We present a patient with myasthenia gravis in whom sugammadex failed to restore the train-of-four ratio (TOFR) sufficiently. When the patient’s TOFR count had recovered to 2, we administered 2 mg/kg of sugammadex. However, the TOFR did not recover to the preoperative value. An additional 2 mg/kg of sugammadex also had no effect. We then administered 30 μg/kg of neostigmine which restored the TOFR to more than the preoperative value. We speculate that exacerbation of myasthenia symptoms during surgery interfered with recovery of TOFR after sugammadex administration.
From the Department of Anesthesiology, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Accepted for publication March 29, 2013.
The authors declare no conflicts of interest.
Reprints will not be available from the author.
Address correspondence to Yasuyuki Sugi, MD, Department: Anesthesiology, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma Jonan-ku Fukuoka, 814-0180 Japan. Address e-mail to firstname.lastname@example.org.
It is difficult to predict the effect of nondepolarizing neuromuscular blocking drugs and anticholinesterase medications in patients with myasthenia gravis (MG) because there is considerable variability in their sensitivity to these drugs.1 Because sugammadex binds plasma rocuronium, it may be an ideal drug for reversing neuromuscular block by this medication in MG patients. Recent case reports have described rapid and safe recovery after sugammadex-induced reversal of the effects of rocuronium in patients with MG.2–5
We present a patient with MG in whom the train-of-four ratio (TOFR) recovered to preoperative values after neostigmine administration, after 4 mg/kg of sugammadex had failed to restore the TOFR to more than the preoperative value. We obtained informed consent from the patient to publish this report.
A 26-year-old woman (weight 64 kg, height 165 cm) with MG was to undergo extended thymectomy. She had first presented with difficulty in speaking and eating 5 months before this admission. An evoked electromyography test had revealed fade in the left abductor pollicis brevis and trapezius muscles, and an edrophonium test was positive. By the time of the present admission, she was taking 80 mg of prednisolone on alternative days and was unable to wash her hair by herself because of weakness of her neck and arm muscles. Her symptoms varied considerably, worsening in the evenings and on the days without prednisolone. She had not taken anticholinesterase medications for 4 months because they had induced abdominal pain. Her preoperative serum concentration of acetylcholine receptor antibodies was 149.0 nmol/mL (<0.2 nmol/mL). Her electrocardiogram and spirometry results were within normal limits, and the Myasthenia Gravis Foundation of America score was IIa, which represents mild weakness affecting muscles other than ocular muscles, predominantly limb and axial muscles.6
During an extended thymectomy, electrocardiogram, noninvasive arterial blood pressure, pulse oximetry, capnography, and neuromuscular function (TOF-Watch SX, Organon, Dublin, Ireland) were monitored and recorded. Stimulating electrodes were applied to her left wrist after careful skin cleansing. An acceleration transducer was applied to the belly of the thumb. The patient did not receive preanesthetic medication, and anesthesia was induced with 3 μg/mL target-controlled infusion of propofol and 0.3 μg/kg/min of remifentanil was started simultaneously. Neuromuscular monitoring began after induction of anesthesia. The ulnar nerve was stimulated to a 5-second tetanus to shorten the stabilizing intervals. After calibration, a 5-minute stabilizing period was started. The TOFR was 0.74 before rocuronium administration. Rocuronium was administered in increments of 1 mg (0.015 mg/kg) to decrease the first twitch (T1) to <5% of control values. The T1 decreased to 3% of the control value after a total of 4 mg of rocuronium. After an additional 2 mg of rocuronium, the trachea was intubated with a 35 Fr double-lumen endobronchial tube (Mallinckrodt™ Endobronchial Tube; Covidien, Athlone, Ireland). Arterial blood pressure was measured invasively after tracheal intubation. Anesthesia was maintained with propofol (3 μg/mL target-control infusion) and remifentanil (0.1–0.3 μg/kg/min). Fentanyl 200 μg was administered during surgery. Two to six milligrams of rocuronium was administered whenever T1 or T2 appeared. In total, the patient received 28 mg of rocuronium intraoperatively. The operation time was 155 minutes. Postoperatively, she was given 2 mg/kg of sugammadex when her T1 had increased to 8%, which is when T2 also appeared. The T1 recovered to 95% of the control value 510 seconds after sugammadex administration. However, the TOFR recovered to only 0.55. Another 2 mg/kg of sugammadex was administered, 5 minutes after which the TOFR remained at 0.55. Since it was deduced that the low TOFR was not due to rocuronium-induced neuromuscular block, 30 μg/kg of neostigmine was administered. The T1 and TOFR recovered to 111% of the control value and 0.86, respectively, 5 minutes after neostigmine administration. Propofol and remifentanil were discontinued. The trachea was extubated once sufficient spontaneous respiration and recovery of consciousness had occurred. The TOFRs at 3 and 7 hours after sugammadex administration were 0.80 and 0.90, respectively. No cholinergic or myasthenic crisis and no respiratory complications occurred. The patient received 50 mg of prednisolone on alternative days, experienced no disability in daily life, and was able to ski 5 months after the operation.
The doses of rocuronium and obtained neuromuscular block were converted to log-dose and probit values. According to least square linear regression analysis, this patient’s median effective dose (ED50) and 95% effective dose (ED95) were 0.024 and 0.054 mg/kg, respectively. ED50 and ED95 values for healthy adults were 0.17 and 0.31 mg/kg, respectively.7
In the present case, the TOFR only recovered to 0.55 after 2 mg/kg of sugammadex and showed no further improvement after another 2 mg/kg of sugammadex. However, it recovered to 0.86 after neostigmine administration. We speculate that the main reason for the insufficient recovery of the TOFR was exacerbation of MG during the surgical procedure. Previous reports describe sugammadex administration as inducing safe and quick recovery from neuromuscular block in MG patients.2–5 We have found no case reports of MG patients requiring anticholinesterase medication after sugammadex administration.
MG is an autoimmune disease caused by autoantibodies against acetylcholine receptors. A myriad of factors can exacerbate the symptoms of MG, and exacerbation may result in myasthenic crisis.8 Factors that can contribute to worsening of MG symptoms include infection, fatigue, surgery (including thymectomy), thyroid disease, medications that affect the neuromuscular junction, and opioids.9,10 Six to thirty-four percent of patients have myasthenic crises after transsternal thymectomy.11–13 A study investigating 122 MG patients undergoing transsternal thymectomy reported that the risk factors for exacerbation of MG were preoperative bulbar symptoms, a history of preoperative myasthenic crisis, serum concentration of acetylcholine receptor antibodies >100 nmol/L, and intraoperative blood loss >1000 mL.14 The mean serum concentration of acetylcholine receptor antibodies in patients with postoperative myasthenic crisis was 204.3 ± 344.1 nmol/L, whereas the mean concentration was 35.5 ± 67.2 nmol/L in patients without postoperative myasthenic crisis.14 Thus, although serum concentrations of acetylcholine receptor antibodies correspond poorly with the clinical severity of the disease, patients with postoperative myasthenic crisis have tendencies to higher serum concentrations of acetylcholine receptor antibodies. The present patient did have bulbar symptoms preoperatively, and her serum concentration of acetylcholine receptor antibodies was >100 nmol/L (149 nmol/L).
In this patient, we confirmed that the TOFRs did not decrease 3 and 7 hours after neostigmine administration. Because the effective duration of neostigmine is 57 minutes,15 prolonged worsening of MG symptoms could have led to a continuing or further decrease in the TOFR. The patient experienced no pulmonary complications, myasthenic crisis, or decrease in TOFR. Thus, the decrease in TOFR seemed to be a temporary reaction to extended thymectomy.
We extubated the trachea when the TOFR had recovered to 0.86. Although a TOFR >0.7 is sufficient to restore tidal volume and vital capacity to preoperative values, a TOFR >0.9 is widely recommended for safe extubation and prevention of postoperative pulmonary complications.16,17 If this criterion was applied to MG patients, who often have depressed TOFR values preoperatively, few would qualify for tracheal extubation in the operating theater. Therefore, we perform tracheal extubation of MG patients once their TOFRs have recovered to preoperative values and they have sufficient tidal volume.18
We present a patient with MG in whom sugammadex failed to restore the TOFR sufficiently. The TOFR recovered to preoperative values after 30 μg/kg of neostigmine administration. Exacerbation of myasthenia symptoms during surgery may have been the main factor interfering with recovery of TOFR after sugammadex administration. This case demonstrates that sugammadex is not therapeutic when the muscle weakness has not been induced by an aminosteroidal neuromuscular blocker, and that quantitative neuromuscular monitoring in patients with MG should be mandatory.
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