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Prediction of Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Myth or Reality
Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Contents lists available at ScienceDirect
journal homepage: www.jcvaonline.com
Editorial
Prediction of Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Myth or Reality MYASTHENIA GRAVIS IS an autoimmune disease affecting the nicotinic acetylcholine receptor of the post-synaptic membrane of the neuromuscular junction, causing muscle fatigue and weakness.1 Myasthenia gravis can be treated with anticholinesterase agents, surgical thymectomy, immunosuppression, and immunotherapies (plasmapheresis).2 The myasthenia gravis patient represents a challenge to the anesthesiologist, and specifically the post-surgical risk of respiratory failure or extended periods of the need for mechanical ventilation in the postoperative period. In this volume, Chigurupati et al3 had reviewed in a retrospective analysis the preoperative variables associated with postoperative mechanical ventilation after transsternal thymectomy in order to predict the patients that would require prolong mechanical ventilation after surgery (ie, 4 300 min). Their study compiles 10 years of experience involving 77 patients with myasthenia gravis, divided into two groups. The group that had prolonged extubation times ( 4 300 min) had variables that correlated with prolonged extubation times: 1) the grade of myasthenia gravis (Osserman’s classification II), 2) the history of myasthenic crisis before surgery requiring endotracheal intubation and mechanical ventilation, 3) the presence of positive results for serum antibodies against acetylcholine receptors, 4) the presence of thymoma in computed tomography scan (CT), and 5) the vital capacity of o 2.9 L. What is new from this report when compared with other previous publications?2,4 For instance, in the Leventhal study there has been a lack of relationship among the scoring system, preoperative predictors, and extubation times in myasthenic gravis patients. The Leuzzi study2 had reviewed in a retrospective analysis the clinical data of 177 patients with myasthenia gravis undergoing thymectomy; 22 patients experienced postoperative respiratory failure after thymectomy. This study showed that Osserman’s grade II, history of myasthenic crisis duration, and lung resection were variables that independently correlated with postoperative myasthenic crisis, reintubation, and the need for mechanical ventilation during the postoperative period. http://dx.doi.org/10.1053/j.jvca.2017.08.014 1053-0770/& 2017 Elsevier Inc. All rights reserved.
When combining together previous findings and this new report3 we must consider multiple factors besides preoperative variables that affect outcomes including intraoperative factors. For instance the Chigurupati study3 reported the use of sevoflurane, opioids, atracurium, and in one-third of the cases thoracic epidural analgesia as part of the management. Per institutional protocol all their patients remained intubated and received mechanical ventilation in the postoperative period. Times of extubation ranged from 7 300 minutes. Is there any indication to maintain all myasthenia gravis patients intubated and mechanically ventilated after surgery in order to determine what preoperative variables can be a risk factor as shown by Chigurupati?3 In a prospective study5 comparing two non-muscle relaxant anesthesia techniques (propofol plus N2O, n ¼ 36 patients; versus sevoflurane plus N2O, n ¼ 32 patients) in myasthenia gravis patients undergoing transsternal thymectomy, it showed that all patients were extubated in the operating room at the conclusion of surgery and none of the patients required reintubation. What is different when comparing to the present study?3 Their study used non-depolarizing muscle relaxant (atracurium). Unfortunately their report has limited information related to the dose or frequency of atracurium used intraoperatively or mention of any attempt to use a reversal agent for the muscle relaxant. This information is relevant in myasthenia gravis patients specifically when the authors are trying to correlate variables with outcomes in the postoperative period. My major criticism to this report is the limited application of their findings particularly when all the patients (n ¼ 77) remained intubated in the postoperative period, and this may mislead the interpretation of their results. Another study6 in patients with myasthenia gravis undergoing thymectomy showed that the preanesthetic train-of-four fade predicts the dose of atracurium requirements in these patients. Based upon the response of train-on-four the authors were able to titrate the dose of atracurium needed and all patients were extubated within 30 minutes after surgery. The Chigurupati3 study only refers that neuromuscular monitoring
Editorial / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
2
was performed using train-of-four without specifics. Use of the train-of-four monitor for titration of the dose of non-depolarization relaxants is commonly used in patients with myasthenia gravis undergoing thymectomy. The use of neuromuscular relaxants should be used with caution in myasthenic patients due to the increased sensitivity to non-depolarizing muscle relaxants that might result in prolonged postoperative partial paralysis associated with increased morbidity and the need for postoperative mechanical ventilation. The newer non-depolarizing muscle relaxant rocuronium has been reported in patients with myasthenia gravis.7,8 A newly introduced cyclodextrin derivative, sugammadex, encapsulates steroidal neuromuscular blocking agents, ensuring full neuromuscular recovery. Sugammadex has been approved as a therapy for reversal of neuromuscular blockade induced by the steroidal non-depolarizing neuromuscular blocking drugs rocuronium and vecuronium. A preliminary report7 involved 10 myasthenia gravis patients undergoing video thoracoscopic surgery who received 0.3 mg/Kg of rocuronium plus additional doses according to the response to train-of-four. At the conclusion of surgery and prior to extubation the patients received intravenously sugammadex 2 mg/Kg. In this report all patients were extubated in the operating room after administration of sugammadex and none of the patients required mechanical ventilation due to respiratory failure or myasthenic crisis. Preliminary reports appear to indicate that it is possible in patients with myasthenia gravis undergoing thymectomy that reversal with sugammadex may facilitate an early extubation, and this should be considered as a factor when immediate extubation is possible. Another area of interest related to myasthenia gravis patients is the presence of thymoma on CT scan as a variable to predict prolonged extubation and the surgical approach (thymectomy) as reported.3 Some centers use the conventional approach with trans-cervical or transsternal thymectomy; however, with the introduction of minimally invasive surgical techniques more
centers are using video-assisted thoracoscopic, or videoassisted robotic thymectomy.9–11 Should minimally invasive thymectomy surgery lead to an early extubation after completion of surgery? Factors that we must consider when there is a need for postoperative mechanical ventilation are based upon preoperative medical condition (evidence of recent myasthenic crisis), positive antibodies for acetycholine receptors, surgical approach (conventional versus minimally invasive surgery), residual anesthetics, reversal of muscle relaxants, and careful planned extubation. It is my opinion and experience based upon scientific evidence that fewer myasthenia gravis patients undergoing thymectomy would need mechanical ventilation in the postoperative period or reintubation. It would be helpful to predict these patients based upon preoperative variables. Previous reports by Leventhal4 have failed to predict the need for mechanical ventilation after surgery, and when compared with a recent study3 where per protocol all their patients remained intubated after surgery, it is difficult at best to make recommendations based upon very few variables that might have an impact on the management of these patients. A focus of attention should be to correlate the variables that have influence on extubation after all conventional methods have failed (taking into consideration intraoperative variables such as: anesthetic technique, muscle relaxants, reversal agents, and myasthenic crisis in the postoperative period among others). Unfortunately, these studies are retrospective in nature, come from a single institution, have limited number of patients studied, and all have devoted their attention to the preoperative predictors. The decision to extubate the patients trachea or maintain mechanical ventilation in the postoperative period in the patient with myasthenia gravis is multifactorial. We should interpret some of the preoperative variable predictors with caution from previous studies (please refer to Table 1) when contemplating mechanical ventilation in the postoperative period. In addition, some intraoperative factors should be taken into consideration.
Table 1 Risk Factors to Predict the Need for Mechanical Ventilation After Thymectomy Preoperative Variables
Duration of myasthenia gravis Z6 years
Grade of myasthenia (Osserman’s)
Previous history of myasthenic crisis History of chronic respiratory disease Preoperative vital capacity r2.9 L Anti-acetylcholine receptor antibodies CT scan for thymoma Pyridostigmine dose 4750 mg/day
Extubation (immediate postoperative period)
Leventhal (24 pts) Retrospective Study (1980)4 Predictor
Leuzzi (177 pts) Retrospective Study (2014)2
Chigurupati (77 pts) Retrospective Study (2017)3
Predictor MG duration 42 years Predictor (grade II) Predictor
Non-predictor
Predictor Predictor
Predictor
Not reported Predictor
Not predictor
Predictor Predictor Predictor (n ¼ 64 pts) Not predictor No more than 350 mg/day None
16 pts
Abbreviations: CT, computed tomography; sMG, myasthenia gravis; Pts, patients.
155 pts successfully weaned within 6 hours 22 pts required prolonged ventilation 46 hours
Predictor (grade II) Predictor
Editorial / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Further prospective studies are needed in the future in patients with myasthenia gravis undergoing minimally invasive videothoracoscopic or robotic thymectomy and to determine the value of preoperative and intraoperative predictors related to outcomes and early extubation in the immediate postoperative period. Also, the attention should be focused on new reversal agents of non-depolarizing muscle relaxants such as sugammadex to avoid prolonged intubation after thymectomy. The recent study3 adds limited information in predicting postoperative mechanical ventilation after thymectomy due in part to their study design and the preoperative variables studied. 1
Javier H. Campos, MD University of Iowa Health Care Iowa City, IA
References 1 Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and mysthenia gravis. Acta Anaesthesiol Scand 2012;56:17–22. 2 Leuzzi G, Meacci E, Cusumano, et al. Thymectomy in myasthenia gravis: Proposal for a predictive score of postoperative myasthenic crisis. Eur J Cardiothorac Surg 2014;45:e76–88.
3
3 Chigurupati K, Gadhinglajkar S, Sreedhar R, et al. Criteria for postoperative mechanical ventilation after thymectomy in patients with Myasthenia Gravis: A retrospective analysis. J Cardiothorac Vasc Anesth 2017. [this issue]. 4 Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology 1980;53:26–30. 5 Della Rocca G, Coccia C, Diana L, et al. Propofol or sevoflurane anesthesia without muscle relaxants allow the early extubation of myasthenic patients. Can J Anaesth 2003;50:547–52. 6 Mann R, Blobner M, Jelen-Esselborn S, et al. Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology 2000;93:346–50. 7 Sungur Ulke Z, Yavru A, Camci E, et al. Rocuronium and sugammadex in patients with myasthenia gravis undergoing thymectomy. Acta Anaesthesiol Scand 2013;57:745–8. 8 de Boer HD, Shields MO, Booij LH. Reversal of neuromuscular blockade with sugammadex in patients with myasthenia gravis: A case series of 21 patients and review of the literature. Eur J Anaesthesiol 2014;31: 715–21. 9 Buentzel J, Straube C, Heinz J, et al. Thymectomy via open surgery or robotic video assisted thoracic surgery: Can a recommendation already be made? Medicine 2017;96:e7161. 10 Buentzel J, Heinz J, Hinterthaner M, et al. Robotic versus thoracoscopic thymectomy: The current evidence. Int J Med Robot 2017. [in press]. 11 Campos JH. Anaesthesia for robotic surgery: Mediastinal mass resection and pulmonary resections. Anaesthesia International 2011:19–22.
1 Address reprint requests to Javier H. Campos, MD, Professor, Executive Medical Director Perioperative Service, Director of Cardiothoracic Anesthesia, University of Iowa Health Care, Iowa City, IA 52241. E-mail address: [email protected] (J. H. Campos).
Contents lists available at ScienceDirect
journal homepage: www.jcvaonline.com
Editorial
Prediction of Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Myth or Reality MYASTHENIA GRAVIS IS an autoimmune disease affecting the nicotinic acetylcholine receptor of the post-synaptic membrane of the neuromuscular junction, causing muscle fatigue and weakness.1 Myasthenia gravis can be treated with anticholinesterase agents, surgical thymectomy, immunosuppression, and immunotherapies (plasmapheresis).2 The myasthenia gravis patient represents a challenge to the anesthesiologist, and specifically the post-surgical risk of respiratory failure or extended periods of the need for mechanical ventilation in the postoperative period. In this volume, Chigurupati et al3 had reviewed in a retrospective analysis the preoperative variables associated with postoperative mechanical ventilation after transsternal thymectomy in order to predict the patients that would require prolong mechanical ventilation after surgery (ie, 4 300 min). Their study compiles 10 years of experience involving 77 patients with myasthenia gravis, divided into two groups. The group that had prolonged extubation times ( 4 300 min) had variables that correlated with prolonged extubation times: 1) the grade of myasthenia gravis (Osserman’s classification II), 2) the history of myasthenic crisis before surgery requiring endotracheal intubation and mechanical ventilation, 3) the presence of positive results for serum antibodies against acetylcholine receptors, 4) the presence of thymoma in computed tomography scan (CT), and 5) the vital capacity of o 2.9 L. What is new from this report when compared with other previous publications?2,4 For instance, in the Leventhal study there has been a lack of relationship among the scoring system, preoperative predictors, and extubation times in myasthenic gravis patients. The Leuzzi study2 had reviewed in a retrospective analysis the clinical data of 177 patients with myasthenia gravis undergoing thymectomy; 22 patients experienced postoperative respiratory failure after thymectomy. This study showed that Osserman’s grade II, history of myasthenic crisis duration, and lung resection were variables that independently correlated with postoperative myasthenic crisis, reintubation, and the need for mechanical ventilation during the postoperative period. http://dx.doi.org/10.1053/j.jvca.2017.08.014 1053-0770/& 2017 Elsevier Inc. All rights reserved.
When combining together previous findings and this new report3 we must consider multiple factors besides preoperative variables that affect outcomes including intraoperative factors. For instance the Chigurupati study3 reported the use of sevoflurane, opioids, atracurium, and in one-third of the cases thoracic epidural analgesia as part of the management. Per institutional protocol all their patients remained intubated and received mechanical ventilation in the postoperative period. Times of extubation ranged from 7 300 minutes. Is there any indication to maintain all myasthenia gravis patients intubated and mechanically ventilated after surgery in order to determine what preoperative variables can be a risk factor as shown by Chigurupati?3 In a prospective study5 comparing two non-muscle relaxant anesthesia techniques (propofol plus N2O, n ¼ 36 patients; versus sevoflurane plus N2O, n ¼ 32 patients) in myasthenia gravis patients undergoing transsternal thymectomy, it showed that all patients were extubated in the operating room at the conclusion of surgery and none of the patients required reintubation. What is different when comparing to the present study?3 Their study used non-depolarizing muscle relaxant (atracurium). Unfortunately their report has limited information related to the dose or frequency of atracurium used intraoperatively or mention of any attempt to use a reversal agent for the muscle relaxant. This information is relevant in myasthenia gravis patients specifically when the authors are trying to correlate variables with outcomes in the postoperative period. My major criticism to this report is the limited application of their findings particularly when all the patients (n ¼ 77) remained intubated in the postoperative period, and this may mislead the interpretation of their results. Another study6 in patients with myasthenia gravis undergoing thymectomy showed that the preanesthetic train-of-four fade predicts the dose of atracurium requirements in these patients. Based upon the response of train-on-four the authors were able to titrate the dose of atracurium needed and all patients were extubated within 30 minutes after surgery. The Chigurupati3 study only refers that neuromuscular monitoring
Editorial / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
2
was performed using train-of-four without specifics. Use of the train-of-four monitor for titration of the dose of non-depolarization relaxants is commonly used in patients with myasthenia gravis undergoing thymectomy. The use of neuromuscular relaxants should be used with caution in myasthenic patients due to the increased sensitivity to non-depolarizing muscle relaxants that might result in prolonged postoperative partial paralysis associated with increased morbidity and the need for postoperative mechanical ventilation. The newer non-depolarizing muscle relaxant rocuronium has been reported in patients with myasthenia gravis.7,8 A newly introduced cyclodextrin derivative, sugammadex, encapsulates steroidal neuromuscular blocking agents, ensuring full neuromuscular recovery. Sugammadex has been approved as a therapy for reversal of neuromuscular blockade induced by the steroidal non-depolarizing neuromuscular blocking drugs rocuronium and vecuronium. A preliminary report7 involved 10 myasthenia gravis patients undergoing video thoracoscopic surgery who received 0.3 mg/Kg of rocuronium plus additional doses according to the response to train-of-four. At the conclusion of surgery and prior to extubation the patients received intravenously sugammadex 2 mg/Kg. In this report all patients were extubated in the operating room after administration of sugammadex and none of the patients required mechanical ventilation due to respiratory failure or myasthenic crisis. Preliminary reports appear to indicate that it is possible in patients with myasthenia gravis undergoing thymectomy that reversal with sugammadex may facilitate an early extubation, and this should be considered as a factor when immediate extubation is possible. Another area of interest related to myasthenia gravis patients is the presence of thymoma on CT scan as a variable to predict prolonged extubation and the surgical approach (thymectomy) as reported.3 Some centers use the conventional approach with trans-cervical or transsternal thymectomy; however, with the introduction of minimally invasive surgical techniques more
centers are using video-assisted thoracoscopic, or videoassisted robotic thymectomy.9–11 Should minimally invasive thymectomy surgery lead to an early extubation after completion of surgery? Factors that we must consider when there is a need for postoperative mechanical ventilation are based upon preoperative medical condition (evidence of recent myasthenic crisis), positive antibodies for acetycholine receptors, surgical approach (conventional versus minimally invasive surgery), residual anesthetics, reversal of muscle relaxants, and careful planned extubation. It is my opinion and experience based upon scientific evidence that fewer myasthenia gravis patients undergoing thymectomy would need mechanical ventilation in the postoperative period or reintubation. It would be helpful to predict these patients based upon preoperative variables. Previous reports by Leventhal4 have failed to predict the need for mechanical ventilation after surgery, and when compared with a recent study3 where per protocol all their patients remained intubated after surgery, it is difficult at best to make recommendations based upon very few variables that might have an impact on the management of these patients. A focus of attention should be to correlate the variables that have influence on extubation after all conventional methods have failed (taking into consideration intraoperative variables such as: anesthetic technique, muscle relaxants, reversal agents, and myasthenic crisis in the postoperative period among others). Unfortunately, these studies are retrospective in nature, come from a single institution, have limited number of patients studied, and all have devoted their attention to the preoperative predictors. The decision to extubate the patients trachea or maintain mechanical ventilation in the postoperative period in the patient with myasthenia gravis is multifactorial. We should interpret some of the preoperative variable predictors with caution from previous studies (please refer to Table 1) when contemplating mechanical ventilation in the postoperative period. In addition, some intraoperative factors should be taken into consideration.
Table 1 Risk Factors to Predict the Need for Mechanical Ventilation After Thymectomy Preoperative Variables
Duration of myasthenia gravis Z6 years
Grade of myasthenia (Osserman’s)
Previous history of myasthenic crisis History of chronic respiratory disease Preoperative vital capacity r2.9 L Anti-acetylcholine receptor antibodies CT scan for thymoma Pyridostigmine dose 4750 mg/day
Extubation (immediate postoperative period)
Leventhal (24 pts) Retrospective Study (1980)4 Predictor
Leuzzi (177 pts) Retrospective Study (2014)2
Chigurupati (77 pts) Retrospective Study (2017)3
Predictor MG duration 42 years Predictor (grade II) Predictor
Non-predictor
Predictor Predictor
Predictor
Not reported Predictor
Not predictor
Predictor Predictor Predictor (n ¼ 64 pts) Not predictor No more than 350 mg/day None
16 pts
Abbreviations: CT, computed tomography; sMG, myasthenia gravis; Pts, patients.
155 pts successfully weaned within 6 hours 22 pts required prolonged ventilation 46 hours
Predictor (grade II) Predictor
Editorial / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Further prospective studies are needed in the future in patients with myasthenia gravis undergoing minimally invasive videothoracoscopic or robotic thymectomy and to determine the value of preoperative and intraoperative predictors related to outcomes and early extubation in the immediate postoperative period. Also, the attention should be focused on new reversal agents of non-depolarizing muscle relaxants such as sugammadex to avoid prolonged intubation after thymectomy. The recent study3 adds limited information in predicting postoperative mechanical ventilation after thymectomy due in part to their study design and the preoperative variables studied. 1
Javier H. Campos, MD University of Iowa Health Care Iowa City, IA
References 1 Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and mysthenia gravis. Acta Anaesthesiol Scand 2012;56:17–22. 2 Leuzzi G, Meacci E, Cusumano, et al. Thymectomy in myasthenia gravis: Proposal for a predictive score of postoperative myasthenic crisis. Eur J Cardiothorac Surg 2014;45:e76–88.
3
3 Chigurupati K, Gadhinglajkar S, Sreedhar R, et al. Criteria for postoperative mechanical ventilation after thymectomy in patients with Myasthenia Gravis: A retrospective analysis. J Cardiothorac Vasc Anesth 2017. [this issue]. 4 Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology 1980;53:26–30. 5 Della Rocca G, Coccia C, Diana L, et al. Propofol or sevoflurane anesthesia without muscle relaxants allow the early extubation of myasthenic patients. Can J Anaesth 2003;50:547–52. 6 Mann R, Blobner M, Jelen-Esselborn S, et al. Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology 2000;93:346–50. 7 Sungur Ulke Z, Yavru A, Camci E, et al. Rocuronium and sugammadex in patients with myasthenia gravis undergoing thymectomy. Acta Anaesthesiol Scand 2013;57:745–8. 8 de Boer HD, Shields MO, Booij LH. Reversal of neuromuscular blockade with sugammadex in patients with myasthenia gravis: A case series of 21 patients and review of the literature. Eur J Anaesthesiol 2014;31: 715–21. 9 Buentzel J, Straube C, Heinz J, et al. Thymectomy via open surgery or robotic video assisted thoracic surgery: Can a recommendation already be made? Medicine 2017;96:e7161. 10 Buentzel J, Heinz J, Hinterthaner M, et al. Robotic versus thoracoscopic thymectomy: The current evidence. Int J Med Robot 2017. [in press]. 11 Campos JH. Anaesthesia for robotic surgery: Mediastinal mass resection and pulmonary resections. Anaesthesia International 2011:19–22.
1 Address reprint requests to Javier H. Campos, MD, Professor, Executive Medical Director Perioperative Service, Director of Cardiothoracic Anesthesia, University of Iowa Health Care, Iowa City, IA 52241. E-mail address: [email protected] (J. H. Campos).