General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report

Suzuki, Yuji; Doi, Matsuyuki; Nakajima, Yoshiyuki

doi:10.1186/s40981-021-00454-8

Cited by 9 publications

(9 citation statements)

References 18 publications

(23 reference statements)

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“…Successful use of remimazolam has been described in spine surgery incorporating motor evoked potential monitoring (Kondo et al, 2020), thyroid surgery with neuromonitoring (Hayamizu et al, 2021), and cardiac surgery with cardiopulmonary bypass (Saito et al, 2021). Remimazolam's successful use in high-risk patients, including endoscopic retrograde cholangiopancreatography in a patient with impaired respiratory function due to myotonic dystrophy (Fukuda et al, 2021), MitraClip implantation in a patient with advanced heart failure (Satoh et al, 2021), and cochlear implant in a patient with mitochondrial myopathy (Suzuki et al, 2021) has been published.…”

Section: Case Reportsmentioning

confidence: 99%

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Kilpatrick¹

2021

Front. Pharmacol.

127

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A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990’s by Glaxo Wellcome. The program focussed on the identification of ester-based benzodiazepine derivatives that are rapidly broken down by esterases. Remimazolam was identified as one of the lead compounds. The project at Glaxo was shelved for strategic reasons at the late lead optimization stage. Via the GSK ventures initiative, the program was acquired by the small biotechnology company, TheraSci, and, through successive acquisitions, developed as the besylate salt at CeNeS and PAION. The development of remimazolam besylate has been slow by industry standards, primarily because of the resource limitations of these small companies. It has, however, recently been approved for anesthesia in Japan and South Korea, procedural sedation in the United States, China, and Europe, and for compassionate use in intensive care unit sedation in Belgium. A second development program of remimazolam was later initiated in China, using a slightly different salt form, remimazolam tosylate. This salt form of the compound has also recently been approved for procedural sedation in China. Remimazolam has the pharmacological profile of a classical benzodiazepine, such as midazolam, but is differentiated from other intravenous benzodiazepines by its rapid conversion to an inactive metabolite resulting in a short onset/offset profile. It is differentiated from other intravenous hypnotic agents, such as propofol, by its low liability for cardiovascular depression, respiratory depression, and injection pain. The benzodiazepine antagonist flumazenil can reverse the effects of remimazolam in case of adverse events and further shorten recovery times. The aim of this review is to provide an analysis of, and perspective on, published non-clinical and clinical information on 1) the pharmacology, metabolism, pharmacokinetics, and pharmacodynamic profile of remimazolam, 2) the profile of remimazolam compared with established agents, 3) gaps in the current understanding of remimazolam, 4) the compound’s discovery and development process and 5) likely future developments in the clinical use of remimazolam.

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Section: Case Reportsmentioning

confidence: 99%

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Kilpatrick¹

2021

Front. Pharmacol.

127

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“…While the loss of consciousness was faster after propofol versus remimazolam induction (46 versus 66 s), blood pressure was significantly lower after propofol induction. 103 Japan VATS Anaesthesia 1 100% Anaphylaxis Hong 9 Korea Arthroscopy Anaesthesia 1 0% Horikoshi 10 Japan Laparoscopy Anaesthesia 1 100% Delayed emergence Huang 11 China LMA insertion Anaesthesia NA 0% Hwang 12 Korea Teratoma resection Anaesthesia 2 0% Kawasaki 13 Japan Liver transplantation Anaesthesia 1 0% Kida 14 Japan CABG Anaesthesia 1 100% Tolerance Kim 107 Korea All kinds Anaesthesia 5 100% Anaphylactoid shock Kim 15 Korea THA Anaesthesia 1 100% Psychogenic coma Kim 16 Korea Laparotomy Anaesthesia 1 0% Kitaura 17 Japan TMVR Anaesthesia 1 0% Koh 18 Japan Spine Anaesthesia 1 100% Heart failure Lee 19 Korea RALP Anaesthesia 1 0% Liu 110 China RALP Anaesthesia 1 100% Precipitation Matsumoto 20 Japan Liver transplantation Anaesthesia 1 0% Matsuo 111 Japan Orthopaedic Anaesthesia 1 100% Precipitation Nakayama 21 Japan Minor orthopaedic Anaesthesia 2 0% Onoda 22 Japan Laparoscopy Anaesthesia 1 0% Saito 23 Japan Cardiac Anaesthesia 1 100% Hypotension Sasaki 112 Japan Dental Anaesthesia 1 100% Precipitation Sato 24 Japan Trepanation Anaesthesia 1 0% Sato 25 Japan Cardiac Anaesthesia 1 100% Hypertension Singal 102 USA Endoscopy Anaesthesia 1 100% Delayed emergence Suzuki 26 Japan ENT Anaesthesia 1 100% Delayed emergence Takemori 27 Japan RALP Anaesthesia 1 100% Delayed emergence Tsurumi 104 Japan Minor orthopaedic Anaesthesia 1 100% Anaphylaxis Uchida 28 Japan ENT Anaesthesia 1 100% Delayed emergence Uchida 29 Japan TEVAR Anaesthesia 1 100% Delayed emergence Uchida 106 Japan Skin graft; laparoscopy Anaesthesia 2 100% Anaphylaxis Yamada 30 Japan Neurosurgery Anaesthesia 3 0% Yamadori 31 Japan Laparotomy Anaesthesia 1 0% Yamamoto …”

Section: Discussionmentioning

confidence: 99%

Remimazolam and serious adverse events

Kempenaers,

Hansen,

Van de Velde

2023

European Journal of Anaesthesiology

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Remimazolam is anticipated to be an interesting anaesthetic and sedative. It combines the pharmacodynamic properties of midazolam with pharmacokinetic properties similar to remifentanil. However, worrisome case reports of anaphylaxis, delayed emergence and re-sedation have emerged recently and necessitate further investigation. PubMed (including MEDLINE) and EMBASE were searched for all studies reporting serious adverse events where remimazolam was administered for sedation or anaesthesia. Thirty-six case reports and 73 trials were identified, involving a total of 6740 patients who received remimazolam. Hypotension was reported in 911 cases, delayed emergence in 68 cases, anaphylaxis in 10 cases and re-sedation in 8 cases. The incidence of hypotension seems to be lower compared with other anaesthetics, even in high-risk patients. Delayed emergence might be related to the metabolism of remimazolam through carboxylesterase 1 (CES1), a tissue esterase predominant in the liver. There is significant interindividual variation, and it is inhibited by flavonoids, fatty acids and alcohol. Individual benzodiazepine sensitivity has also been reported. A higher BMI, older age and low plasma albumin concentration are risk factors for delayed emergence. Anaphylaxis might be related to a non-IgE-mediated effect of the excipient dextran-40 or a partially IgE-mediated reaction to remimazolam itself. Resedation has been reported after flumazenil reversal and is explained by the specific pharmacokinetic properties of flumazenil and remimazolam. Reversal by flumazenil should be reserved for and used carefully in patients with delayed emergence. Visual Abstract http://links.lww.com/EJA/A864.

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“…In August 2022, we searched the PubMed database using the following keywords: <remimazolam> AND <MELAS> or <mitochondrial disease>. The results yielded two case report articles [ 22 , 23 ], neither of which reported on pediatric cases. Since MELAS is a very rare disease, further reports are desirable for more appropriate anesthetic management.…”

Section: Discussionmentioning

confidence: 99%

General anesthesia with remimazolam for a pediatric patient with MELAS and recurrent epilepsy: a case report

et al. 2022

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Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease. We report here the safe use of remimazolam in a pediatric MELAS patient. Case presentation A 10-year-old girl (118 cm, 16 kg) was scheduled for an open gastrostomy to improve nutrition and epileptic seizure control. We induced and maintained general anesthesia with remimazolam, remifentanil, fentanyl, and rocuronium. We also performed a bilateral subcostal transversus abdominis plane block before the surgery. The surgery finished uneventfully. After we discontinued remimazolam administration, the patient woke up immediately but calmly without flumazenil. Epileptic seizures did not occur during intra- and early post-operative periods. Conclusion Remimazolam enabled us to provide a pediatric MELAS patient with general anesthesia without causing delayed emergence or epileptic seizures.

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General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report

Cited by 9 publications

References 18 publications

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Remimazolam and serious adverse events

General anesthesia with remimazolam for a pediatric patient with MELAS and recurrent epilepsy: a case report

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