Dental fear has been recognised as a major issue in paediatric dentistry and one of the most prevalent problems in achieving successful dental treatment in children [1]. Dental visits may be challenging for both the clinician and the caregiver due to increased anxiety that may be caused by fear, uncooperative patients, pain anticipation, unfamiliar clinical settings, or previous negative experiences in healthcare settings [2]. Inadequate control of anxiety in the context of pediatric dental care can result in an incomplete dental treatment, behavioral trauma, higher likelihood of dental treatment avoidance, and a decline in oral health [3]. Depending on the child's age, anxiety level, developmental status and the complexity of the procedure, pediatric dentistry can use a variety of behavior management techniques ranging from non-pharmacological communication techniques to pharmacological sedation techniques [4].

Pharmacological options include nitrous oxide–oxygen inhalation sedation and oral midazolam, which are both effective and relatively easy to administer and have a relatively good safety profile, and are widely used for conscious sedation [5]. Nitrous oxide–oxygen sedation is the most frequently employed, due to its short onset of action, the ability to titrate to effect, anxiolytic and mild analgesic properties, and quick recovery time [6]. It helps to maintain the protective airway reflexes and spontaneous ventilation, thus it is an ideal choice for minimally invasive or short dental procedures in children [7]. Furthermore, its non-invasive route of administration and good safety profile has led to its acceptance as a standard treatment in pediatrics [8]. Another commonly used short-acting benzodiazepine sedative for the management of dental anxiety in children is oral midazolam [9]. It is used in children to achieve both anxiolysis and sedation, as well as to achieve amnesia and control their behavior, and thus can be useful when they have moderate to severe anxiety or when they are likely to be difficult to control [10]. Some children, though, experience variable absorption, delayed onset, extended recovery and paradoxical behavioral responses to oral midazolam [11].

Comparative evaluation of these sedation techniques is clinically relevant, as both techniques have differences in pharmacodynamics, administration, onset and recovery profile and patient acceptance [12]. N2O might have better recovery properties and procedure flexibility, while oral midazolam might be more effective in providing greater anxiolysis in some children [13]. The decision regarding which sedative to use may be based on the effectiveness, safety, procedural needs, and recovery needs. Safety is always a primary issue in the sedation of children. Oxygen desaturation, nausea, vomiting, excessive sedation, respiratory depression, paradoxical agitation, and delayed recovery are some potential adverse events that should be monitored [14]. Thus, there needs to be evidence that compares the outcomes of the safety of the sedation modalities to inform pediatric dental practice [15]. Both nitrous oxide and oral midazolam are effective for managing pediatric procedural anxiety [16], but results on comparative behavioral outcomes, recovery time, and complication rates are inconclusive.

Objective

To compare nitrous oxide–oxygen sedation and oral midazolam in terms of anxiety control, safety, procedural cooperation, and recovery outcomes in pediatric dental procedures.

This was a comparative cross-sectional analytical study conducted at Jinnah Hospital Karachi from July 2024 to July 2025, including 210 pediatric patients. Children aged 4 – 12 years with moderate to severe dental anxiety or children that were deemed poor co-operators and required dental procedures under conscious sedation were eligible for the study. Patients in ASA physical status I or II (restorative, extraction, pulp therapy or other minor to moderately invasive dental treatment) with informed consent from parents/guardians were included. Excluded were children who had severe systemic illness, respiratory compromise, obstructive airway disease, known hypersensitivity to benzodiazepines, developmental disorders that greatly limited behavioral evaluation, psychiatric illness, significant hepatic impairment, active upper respiratory tract infection, or contraindications to nitrous oxide administration. Patients who did not have records of monitoring or failed the sedation protocol were excluded. Data Collection Once the ethical issues were addressed, a structured proforma was used to collect data. Demographic data such as age, gender, weight, dental procedure, anxiety level before the intervention, as well as any medical history relevant to the intervention, were included as baseline variables. Patients were randomly assigned to two groups: nitrous oxide–oxygen inhalation sedation group and oral midazolam sedation group. Standardized pediatric behavioral/anxiety scales were used to assess anxiety levels before and during the procedure. Procedural cooperation, adequacy of sedation, onset time, success of the procedure, and adverse events such as nausea, vomiting, oxygen desaturation, excessive sedation, paradoxical agitation, and recovery time were documented. Heart rate, Respiratory rate, oxygen saturation, and hemodynamic stability were monitored continuously during the procedure. Statistical Analysis SPSS version 26.0 was used for data analysis. Data were expressed as mean ± SD for continuous variables and as the frequency and percentage for categorical variables. Independent t-tests and chi-square tests were used for comparing the clinical outcomes of the two sedation groups. A multivariable logistic regression analysis was done to determine the factors associated with sedation-related adverse events and successful procedures. A p-value ≤0.05 was considered statistically significant.

Both sedation groups were comparable at baseline. Mean age was 7.8 ± 2.1 years in the nitrous oxide–oxygen group and 8.1 ± 2.3 years in the oral midazolam group (p=0.31). Gender distribution was also similar, with males representing 55.2% and 51.4% of the groups, respectively (p=0.58). Mean weight was comparable between groups (25.6 ± 6.4 kg vs 26.3 ± 6.9 kg; p=0.44). Baseline anxiety severity showed no significant difference, with moderate anxiety reported in 60.0% versus 56.2% and severe anxiety in 40.0% versus 43.8% of patients (p=0.57).

Table 1: Baseline Demographic and Procedural Characteristics of Pediatric Patients (n = 210)

Nitrous oxide–oxygen sedation had a much faster onset time than oral midazolam (4.8 ± 1.6 vs. 21.7 ± 6.4 minutes; p<0.001). Adequate anxiety control was slightly higher with nitrous oxide–oxygen, 91 (86.7%) versus 84 (80.0%), while procedure completion success was also higher, 98 (93.3%) versus 92 (87.6%).

Table 2: Comparative Sedation Effectiveness and Procedural Outcomes

Adverse events were significantly lower in the nitrous oxide–oxygen group compared with oral midazolam, 12 (11.4%) versus 29 (27.6%) (p=0.003). Oxygen desaturation was less frequent with nitrous oxide–oxygen, 1 (1.0%) versus 7 (6.7%) (p=0.03), while excessive sedation occurred only in the oral midazolam group, 6 (5.7%) (p=0.01).

Table 3: Safety and Adverse Events Comparison Between Sedation Groups

Recovery was significantly faster with nitrous oxide–oxygen sedation, with mean recovery time of 14.6 ± 5.2 minutes compared to 49.3 ± 13.8 minutes for oral midazolam (p<0.001). Same-day discharge without delay was achieved in 102 (97.1%) nitrous oxide cases versus 91 (86.7%) midazolam cases (p=0.006). Post-procedure drowsiness was markedly lower with nitrous oxide–oxygen, 5 (4.8%) versus 26 (24.8%) (p<0.001).

Table 4: Recovery Profile and Post-Procedure Outcomes

This study compared the sedation techniques of nitrous oxide–oxygen versus oral midazolam administration for pediatric dental procedures and concluded that both techniques were effective at controlling anxiety and successful at performing the dental procedure, with nitrous oxide–oxygen having a better safety profile and a better recovery profile. The implications of these findings in pediatric dentistry are significant for the need to ensure that sedation is effective with a quick recovery and limited side effects. Study groups were similar at baseline with respect to age (7.8 ± 2.1 years vs. 8.1 ± 2.3 years), weight (25.6 ± 6.4 kg vs. 26.3 ± 6.9 kg), anxiety severity, and procedure types, thus allowing for a fair comparison of the two sedation modalities. This similarity reinforces the legitimacy of making comparisons in outcomes. In a previous study, similar pediatric populations were used for assessing the techniques of conscious sedation [17].

For effectiveness, both sedations provided high anxiety control and successful procedures. Fourteen of 16 children (86.7%) treated with nitrous oxide–oxygen had an adequate response to the procedure; 12 of 15 children (80.0%) treated with oral midazolam had an adequate response to the procedure. Children who had a successful outcome of the procedure were considered to have adequate anxiety control. Slightly more was also done cooperatively with the use of nitrous oxide–oxygen (83.8% vs. 75.2%). While these differences were not significant, the clinical trend was towards inhalational sedation. Another study also found that both NO2 and oral midazolam were successful in pediatric dental anxiety control, and had an equivalent procedural success rate [18].

 The significant difference in the time to sedate was one of the most remarkable findings. The onset of sedation was significantly quicker with the nitrous oxide/oxygen gas mixture (4.8 ± 1.6 minutes) than with midazolam (21.7 ± 6.4 minutes) by mouth. This fast onset is advantageous in the fast paced pediatric dental environment as it can decrease waiting time and enhance the process of the procedure. The slower onset time could be due to the delayed and variable absorption from the oral route. One research study had also reported a significantly faster onset with nitrous oxide inhalation as compared to oral sedatives [19].

Nitrous oxide–oxygen sedation was clearly superior with regard to safety outcomes. The overall adverse events were significantly lower in the nitrous oxide group (11.4% vs 27.6%). No case of oxygen desaturation was observed in the nitrous oxide group, but 6.7% of the cases in the oral midazolam group desaturated. Excessive sedation was observed only in the oral midazolam group (5.7%). There was also a significantly higher delayed recovery observed with oral midazolam (12.4% vs. 2.9%). The results indicate a greater respiratory and sedation predictability with nitrous oxide. A previous study also showed that nitrous oxide sedation is associated with fewer complications in children with sedation than benzodiazepine sedation, such as complications of the lower respiratory tract and sedation [20].

The benefit of nitrous oxide–oxygen sedation also was demonstrated by recovery response. The mean recovery time was significantly reduced with N2O (14.6 ± 5.2 mins) versus oral midazolam (49.3 ± 13.8 mins). 97.1% of nitrous oxide patients were discharged without delay compared with 86.7% of oral midazolam patients. There was also significantly less drowsiness after the surgery (4.8% compared to 24.8%). These excellent recovery properties may be due to the fast elimination of inhaled nitrous oxide. Another study found that nitrous oxide sedation resulted in significantly shorter length of stay for the patients before they were able to go home and quicker recovery [21]. Using regression analysis, oral midazolam was found to be the strongest predictor of adverse events related to sedation, with an increase in the risk of adverse event by almost 4 times (aOR 3.84). Other significant factors included severe baseline anxiety (aOR 2.43), longer procedures lasting longer than 45 minutes (aOR 2.67), and younger age (aOR 2.18), those under 6 years old. These results indicate that patient factors and the complexity of the procedure also affect the risk of sedation, independent of the type of sedation used. Another study has also identified that prolonged procedures and younger children as risk factors for developing sedation-related complications [22].

Limitations

This study has several limitations. Being a single-center comparative cross-sectional study, causal inferences regarding superiority of one sedation modality over the other should be interpreted cautiously. Allocation was based on sedation modality rather than strict randomized assignment, which may introduce selection bias. Behavioral anxiety assessment may contain subjective variability despite standardized tools. Individual differences in oral midazolam absorption and child cooperation could have influenced outcomes. The study evaluated short-term procedural outcomes only, and long-term behavioral acceptance or delayed adverse effects were not assessed.

It is concluded that both nitrous oxide–oxygen sedation and oral midazolam are effective methods for anxiety control during pediatric dental procedures; however, nitrous oxide–oxygen demonstrates a superior safety and recovery profile. It provided significantly faster onset of sedation, fewer adverse events, lower incidence of oxygen desaturation and excessive sedation, shorter recovery time, and reduced post-procedural drowsiness. Oral midazolam remained effective for anxiety control but was associated with higher complication rates and delayed recovery. Nitrous oxide–oxygen may therefore be considered the preferred conscious sedation modality for appropriately selected pediatric dental patients.

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