Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries

Abstract

Purpose

Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries.

Patients and Methods

Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg⁻¹), Group D (intranasal dexmedetomidine 2 mcg kg⁻¹), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS).

Results

Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010).

Conclusion

Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation.

Trial Registration

NCT 04720963, January 22, 2021, ClinicalTrials.Gov.

Keywords:

• dexmedetomidine
• paediatrics
• preoperative anxiety
• premedication
• remimazolam

Abbreviations

ANOVA, Analysis of variance; ASA, American Society of Anesthesiologists; BS, Behavior score; CI, Confidence interval; CRF, Case report form; EA, Emergence agitation; GCP, Good clinical practice; HR, Heart rate; IN, Intranasal; IQR, Interquartile range; IV, Intravenous; LMA, Laryngeal mask airway; MAC, Minimum alveolar concentration; MAS, Mask acceptance scores; MD, Median difference; m-Ypas, Modified Yale Preoperative Anxiety Scale; OR, Odds ratio; PACU, Post-anesthesia care unit; PAED, Post-anesthesia emergence delirium; PSAS, Parental separation anxiety scores; RSS, Ramsay Sedation Scale; SD, Standard deviation.

Data Sharing Statement

The data are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

This randomized, double-blind, placebo-controlled clinical trial was approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (No.LCKY 2020-426, December 22, 2020) and written informed consent was obtained from the parents or legal guardians of all subjects participating in the study.

Acknowledgments

We thank all participants in this study.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This study was funded by the Major Science Technology Projects of Wenzhou, Zhejiang, China (ZY2023030) and Social Development Science and Technology Project of Taizhou City of China (20ywa59) and Wenzhou Science and Technology Bureau (Y20220948).