Anesth Pain Med 2011; 6: 290～293 ￭Case Report￭
Clinical manifestations and anesthetic management of Kearns-Sayre syndrome -A case report-
Department of Anesthesiology and Pain Medicine, School of Medicine, Yeungnam University, Daegu, Korea
Hae Mi Lee, Su Jeong Heo, and Dae Lim Jee
Kearns-Sayre syndrome (KSS) is a mitochondrial disorder resulting affected by the disease [2]. in multi-system dysfunction. A 14-year-old boy with KSS underwent A careful approach is needed during anesthesia because external levator muscle resection for correction of ptosis. There life-threatening complications and sensitivity to some anesthetic were no abnormalities on the pre-operative evaluation, except for low-grade heart block and ocular problems. General anesthesia agents and muscle relaxants can occur in patients with was conducted with a minimum dose of thiopental sodium and mitochondrial myopathies, including KSS [3-5]. This paper sevoflurane under close monitoring, and a laryngeal mask was presents a patient with KSS who underwent elective surgery inserted without muscle relaxation. The surgery was uneventful; however, a careful approach was required during anesthesia under general anesthesia and discusses the anesthetic because life-threatening complications may occur in patients with management. KSS. (Anesth Pain Med 2011; 6: 290∼293)
Key Words: General anesthesia, Kearns-Sayre syndrome, Mito- CASE REPORT chondrial disease. A 14-year-old boy, 153 cm in height and weighing 43.4 kg, was admitted for external levator muscle resection due to Kearns-Sayre syndrome (KSS), first described by Kearns and bilateral ptosis, which had progressed over 5 years. There was Sayre in 1958, is a rare mitochondrial myopathy characterized no significant family or medical history, including ocular by a triad of chronic progressive external ophthalmoplegia, trauma or disease. According to his mother, as a child the pigmentary retinopathy, and at least one of the followings: patient was less active physically, easily exhausted, and smaller cardiac conduction defects; cerebellar ataxia; or an elevated than other children of his age; however, no cognitive deficits CSF protein level (＞100 mg/dl) that occurs before 20 years or cerebellar symptoms were evident. At 12 years of age, he of age [1]. Early diagnosis is usually made with symptoms of was evaluated in the Opthalmologic Department for ptosis. ptosis and the disease involves many organs, such as the eyes, Ocular motility was slightly limited bilaterally in the lateral muscles, heart, liver, kidneys, pancreas, thyroid and parathyroid direction of gaze, and the marginal reflex distance and levator glands, and peripheral and central nervous systems. No single function were depressed on the left side greater than the right. treatment has been shown to be effective, with the exception Multiple pigmentary changes (salt- and pepper-like appearance, of cardiac pacing; thus, treatment remains supportive with early stage) were noted in the entire retinas of both eyes on close monitoring and follow-up. The prognosis is poor and the fundoscopic examination. During the pediatric evaluation, morbidity depends on the severity and number of organs physical development was noted to be delayed (height, 5th percentile; weight, 15th percentile). No neurologic abnormalities Received: January 3, 2011. were noted, and endocrinologic studies, including blood glucose Revised: 1st, January 18, 2011; 2nd, February 16, 2011. − Accepted: March 3, 2011. (96 mg/dl) and parathyroid hormone (47.01 pg/ml [normal, 15 Corresponding author: Dae Lim Jee, M.D., Department of Anesthesiology 65 pg/ml]), were within normal limits. Routine laboratory data and Pain Medicine, School of Medicine, Yeungnam University, Daemyeong and chest x-rays were normal, with the exception of a right 5-dong, Nam-gu, Daegu 705-717, Korea. Tel: 82-53-620-3367, Fax: 82-53-626-5275, E-mail: [email protected] bundle branch block with a wide QRS complex (120 ms) and
290 Hae Mi Lee, et al : Clinical manifestations and anesthetic management of Kearns-Sayre syndrome 291
Fig. 1. A ragged red fiber with characteristic red peripheral staining is Fig. 2. Abnormal proliferations of mitochondria are shown. The shown (modified Gomori trichrome, ×400). mitochondria are large and vacuolated (electron microscope, ×12,500). left axis deviation on ECG. Serum lactate, pyruvate, and CSF glucose 37.5 g ＋ NaCl 2.25 g in 1000 ml) was administered. protein levels were not measured. The patient was discharged the day after the surgery without General anesthesia was planned with sevoflurane and any complications. monitoring of the ECG, non-invasive blood pressure, SpO2, The pathologic findings from the isolated right external and EtCO2. As sensitivity to the muscle relaxant was levator muscle demonstrated ragged red fibers based on anticipated, the laryngeal mask airway was considered without modified Gomori trichrome staining (Fig. 1) and multiple large, muscle relaxation. Pacemaker preparation, temperature atypical mitochondria with vacuoles on electron microscopy monitoring, and use of lactate-free solution were also (Fig. 2), which were consistent with mitochondrial disease. contemplated. Mitochondrial DNA was examined; however, no deletions or In the operating room, the vital signs were as follows: heart mutations were detected. rate (HR), 88 beats/min; body temperature (BT), 36.9oC; and respiratory rate (RR), 20 breaths/min. Atropine sulfate was DISCUSSION injected intramuscularly, after anesthesia was conducted with 125 mg of thiopental sodium and 25 μg of fentanyl citrate Mitochondrial myopathies result from impaired respiratory without muscle relaxation under ECG monitoring. With oxygen chain activity or oxidative phosphorylation in mitochondria [6]. and nitrous oxide (3.0 L/min each), 8.0 vol% of sevoflurane Mitochondrial myopathies are induced by point mutations or was delivered by manual ventilation for approximately 1 deletions of mitochondrial DNA, and patients with KSS minute. A no. 3 flexible laryngeal mask was applied when the typically have 45−75% deletions of total mitochondrial DNA end-tidal sevoflurane reached 5.0 vol%. At that time, the BP [7]. However, many patients have no detectable deletions, as was 80/40 mmHg and the HR was 64 beats/min. Sevoflurane in the current case, and this may be due to point mutations or was administered at 0.8−1.5 vol% during most of the surgical deletions which are too small to detect [8]. Once cellular procedure and the following parameters were maintained: BP, energy production falls below a certain threshold in cells with
90−110/45−60 mmHg; HR, 60−80 beats/min; EtCO2, 34−36 abnormal mitochondria, compensatory proliferation of mitochon- mmHg; and SpO2, 99%. A local anesthetic was infiltrated dria occurs and abnormal clusters of distorted and swollen before the incision for hemodynamic stability and mitochondria are shown as a bright red staining material with post-operative pain control by surgeon. There were no notable modified Gomori trichrome staining, hence referred to as events during the operation, and the laryngeal mask was ragged red fibers [6]. removed after the patient was fully awake with his own Typical clinical features of KSS include ptosis, opthal- respiratory efforts. The total time taken for the operation was moplegia, pigmentary retinopathy, cardiac conduction defects 55 min and 250 ml of a glucose-containing solution (SD 1 : 3; and/or cardiomyopathy, sensorineural deafness, muscle weak- 292 Anesth Pain Med Vol. 6, No. 3, 2011 ness, ataxia, dementia, nystagmus, developmental delay or obtained and the risk of a cardiac attack should be considered regression, mental retardation, scoliosis, and endocrine disorders at any time, including during anesthesia. As Torsades de [7,9]. Serum lactate and pyruvate levels are usually increased, Pointes has been reported in patients with KSS [12], thus lactic acidosis is induced [2]. Intracranial degenerations evaluation of the QT interval and electrolyte status are recom- are common and elevated protein in the CSF indicates damage mended and drugs that interfere with AV conduction should be to the CNS [10]. Sometimes mitochondrial myopathies can avoided during anesthesia. Right bundle branch block and left mimic myasthenia gravis [8], as proximal muscle weakness and axis deviation were shown on ECG in our case; however, ptosis are the main presenting symptoms, therefore differential anesthesia was planned without cardiac echocardiography diagnosis should be made if necessary. However, only limited because cardiomegaly was not noted and the heart sounds were studies were performed in this case because the symptoms clear and regular without cardiac symptoms. Left axis deviation already met the criteria for KSS and it was regarded as an can be considered as a normal variant; however, it appeared to early stage. be indicative of left anterior hemi-block or transient second As KSS involves multi-organs and the symptoms primarily degree AVB in this case. Because the physical status of the arise in childhood, anesthetic management should be considered patient was good with low grade AVB, complete heart block not only for surgery, but also for diagnosis. Patients with was not thought to occur intra-operatively; however, pacemaker mitochondrial diseases need pre-operative evaluation with a insertion is recommended in the near future. particular focus on cardiac, respiratory, neurologic, musculo- Respiratory dysfunction may develop in association with skeletal, endocrine, and metabolic compromise. As cardiac ventilatory drive suppression to hypoxemia and hypercapnia, manifestations are the most important prognostic factor and sensitivity to anesthetic induction agents, and the prolonged complete atrioventricular block (AVB) is the major cause of effect of neuromuscular blocking agents [13]. Pre-medication death in patients with KSS, pacemaker insertion should be with sedatives and opioids are avoided because the respiratory considered prior to anesthesia depending on the patient's response to hypoxemia is impaired [3]. In some patients, physical status. Weaning from a ventilator could be difficult respiratory myopathy leads to a restrictive lung disease as a due to muscle weakness and sensitivity to anesthetic agents, result of progressive scoliosis and kyphoscoliosis, thus a wide thus careful assessment is needed. Malignant hyperthermia has spectrum of pulmonary pathologies may also occur [14]. been reported in a patient with mitochondrial myopathy accom- Weaning from mechanical ventilation could be difficult, panied by myoadenylate deaminase deficiency [11], therefore presenting as recurrent pneumonia and respiratory failure. avoidance of triggering factors and monitoring of HR, EtCO2, Therefore, extubation should be performed after confirmation of body temperature, and acid-base status are recommended in the proper tidal volume and respiratory rate without difficulty highly affected patients. Lactate solution is better to avoid in in breathing. As minimum doses of anesthetic agents were patients with metabolic acidosis and insulin or sodium used and the disease was not far advanced, there were no bicarbonate can be used to correct the blood glucose level or respiratory problems in this case. acid-base status. Sensitivity to volatile agents, barbiturates, propofol, and Cardiac involvement has been limited almost exclusively to etomidate has been suggested in patients with mitochondrial the conducting tissues rather than the myocardium [5]. Develo- disease; however, most induction agents are known to be safe pment of a cardiac conduction defect may result in syncope, when used with caution [3], thus induction with small heart failure, and sudden cardiac death in up to 57% of incremental doses with BIS monitoring is recommended. patients, with a mortality rate of 20% [7]. As the disease Isoflurane was used for the agent of choice in the past, but eventually progresses to AVB in most patients, prophylactic sevoflurane is now recommended because of its low solubility, pacemaker insertion has been advised [2]. Although there are low pungency, and little propensity to produce arrhythmias [4]. differences among the reports, pacemaker insertion has been However, whether or not to use neuromuscular blocking agents recommended in the early stages to second degree AVB, even is still debating matter of debate. Robertson [13] reported a when the patients are asymptomatic [2]. The interval between child who was extremely sensitive to non-depolarizing recognition of heart block and death varied from days or neuromuscular blocking drugs, the effects of which were not months up to 6 and 7 years in a study depending upon the reversed by anti-cholinesterases. However, D'Ambra et al. [15] patient’s status [9]. Therefore, an ECG follow-up should be suggested that the disease does not involve the neuromuscular Hae Mi Lee, et al : Clinical manifestations and anesthetic management of Kearns-Sayre syndrome 293 junction and in many references, neuromuscular blocking drugs 2. Chawla S, Coku J, Forbes T, Kannan S. Kearns-Sayre syndrome are used uneventfully during the peri-operative period. It is presenting as complete heart block. Pediatr Cardiol 2008; 29: 659-62. better not to use muscle relaxants if not mandatory; however, 3. Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young as muscle relaxants are not absolutely contraindicated, it can WL. Miller's anesthesia. 7th ed. Philadelphia, Elsvier Inc. 2010, be administered with small incremental doses under observation pp 1179-80. with neuromuscular monitoring devices. In this case, small 4. Wallace JJ, Perndt H, Skinner M. Anaesthesia and mitochondrial doses of thiopental sodium (＜3 mg/kg) and no muscle disease. 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