Delayed emergence after remimazolam induction in end-stage liver disease. Comment on Br J Anaesth 2021; 127: 415–23

Singal, Amit; Naftalovich, Rotem; Syed, Asad R.; Chaudhry, Faraz; Discepola, Patrick; Rodriguez-Correa, Daniel T.

doi:10.1016/j.bja.2022.09.006

Cited by 6 publications

(5 citation statements)

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“…Table 4 shows a summary of all case reports and trials where delayed emergence was reported when remimazolam was given as a continuous infusion for general anaesthesia (and not for sedation) and one case report by Singal et al where remimazolam was only given for induction of anaesthesia but the patient still experienced delayed emergence. 102 Of the 1279 patients who were given a continuous remimazolam infusion for general anaesthesia, 260 received flumazenil. Of those receiving flumazenil, 203 received it at the end of surgery without awaiting spontaneous awakening, 29 received it when still sedated 30 min after the end of the infusion, 24 received it when they were still sedated after spontaneous breathing had resumed and 4 patients received it at different time points when the anaesthesiologist felt that recovery was prolonged.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Stöhr et al 125 demonstrated that after a single dose of remimazolam, severe hepatic impairment (Child–Pugh C) is associated with 38% slower elimination of remimazolam, and end-stage renal disease is associated with urine concentrations of the metabolite three times higher than normal, 4 h after bolus injection. Singal et al and Uchida et al both report a case of delayed emergence in a patient with severe hepatic impairment 28,102 . Shimamoto et al 126 showed that patients with delayed emergence, had a higher BMI, were older, and had a lower plasma albumin concentration.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Remimazolam and serious adverse events

Kempenaers,

Hansen,

Van de Velde

2023

European Journal of Anaesthesiology

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“…As remimazolam is primarily metabolized in the liver [57 ▪▪ ,58], severe hepatic impairment can cause a prolonged effect of remimazolam [59 ▪▪ ]. Remimazolam tolerance has been reported in long-term benzodiazepine users, such that some patients do not respond to even high doses of remimazolam [60,61,62 ▪ ].…”

Section: Possible Contraindications For Remimazolammentioning

confidence: 99%

Remimazolam: its clinical pharmacology and evolving role in anesthesia and sedation practice

Masui

2024

Current Opinion in Anaesthesiology

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Purpose of review Remimazolam is a novel benzodiazepine anesthetic/sedative, designed as a rapidly metabolized carboxylic acid. Since its recent launch, the role of remimazolam in modern anesthesia and sedation practice is still evolving. This review aims to outline the clinical pharmacology and clinical utility of remimazolam to elucidate its potential advantages and limitations. Recent findings Remimazolam is “short-acting” but not ultra-short-acting compared with propofol based on context-sensitive decrement times. But compared to propofol, the availability of the benzodiazepine antagonist, flumazenil, is considered an advantage, particularly in certain emergency situations such as in patients with difficult airways. However, because flumazenil is shorter acting than remimazolam when remimazolam accumulates or is present in a high concentration, the reappearance of remimazolam sedation may occur after the initial reversal of anesthesia/sedation from flumazenil administration. Although it is beneficial that remimazolam causes less respiratory depression and hypotension than propofol, serious respiratory depression and hypotension can still occur. Remimazolam administration causes minimal or no pain on injection. Remimazolam is associated with less postoperative nausea and vomiting than inhaled anesthetics, but propofol is clearly superior in this regard. The anesthetic/sedative effects may be prolonged by severe hepatic impairment; remimazolam tolerance can occur in long-term benzodiazepine users. Summary Remimazolam may be beneficial to use in procedural sedation and general anesthesia for patients with difficult airways or hemodynamic instability. Further clinical studies with remimazolam are warranted to identify the potential benefits in other settings and patient populations.

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Remimazolam – Update zu Grundlagen und klinischem Potenzial

Scheckenbach,

Drexler

2024

Anaesthesiologie

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Delayed emergence after remimazolam induction in end-stage liver disease. Comment on Br J Anaesth 2021; 127: 415–23

Cited by 6 publications

References 6 publications

Remimazolam and serious adverse events

Remimazolam and serious adverse events

Remimazolam: its clinical pharmacology and evolving role in anesthesia and sedation practice

Remimazolam – Update zu Grundlagen und klinischem Potenzial

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