Total intravenous anesthesia induced and maintained by a combination of remimazolam and remifentanil without a neuromuscular blocking agent: a prospective, observational pilot study

Abstract

Background A novel short-acting benzodiazepine, Remimazolam, has recently been approved for general anesthesia and sedation. Hence, we investigated the feasibility and safety of remimazolam during the induction and maintenance of general anesthesia without using a neuromuscular blocking agent (NMBA) in patients undergoing hysteroscopic surgery. Methods This prospective observational study included 38 patients undergoing hysteroscopic surgery. Remimazolam and remifentanil were the main anesthetic agents without an NMBA, and a supraglottic airway was inserted to protect the airway. The induction time, amount of each anesthetic agent used during anesthesia, intraoperative bispectral index (BIS) hemodynamic parameters, and recovery profiles were measured. Results General anesthesia was successfully administered to 37 patients using remimazolam and remifentanil without NMBA. The induction doses of remimazolam and remifentanil were 0.4 mg/kg (interquartile range [IQR] 0.34–0.47 mg/kg) and 1.07 μg/kg (IQR, 0.90–1.29 μg/kg), respectively. Additionally, the maintenance doses of remimazolam and remifentanil were 1.14 mg/kg/h (IQR, 0.88–1.55 mg/kg/h) and 0.06 μg/kg/min (IQR, 0.04–0.08 μg/kg/min), respectively. Intraoperative BIS values had risen temporarily > 60 in eight patients (21.6%) despite administration of 2 mg/kg/h of remimazolam; thus, they were treated with supplementary midazolam. The median recovery time was 7 min (IQR, 5–8 min) after 40 min (IQR, 40.0–57.5 min) of total mean anesthesia time. There was no correlation between the infusion dose of remimazolam and recovery profiles, such as recovery time, final BIS of anesthesia, modified observer assessment of alertness/sedation (OAA/S) scale or post-anesthesia recovery (PAR) score when arriving at the PACU, and length of stay in the PACU (all P > 0.05). Conclusion Remimazolam can be combined with remifentanil without an NMBA in female patients who undergo hysteroscopic surgery, during which a supraglottic airway is a feasible method to protect the airway. Trial registration The study protocol was registered at ClinicalTrials.gov (NCT05025410) on 27/08/2021.

Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure

“…28 In addition, intra-operative BIS values were reported to increase to more than 60 even when patients were confirmed to reach sufficient hypnotic levels for general anaesthesia based on other hypnotic depth indicators, such as spectral edge frequency and pupil diameter. 7 Moreover, BIS value took approximately twice as long (135 s) to fall to less than 60 as the time taken to achieve an MOAA/S score of 1 or less (63 s), 8 and it did not correlate well with loss of consciousness in remimazolam anaesthesia. 2,8,29 Notably, in our study, BIS values during word presentation for 15 min were maintained at more than 60 (60 to 80) for more than 13.5 min despite a MOAA/S score of 2 or less.…”

“…4,5 However, the bispectral index (BIS TM , Medtronic, Dublin, Ireland) of some patients administered remimazolam for general anaesthesia cannot be maintained at less than 60, typically recommended for general anaesthesia, even if they have been given the maximum dose, 12 mg kg À1 h À1 for induction and 2 mg kg À1 h À1 for maintenance. [6][7][8] Postoperative interviews suggested that most patients had no memory formation during remimazolam anaesthesia at the level associated with a BIS of more than 60. 7,8 Nevertheless, we cannot be certain that memory formation did not occur solely based on the current evidence.…”

“…[6][7][8] Postoperative interviews suggested that most patients had no memory formation during remimazolam anaesthesia at the level associated with a BIS of more than 60. 7,8 Nevertheless, we cannot be certain that memory formation did not occur solely based on the current evidence. This is because there is no established method to evaluate memory formation during remimazolam anaesthesia, and most available observations are anecdotal and have been obtained within the scope of clinical practice.…”

“…Clinical investigations have demonstrated the noninferiority of remimazolam to propofol under general anaesthesia 4,5 . However, the bispectral index (BIS TM , Medtronic, Dublin, Ireland) of some patients administered remimazolam for general anaesthesia cannot be maintained at less than 60, typically recommended for general anaesthesia, even if they have been given the maximum dose, 12 mg kg −1 h −1 for induction and 2 mg kg −1 h −1 for maintenance 6–8 . Postoperative interviews suggested that most patients had no memory formation during remimazolam anaesthesia at the level associated with a BIS of more than 60 7,8 .…”

Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review

“…Remimazolam is a novel, ultra-short acting benzodiazepine, combining the pharmacodynamic profile of midazolam with a speed of onset and breakdown similar to remifentanil. Its use has been described for both procedural sedation and as part of a TIVA regimen along with an opioid [23]. Anaesthetic drugs and benzodiazepines bind to the gamma-aminobutyric acid A receptor at both distinct and overlapping sites.…”