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Canadian Journal of Anesthesia 47:562-565 (2000)
© Canadian Anesthesiologists' Society, 2000
Clinical Report

Neuromuscular interaction of sevoflurane - cisatracurium in a myasthenic patient

Anis S. Baraka, MD FRCA, Samar K. Taha, MD and Nadine I. Kawkabani, MD

From the Department of Anesthesiology, American University of Beirut, Beirut, Lebanon.

Address correspondence to: Anis Baraka MD FRCA. Fax: 961-1-744464; E-mail: abaraka{at}aub.edu.lb


   Abstract
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 Abstract
Introduction
 Case report
 Discussion
 References
 
Purpose: To describe the influence of sevoflurane anesthesia on cisatracurium neuromuscular block in a myasthenic patient undergoing thymectomy.

Clinical features: A myasthenic patient (Osserman IIB) was managed for one year before surgery with 60 mg pyridostigmine qid, 50 mg immuran tid and 30 mg prednisone therapy. Pyridostigmine was interrupted three months before surgery, and five sessions of plasmapheresis were done within 13 days before surgery. The neuromuscular response was monitored by Datex electromyographic response to train-of-four stimulation of the ulnar nerve. Sevoflurane 4% decreased the T1/C ratio by 20%. Administration of 0.025 mg•kg–1 cisatracurium, during sevoflurane anesthesia, was followed by complete neuromuscular block for 45 min. Discontinuation of sevoflurane resulted, after 10 min, in recovery of the T1 which reached T1/C ratio of 50% after 30 min.

Conclusion: The marked sensitivity of this myasthenic patient to 0.5 x ED95 of cisatracurium can be attributed to potentiation of cisatracurium neuromuscular block by sevoflurane, as evidenced by the reappearance of the first twitch of the train-of-four response 10 min after sevoflurane was discontinued.


   Introduction
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 Abstract
 Introduction
Case report
 Discussion
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IN a previous report we showed that, in a myasthenic patient undergoing thymectomy, the non-depolarizing muscle relaxant cisatracurium resulted in a more marked neuromuscular block than in normal patients.1 This was attributed to the decreased "safety margin" of neuromuscular transmission in patients suffering from myasthenia gravis, with a subsequent increased sensitivity to non-depolarizing neuromuscular block.2–4

Previous reports have also shown that inhalational anesthetics such as halothane and isoflurane can depress neuromuscular transmission in myasthenic patients.5–6 Sevoflurane is an inhalation anesthetic with a low muscle-gas partition coefficient.7 No study has been published to demonstrate the neuromuscular effect of sevoflurane and its interaction with muscle relaxants in myasthenic patients.

The present report investigated the neuromuscular interaction of sevoflurane-cisatracurium in a myasthenic patient undergoing thymectomy.


   Case report
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 Abstract
 Introduction
 Case report
Discussion
 References
 
A 42-yr-old, 70 kg woman, who had suffered from myasthenia gravis for one year, was scheduled for transsternal thymectomy. The main complaints were dysphagia, diplopia, generalized moderate muscle weakness, denoting Osserman IIB classification. Acetylcholine receptor antibodies were detected in the patient's plasma 86,00 nmol–1L (normal value <0.4 nmol–1L), and repetitive nerve stimulation revealed 53% decrement. Computed tomography scan revealed normal sized thymus. The patient was treated with 60 mg pyridostigmine qid, 50 mg immuran tid and 30 mg prednisone daily po. Pyridostigmine was stopped three months before surgery. The patient underwent within the 13 days before surgery, five sessions of plasmapheresis, that were followed by marked clinical improvement.

Neuromuscular transmission was monitored three minutes before induction of anesthesia by electromyography (EMG) using a Datex relaxograph monitor. The ulnar nerve was stimulated supramaximally at the wrist every 20 sec and the resulting EMG response of the adductor pollicis muscle was displayed. The monitor uses the train-of-four (TOF) principle at a stimulus frequency of 2Hz, and computes the ratio of the first twitch of TOF to the control twitch (T1/C) ratio, as well as the ratio of the fourth twitch to the first twitch (T4/T1) ratio.

Anesthesia was induced and maintained by sevoflurane 4% in 3 L 50% N2O:O2. Five minutes after induction of anesthesia, the EMG monitor showed a 20% decrease of T1/C ratio when 0.025 mg•kg–1 cisatracurium (0.5 ED95) was injected iv. The trachea was intubated with a 7.5 mm endotracheal tube. Administration of cisatracurium produced complete neuromuscular block in 120 sec, and no twitch response was recorded during the following 45 min (FigureGo A). Sevoflurane was then turned off, and 10 min later, T1 appeared and reached T1/C of 50% after 30 min (FigureGo B). A mixture of 0.05 mg•kg–1 neostigmine and 0.02 mg•kg–1 atropine was then administered, and was followed after 10 min by complete recovery of neuromuscular transmission, as evidenced by a T4/T1 ratio of 1.0 (FigureGo C).



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  		FIGURE Electromyographic response to train-of-four stimulation of the ulnar nerve:

A. Sevoflurane 4% decreased T1/C ratio to 0.8 after five minutes. Administration of 0.025 mg•kg–1 cisatracurium, during continued sevoflurane anesthesia, resulted in complete neuromuscular block which lasted for 45 min.

B. Electromyographic tracing 10 min after discontinuation of sevoflurane. Recovery of the neuromuscular transmission reached T1/C ratio of 0.5 after 30 min.

C. Administration of 0.05 mg•kg–1 neostigmine at T1/C ratio of 0.5 resulted in complete recovery, T4/T1 ratio of 1.0, after 10 min.

 
Following recovery of neuromuscular transmission, N20 was discontinued. The patient became conscious, resumed adequate spontaneous respiration and the trachea was extubated. The postoperative course showed a marked improvement in muscle power.


   Discussion
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 Abstract
 Introduction
 Case report
 Discussion
References
 
Myasthenia gravis is an autoimmune disease8 resulting from the production of antibodies against the endplate acetylcholine receptors9 and, hence, the "safety margin" of the neuromuscular transmission is decreased.2,3 Thus, myasthenic patients are sensitive to non depolarizing muscle relaxants,4 including cisatracurium.1 Also, potent volatile anesthetics may impair neuromuscular transmission in the myasthenic patient.5,6 In our patient, administration of 0.025 mg•kg–1 (= 0.5ED95) cisatracurium following sevoflurane anesthesia, resulted in rapid and complete neuromuscular block which was maintained for 45 min. This contrasts with the normal clinical duration of cisatracurium neuromuscular block which is observed in non-myasthenic patients during barbiturate/nitrous oxide/opioid anesthesia, when the time to 25% twitch recovery ranges from 33-45 min after a single bolus of 0.1 mg•kg–1 (= 2 x ED95) cisatracurium,10 which is four times the dose used in our myasthenic patient.

The marked sensitivity of this myasthenic patient to a small dose of cisatracurium compared with normal patients or to our previously reported myasthenic patient1 may be a normal variation response of the myasthenic patients to muscle relaxants, to the preoperative cessation of anticholinesterase therapy, or to potentiation of cisatracurium neuromuscular block by sevoflurane. The relatively rapid recovery of neuromuscular transmission following discontinuation of sevoflurane suggests that sevoflurane can markedly potentiate cisatracurium neuromuscular block in myasthenic patients.

Inhalational anesthetics may affect the neuromuscular transmission by presynaptic inhibition of acetylcholine mobilization and release, as well as by a decreased postsynaptic response;10–12 the neuromuscular transmission is depressed in this order: sevoflurane, enflurane, isoflurane and halothane.11 Volatile anesthetics can also potentiate the neuromuscular block of non-depolarizing muscle relaxants in a concentration-dependent manner, by acting mainly at the post junctional membrane.11 A recent report has shown that sevoflurane produces time-dependent potentiation of vecuronium neuromuscular block.12 Potentiation of nondepolarizing block by sevoflurane may be exaggerated in the myasthenic patients.

Potent volatile anesthetics such as sevoflurane and isoflurane not only potentiate non-depolarizing blockers in a dose dependent manner but also delay recovery of the neuromuscular transmission and impair neostigmine antagonism:13 discontinuation of the anesthetic will enhance recovery and improve reversal.13 However, elimination of volatile anesthetics is time-dependent. Thus, if the administration of isoflurane or sevoflurane is discontinued at the time of reversal, the impaired antagonism with neostigmine is reduced but not eliminated.13 In our patient, sevoflurane was discontinued 30 min before reversal, when the T1/C ratio reached 0.5. Subsequent reversal with neostigmine completely antagonized the residual neuromuscular block.

In conclusion, the present report shows a marked potentiation of neuromuscular block following the combination of sevoflurane and cisatracurium in a myasthenic patient. We recommend neuromuscular monitoring and titration of the dose of cisatracurium whenever it is administered during sevoflurane anesthesia, particularly in myasthenic patients. Also, the volatile anesthetic should be discontinued prior to reversal of neuromuscular block in order to enhance recovery of neuromuscular transmission.

Accepted for publication March 3, 2000.


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

2 Elmquist D, Hofmann WW, Kugelberg J, Quastel DMJ. An electrophysiological investigation of neuromuscular transmission in myasthenia gravis. J Physiol (Lond) 1964; 174: 417–34.

3 Grob D, Namba T. Characteristics and mechanism of neuromuscular block in myasthenia gravis. Ann NY Acad Sci 1976; 274: 143–73.

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

5 Nilsson E, Paloheimo M, Müller K, Heinonen J. Halothane-induced variability in the neuromuscular transmission of patients with myasthenia gravis. Acta Anaesthesiol Scand 1989; 33: 395–401.[Medline]

6 Nilsson E, Muller K. Neuromuscular effects of isoflurane in patients with myasthenia gravis. Acta Anaesthesiol Scand 1990; 34: 126–31.[Medline]

7 Yasuda N, Targ AG, Eger EI II. Solubility of I-653, sevoflurane, isoflurane, and halothane in human tissues. Anesth Analg 1989; 69: 370–3.[Abstract/Free Full Text]

8 Simpson JA. Myasthenia gravis a new hypothesis. Scott Med J 1960; 5: 419–36.

9 Lindstrom JM, Lennon VA, Seybold ME, Whittingham S. Experimental autoimmune myasthenia gravis and myasthenia gravis: biochemical and immunochemical aspects. Ann NY Acad Sci 1976; 274: 254–74.[Abstract]

10 Belmont MR, Lien CA, Quessy S, et al. The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995; 82: 1139–45.[Medline]

11 Saitoh Y, Toyooka H, Amaha K. Recoveries of post-tetanic twitch and train-of-four responses after administration of vecuronium with different inhalation anaesthetics and neuroleptanaesthesia. Br J Anaesth 1993; 70: 402–4.[Abstract/Free Full Text]

12 Ahmed AAK, Kumagai M, Otake T, Kurata Y, Amaki Y. Sevoflurane exposure time and the neuromuscular blocking effect of vecuronium. Can J Anaesth 1999; 46: 429–32.[Abstract/Free Full Text]

13 Morita T, Tsukagoshi H, Sugaya T, Saito S, Sato H, Fujita T. Inadequate antagonism of vecuronium-induced neuromuscular block by neostigmine during sevoflurane or isoflurane anesthesia. Anesth Analg 1995; 80: 1175–80.[Abstract]




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