Abstract
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Background
Leigh syndrome is a mitochondrial disorder in which impaired oxidative phosphorylation causes progressive neurologic damage. Brainstem lesions may cause central hypoventilation, apnea, and recurrent pulmonary infection, increasing perioperative risk.
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Case
We describe a patient with Leigh syndrome who had chronic central respiratory dysfunction, recurrent pneumonia, and a recent intensive care admission for sepsis and who subsequently underwent tracheostomy under general anesthesia. Anesthesia was induced and maintained with remimazolam and remifentanil. Hemodynamic parameters remained acceptable neuromuscular recovery, spontaneous ventilation remained inadequate, and the patient was returned to the intensive care unit with ventilatory support.
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Conclusion
In mitochondrial disease, propofol warrants careful consideration because of concerns regarding mitochondrial effects and propofol infusion syndrome. Remimazolam was selected based on severe respiratory vulnerability, recent multiorgan illness, and the anticipated need for postoperative ventilatory support, rather than as evidence of superiority over other agents.
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Keywords: Leigh syndrome; remimazolam; central respiratory failure; mitochondrial disease; tracheostomy; general anesthesia
Leigh syndrome typically presents in infancy or childhood and results from impaired mitochondrial energy production. Neurologic deterioration is often accompanied by characteristic bilateral lesions in the basal ganglia, brainstem, and related structures, although the disorder is genetically and clinically heterogeneous [
1,
2].
Respiratory involvement is a major determinant of outcome in Leigh syndrome. Brainstem dysfunction may cause central apnea or hypoventilation, and bulbar dysfunction, ineffective cough, reduced mobility, and skeletal deformity can further impair airway clearance and increase the likelihood of recurrent pneumonia [
2].
From an anesthetic perspective, the central issue is not only possible sensitivity to specific drugs but also the patient's limited physiologic reserve. Fasting, infection, temperature imbalance, hypoxemia, acid-base disturbance, and postoperative respiratory weakness may all contribute to perioperative instability in patients with mitochondrial disease [
3-
5].
We report the use of remimazolam for tracheostomy in a young woman with Leigh syndrome complicated by chronic central respiratory failure, recurrent pneumonia, and a recent intensive care admission after sepsis.
Case Report
A 21-year-old woman with Leigh syndrome was scheduled for tracheostomy to secure a long-term airway because of recurrent pneumonia and respiratory failure requiring prolonged ventilatory support. General anesthesia was planned. She had severe psychomotor developmental delay, weighed 39.5 kg, and was 138 cm tall. Brain computed tomography showed marked cerebral and brainstem atrophy, necrotic changes in both basal ganglia, and diffuse ventriculomegaly. She was bedridden and had scoliosis, diabetes mellitus, uncontrolled seizures, recurrent pneumonia, and recurrent pancreatitis. Two months before surgery, she developed septic shock due to multidrug-resistant Acinetobacter baumannii, which progressed to multiorgan failure. Eleven days before surgery, she underwent endotracheal intubation for acute respiratory acidosis. In view of recurrent pneumonia and repeated apneic episodes, tracheostomy was planned to provide a more stable long-term airway. Nutritional support was being delivered through a gastrostomy tube.
No premedication was given. On physical examination, the patient was drowsy and uncooperative. Heart sounds were normal, but coarse breath sounds were noted on auscultation. Chest anteroposterior radiography demonstrated severe thoracic scoliosis with rightward tracheal deviation of 3 cm. Preoperative laboratory findings were as follows: hemoglobin 9.0 g/dL, hematocrit 28.9%, blood glucose 138 mg/dL, and C-reactive protein 0.34 mg/dL. Because of apnea related to central respiratory failure and her recent septic condition, she was already receiving ventilatory support after intubation in synchronized intermittent mandatory ventilation-pressure support mode with an FiO2 of 21%, PEEP of 6 cmH2O, trigger flow of 5 L/min, pressure control level of 13 cmH2O, pressure support level of 8 cmH2O, and respiratory rate of 16 breaths/min. Arterial blood gas analysis showed a pH of 7.34, PaCO2 of 48 mmHg, PaO2 of 47 mmHg, base excess of -0.1 mmol/L, oxygen saturation of 79.7%, and lactate of 13 mg/dL.
These findings reflected the combined effect of central hypoventilation from Leigh syndrome and ongoing sepsis-related respiratory compromise. Despite mechanical ventilatory support, oxygenation remained inadequate, and tracheostomy was therefore indicated to secure a stable long-term airway rather than representing a decision to proceed with elective surgery in a compromised patient.
Because the patient had severe neurologic injury and marked respiratory vulnerability, general anesthesia with remimazolam and remifentanil was planned in view of its hemodynamic stability and reversibility. Both induction and maintenance were achieved with remimazolam and remifentanil. Remimazolam was administered as a loading infusion at 12 mg/kg/h for 2 minutes and then continued at 1 mg/kg/h for maintenance. Remifentanil was infused continuously at 0.01 mcg/kg/min throughout the procedure. Rocuronium 10 mg was given for neuromuscular blockade. Before surgery, flumazenil, the antagonist of remimazolam, and sugammadex, the reversal agent for rocuronium, were prepared in case they were needed. The patient arrived in the operating room already intubated, and anesthesia was initiated through the existing endotracheal tube without any additional airway device. On arrival, her heart rate was 83 beats/min and blood pressure was 150/90 mmHg. During surgery, the bispectral index was maintained between 40 and 50. Heart rate remained within 70-100 beats/min, and systolic blood pressure was stable between 130 and 160 mmHg. Hartmann solution was infused intraoperatively, with a total volume of 400 mL. Urine output was 60 mL, and body temperature remained stable at 37.0°C. The train-of-four count was 0 throughout the operation. The procedure lasted 605 seconds and was completed without complication. In the operating room, sugammadex 100 mg was administered, and the train-of-four recovered to 98%; however, adequate spontaneous ventilation did not return because of the patient's preexisting condition and central respiratory failure. She was therefore transferred to the intensive care unit and placed on pressure-controlled ventilation. One day later, spontaneous breathing gradually improved, and ventilatory support was changed to synchronized intermittent mandatory ventilation-pressure support mode with an FiO2 of 21%, PEEP of 5 cmH2O, trigger flow of 2 L/min, pressure control level of 12 cmH2O, pressure support level of 12 cmH2O, and respiratory rate of 17 breaths/min. Ten days after surgery, tracheal edema caused airway narrowing such that only one-eighth of the tracheal lumen was visible on endoscopy, and intravenous dexamethasone was administered for 3 days. Pleural effusion also increased, and she remained in the intensive care unit for observation for 4 weeks before transfer to the general ward. Even after transfer, sepsis and respiratory acidosis repeatedly worsened and improved. After a plan was made to replace the tracheostomy cannula every 1-2 months, she was discharged home with a home ventilator.
Discussion
Leigh syndrome is a neurometabolic disorder caused by mitochondrial dysfunction, and symmetric lesions in the brainstem and deep gray nuclei are among its characteristic radiologic and pathologic findings [
1,
2]. Because these regions are essential for respiratory control, airway protection, and autonomic regulation, anesthetic management is often challenged more by limited physiologic reserve than by any single uniform pharmacologic abnormality.
Respiratory failure is one of the major determinants of prognosis in Leigh syndrome [
1]. Central hypoventilation, apneic episodes, ineffective cough, recurrent aspiration or infection, and reduced mobility may all contribute to prolonged ventilatory dependence. In the present case, repeated pneumonia, impaired consciousness, and prior intubation suggested a particularly high risk of postoperative respiratory insufficiency.
Perioperative risk in Leigh syndrome should therefore be considered within the broader framework of mitochondrial disease and advanced neurologic impairment [
3-
5]. The interaction among chronic respiratory dysfunction, recent sepsis, nutritional stress, immobility, and impaired airway clearance may be clinically more important than any isolated concern regarding anesthetic drug sensitivity.
Accordingly, practical anesthetic goals in mitochondrial disease include minimizing prolonged fasting when possible, maintaining oxygenation and ventilation, preserving circulatory stability, maintaining normothermia, correcting metabolic disturbances, and planning carefully for postoperative respiratory support [
3-
5]. In patients who already have central respiratory failure, the postoperative strategy may be as important as the choice of hypnotic agent.
Propofol remains a widely used anesthetic agent, but caution is warranted in mitochondrial disorders because experimental studies have demonstrated inhibitory effects on mitochondrial function, including electron transport and fatty acid oxidation [
6]. Clinical concern is reinforced by propofol-related infusion syndrome, a rare but potentially fatal complication that is usually associated with prolonged infusion, critical illness, or high cumulative exposure [
7,
8].
Propofol-related infusion syndrome has been linked to severe metabolic acidosis, rhabdomyolysis, hyperkalemia, cardiac dysfunction, renal failure, and death [
8,
9]. In addition, case reports suggest that unrecognized mitochondrial disease may increase susceptibility in some patients [
9]. These findings do not make propofol absolutely contraindicated in all patients with mitochondrial disease, but they do support individualized assessment of dose, duration, and overall physiologic context [
3,
4].
Our decision-making therefore focused less on excluding a single drug categorically and more on selecting an anesthetic strategy that matched this patient's clinical condition. Given her recent multiorgan illness and substantial respiratory risk, we sought an approach that allowed controlled titration during surgery together with a clear postoperative airway plan.
Remimazolam is an ultra-short-acting benzodiazepine that is metabolized by tissue esterases and has been reported to provide predictable sedation or anesthesia with relatively stable hemodynamics [
10-
13]. Reversal with flumazenil is another practical advantage when rapid neurologic assessment is desired, although overall recovery still depends on the patient's underlying neurologic and respiratory status [
12,
14].
For these reasons, remimazolam was chosen in this case as an individualized option rather than as an established best agent for Leigh syndrome. Our experience suggests that its use was feasible in this setting, but the finding should be interpreted in light of the patient's baseline risk for ventilator dependence, the limited value of a single case, and the ongoing uncertainty regarding anesthetic selection in mitochondrial disease.
The doses of remifentanil and rocuronium were also selected with the patient's clinical condition in mind. Remifentanil was initiated at a low infusion rate of 0.01 mcg/kg/min because of concern that higher doses might compromise hemodynamic stability in the setting of recent septic shock; because the bispectral index remained within the target range and blood pressure did not increase further during surgery, the rate was not titrated upward. Rocuronium was administered at a reduced dose of 10 mg (approximately 0.25 mg/kg) because progressive neuromuscular involvement in Leigh syndrome was expected to increase sensitivity to neuromuscular blocking agents; continuous train-of-four monitoring confirmed sustained relaxation throughout surgery without the need for additional doses.
In this patient, adequate spontaneous breathing did not return after recovery of the train-of-four at the end of surgery, and the need for transfer to the intensive care unit with ventilatory support is more plausibly explained by preexisting central respiratory failure and impaired brainstem function than by residual neuromuscular blockade [
2,
15]. Previous reports have also described difficult or delayed respiratory recovery after general anesthesia in patients with Leigh syndrome [
1,
2].
Moreover, the patient had already been intubated before surgery and required secure long-term airway access because of recurrent pneumonia and repeated apnea; immediate recovery of spontaneous breathing after tracheostomy was therefore not necessarily the primary postoperative goal. Continued ventilatory support in the intensive care unit, together with ongoing assessment of respiration, acid-base balance, infection, secretion clearance, and neurologic status, was more consistent with her underlying pathophysiology [
3-
5].
The clinical course and prognosis in this case cannot be attributed to a single anesthetic agent alone [
4,
5]. In addition to progressive neurologic injury from Leigh syndrome, the patient also had sepsis, recurrent pneumonia, scoliosis, poorly controlled seizures, diabetes mellitus, recurrent pancreatitis, and dependence on enteral feeding; the postoperative respiratory course and overall outcome were more likely shaped by multiple interacting factors [
2,
4,
5].
Thus, although stable intraoperative hemodynamics were observed during anesthesia with remimazolam, this observation alone does not justify concluding that remimazolam improved the patient's long-term outcome or was superior to other anesthetic techniques [
5,
11,
13,
14,
16].
This report has several limitations. First, as a single case, it cannot establish a causal relationship between anesthetic choice and clinical course, and its generalizability is limited. Second, because there was no direct comparison with other anesthetic strategies such as propofol, the relative advantages and disadvantages of remimazolam cannot be quantified [
11,
14,
16]. Third, the patient had numerous confounding factors—including central respiratory failure, active infection, metabolic vulnerability, and structural thoracic abnormalities—making it difficult to isolate a single explanation for delayed postoperative respiratory recovery [
2,
15].Fourth, long-term physiologic and clinical follow-up data, including mitochondrial function, lactate trends, and long-term outcome, were limited, which constrains interpretation of the longer-term implications of this anesthetic choice [
4,
5]. Ultimately, this case should be interpreted as a technical experience showing that remimazolam-based general anesthesia was feasible in a patient with severe Leigh syndrome, and further accumulation of cases and comparative studies is needed [
5,
14,
16].
Conclusion
Leigh syndrome may confer substantial perioperative risk because mitochondrial dysfunction often coexists with brainstem-related respiratory impairment, recurrent pulmonary complications, and limited physiologic reserve [
2-
4].
In this case, remimazolam and remifentanil were used successfully for tracheostomy in the setting of recent sepsis, chronic central respiratory failure, and an anticipated need for postoperative ventilatory support.
This experience should not be interpreted as proof that remimazolam is superior to propofol or to other anesthetic techniques. Rather, it illustrates that anesthetic planning in mitochondrial disease should integrate drug selection with the patient's overall respiratory status, metabolic vulnerability, and postoperative airway strategy [
3-
5].
This case report was approved by the Institutional Review Board of Gangneung Asan Hospital (IRB No. 2026-04-002), which waived the requirement for informed consent due to the retrospective nature of the report. Written informed consent for publication could not be obtained as the patient's legal guardian was unreachable despite repeated attempts to make contact. The requirement for written informed consent was therefore formally waived by the Institutional Review Board of Gangneung Asan Hospital.
Notes
Conflict of Interest
The author declares no conflict of interest.
Funding
No funding was received for this work.
Data Availability Statement
Not applicable.
Ethics Approval and Consent to Participate
This case report was approved by the Institutional Review Board of Gangneung Asan Hospital (IRB No. 2026-04-002)
Authors' Contributions
Conceptualization: YKK, DHK. Methodology: YKK, DHK. Project administration: YKK, DHK. Writing – original draft: YKK, DHK. Writing – review & editing: YKK, DHK.
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