Anesthetic Management for a Patient with Kearns-Sayre Syndrome

Abstract

Kearns-Sayre syndrome (KSS), a form of mitochondrial myopathy, is an extremely rare disease accompanied by progressive external ophthalmoplegia, pigmented degeneration of the retina, and heart block [1,2]. We report a patient with KSS who underwent emergency surgery under general anesthesia uneventfully, but who developed respiratory depression and rate-dependent left bundle-branch block, postoperatively. Case Report A 51-yr-old male, weighting 63 kg, was admitted to our hospital with a chief complaint of right lower abdominal pain. He underwent exploratory laparotomy for possible appendicitis. His past medical history was remarkable as follows: KSS began at the age of 27 yr, and the definitive diagnosis of KSS was made by skeletal muscle biopsy when he was 37 yr old [1]. Four years prior to admission, the patient complained of palpitations and dyspnea on mild exertion. He developed peripheral edema and hepatomegaly. At 48 yr of age he received a cardiac pacemaker for complete atrioventricular block and received digitalis and verapamil for paroxysmal atrial tachycardia. On this admission, his arterial blood pressure was 92/70 mm Hg, and his heart rate was 66 bpm paced with atrial fibrillation. In addition to the three criteria of KSS, he had slight proximal muscular weakness and bilateral sensorineural hearing loss. Preoperative laboratory data showed increased white blood cell count and slight hepatic dysfunction. Chest radiograph showed an enlargement of the cardiothoracic ratio (64%). Echocardiography showed biventricular enlargement and diffuse hypokinesia, and a decreased left ventricular ejection fraction (35%). A diagnosis of dilative cardiomyopathy was made. Blood gases on room air were normal. The patient was premedicated with scopolamine 0.2 mg and hydroxyzine 25 mg intramuscularly. On arrival in the operating room, his arterial blood pressure was 145/90 mm Hg, and his heart rate was 60 bpm with artificial pacing rhythm. Before induction of anesthesia, an electromyogram (Relaxograph, Helsinki, Finland) was placed to obtain control values for neuromuscular block with electrical train-of-four stimulation to the right ulnar nerve. Thiopental 200 mg and vecuronium 6.3 mg (0.1 mg/kg) were given for induction of anesthesia. The trachea was intubated with an 8.5-mm endotracheal tube. Anesthesia was maintained with a mixture of nitrous oxide (3 L/min) and oxygen (3 L/min), and 0.2%-0.6% isoflurane, supplemented with a bolus intravenous (IV) injection of fentanyl (100 micro gram). Supplemental doses of vecuronium 1.9 mg (0.03 mg/kg) were administered when the value of T1 recovered to 25% of the control value. Prostaglandin E1 was administered at the rate of 0.05 micro gram centered dot kg-1 centered dot min-1 to reduce afterload. Arterial blood pressure and heart rate were stable (120/80 mm Hg, 60 bpm paced), as were percutaneous hemoglobin oxygen saturation (98%-100%), end-tidal carbon dioxide concentration (33-36 mm Hg), and rectal temperature (38.1 degrees C) during the course of surgery. Appendectomy with abdominal drainage was performed and the surgery was completed in 55 min. The estimated blood loss was 60 mL. Atropine sulfate 1 mg and neostigmine 2 mg were administered IV to reverse the muscle relaxant when the value of T1 recovered to 25% of the control value. After reversal, the tidal volume was more than 600 mL, the respiratory rate was 12-14 breaths/min, and the value of T1 reached 80% of the control value. The patient was fully awake, and his trachea was extubated. During surgery, lactated Ringer's solution, 500 mL, containing maltose and plasma expander (Hespander Registered Trademark; Kyorin Pharmaceutical Co., Ltd., Tokyo, Japan) 250 mL were given, and his urine output was 80 mL. Upon arrival at the intensive care unit (ICU), the patient complained of dyspnea and became cyanotic and unresponsive. He did not show airway obstruction, but was obviously weak and tachypneic. Oxygen was immediately administered via a mask. His blood pressure was 160/95 mm Hg, and heart rate was 100 bpm with atrial fibrillation. Arterial blood gas analysis revealed a pHa of 7.17, PaO2 of 139 mm Hg, PaCO2 of 72 mm Hg, and a base excess of -4.0 mM/L. He was tracheally reintubated and mechanically ventilated. Shortly after intubation, the electrocardiogram (ECG) showed a pattern of ventricular tachycardia later diagnosed as a rate-dependent left bundle-branch block Figure 1a, and for which lidocaine 60 mg was administered. The ECG pattern did not change, and arterial blood pressure and heart rate further increased to 170/110 mm Hg and 110 bpm. Five minutes later, his arterial blood pressure and heart rate decreased to 150/90 mm Hg and 80 bpm, and his ECG showed atrial fibrillation with ST-segment depression Figure 1b. At this time, blood gas analysis (FiO2 = 0.5) revealed a pHa of 7.34, PaO2 of 129 mm Hg, PaCO2 of 46 mm Hg, and a base excess of -1.2 mM/1. The patient was given diazepam 10 mg IV for sedation, and his blood pressure decreased to 80/40 mm Hg. Dopamine 3-5 micro gram centered dot kg-1 centered dot min-1 was started to support myocardial contractility and maintain urine output. Vital signs were stabilized, and the ECG returned to the preoperative pattern Figure 1c. The following morning he was fully awake and met all extubation criteria. His trachea was extubated, and he had an otherwise uneventful postoperative course.Figure 1: The changes in the electrocardiogram observed at the intensive care unit. a, Rate-dependent left bundle-branch block; blood pressure was 170/110 mm Hg and heart rate, 110 bpm. b, Atrial fibrillation with ST segment depression at 5 min after reintubation; blood pressure was 150/90 mm Hg and heart rate, 80 bpm. c, Artificial pacing rhythm after ventilation and sedation; blood pressure was 100/50 mm Hg and heart rate, 60 bpm.Discussion Only 267 cases of KSS have been reported since 1966, and there have been only a few reports in the literature regarding anesthesia management for patients with mitochondrial myopathies, including KSS [3-7]. Therefore, the knowledge of anesthetic considerations for this syndrome is very limited. Klockgether-Radke et al. [3] reported two cases of KSS for which propofol-alfentanyl or propofol-fentanyl with vecuronium was used without postoperative muscle hypotonia. Burns and Shelly [4] presented the anesthetic management of an infant with mitochondrial myopathy. Anesthesia was maintained with isoflurane and nitrous oxide in oxygen under spontaneous ventilation without postoperative complications. Fritz et al. [5] used local anesthesia with sedation for eye surgery on a patient with KSS. Recently, Maslow and Lisbon [6] reviewed anesthetic considerations in patients with mitochondrial dysfunction and described the pathophysiologic abnormalities of mitochondrial myopathy. They chose a spinal anesthetic for an internal fixation of ankle fracture in their report, because spinal anesthesia allows maintenance of the patient's airway and avoidance of drugs with potential to trigger malignant hyperthermia. Ours is the first reported patient with KSS who developed postoperative respiratory depression. In addition, this is the first case of a patient with KSS and dilative cardiomyopathy who received general anesthesia. KSS affects cardiac conduction, resulting in progressive heart block in most cases. As a matter of fact, our patient had a cardiac pacemaker for his atrioventricular block. Furthermore, patients with KSS may develop congestive heart failure due to dilative cardiomyopathy [8,9]. The deletion of mitochondrial deoxyribonucleic acid in the myocardium may be the cause of myocardial dysfunction [10,11]. Therefore, not only the cardiac conduction system but also cardiac function should be thoroughly evaluated prior to surgery. We chose general anesthesia for our patient since surgery might not be a simple appendectomy. Direct myocardial depression produced by volatile anesthetics must be considered, although the vasodilating properties of isoflurane without reduced cardiac output would theoretically be desirable [12]. We used low concentrations of isoflurane with fentanyl for maintaining anesthesia to avoid depressing cardiac function, and infusion of prostaglandin E1 to reduce the cardiac afterload [12]. Arterial blood pressure was well maintained during surgery without requiring inotropic drugs. The pacemaker consistently captured during surgery. However, the patient developed rate-dependent left bundle-branch block in the ICU when the rate-pressure product increased, probably due to hypercapnia secondary to respiratory depression. Care should be taken with the administration of muscle relaxants in patients with mitochondrial myopathy, even though D'Ambra et al. [7] reported that the response to depolarizing and nondepolarizing muscle relaxants was almost within normal limits. We used a relatively short-acting muscle relaxant, vecuronium, with monitored neuromuscular block, and observed that the duration of action with vecuronium was not different from that in healthy patients [13]. However, the patient developed respiratory depression shortly after arrival in the ICU, despite the fact that neuromuscular block was sufficiently reversed and he was fully awake at the end of surgery. Respiratory muscle weakness might occur due to premedication, or there may be residual effects of muscle relaxants and inhaled anesthetics, particularly in a patient with myopathy. Preoperatively, our patient had only slight proximal muscle weakness. It is reported that the degree of clinical muscle weakness in patients with mitochondrial myopathy does not correlate with severity of biochemical defects in muscles [14]. Therefore, it is likely that muscle weakness was the reason for respiratory depression; however, respiratory depression of central origin cannot be completely ruled out. Patients with mitochondrial myopathy can have central nervous system abnormalities. In summary, our case suggests that even though patients with KSS do not appear to have significant muscle weakness, care should be taken to monitor respiratory status very closely during the postoperative period, even after sufficient recovery from general anesthetics and muscle relaxants. Our case also suggests that general anesthesia can be used safely even in patients with complicated KSS, keeping in mind that these patients could have compromised myocardial function, cardiac conduction defects, and metabolic abnormalities.