Remimazolam as an Adjunct to General Anesthesia in Children: Adverse Events and Outcomes in a Large Cohort of 418 Cases

Abstract

Remimazolam was first approved in 2020 as a general anesthetic for adults and still does not have pediatric labeling. Our study will be the first pilot program that administers remimazolam as an adjunct to a general endotracheal anesthetic in children. Between August 2020 and December 2022, electronic medical records were collected for all children who received remimazolam during anesthesia. The remimazolam dosing regimen was extrapolated from the adult package insert, with intravenous induction doses of 12 mg/kg/h administered until the desired effect was achieved. Subsequent infusions were given at a rate of 1–2 mg/kg/h, accompanied by intermittent boluses of 0.2 mg/kg, with all dosing adjustments made according to the anesthesiologist’s clinical discretion. A total of 418 children (mean 4.6 yrs, 68.7% ASA 1 and 2) underwent surgeries which averaged 81.2 min. A total of 75.2% of patients had greater than a 20% change (increase or decrease) in MAP (lowest or highest) from baseline, and 203 (49.3%) patients had greater than a 30% change (increase or decrease) in MAP (lowest or highest) from baseline. A total of 5% received ephedrine to treat unanticipated hemodynamic variability. Discharge criteria were met within an average of 13.8 min after arrival at the post-anesthesia care unit. Remimazolam may offer the benefits of rapid recovery following general endotracheal anesthesia. The risk of hemodynamic variability which necessitates and responds to ephedrine should be anticipated.

Clinical Application and Research Progress of Remimazolam for Pediatric Patients

“…The results show that remimazolam has high clearance rates of 15.9 [12.9-18.2] mL/kg/min (median [IQR]), a small volume of distribution of 0.11 [0.08-0.14] L/kg and a short terminal half-life of 67 min. The 4-hour context-sensitive half-time (CSHT) of remimazolam in children is 17 [12][13][14][15][16][17][18][19][20][21] min, which is comparable to that of propofol, indicating that remimazolam has a rapid decay curve 1222 similar to that of propofol. Notably, the weight-corrected pharmacokinetic characteristics of remimazolam in children are similar to data from previous studies in adults.…”

“…A cohort study 14 involving 418 children (4.6±4.52 years) (mean±SD) showed that after 109.4±83.1 min intravenous infusion, the mean time of remimazolam (induction dose 12 mg/kg/h, maintenance dose 1–2 mg/kg/h) from ceasing administration to spontaneous eye-opening was 34.3±15.8 min, which was longer than the time in adults (average 19 min). 15 The discrepancy may have been due to differing degrees of sedation in the presence or absence of endotracheal intubation between children and adults in the abovementioned studies.…”

“… 39 One report showed that remimazolam increased the risk of nausea and vomiting in children, which may be related to the fact that remimazolam does not produce a direct antiemetic effect similar to propofol. 14 In bronchoscopy practices, 2 of the 25 children treated with remimazolam for general anesthesia induction and maintenance experienced intraoperative body movements, while no children treated with midazolam had intraoperative body movements. 35 Because the volume distribution of remimazolam is relatively small, a potential risk of overdose exists during rapid infusion in pediatric patients.…”

Postoperative Sedation Options in ICU

“…Therefore, despite being an effective choice for short-term continuous sedation, particularly for ICU patients postoperatively, it is worth noting that some studies have demonstrated that remimazolam can impact circulation and breathing, which may serve as a limiting factor for its postoperative use [79] [80] [81].…”

Remimazolam for Pediatric Procedural Sedation: Results of an Institutional Pilot Program

“…Given the limited scope of remimazolam’s use in pediatrics, there is an urgent need for detailed examination and dissemination of pediatric experiences with this drug. While our previous work touched upon remimazolam’s application in general anesthesia in a pediatric cohort [ 6 ], specific investigations into its efficacy and safety in pediatric sedation are sparse. This study aims to bridge this knowledge gap by presenting the outcomes of the first-ever pediatric sedation program using remimazolam, with dosages extrapolated based on approved adult labeling.…”