Retrospective Analysis of Midazolam Hydrochloride Oral Solution for Preoperative Anxiety and Sedation in Pediatric Patients: Evaluation of Efficacy and Safety

Retrospective Analysis of Midazolam Hydrochloride Oral Solution for Preoperative Anxiety and Sedation in Pediatric Patients: Evaluation of Efficacy and Safety | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Retrospective Analysis of Midazolam Hydrochloride Oral Solution for Preoperative Anxiety and Sedation in Pediatric Patients: Evaluation of Efficacy and Safety Xiaolin Tang, Wenjie Su, Xie Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8614681/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Midazolam is widely used for preoperative anxiety and sedation in pediatric patients.This study aims to analyze the effectiveness of midazolam hydrochloride oral solution in alleviating preoperative anxiety and providing sedation in pediatric patients, while concurrently evaluating its safety profile. Methods In this retrospective study, 52 pediatric patients were enrolled. Anxiety and sedation levels were primarily assessed using an anxiolysis score and the Ramsay Sedation Score. The primary efficacy endpoints were the proportion of children achieving successful anxiolysis and successful sedation within 30 minutes post-administration. Secondary efficacy endpoints included the time from administration to successful anxiolysis and successful sedation, the parental separation score or a cooperation score, satisfaction ratings from both guardians and anesthesiologists regarding the medication, and the pediatric post-anesthesia care unit (PACU) recovery time. Furthermore, the incidence of adverse events, including those related to the gastrointestinal, respiratory, and nervous systems, was analyzed. Results Within 30 minutes, the successful anxiolysis rate was 100%, with a failure rate of 0%. The mean time to achieve successful anxiolysis was 7.72 ± 3.50 minutes. The Ramsay sedation success rate was 83.72%, with a failure rate of 16.28%. The mean time to achieve successful sedation was 16.08 ± 4.96 minutes.The cooperation score was 3.9 ± 0.21.Postoperative guardian satisfaction score averaged 4.30 ± 0.74, and anesthesiologist satisfaction score averaged 4.21 ± 0.91. The mean PACU recovery time was 101.16 ± 41.84 minutes.Regarding adverse events, the incidence of both nausea and vomiting was 13.96%, while the incidence of prolonged sedation was 32.56%. Conclusion Midazolam hydrochloride oral solution is effective in alleviating preoperative anxiety and providing satisfactory sedation in pediatric patients. Furthermore, it demonstrates high satisfaction rates among both guardians and anesthesiologists. The treatment was well-tolerated with no serious adverse events reported, thereby confirming its favorable efficacy and safety profile. Ethics The study population comprised pediatric patients who underwent elective surgery under general anesthesia at Sichuan Provincial People's Hospital between April and August 2025. The study received approved from the Institutional Ethics Committee (approval no. 2025836), and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877). Pediatric Preoperative Anxiety Sedation Midazolam Premedication Figures Figure 1 Figure 2 1. Introduction During the preoperative and anesthesia preparation phase, children often exhibit signs of preoperative anxiety—such as fear, anger, crying, and aggressive behavior—due to the unfamiliar environment, the presence of medical staff, and fear of pain [ 1 ] . Firstly, preoperative anxiety can exacerbate pain perception, prolong both anesthesia induction and postoperative recovery times, increase the risk of postoperative delirium, heighten the requirement for analgesics, and elevate anesthetic risks [ 2 ] . Secondly, this anxiety impairs the child's ability to adapt to the unfamiliar medical setting and may raise the incidence of accidental injury. Finally, children experiencing preoperative anxiety are up to three times more likely to develop delirium, nightmares, separation anxiety, sleep disturbances, night crying, enuresis, temper tantrums, apathy, withdrawal, eating disorders, and negative behavioral changes such as increased fear of medical personnel [ 3 – 8 ] . These negative behaviors can persist for up to one year [ 3 ] and may hinder normal child development as well as future medical encounters [ 5 ] . Given that approximately 42–75% of children experience preoperative anxiety [ 9 ] , effective interventions to mitigate and prevent this clinical issue are essential. Midazolam is a short-acting benzodiazepine characterized by sedative, amnestic, anxiolytic, muscle relaxant, and anticonvulsant properties. Its advantages include rapid onset, high metabolic clearance, and the induction of anterograde amnesia, making it widely used for pediatric sedation [10; 11] . It exerts its clinical effects by binding to the receptor complex, thereby potentiating the neuronal inhibition mediated by the neurotransmitter γ-aminobutyric acid (GABA) [ 12 ] . Midazolam has a faster onset and shorter duration of action compared to other benzodiazepines, such as diazepam and lorazepam [ 13 ] . It can be administered via intravenous, intramuscular, intranasal, and oral routes. The oral route is often preferred in pediatric patients due to its ease of administration, non-invasiveness, and high acceptability [14; 15] .Flavored oral solutions improve palatability by masking the bitter taste of midazolam, enhancing compliance without affecting its metabolism. Numerous high-quality randomized controlled trials have demonstrated that oral midazolam reduces separation anxiety in children and their parents, decreases the incidence of negative preoperative behaviors—including crying—and improves acceptance of mask induction during anesthesia [ 16 ] . Owing to its safety profile, rapid onset, and reliable amnestic effect, midazolam oral solution is considered an ideal sedative for children [ 17 – 19 ] . Nonetheless, adverse events—including those involving the digestive, respiratory, and nervous systems—may still occur [20; 21] . The recommended dosage of midazolam oral solution for pediatric use is 0.5–1 mg/kg [ 17 ] . 2. Materials and Methods 2.1. Study Design This study employed a retrospective cohort design to evaluate the efficacy and safety of midazolam hydrochloride oral solution in managing preoperative anxiety and providing sedation in pediatric patients. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the ethics board of Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China (No. 2025 − 836) and waived the requirement for informed consent due to the retrospective nature of the study design and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877). 2.2 Study Population This retrospective study enrolled 52 pediatric patients who had received midazolam hydrochloride oral solution and undergone elective surgery under general anesthesia. Participants were included if they met all inclusion criteria and none of the exclusion criteria. Inclusion criteria were : Aged between 6 months and 16 years (inclusive), either sex. Scheduled for elective surgery (e.g., in general surgery, urology, orthopedics, otorhinolaryngology, or stomatology) requiring preoperative sedative medication. Exclusion criteria were : Known hypersensitivity to any component of midazolam oral solution. Diagnosis of acute angle-closure glaucoma or inadequately treated open-angle glaucoma. Concurrent participation in another interventional clinical trial. Considered by the investigator to be unsuitable for participation for any other reason. Study termination criteria were : Discovery of a serious violation of inclusion/exclusion criteria after enrollment. Voluntary withdrawal requested by the participant's legal guardian or the participant themselves. Loss to follow-up, defined as the investigator's inability to make contact with the participant after more than three contact attempts over three consecutive days. Any other circumstance deemed by the investigator to warrant discontinuation from the trial. 2.3. Study Methods Data were retrospectively collected from 52 pediatric patients who had received midazolam hydrochloride oral solution (Specification: 0.2% [10 ml: 20 mg, calculated as C18H13ClFN3·HCl; manufactured by Jiangsu Enhua Pharmaceutical Co., Ltd.]) and undergone elective surgery under general anesthesia. The collected data included Ramsay Sedation Scores (Table 1 ) and anxiolysis scores (Table 2 ) measured at the following time points: within 1 hour before oral administration (T0), and subsequently at 5–10 minute intervals after administration (T1, T2, T3, T4, T5). Data were collected using a self-designed questionnaire (see Supplementary File 1). Vital signs, including pulse rate, respiratory rate, and SpO₂, were recorded during different periods: within 1 hour before drug administration, and then continuously monitored from the start of administration until the initiation of general anesthesia, with recordings made approximately every 5 minutes. The patient cooperation score was assessed after the administration of general anesthetic agents. The Post-Anesthesia Care Unit (PACU) recovery time was documented. Satisfaction evaluations from both guardians and anesthesiologists were recorded on the second day following drug administration. Adverse events occurring after the administration of midazolam oral solution were collected. These included respiratory complications (e.g., hypoxia, laryngospasm), digestive system complications (e.g., nausea, vomiting), and nervous system complications (e.g., drowsiness, prolonged sedation). The dosage was administered as follows: Younger children (≥ 6 months, < 6 years): 1.0 mg/kg Older children (≥ 6 years): 0.5 mg/kg The maximum total administered dose did not exceed 20 mg. Table 1 Ramsay Sedation Scale Category Score Description Awake 1 Patient is anxious, agitated, or restless. 2 Patient is cooperative, oriented, and tranquil. 3 Patient responds to commands only. Asleep 4 Patient exhibits a brisk response to a light glabellar tap or loud auditory stimulus. 5 Patient exhibits a sluggish response to a light glabellar tap or loud auditory stimulus. 6 Patient exhibits no response to a light glabellar tap or loud auditory stimulus. Table 2 Anxiolysis Score Score Description 1 Apprehensive, restless, crying, and/or resists reassurance. 2 Fearful, moderate apprehension. 3 Mildly fearful, easily reassured by strangers, non-aggressive. 4 No signs of fear or anxiety. 5 Patient is asleep. 2.4. Evaluation Criteria 2.4.1. Primary Efficacy Endpoints The proportion of participants achieving successful anxiolysis within 30 minutes post-administration. *Note: Successful anxiolysis was defined as achieving an anxiolysis score of 3 or higher within 30 minutes post-administration without the use of rescue medication.* The proportion of participants achieving successful Ramsay sedation within 30 minutes post-administration. *Note: Successful sedation was defined as achieving a Ramsay Sedation Score of 3 or higher within 30 minutes post-administration without the use of rescue medication.* 2.4.2. Secondary Efficacy Endpoints Time from drug administration to successful anxiolysis. Time from drug administration to successful sedation. Cooperation degree (Table 3 ) in participants who achieved sedation success. o Note o Satisfactory cooperation was defined as a cooperation score between 3 and 5 points without the use of rescue medication. Satisfaction ratings from guardians and anesthesiologists (Table 4 ). o Note o Comprehensive assessment based on factors such as palatability, sedative effect, and duration of action. Pediatric Post-Anesthesia Care Unit (PACU) recovery time. Incidence of adverse events following administration of midazolam oral solution, including: Respiratory complications (e.g., hypoxia, laryngospasm). Digestive system complications (e.g., nausea, vomiting). Circulatory system complications (e.g., significant tachycardia or bradycardia). Nervous system complications (e.g., drowsiness, prolonged sedation). Table 3 Cooperation Score Score Description 1 Vigorously resists the procedure. 2 Cooperation is achieved only with considerable effort by the staff. 3 Reluctantly accepts the procedure. 4 Readily accepts the procedure. 5 Patient is asleep. Table 4 Satisfaction Rating Score Description 1 Very Dissatisfied 2 Dissatisfied 3 Moderately Satisfied 4 Satisfied 5 Very Satisfied 2.5. Statistical Analysis Statistical analyses were performed using SPSS software (version 22.0). Continuous data were summarized using descriptive statistics, including number of cases (n), mean, median, standard deviation, minimum, and maximum values. Categorical data were presented as frequency tables and percentages. The proportions of participants achieving successful anxiolysis and successful Ramsay sedation within 30 minutes post-administration were calculated, along with their corresponding two-sided 95% confidence intervals (CI) using the Clopper-Pearson exact method. The time intervals from drug administration to successful anxiolysis and from drug administration to successful sedation were analyzed using the Kaplan-Meier methodology. 3. Results 3.1. Baseline Characteristics of the Pediatric Cohort A total of 52 pediatric patients were initially included in this study. Among them, 9 cases were excluded: guardians of 4 children declined to participate on the day of surgery, guardians of 1 child withdrew due to difficulty with ingestion, and investigators determined that 4 children did not meet the inclusion criteria on the day of surgery. Consequently, 43 pediatric patients were ultimately included in the final analysis (Figure 1). The demographic and baseline characteristics of the included children are presented in Table 5. Table 5. Demographic and Baseline Characteristics of the Pediatric Cohort Variables (Mean ± SD or n) Sex (Male/Female) 37/6 Age (months) 41.53±38.61 Age Group (<6 years / ≥6 years) 37/6 Weight (kg) 16.91±10.72 BMI（kg/m 2 ） 16.80±2.66 ASA(I/II) 42/1 3.2. Anxiolytic and Sedative Effects Analysis using the Clopper-Pearson method indicated that among the 43 children, 43 achieved an anxiolysis score of ≥3 within 30 minutes post-administration, yielding a successful anxiolysis rate of 100% (95% CI: 91.75%, 100.00%). Furthermore, 39 children attained an anxiolysis score of ≥4, corresponding to a success rate of 90.72% (95% CI: 78.1%, 97.5%). Regarding sedation, 36 children achieved a Ramsay Sedation Score of ≥3 within 30 minutes, resulting in a successful sedation rate of 83.72% (95% CI: 69.7% - 92.7%). Kaplan-Meier analysis revealed that the mean time to achieve successful anxiolysis (score ≥3) was 7.72 ± 0.53 minutes (95% CI: 6.68 – 8.77), with an overall median time of 6 minutes (95% CI: 5.65 – 6.35). Successful anxiolysis occurred predominantly in the early phase post-administration, with cumulative success rates reaching 95.3% at 15 minutes and 100% at 30 minutes. For the higher threshold (anxiolysis score ≥4), the mean time to achievement was 17.56 ± 2.20 minutes (95% CI: 13.25 – 21.87), with an overall median time of 13 minutes (95% CI: 12.59 – 13.41). The cumulative success rates for an anxiolysis score ≥4 were 60.8% at 15 minutes and 90.7% at 30 minutes. The mean time to achieve successful Ramsay sedation (score ≥3) was 18.35 ± 1.04 minutes (95% CI: 16.31 – 20.39), with an overall median time of 19 minutes (95% CI: 13.89 – 24.11). In contrast to anxiolysis, the successful attainment of sedation occurred primarily in the later phase, with cumulative success rates of 44.20% at 15 minutes and 83.72% at 30 minutes (Table 6). The individual times to successful anxiolysis and sedation for each child are illustrated in Figure 2. Anxiolysis and Ramsay Sedation Scores at various time points are detailed in Table 7. Notably, all children achieved an anxiolysis score of ≥3 from time point T3 onwards. Table 6. Number and Success Rate of Successful Anxiolysis and Ramsay Sedation, with Median and Mean Times Variables n/N Proportion 95% CI(%) Median Time (min) 95% CI (min) for Median Mean Time (min, Mean ± SD) 95% CI (min) for Mean Successful Ramsay Sedation 36/43 83.72% 69.7-92.7 19 13.89-24.11 18.35±1.04 16.31–20.39 Successful Anxiolysis (Score ≥3) 43/43 100% 91.75-100.00 6 5.65-6.35 7.72±0.53 6.68–8.77 Anxiolysis Score ≥4 39/43 90.72% 78.1-97.5 13 12.59-13.41 17.56±2.20 13.25–21.87 Note: CI = Confidence Interval. Table 7. Anxiolysis and Ramsay Sedation Scores at Different Time Intervals Measurement times Anxiolysis Score (Mean±SD) Ramsay Sedation Score (Mean±SD) T0（n=43） 1.93±0.83 1.47±0.50 T1（n=43） 2.86±0.80 1.84±0.53 T2（n=43） 3.63±0.58 2.40±0.54 T3（n=40） 3.88±0.40 2.80±0.56 T4（n=31） 3.87+0.34 2.78±0.43 T5（n=8） 4.00±0.53 2.78±0.67 3.3. Child Cooperation, Satisfaction, and PACU Recovery Time During anesthesia induction, the mean cooperation score was 3.95 ± 0.21. Among the 43 children, only two received a score of 3, both occurring during intravenous propofol injection. This was attributed to propofol injection pain, which was not entirely prevented despite the pre-emptive administration of lidocaine mixed into the propofol solution. The remaining children all received a score of 4. The PACU recovery time, defined as the duration from PACU arrival until fully awake and ready for discharge, averaged 101.16 ± 41.84 minutes. Satisfaction surveys conducted on the first postoperative day revealed a mean guardian satisfaction score of 4.30 ± 0.74 and a mean anesthesiologist satisfaction score of 4.21 ± 0.91. The difference between these scores was not statistically significant (Table 8). Furthermore, a comparison of PACU recovery times between children aged ≤2 years and those >2 years showed a statistically significant prolongation in the younger age group (≤2 years) (Table 9). This indicates that younger age (≤2 years) may be associated with prolonged recovery, suggesting that the dosage requirement for midazolam oral solution in this specific population warrants further investigation. Table 8. Child Cooperation Score, Guardian and Anesthesiologist Satisfaction Ratings, and PACU Recovery Time Variables (Mean±SD) P-value Cooperation Score 3.95±0.21 PACU Recovery Time (min) 101.16±41.84 Guardian Satisfaction 4.30±0.74 0.285 Anesthesiologist Satisfaction 4.21±0.91 Table 9. PACU Recovery Time by Age Group Age PACU Recovery Time (min), Mean ± SD P-value ≤2（year,n=21） 114.90±42.03 0.034 ＞2（year,n=22） 88.04±38.10 3.4. Adverse Events Among all pediatric patients, six experienced nausea, which was followed by vomiting. These events occurred immediately after drug administration. The vomitus consisted solely of the medication, with no gastric contents, and no instances of aspiration occurred. No patients experienced adverse events such as hypoxia or laryngospasm. Prolonged sedation, defined as a PACU recovery time exceeding 2 hours, was observed in 14 children. Notably, all 14 children were under 6 years of age and had received the 1.0 mg/kg dose (Table 10). Table 10.Incidence of Adverse Events System Adverse Event Number of Cases (n=43) Incidence (%) Digestive System Nausea 6 13.96 Vomiting 6 13.96 Respiratory System Hypoxia 0 0 Laryngospasm 0 0 Nervous System Drowsiness 0 0 Prolonged Sedation 14 32.56 4. Discussion Preoperative anxiety in pediatric patients can activate the sympathetic, parasympathetic, and endocrine systems, leading to numerous adverse clinical outcomes, including postoperative psychological trauma, emergence delirium, altered sleep patterns, and aggressive behavior [3; 22] . The primary factors contributing to pediatric anxiety include separation from guardians, fear of doctors and syringes, limited understanding of their illness, and the inherent stress of undergoing surgery. Consequently, anesthesiologists employ various pharmacological agents to mitigate this stress response. The primary objectives of pediatric premedication are anxiolysis to facilitate smooth separation from guardians and entry into the operating room, thereby enhancing anesthesia safety. Additional goals include amnesia, attenuation of the stress response, reduction of total anesthetic requirements, decreased risk of aspiration, reduced salivary secretions, antiemesis, and analgesia [ 14 ] . Midazolam, a benzodiazepine, offers advantages such as rapid onset, anterograde amnesia, and minimal respiratory depression. It is commonly used for sedation prior to surgery, radiographic imaging, and invasive procedures [ 23 – 26 ] . It remains the most frequently used sedative for anxiolysis in children, with the oral route being the first-line choice due to its ease of administration, non-invasiveness, and high acceptability in the pediatric population [ 23 ] . The findings of this study demonstrate that midazolam hydrochloride oral solution, administered at doses of 1.0 mg/kg for children aged 6 months (inclusive) to 6 years and 0.5 mg/kg for those aged 6 years (inclusive) to 16 years, effectively alleviates preoperative anxiety and provides satisfactory sedation within 30 minutes of administration. This facilitates improved cooperation with healthcare staff during anesthesia induction. Furthermore, the treatment was associated with high satisfaction rates among both guardians and anesthesiologists. In this study, the successful anxiolysis rate within 30 minutes post-administration was 100%, with no failures observed. Among the children, 40 (93.02%) achieved an anxiolysis score of ≥ 4. The successful Ramsay sedation rate was 83.72%, with a failure rate of 16.28%. These findings exhibit some divergence from certain other studies; for instance, investigations by Sultan Keles and Wheeler reported oral midazolam sedation success rates of 96.2% and 93%, respectively [27; 28] . This discrepancy may be attributable to differences in study design, the specific sedation scales employed, and investigator subjectivity, warranting caution when directly comparing sedation success rates across studies. For example, the defined timeframes for assessing successful sedation vary among studies [27; 29] . Furthermore, some studies utilize different sedation scales to evaluate efficacy, such as the Observer's Assessment of Alertness/Sedation (OAA/S) scale [16; 30] . Our study employed the Ramsay Sedation Scale due to its practicality and ease of use, allowing for rapid and repeated assessments within short timeframes. However, it relies heavily on the observer's judgment and is characterized by its significant subjectivity. In this study, the mean times to achieve an anxiolysis score of 4 and successful sedation were 13.70 ± 5.94 minutes and 16.08 ± 4.96 minutes, respectively. This finding is consistent with prior studies indicating that oral midazolam typically exerts its sedative effect within 15–30 minutes [17; 31] . Our results suggest a high level of cooperation prior to anesthesia induction in the pediatric cohort, with the vast majority readily accepting interventions and calmly accompanying medical staff into the operating room. This high level of cooperation obviated the need for stronger sedative agents like propofol to facilitate smooth induction in most cases. Only two children exhibited lower cooperation scores, which we attribute to possible propofol injection pain. It is noteworthy that despite the prophylactic addition of lidocaine to the propofol solution, this measure does not completely prevent injection pain. In children not receiving preoperative medication, preoperative crying can lead to increased secretions, elevated risk of respiratory complications, and increased heart rate and oxygen consumption. Poor cooperation can also prolong the time required to establish monitoring equipment and shorten the period available for pre-oxygenation. Consequently, the use of potent sedative agents like propofol may become necessary, potentially causing respiratory depression. Compared to adults, children have lower oxygen reserves and higher oxygen consumption, which increases the risk of severe adverse events, including hypoxic encephalopathy, cardiac arrest, or even death [ 32 – 36 ] . Regarding whether the medication prolongs PACU recovery time, we only performed descriptive statistics due to the lack of a control group. One study reported a mean PACU recovery time of 81.88 ± 17.53 minutes following pediatric laparoscopic surgery [ 37 ] . While this differs from our findings, considerations such as variations in surgical type, patient age, and anesthetic regimens must be accounted for, necessitating further investigation for confirmation. Furthermore, we compared PACU recovery times between children aged ≤ 2 years and those > 2 years. The recovery time was significantly longer in the ≤ 2 years age group, and this difference was statistically significant (Table 9 ). This indicates that younger age (≤ 2 years) may be associated with prolonged recovery, suggesting that the dosage regimen of midazolam oral solution for this specific population warrants further exploration. Furthermore, postoperative follow-up surveys were conducted to assess satisfaction with the medication among both guardians and anesthesiologists. The results indicated high satisfaction ratings from both groups, which can contribute to fostering trust between anesthesiologists and patients' families. Regarding adverse events, within the scope of our analysis, the primary occurrences were nausea, vomiting, and prolonged sedation. No other serious adverse events, including laryngospasm or hypoxia, were reported. It is noteworthy that all instances of nausea and vomiting occurred immediately after drug ingestion and were not observed during general anesthesia induction, emergence, or in the PACU. This suggests these events might be related to the child's resistance to taking the medication itself, rather than being a direct effect of the midazolam oral solution. Conversely, the incidence of prolonged sedation was notably high at 32.56%. Analysis revealed that all children experiencing prolonged sedation were under 6 years of age and had received the 1.0 mg/kg dose. In the absence of a control group, a definitive causal link between the medication and prolonged sedation cannot be established; however, younger age appears to be a significant contributing factor. Despite our findings demonstrating the satisfactory efficacy of midazolam hydrochloride oral solution for preoperative anxiolysis and sedation in children, this study has several limitations. First, its design was single-center and open-label, with all outcomes evaluated solely in children who received the study drug and without a control group for comparison. Additionally, the sample size was relatively small. Second, the assessment of both the anxiolysis and Ramsay sedation scores involves a degree of subjectivity, which could potentially influence the results. Finally, the wide age range of the included children and the different dosages used for various age groups might also have introduced bias into the study findings. Conclusion This study demonstrates that administration of midazolam hydrochloride oral solution at a dose of 0.5-1.0 mg/kg, 30 minutes prior to anesthesia induction, provides adequate anxiolysis and sedation levels in pediatric patients. The treatment yielded satisfactory outcomes for both anesthesiologists and guardians, facilitating smooth induction of anesthesia without the occurrence of serious adverse events. However, it is important to note the potential for prolonged postoperative recovery time in the PACU, particularly in children aged 2 years or younger. Declarations Ethics approval and consent to participate The study received approved from the Institutional Ethics Committee (approval no. 2025836), and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877). The study waived the requirement for informed consent due to the retrospective nature of the study design Consent for publication Not Applicable. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no conflicts of interest Funding None. Authors' contributions Study concept/design: Xiaolin Tang, Wenjie Su, Xie Wang. Data collection: Xiaolin Tang, Xie Wang. Data analysis: Xiaolin Tang, Wenjie Su. Writing, drafting, and revision of manuscript: Xiaolin Tang, Wenjie Su, Xie Wang. Final approval of paper: all authors. Acknowledgements The authors wish to express their gratitude to the Department of Pediatric Surgery for the support provided. References Bizzio R, Cianelli R, Villegas N, et al. Exploring Non-Pharmacological Management among Anesthesia Providers to Reduce Preoperative Distress in Children[J]. J Pediatr Nurs. 2020;50:105–12. Wang R, Huang X, Wang Y, et al. Non-pharmacologic Approaches in Preoperative Anxiety, a Comprehensive Review[J]. Front Public Health. 2022;10:854673. Kain ZN, Mayes LC, Caldwell-Andrews AA, et al. Preoperative anxiety, postoperative pain, and behavioral recovery in young children undergoing surgery[J]. Pediatrics. 2006;118(2):651–8. Hou H, Li X, Song Y, et al. 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Brosius KK, Bannister CF. Oral midazolam premedication in preadolescents and adolescents[J]. Anesth Analg, 2002, 94(1): 31 – 6, table of contents. Peretz B, Kharouba J, Somri M. A comparison of two different dosages of oral midazolam in the same pediatric dental patients[J]. Pediatr Dent. 2014;36(3):228–32. Zhao K, Li Y, Wang Q, et al. Effect of high-flow nasal oxygen therapy on perioperative hypoxemia in children: a systematic review and meta-analysis[J]. BMC Anesthesiol. 2025;25(1):428. Stinson HR, Srinivasan V, Topjian AA, et al. Failure of Invasive Airway Placement on the First Attempt Is Associated With Progression to Cardiac Arrest in Pediatric Acute Respiratory Compromise[J]. Pediatr Crit Care Med. 2018;19(1):9–16. De Graaff JC, Bijker JB, Kappen TH, et al. Incidence of intraoperative hypoxemia in children in relation to age[J]. Anesth Analg. 2013;117(1):169–75. Lerman J. Perioperative respiratory complications in children[J]. Lancet. 2010;376(9743):745–6. Habre W, Disma N, Virag K, et al. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe[J]. Lancet Respir Med. 2017;5(5):412–25. Liang ZJ, Liang JM, Nong XL, et al. Effect of intravenous different drugs on the prevention of restlessness during recovery period of pediatric laparoscopic surgery: a randomized control trial[J]. J Anesth. 2025;39(1):15–22. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8614681","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":598484054,"identity":"b171b527-3e40-439c-827d-7818801006ea","order_by":0,"name":"Xiaolin Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIie3PPQrCMACG4U+EuFRdEwo9Q6AgDoJXaSlk6qBbx0Khq7MInsMxErBLDtBVC87eQOPf4pBmdMg7lAT6ED7A5/vDCJKBHJTAZGQ+WAG0j0yR4EVIIAHJHQgrv4QmjoQ3mVTrA9KadafwxhcRK4fnS2sj+pqorUZMQiGo5CIOQeI4t5E252pc3yMS5jNDVLpHYM4WsnwT8xvTjuTzCiJCgzfZ9ZLXltpsCUQ212YLq/q2NNmxW9dINyN1bItiEdGmOnc28mxovboQn8/n8/30AM+kSPdzgBLhAAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China","correspondingAuthor":true,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Tang","suffix":""},{"id":598484055,"identity":"b9b557ca-c06d-4c36-9e14-252214e35831","order_by":1,"name":"Wenjie Su","email":"","orcid":"","institution":"Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Wenjie","middleName":"","lastName":"Su","suffix":""},{"id":598484058,"identity":"f78977cd-c8df-4ace-9ff1-2fcc4a1bc89b","order_by":2,"name":"Xie Wang","email":"","orcid":"","institution":"Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Xie","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-01-16 02:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8614681/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8614681/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104175383,"identity":"ffea1e62-6ebf-48c4-b046-890e383a0d1d","added_by":"auto","created_at":"2026-03-08 16:27:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58758,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8614681/v1/985b48e6b6312d2d64eb97ad.png"},{"id":104175384,"identity":"a674db33-fe4a-445b-9f71-06108e1252be","added_by":"auto","created_at":"2026-03-08 16:27:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":110305,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8614681/v1/b4f24b67c60f1309013d330f.png"},{"id":104430011,"identity":"7a2a36c4-0803-47e1-9fd3-a509cc41a2de","added_by":"auto","created_at":"2026-03-11 15:27:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1151404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8614681/v1/c2971e64-a96f-4c42-8876-7c68caee7ba5.pdf"},{"id":104404336,"identity":"50ef1e2b-fc6f-42e1-8ad9-4ab46b3c5202","added_by":"auto","created_at":"2026-03-11 12:20:02","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":16703,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8614681/v1/d09f15590f68ea7ea9c1297c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Retrospective Analysis of Midazolam Hydrochloride Oral Solution for Preoperative Anxiety and Sedation in Pediatric Patients: Evaluation of Efficacy and Safety","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDuring the preoperative and anesthesia preparation phase, children often exhibit signs of preoperative anxiety\u0026mdash;such as fear, anger, crying, and aggressive behavior\u0026mdash;due to the unfamiliar environment, the presence of medical staff, and fear of pain \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Firstly, preoperative anxiety can exacerbate pain perception, prolong both anesthesia induction and postoperative recovery times, increase the risk of postoperative delirium, heighten the requirement for analgesics, and elevate anesthetic risks \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Secondly, this anxiety impairs the child's ability to adapt to the unfamiliar medical setting and may raise the incidence of accidental injury. Finally, children experiencing preoperative anxiety are up to three times more likely to develop delirium, nightmares, separation anxiety, sleep disturbances, night crying, enuresis, temper tantrums, apathy, withdrawal, eating disorders, and negative behavioral changes such as increased fear of medical personnel \u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. These negative behaviors can persist for up to one year \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e and may hinder normal child development as well as future medical encounters \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Given that approximately 42\u0026ndash;75% of children experience preoperative anxiety \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, effective interventions to mitigate and prevent this clinical issue are essential.\u003c/p\u003e \u003cp\u003eMidazolam is a short-acting benzodiazepine characterized by sedative, amnestic, anxiolytic, muscle relaxant, and anticonvulsant properties. Its advantages include rapid onset, high metabolic clearance, and the induction of anterograde amnesia, making it widely used for pediatric sedation \u003csup\u003e[10; 11]\u003c/sup\u003e. It exerts its clinical effects by binding to the receptor complex, thereby potentiating the neuronal inhibition mediated by the neurotransmitter γ-aminobutyric acid (GABA) \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Midazolam has a faster onset and shorter duration of action compared to other benzodiazepines, such as diazepam and lorazepam\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. It can be administered via intravenous, intramuscular, intranasal, and oral routes. The oral route is often preferred in pediatric patients due to its ease of administration, non-invasiveness, and high acceptability\u003csup\u003e[14; 15]\u003c/sup\u003e.Flavored oral solutions improve palatability by masking the bitter taste of midazolam, enhancing compliance without affecting its metabolism. Numerous high-quality randomized controlled trials have demonstrated that oral midazolam reduces separation anxiety in children and their parents, decreases the incidence of negative preoperative behaviors\u0026mdash;including crying\u0026mdash;and improves acceptance of mask induction during anesthesia \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Owing to its safety profile, rapid onset, and reliable amnestic effect, midazolam oral solution is considered an ideal sedative for children \u003csup\u003e[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Nonetheless, adverse events\u0026mdash;including those involving the digestive, respiratory, and nervous systems\u0026mdash;may still occur \u003csup\u003e[20; 21]\u003c/sup\u003e. The recommended dosage of midazolam oral solution for pediatric use is 0.5\u0026ndash;1 mg/kg \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study Design\u003c/h2\u003e \u003cp\u003eThis study employed a retrospective cohort design to evaluate the efficacy and safety of midazolam hydrochloride oral solution in managing preoperative anxiety and providing sedation in pediatric patients. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the ethics board of Sichuan Provincial People\u0026rsquo;s Hospital, University of Electronic Science and Technology of China (No. 2025\u0026thinsp;\u0026minus;\u0026thinsp;836) and waived the requirement for informed consent due to the retrospective nature of the study design and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study Population\u003c/h2\u003e \u003cp\u003eThis retrospective study enrolled 52 pediatric patients who had received midazolam hydrochloride oral solution and undergone elective surgery under general anesthesia. Participants were included if they met all inclusion criteria and none of the exclusion criteria.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInclusion criteria were\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAged between 6 months and 16 years (inclusive), either sex.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eScheduled for elective surgery (e.g., in general surgery, urology, orthopedics, otorhinolaryngology, or stomatology) requiring preoperative sedative medication.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eExclusion criteria were\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eKnown hypersensitivity to any component of midazolam oral solution.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDiagnosis of acute angle-closure glaucoma or inadequately treated open-angle glaucoma.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eConcurrent participation in another interventional clinical trial.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eConsidered by the investigator to be unsuitable for participation for any other reason.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy termination criteria were\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDiscovery of a serious violation of inclusion/exclusion criteria after enrollment.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eVoluntary withdrawal requested by the participant's legal guardian or the participant themselves.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eLoss to follow-up, defined as the investigator's inability to make contact with the participant after more than three contact attempts over three consecutive days.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAny other circumstance deemed by the investigator to warrant discontinuation from the trial.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Study Methods\u003c/h2\u003e \u003cp\u003eData were retrospectively collected from 52 pediatric patients who had received midazolam hydrochloride oral solution (Specification: 0.2% [10 ml: 20 mg, calculated as C18H13ClFN3\u0026middot;HCl; manufactured by Jiangsu Enhua Pharmaceutical Co., Ltd.]) and undergone elective surgery under general anesthesia.\u003c/p\u003e \u003cp\u003eThe collected data included Ramsay Sedation Scores (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and anxiolysis scores (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) measured at the following time points: within 1 hour before oral administration (T0), and subsequently at 5\u0026ndash;10 minute intervals after administration (T1, T2, T3, T4, T5). Data were collected using a self-designed questionnaire (see Supplementary File 1).\u003c/p\u003e \u003cp\u003eVital signs, including pulse rate, respiratory rate, and SpO₂, were recorded during different periods: within 1 hour before drug administration, and then continuously monitored from the start of administration until the initiation of general anesthesia, with recordings made approximately every 5 minutes.\u003c/p\u003e \u003cp\u003eThe patient cooperation score was assessed after the administration of general anesthetic agents. The Post-Anesthesia Care Unit (PACU) recovery time was documented. Satisfaction evaluations from both guardians and anesthesiologists were recorded on the second day following drug administration.\u003c/p\u003e \u003cp\u003eAdverse events occurring after the administration of midazolam oral solution were collected. These included respiratory complications (e.g., hypoxia, laryngospasm), digestive system complications (e.g., nausea, vomiting), and nervous system complications (e.g., drowsiness, prolonged sedation).\u003c/p\u003e \u003cp\u003eThe dosage was administered as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eYounger children (\u0026ge;\u0026thinsp;6 months, \u0026lt;\u0026thinsp;6 years): 1.0 mg/kg\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eOlder children (\u0026ge;\u0026thinsp;6 years): 0.5 mg/kg\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThe maximum total administered dose did not exceed 20 mg.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRamsay Sedation Scale\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAwake\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient is anxious, agitated, or restless.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient is cooperative, oriented, and tranquil.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient responds to commands only.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAsleep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient exhibits a brisk response to a light glabellar tap or loud auditory stimulus.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient exhibits a sluggish response to a light glabellar tap or loud auditory stimulus.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient exhibits no response to a light glabellar tap or loud auditory stimulus.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnxiolysis Score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApprehensive, restless, crying, and/or resists reassurance.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFearful, moderate apprehension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMildly fearful, easily reassured by strangers, non-aggressive.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo signs of fear or anxiety.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient is asleep.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Evaluation Criteria\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1. Primary Efficacy Endpoints\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThe proportion of participants achieving successful anxiolysis within 30 minutes post-administration.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003e*Note: Successful anxiolysis was defined as achieving an anxiolysis score of 3 or higher within 30 minutes post-administration without the use of rescue medication.*\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThe proportion of participants achieving successful Ramsay sedation within 30 minutes post-administration.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003e*Note: Successful sedation was defined as achieving a Ramsay Sedation Score of 3 or higher within 30 minutes post-administration without the use of rescue medication.*\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2. Secondary Efficacy Endpoints\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eTime from drug administration to successful anxiolysis.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTime from drug administration to successful sedation.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCooperation degree (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) in participants who achieved sedation success.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eo Note\u003c/strong\u003e \u003cp\u003eo \u003cem\u003eSatisfactory cooperation was defined as a cooperation score between 3 and 5 points without the use of rescue medication.\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSatisfaction ratings from guardians and anesthesiologists (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eo Note\u003c/strong\u003e \u003cp\u003eo \u003cem\u003eComprehensive assessment based on factors such as palatability, sedative effect, and duration of action.\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePediatric Post-Anesthesia Care Unit (PACU) recovery time.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIncidence of adverse events following administration of midazolam oral solution, including:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eRespiratory complications (e.g., hypoxia, laryngospasm).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDigestive system complications (e.g., nausea, vomiting).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCirculatory system complications (e.g., significant tachycardia or bradycardia).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNervous system complications (e.g., drowsiness, prolonged sedation).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCooperation Score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eScore Description\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVigorously resists the procedure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCooperation is achieved only with considerable effort by the staff.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReluctantly accepts the procedure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReadily accepts the procedure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient is asleep.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSatisfaction Rating\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eScore Description\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery Dissatisfied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDissatisfied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModerately Satisfied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSatisfied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery Satisfied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS software (version 22.0). Continuous data were summarized using descriptive statistics, including number of cases (n), mean, median, standard deviation, minimum, and maximum values. Categorical data were presented as frequency tables and percentages.\u003c/p\u003e \u003cp\u003eThe proportions of participants achieving successful anxiolysis and successful Ramsay sedation within 30 minutes post-administration were calculated, along with their corresponding two-sided 95% confidence intervals (CI) using the Clopper-Pearson exact method.\u003c/p\u003e \u003cp\u003eThe time intervals from drug administration to successful anxiolysis and from drug administration to successful sedation were analyzed using the Kaplan-Meier methodology.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003ch3\u003e3.1. Baseline Characteristics of the Pediatric Cohort\u003c/h3\u003e\n\u003cp\u003eA total of 52 pediatric patients were initially included in this study. Among them, 9 cases were excluded: guardians of 4 children declined to participate on the day of surgery, guardians of 1 child withdrew due to difficulty with ingestion, and investigators determined that 4 children did not meet the inclusion criteria on the day of surgery. Consequently, 43 pediatric patients were ultimately included in the final analysis (Figure 1). The demographic and baseline characteristics of the included children are presented in Table 5.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 553px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 5. Demographic and Baseline Characteristics of the Pediatric Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eSex (Male/Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e37/6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eAge (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e41.53\u0026plusmn;38.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eAge Group (\u0026lt;6 years / \u0026ge;6 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e37/6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e16.91\u0026plusmn;10.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eBMI（kg/m\u003csup\u003e2\u003c/sup\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e16.80\u0026plusmn;2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eASA(I/II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003e42/1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e3.2. Anxiolytic and Sedative Effects\u003c/h3\u003e\n\u003cp\u003eAnalysis using the Clopper-Pearson method indicated that among the 43 children, 43 achieved an anxiolysis score of \u0026ge;3 within 30 minutes post-administration, yielding a successful anxiolysis rate of 100% (95% CI: 91.75%, 100.00%). Furthermore, 39 children attained an anxiolysis score of \u0026ge;4, corresponding to a success rate of 90.72% (95% CI: 78.1%, 97.5%). Regarding sedation, 36 children achieved a Ramsay Sedation Score of \u0026ge;3 within 30 minutes, resulting in a successful sedation rate of 83.72% (95% CI: 69.7% - 92.7%).\u003c/p\u003e\n\u003cp\u003eKaplan-Meier analysis revealed that the mean time to achieve successful anxiolysis (score \u0026ge;3) was 7.72 \u0026plusmn; 0.53 minutes (95% CI: 6.68 \u0026ndash; 8.77), with an overall median time of 6 minutes (95% CI: 5.65 \u0026ndash; 6.35). Successful anxiolysis occurred predominantly in the early phase post-administration, with cumulative success rates reaching 95.3% at 15 minutes and 100% at 30 minutes. For the higher threshold (anxiolysis score \u0026ge;4), the mean time to achievement was 17.56 \u0026plusmn; 2.20 minutes (95% CI: 13.25 \u0026ndash; 21.87), with an overall median time of 13 minutes (95% CI: 12.59 \u0026ndash; 13.41). The cumulative success rates for an anxiolysis score \u0026ge;4 were 60.8% at 15 minutes and 90.7% at 30 minutes.\u003c/p\u003e\n\u003cp\u003eThe mean time to achieve successful Ramsay sedation (score \u0026ge;3) was 18.35 \u0026plusmn; 1.04 minutes (95% CI: 16.31 \u0026ndash; 20.39), with an overall median time of 19 minutes (95% CI: 13.89 \u0026ndash; 24.11). In contrast to anxiolysis, the successful attainment of sedation occurred primarily in the later phase, with cumulative success rates of 44.20% at 15 minutes and 83.72% at 30 minutes (Table 6). The individual times to successful anxiolysis and sedation for each child are illustrated in Figure 2.\u003c/p\u003e\n\u003cp\u003eAnxiolysis and Ramsay Sedation Scores at various time points are detailed in Table 7. Notably, all children achieved an anxiolysis score of \u0026ge;3 from time point T3 onwards.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"776\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 776px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 6. Number and Success Rate of Successful Anxiolysis and Ramsay Sedation, with Median and Mean Times\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003en/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eProportion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e95% CI(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eMedian Time (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e95% CI (min) for Median\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eMean Time (min, Mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e95% CI (min) for Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eSuccessful Ramsay Sedation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e36/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e83.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e69.7-92.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e13.89-24.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e18.35\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e16.31\u0026ndash;20.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eSuccessful Anxiolysis (Score \u0026ge;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e43/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e91.75-100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e5.65-6.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e7.72\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e6.68\u0026ndash;8.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eAnxiolysis Score \u0026ge;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e39/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e90.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e78.1-97.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e12.59-13.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e17.56\u0026plusmn;2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e13.25\u0026ndash;21.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 213px;\"\u003e\n \u003cp\u003e\u003cem\u003eNote: CI = Confidence Interval.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 552px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 7. Anxiolysis and Ramsay Sedation Scores at Different Time Intervals\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eMeasurement times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003eAnxiolysis Score (Mean\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003eRamsay Sedation Score (Mean\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT0（n=43）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e1.93\u0026plusmn;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e1.47\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT1（n=43）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e2.86\u0026plusmn;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e1.84\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT2（n=43）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e3.63\u0026plusmn;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e2.40\u0026plusmn;0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT3（n=40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e3.88\u0026plusmn;0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e2.80\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT4（n=31）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e3.87+0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e2.78\u0026plusmn;0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003eT5（n=8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e4.00\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 201px;\"\u003e\n \u003cp\u003e2.78\u0026plusmn;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e3.3. Child Cooperation, Satisfaction, and PACU Recovery Time\u003c/h3\u003e\n\u003cp\u003eDuring anesthesia induction, the mean cooperation score was 3.95 \u0026plusmn; 0.21. Among the 43 children, only two received a score of 3, both occurring during intravenous propofol injection. This was attributed to propofol injection pain, which was not entirely prevented despite the pre-emptive administration of lidocaine mixed into the propofol solution. The remaining children all received a score of 4.\u003c/p\u003e\n\u003cp\u003eThe PACU recovery time, defined as the duration from PACU arrival until fully awake and ready for discharge, averaged 101.16 \u0026plusmn; 41.84 minutes.\u003c/p\u003e\n\u003cp\u003eSatisfaction surveys conducted on the first postoperative day revealed a mean guardian satisfaction score of 4.30 \u0026plusmn; 0.74 and a mean anesthesiologist satisfaction score of 4.21 \u0026plusmn; 0.91. The difference between these scores was not statistically significant (Table 8).\u003c/p\u003e\n\u003cp\u003eFurthermore, a comparison of PACU recovery times between children aged \u0026le;2 years and those \u0026gt;2 years showed a statistically significant prolongation in the younger age group (\u0026le;2 years) (Table 9). This indicates that younger age (\u0026le;2 years) may be associated with prolonged recovery, suggesting that the dosage requirement for midazolam oral solution in this specific population warrants further investigation.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\" style=\"margin-right: calc(18%); width: 82%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 97.0175%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 8. Child Cooperation Score, Guardian and Anesthesiologist Satisfaction Ratings, and PACU Recovery Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.743%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2914%;\"\u003e\n \u003cp\u003e(Mean\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.9298%;\" colspan=\"2\"\u003eP-value\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.743%;\"\u003e\n \u003cp\u003eCooperation Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5725%;\"\u003e\n \u003cp\u003e3.95\u0026plusmn;0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.3236%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.743%;\"\u003e\n \u003cp\u003ePACU Recovery Time (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5725%;\"\u003e\n \u003cp\u003e101.16\u0026plusmn;41.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.3236%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.743%;\"\u003e\n \u003cp\u003eGuardian Satisfaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5725%;\"\u003e\n \u003cp\u003e4.30\u0026plusmn;0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 13.3236%;\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.743%;\"\u003e\n \u003cp\u003eAnesthesiologist Satisfaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5725%;\"\u003e\n \u003cp\u003e4.21\u0026plusmn;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"560\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 560px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 9. PACU Recovery Time by Age Group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 313px;\"\u003e\n \u003cp\u003ePACU Recovery Time (min), Mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026le;2（year,n=21）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 313px;\"\u003e\n \u003cp\u003e114.90\u0026plusmn;42.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e＞2（year,n=22）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 313px;\"\u003e\n \u003cp\u003e88.04\u0026plusmn;38.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e3.4. Adverse Events\u003c/h3\u003e\n\u003cp\u003eAmong all pediatric patients, six experienced nausea, which was followed by vomiting. These events occurred immediately after drug administration. The vomitus consisted solely of the medication, with no gastric contents, and no instances of aspiration occurred. No patients experienced adverse events such as hypoxia or laryngospasm.\u003c/p\u003e\n\u003cp\u003eProlonged sedation, defined as a PACU recovery time exceeding 2 hours, was observed in 14 children. Notably, all 14 children were under 6 years of age and had received the 1.0 mg/kg dose (Table 10).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"596\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 596px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 10.Incidence of Adverse Events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eSystem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eAdverse Event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eNumber of Cases (n=43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eIncidence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003eDigestive System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e13.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e13.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003eRespiratory System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eHypoxia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eLaryngospasm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003eNervous System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eDrowsiness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eProlonged Sedation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e32.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"4. Discussion","content":"\u003cp\u003ePreoperative anxiety in pediatric patients can activate the sympathetic, parasympathetic, and endocrine systems, leading to numerous adverse clinical outcomes, including postoperative psychological trauma, emergence delirium, altered sleep patterns, and aggressive behavior \u003csup\u003e[3; 22]\u003c/sup\u003e. The primary factors contributing to pediatric anxiety include separation from guardians, fear of doctors and syringes, limited understanding of their illness, and the inherent stress of undergoing surgery. Consequently, anesthesiologists employ various pharmacological agents to mitigate this stress response. The primary objectives of pediatric premedication are anxiolysis to facilitate smooth separation from guardians and entry into the operating room, thereby enhancing anesthesia safety. Additional goals include amnesia, attenuation of the stress response, reduction of total anesthetic requirements, decreased risk of aspiration, reduced salivary secretions, antiemesis, and analgesia\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMidazolam, a benzodiazepine, offers advantages such as rapid onset, anterograde amnesia, and minimal respiratory depression. It is commonly used for sedation prior to surgery, radiographic imaging, and invasive procedures \u003csup\u003e[\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. It remains the most frequently used sedative for anxiolysis in children, with the oral route being the first-line choice due to its ease of administration, non-invasiveness, and high acceptability in the pediatric population\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe findings of this study demonstrate that midazolam hydrochloride oral solution, administered at doses of 1.0 mg/kg for children aged 6 months (inclusive) to 6 years and 0.5 mg/kg for those aged 6 years (inclusive) to 16 years, effectively alleviates preoperative anxiety and provides satisfactory sedation within 30 minutes of administration. This facilitates improved cooperation with healthcare staff during anesthesia induction. Furthermore, the treatment was associated with high satisfaction rates among both guardians and anesthesiologists.\u003c/p\u003e \u003cp\u003eIn this study, the successful anxiolysis rate within 30 minutes post-administration was 100%, with no failures observed. Among the children, 40 (93.02%) achieved an anxiolysis score of \u0026ge;\u0026thinsp;4. The successful Ramsay sedation rate was 83.72%, with a failure rate of 16.28%. These findings exhibit some divergence from certain other studies; for instance, investigations by Sultan Keles and Wheeler reported oral midazolam sedation success rates of 96.2% and 93%, respectively \u003csup\u003e[27; 28]\u003c/sup\u003e. This discrepancy may be attributable to differences in study design, the specific sedation scales employed, and investigator subjectivity, warranting caution when directly comparing sedation success rates across studies. For example, the defined timeframes for assessing successful sedation vary among studies\u003csup\u003e[27; 29]\u003c/sup\u003e. Furthermore, some studies utilize different sedation scales to evaluate efficacy, such as the Observer's Assessment of Alertness/Sedation (OAA/S) scale\u003csup\u003e[16; 30]\u003c/sup\u003e. Our study employed the Ramsay Sedation Scale due to its practicality and ease of use, allowing for rapid and repeated assessments within short timeframes. However, it relies heavily on the observer's judgment and is characterized by its significant subjectivity.\u003c/p\u003e \u003cp\u003eIn this study, the mean times to achieve an anxiolysis score of 4 and successful sedation were 13.70\u0026thinsp;\u0026plusmn;\u0026thinsp;5.94 minutes and 16.08\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96 minutes, respectively. This finding is consistent with prior studies indicating that oral midazolam typically exerts its sedative effect within 15\u0026ndash;30 minutes \u003csup\u003e[17; 31]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur results suggest a high level of cooperation prior to anesthesia induction in the pediatric cohort, with the vast majority readily accepting interventions and calmly accompanying medical staff into the operating room. This high level of cooperation obviated the need for stronger sedative agents like propofol to facilitate smooth induction in most cases. Only two children exhibited lower cooperation scores, which we attribute to possible propofol injection pain. It is noteworthy that despite the prophylactic addition of lidocaine to the propofol solution, this measure does not completely prevent injection pain.\u003c/p\u003e \u003cp\u003eIn children not receiving preoperative medication, preoperative crying can lead to increased secretions, elevated risk of respiratory complications, and increased heart rate and oxygen consumption. Poor cooperation can also prolong the time required to establish monitoring equipment and shorten the period available for pre-oxygenation. Consequently, the use of potent sedative agents like propofol may become necessary, potentially causing respiratory depression. Compared to adults, children have lower oxygen reserves and higher oxygen consumption, which increases the risk of severe adverse events, including hypoxic encephalopathy, cardiac arrest, or even death \u003csup\u003e[\u003cspan additionalcitationids=\"CR33 CR34 CR35\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding whether the medication prolongs PACU recovery time, we only performed descriptive statistics due to the lack of a control group. One study reported a mean PACU recovery time of 81.88\u0026thinsp;\u0026plusmn;\u0026thinsp;17.53 minutes following pediatric laparoscopic surgery \u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e. While this differs from our findings, considerations such as variations in surgical type, patient age, and anesthetic regimens must be accounted for, necessitating further investigation for confirmation.\u003c/p\u003e \u003cp\u003eFurthermore, we compared PACU recovery times between children aged\u0026thinsp;\u0026le;\u0026thinsp;2 years and those\u0026thinsp;\u0026gt;\u0026thinsp;2 years. The recovery time was significantly longer in the \u0026le;\u0026thinsp;2 years age group, and this difference was statistically significant (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e9\u003c/span\u003e). This indicates that younger age (\u0026le;\u0026thinsp;2 years) may be associated with prolonged recovery, suggesting that the dosage regimen of midazolam oral solution for this specific population warrants further exploration.\u003c/p\u003e \u003cp\u003eFurthermore, postoperative follow-up surveys were conducted to assess satisfaction with the medication among both guardians and anesthesiologists. The results indicated high satisfaction ratings from both groups, which can contribute to fostering trust between anesthesiologists and patients' families.\u003c/p\u003e \u003cp\u003eRegarding adverse events, within the scope of our analysis, the primary occurrences were nausea, vomiting, and prolonged sedation. No other serious adverse events, including laryngospasm or hypoxia, were reported. It is noteworthy that all instances of nausea and vomiting occurred immediately after drug ingestion and were not observed during general anesthesia induction, emergence, or in the PACU. This suggests these events might be related to the child's resistance to taking the medication itself, rather than being a direct effect of the midazolam oral solution. Conversely, the incidence of prolonged sedation was notably high at 32.56%. Analysis revealed that all children experiencing prolonged sedation were under 6 years of age and had received the 1.0 mg/kg dose. In the absence of a control group, a definitive causal link between the medication and prolonged sedation cannot be established; however, younger age appears to be a significant contributing factor.\u003c/p\u003e \u003cp\u003eDespite our findings demonstrating the satisfactory efficacy of midazolam hydrochloride oral solution for preoperative anxiolysis and sedation in children, this study has several limitations. First, its design was single-center and open-label, with all outcomes evaluated solely in children who received the study drug and without a control group for comparison. Additionally, the sample size was relatively small. Second, the assessment of both the anxiolysis and Ramsay sedation scores involves a degree of subjectivity, which could potentially influence the results. Finally, the wide age range of the included children and the different dosages used for various age groups might also have introduced bias into the study findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates that administration of midazolam hydrochloride oral solution at a dose of 0.5-1.0 mg/kg, 30 minutes prior to anesthesia induction, provides adequate anxiolysis and sedation levels in pediatric patients. The treatment yielded satisfactory outcomes for both anesthesiologists and guardians, facilitating smooth induction of anesthesia without the occurrence of serious adverse events. However, it is important to note the potential for prolonged postoperative recovery time in the PACU, particularly in children aged 2 years or younger.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe study received approved from the Institutional Ethics Committee (approval no. 2025836), and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877). The study\u0026nbsp;waived the requirement for informed consent due to the retrospective nature of the study design\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eStudy concept/design: Xiaolin Tang, Wenjie Su, Xie Wang.\u003c/p\u003e\n\u003cp\u003eData collection: Xiaolin Tang, Xie Wang.\u003c/p\u003e\n\u003cp\u003eData analysis: Xiaolin Tang, Wenjie Su.\u003c/p\u003e\n\u003cp\u003eWriting, drafting, and revision of manuscript: Xiaolin Tang, Wenjie Su, Xie Wang.\u003c/p\u003e\n\u003cp\u003eFinal approval of paper: all authors.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors wish to express their gratitude to the Department of Pediatric Surgery for the support provided.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBizzio R, Cianelli R, Villegas N, et al. 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BMC Anesthesiol. 2023;23(1):95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed MI, Farrell MA, Parrish K, et al. Preoperative anxiety in children risk factors and non-pharmacological management[J]. Middle East J Anaesthesiol. 2011;21(2):153\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrasković B, Simin JM, Kvrgić IM. Psychological aspects of pediatric anesthesia[J]. Med Pregl. 2015;68(1\u0026ndash;2):29\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldakhil SK, Salam M, Albelali AA, et al. The prevalence of emergence delirium and its associated factors among children at a postoperative unit: A retrospective cohort at a Middle Eastern hospital[J]. Saudi J Anaesth. 2020;14(2):169\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarreto A, Rangel Da Rocha Paschoal AC, Barbosa Farias C, et al. [Risk factors associated with anesthesia emergence delirium in children undergoing outpatient surgery][J]. Braz J Anesthesiol. 2018;68(2):162\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu W, Xu R, Jia J et al. Research Progress on Risk Factors of Preoperative Anxiety in Children: A Scoping Review[J]. Int J Environ Res Public Health, 2022, 19(16).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng L, Morford KL, Levander XA. Benzodiazepines and Related Sedatives[J]. Med Clin North Am. 2022;106(1):113\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMason KP, Seth N. The pearls of pediatric sedation: polish the old and embrace the new[J]. Minerva Anestesiol. 2019;85(10):1105\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlkkola KT, Ahonen J. Midazolam and other benzodiazepines[J]. Handb Exp Pharmacol, 2008, (182): 335\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlumer JL. Clinical pharmacology of midazolam in infants and children[J]. Clin Pharmacokinet. 1998;35(1):37\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDave NM. Premedication and Induction of Anaesthesia in paediatric patients[J]. Indian J Anaesth. 2019;63(9):713\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManoj M, Satya Prakash MVS, Swaminathan S, et al. Comparison of ease of administration of intranasal midazolam spray and oral midazolam syrup by parents as premedication to children undergoing elective surgery[J]. J Anesth. 2017;31(3):351\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManso MA, Guittet C, Vandenhende F, et al. Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: A systematic review[J]. Paediatr Anaesth. 2019;29(11):1094\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng X, Chen Z, Zhang L, et al. Efficacy and Safety of Midazolam Oral Solution for Sedative Hypnosis and Anti-anxiety in Children: A Systematic Review and Meta-Analysis[J]. Front Pharmacol. 2020;11:225.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnnan BNY, Owusu Darkwa E, Anno A, et al. Appropriateness and safety of using the intranasal route for sedation during pediatric computed tomography: A randomized controlled trial at Korle-Bu teaching hospital[J]. J Int Med Res. 2025;53(7):3000605251357455.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBinh NQ, Ngoc VTN, Khanh PQ et al. Efficacy of Oral Midazolam for Sedation and Amnesia in Preschool Children with Dental Anxiety: A Double-Blind, Randomized Controlled Trial[J]. Dent J (Basel), 2025, 13(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNys M, Garip M, Coropciuc R et al. Complications of Intravenous Midazolam-Fentanyl Sedation in Children and Adults Undergoing Oral Surgery: A Retrospective Study[J]. J Clin Med, 2025, 14(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Lei R. Study on the sedative effect and safety of oral midazolam combined with dexmedetomidine nasal drops in children during magnetic resonance imaging examination[J]. Front Pediatr. 2024;12:1500277.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFortier MA, Del Rosario AM, Martin SR, et al. Perioperative anxiety in children[J]. Paediatr Anaesth. 2010;20(4):318\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLethin M, Paluska MR, Petersen TR, et al. Midazolam for Anesthetic Premedication in Children: Considerations and Alternatives[J]. Cureus. 2023;15(12):e50309.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNathan JE. Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience[J]. J Clin Pediatr Dent. 2022;46(2):152\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarra R, Piersanti A, Del Vicario M et al. Clinical Evaluation of Oral Midazolam Containing Cyclodextrin in Pediatric Magnetic Resonance: A Retrospective Cohort Study[J]. J Pers Med, 2024, 14(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiao H, Chen J, Lv P, et al. Efficacy of premedication with intravenous midazolam on preoperative anxiety and mask compliance in pediatric patients: a randomized controlled trial[J]. Transl Pediatr. 2022;11(11):1751\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeles S, Kocaturk O. Comparison of oral dexmedetomidine and midazolam for premedication and emergence delirium in children after dental procedures under general anesthesia: a retrospective study[J]. Drug Des Devel Ther. 2018;12:647\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWheeler DS, Jensen RA, Poss WB. A randomized, blinded comparison of chloral hydrate and midazolam sedation in children undergoing echocardiography[J]. Clin Pediatr (Phila). 2001;40(7):381\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong H, Liu J, Liu G, et al. Effective doses of midazolam oral solution for the prevention of preoperative anxiety in paediatric patients[J]. Int J Paediatr Dent. 2024;34(5):621\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrosius KK, Bannister CF. Oral midazolam premedication in preadolescents and adolescents[J]. Anesth Analg, 2002, 94(1): 31\u0026thinsp;\u0026ndash;\u0026thinsp;6, table of contents.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeretz B, Kharouba J, Somri M. A comparison of two different dosages of oral midazolam in the same pediatric dental patients[J]. Pediatr Dent. 2014;36(3):228\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao K, Li Y, Wang Q, et al. Effect of high-flow nasal oxygen therapy on perioperative hypoxemia in children: a systematic review and meta-analysis[J]. BMC Anesthesiol. 2025;25(1):428.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStinson HR, Srinivasan V, Topjian AA, et al. Failure of Invasive Airway Placement on the First Attempt Is Associated With Progression to Cardiac Arrest in Pediatric Acute Respiratory Compromise[J]. Pediatr Crit Care Med. 2018;19(1):9\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Graaff JC, Bijker JB, Kappen TH, et al. Incidence of intraoperative hypoxemia in children in relation to age[J]. Anesth Analg. 2013;117(1):169\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLerman J. Perioperative respiratory complications in children[J]. Lancet. 2010;376(9743):745\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHabre W, Disma N, Virag K, et al. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe[J]. Lancet Respir Med. 2017;5(5):412\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang ZJ, Liang JM, Nong XL, et al. Effect of intravenous different drugs on the prevention of restlessness during recovery period of pediatric laparoscopic surgery: a randomized control trial[J]. J Anesth. 2025;39(1):15\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pediatric, Preoperative Anxiety, Sedation, Midazolam, Premedication","lastPublishedDoi":"10.21203/rs.3.rs-8614681/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8614681/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch3\u003eBackground\u003c/h3\u003e\n\u003cp\u003eMidazolam is widely used for preoperative anxiety and sedation in pediatric patients.This study aims to analyze the effectiveness of midazolam hydrochloride oral solution in alleviating preoperative anxiety and providing sedation in pediatric patients, while concurrently evaluating its safety profile.\u003c/p\u003e\n\u003ch3\u003eMethods\u003c/h3\u003e\n\u003cp\u003eIn this retrospective study, 52 pediatric patients were enrolled. Anxiety and sedation levels were primarily assessed using an anxiolysis score and the Ramsay Sedation Score. The primary efficacy endpoints were the proportion of children achieving successful anxiolysis and successful sedation within 30 minutes post-administration. Secondary efficacy endpoints included the time from administration to successful anxiolysis and successful sedation, the parental separation score or a cooperation score, satisfaction ratings from both guardians and anesthesiologists regarding the medication, and the pediatric post-anesthesia care unit (PACU) recovery time. Furthermore, the incidence of adverse events, including those related to the gastrointestinal, respiratory, and nervous systems, was analyzed.\u003c/p\u003e\n\u003ch3\u003eResults\u003c/h3\u003e\n\u003cp\u003eWithin 30 minutes, the successful anxiolysis rate was 100%, with a failure rate of 0%. The mean time to achieve successful anxiolysis was 7.72 ± 3.50 minutes. The Ramsay sedation success rate was 83.72%, with a failure rate of 16.28%. The mean time to achieve successful sedation was 16.08 ± 4.96 minutes.The cooperation score was 3.9 ± 0.21.Postoperative guardian satisfaction score averaged 4.30 ± 0.74, and anesthesiologist satisfaction score averaged 4.21 ± 0.91. The mean PACU recovery time was 101.16 ± 41.84 minutes.Regarding adverse events, the incidence of both nausea and vomiting was 13.96%, while the incidence of prolonged sedation was 32.56%.\u003c/p\u003e\n\u003ch3\u003eConclusion\u003c/h3\u003e\n\u003cp\u003eMidazolam hydrochloride oral solution is effective in alleviating preoperative anxiety and providing satisfactory sedation in pediatric patients. Furthermore, it demonstrates high satisfaction rates among both guardians and anesthesiologists. The treatment was well-tolerated with no serious adverse events reported, thereby confirming its favorable efficacy and safety profile.\u003c/p\u003e\n\u003ch3\u003eEthics\u003c/h3\u003e\n\u003cp\u003eThe study population comprised pediatric patients who underwent elective surgery under general anesthesia at Sichuan Provincial People's Hospital between April and August 2025. The study received approved from the Institutional Ethics Committee (approval no. 2025836), and was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2500115877).\u003c/p\u003e","manuscriptTitle":"Retrospective Analysis of Midazolam Hydrochloride Oral Solution for Preoperative Anxiety and Sedation in Pediatric Patients: Evaluation of Efficacy and Safety","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 16:27:04","doi":"10.21203/rs.3.rs-8614681/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"55a48cf4-f6b0-48f8-98bc-5a22067d3e9d","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T15:25:58+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 16:27:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8614681","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8614681","identity":"rs-8614681","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}