Anesth Analg 2003;97:1539-1541
© 2003 International Anesthesia Research Society
GENERAL ARTICLES
Anesthesia for Corrective Spinal Surgery in a Patient with Leigh’s Disease
Michael A. Cooper, FRCA, and
Richard Fox, FRCA
From the Department of Anesthesia, The Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK
Address correspondence to Dr. Richard Fox, Department of Anesthesia, The Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom. Address email to rfox{at}rnoh.nhs.uk
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Abstract
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We report a case of anesthesia for posterior spinal fusion in a woman with Leigh’s disease. This is a syndrome with a heterogeneous phenotype including ocular signs, motor signs, and respiratory disorder. It is associated with defects in the enzymes of the mitochondrial respiratory chain and central neural degeneration. Anesthesia is associated with worsening of the respiratory symptoms. Our patient underwent major spinal surgery as a palliative procedure. Her postoperative course was complicated by acute lung injury and sepsis. She ultimately failed a prolonged respiratory wean. Serial magnetic resonance imaging revealed a rapidly progressive necrosis of her brain stem and cervical spinal cord consistent with activation of her underlying Leigh’s disease. This is the first report of spinal surgery in this patient group. It is also the first radiological demonstration of Leigh’s disease reactivation in the postoperative period. Anesthesia and surgery are hazardous in this patient population, and respiratory symptoms make this a high-risk group. Surgery should only be undertaken with caution and after frank consent. Early postoperative imaging is recommended if there are respiratory complications. No drug prophylaxis has been shown to alter disease activation.
IMPLICATIONS: Patients suffering from Leigh’s disease are at high risk of serious postoperative respiratory morbidity. We present a case that demonstrates delayed respiratory complications and link this postoperative adverse outcome to aggressive reactivation of the underlying neurodegenerative condition.
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Introduction
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We report a case of spinal surgery to correct progressive thoracic scoliosis in a woman with Leigh’s disease (LD). Anesthesia has been reported in patients with LD, as has adverse postoperative outcome (1–3). Respiratory failure is both the most common cause of death in patients with LD and the most common cause of postoperative morbidity and mortality in this group. However, the cause of deterioration in the perioperative period has been unclear. We describe delayed postoperative respiratory failure in the intensive care environment and demonstrate radiological evidence of reactivation of brainstem vasculonecrosis, which is typical of LD, as the underlying pathology. This is the first report linking disease reactivation and adverse outcome and providing supporting radiological evidence.
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Case Reports
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A 21-yr-old woman, diagnosed with LD as an infant, presented for elective spinal deformity correction. Her spinal abnormality consisted of a progressive left thoracic scoliosis, size 100 degrees as measured by the Cobb angle (4), and a secondary right lumbar spinal curve with severe pelvic obliquity. Surgery was palliative and aimed at halting thoracic curve progression. This reduces pain, helps maintain an erect posture and facilitates nursing care. This, in turn, is associated with reduced respiratory morbidity. Scoliosis surgery may help prevent deterioration but rarely improves respiratory function.
At preoperative assessment she was 25 kg. She had limited, nonverbal communication, poorly coordinated swallowing reflexes, and a weak cough. Muscle tone was increased with fixed flexion deformities of upper and lower limb joints. Formal spirometry was not possible, but arterial blood gases were normal, including a normal lactate level, while breathing room air. Her only medication was oral baclofen. She was referred for percutaneous gastrostomy formation and, after a period of nutritional supplementation, was admitted for surgery. Discussion of consent with her parents included a frank assessment of postoperative complications, including tracheostomy formation and mortality.
The surgical procedure was a single-stage posterior instrumented spinal fusion from pelvis to the second thoracic vertebrae. Anesthesia was induced with IV propofol and maintained with intermittent positive pressure ventilation with desflurane in oxygen and air, supplemented with intermittent IV fentanyl. Tracheal intubation was aided by vecuronium. The procedure took 7 h with an estimated blood loss of 7000 mL. Fluid management consisted of 3000 mL compound sodium lactate, 3000 mL 10% starch, 3000 mL of packed red blood cells, and 600 mL of fresh-frozen plasma. The patient was transferred, ventilated, to intensive care.
Her arterial blood gas results, taken immediately on arrival in intensive care, were as follows: PO2, 222 mm Hg; PCO2, 26.3 mm Hg; pH, 7.41; base excess, -7.1 mmol/L; and lactate, 3.6 mmol/L. A measured coagulopathy was supported with 330 mL pooled platelets and 1000 mL fresh-frozen plasma. Ventilation, using an Evita 2 machine in BiPAP-SIMV mode, was uneventful. No further organ support was needed. Tracheal extubation on the first postoperative day to noninvasive ventilatory support was unsuccessful. Reintubation was required within 1 h. Clinical deterioration followed with pulmonary consolidation (Fig. 1) and a clinical picture of sepsis, requiring cardiovascular support with norepinephrine. Serial cultures revealed mixed coliforms from blood and sputum. Subsequently, Pseudomonas aeruginosa was isolated from sputum. Antibiotic therapy was adjusted as results and sensitivities became available.
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Figure 1. Supine anterior-posterior chest radiograph showing marked consolidation. The internal fixation system is evident.
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A tracheostomy was fashioned on Day 16 of intensive care admission. By Day 28 respiratory support consisted of periods of spontaneous ventilation via a t-piece and periods of continuous positive airways pressure of 5 cm of water. An episode of Gram-positive sepsis delayed progression. This episode was treated with ciprofloxacin and teicoplanin. Subsequently it became difficult to re-establish a spontaneous respiratory pattern. Frequent apneic periods developed and spontaneous respiratory effort ceased on Day 45. No sedation had been used since Day 32, temperature and biochemical indices were normal, and respiratory stimulants (theophylline, caffeine) were ineffective. Serial magnetic resonance imaging showed old cerebral and ventricular changes typical of LD. The images also showed new progressive necrosis of the pons, medulla, and upper cervical cord consistent with aggressive disease reactivation (Figs. 2 and 3).
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Figure 2. A, T2 weighted magnetic resonance imaging scan from intensive care admission Day 37. B, T2 weighted magnetic resonance imaging scan taken on intensive care admission Day 58. Necrosis of the brainstem and upper cervical spinal cord is shown.
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Figure 3. T1 weighted magnetic resonance imaging scan post-Gadolinium contrast. Enhancement of the necrotic area in the brainstem and spinal cord is evident.
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After multidisciplinary review and a series of open discussions with the patient’s relatives, further support was not instituted and the patient died on Day 62 postprocedure.
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Discussion
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In 1951 Dennis Leigh (5) described the case of a 7-month-old child who presented with spasticity, pyrexia, and blindness. Postmortem examination revealed symmetrical vascular proliferation and tissue necrosis extending from the thalamus to the thoracic spinal cord. This pattern of central damage is diagnostic of LD and may be accompanied by optic demyelination, areas of spongiform cavitation, and focal gray and white matter necrosis of the spinal cord (6). It is thought that LD is a mitochondrial encephalopathy (7). Disorder of cytochrome c oxidase and pyruvate dehydrogenase function is frequently found in tissue biopsy and increased serum and cerebrospinal fluid lactate levels may be present (7–12).
This syndrome most commonly presents in infancy. The subsequent phenotype is characterized by cognitive delay, seizure disorder, blindness, nystagmus, and a wide range of motor signs (8,9). An irregular respiratory pattern with frequent apneas often develops, and respiratory failure is the most common cause of death (8,13). Anesthesia has been undertaken in this group. The small literature base indicates frequent postoperative mortality. This is frequently attributable to respiratory failure and occurs in patients with preoperative respiratory signs such as stridor or grunting respiration (2). There are no reports of postoperative imaging in these cases. Our patient showed a delayed failure in respiratory drive that occurred separately to her initial problem of probable aspiration and respiratory tract infection. Imaging demonstrated rapid necrosis of her brainstem. This indicated a reactivation of her underlying disease as the cause of failure to wean from respiratory support and, ultimately, of death. This link, possibly explaining the frequent rates of postoperative respiratory mortality in LD, has not been demonstrated before. Our patient did not have the respiratory symptoms associated with postoperative respiratory mortality. However, the presence of poor bulbar function, poor cough, and poor cooperation with physiotherapy probably moved her to such a risk cohort. This seems likely, but it does not explain the delayed respiratory sequelae that we observed.
Interventions aimed at ameliorating the metabolic disorder that may underlie neural injury include the use of pyruvate dehydrogenase activators (14), feeding with ketogenic substrates (15), and chronic thiamine and riboflavin supplementation (16). Similar strategies, including restricting lactate-containing fluid, have been used in the perioperative phase (3). We did not use these techniques, as our patient did not show evidence of a metabolic disorder producing lactemia. Within the diagnosis of LD it seems that there are different subgroups, as evidenced by different enzyme disorders, different patterns of inheritance, and different disease phenotypes. It is not clear which, if any, of these groups may respond to this type of treatment in terms of limiting neural necrosis.
We have reported a palliative surgical procedure in a woman with a rare and complicated disease. Surgery in patients with LD presents a great challenge and is accompanied by a high risk of mortality. Our results imply that it is disease reactivation that is causal to the postoperative clinical deterioration. This may occur late and the role of imaging in such cases where failure to wean from respiratory support occurs is highlighted.
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References
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Accepted for publication May 23, 2003.
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Abstract
Introduction
