient who was ventilated for 19 hr postoperatively.



View larger version (13K):
[in this window]
[in a new window]
  		FIGURE 2 Preoperative and postoperative clinical assessment (Osserman staging) in myasthenia gravis patients who had delayed ({circ}) or immediate ({blacklozenge}) postoperative extubation (median and range).

 
The Leventhal scoring system had a sensitivity of 22.2%, a specificity of 77.8%, a positive predictive value of 25% and a negative predictive value of 75% for assessing the need of postoperative ventilatory support.


   Discussion
TOP
 Abstract
 Methods
 Results
 Discussion
APPENDIX
 References
 
In this retrospective series, eight of 36 patients with MG required short-term postoperative ventilatory support but had similar clinical improvement compared with patients extubated immediately after thymectomy. Neither the severity of MG nor any surgical variable or histological finding were useful to predict difficulties with weaning from mechanical ventilation. Importantly, a combined epidural and general anesthetic technique appeared to facilitate early extubation.

Although determination of any multivariate scoring system is often fraught with methodological errors, current anesthesia textbooks still refer to Leventhal's criteria to predict the need for postoperative ventilatory support in MG.12,13 The validity of this scoring has been confirmed in a series of 41 patients undergoing thymectomy through transcervical, transsternal and thoracic approach.14 In contrast, no predictive value was demonstrated when applied only to transcervical thymectomy patients.15 Likewise, we documented low sensitivity and low positive predictive values in a our series involving three different surgical approaches.

In their original retrospective study, Leventhal et al. applied stepwise multivariate discriminant analysis to 21 preoperative factors among 24 patients.8 Knowing that the number of variables examined should be no more than 10% of the number of outcomes (postoperative ventilation),16 data on more than 600 patients should have been collected or/and the number of potential predictors should have been markedly restricted (e.g., four factors examined in 120 patients) to establish a stable and accurate scoring system. Hence, in our small series, we only performed a univariate analysis to detect possible risk factors; a multicentre study or pooling of several previous investigations, would have been necessary to apply multivariate analysis and to detect the independent predictors of postoperative respiratory insufficiency.

Our data suggest that the ability to sustain spontaneous ventilation after thymectomy appears to be less dependent on the clinical severity of MG evaluated by Leventhal'scoring than on the recent development of perioperative medical care. The combination of several factors likely contributed to facilitate postoperative extubation over the last seven years. It is possible that preoperative muscular atrophy was attenuated by using lower doses of corticosteroids and that neuromuscular function was further optimized by using other immunosuppressive drugs and plasmapheresis which eliminates circulating auto-antibodies against acetycholine receptors.4,17 In addition, the risk of respiratory failure may have been decreased by using less invasive surgical approaches (cervicotomy, partial sternotomy or mini-thoracotomy), avoiding myorelaxants and long acting anesthetic agents and by providing adequate postoperative analgesia.15,18,19

In our institution, - from 1980 to 1993 -, non-standardized balanced anesthesia protocols were applied and included various inhaled agents, small doses of opiates and, in some cases, muscle relaxants. Postoperative pain was poorly controlled due to fear of respiratory depression and the need for ventilatory support was more frequent when muscle relaxants were given intraoperatively. Since 1994, we have elected to perform thoracic epidural anesthesia in combination with general anesthesia in all patients undergoing thymectomy via a sternal or thoracic approach. Using a similar anesthetic technique, Suwanchida et al.20 confirmed the higher incidence of early extubation compared with balanced anesthesia (78 vs 29%). Not surprisingly, emergence from anesthesia was facilitated by providing maximal analgesia, minimizing the interactions with opiates and muscle relaxants and by rapid elimination of propofol.21 The inherent sedative properties of neuraxial blockade has been shown to reduce the requirements for general anesthetic agents by approximately 50%22 and the addition of opiates to epidural bupivacaine further enhances such synergistic effect.23

Nondepolarizing muscle relaxants were avoided and adequate surgical conditions were provided by iv propofol anesthesia. Good intubating conditions with acceptable jaw mobility and vocal cord relaxation can be obtained under propofol anesthesia without using muscle relaxants.24 Experimental data suggest that propofol attenuates skeletal muscle contractions by presynaptic inhibition of acetylcholine release and by slowing of calcium shifts through the muscle membrane.25

The decrease in available acetycholine receptors explains the resistance of MG patients to succinylcholine and the increased sensitivity to nondepolarizing relaxants and inhaled anesthetics which is associated with longer duration of the disease, higher preoperative pyridostigmine dose and elevated level of circulating antibodies.26 Although it seems prudent to avoid muscle relaxants, several recent studies have reported early extubation when muscle relaxants (vecuronium, atracurium, cisatracurium) were used in association with short-acting inhaled anesthetics (desflurane, sevoflurane) and iv opiates.26–30 In such cases, neuromuscular monitoring is particularly helpful to titrate the administration of muscle relaxants but also as a diagnostic tool: a marked decrement in the preanesthetic muscular response to repetitive stimulation (T4/T1 <0.9) identifies patients who require less than 30% of the usual atracurium dose to achieve 95% neuromuscular blockade (ED95).29

Although this report is subjected to the limitations of a retrospective study including missing data, bias in investigator assessment as well as poor control of preoperative, surgical and anesthetic variables, it provides the opportunity to gather information on a large number of patients with a rare disorder and to assess the clinical impact of a new anesthetic approach on patients' outcome in a single medical centre. Randomized controlled trials are not always possible for ethical considerations, clinical judgement and unwillingness on the part of the investigators or patients.31 Therefore, we must also rely on observational studies to identify risk factors for morbidity/mortality and to evaluate new healthcare interventions.

In an era of cost-containment, it is significant that provision of medical care is aimed at reducing the length of hospital stay, particularly in ICUs, while preserving or improving outcome and quality of life. Standardization of anesthesia procedures has been demonstrated to reduce the risk of human errors and to decrease medical charges. In our study, the shift in management of MG patients from balanced anesthesia (with various agents) to a standardized combined technique (without muscle relaxants) provided optimal operating conditions, improved patient comfort following transsternal and thoracic incision, avoided the need for postoperative ventilatory support and resulted in fewer admissions in ICU and shorter duration of hospital stay.


   APPENDIX
TOP
 Abstract
 Methods
 Results
 Discussion
 APPENDIX
References
 
MPredictors for postoperative need of mechanical ventilation (based on reference #8)

Duration of myasthenia gravis 72 mo: 12 points

History of chronic respiratory disease : 10 points

Pyridostigmine dosage >750 mg/day: 8 points

Vital capacity <2.9 L: 4 points

Accepted for publication January 17, 2001.


   References
TOP
 Abstract
 Methods
 Results
 Discussion
 APPENDIX
 References
 
1 Drachman DB. Myasthenia gravis (first of two parts). N Engl J Med 1978; 298: 136–42.[Medline]

2 Moulian N, Wakkach A, Guyon T, et al. Respective role of thymus and muscle in autoimmune myasthenia gravis. Ann N Y Acad Sci 1998; 841: 397–406.[Free Full Text]

3 Papatestas AE, Genkins G, Kornfeld P, et al. Effects of thymectomy in myasthenia gravis. Ann Surg 1987; 206: 79–88.[Medline]

4 Wittbrodt ET. Drugs and myasthenia gravis. An update. Arch Intern Med 1997; 157: 399–408.[Abstract]

5 Gripp S, Hilgers K, Wurm R, Schmitt G. Thymoma. Prognostic factors and treatment outcomes. Cancer 1998; 83: 1495–1503.[Medline]

6 Gracey DR, Divertie MB, Howard FM Jr, Payne WS. Postoperative respiratory care after transsternal thymectomy in myasthenia gravis. A 3-year experience in 53 patients. Chest 1984; 86: 67–71.[Abstract/Free Full Text]

7 Baraka A. Anaesthesia and myasthenia gravis. Can J Anaesth 1992; 39: 476–86.[Abstract/Free Full Text]

8 Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology 1980; 53: 26–30.[Medline]

9 Burgess FW, Wilcosky B Jr. Thoracic epidural anesthesia for transsternal thymectomy in myasthenia gravis. Anesth Analg 1989; 69: 529–31.[Free Full Text]

10 Secher O. Anaesthetic management of the myasthenic patient. A review of 33 cases. Acta Anaesthesiol Scand 1967; 11: 245–59.[Medline]

11 Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 1971; 38: 497–537.[Medline]

12 Benumof JL. Anaesthesia for Thoracic Surgery, 2nd ed. Philadelphia: W.B. Saunders Company Inc., 1995: 575–9.

13 Roizen MF. Anesthetic implications of concurrent diseases. In: Miller RD (Ed.). Anesthesia, 4th ed. New York: Churchill Livingstone Inc., 1994: 966–8.

14 Grant RP, Jenkins LC. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis: thymectomy compared to other surgical procedures. Can Anaesth Soc J 1982; 29: 112–6.[Medline]

15 Eisenkraft JB, Papatestas AE, Kahn CH, Mora CT, Fagerstrom R, Genkins G. Predicting the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology 1986; 65: 79–82.[Medline]

16 Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49: 1373–9.[Medline]

17 d'Empaire G, Hoaglin DC, Perlo VP, Pontoppidan H. Effect of prethymectomy plasma exchange on postoperative respiratory function in myasthenia gravis. J Thorac Cardiovasc Surg 1985; 89: 592–6.[Abstract]

18 Machens A, Busch C, Emskötter T, Izbicki JR. Morbidity after transsternal thymectomy for myasthenia gravis: a changing perspective? Thorac Cardiovasc Surg 1998; 46: 37–40.[Medline]

19 Naguib M, El Dawlatly AA, Ashour M, Bamgboye EA. Multivariate determinants of the need for postoperative ventilation in myasthenia gravis. Can J Anaesth 1996; 43: 1006–13.[Abstract/Free Full Text]

20 Suwanchinda V, Yok-Ubol B, Prakanrattana U, Udomphunthurak S. Combined thoracic epidural with light general anesthesia for thymectomy in myasthenia gravis. J Med Assoc Thai 1995; 78: 605–10.[Medline]

21 O'Flaherty D, Pennant JH, Rao K, Giesecke AH. Total intravenous anesthesia with propofol for transsternal thymectomy in myasthenia gravis. J Clin Anesth 1992; 4: 241–4.[Medline]

22 Hodgson PS, Liu SS, Gras TW. Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial. Anesthesiology 1999; 91: 1687–92.[Medline]

23 Kirsch JR, Diringer MN, Borel CO, Hanley DF, Merritt WT, Bulkley GB. Preoperative lumbar epidural morphine improves postoperative analgesia and ventilatory function after transsternal thymectomy in patients with myasthenia gravis. Crit Care Med 1991; 19: 1474–9.[Medline]

24 Scheller MS, Zornow MH, Saidman LJ. Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil. Anesth Analg 1992; 75: 788–93.[Abstract/Free Full Text]

25 Abdel-Zaher AO, Askar FG. The myoneural effects of propofol emulsion (diprivan) on the nerve-muscle preparations of rats. Pharmacol Res 1997; 36: 323–32.[Medline]

26 Nilsson E, Meretoja OA. Vecuronium dose-response and maintenance requirements in patients with myasthenia gravis. Anesthesiology 1990; 73: 28–32.[Medline]

27 Ramsey FM, Smith GD. Clinical use of atracurium in myasthenia gravis: a case report. Can Anaesth Soc J 1985; 32: 642–5.[Medline]

28 Baraka A, Siddik S, Kawkabani N. Cisatracurium in a myasthenic patient undergoing thymectomy. Can J Anesth 1999; 46: 779–82.[Abstract/Free Full Text]

29 Baraka A, Taha SK, Kawkabani N. Neuromuscular interaction of sevoflurane-cisatracurium in a myasthenic patient. Can J Anesth 2000; 47: 562–5.[Abstract/Free Full Text]

30 Mann R, Blobner M, Jelen-Esselborn S, Busley R, Werner C. Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology 2000; 93: 346–50.[Medline]

31 Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000; 342: 1887–92.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
M. Al-Abdullatief, A. Wahood, N. Al-Shirawi, Y. Arabi, M. Wahba, M. Al-Jumah, S. Al-Sheha, and N. Yamani
Awake anaesthesia for major thoracic surgical procedures: an observational study
Eur. J. Cardiothorac. Surg., August 1, 2007; 32(2): 346 - 350.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Meraouna, G. Cizeron-Clairac, R. L. Panse, J. Bismuth, F. Truffault, C. Tallaksen, and S. Berrih-Aknin
The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis
Blood, July 15, 2006; 108(2): 432 - 440.
[Abstract] [Full Text] [PDF]

Home page
 Canadian J. AnesthesiaHome page
G. Della Rocca, C. Coccia, L. Diana, L. Pompei, M. G. Costa, E. Tomaselli, P. Di Marco, V. Vilardi, and P. Pietropaoli
Propofol or sevoflurane anesthesia without muscle relaxants allow the early extubation of myasthenic patients: [L'anesthesie au propofol ou au sevoflurane, sans myorelaxants, permet une extubation precoce chez des patients myastheniques]
Can J Anesth, June 1, 2003; 50(6): 547 - 552.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chevalley, C.
Right arrow Articles by Licker, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chevalley, C.
Right arrow Articles by Licker, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS