Aug 5, 1992 - sure, 150/90 mm Hg; and oxygen saturation, 99%. The patient was ... arterial carbon dioxide below 50 torr and arterial oxygen above 100 torr.
Anesth Prog 40:127-129 1993
CASE REPORT
Total Intravenous Anesthesia with Propofol for Thymectomy in a Patient with Myasthenia Gravis James A. Roelofse, MMED, PhD, and Peter J. Roth, MMED Maxillo-facial Anesthesia, Oral and Dental Teaching Hospital, Faculty of Dentistry, University of Stellenbosch, Tygerberg 7505, South Africa
Experience with the use of propofol for induction and maintenance of anesthesia in patients with myasthenia gravis is limited. This case report documents the safe use of propofol in a patient with myasthenia gravis. Because of its unique pharmacodynamic and pharmacokinetic profile, propofol may be an ideal agent for safe use in the young patient with myasthenia gravis.
CASE REPORT
A 22-yr-old, 58-kg female with a diagnosis of MG was admitted for thymectomy under general anesthesia. She was being treated with 60 mg pyridostigmine orally four times daily. Preoperative investigations showed no evidence of cardiac, renal, or hepatic disease. The anticholinesterase medication was withdrawn 12 hr preoperatively. Premedication consisted of 10 mg diazepam orally 60 min before induction of anesthesia. On arrival in the operating theater, an intravenous cannula was inserted in a vein on the dorsum of the hand under local anesthesia. A Dinamap adult/pediatric vital signs monitor (Critikon, Tampa, FL), Ohmeda Biox pulse oximeter (Bioximetry Technology, Boulder, CO), electrocardiograph, temperature monitor, and capnograph were connected to the patient. Train-of-four stimulation was applied to the ulnar nerve at the wrist every 10 sec to monitor neuromuscular function. Baseline vital signs were as follows: heart rate, 70 beats/min; rectal temperature, 37.0° C; blood pressure, 150/90 mm Hg; and oxygen saturation, 99%. The patient was preoxygenated with 100% oxygen via a face mask. Anesthesia was induced with propofol (3 mg/kg) and alfentanil (2 ,ug/kg), immediately followed by a continuous infusion of 10 mg/kg-hr of propofol using an automatic pump (WELMED P 1000 Infusion pump, WELMED, London, UK). The propofol infusion rate was stepped down to 8 mg/kg-hr after 10 min, and then to 6 mg/kg-hr after another 10 min for maintenance of anesthesia. A nasal endotracheal tube was inserted without the aid of a muscle relaxant. Throughout anesthesia the patient was ventilated with oxygen in nitrous oxide (FiO2 = 0.5), and the end-tidal carbon dioxide was maintained at 32 to 38 torr. No inhalational anesthetic agent was used. Five minutes before transstemal stemotomy the patient received intravenous sufentanil (5 ,ug/kg). The patient's intraoperative course was uneventful, with the heart rate remaining between 60 and 70 beats/ min, blood pressure 130-140/70-80 mm Hg, and rectal
yasthenia gravis (MG) is an autoimmune disease characterized by a reduction of as much as 70% to 89% in the number of functional acetylcholine receptors at the neuromuscular junction.1 It has a worldwide incidence of one per 20,000 and is more common in females than males (6:4 female:male ratio).2 MG is of particular interest to the anesthetist because neuromuscular function may be altered during general anesthesia. Patients with MG are known to be unusually sensitive to the neuromuscular-blocking effects of nondepolarizing muscle relaxants, agents that are commonly used during anesthesia.3 Myasthenics are also more sensitive than normal subjects to the neuromuscular effects of ether-type volatile anesthetic agents.4 There is no general agreement on the anesthetic management of the MG patient for thymectomy. The following report describes the successful use of intravenous propofol (Diprivan) for anesthesia in a young woman with MG.
Received August 5, 1992; accepted for publication September 10, 1993. Address correspondence to Dr. James A. Roelofse, Faculty of Dentistry, University of Stellenbosch, Private Bag Xl, TYGERBERG 7505, South Africa. C 1993 by the American Dental Society of Anesthesiology
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128 Propofol and Myasthenia Gravis
temperature 37.0 to 37.20 C. The procedure lasted 100 min.
Anticholinesterase therapy was reintroduced at the end of the operation, the patient receiving 0.5 mg neostigmine intravenously, which was repeated after 4 hr. The patient was awake and breathing spontaneously at the end of the procedure. The suitability for extubation was then assessed. The patient had a sustained grip strength, a tidal volume of 8 mL/kg, and was able to maintain arterial carbon dioxide below 50 torr and arterial oxygen above 100 torr. The patient was extubated in the recovery room, where the ability to cough and maintain a headlift for 5 sec was tested. Oxygen was delivered via a face mask. The patient was transferred to the intensive care unit. Postoperative analgesia was provided by intramuscular meperidine (1 mg/kg as needed) and diclofenac (75 mg every 12 hr). Oral anticholinesterase therapy was reintroduced at half the preoperative dosage. The postoperative course was uneventful.
DISCUSSION
Thymectomy as a surgical treatment for MG was successfully introduced by Blalock.5 Early thymectomy is now the treatment of choice for most MG patients. Patients should ideally be admitted for surgery during a remission. A thorough physical examination must be carried out, as MG is sometimes associated with other diseases.6 Most patients are on pyridostigmine therapy, and the dose should be adjusted to individual need. Some anesthetists reduce the dose of pyridostigmine preoperatively by as much as 20%.6 Most MG patients for thymectomy, as in our case, are relatively young. Therefore, the routine use of postoperafive ventilation7 has been challenged. Early extubation has been proposed. If this is being planned, the anesthetist must use an anesthetic technique not associated with delayed recovery or postoperative respiratory depression. However, MG patients may have compromised respiratory function postoperatively. The use of an agent that is cleared from the body quickly may make the difference between routine, uneventful recovery and having to place the MG patient on a ventilator in an intensive care unit. In the past, many different anesthetic techniques have been used.346 Traditionally, great reliance has been placed on the volatile anesthetic agents for induction and maintenance of anesthesia in MG patients.b These agents may be associated, however, with delayed recovery after anesthesia. MG patients are also more sensitive than normal patients to neuromuscular depression by the volatile anesthetic agents.' From a theoretical standpoint, isoflu-
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rane, because of its low fat solubility and its rapid and almost complete elimination by the lungs, should ensure that recovery from its neuromuscular depressant effect is rapid. Nilsson and MUller8 demonstrated, however, that isoflurane has approximately twice the neuromuscular depressant effect on myasthenic neuromuscular transmission as does halothane. Isoflurane can provide good intubating and operating conditions without the need for muscle relaxants. MG patients are known to be quite sensitive to the neuromuscular blocking effects of nondepolarizing muscle relaxants.3 For this reason volatile anesthetic agents have become more popular. Nevertheless, patients with cardiovascular disease may not tolerate the effects of the volatile anesthetic agents. Pancuronium and tubocurarine have been used for muscle relaxation in MG patients.6 There are also several reports of the successful use of vecuronium.9 Eisenkraft6 feels that, of the nondepolarizing muscle relaxants, atracurium presents a good choice because of its short duration of action and reliable pharmacokinetics. The choice of a nondepolarizing muscle relaxant depends on the personal preference of the anesthetist; monitoring of neuromuscular transmission is, however, mandatory. MG patients can be intubated after use of an inhalational anesthetic agent, a nondepolarizing muscle relaxant, intravenous lidocaine, or even large doses of opioids. The lack of response to intubation in our patient-no coughing or bucking-may have been due to the intravenous propofol. Most authors agree that propofol is associated with respiratory depression, at least during the induction phase.10 This facilitates endotracheal intubation without neuromuscular blocking agents. When planning our anesthetic technique for this patient, we were looking for an anesthetic agent that would provide hemodynamic stability, a low incidence of postoperative nausea and vomiting, and smooth emergence from anesthesia. After using propofol for induction and maintenance of anesthesia, the most striking features in our case were the fast recovery from anesthesia, the rapid orientation, and the minimal interference with psychomotor activity and coordination after prolonged anesthesia. With any anesthetic technique, one should be concerned about the possibility of intraoperative awareness. No such problems were encountered in our case. Due to its pharmacokinetics and pharmacodynamics" propofol could be a step towards the goal of an ideal anesthetic agent for MG patients. It is rapidly cleared from the body, primarily by hepatic metabolism (mainly conjugation). The drug is highly lipophilic and distributes extensively from the blood into tissues. Thus, even after many hours of infusion, recovery still depends on redistribution rather than elimination processes. Its metabolites have no pharmacological activity. Postoperative re-
Anesth Prog 40:127-129 1993
covery after propofol is faster than after halothane anes-
thesia.12 Propofol has been found to cause significant decreases in minute volume, especially in the first 4 min after administration.13 The changes in breathing pattem suggest that respiratory depression of propofol may result from a decrease in central respiratory drive. However, once the infusion is discontinued, there is rapid emergence from anesthesia.
CONCLUSIONS This study with propofol complements the results obtained in studies in which propofol was used for continuous infusion during anesthesia."1 The drug is associated with smooth induction, adequate anesthesia, absence of major side effects, fast recovery, and minimal postoperative nausea and vomiting. An infusion of propofol supplemented with the short-acting opioid analgesic sufentanil, provided satisfactory anesthetic conditions for our patient suffering from MG. REFERENCES 1. Nilsson E, Paloheimo M, Muller K, Heinonen J: Halothane-induced variability in the neuromuscular transmission of patients with myasthenia gravis. Acta Anaesthesiol Scand 1989; 33:395-401. 2. Osserman KE, Genkins G: Studies in myasthenia gravisreview of a 20 year experience in over 1,200 patients. Mount Sinai J Med 1971;38:497-537.
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3. Azar I: The response of patients with neuromuscular disorders to muscle relaxants: a review. Anesthesiology 1984;61: 173-187. 4. Eisenkraft JB, Papatestas AE, Sivak M: Neuromuscular effects of halogenated agents in patients with myasthenia gravis. Anesthesiology 1984;61:A307. 5. Blalock A: Tumors of the thymic region and myasthenia gravis. Am J Surg 1941;54:149-150. 6. Eisenkraft JB: Myasthenia gravis and thymic surgeryanaesthetic considerations. In: Gothard JWW, ed: Bailliere's Clinical Anaesthesiology, Vol. 1. London, Bailliere Tindall, 1987:133-162. 7. Baird WLM, Norris W: The immediate postoperative care of the myastenia patient following thymectomy. Br J Anaesth 1965;36:174-176. 8. Nillson E, Muller K: Neuromuscular effects of isoflurane in patients with myasthenia gravis. Acta Anaesthesiol Scand 1990; 34:126-131. 9. Pelton CI: Vecuronium in myasthenia gravis. Anaesthesia 1985;40:82-83. 10. Von Buelow S, Busse J, Kentgens A: First clinical experience with propofol. Anaesthesiol Int Care Med 1988;201:4246. 11. Dundee JW, Clarke RSJ: Propofol. Eur J Anaesthesiol 1989;6:5-22. 12. Motsch J, Boullay J: Eine Vergleichende Untersuchung zur Aufwachphase nach Disoprivan und Halothan-Anaesthesien im kindesalter. Fortschr Anaesth 1989;3:42-45. 13. Grounds RM, Maxwell DL, Taylor MB, Aber V, Royston D: Acute ventilatory changes during induction of anaesthesia with thiopentone or propofol in man. Br J Anaesth 1987;59: 1098-1102.
