General Anesthesia with Remimazolam in a Patient with Mitochondrial Encephalomyopathy: A Case Report

Design

Case presentation

A 54-year-old woman with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes underwent cochlear implantation for progressive bilateral sensorineural deafness. Preoperative evaluation revealed asymmetric left ventricular hypertrophy, reduced ejection fraction (45%), diabetic nephropathy with an estimated glomerular filtration rate of 27 mL/min, and poorly controlled diabetes (HbA1c 12.5%). She was on imidapril (Non-FDA approved ACE inhibitor) and subcutaneous insulin.

Anesthesia was induced with remimazolam (0.2 mg/kg bolus, 1 mg/kg/h infusion) and remifentanil (0.2–0.25 mcg/kg/min). Rocuronium (30 mg) facilitated tracheal intubation, monitored with train-of-four (TOF). Continuous arterial pressure monitoring and blood gas analysis showed stable lactate levels (1.8-1.9 mmol/L) and pH (7.41-7.45). The surgery lasted 1 hour and 34 minutes. Neuromuscular function recovered without additional rocuronium. After extubation, delayed responsiveness was addressed with flumazenil (200 mcg), improving verbal responses within 2 minutes.

Postoperative complaints of sore throat and nausea were managed with acetaminophen and metoclopramide. The patient was stable upon discharge from the operating room.

Study Author Conclusions

Remimazolam Anesthesia for Transcatheter Mitral Valve Repair in a Patient with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) Syndrome: A Case Report

Design

Case presentation

A 47-year-old man with MELAS syndrome and severe heart failure (NYHA III) underwent successful transcatheter mitral valve repair using the MitraClip device under general anesthesia with remimazolam and remifentanil. His history included short stature, deafness, renal failure requiring hemodialysis, neurological deficits, and cardiac abnormalities, including Wolff-Parkinson-White syndrome and moderate mitral regurgitation with low left ventricular ejection fraction (LVEF 0.3). Preoperative management included oxygen therapy, diuretics, and dobutamine infusion at 3 mcg/kg/min, which was continued until extubation.

Anesthesia was induced with remimazolam (12 mg/kg/h), administered until loss of consciousness (approximately 1 minute), and remifentanil (0.3 mcg/kg/min), with rocuronium 0.6 mg/kg for intubation; anesthesia was maintained with remimazolam at 1.1–1.2 mg/kg/h and remifentanil at 0.1 mc/kg/min. Bicarbonate Ringer’s solution with 1% glucose was administered intravenously, and 100 mL of 7% sodium bicarbonate was given to address metabolic acidosis during surgery.

The procedure was completed without complications. Remimazolam infusion was stopped approximately 10 minutes before the end of the procedure. Flumazenil (0.5 mg) and sugammadex (4 mg/kg) were administered to reverse sedation and neuromuscular blockade, respectively. The patient regained consciousness and spontaneous breathing 1 minute after flumazenil administration and was extubated without issues. Postoperative recovery was uneventful, with stable hemodynamics. The patient left the ICU the following day, began rehabilitation, and was discharged five days post-surgery.

Study Author Conclusions

General Anesthesia with Remimazolam for a Pediatric Patient with MELAS and Recurrent Epilepsy: A Case Report

Design

Case presentation

A 10-year-old autistic girl underwent a gastrostomy to improve nutrition and epileptic seizure control secondary to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Despite initial feeding tubes, her condition continued to be unstable. General anesthesia (GA) with remimazolam was chosen for the procedure due to its short half-life and anti-epileptic properties. Anesthesia was monitored using bispectral index (BIS) with a target of 40 and that of muscle relaxation by electromyographic module with a target value of train-of-four (TOF) count 1 or less. To avoid exacerbation of hyperlactatemia, saline was used as an intraoperative infusion fluid. A warm air heating device was used to prevent shivering-induced hyperlactatemia and hypothermia-induced mitochondrial dysfunction. Remimazolam was administered at a bolus of 0.2 mg/kg, followed by a continuous infusion of 2.0 mg/kg/h, alongside remifentanil, fentanyl, and rocuronium medications. Total doses were as follow: remimazolam 48.5 mg, remifentanil 0.38 mg, fentanyl 0.025 mg, and rocuronium 15 mg. Following the discontinuation of drugs, the patient was successfully extubated without any complications. She did complain of pain at the surgical gastromy site, though this was resolved with one dose of acetaminophen. No seizures occurred during and immediately post-surgery; seizure episodes did resume on post-op day 5, but were significantly less than before surgery.

Study Author Conclusions

In conclusion, we safely managed GA with remimazolam in a pediatric MELAS patient undergoing open gastrostomy. No intraoperative or early postoperative epileptic seizures occurred. Remimazolam could be a new anesthetic option for MELAS patients with epilepsy.

Use of remimazolam as an adjunct to general anesthesia for an adolescent with MELAS syndrome

Design

Case presentation

A case report describes the perioperative management of a 12-year-old female with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome undergoing strabismus surgery. The anesthetic regimen was carefully tailored to mitigate perioperative risks associated with mitochondrial dysfunction, including impaired oxidative phosphorylation, multi-organ involvement, and the potential adverse effects of volatile anesthetics and propofol. Anesthesia was induced with dexmedetomidine (0.2 mcg/kg), remifentanil (1 mcg/kg), and etomidate (0.3 mg/kg). Maintenance included infusions of dexmedetomidine (0.5-1 mcg/kg/hr), remifentanil (0.3-0.4 mcg/kg/min), and remimazolam (5-10 mcg/kg/min). Glycopyrrolate was used to prevent oculocardiac reflex. Depth of anesthesia was monitored using bispectral index (BIS) values, which were maintained between 50–60 throughout the procedure. Neuromuscular blockade was achieved with rocuronium and successfully reversed with sugammadex.

The intraoperative course was largely uneventful, aside from a transient episode of bradycardia attributed to an oculocardiac reflex, which resolved with glycopyrrolate. Recovery was prompt, facilitated by the rapid metabolism and context-sensitive half-life of the chosen agents, and the patient was discharged without complications. The selection of anesthetic agents aimed to minimize mitochondrial toxicity and avoid adverse metabolic effects. Remimazolam was specifically chosen as an alternative to propofol due to its novel pharmacokinetics, including rapid hydrolysis by tissue esterases and minimal impact on oxidative phosphorylation. In alignment with prior evidence, intravenous fluids containing lactate were avoided, and 0.9% saline was administered. This approach demonstrated effective hemodynamic stability and rapid recovery while addressing the unique challenges posed by MELAS, including susceptibility to arrhythmias, metabolic acidosis, and respiratory dysfunction.

Study Author Conclusions

Anesthesia Management for Percutaneous Mitral Valve Repair in a Patient with Mitochondrial Cardiomyopathy and Low Cardiac Function: A Case Report

Design

Case presentation

A 57-year-old patient with mitochondrial disease (MELAS syndrome), chronic cardiac failure, dilated cardiomyopathy, presented with worsening symptoms of fatigue and shortness of breath. Echocardiography revealed worsening ejection fraction of 26%, left ventricular hypertrophy, moderate-to-severe mitral valve regurgitation and pulmonary hypertension. Given limitations with medication treatment, open surgery was discussed; however, a less invasive approach via percutaneous mitral valve repair with MitraClip was chosen. The anesthetic plan emphasized minimizing mitochondrial and circulatory dysfunction risks, utilizing remimazolam as the primary agent due to its favorable hemodynamic profile and lack of reported mitochondrial toxicity.

The anesthesia regimen involved initial sedation with dexmedetomidine, followed by induction using remimazolam (4 mg/kg/h) in combination with remifentanil and low-dose noradrenaline and dobutamine to stabilize hemodynamics. Anesthesia was maintained with remimazolam at doses between 0.35-1.0 mg/kg/h, achieving stable bispectral index (BIS) values between 40 and 60, while transesophageal echocardiography allowed continuous monitoring of cardiac function during the procedure. Circulatory parameters remained stable throughout, and intraoperative lactate levels were within normal limits, underscoring the absence of mitochondrial dysfunction. Remimazolam was discontinued after the procedure was completed and at 16 minutes, the patient became conscious and started breathing spontaneously, leading to extubation. The patient recovered uneventfully, achieving extubation without requiring flumazenil and demonstrating stable hemodynamics postoperatively.

Study Author Conclusions

In conclusion, anesthesia using remimazolam for percutaneous mitral valve repair was safely managed in a patient with mitochondrial cardiomyopathy. Remimazolam could be a viable anesthetic option for patients with mitochondrial dysfunction and reduced cardiac function.

A Remimazolam and Remifentanil Anesthetic for a Pediatric Patient With a Medium-Chain Acyl-CoA Dehydrogenase Deficiency: A Case Report

Design

Case presentation

A 5-year-old patient (42 in, 17 kg) with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency presented for laparoscopic inguinal hernia repair. His MCAD deficiency was diagnosed at 1 month of age, with enzyme activity at 17% of the normal value. He had not experienced any MCAD deficiency episodes (e.g., hypoglycemia) previously. The day prior to surgery, he received 7.5% glucose at 4.4 mg/kg/min starting from dinner until the time of surgery.

For surgery, anesthesia was induced with remimazolam 4 mg and remifentanil 0.5 mcg/kg/min, with maintenance doses of remimazolam at 2 mg/kg/h and remifentanil at 0.5 mcg/kg/min, targeting a bispectral index (BIS) range of 60-70. Rocuronium 15 mg was given for tracheal intubation, and analgesia included nerve blocks with 12 mL of 0.25% levobupivacaine and intraoperative administration of acetaminophen and fentanyl. Proactive glucose management featured continuous infusion acetate Ringer's with 5% glucose intraoperatively, delivering 5 mg/kg/min, closely monitored to maintain normoglycemia; postoperatively, 7.5% glucose was resumed at 4.5 mg/kg/min (duration not stated).

Anesthesia and surgery lasted 107 and 35 minutes, respectively. The patient experienced no metabolic complications, hypoglycemia, or significant postoperative nausea or vomiting. He was discharged the following day without issue.

Study Author Conclusions

The case emphasized the use of remimazolam alongside a structured glucose infusion protocol to prevent metabolic decompensation, a common risk for patients with fatty acid oxidation disorders. Remimazolam's ultrashort action, combined with its minimal impact on fatty acid metabolism and availability of flumazenil as a reversal agent, demonstrated its clinical utility in this context. BIS-guided anesthesia, while stable, presented limitations in precisely reflecting depths of sedation in pediatric patients, as evidenced by a delayed emergence exceeding 30 minutes following remimazolam cessation.

While guidelines recommend glucose infusions at 5-10 mg/kg/min in patients with MCAD deficiency, this case shows infusion rates of <5 mg/kg/min may be acceptable when MCAD deficiency is mild and surgery is minimally invasive; close glucose monitoring is still essential. The safety and appropriateness of remimazolam as a primary anesthetic in pediatric patients with MCAD deficiency is highlighted by this successful report, underscoring the importance of multidisciplinary care and rigorous glucose monitoring to mitigate perioperative risks.

Remimazolam Anesthesia for a Pediatric Patient With Glutaric Aciduria Type I: A Case Report

Design

Case presentation

A 4-year-old girl with glutaric aciduria type I (GA-1) was scheduled to undergo laparoscopic gastrostomy. Anesthesia induction was performed with atropine 0.1 mg/kg and a continuous infusion of remimazolam 12 mg/kg/h. After loss of consciousness, remimazolam was reduced to 2 mg/kg/h, with administration of fentanyl 2 mcg/kg and rocuronium 0.6 mg/kg.

Anesthesia was maintained with a continuous infusion of remimazolam at 1.5-2 mg/kg/h and remifentanil at 0.2-0.5 mcg/kg/min. Boluses of remimazolam and fentanyl were administered without significant hemodynamic changes. Prior to end of surgery, 0.375% ropivacaine was used as local anesthesia, with intravenous administration of acetaminophen 15 mg/kg and ondansetron 0.1 mg/kg. Sugammadex 2 mg/kg was used to reverse rocuronium, and flumazenil 0.004 mg/kg was administered upon remimazolam discontinuation. 

Postoperatively, the patient did not report episodes of unbearable pain, hyperthermia, nausea, or vomiting. The patient was discharged 7 days after surgery with no sequelae.

Study Author Conclusions

The authors successfully performed general anesthesia with a total intravenous infusion of remimazolam for a pediatric patient with GA-1. The characteristics of remimazolam are suitable for general anesthesia in patients with GA-1, and it is considered to be a viable option. Multimodal perioperative management, which includes not only appropriate anesthetic selection but also the prevention of hypercatabolism, is essential for patients with GA-1.

Remimazolam in pediatric surgery under general anesthesia: a case series

Design

Case presentation

A 16-month-old girl required cardiopulmonary resuscitation 1 month prior to surgery due to cyanosis, and was subsequently mechanically ventilated. Failure to wean off the ventilator resulted in a scheduled tracheostomy.

The patient had a medical history of Leigh’s syndrome, so there was a risk of mitochondrial dysfunction with propofol and thiopental. Thus, the decision was made to use remimazolam, starting at 10 mg/kg/h for anesthesia induction. After sedation, rocuronium was administered, and remimazolam was maintained at 2.5 mg/kg/h. After surgery, a tracheostomy tube was placed, and upon recovering from anesthesia, the patient was transferred to the pediatric intensive care unit uneventfully.

Study Author Conclusions

The characteristics of benzodiazepine drugs, along with this particular case, suggest that remimazolam could be alternative for patients with a history of seizures. In addition, total intravenous anesthesia using remimazolam is a method that can achieve an appropriate depth of anesthesia during shared airway surgery, even if there is air leakage.

For pediatric cases, when there's hesitance towards using propofol due to concerns such as pain, propofol infusion syndrome, or mitochondrial dysfunction, remimazolam emerges as a viable alternative. However, there are several limitations and precautions associated with its use in pediatric patients, including the need for further research, the potential for higher BIS values.