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Reversal of neuromuscular blockade with sugammadex in patients with myasthenia gravis: A case series of 21 patients and review of the literature

de Boer, Hans D.; Shields, Martin O.; Booij, Leo H.D.J.

European Journal of Anaesthesiology: December 2014 - Volume 31 - Issue 12 - p 715–721
doi: 10.1097/EJA.0000000000000153
Correspondence
Free

From the Department of Anaesthesia and Pain Medicine, Martini General Hospital Groningen, the Netherlands (HDDB), Department of Anaesthesia, Royal Victoria Hospital, Belfast, Ireland (MOS), and Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (LHDJB)

Correspondence to Hans D. de Boer, MD, PhD, Department of Anaesthesia and Pain Medicine, Martini General Hospital Groningen, P.O. Box 30033, 9700 RM Groningen, the Netherlands E-mail: hd.de.boer@mzh.nl

Published online 4 September 2014

Editor,

Myasthenia gravis is an autoimmune disease involving the destruction of nicotinic acetylcholine receptors at the neuromuscular junction of striated muscles. The disease is characterised by weakness and exercise-induced fatigue of skeletal muscles. The incidence of myasthenia gravis is 3 to 7 per 100 000.1–4 Patients suffering from myasthenia gravis who need surgery under general anaesthesia are not very common. The combination of anaesthesia and myasthenia gravis can be challenging for the anaesthesiologist because it is associated with an increased risk of severe complications or death.1–4

Perioperative anaesthesia management is important. One of the challenges is the increased sensitivity to nondepolarising neuromuscular blocking agents (NMBAs), which may result in prolonged postoperative partial paralysis associated with respiratory morbidity and mortality and the need for postoperative mechanical ventilation. Therefore, NMBAs should be administered with care (i.e. smaller doses and less frequent repeat doses) in patients with myasthenia gravis. However, even small amounts of NMBAs can lead to profound (or intense) neuromuscular blockade and prolonged spontaneous recovery.5 It is therefore recommended that postoperative residual paralysis is reversed pharmacologically at the end of surgery in all patients, but especially in vulnerable patients such as those with myasthenia gravis.6

Reversal of neuromuscular blockade with conventional cholinesterase inhibitors such as neostigmine is inefficient in myasthenia gravis, as these patients are already taking pyridostigmine. The chronic use of cholinesterase inhibitors can result in a maximal inhibition of this enzyme, and therefore, this method of reversal of NMBAs is less effective.1,2,5

Sugammadex is a modified γ-cyclodextrin that rapidly reverses the effect of rocuronium or vecuronium-induced neuromuscular blockade.7 Encapsulation of the rocuronium or vecuronium molecule by sugammadex results in a rapid decrease in free plasma concentration, and subsequently that at the nicotinic receptor in the motor endplate. This usually leads to rapid and complete recovery from neuromuscular blockade within minutes. Sugammadex has been evaluated in both healthy and more vulnerable patients, such as those with cardiac or pulmonary disease.8,9 However, data published on reversal of neuromuscular blockade with sugammadex in patients with myasthenia gravis are sparse and consist of case reports only. This study was performed in order to investigate the reversal strategy with sugammadex and any interference of this reversal strategy with the underlying treatment of myasthenia gravis patients.

This two-centre study, which was performed in the Royal Hospitals, Belfast, UK and the Martini General Hospital Groningen, the Netherlands, was designed as a case series in which patients’ charts from the period between November 2008 and April 2014 were retrieved from the hospital archives. The search criteria were patients diagnosed with myasthenia gravis who underwent surgery under general anaesthesia. If the search criteria were met, the patient was included in the study and data were stored anonymously in a separate file and evaluated. The relevant demographic data and data on anaesthesia and neuromuscular management were retrieved and analysed. Patients were evaluated for Osserman classification of their myasthenia.10

The institutional ethical committee of each hospital was consulted for approval of the study. The local ethical committee of the Martini General Hospital Groningen, Groningen, the Netherlands (Chairperson Dr A.W.F. Rutgers) approved the study on 11 June 2013 (MEC-number 2013-33). As only patients’ charts (as individual cases) were retrieved anonymously from the hospital archives and no clinical interventions were undertaken, ethical committee approval of the Royal Hospitals, Belfast, UK, was not needed.

The review of the literature was performed in PubMed with search criteria ‘sugammadex’ and ‘myasthenia gravis’. Inclusion criteria were patients treated with sugammadex, and articles in the English language, or at least having an abstract in English containing neuromuscular data, including doses of NMBA and sugammadex. These publications were collected and analysed for neuromuscular management including efficacy and safety, NMBA used, monitoring data, the dose of sugammadex and the reversal times. Anaesthesia management was evaluated, including the continuation of pyridostigmine, and postoperative recovery and outcome.

Data from 21 patients were included in the analysis. Demographic information, the total dose of pyridostigmine and the type of surgery performed are summarised in Table 1. Pyridostigmine was continued preoperatively in all patients.

Table 1

Table 1

Perioperative and postoperative standard monitoring of the patients consisted of electrocardiograph, oxygen saturation and blood pressure using either a noninvasive or an invasive technique, depending on the type of surgery and the patient's history. Patients were anaesthetised using either a total intravenous anaesthesia (TIVA) technique with a target-controlled infusion of propofol (target 3.0 to 6.0 μg ml−1) and infusion of remifentanil (0.1 to 0.4 μg kg−1 min−1), or with a bolus dose of propofol (1 to 2 mg kg−1) and sevoflurane (end-tidal concentration 1.0 to 2.0%) for maintenance of anaesthesia.

Neuromuscular monitoring was performed as defined in the guidelines for Good Clinical Practice in neuromuscular monitoring, by acceleromyography using a TOF-watch SX (N.V. Organon, Oss, Netherlands) in all patients. In each case, the ulnar nerve was supramaximally stimulated near the wrist with square wave pulses of 0.2 ms, delivered as a train-of-four (TOF) or posttetanic count (PTC). The contractions of the adductor pollicis muscle were measured quantitatively using acceleromyography. Recovery of neuromuscular function was defined as a TOF ratio of more than 0.9 or 90% of the baseline TOF ratio prior to NMBA administration.11,12 The level of neuromuscular blockade was defined as follows: intense (or profound) neuromuscular blockade, no responses to either TOF or PTC; deep neuromuscular blockade, response to PTC, but not to TOF stimulation; and moderate neuromuscular blockade, the reappearance of the response to TOF stimulation.12

Myasthenia patients were assessed as Osserman class II (n = 13) or III (n = 8). Most patients were female (13 vs. eight men). The average age was 56 years (range 26 to 80 years) and the average weight was 77.6 kg (range 54 to 123 kg). The average daily dose of pyridostigmine was 275 mg (range 0 to 480 mg). The neuromuscular management data, including NMBAs used, the maximum level of neuromuscular blockade, type of anaesthesia, sugammadex dose and the neuromuscular recovery characteristics, are summarised in Table 2.

Table 2

Table 2

The TOF ratios immediately before NMBA administration were more than 0.9 in all but one case, in which it was 0.45. Rocuronium was used in 13 patients and vecuronium in eight patients. The intubating dose of rocuronium and vecuronium ranged from 0.1 to 1.0 and 0.1 to 0.2 mg kg−1, respectively. In 18 patients, the initial intubating dose of NMBA was followed by a repeat dose of the same drug; in the remaining three cases, the patient received a single intubating dose of rocuronium. The maximal level of neuromuscular blockade was moderate in one patient (rocuronium), deep in seven patients (rocuronium) and intense (or profound) in 13 patients (rocuronium n = 11, vecuronium n = 2). All surgical procedures were uneventful. Upon completion of surgery, sugammadex 2 or 4 mg kg−1 was administered to reverse residual moderate (12 patients; rocuronium n = 10, vecuronium n = 2) or deep neuromuscular blockade (nine patients, rocuronium), respectively. The mean reversal time, which was defined as the time from administration of sugammadex to recovery of a TOF ratio of more than 0.9, was 79.7 s (range 30 to 268 s) for moderate neuromuscular blockade and 165 s (range 105 to 240 s) for deep neuromuscular blockade. For moderate neuromuscular block induced by either rocuronium or vecuronium, there was no significant difference in reversal times. A summary of neuromuscular characteristics is shown in Table 2. After the TOF ratio had remained stable (>0.9) for a few minutes, the trachea was extubated and the patient was transferred to the postanaesthesia care unit (PACU).

In both hospitals, the possibility of postoperative recurrence of neuromuscular blockade (recurarisation) was assessed by monitoring oxygen saturation, breathing pattern and respiratory rate in the PACU for at least 120 min after the administration of sugammadex. In the Martini General Hospital, the possibility of postoperative recurrence of neuromuscular blockade was also assessed by monitoring neuromuscular function in the PACU (TOF stimulation every 5 min for at least 30 min). Recurrence of neuromuscular blockade was defined as deterioration in clinical signs or as a relapse to a lower TOF ratio attributed to neuromuscular blockade.

No signs of recurarisation were reported in the PACU and no patient required admission to the ICU following surgery; all were discharged directly from the PACU to a surgical ward. Oral pyridostigmine was administered when patients were able to tolerate swallowing safely, which usually coincided with the scheduled timing of the drug.

The literature search on sugammadex and myasthenia gravis found 21 articles, of which 15 met the inclusion criteria. In one publication, the purpose was not to evaluate recovery after sugammadex but the difference in recovery of two different muscle groups. In the remaining 14 publications, which are presented in Table 3, 24 cases of patients with myasthenia gravis were described.13–25 In 23 cases, rocuronium was used to induce neuromuscular block; vecuronium was used in only one patient. The results of the literature search are discussed in the following section.

Table 3

Table 3

In all patients, the reversal of rocuronium or vecuronium-induced neuromuscular blockade by sugammadex was fast and complete. All 21 patients recovered after reversal with sugammadex to the initial preoperative level of neuromuscular function. The recovery times from deep neuromuscular blockade were slightly longer than the reversal times from moderate neuromuscular blockade. There was no significant difference in the recovery time of reversal from either rocuronium or vecuronium-induced neuromuscular blockade. Neuromuscular blockade was reversed in all patients within 4 min and no signs of residual curarisation or recurarisation occurred irrespective of the NMBA used.

Myasthenia gravis patients are challenging to the anaesthesiologist because even the smallest dose of NMBA can lead to profound (or intense) neuromuscular blockade with prolonged spontaneous recovery or inadequate reversal by neostigmine.5 However, neuromuscular blockade is needed to create optimal intubation conditions and avoid vocal cord sequelae such as postoperative hoarseness, oedema or haematoma of the vocal cords, or even lacerations of the vocal cords. Therefore, anaesthesiologists often administer small doses of NMBA, but these patients often need postoperative mechanical ventilation and are admitted to the ICU. There is wide variability in the response to NMBAs and it is impossible to predict the appropriate initial dose of NMBA in such patients.11

Myasthenia gravis patients have been shown to be resistant to the depolarising NMBA succinylcholine with an ED95 that is 2.6 times higher than that in the healthy patient population.26 Therefore, succinylcholine is not recommended in myasthenia patients because the usual doses of 1.5 to 2.0 mg kg−1 may not only induce an inadequate neuromuscular blockade but also well known undesirable side effects such as bradycardia.26,27

Short-acting NMBAs such as mivacurium (1 to 2 x ED95) are used in small doses and can result in acceptable neuromuscular blockade with safe recovery, as reported in several publications. However, the ED95 of these drugs in myasthenia gravis patients is unknown. The use of intermediate NMBAs such as rocuronium, vecuronium and cis-atracurium has been reported to be adequate, but often in reduced doses that ranged between 0.1 and 0.5 times the standard doses.5,23,28–33 The ED95 for vecuronium in myasthenia gravis patients is 56% of normal, but for rocuronium, the ED95 in these patients is unknown.2,24 However, rocuronium should be given in doses smaller than the standard dose for patients without the disease. In our patients, the intubating dose of rocuronium and vecuronium ranged from 0.1 to 1.0 mg kg−1 and from 0.1 to 0.2 mg kg−1, respectively.

Repeat administration of rocuronium or vecuronium was indicated in 18 patients in order to achieve satisfactory neuromuscular blockade throughout the surgical procedure. Three patients in the rocuronium group did not receive follow-up doses. One patient who had an initial TOF ratio of 0.45 received a single intubating dose of 0.15 mg kg−1, which resulted in deep neuromuscular blockade, sufficient for the surgical procedure. In the other two patients, a rapid sequence induction procedure was performed with rocuronium 1.0 mg kg−1, which was also sufficient for the whole surgical procedure.

As spontaneous recovery of neuromuscular blockade in myasthenia gravis is much slower than in patients without the disease, it is mandatory to apply objective quantitative neuromuscular monitoring and important to reverse neuromuscular blockade pharmacologically.24 Reversal of neuromuscular blockade leads to restoration of neuromuscular function to the preoperative level and prevents postoperative residual curarisation with the risk of increased morbidity and mortality.

Reversal of neuromuscular blockade in myasthenia gravis patients who are already receiving cholinesterase inhibitor medication is complicated by a variable response and unreliable effect.1,2,5 Moreover, patients using acetylcholinesterase inhibitors chronically may already have optimal inhibition of the enzyme, and reversal of nondepolarising neuromuscular blockade with these compounds is therefore not possible. Additional doses of cholinesterase inhibitors may even lead to a cholinergic crisis, characterised by muscle weakness, bradycardia and increased secretions and gut motility. 2,5,34,35 Rocuronium-induced neuromuscular blockade can be reversed by cholinesterase inhibitors such as neostigmine, edrophonium or pyridostigmine in some patients with myasthenia gravis. However, cholinesterase inhibitors have a number of undesirable side effects (bradycardia, bronchoconstriction, hypersalivation, abdominal cramps and nausea and vomiting), which can be counteracted by coadministration of muscarinic antagonists (atropine or glycopyrrolate). Importantly, such muscarinic antagonists also have side effects (blurred vision, dry mouth and tachycardia). Furthermore, cholinesterase inhibitors are unable to reverse deep neuromuscular blockade due to their mechanism of action.35,36

In our patients, the pre-NMBA TOF ratio ranged from 0.45 to 1.0 and administration of the NMBA resulted in a maximal depth of neuromuscular blockade ranging from a TOF ratio of 0 to 0.19, or a PTC of 0 to 1. After reversal of neuromuscular blockade with sugammadex, all patients recovered from neuromuscular blockade to their preoperative TOF ratio, indicating that sugammadex reversal was complete and led to a rapid reappearance of normal muscle activity in our patients with myasthenia gravis.

The results of our case series are in line with the results found in the literature. We reviewed publications describing the use of sugammadex for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. When used in the recommended dosage, the recovery was fast and complete. However, in two cases, moderate neuromuscular blockade was reversed with a lower dose of sugammadex than recommended (0.5 mg kg−1and additional doses of 1.5 and 1.25 mg kg−1).14,19 The recovery time (168 s) was available in only one of these reports.19

In another case, a very high dose of 12.0 mg kg−1 of sugammadex was administered.15 In this case, a patient with an Osserman-Jenkins score of IIIa and initial TOF ratio of 0.97 was given rocuronium 30 mg. At the end of surgery, monitoring showed a TOF ratio of 0.36 and several bolus doses of sugammadex (to a total of 12.0 mg kg−1) were administered before the patient's trachea was extubated at a TOF ratio of 0.71. The authors did not indicate clearly the cause or any consequences of the delay in recovery.

In one case in which vecuronium was used to induce neuromuscular blockade, sugammadex 3.0 mg kg−1 was administered, but no information about the level of neuromuscular blockade or the exact recovery time was provided.4

In most of the cases in which the depth of neuromuscular blockade was based on quantitative neuromuscular monitoring, sugammadex was administered in a dose of either 2.0 or 4.0 mg kg−1 for moderate or deep neuromuscular block, respectively. These recovery times were in line with the recovery times found in our patients and also, as seen in our patients, without signs of postoperative residual curarisation or recurarisation.13,16–25 This means that recommended doses of sugammadex 2.0 or 4.0 mg kg−1 have produced similar recovery times in all published myasthenia gravis patients for whom detailed information is available. These findings are also in line with the recovery times in patients without neuromuscular disease.

Patients with myasthenia gravis may present for any type of surgery and need to be evaluated preoperatively. This evaluation should include assessment of respiratory and bulbar function. A reduced forced vital capacity and poor bulbar function are strong indicators of risk that postoperative mechanical ventilation will become necessary.3 None of our patients needed postoperative mechanical ventilation and none was transferred to the ICU. Myasthenia gravis patients may also suffer from cardiac arrhythmias, such as atrial fibrillation and bradycardia.2 This may evoke complications when neuromuscular blockade is reversed with cholinesterase inhibitors and muscarinic antagonists such as atropine.

Preoperative optimisation of neuromuscular function is important and therefore cholinesterase inhibitors should be continued perioperatively.5,24 The TOF ratio in myasthenia gravis patients immediately prior to NMBA administration has frequently been reported to be less than 0.9 as a result of the disease itself, but also due to the effects of discontinuation of pyridostigmine.11 Discontinuation of cholinesterase inhibitors in combination with general anaesthesia, including neuromuscular blockade, may lead to weakness of pharyngeal muscles, disco-ordinated swallowing and airway obstruction, and a reduction of the ventilatory response to hypercapnia may result following anaesthesia.3,37,38 This may partly be explained by the lingering effects of hypnotic agents and the use of NMBAs. The quality and speed of reversal of muscle paralysis seen following sugammadex and the administration of pyridostigmine immediately following surgery should reduce this risk in patients with myasthenia gravis.

Reversal of neuromuscular blockade with sugammadex does not interfere with cholinergic transmission, and therefore, continuation of cholinesterase inhibitors does not affect the efficacy of reversal of neuromuscular blockade by sugammadex as seen in our patients, but also in the patients presented in the review of the literature. This strategy, including continuation of cholinesterase inhibitors and reversal with sugammadex, will preserve optimal neuromuscular function.

Reversal of neuromuscular blockade in myasthenia gravis by sugammadex both in our own patients and in the patients reported in the literature demonstrated rapid and complete recovery of neuromuscular function without signs of postoperative residual neuromuscular blockade. Importantly, postoperative residual neuromuscular blockade or recurarisation should not only be assessed in normal patients when indicated but also in the more vulnerable myasthenia gravis patients. This assessment should consist of quantitative neuromuscular monitoring in the PACU because evaluation of clinical signs of residual neuromuscular blockade or recurarisation is not reliable and lacks the accuracy to exclude the presence of residual neuromuscular blockade.39 Reversal of neuromuscular blockade by sugammadex may eliminate the risk of residual neuromuscular blockade in this vulnerable patient population, as reported in patients without myasthenia gravis.40 These findings are supported by results found in the literature.

Our cases series suggests that the combination of either rocuronium or vecuronium and sugammadex is beneficial in myasthenia gravis by eliminating the risk of residual paralysis.

We suggest that the perioperative management strategy for patients with myasthenia gravis should include assessment of respiratory and bulbar function, continuation of cholinesterase inhibitors, quantitative neuromuscular monitoring, administration of aminosteroidal NMBAs (rocuronium or vecuronium) and reversal of neuromuscular blockade with sugammadex.

This strategy represents a departure from traditional teaching. It is simple and easy to follow and is effective in all patients irrespective of the severity of their symptoms or the inter-patient variability seen in response to NMBAs. Finally, it adds many aspects of safety, particularly a greatly reduced need for postoperative mechanical ventilation in the ICU, and may prevent dangerous postoperative curarisation in this vulnerable patient population.

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Acknowledgements relating to this article

Assistance with the letter: none.

Financial support and sponsorship: none.

Conflict of interest: all three authors have provided lectures about sugammadex sponsored by the pharmaceutical company Merck Sharp & Dohme.

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References

1. Hirsch NP. Neuromuscular junction in health and disease. Br J Anaesth 2007; 99:132–138.
2. Briggs ED, Kirsch JR. Anesthetic implications of neuromuscular disease. J Anesth 2003; 17:177–185.
3. Dillon FX. Anesthesia issues in the perioperative management of myasthenia gravis. Semin Neurol 2004; 24:83–94.
4. Rudzka-Nowak A, Piechota M. Anaesthetic management of a patient with myasthenia gravis for abdominal surgery using sugammadex. Arch Med Sci 2011; 7:361–364.
5. Tripathi M, Kaushik S, Dubey P. The effect of the use of pyridostigmine and requirement of vecuronium in patients with myasthenia gravis. J Postgrad Med 2003; 49:311–315.
6. Arbous MS, Meursing AEE, van Kleef JW, et al. Impact of anesthesia management characteristics on severe morbidity and mortality. Anesthesiology 2005; 102:257–268.
7. Bom A, Bradley M, Cameron K, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl 2002; 41:266–270.
8. Amao R, Zornow MH, Cowan RM, et al. Use of sugammadex in patients with a history of pulmonary disease. J Clin Anesth 2012; 24:289–297.
9. Dahl V, Pendeville PE, Hollmann MW, et al. Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in cardiac patients undergoing noncardiac surgery. Eur J Anaesthesiol 2009; 26:874–884.
10. Osserman KE, Jenkins G. Studies on myasthenia gravis. Review of a twenty-year experience in over 1200 patients. Mount Sinai J Med 1971; 38:497–537.
11. Mann R, Blobner M, Jelen-Esselborn S, et al. Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology 2000; 93:346–350.
12. Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007; 51:789–808.
13. Nakamori E, Nitahara K, Sugi Y, et al. Reversal of rocuronium induced neuromuscular block with sugammadex in a patient with myasthenia gravis. Masui 2013; 62:972–974.
14. Sugawara A, Sasakawa T, Hasegawa N, et al. Administration of sugammadex to a patient with myasthenia gravis with fade of the train-of-four ratio. Masui 2011; 60:1082–1085.
15. Kiss G, Lacour A, d’Hollander A. Fade of train-of-four ratio despite administration of more than 12 mg/kg sugammadex in a myasthenia gravis patient receiving rocuronium. Br J Anaesth 2013; 110:854–855.
16. Sungur Ulke Z, Yavru A, Camci E, et al. Rocuronium and sugammadex in patients with myasthenia gravis undergoing thymectomy. Acta Anaesthesiol Scand 2013; 57:745–748.
17. Takeda A, Kawamura M, Hamaya I, et al. Case of anesthesia for thoracoscopic thymectomy in a pediatric patient with myasthenia gravis: reversal of rocuronium-induced neuromuscular blockade with sugammadex. Masui 2012; 61:855–858.
18. Garcia V, Diemunsch P, Boet S. Use of rocuronium and sugammadex for caesarean delivery in a patient with myasthenia gravis. Int J Obstet Anesth 2012; 21:286–287.
19. Jakubiak J, Gaszyński T, Gaszyński W. Neuromuscular block reversal with sugammadex in a morbidly obese patient with myasthenia gravis. Anaesthesiol Intensive Ther 2012; 44:28–30.
20. Komasawa N, Noma H, Sugi T, et al. Effective reversal of muscle relaxation by rocuronium using sugammadex in a patient with myasthenia gravis undergoing laparoscopic cholecystectomy. Masui 2011; 60:476–479.
21. Argiriadou H, Anastasiadis K, Thomaidou E, Vasilakos D. Reversal of neuromuscular blockade with sugammadex in an obese myasthenic patient undergoing thymectomy. J Anesth 2011; 25:316–317.
22. de Boer HD, van Egmond J, Driessen JJ, Booij LH. Sugammadex in patients with myasthenia gravis. Anaesthesia 2010; 65:653.
23. Petrun AM, Mekis D, Kamenik M. Successful use of rocuronium and sugammadex in a patient with myasthenia. Eur J Anaesthesiol 2010; 27:917–918.
24. de Boer HD, van Egmond J, Driessen JJ, Booij LH. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex. Rev Esp Anestesiol Reanim 2010; 57:181–184.
25. Unterbuchner C, Fink H, Blobner M. The use of sugammadex in a patient with myasthenia gravis. Anaesthesia 2010; 65:302–305.
26. Eisenkraft JB, Book WJ, Mann SM, et al. Resistance to succinylcholine in myasthenia gravis: a dose-response study. Anesthesiology 1988; 69:760–763.
27. Romero A, Joshi GP. Neuromuscular disease and anesthesia. Muscle Nerve 2013; 48:451–460.
28. Zahid I, Sharif S, Routledge T, Scarci M. Video-assisted thoracoscopic surgery or transsternal thymectomy in the treatment of myasthenia gravis? Interact Cardiovasc Thorac Surg 2011; 12:40–46.
29. Paterson IG, Hood JR, Russell SH, et al. Mivacurium in the myasthenic patient. Br J Anaesth 1994; 73:494–498.
30. Baraka A, Siddik S, Kawkabani N. Cisatracurium in a myasthenic patient undergoing thymectomy. Can J Anaesth 1999; 46:779–782.
31. Sanfilippo M, Fierro G, Cavalletti MV, et al. Rocuronium in two myasthenic patients undergoing thymectomy. Acta Anaesthesiol Scand 1997; 41:1365–1366.
32. Sungur Ulke Z, Senturk M. Mivacurium in patients with myasthenia gravis undergoing video-assisted thoracoscopic thymectomy. Br J Anaesth 2009; 103:310–311.
33. Seigne RD, Scott RP. Mivacurium chloride and myasthenia gravis. Br J Anaesth 1994; 72:468–469.
34. Osmer C, Vogele C, Zickmann B, Hempelmann G. Comparative use of muscle relaxants and their reversal in three European countries: a survey in France, Germany and Great Britain. Eur J Anaesthesiol 1996; 13:389–399.
35. Osmer C, Vogele C, Zickmann B, Hempelmann G. Effects of four anticholinesterase-anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure. Acta Anaesthesiol Scand 1998; 42:460–463.
36. Baurain MJ, Hoton F, D’Hollander AA, Cantraine FR. Is recovery of neuromuscular transmission complete after the use of neostigmine to antagonize block produced by rocuronium, vecuronium, atracurium and pancuronium? Br J Anaesth 1997; 77:496–499.
37. Heliopoulos I, Patlakas G, Vadikolias K, et al. Maximal voluntary ventilation in myasthenia gravis. Muscle Nerve 2003; 27:715–719.
38. Eikermann M, Zaremba S, Malhotra A, et al. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth 2008; 101:344–349.
39. Plaud B, DeBaene B, Donati F, Marty J. Residual paralysis after emergence from anesthesia. Anesthesiology 2010; 112:1013–1022.
40. Eikermann M, Brueckmann B, Sasaki N, et al. The use of sugammadex eliminated postoperative residual neuromuscular blockade at postanaesthesia care unit admission in abdominal surgery: 9AP 1-5. Eur J Anaesth 2013; 30:140–141.
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