Total Intravenous Anesthesia with Propofol for Transsternal Thymectomy in Myasthenia Gravis

David O’Flaherty, MB, FFARCSI,* John H. Pennant, MB, FCAnaes,* Krishna Rao, MD,? Adolf H. Giesecke, MD$ Department

of Anesthesiology,

Patients with myasthenia gravis (MC) represent a significant management problem for the anesthesiologist. Anesthetic concerns center on the MG patient’s unpredictable response to muscle relaxants and increased susceptibility to postoperative respiratory failure, resulting in prolonged dependence on mechanical ventilation. We describe the first reported use of total intravenous anesthesia with propofol to provide satisfactory surgkal conditions in two patients with MG undergoing trans. sternal thymectomy. Propofol is a suitable drug for intubation and continuous infusion anesthesia, allowing fine control of anesthetic depth, good operating conditions, and a recovery profile suitable for MG patients undergoing surgery. Keywords: Propofol; myasthenia gravis; thymectomy, transsternal; anesthesia, intravenous.

Introduction

Dallas, TX.

cle fatigue, ptosis, ophthalmoplegia, and other signs and symptoms develop secondary to the destruction of postsynaptic acetylcholine receptors.’ Patients with MC represent a significant management problem for the anesthesiologist. Anesthetic concerns center on the MC patient’s unpredictable response to muscle relaxants and increased susceptibility to postoperative respiratory failure, resulting in prolonged dependence on mechanical ventilation.zml Early surgical intervention in the form of transcervical or transsternal thymectomy has become a mainstay in the aggressive management of selected MG patients.’ In these case reports, we describe the previously unreported use of total intravenous (IV) anesthesia with propofol to provide satisfactory surgical conditions in two MG patients undergoing transsternal thymectomy.

Case Reports

Myasthenia gravis (MG) is an autoimmune disorder acterized by varying degrees of muscle weakness.

charMus-

*Assistant Professor tFellow SProfessor and Chairman Address reprint requests to Dr. O’Flaherty at the Department of Anesthesiology, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9068, USA. Received for publication July 26, 1991; revised manuscript cepted for publication December 5, 1991. 0 1992 Butterworth-Heinemann .I. Clin. Anesth. 4:241-244,

University of Texas,

1992.

ac-

Case 1 A 44-year-old woman who, at 16 years of age, had MG diagnosed by a positive edrophonium (Tensilon) test and repetitive low-rate nerve stimulation, was to undergo a transsternal thymectomy for progressive MG. Past medical history was significant for hypertension, which was responsive to diuretic therapy. Her oral medications included pyridostigmine 60 mg four times daily, plus 180 mg of the slow-release form at bedtime, and prednisolone 40 mg daily. Physical examination showed an obese (132 kg) woman with moderate ptosis. Blood pressure (BP) was 150/80 mmHg, heart rate (HR) 80 beats per minute (bpm), and respiration 16 breaths per minute. Preoperative respiratory function tests showed a restrictive defect, with 58% predicted vital capacity and 68% predicted total lung capacity. Arterial blood gases J. Clin. Anesth.,

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Case Reports were acceptable [arterial oxygen tension (Pa&) 97 mmHg, arterial carbon dioxide tension (PaCQ) 45 mmHg, pH 7.38, bicarbonate (HCO,) 24 mEq/L]. She continued her usual medications preoperatively, including the morning of surgery. On arrival in the operating room (OR), IV and radial artery catheters were inserted. Hydrocortisone 100 mg IV was given. Intraoperative monitoring included an electrocardiogram (ECG), pulse oximeter, noninvasive BP monitor, peripheral nerve stimulator, capnograph, and urinary catheter. After preoxygenation with loo?% oxygen ((IL’), general anesthesia was induced with propofol 2 mgikg and fentanyl 2 pgikg to the end point of loss of eyelash reflex. Direct laryngoscopy and tracheal intubation were performed without difficulty, with no evidence of coughing or bucking. Anesthesia was maintained using a continuous infu133 pg/ sion of propofol 167 kg/kg/ min for 10 minutes, kgimin for 10 more minutes, and 100 kgikgimin with further titration of‘ the infusion rate according to hemodynamic response. This infusion was supplemented with a total offentanyl2 pgikg given in two incremental doses. Mechanical ventilation with an air-O, mixture was continued throughout the case. Inhalational anesthetic drugs and neuromuscular blocking drugs were not used. Capnography was used to maintain an end-tidal partial pressure of carbon dioxide (Pt , CO,) of 35 mmHg. Arterial oxygen saturation (SpO,) using pulse oximetry remained above 98% throughout. No hemodynamic response to skin incision or sternotomy occurred, nor was there any patient movement in response to surgery. Following induction, the patient’s BP remained within 15% normal (150180 mmHg), with HR approximately 90 bpm. Total operating time was 190 minutes. Estimated blood loss was 550 ml. Intraoperative fluid administration included 2,100 ml of lactated Ringer’s solution. ‘I‘en minutes before the completion of surgery. the propofol infusion was reduced to a rate of 2.5 ~gikgimin; it was discontinued during skin closure. A total of 2,250 mg of propofol had been given. The patient opened her eyes 3 minutes later, responding to commands. The endotracheal tube was removed on demonstration of a maximal inspiratory force of -30 mmHg. The patient was observed in the OR for an additional 20 minutes, during which time she continued to demonstrate satisfactory respiration and mental status. Her SpO, remained at lOOc/c on supplementary 0, by face mask. The patient was transported to the postanesthesia care unit (PACU), where she received small incremental doses of IV morphine for postoperative analgesia. ‘I’he remainder of her postoperative course was unremarkable.

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Case 2 A 26-year-old, 76 kg male with ocular MG presented for thymectomy. The disease had been diagnosed 2 years earlier using a positive edrophonium (Tensilon) test. His symptoms were limited to diplopia and ptosis unrespon-

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sive to pyridostigmine. His present medication was prednisolone 60 mg orally daily. His past medical and surgical history was otherwise unremarkable. Physically examination showed a healthy patient with no discernible abnormalities and an adequate airway. Results of pulmonar) function tests and arterial blood gases were within normal limits [PaO, 9.5 mmHg, oxygen saturation 97’2, PaCO, 43 mmHg on room air]. ‘I‘hymectomy was proposed to improve the patient’s symptoms and prevent the development of more serious sequelae. On the morning of surgery, he was given prednisolone 60 mg and sodium citrate 30 ml orally. In the OR, he received hydrocortisone 100 mg IV. Intraoperativr monitoring included an ECG. pulse oximeter, noninvasive BP monitor. peripheral nerve stimulator. capnograph, and urinarv catheter. Following preoxygena;.ion. anesthesia was induced lvit 11 fentanyl 2.5 pgikg and propofol 2.0 mgikg to the end point of’ loss of ryelash reflex. Direct laryngoscopy and tracheal intubation were performed without difficult\. Anesthesia was maintained using a continuous infusion of’ propofol 167 kg/kg&n for IO minutes, 133 kg/kg/ min Ji)r IO more minutes. and 100 ~gikgimin with f’ilr(her titration of’ the infusion rate according to hemod\ namic response. This infusion was supplemented with f&tan)-I 2.5 pgikg. Mechanical ventilation with an air0, nrixtllre was continued throughout the case. Inhalational anesthetic dl-ugs and neuromuscular blockers were not used. (:apnography was used to maintain P, ,CO, a~ 35 mmHg. I’~11se oximetry remained at 98% throughollt. .I‘here was no hemodynan~ic response to skin incision or sternotomy and no patient movement in response to surgel-) ‘1‘0~1 operating time was 160 minutes. Blood 10s.~ u as 200 ml. Hen~od)namic and respiratory parameters remained lvithin acceptable limits. ‘I‘he infusion ~vas stopped LI~OII completion of’ skin ( losure. :\ total of’ I ,6.50 mg 01‘propofol had been given. sponEight minutes later, the patient began breathing later, he responded IO intaneo~~sl~. pl‘en minutes mands. i\f‘ter fulfilling the routine clinical criteria, he was extubated. IIe was observed in the OR for an additional 20 minutes, during which time he continued to demonstrate satisfactory respiration and mental SLILLIS. His SpQ remained at 100% on supplemental-!, 0: I)> f&e mask. BP was I:%)/74 mmHg, HR was 7.5 bpm. and respirator! rate was 24 breaths per minute. I‘he patient was transferred to the PACLT. where he continued to be easily aroused, with normal \,erbal and motor responses. ~l‘he patient did not require an! analgesia in the inmediate postoperative period. ‘I‘he postoperative course was unremarkable. Hydrocortisone 100 mg IV four times daily was continued until the morning after surgery, when his normal oral prednisolone regimen was resumed. Arterial blood gas analysis showed PaO, IO5 mmHg, PaCO, 34 mmHg, pH 7.49, and HCO, 29 mEq/I,, at which stage supplemental 0, w;ts discontinued. The patient did not experience an\ episodes of postoperative muscle weakness and was discharged to a general war-d. His subsequent hospital sta\ was uneventful.

TWA with propofol for thymectomy in myasthenia

Discussion MC; is a disease characterized by progressive muscle weakness and eventual respiratory failure. The most severely affected may develop bulbar and respiratory fatigue, which may require intensive therapy.’ In recent years, thymectomy has been increasingly recommended to achieve prolonged remission, producing an improvement in approximately 60% to 70% of patients.j,6 Anesthetic considerations in the MC patient include marked sensitivity to nondepolarizing skeletal muscle relaxants, the potential interaction of anticholinesterases with both the depolarizing and nondepolarizing muscle relaxants, and an increased risk of perioperative respiratory insufficiency requiring prolonged intubation. Impairment of neuromuscular transmission by nondepolarizing blocking drugs is enhanced to a varying degree by various halogenated anesthetics and is concentration dependent. Furthermore, maintenance of anesthesia with enflurane or isoflurane can substantially impede antagonism of nondepolarizing drugs by anticholinesterases.’ Several recent studies have suggested a role for the newer, shorter-acting relaxants atracurium and vecuronium, albeit at reduced doses.8,9 However, most anesthesiologists avoid muscle relaxants unless they are absolutely necessary. Potential complications may arise in MG from anticholinesterases to reverse neuromuscular blockade from nondepolarizing muscle relaxants. Regional anesthesia to produce muscle relaxation for surgery may be desirable for patients presenting in the early stages of MG. Thoracic epidural anesthesia for intrathoracic surgery has been used extensively. The benefit of optimal postoperative analgesia would be especially relevant in the MC; patient. Continuous IV infusions have been the subject of recent research following the development of hypnotic drugs with appropriate pharmacokinetic profiles.1” Potential advantages of continuous-infusion anesthesia, such as minimal cardiorespiratory depression and rapid recovery, could prove helpful in the management of MG.” Propofol has a large apparent steady-state volume of distribution (150 to 1,000 liters in a healthy 70 kg patient), and a loading dose is best administered prior to a continuous infusion to facilitate the rapid achievement of steady drug concentrations.” Following the loading dose, the infusion scheme we used involved a three-stage dose-reduction regimen for approximately the first 30 minutes of maintenance, at which stage changes in vital signs that indicated a response to surgical stimulation or lightening of anesthesia were controlled by increasing the infusion rate.13 We elected to intubate the trachea using propofol alone, since this drug has been shown to obtund airway reflexes and allow relatively easy intubation with minimal coughing in the majority of patients.14-I7 This maneuver also allowed us to avoid the complications associated with muscle relaxants. Although other IV induction drugs are used alone to intubate the trachea, this is not accomplished as satisfactorily as with propofol. McKeating

grads:

O’Flaherty

et al.

et al.‘5 found that visualization of the vocal cords by standard laryngoscopy was possible more often after propofol alone than after thiopentone alone. Pharyngeal and laryngeal reactivity were similarly depressed more frequently with propofol. De Grood et al.17 found greater relaxation of the vocal cords after induction of anesthesia with propofol in comparison with etomidate. While propofol alone is not the panacea for intubation, it depresses upper airway reflex activity more than other commonly used IV induction drugs. Our intubation dose of propofol 2 mgikg is lower than in other reports; however, this dosage must be considered against a background of concomitant opioid administration in patients suffering from MG. The avoidance of muscle relaxants with this anesthetic technique facilitates surgical access by making isolation of the phrenic nerves much easier. These nerves are often adherent to the lateral aspects of the thymus, and dissection is all the more difficult in individuals with a fatty mediastinum. The rapid elimination pharmacokinetics of propofol permitted prompt recovery of consciousness, airway reflexes, and respiratory function at the end of surgery, precluding a prolonged period of intubation and ventilation. Although inhalation anesthesia alone is an option to accomplish intubation, the early recovery associated with total IV anesthesia with propofol is possibly more suitable for MC patients. In conclusion, these case reports indicate that propofol by infusion offers one suitable technique for anesthesia for transsternal thymectomy. Titration of infusion rate according to patient needs affords good operating conditions, while the kinetic profile of the hypnotic drug aids rapid recovery and early extubation.

References 1. Seybold ME: Myasthenia gravis: a clinical and basic science review.,JAMA 1983;250:2516-21. 2. Sivak ED, Mehta A, Hanson M, Cosgrove DM: Postoperative ventilatory dependency following thymectomy for myasthenia gravis. Clove Clzn Q 1984:51:585-g. 3. Gracey DR, Divertie MB, Howard FM, Payne WS: Postoperative respiratory care after transsternal thymectomy in myasthenia gravis. A Y-year experience in 53 patients. Chest 1984;86:67-71. 4. Grant RP,Jenkins LC: Prediction of the need for postoperative mechanical ventilation in myasthenia gravis: thymectomy compared to other surgical procedures. Can Anaesth Sot J 1982;29:112-6. 5. Mantegazza R, Beghi E, Pareyson D, Antozzi C, Peluchetti D: A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy. J Neural 1990;237:339-44. 6. Papatestas AE, Genkins G, Kornfeld P: Effects of thymectomy in myasthenia gravis. Ann Surg 1987;206:79-88. Baurain M, d’Hollander A, Melot C, Dernivoi B, Barvais L: Effects of residual concentrations of isoflurane on the reversal of vecuronium-induced neuromuscular blockade. Anesthesiology 1991;74:474-8. Baraka A, Dajani A: Atracurium in myasthenics undergoing thymectomy. Anesth Analg 1984;63: 1127-30.

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Case Reports 9. Ward S, Wright DJ: Neuromuscular blockade in myasthenia gravis with atracurium hesylate. Anuesthesia 1984;39:51-3. 10. Cockshott ID, Briggs LP, Douglas ElJ. White M: Pharmacokinetics of propofol in female patients. RrJ Anaerth 1987;59: 1103% 10. eval1 1. Kashtan H, Edelist G, Mallon J, Kapala I): Comparative uation of propofol and thiopentone for total intravenous anaesthesia. Cnn J Ancwsth 1990;37:170-6. 12. Gepts E, Carnu F. Cockshott ID, Douglas EJ: Disposition of propofol administered as constant rate intravenous infusions in humans. ilnnrth Adg 1987:66:1256-63. 13. Roberts FL, Dixon J, Lewis GTK, Tackley KM, Prys-Roberts

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(:: Itlduction and maintenance of’pr-opofol anaesthesia. A mat,ual infusion scheme. Armedhe,& 19X8:43: 14-7. Callar SK: Propofol allows intuhation without relaxants [Abstract]. Ane.&usiolog? 1990;73:A22. McKeating K, Bali IM. Dundee JW: The effects of thiopenAnarthewr tone and propofol on upper airway integrity. 19X8:43:638-40. Keaveney JP. Knell cl: Intubation under induction doses of propoli~l. ,Ancmth& 1988;43:80I. De (;I-ood P, Mitsukuri S, Van Egmond J, Kutren JyI. ( .I ul J F: (Comparison of etomidate and propofol for anesthesia in microlar\ ngeal surgerv. ,~rmr.sthe.~itr 1987;42:366-72.

Total intravenous anesthesia with propofol for transsternal thymectomy in myasthenia gravis.

Patients with myasthenia gravis (MG) represent a significant management problem for the anesthesiologist. Anesthetic concerns center on the MG patient...
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