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Myasthenia gravis: a careful perioperative anesthetic management of coronary artery bypass grafting.

ABSTRACT

Nowadays, even hazardous cardiac surgery can be performed on patients with autoimmune diseases like myasthenia gravis. It requires a sensitive perioperative anesthetic approach especially in relation to nondepolarizing muscle relaxant administration. Myasthenic patients produce antibodies against the end-plate acetylcholine receptors causing muscle weakness and sensitivity to nondepolarizing muscle relaxants that could lead to respiratory failure. Perioperative nurse care is critical for uncomplicated course of treatment; therefore, apprehension of surgical procedure should be helpful on an everyday basis. We describe successful management without any pulmonary complications of two patients with myasthenia gravis undergoing coronary artery bypass grafting. In addition, antiacetylcholine receptor antibodies concentrations were evaluated during treatment time. In conclusion, we have found that reduced titrated doses of cisatracurium may be safely used in patients with myasthenia gravis undergoing cardiac surgery without anesthesia and respiratory-related complications.

Keywords: anesthesia, cardiac surgery, cisatracurium, muscle relaxants, myasthenia gravis

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Recent advances in medicine have made cardiac surgery safer than decades ago. Most of the common cardiovascular procedures, for example, coronary artery bypass grafting (CABG), may be nowadays performed on older and sicker patients, even those with autoimmune disease. Myasthenia gravis (MG) is an autoimmune disease characterized by production of antibodies against the end-plate acetylcholine receptors resulting in decreased numbers of active units. It causes functional block of a neuromuscular junction manifested by weakness and fatigue of the voluntary muscles with improvement after resting (Drachman, 1978; Lindstrom, Seybold, Lennon, Whittingham, & Duane, 1976). Therefore, myasthenic patients are sensitive to nondepolarizing muscle relaxants (Baraka, 1992), including cisatracurium (Baraka, Siddik, & Kawkabani, 1999), and requirements for them during anesthesia are patient dependent (Baraka et al., 1999; Nilsson & Meretoja, 1990). What is more important is that success of the whole cardiac surgery with cardiopulmonary bypass institution (CPB) without any complications depends on very careful perioperative care, especially neuro nurse care. As we could expect, initial neurological state should be crucial for uneventful course of treatment. There are not many data concerning myasthenic patients undergoing cardiac surgery, yet some reports describe auspicious general anesthesia with incremental doses of nondepolarizing muscle relaxants for thymectomy or other elective surgery (Baraka, Taha, & Kawkabani, 2000; Itoh & Shibata, 2001; Itoh, Shibata, & Nitta, 2002; Mann, Blobner, Jelen-Esselborn, Busley, & Werner, 2000). In the present report, we describe the successful anesthetic management of two patients with MG undergoing CABG.

Case Report

Two men, a 73 year old (80 kg) and a 70 year old (70 kg), experienced angina pectoris followed by myocardial infarction and seropositive MG. Both were diagnosed with MG confirmed with electromyography, anticholinesterase tests, and serum levels of antiacetylcholine receptor (anti-AChR) antibodies. The detailed data concerning MG are shown in Table 1.

Preoperative cardiac examinations revealed a three-vessel disease with the ejection fraction of 53% and 56%, respectively. Patients were scheduled for normothermic CABG surgery: the first one with one arterial and three venous grafts and the other one with one arterial and two venous grafts. On the day preceding surgery, muscle strength and bulbar system were found normal. Respiratory function tests revealed vital capacity (VC) of 103% (percentage of predicted values), forced VC (FVC) of 111%, and forced expiratory volume in 1 second of 121% for the first patient and VC of 88%,+ FVC of 82%, and forced expiratory volume in 1 second of 100% for the second patient. Arterial blood gases were within nonnal ranges.

The patients received routine myasthenic drugs on the morning of surgery (Table 1). Hydroxyzine (Hydroxyzinum) of 0.5 mg/kg intramuscular and morphine (Morphini Sulfas) of 5 mg intramuscular were injected as premedication 1 hour before the induction of anesthesia. Esomeprazole (Nexium) of 40 mg and hydrocortisone (Corhydron 100) of 100 mg intravenous were administered. In the operating room, intravenous and radial artery catheters were inserted, and standard intraoperative monitoring was applied. After preoxygenation (100% oxygen), general anesthesia was induced with 0.3 mg/kg of etomidate (Etomidate-Lipuro) and 5 [micro]g/kg of fentanyl (Fentanyl). TOF GUARD (BioMeter International, Odense, Denmark) was applied, and after stabilizing the continuous response for the ulnar nerve stimulation with a supramaximal stimulus, the baseline height of the first twitch ([T.sub.o]%) and train-of-four ratio (TOF%) were measured. Amplitude of the first twitch response ([T.sub.1]) of each train compared with control response ([T.sub.1]/[T.sub.0]) and the [T.sub.4]/[T.sub.1] (TOF%) were recorded every 15 seconds. After baseline measurements, the initial dose of 10 [micro]g/kg of cisatracurium (Nimbex) was administered. The next incremental dose of 10 [micro]g/kg of cisatracurium was given when three consecutive twitch responses ([T.sub.1]/[T.sub.0]) remained unchanged. At the neuromuscular blockade of <90%, additional incremental doses of 10 [micro]g/kg of cisatracurium were added until 90% or more blockade was achieved (Table 2). Trachea was intubated, anesthesia was maintained with midazolam (Midanium), and fentanyl infusions were titrated at a variable rate according to hemodynamic responses. Lungs were ventilated with an air-oxygen mixture, and normocapnia was maintained. In addition, small dose of sevoflurane (Sevorane; 0.4%-0.6%) was used until cardiopulmonary bypass was instituted. Body temperature measured at the esophagus was maintained at 34.0[degrees]C-36.9[degrees]C.

The time from the end of cisatracurium injection until maximum neuromuscular block (onset time), degree of maximal block, and the time of recovery of the first twitch in TOF to 25% of the control value (recovery time) were recorded (Table 2). Maintenance doses of 0.015 mg/kg of cisatracurium were administered at recovery of TOF ratio to 25%, and time intervals between doses were monitored. In the first patient, after second maintenance dose resulting in 100% blockade, doses were reduced to 0.01 mg/kg.

The typical CPB technique and normothermia were applied. Weaning from CPB was carried out uneventfully with inotropic support and vasodilator therapy. There were no diaphragmatic or other muscle movements during the procedure; at the end of anesthesia, TOF ratios were 100% and 96%, respectively.

After surgery, patients were transferred to the intensive care unit for elective overnight ventilation; midazolam and fentanyl infusions were discontinued early morning of the following day, no anticholinesterase drugs were added, and patients received their normal myasthenic therapy via the nasogastric tube. The first patient developed perioperative inferior myocardial infarction; with necessary tests performed and hemodynamic parameters stable, the patient was qualified for noninvasive treatment. In the second patient, the postoperative course was uneventful. In the morning of the day after surgery, both patients were awake and with logical contact. The FVC measured with a Wright's respirometer were 1.2 and 0.8 L, respectively; tidal volume was 7-10 ml/kg, and spontaneous respiratory rate was from 10 to 15 in both. Tracheal tube was removed, and oxygen was given via face mask. Blood gas tensions were within normal values before and after extubation. After extubation, Visual Analogue Scale scores were recorded every day to assess and manage pain (below Visual Analogue Scale score of 3).

Arterial blood samples for evaluation of serum anti-AChR antibody concentrations were taken before surgery, at the end of anesthesia, after extubation, and at discharge (Table 3). The second patient was discharged to the general ward on the third postoperative day, whereas the first one was discharged on the fifth day because of cardiac complications.

Discussion

Our case report shows the successful management of two myasthenic patients for normothermic cardiac surgery with titrated cisatracurium doses without prolonged postoperative artificial lung ventilation. It confirms previous findings (Asai et al., 2004; Hayashida et al., 2000) that such patients may safely undergo CPB for CABG with cisatracurium as a muscle relaxant.

There have been many approaches to manage myasthenic patients during major surgery. Some authors prefer general anesthesia without muscle relaxants (Ju-Mei, 2006; Kiran, Choudhury, Saxena, & Kapoor, 2000) with inhaled agents for inducing neuromuscular blockade (Nilsson & Muller, 1990; Nishi, Nakagawa, Komatsu, Natsuyama, & Tanaka, 1993). Others have shown sevoflurane as a sufficient sole anesthetic without muscle relaxants for myasthenic patients undergoing thymectomy (Kiran, Choudhury, Saxena, & Kapoor, 2000). Moreover, sevoflurane seems to be the best choice for cardiac surgery because of its cardioprotective properties (De Hert et al., 2002). However, deep inhaled anesthesia sufficient for intubation and prevention of any body movements is hazardous in cardiac surgery because of its hemodynamic side effects. Others prefer total intravenous anesthesia because propofol has lesser neuromuscular effects than sevoflurane especially in patients with MG (Itoh & Shibata, 2001; Suzuki et al., 1999). Successful total intravenous anesthesia using propofol without muscle relaxants in patients with MG was described (Ju-Mei, 2006). Propofol has also been widely used in cardiac anesthesia; however, it can also cause hemodynamic disturbances. Some authors recommend a balanced technique, including muscle relaxants with reduced and titrated incremental doses and neuromuscular monitoring (Baraka et al., 2000; Itoh et al., 2002; Mann et al., 2000).

Hypothermia during CPB reduces muscle strength in the presence of muscle relaxants or otherwise (Buzello, Schluermann, Schindler, & Spillner, 1985; Heier & Caldwell, 2006). Our patients undergone coronary revascularization with normothermic CPB; therefore, we were afraid of any unexpected movements hazardous for procedure. Cisatracurium was chosen because of its nonenzymatic degradation (Hofmann) to nonactive metabolic product and successful applications in myasthenic patients undergoing thymectomy (Baraka et ah, 1999, 2000). Administered drugs were reduced and given with titrated incremental doses because of varied demands for cisatracurium in this group of patients. On the other hand, sugammadex is now available, so neuromuscular blockade could be safely and fully antagonized by this agent even in patients with MG (Argiriadou, Anastasiadis, Thomaidou, & Vasilakos, 2011; De Boer, van Egmond, Driessen, & Booij, 2010), but not with cisatracurium. It requires to use aminosteroid type of muscle relaxant like vecuronium. Its degradation needs to employ hepar because of enzymatic process and burden additional work for this organ that could be disadvantageous for hepar during CPB. Small doses of sevoflurane were administered for cardiac protection (De Hert et ah, 2002) despite the fact that it augmented neuromuscular block in myasthenic patients (Baraka et ah, 2000; Itoh & Shibata, 2001). In addition, sevoflurane was discontinued at the time of CPB institution.

There are reports about slightly prolonged respiratory insufficiency after cardiac surgery in myasthenic patients. Authors (Aps & O'Sullivan, 1987) describe a patient undergoing cardiac surgery under general anesthesia combined with incremental doses of atracurium extubated on the morning after surgery, yet soon reintubated, with fully successful extubation performed after further 24 hours. Others (Asai et ah, 2004) report the 3-day mechanical ventilation after CABG in patients with MG, without anesthetic regimen described, unfortunately.

Careful perioperative management is considered crucial for uneventful course of procedure, especially neuro nurse involvement. The most common complication among patients with MG is respiratory failure; its incidence relates to patient's initial neurological status and perioperative nursing care. It is obvious that nurses spend most of their time bedside that allows perceiving any worrisome symptoms and reacting properly. Normal bulbar system, lack of muscle strength impairment, and respiratory failure symptoms before procedure are crucial for the course of treatment, as shown in our report. Apprehension of surgical procedure should be helpful on everyday basis for nursing care of patients with MG undergoing cardiac surgery to avoid any complications.

Literature findings on the presence of anti-AChR antibodies and sensitivity to nondepolarizing neuromuscular blocking drugs in myasthenic patients undergoing cardiac surgery with CPB are inconsistent. It was shown that increased anti-AChR antibody levels were associated with increased sensitivity to vecuronium (Nilsson & Meretoja, 1990), but no relation between anti-AChR antibody levels and atracurium requirements was found (Hayashida et ah, 2000).

Our findings indicate that, in some myasthenic patients, the antibody concentration declined at the end of procedure and consecutively increased to stabilize near the initial value on discharge. A decrease in anti-AChR antibody concentration may have been caused by CPB institution, hemodilution, and adsorption of antibodies to the pump components. In some patients, however, that may not be the case because antibody concentration in our second patient did not change spectacularly throughout the hospitalization period. This issue requires further studies.

Summary

In conclusion, we found that reduced titrated doses of cisatracurium are safe during general anesthesia in myasthenic patients undergoing cardiac surgery once combined with continuous neuromuscular monitoring and careful perioperative management.

DOI: 10.1097/JNN.0000000000000138

References

Aps, C., & O'Sullivan, G. (1987). Myasthenia gravis and cardiac surgery. A case report. British Journal of Anaesthesia, 59(2), 265-268.

Argiriadou, H., Anastasiadis, K., Thomaidou, E., & Vasilakos, D. (2011). Reversal of neuromuscular blockade with sugammadex in an obese myasthenic patient undergoing thymectomy. Journal of Anesthesia, 25(2), 316-317.

Asai, K., Suzuki, K., Washiyama, N., Terada, H., Yamashita, K., & Kazui, T. (2004). Combined operation for myasthenia gravis and coronary artery disease. Japanese Journal of Thoracic and Cardiovascular Surgery, 52(2), 65-67.

Baraka, A. (1992). Anaesthesia and myasthenia gravis. Canadian Journal of Anaesthesia, 39(5), 476-486.

Baraka, A., Siddik, S., & Kawkabani, N. (1999). Cisatracurium in a myasthenic patient undergoing thymectomy. Canadian Journal of Anaesthesia, 46(8), 779-782.

Baraka, A. S., Taha, S. K., & Kawkabani, N. I. (2000). Neuromuscular interaction of sevoflurane-cisatracurium in a myasthenic patient. Canadian Journal of Anaesthesia, 47(6), 562-565.

Buzello, W., Schluermann, D., Schindler, M., & Spillner, G. (1985). Hypothermic cardiopulmonary bypass and neuromuscular blockade by pancuronium and vecuronium. Anesthesiology, 62(2), 201-204.

De Boer, H. D., van Egmond, J., Driessen, J. J., & Booij, L. H. J. D. (2010). Sugammadex in patients with myasthenia gravis. Anaesthesia, 65(6), 653.

De Hert, S. G., Pieter, W., Mertens, E., Van Sommeren, E. W., De Blier, I. G., Stockman, B. A., & Rodrigus, I. E. (2002). Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology, 97(1), 42-49.

Drachman, D. B. (1978). Myasthenia gravis. New England Journal of Medicine, 298(3), 136-142.

Hayashida, N., Kawara, T., Akasu, K., Kai, E., Kosuga, T., Chihara, S., ... Aoyagi, S. (2000). Coronary artery bypass surgery in a patient with myasthenia gravis. Kurume Medical Journal, 47(2), 173-175.

Heier, T., & Caldwell, J. E. (2006). Impact of hypothermia on the response to neuromuscular blocking drugs. Anesthesiology, 104(5), 1070-1080.

Itoh, H., & Shibata, K. (2001). Comparison between sevoflurane and propofol neuromuscular effects in a patient with myasthenia gravis: Effective doses of vecuronium. Anesthesiology, 95(3), 803-805.

Itoh, H., Shibata, K., & Nitta, S. (2002). Sensitivity to vecuronium in seropositive and seronegative patients with myasthenia gravis. Anesthesia and Analgesia, 95(1), 109-113.

Ju-Mei, N. (2006). Total intravenous anesthesia with propofol and remifentanil for video-assisted thoracoscopic thymectomy in patients with myasthenia gravis. Anesthesia and Analgesia, 703(1), 256-257.

Kiran, U., Choudhury, M., Saxena, N., & Kapoor, P. (2000). Sevoflurane as a sole anaesthetic for thymectomy in myasthenia gravis. Acta Anaesthesiologica Scandinavica, 44(3), 351-353.

Lindstrom, J. M., Seybold, M. E., Lennon, V. A., Whittingham, S., & Duane, D. D. (1976). Antibody to acetylcholine receptor in myasthenia gravis: Prevalence, clinical correlates, and diagnostic value. Neurology, 2(5(11), 1054-1059.

Mann, R., Blobner, M., Jelen-Esselborn, S., Busley, R., & Werner, C. (2000). Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology, 93(2), 346-350.

Nilsson, E., & Meretoja, O. A. (1990). Vecuronium dose-response and maintenance requirements in patients with myasthenia gravis. Anesthesiology, 73(1), 28-32.

Nilsson, E., & Muller, K. (1990). Neuromuscular effects of isoflurane in patients with myasthenia gravis. Acta Anaesthesiologica Scandinavica, 34(2), 126-131.

Nishi, M., Nakagawa, H., Komatsu, R., Natsuyama, T., & Tanaka, Y. (1993). Neuromuscular effects of sevoflurane in a patient with myasthenia gravis. Journal of Anesthesia, 7(2), 237-239.

Suzuki, T., Munakata, K., Watanabe, N., Katsumata, N., Saeki, S., & Ogawa, S. (1999). Augmentation of vecuronium-induced neuromuscular block during sevoflurane anaesthesia: Comparison with balanced anaesthesia using propofol or midazolam. British Journal of Anaesthesia, 83(3), 485-487.

Questions or comments about this article may be directed to Michal Kowalczyk, MD PhD, atmichalkowalczyk@vp.pl. He is a Research Assistant and Specialist in Anesthesiology and Intensive Therapy, 1st Department of Anesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.

Andrzej Nestorowicz, MD, is a Professor and Specialist in Anesthesiology and Intensive Therapy, Head of 1st Department of Anesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.

Katarzyna Stachurska, MD, is an Assistant and Specialist in Anesthesiology and Intensive Therapy, 1st Department of Anesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.

Anna Fijalkowska, PhD MD, is a Research Assistant and Specialist in Anesthesiology and Intensive Therapy, 1st Department of Anesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.

Janusz Stazka, MD, is a Professor and Specialist in Cardiosurgery, Department of Cardiosurgery, Medical University of Lublin, Lublin, Poland.

The authors declare no conflicts of interest.
TABLE 1. Medical History and Preoperative Treatment of Myasthenia
Gravis

Patient   Osserman     Duration of     Thymectomy
No.        Class     Disease (Years)   (Years Ago)    Crisis Rate (a)

1            MB            20           Yes (17)     Once/17 years ago
2            MB             5              No        Once/5 years ago

                       Treatment (mg/day)

Patient
No.       Pyridostigmine   Prednisone   Azathioprine

1              240             10            No
2              480             45           100

(a) With mechanical ventilation support.

TABLE 2. Neuromuscular Data and Cisatracurium Administration

Patient   Baseline       End of         [T.sub.1]/[T.sub.0] (b)
No.        TOF (a)     Anesthesia:        Ratio (%) After
          Ratio (%)   TOF Ratio (%)   Cisatracurium Titration
                                           for Intubation
                                           ([micro]g/kg)

                                      10    20    30    40

1            100           100        13    56    88    96
2            96            96         61    74    93    --

Patient       Total       Onset Time   Recovery Time    Intervals
No.        Intubation     (Minutes)      (Minutes)       Between
              Dose                                     Maintenance
          ([micro]g/kg)                                   Doses
                                                        (Minutes)

1              40            5.17          51.6           24-38
2              30            2.13          20.08          10-30

Patient    Total Dose      Time of
No.       ([micro]g/kg)   Anesthesia
                          (Minutes)

1              100           285
2              189           266

(a) TOF%--train of four. (b) [T.sub.1]/[T.sub.0]: amplitude of the
first twitch response of each train compared with control response.

TABLE 3. Serum Antiacetylcholine Receptor Antibodies Level During
Hospitalization

Patient No.    Before      At the       After      At Hospital
              Surgery      end of     Extubation    Discharge
              (nmol/L)   Anesthesia    (nmol/L)     (nmol/L)
                          (nmol/L)

1              20.28        3.75         6.73         16.85
2              12.77        12.0         12.0         14.0
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Title Annotation:Case Study
Author:Kowalczyk, Michal; Nestorowicz, Andrzej; Stachurska, Katarzyna; Fijalkowska, Anna; Stazka, Janusz
Publication:Journal of Neuroscience Nursing
Article Type:Clinical report
Date:Jun 1, 2015
Words:2964
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