Year : 2020 | Volume
| Issue : 2 | Page : 244-248
Myasthenia gravis and sugammadex: A case report and review of the literature
Sujana Dontukurthy1, Carrie Wisler2, Vidya Raman1, Joseph D Tobias3
1 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital; Department of Anesthesiology and Pain Medicine, The Ohio State University, College of Medicine, Columbus, Ohio, USA
2 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA
3 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital; Department of Anesthesiology and Pain Medicine, The Ohio State University, College of Medicine; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
Dr. Sujana Dontukurthy
Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, Ohio - 43205
Source of Support: None, Conflict of Interest: None
|Date of Submission||14-Nov-2019|
|Date of Acceptance||15-Nov-2019|
|Date of Web Publication||5-Mar-2020|
Anesthesia care during surgical procedures in patients with myasthenia gravis (MG) can be challenging, as these patients have increased sensitivity to neuromuscular blocking agents (NMBAs) and may be at high risk for postoperative weakness and respiratory failure. Even intermediate-acting NMBAs may have a prolonged effect resulting in residual weakness after reversal with acetylcholinesterase inhibitors (neostigmine). Sugammadex (Bridion®, Merck and Co, Whithouse Stations, New Jersey) is a novel pharmacologic agent that reverses neuromuscular blockade by encapsulating rocuronium or vecuronium. We report the perioperative management of a 13-year-old adolescent girl with MG undergoing thymectomy. The use of sugammadex for reversal of neuromuscular blockade is discussed and the previous reports regarding its use in patients with MG are reviewed.
Keywords: Myasthenia gravis; neuromuscular blockade; rocuronium; sugammadex
|How to cite this article:|
Dontukurthy S, Wisler C, Raman V, Tobias JD. Myasthenia gravis and sugammadex: A case report and review of the literature. Saudi J Anaesth 2020;14:244-8
|How to cite this URL:|
Dontukurthy S, Wisler C, Raman V, Tobias JD. Myasthenia gravis and sugammadex: A case report and review of the literature. Saudi J Anaesth [serial online] 2020 [cited 2020 Mar 30];14:244-8. Available from: http://www.saudija.org/text.asp?2020/14/2/244/280095
| Introduction|| |
Myasthenia gravis (MG) is an autoimmune disorder with antibodies directed against the acetylcholine receptor, thereby affecting neuromuscular transmission characterized by muscle weakness. The skeletal muscle weakness progresses with exercise and improves with rest. The prevalence is approximately 20 in 100,000 with women affected twice as often as men. In children, MG presents as either transient neonatal MG or juvenile myasthenia gravis (JMG). Neonatal MG occurs in 20% of infants born to mothers with active MG due to passive trans-placental passage of the antibodies. It presents with hypotonia and poor feeding with a spontaneous resolution by 2–3 months of age. Juvenile MG shares the same pathophysiology as adult MG but generally presents with ocular symptoms as opposed to the generalized skeletal muscle weakness that is seen in adults. The incidence of generalized symptoms varies from 25–75% in JMG.
The management in JMC is different from adults. In children, due to concerns regarding the adverse effects of long-term corticosteroid use including osteoporosis, growth retardation, and immunosuppression-linked malignancies, thymectomy is considered earlier than in adults. Anesthesia care during surgical procedures in patients with MG can be challenging, as these patients have increased sensitivity to neuromuscular blocking agents (NMBA) and may be at high risk for postoperative weakness and respiratory failure. We report the perioperative management of a 13-year-old adolescent girl undergoing thymectomy for JMG. The use of sugammadex, a novel agent for reversal of neuromuscular blockade, is discussed and the previous reports regarding its use in patients with MG are reviewed.
| Case Report|| |
Publication of this case report followed the regulations of the Institutional Review Board of Nationwide Children's Hospital. A 13-year-old, 78 kg adolescent girl, presented to the emergency department with a 2-month history of symptoms of generalized muscle weakness, which started with intermittent episodes of weakness in the legs. The diagnosis of JMG was confirmed by electromyography and elevated serum acetylcholine receptor antibodies. Initial treatment included pyridostigmine (60 mg by mouth every 4 h) and plasmapheresis on alternate days, which improved her neurologic symptoms. She was scheduled for elective thoracoscopic-assisted thymectomy. The preoperative physical examination was unremarkable. The NIF was -50 cmH2O and the vital capacity was 3300 mL (42 mL/kg). On the day of surgery, the patient was held nil per os for 8 h except for her usual morning dose of pyridostigmine. The patient was transported to the operating room and standard American Society of Anesthesiologists monitors were placed. Neuromuscular blockade was monitored using visual observation of the train-of-four (TOF). General anesthesia was induced with fentanyl (100 μg) and propofol (200 mg) followed by neuromuscular blockade with rocuronium (50 mg) to facilitate tracheal intubation. Anesthesia was maintained with desflurane (expired concentration 5–6%) and hydromorphone (total dose of 1 mg administered in increments). Intermittent doses of rocuronium (5 mg) were administered based on the TOF ratio. The surgical procedure, which lasted 120 min, was uneventful. At the completion of the surgical procedure, the patient's TOF count was 0/4, 20 min after the administration of the last dose of rocuronium (5 mg). Sugammadex (300 mg) was administered and within 10 min, a full reversal of residual neuromuscular blockade was demonstrated by return of the TOF to baseline. When the patient was awake with an adequate tidal volume, her trachea was extubated. The patient was transferred to the postoperative anesthesia care unit (PACU) and then admitted to the inpatient ward. The remainder of her postoperative course was unremarkable and she was discharged home on postoperative day 3.
| Discussion|| |
Normal neuromuscular transmission results from the release of acetylcholine from the presynaptic nerve terminal, its movement across the synaptic cleft, and binding to the postsynaptic nicotinic receptor on the sarcolemma of the skeletal muscle. Depolarization of the presynaptic axonal membrane opens calcium channels (P channel). The movement of calcium through the channels in the presynaptic membrane results in the movement of synaptic vesicles to and fusion with the membrane. This is followed by the release of acetylcholine into the synaptic cleft. After its release from the synaptic vesicles, acetylcholine diffuses across the synaptic cleft and binds to acetylcholine receptors on the postsynaptic membrane (sarcolemma). This results in depolarization of the sarcolemma, the release of calcium from the sarcoplasmic reticulum, and muscle contraction.
The acetylcholine receptor (nicotinic receptor on the sarcolemma) is a pentameric protein composed of five subunits. There are five possible subunits (alpha, beta, gamma, delta, and epsilon), each of which is encoded by a different gene. The acetylcholine receptor occupies the entire membrane from the outside of the muscle through the cell membrane to the inside and thereby regulates the transmembrane movement of ions. The receptor acts to convert the chemical stimulus (acetylcholine) into an electrical impulse that results in the depolarization of the sarcolemma. The depolarization of the sarcolemma results in the release of calcium from the sarcoplasmic reticulum (SR) and muscle contraction. Cessation of muscle contraction is mediated by the metabolism of acetylcholine by the enzyme acetylcholinesterase, which is present in the synaptic cleft. Once acetylcholine is metabolized, the sarcolemma can repolarize, thereby resetting the muscle for the next round of depolarization. Failure to metabolize acetylcholine that is bound to the receptor results in prolonged depolarization, inability to repolarize the sarcolemma, and cessation of further contraction.
Non-depolarizing NMBAs act as competitive antagonists of acetylcholine at the receptor of the neuromuscular junction. At the completion of the surgical procedure, medications (neostigmine, edrophonium) that inhibit acetylcholinesterase are administered to competitively reverse residual neuromuscular blockade and allow for spontaneous ventilation and tracheal extubation., For anticholinesterase inhibitors to be effective in reversing competitive blockade of neuromuscular transmission, the concentration of the NMBA in the synaptic cleft must be relatively low. The reversal of neuromuscular blockade by acetylcholinesterase inhibitors is likely to be adequate only if there is significant residual neuromuscular function present as demonstrated by TOF stimulation of a peripheral nerve.
Despite the use of appropriate doses of acetylcholinesterase inhibitors, residual neuromuscular blockade may be present in a significant number of patients during the postoperative period., This residual neuromuscular blockade may impact not only respiratory function but also upper airway patency, thereby compromising postoperative ventilation and increasing the incidence of critical postoperative respiratory events.,, Although the incidence is lower in children, residual neuromuscular blockade has been noted in 28.1% of pediatric patients with severe residual blockade (TOF ratio ≤0.7) present in 6.5%. In addition, although generally thought to potentiate neuromuscular function, neostigmine may actually have a negative impact postoperative respiratory function as it impairs upper airway dilator muscle activity.
Additional issues must be considered in patients with MG. Patients with MG have significant variability in sensitivity to both depolarizing and non-depolarizing NMBAs, even intermediate-acting agents such as atracurium or vecuornium. The enzyme butyrylcholinesterase is inhibited by cholinesterase inhibitors (pydridostigmine), thereby prolonging the duration of action of succinylcholine. When attempting to reverse the residual effect of non-depolarizing NMBAs, neostigmine may not be effective as acetylcholinesterase is already maximally inhibited by pyridostigmine. These factors magnify the potential for postoperative weakness and respiratory failure in patients with MG.
Alternatively, the short-acting NMBA, mivacurium, has been suggested as a suitable agent to allow for neuromuscular blockade to facilitate endotracheal intubation and yet have effects that rapidly dissipate without residual neuromuscular blockade.,, However, the supply of mivacurium has been variable in recent years and it is not uniformly available on hospital formularies. Endotracheal intubation can also be facilitated by inhalational or intravenous anesthetic agents without the need for NMBAs.,,
Sugammadex (Bridion®, Merck and Co, Whithouse Stations, New Jersey) is a novel pharmacologic agent, which was approved for clinical use in adults in December 2015 by the United States Food and Drug Administration (FDA). It reverses neuromuscular blockade with a mechanism that differs completely from acetylcholinesterase inhibitors, by encapsulating rocuronium or vecuronium. Although not specifically approved by the FDA for use in pediatric patients, there is significant literature describing its safe and effective use in infants and children with the suggestion that it offers the same advantages over neostigmine as those reported in adults.,,,,
Systematic searches of PubMed® and Google were conducted using the search terms sugammadex and myasthenia gravis (August 2019) to identify articles from the English language regarding the use of sugammadex in patients with myasthenia gravis. The abstracts from the publications were reviewed and those pertaining to the current subject matter were included for further review. In addition, the reference lists of these publications were reviewed to ensure that all reports regarding the use of sugammadex in patients with MG had been identified. This review revealed only one case report in the English language describing the use of sugammadex in a pediatric-aged patient with MG. The reported described the use of sugammadex to reverse neuromuscular blockade induced by rocuronium in a neonate with transient neonatal MG following surgical repair of pyloric stenosis. In addition to this single report in a pediatric patient, other anecdotal reports were identified in adults [Table 1]. These cases demonstrate the effective reversal of neuromuscular blockade by sugammadex in patients with MG. Neuromuscular blockade was induced by rocuronium in all of the cases except for one (reference 27 where the patient received vecuronium). Reversal was accomplished with sugammadex in doses ranging from 2–4 mg/kg.
|Table 1: Reports of the successful use of sugammadex in patients with myasthenia gravis|
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While the majority of cases have demonstrated the effective use of sugammadex to reverse neuromuscular blockade in patients with MG, failures have also been reported [Table 2].,,, Failure occurred despite large or repeated doses of sugammadex (total dose up to 16 mg/kg). These cases did not seem to relate only to the severity of illness as two of the patients had mild clinical symptoms and were undergoing elective surgical procedures. All 4 of the patients were chronically treated with pyridigostigmine, which is common practice in adults with MG. Of note, all four of the patients improved when a cholinesterase inhibitor (either neostigmine or pyridostigmine) was administered after sugammadex.
|Table 2: Reports of failures of sugammadex in patients with myasthenia gravis|
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One of the challenges of anesthesia care in patients with MG is the management of NMBAs. In many circumstances, NMBAs can be avoided or lower doses used to accomplish endotracheal intubation. In our patient, the initial dose of rocuronium was 50 mg or approximately 0.6 mg/kg. Although it is possible that a lower dose (5–10 mg) may have been effective or endotracheal intubation accomplished without an NMBA, the availability of sugammadex expands the clinical options for patients with underlying neuromuscular weakness. Prior to its availability, reversal of the effects of the NMBA regardless of the dose was problematic with the potential for residual neuromuscular blockade to result in postoperative weakness and respiratory failure. Sugammadex is a novel pharmacologic agent that reverses neuromuscular blockade by encapsulating rocuronium or vecuronium. In general, its effects are more complete than cholinesterase inhibitors with a limited chance of residual neuromuscular blockade even in healthy patients. The majority of the literature has demonstrated the potential utility of this agent in patients with MG. However, anecdotal reports emphasize the difficulties of caring for such patients as failures have been reported. Of note, reversal of neuromuscular blockade was eventually achieved with the use of a cholinesterase inhibitor (neostigmine or pyridostigmine) in addition to sugammadex. Anesthesia care during surgical procedures in patients with MG can be challenging, as these patients have increased sensitivity to NMBAs and may be at high risk for postoperative weakness and respiratory failure.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Papazian, O. Transient neonatal myasthenia gravis. J Child Neurol 1992;7:135-141.
Kim AG, Upah SA, Brandsema JF, Yum SW, Blinman TA. Thoracoscopic thymectomy for juvenile myasthenia gravis. Pediatr Surg Int 2019;35:603-10.
de Souza CM, Romero FE, Tardelli MA. Assessment of neuromuscular blockade in children at the time of block reversal and the removal of the endotracheal tube. Rev Bras Anestesiol 2011;61:145-9.
Meretoja OA. Neuromuscular block and current treatment strategies for its reversal in children. Paediatr Anaesth 2010;20:591-604.
Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg 2008;107:130-7.
Shorten GD. Postoperative residual curarisation: Incidence, aetiology and associated morbidity. Anaesth Intensive Care 1993;21:782-9.
Eriksson LI. The effects of residual neuromuscular blockade and volatile anesthetics on the control of ventilation. Anesth Analg 1999;89:243-51.
Ghoneim AA, El Beltagy MA. Comparative study between sugammadex and neostigmine in neurosurgical anesthesia in pediatric patients. Saudi J Anaesth 2015;9:247-52.
] [Full text]
Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth 2008;101:344-9.
Wainwright AP, Brodrick PM. Suxamethonium in myasthenia gravis. Anaesthesia 1987;42:950-7.
Eisenkraft JB, Jeffrey Book W, Papatestas AE. Sensitivity to vecuronium in myasthenia gravis: A dose-response study. Can J Anaesth 1990;37:301-6.
Patterson IG, Hood JR, Russell SH, Weston MD, Hirsch NP. Mivacurium in the myasthenic patients. Br J Anaesth 1994;73:494-8.
Seigne RD, Scott RP. Mivacurium chloride and myasthenia gravis. Br J Anaesth 1994;72;468-9.
Sungur Ulke Z, Senturk M. Mivacurium in patients with myasthenia gravis undergoing video-assisted thoracoscopic thymectomy. Br J Anaesth 2009;103:310-1.
Politis GD, Tobias JD. Rapid sequence intubation without a neuromuscular blocking agent in a 14-year-old female patient with myasthenia gravis. Paediatr Anaesth 2007;17:285-8.
El-Dawlatly AA, Ashour MH. Anaesthesia for thymectomy in myasthenia gravis: A non-muscle-relaxant technique. Anaesth Intensive Care 1994;22:458-60.
Alexander R, Olufolabi AJ, Booth J, El-Moalem HE, Glass PS. Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants. Anaesthesia 1999;54:1037-40.
Fodale V, Pratico C, Piana F, Caruso A, Lucanto T, Coniglio S, et al
. Propofol and remifentanil without muscle relaxants in a patient with myasthenia gravis for emergency surgery. Can J Anaesth 2003;50:1083-4.
Tobias JD. Current evidence for the use of sugammadex in children. Paediatr Anaesth 2017;27:118-25.
Ghoneim AA, El Beltagy MA. Comparative study between sugammadex and neostigmine in neurosurgical anesthesia in pediatric patients. Saudi J Anaesth 2015;9:247-52.
] [Full text]
Ozgün C, Cakan T, Baltacı B, Başar H. Comparison of reversal and adverse effects of sugammadex and combination of anticholinergic-anticholinesterase agents in pediatric patients. J Res Med Sci 2014;19:762-8.
Kara T, Ozbagriacik O, Turk HS, Isil CT, Gokuc O, Unsal O, et al
. Sugammadex versus neostigmine in pediatric patients: A prospective randomized study. Rev Bras Anestesiol 2014;64:400-5.
Rubin JE, Ramamurthi RJ. The role of sugammadex in symptomatic transient neonatal myasthenia gravis: A case report. Anesth Analg Case Rep 2017;9:271-3.
Kondo M, Yoshikawa Y, Terada H, Yamakage M. Anesthetic management of total aortic arch replacement in a myasthenia gravis patient under deep hypothermic circulatory arrest. Case Rep Anesthesiol 2019 (in press).
Casarotti P, Mendola C, Cammarota G, Della Corte F. High-dose rocuronium for rapid-sequence induction and reversal with sugammadex in two myasthenic patients. Acta Anaesthesiol Scand 2014;58:1154-8.
Sungur Ulke Z, Yavru A, Camci E, Ozkan B, Toker A, Senturk M. Rocuronium and sugammadex in patients with myasthenia gravis undergoing thymectomy. Acta Anaesthesiol Scand 2013;57:745-8.
Rudzka-Nowak A, Piechota M. Anaesthetic management of a patient with myasthenia gravis for abdominal surgery using sugammadex. Arch Med Sci 2011;7:361-4.
de Boer HD, van Egmond J, Driessen JJ, Booij LH. Sugammadex in patients with myasthenia gravis. Anaesthesia 2010;65:653.
Petrun AM, Mekis D, Kamenik M. Successful use of rocuronium and sugammadex in a patient with myasthenia. Eur J Anaesthesiol 2010;27:917-8.
Unterbuchner C, Fink H, Blobner M. The use of sugammadex in a patient with myasthenia gravis. Anaesthesia 2010;65:302-5.
Soyoral L, Gotkas U, Cegin MB, Baydi V. Successful use of sugammadex for caesarian section in a patient with myasthenia gravis. Rev Bras Anestesiol 2017;67:221-2.
Kim RK, Kim SY. Rapid return of spontaneous respiration after general anesthesia with sugammadex in a patient with myasthenia gravis. Kim J Lifestyle Med 2016;6:43-6.
Shah D, Dharmarajan A. Use of sugammadex in an octagenerian with myaesthenia gravis undergoing emergency laparotomy. J Clin Anesth 2017;37:109-10.
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.
Argiriadou H, Anastasiadis K, Thomaidou E, Vasilakos D. Reversal of neuromuscular blockade with sugammadex in an obese myasthenic patient undergoing thymectomy. J Anesth 2011;25:316-7.
Pühringer FK, Kristen P, Rex C. Sugammadex reversal of rocuronium-induced neuromuscular block in Caesarean section patients: A series of seven cases. Br J Anaesth 2010;105:657-60.
Fernandes HDS, Ximenes JLS, Nunes DI, Ashmawi HA, Vieira JE. Failure of reversion of neuromuscular block with sugammadex in patient with myasthenia gravis: Case report and brief review of literature. BMC Anesthesiol 2019;19:160.
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;21:286-7.
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;110:854-5.
Sugi Y, Nitahara K, Shiroshita T, Higa K. Restoration of train-of-four ratio with neostigmine after insufficient recovery with sugammadex in a patient with myasthenia gravis. AA Case Rep 2013;1:43-5.
[Table 1], [Table 2]