European Journal of Cardiovascular Medicine

Preoperative anxiety is a common and significant concern in pediatric patients, manifesting as agitation, fear of parental separation, and resistance to medical procedures such as intravenous cannulation or anesthesia induction. Studies have shown that up to 60–70% of children experience anxiety during the perioperative period, which can lead to negative behavioral outcomes and physiological responses such as increased heart rate, blood pressure, and cortisol levels.^1,2

Effective premedication in children plays a pivotal role in alleviating anxiety, facilitating smooth parental separation, easing intravenous access, and ensuring a stress-free induction of anesthesia.³ An ideal premedicant should be non-invasive, palatable, rapidly acting, and free from significant side effects while providing sedation and anxiolysis.⁴ Several pharmacological agents including benzodiazepines, opioids, and alpha-2 adrenergic agonists have been used via various routes such as oral, intravenous, rectal, and intranasal.⁵

Among these routes, intranasal administration has gained popularity due to its ease, non-invasiveness, and high vascularity of the nasal mucosa, which permits rapid drug absorption directly into systemic circulation, bypassing hepatic first-pass metabolism.⁶ This route is particularly advantageous in uncooperative children where oral or injectable methods may be distressing.

Dexmedetomidine, a highly selective alpha-2 adrenergic agonist, is known for its sedative, anxiolytic, and analgesic properties without causing significant respiratory depression.⁷ It acts on the locus coeruleus and spinal cord to produce sedation and analgesia. Conversely, ketamine, an NMDA receptor antagonist, induces a dissociative anesthetic state with preserved respiratory reflexes and has a rapid onset with good analgesic properties.⁸ While ketamine may provide faster sedation, it is often associated with excessive salivation, hallucinations, and emergence reactions in children.⁹

Recent studies have investigated the comparative effectiveness of these agents via the intranasal route in pediatric premedication settings. However, results have varied based on dosage, onset time, and outcome measures such as sedation scores, parental separation ease, and side effects.¹⁰

This study aims to compare the efficacy and safety of intranasal dexmedetomidine and intranasal ketamine as premedication agents in pediatric patients undergoing elective surgery under general anesthesia. The parameters evaluated include onset and depth of sedation, parental separation, mask acceptance, IV cannula tolerance, hemodynamic stability, and incidence of side effects.

This was a prospective, randomized, double-blind clinical study conducted at the Department of Anaesthesiology, Tertiary Care Institute of India, over a period of 18 months. The study was approved by the Institutional Ethics Committee and written informed consent was obtained from the parents or legal guardians of all participating children.

Study Population

A total of 66 pediatric patients, aged between 2 to 8 years, classified as American Society of Anesthesiologists (ASA) physical status I or II, and scheduled for elective surgeries under general anesthesia were enrolled. Children with known hypersensitivity to study drugs, nasal obstruction or pathology, congenital anomalies, psychiatric illness, or those on sedative or antiepileptic medications were excluded.

Randomization and Blinding

Participants were randomly assigned into two equal groups of 33 patients each using a computer-generated random number table. Group allocation was concealed using opaque sealed envelopes. The attending anesthesiologist responsible for outcome assessments and the patients' guardians were blinded to group assignments. The study drugs were prepared and administered by a second anesthesiologist who was not involved in subsequent assessments.

Intervention Protocol

• Group D: Received intranasal dexmedetomidine at a dose of 1 µg/kg.
• Group K: Received intranasal ketamine at a dose of 5 mg/kg.

The calculated dose of the assigned drug was diluted to a total volume of 1 mL and administered using a Mucosal Atomization Device (MAD) into both nostrils (0.5 mL per nostril), 30 minutes prior to the scheduled surgery time while the patient was in the preoperative area under parental presence.

Monitoring and Data Collection

Baseline vital parameters including heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR), and oxygen saturation (SpO₂) were recorded prior to drug administration and at 10-minute intervals for the next 30 minutes, until the child was shifted to the operating room.

The following clinical parameters were assessed:

1. Sedation Level – Assessed using a Five-Point Sedation Scale:
• 1 = Agitated
• 2 = Awake and alert
• 3 = Drowsy but responsive to verbal stimulus
• 4 = Asleep but arousable to physical stimulus
• 5 = Asleep and unarousable
2. Parental Separation Anxiety Score (PSAS):
• 1 = Excellent (unafraid, cooperative)
• 2 = Good (slight fear or crying, easily reassured)
• 3 = Fair (moderate fear, not quiet with reassurance)
• 4 = Poor (crying, needing restraint)
3. Intravenous (IV) Cannula Acceptance Scale:
• 1 = Excellent (no reaction)
• 2 = Good (mild resistance)
• 3 = Poor (crying, resistance)
4. Mask Acceptance Scale (Quality of Induction):
• 1 = Excellent (accepts mask calmly)
• 2 = Good (minimal resistance)
• 3 = Poor (fighting or crying)

Each of the above parameters was evaluated at the time of parental separation, IV cannulation, and mask application during anesthesia induction.

Intraoperative and Postoperative Monitoring

Intraoperative HR, SBP, and SpO₂ were monitored continuously and recorded at 15-minute intervals. Postoperative vital parameters and sedation levels were assessed in the Post Anesthesia Care Unit (PACU) for 30 minutes.

Assessment of Side Effects

All patients were observed for any adverse effects, such as:

• Excessive salivation
• Nausea and vomiting
• Hallucinations or emergence delirium
• Bradycardia (HR < 60 bpm)
• Hypoxia (SpO₂ < 94%)
• Airway complications (coughing, laryngospasm, etc.)

Any such event was promptly managed according to institutional protocol.

Statistical Analysis

All data were compiled and analyzed using Statistical Package for the Social Sciences (SPSS) software version XX. Continuous variables were expressed as mean ± standard deviation (SD) and compared using unpaired t-test. Categorical variables were expressed as frequencies or percentages and compared using Chi-square or Fisher’s exact test. A p-value < 0.05 was considered statistically significant.

Table 1 presents the demographic data of the study participants. The mean age and weight were comparable between the dexmedetomidine and ketamine groups, with no statistically significant differences. The gender distribution was also similar, confirming that both groups were demographically well-matched at baseline.

Table 2 summarizes the clinical outcomes related to sedation and cooperation between the two groups. The mean sedation score was significantly better in Group D (2.8 ± 0.5) compared to Group K (3.2 ± 0.6) (p < 0.05), indicating deeper sedation. Ease of parental separation was achieved in 85% of patients in Group D versus 68% in Group K (p < 0.05). IV cannula acceptance was good in 80% of Group D and 70% of Group K, though this difference was not statistically significant. Mask acceptance was smooth in 88% of Group D compared to 76% in Group K (p < 0.05). Importantly, the onset of sedation was significantly faster in Group K (15.6 ± 2.8 minutes) than in Group D (25.3 ± 3.1 minutes, p < 0.01).

Table 3 presents the hemodynamic trends observed at various time points. Both groups showed comparable baseline values for heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR), and oxygen saturation (SpO₂). At 10 minutes post-drug administration, Group D (Dexmedetomidine) exhibited a noticeable reduction in HR and SBP, while RR and SpO₂ remained stable across both groups. During the intraoperative and postoperative periods, all parameters remained within normal physiological limits, with a mild but consistent decrease in HR in the dexmedetomidine group. Overall, both drugs maintained hemodynamic stability throughout the study.

Table 4 outlines the incidence of side effects observed in both study groups. Group K (Ketamine) showed a higher frequency of adverse effects, including nausea/vomiting (10%), excessive salivation (12%), and hallucinations (8%). In contrast, Group D (Dexmedetomidine) had minimal side effects, with only 2% experiencing mild nausea and 4% showing mild bradycardia. No hallucinations or salivation were noted in this group. Overall, dexmedetomidine was better tolerated with fewer adverse effects.

Table 1: Demographic Data

Table 2: Sedation and Clinical Scores

Table 3: Hemodynamic Profile

Table 4: Side Effects

The present study demonstrates that while intranasal ketamine offers a faster onset of sedation, intranasal dexmedetomidine provides a smoother and more cooperative induction with better parental separation, higher mask acceptance, and fewer side effects. These findings reinforce the clinical utility of dexmedetomidine as a safer and more predictable premedication agent in pediatric anesthesia.

The faster onset observed with ketamine (15.6 ± 2.8 min vs. 25.3 ± 3.1 min in the dexmedetomidine group) is consistent with its dissociative mechanism of action and rapid absorption through the nasal mucosa, making it a useful agent when a quick onset is necessary.11 However, this advantage is often counterbalanced by its higher incidence of side effects, such as hypersalivation, emergence delirium, and nausea, which were also evident in our study population.

Dexmedetomidine, a highly selective alpha-2 adrenergic agonist, was associated with superior sedation quality, enhanced parental separation (85%), and smooth mask acceptance (88%), all of which are critical parameters in pediatric preoperative care. These benefits arise from its unique mechanism that mimics natural sleep pathways via the locus coeruleus, providing sedation without respiratory depression—a highly desirable property in children.¹²

Hemodynamically, dexmedetomidine led to a modest but clinically stable reduction in heart rate and systolic blood pressure, attributed to its central sympatholytic effects.¹³ Importantly, oxygen saturation remained unaffected in both groups, affirming the safety of the intranasal route. In contrast, ketamine maintained stable hemodynamics but exhibited higher sympathetic stimulation and a greater incidence of postoperative nausea and hallucinations.

Several studies corroborate our findings. For instance, Surendar et al. reported that intranasal dexmedetomidine resulted in better sedation and behavior scores during dental procedures compared to ketamine and midazolam, with no major adverse events.¹⁴ Similarly, Kakani Janakibabu et al. found that dexmedetomidine at 1–2 μg/kg provided effective sedation and improved IV cannulation acceptance, with minimal side effects, supporting its use as a premedicant in children.¹⁵

Taken together, the results of our study, supported by current literature, suggest that while ketamine may be considered for scenarios requiring rapid sedation, dexmedetomidine should be preferred in situations where quality of induction, minimal distress, and better postoperative behavior are priorities.

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