European Journal of Cardiovascular Medicine

One of the most common challenges faced by anaesthesiologists in the operating room is to facilitate smooth induction of anaesthesia for children inorder to minimize their distress. Anxiety and fear often increases during parental separation in paediatric population. In paediatric anaesthesia, the children are usually sedated before transfer to operating room to overcome come these challenges. Hence, the goal of preanaesthetic medication in children was to alleviate the anxiety and psychological trauma and also to facilitate smooth induction of anaesthesia without causing delay in recovery.

Many drugs have been trialed so far in multiple studies with varying doses to find out the appropriate sedative premedicant and its best administration route in children. Hence, the premedicant to be used should have an easily acceptable, nontraumatic route of administration so as to avoid further stress to the children. The most commonly used drugs currently in use for these purposes are midazolam, ketamine, dexmedetomidine, transmucosal fentanyl and meperidine^[1-4].

There was a continuous effort over time with multiple studies to find out a better premedicant that can be administered with ease in various routes, with less traumatic, less pungent and minimal or no respiratory depression properties together providing good sedation, anxiolysis, amnesia and analgesia for young children. Dexmedetomidine is a highly selective α2 adrenoreceptor agonist that has sedative, anxiolytic, analgesic, and hypnotic effects and these properties made dexmedetomidine a suitable premedicant for sedation and analgesia during the perioperative period^[5].

Smooth induction of anaesthesia in children reduces anxiety, improves cooperation, and prevents psychological trauma. Among non‑invasive routes, intranasal administration has proven to be more effective. The spray form, delivered via mucosal atomization, ensures better mucosal coverage and rapid absorption.

Intranasal application is a noninvasive, relatively easy route that offers rapid onset of action and high bioavailability because of its ability to bypass hepatic firstpass metabolism and the rich vascularity of the airway mucosa^[6,7]. The additional advantages of this route includes good tolerability, does not require patient cooperation and lacks pungency or an unpleasant taste. All these factors makes intranasal route more reliable among various routes for administering preanaesthetics and sedatives in children.

Although intranasal drug delivery was widely used for paediatric sedation, the method of administration can significantly influence its effectiveness. Spray method differs by its drug distribution across the nasal mucosa, which directly affects the absorption rate and onset of action^[8]. Therefore in our study we decided to analyse the effectiveness of spray method of administration in sedative premedication.

The present study was carried out to analyse the efficacy of intranasal dexmedetomidine as premedication in terms of sedation onset time and optimal sedation level along with hemodynamic safety.

AIM AND OBJECTIVES

Aim: To evaluate the efficacy of intranasal dexmedetomidine administration as spray for premedication in children aged ≤ 8 years undergoing elective surgeries.

Objectives: The primary objective of this study was to evaluate the effectiveness of intranasal dexmedetomidine as spray in terms of sedation onset time and satisfactory sedation level 30 minutes after premedication. The secondary objectives includes monitoring the hemodynamic stability specifically heart rate and oxygen saturation following the drug administration.

Study design: Prospective observational study.

Setting: Government Medical College & Hospital, Cuddalore District, Chidambaram.

Study period: August 2023 – August 2024.

Sample size: 30 paediatric patients.

Inclusion criteria: Age ≤ 8 year, Both Males & Females, Children with American Society of Anesthesiologists physical status classification of I & II.

Exclusion criteria: Parental refusal, Children with ASA physical status  classification of III & IV, Children with history of upper respiratory tract infection, CNS dysfunction, cardiovascular dysfunction. Allergic to the drug under study. Children with any intranasal pathology, nasal obstruction (mass), epistaxis, nasal congestion, sinusitis. Children with any congenital anomaly.

METHODOLOGY

After obtaining institutional ethical committee approval, the study was started in Government Medical College and Hospital, Cuddalore District, in the Department of anaesthesiology. All the participants of age 8 years or below who got admitted in Government Medical College and Hospital, Cuddalore district, Chidambaram during the study period posted for all types of elective surgeries were approached for participation in the study. A participant information sheet was also provided to the parent/legally acceptable representative of all the participants and the investigator explained about the study to each of them in the local dialect. Following which an assent/informed consent was obtained.

A total of 30 participants were included into the study. The drug used for premedication was dexmedetomidine. A dose of 2mcg/kg was provided intranasally as spray via Mucosal Atomization Device (MAD) 30 minutes prior to surgery.

Gadgets for drug administration: Atomizer/MAD

Administration technique: The calculated dose is limited to maximum volume of 0.5ml per nostril. The patients are then placed in semi-reclined position and the drug is sprayed quickly and steadily to attain maximum atomisation effect. Limiting the volume to approximately 0.3–0.5ml per nostril, positioning the patients, and steady drug administration are the precautions to be taken into consideration so as to avoid runoff of drug into oropharynx, overflow from nostrils and to ensure effective absorption.

Method of administering the premedicant: The preoperative baseline parameters like heart rate, oxygen saturation were recorded prior to the procedure.

The patients were given intranasal dexmedetomidine in a dose of 2 mcg/kg by spray using Mucosal Atomization Device (MAD). An equal volume of drug was administered to each nostril when the child is in either supine, semi-reclined or sitting posture. The drug was given as quickly as possible to ensure the atomisation effect.

Patients were monitored to evaluate the sedative effects of the drug. Sedation levels and hemodynamic parameters like heart rate, oxygen saturation were monitored at 5, 10, 15, 20, 25, 30 minutes. The level of sedation was assessed using the University of Michigan Sedation Scale (UMSS) with a score of 3 or 4 considered indicative of satisfactory sedation. The time taken to reach this level of sedation was also noted. At the end 30 minutes the level of satisfactory sedation was noted.

University of Michigan Sedation Scale (UMSS): The University of Michigan Sedation Scale (UMSS) is a simple and widely used clinical tool to assess the depth of sedation, especially in paediatric patients receiving sedatives such as dexmedetomidine.

Sedation Level and Clinical Description by UMSS

STATISTICAL ANALYSIS

At the end of the study the data collected were entered into Microsoft excel and a master chart was created. The master chart was then loaded onto statistical package for social sciences (SPSS) version 26 for further statistical analysis. Both quantitative and qualitative variables were present in the study. The quantitative variables were expressed using mean and standard deviation. The qualitative variables using frequency and percentage.

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Figure 7.2                                                                                           Figure 7.3

Figure 7.4                                                                                           Figure 7.5

Figure 7.6                                                                                          Figure 7.7

Demographic and anthropometric characteristics:

The majority of children (70%) fall within the 3–8 years age range, with 30% in 3-5 year and 40% in 5-8 year brackets. The comparable proportions across different age groups shows a balanced spread reducing age-related confounding in the outcome analysis.

The distribution of sexes shows a near-equitable allocation. Among 30 participants included in the study, males comprised 53.3% and females accounted 46.7% respectively. Despite of slight male predominance the sex ratio appears relatively balanced, minimizing gender-related bias in hemodynamic or sedation outcomes. This study was not biased towards one gender and shows a balanced procedural outcome.

Consequently, the mean height, weight and BMI were 100.9 ± 10.8 cm, 15.5 ± 4.6 kg and 15 ± 2.1 kg/m² respectively. So, baseline anthropometric parameters are balanced throughout study population. Overall these statistics suggest a relatively balanced homogeneous distribution of demographic and anthropometric parameters among study group.

ASA physical status:

Majority of participants fall into ASA I category. The proportional distributions of participants in ASA I and II category are 90% and 10% respectively, supporting that the study participants are overall healthy before intervention.

Hemodynamic parameters:

Vital characteristics like heart rate, oxygen saturation were measured at 0 minutes and thereafter every 5 minutes over 30 minutes following premedication.

The base line (0 minute) mean heart rate was 107.97 ± 18.65 bpm. By 30 minutes, the heart rate decreased to 93.10 ± 15.72 bpm. Heart rate showed a consistent decreasing trend over time reflecting the expected bradycardic effect of dexmedetomidine. The initial steeper decline aligns with faster pharmacodynamic action in the spray group suggesting a more rapid onset of autonomic stability or sedation. Importantly, at any interval the heart rate fall remained within safe physiological limits. Despite the faster decline in heart rate during initial few minutes, no episodes of clinically significant bradycardia (if HR fall > 20%) was noted throughout the observation.

The oxygen saturation (SpO₂) remained consistently above 98% throughout the observation period. This affirms that neither intervention compromised oxygenation during the observation period.

From these observations it was confirmed that intranasal dexmedetomidine as spray formulations were hemodynamically safe and well-tolerated in paediatric patients. The safety profile noted in our study aligns with the observations made by Yuen et al. (2012)^[9] (2014)^[10] who consistently reported stable hemodynamics with different doses of intranasal dexmedetomidine. Similar findings of stable heart rate and oxygen saturation with a slightly more rapid initial decline in heart rate but within physiological limits was observed in studies by Shilpi Verma et al. (2022)^[11] and Dr. Puvaneswari M. (2023)^[12].

Satisfactory sedation level

The level of sedation was assessed at baseline 0 minute and at 5 minutes interval for 30 minutes post administration of intranasal dexmedetomidine using the University of Michigan Sedation Scale (UMSS), with a score of 3 or above considered satisfactory.

At baseline (0 minute), all children had a sedation score of 0, indicating a fully awake pre-intervention state. This uniform baseline confirms that no residual sedation or premedication affected the initial status, enhancing internal validity.

By 5 minutes, 60% achieved a sedation score of 2, suggested that the nasal spray like had a quicker onset of action possibly due to mucosal absorption dynamics. With time the level of sedation deepens and a more rapid sedation trajectory with 30% in score of 3 by 10 minutes. Similar observation of significant difference in sedation onset time, with faster sedation trajectory was highlighted in the study by Li et al. (2018)^[13]. They reported that the bioavailability and the quicker onset of dexmedetomidine through intranasal route with spray could be possibly due to uniform distribution of drug over nasal mucosa favoured by atomisation that likely enhanced the absorption and accelerated the onset of action.

At 15 minutes, the participants were split across scores 2 (23.33%), 3 (56.66%), and 4 (13.33%). In that time frame more than 50% of children had achieved a sedation score ≥3 indicating a significantly higher sedation intensity by 15 minutes, suggesting that it likely reached clinically satisfactory sedation levels (UMSS ≥3) faster. Similar observation was noted in studies by  Li et al. (2018)^{[13 ]} and  X.R. Song et al. (2016)^[14].

By 20 minutes 70% reached score 4 (deep sedation) and by 25 minutes, large proportion (73.33%) of participants were at score 4, suggesting peak sedation was achieved.

At 30 minutes, almost all the participants reached near-maximal sedation, with 86.67% attaining score 4. However, a subset among the participants remained at score 3 (13.33%), indicating a slightly delayed peak. On the whole, the dexmedetomidine spray  maintained a more rapid and robust sedative profile over time.

According to the meta-analysis by Jong Hun Jun et al. (2017)^[15], dexmedetomidine when administered intranasally 30 to 45 minutes prior to procedure, produced a satisfactory sedation with minimal or no adverse effects. They observed peak sedative effects between 30-45 minutes, which closely aligns with our findings where satisfactory sedation (UMSS ≥ 3) was achieved in 100% of participants  by 30 minutes with no signs of oxygen desaturation or clinically significant bradycardia.

One of the earliest studies by Wilton et al. (1988)^[16] with midazolam reported the effectiveness of intranasal route in rapid onset of sedation regardless of the sedative agent. The hemodynamic stability of dexmedetomidine has been well documented in studies by Yuen et al.(2012)^[9] (2014)^[10] and Anupriya J, Kurhekar P (2019)^[17]. These studies further supports our observations regarding the sedative effectiveness and hemodynamic stability of dexmedetomidine administered intranasally.

The above study showed that the spray method of intranasal dexmedetomidine administration provided a faster onset and more consistent sedation with stable heart rate trends and preserved oxygen saturation supporting their use as an effective and safe premedication with improved ease of separation and readiness for induction within 25–30 minutes when timed appropriately especially in the paediatric population.

SUMMARY

Premedications are given to make the patients prepared prior to any planned medical or surgical procedures. The premedication finds it utility in both procedural and perioperative period. The present study was carried out to evaluate the efficacy of intranasal dexmedetomidine spray for premedication in paediatric children aged ≤ 8 years undergoing elective surgeries by evaluating the sedation onset, level of sedation, hemodynamic parameters and the level of satisfactory sedation 30 minutes after premedication.

The main objective was to evaluate the onset and level of sedation with UMSS ≥3 considered as satisfactory sedation and parameters like heart rate and oxygen saturation were monitored at 5 minutes intervals up to 30 minutes to assess hemodynamic stability.

Throughout the observation period the oxygen saturation remained within normal limits in all patients. There was a gradual decline in heart rate trend but within normal physiological limits.

Among 30 paediatric patients who received intranasal dexmedetomidine spray 100 % achieved UMSS ≥ 3 by 30 minutes. 86.67 % reached deep sedation (UMSS 4). Heart rate and oxygen saturation remained stable with no adverse events.

To summarise, the spray mode proved to be more efficient in achieving early sedation while maintaining stable cardiopulmonary parameters. The present study suggested that intranasal dexmedetomidine spray was a more effective option for sedative premedication in children, especially when timely onset was essential for planned procedures.

In conclusion, the spray form of intranasal dexmedetomidine was found to be  safe and effective by providing earlier and more consistent sedation, making it a preferred choice for paediatric procedural premedication when timed properly.

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