European Journal of Cardiovascular Medicine

Preoperative anxiety is common in paediatric surgical patients and activates the hypothalamic–pituitary–adrenal axis, increasing cortisol and catecholamine release, which may elevate heart rate and blood pressure, impair immunity, and heighten postoperative distress [1–3]. Midazolam, a benzodiazepine, provides rapid anxiolysis, sedation, and amnesia, but may cause paradoxical agitation, cognitive impairment, and dose-dependent respiratory depression [4–8]. Oral midazolam reliably reduces anxiety but often produces stronger amnesia than anxiolysis [9].

α2-Adrenergic agonists, such as dexmedetomidine, provide cooperative sedation, anxiolysis, and analgesia without respiratory compromise, offering a major advantage in children [10]. Its high intranasal bioavailability ensures predictable sedation, comparable or superior to oral midazolam, and it is increasingly used in procedural and perioperative settings [11–15].

Objective:

To compare intranasal dexmedetomidine and oral midazolam for preoperative anxiolysis in paediatric patients, with a focus on cardiovascular stability, sedation, and postoperative analgesic requirements.

Study Design: Prospective, randomized, double-blind study approved by the Institutional Ethics Committee, (Ref no. 0019/ethics/R.cell-14) King George’s Medical University, Lucknow. Written informed consent obtained from parents. Participants: ASA I–II children aged 5–12 years scheduled for elective surgery lasting 1.5–3 hours under general anaesthesia. Exclusions: allergy to study drugs, hepatic/renal dysfunction, cardiac arrhythmias, congenital heart disease, developmental delay, neurological disorders. Randomization & Blinding: • Group I: Oral midazolam 0.5 mg/kg + intranasal saline • Group II: Intranasal dexmedetomidine 0.8 µg/kg + oral placebo (5% dextrose) Premedication was administered 60 minutes before induction by an anaesthesiology resident not involved in assessment. Measurements: • Cardiovascular: HR, SBP, SpO₂ at baseline, 0, 5, 10, 20, 40, 60 minutes, and postoperatively. • Anxiety Assessment: Preoperative anxiety was assessed using the Modified Yale Preoperative Anxiety Scale (mYPAS), a validated tool for children aged 5–12 years, with scores ranging from 23.4 to 100. Anxiety was recorded at the following time points: 1. Baseline (before premedication) 2. 40 minutes post-premedication (prior to venepuncture) 3. 60 minutes post-premedication (at induction) 4. Recovery room Higher mYPAS scores indicate greater anxiety. Significant differences in scores between groups were analyzed using the Mann–Whitney U test. • Sedation: Ramsay Sedation Score (RSS ≥3). (Table 1) • Pain: Modified Objective Pain Score (MOPS). (Table 2) • Rescue analgesia: Fentanyl 1 µg/kg for >25% increase in HR or SBP; postoperative paracetamol 10 mg/kg. • Safety: Adverse events (bradycardia, hypotension, respiratory depression, nausea, vomiting). Anaesthesia Management Standard monitors (ECG, NIBP, SpO₂) were applied. Anaesthesia was induced with propofol and atracurium and maintained with isoflurane in 50% N₂O/O₂ with supplemental atracurium. Fentanyl 1 µg/kg was used for analgesia; rescue fentanyl 1 µg/kg was administered for a >25% rise in HR or MAP from baseline. Ventilation was provided using the Jackson–Rees modification of the Ayre’s T-piece. Neuromuscular blockade was reversed at the end of surgery, and monitoring continued until PACU discharge. Statistical Analysis: SPSS v15.0. Continuous data: mean ± SD; compared with unpaired t-test. Categorical data: chi-square test. Non-parametric data: Mann-Whitney U test. p < 0.05 considered significant.

A total of 60 paediatric patients were randomized into two groups of 30 each. Baseline demographic variables (age, weight, sex distribution) were comparable between the groups (p > 0.05).

Heart rate and systolic blood pressure remained comparable up to 20 minutes after premedication (p > 0.05). Significant intergroup differences emerged at 40 minutes, 60 minutes, and postoperatively, with Group I (oral midazolam) showing higher HR and SBP values than Group II (intranasal dexmedetomidine) (p < 0.05). SpO₂ remained >95% in all patients at all assessment points.

Baseline mYPAS scores were comparable (p > 0.05). Significant differences occurred at 40 minutes, 60 minutes, and in the recovery room, where Group II demonstrated lower anxiety scores than Group I (p < 0.05). Sedation scores (Ramsay scale) showed no significant differences between groups. (Table 3)

Postoperative pain scores were lower in Group II during the first four hours, though not statistically significant. Rescue analgesia requirement (fentanyl) was significantly lower in Group II than Group I (p < 0.05).

No significant adverse effects or episodes of desaturation were observed in either group.

Tables

Table1: Ramsay Sedation Score:

Table 2: Modified Objective Pain Score:

Table 3: Key Outcomes and Side Effects

*Significant (p < 0.05)

This randomized controlled trial compared intranasal dexmedetomidine with oral midazolam in children undergoing elective surgery. Baseline demographic variables were comparable between groups, in line with previous paediatric studies evaluating these agents [4,5].

Dexmedetomidine produced significantly lower heart rate and systolic blood pressure after 40 minutes and in the postoperative period, consistent with its known central sympatholytic action and attenuation of catecholamine release [10]. Oxygen saturation remained stable throughout, corroborating evidence that dexmedetomidine preserves respiratory drive even at sedative doses [10,11].

Preoperative anxiety scores assessed using the Modified Yale Preoperative Anxiety Scale were significantly lower with dexmedetomidine at 40 minutes, 60 minutes, venepuncture, and recovery. The mYPAS is a validated and sensitive tool for paediatric perioperative anxiety assessment [1]. These results align with earlier studies showing superior anxiolysis and smoother separation with intranasal dexmedetomidine compared with oral midazolam [11–13].

Sedation scores remained similar between groups; however, dexmedetomidine produced calmer behaviour during transfer and induction. Early postoperative pain scores were lower, and the need for rescue fentanyl was reduced in the dexmedetomidine group, reflecting its analgesia-sparing properties and favourable pharmacodynamic profile [10,12].

Findings of previous clinical trials further support these observations, demonstrating improved parental separation, reduced agitation, and better perioperative behaviour with dexmedetomidine across a range of paediatric procedural and surgical settings [12–15]. Its noninvasive intranasal route, predictable onset, and cooperative sedation pattern enhance its suitability for paediatric premedication.

Overall, this study reinforces evidence that intranasal dexmedetomidine offers superior anxiolysis, comparable sedation, stable haemodynamics, and reduced analgesic requirements compared with oral midazolam. These findings support its role as a safe and effective alternative for paediatric preoperative premedication.

Intranasal dexmedetomidine 0.8 µg/kg provided superior preoperative anxiolysis, smoother parental separation, and reduced postoperative opioid requirements compared with oral midazolam 0.5 mg/kg in children aged 5–12 years undergoing elective surgery. Both agents preserved cardiovascular stability, with heart rate and blood pressure maintained within safe limits, and no clinically significant bradycardia or hypotension. Minor nausea occurred in two midazolam cases, with no vomiting or excessive sedation in either group. Intranasal dexmedetomidine is thus a safe, hemodynamically stable, and more effective alternative for paediatric premedication.

Limitations

1. Sedation and anxiety were not assessed continuously to determine exact onset and peak effect times.

2. Relatively small sample size (n=60).

3. Age-related physiological and pharmacokinetic differences were not analysed separately.

Recommendations

Future larger studies should

• use continuous observational scoring to identify precise onset and peak effect,

• compare different doses of intranasal dexmedetomidine, and

• include wider age subgroups and plasma drug level monitoring.

1. Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: A comparison of four routes of administration. Paediatr Anaesth. 202;12:685-9.

2. Kain ZN, Hofstadter MB, Mayes LC, Krivutza DM, Alexander G, Wang SM, et al. Midazolam: Effects on amnesia and anxiety in children. Anesthesiology. 2000;93:676-84.

3. Bergendahl H, Lönnqvist PA, Eksborg S. Clonidine: An alternative to benzodiazepines for premedication in children. Curr Opin Anaesthesiol. 2005;18:608-13.

4. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93:382-94.

5. Anttila M, Penttila J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. J Clin Pharmacol. 2003;56:691-3.

6. Yuen VM, Hui TW, Irwin MG, Yuen MK. A comparison of intranasal dexmedetomidine and oral midazolam for premedication in pediatric anesthesia: A double-blinded randomized controlled trial. Anesth Analg. 2008;106:1715-21.

7. Ghali AM, Mahfouz AK, Al-Bahrani M. Preanesthetic medication in children: A comparison of intranasal dexmedetomidine versus oral midazolam. Saudi J Anaesth. 2011;5:387-91.

8. Akin A, Bayram A, Esmaoglu A, Tosun Z, Aksu R, Altuntas R, et al. Dexmedetomidine vs midazolam for premedication of pediatric patients undergoing anesthesia. Paediatr Anaesth. 2012;22:871-6.

9. Sheta SA, Al-Sarheed MA, Abdelhalim AA. Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: A double-blinded randomized controlled trial. Paediatr Anaesth. 2014;24:181-9.

10. Bhadla S, Prajapati D, Louis T, Puri G, Panchal S, Bhuva M. Comparison between dexmedetomidine and midazolam premedication in pediatric ophthalmic day-care surgeries. Anesth Essays Res. 2013;7:248-56.

11. Mostafa MG, Morsy KM. Premedication with intranasal dexmedetomidine, midazolam and ketamine for children undergoing bone marrow biopsy and aspirate. Egypt J Anaesth. 2013;29:131-5.

12. Segovia BL, García-Cuevas MA, Ramírez-Casillas IL, Guerrero-Romero JF, Botello-Buenrostro I, Monroy-Torres R, et al. Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. An Pediatr. 2014;81:226-31.

13. Peng K, Wu SR, Ji FH, Li J. Premedication with dexmedetomidine in pediatric patients: A systematic review and meta-analysis. Clinics. 2014;69:777-86.

14. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists: Their pharmacology and therapeutic role. Anaesthesia. 1999;54:146-65.

15. Kain ZN, Mayes LC, Cicchetti DV, Bagnall AL, Finley JD, Hofstadter MB. Yale Preoperative Anxiety Scale: Comparison with a gold standard. Anesth Analg. 1997;85:783-8.