Comparison Between Intranasal Dexmedetomidine, Ketamine or Midazolam for Reducing Anxiety and Respiratory Complications in Children Undergoing Adenotonsillectomy
Phase: NA
Conditions: Adenotonsillectomy
Sponsor: Zagazig University

Introduction 
 
Preoperative anxiety and  respiratory complications  are the commonest  
complications in children undergoing adenotonsillectomy  ]1 [. Perioperative 
respiratory complications are the most common and dangerous 
complication during pediatric anesthesia, manifested as minor adverse 
events (oxygen desaturation, airway obstruction, coughing, or wheezing) 
and major adverse events (laryngospasm and bronchospasm). These 
complications can prolong hospitalization time and costs, and bring varying 
degrees of physical and psychological trauma to children and parents ]2[. 
Anxiety in children undergoing surgery is characterized by subjective 
feelings of tension, apprehension, nervousness, and worry that may be 
expressed in various forms ]3[.Postoperative maladaptive behaviors, such 
as new onset enuresis, feeding difficulties, apathy , and sleep disturbances, 
may also result from preoperative anxiety ]4 [ . 
In fact, studies in 60% of all children undergoing surgery may present with 
negative behavioral changes at 2 weeks postoperatively ]5[. Variables such 
as age, and anxiety of the child and parent in the preoperative holding area 
have been identified as predictors for these behavioral changes. Extreme 
anxiety during induction of anesthesia is also associated with an increase 
of these postoperative negative behavioral change
 
  ] 6 [. 

Premedication in children is helpful for both separating the child from their 
parent and reducing the child’s stress and anxiety, thus facilitating smooth 
induction of anesthesia ]7[. 
 Many drugs can be taken by the intranasal route such as glucocorticoids, 
nasal 
decongestants, 
naloxone, 
midazolam, 
ketamine, 
and 
dexmedetomidine  ]8[. The administration of intranasal dexmedetomidine, 
ketamine or midazolam avoids the need for intravenous cannulation. 
Intranasal drug administration is a relatively easy noninvasive route with 
high bioavailability as it bypasses first-pass hepatic metabolism and also 
because of the high blood supply in the nasal mucosa ]9[. 
Dexmedetomidine is a selective alpha 2 agonist like clonidine, but with 
higher affinity to the alpha 2 receptor. Dexmedetomidine produces dose-
dependent sedation, anxiolysis, and analgesia without respiratory 
depression. Dexmedetomidine triggers and maintains natural sleeping 
status without eye movement by stimulating the locus coeruleus in the 
brain stem, so it increases the activity of inhibitory gamma aminobutyric 
acid (GABA) neurons in the ventrolateral preoptic nucleus ]10 [. 
Ketamine is proved to interact with many receptors, including the N-methyl-
D-aspartate receptor (NMDA-R) producing a dissociative anesthesia. 

Ketamine is known to reduce central sensitization to pain, decrease overall 
opioid utilization, and produce effective sedation ]11[. 
Intranasal midazolam is one of the benzodiazepines. It is characterized by 
rapid onset (10–12 min) and short duration, with high bioavailability (55–
83%) ]12[. the benzodiazepine receptors are found to be expressed in 
olfactory nerves. Therefore, it is likely that intranasal midazolam acts on the 
benzodiazepine receptors of olfactory neurons in the nasal epithelium and 
that this nerve impulse affects hippocampal function, leading to an 
increased amnesic effect. In contrast to the amnesic effect, the neuronal 
process of sedation may be associated with a wider network of the brain 
]13 [. 
A study using  intranasal  dexmedetomidine at a dose of 1 μg/kg as a 
sedative premedication has demonstrated a favorable perioperative 
anxiolysis 
without 
prolongation 
in 
anesthesia 
recovery, 
and 
its 
hemodynamic effect was well tolerated by the patients ]14 [. 
A literature review by Poonai et al. (2017) identifed seven prospective 
studies involving 264 participants, evaluating IN ketamine for procedural 
sedation and anxiety in children outside the operating room . In this 
systematic review , IN ketamine produced adequate sedation to perform 
the procedures under study, resulting in adequate sedation for 85% of 

participants. However, the superiority of IN ketamine over comparators was 
inconsistent ]15[. 
 Also regarding the literature evaluating intranasal (IN) medications for the 
treatment of procedural anxiety, evidence supports the use of IN 
midazolam for its amnestic and anti-anxiety properties. Multiple studies 
have shown IN midazolam to be safe and effective in the treatment of 
procedural anxiety during laceration repair in  pediatric emergency 
department ]16[. 
Because the published literatures did not reveal which of intranasal 
dexmedetomidine, ketamine or midazolam is more efficient in prevention or 
at least lowering the incidence of respiratory complications and anxiety 
after tonsillectomy and adenoidectomy in children , so this thesis will be 
carried on to reveal that. 
Rationale 
 
• Perioperative respiratory complications and anxiety are the most common 
complication during pediatric anesthesia, that can prolong hospitalization 
time and costs, and bring varying degrees of physical and psychological 
trauma to children and parents. 

• Many drugs can be used intranasally to decrease these complications such 
as glucocorticoids, fentanyl, naloxone, midazolam, ketamine, and 
dexmedetomidine. 
• In this study we will compare between Intranasal Dexmedetomidine, 
ketamine, or midazolam as premedication in prevention of  anxiety and 
respiratory complication in children undergoing adenotonsillectomy. 
  
 
 
 
Research question 
 
Which of these intranasal drugs can be more efficient as premedication for 
prevention of preoperative anxiety and Respiratory complications in 
children undergoing adenotonsillectomy using intranasal dexmedetomidine, 
ketamine or midazolam? 
 
 
 
 

  
Hypothesis  
Null hypothesis:  
• No difference between the effect of intranasal dexmedetomidine, 
ketamine or midazolam as a premedication for prevention of anxiety 
and 
respiratory 
complications 
in 
children 
undergoing 
adenotonsillectomy. 
Alternatives hypothesis: 
• there 
is 
a 
difference 
between 
the 
effect 
of 
intranasal 
dexmedetomidine, midazolam or ketamine as a premedication for 
prevention of anxiety and respiratory complications in children 
undergoing adenotonsillectomy, one of them is better than the others. 
 
 
Aim of the work 
Prevention or decreasing the  preoperative anxiety and respiratory 
complications in children undergoing adenotonsillectomy using intranasal 
dexmedetomidine, ketamine or midazolam as a premedication. 
 
 

 
Objectives. 
To determine the incidence and severity of laryngospasm during 30 
minutes after extubation in all group. 
To assess and compare the level of sedation and distress in the groups. 
 To determine time of  discharge from  post anesthesia care unit. 
 
Methods 
• Type of study: prospective randomized controlled clinical trial. 
• Sample size calculation 
By assuming that the mean of the heart rate intraoperative before induction 
of general anesthesia among groups taken intranasal dexmedetomidine 
and intranasal ketamine was105.29±6.02beat/minutes and among groups 
taken intranasal dexmedetomidine and intranasal midazolam was 
108.45±5.47beat/minutes with CI 95% and power of test 80%, the sample 
size is calculated to be 148 patients allocated into 4 groups, each group will 
be 37 patients. 
Inclusion criteria   
- Parent or first-degree relative acceptance 
- Children with age ranged from 4 to8 

- Body mass index is equal to or greater than  5th  and not more than 
85th percentiles  
- ASA classifications Ⅰand Ⅱ 
- Both sex 
Exclusion criteria 
- History of difficult intubation or extubation, cardiac, respiratory, renal and 
muscle diseases beside passive smoking and allergy to the tested drugs 
- History of obstructive sleep apnea (OSA). 
- The presence of the upper respiratory tract infection 
- The need to reoperation after tonsillectomy due to hemorrhage of more 
than 100ml of blood during surgery 
- Surgery duration is longer than 1.5 hour. 
Site of the study: The study will be carried out at zagazig University 
hospitals, zagazig city, sharkia, Egypt. 
Duration of the study 6 month’s  
Ethical approval: the study will be done after obtaining approval from 
university institutional review board (IRB). A written informed consent will 
be obtained from the parents or first degree relative of all patients 
participating in the study. the study will be carried out in according to the 

Code of Ethics of the World Medical Association (declaration of Helsinki) 
for studies involving humans. 
All children will be visited the night before the surgery for assessment, 
preparation and take an informed consent on the type of anesthesia which 
intended to be given from their parents or first-degree guardians.  
Assessment of patients includes identification of patient’ age/years, body, 
weight/kg, BMI and vital signs, taking history about medical disorders, 
previous surgical procedure, the current medications, examination of 
various body systems, and asking for routine investigation as complete 
blood count, sedimentation rate and bleeding time. 
 All children are routinely required to preoperatively fast 8 hours for solids 
and 2 hours for clear liquids. the study is double- blinded. The patients and 
anesthesia assistant (the person evaluating the effect of the tested drug) 
will not be informed about tested drug. Only the anesthesiologist (the 
person prescribing the tested drug) will be aware of the tested drug to take 
the necessary measures in case of occurrence of any adverse medical 
complications. According to a computer-generated randomization chart, 
patients will be allocated into 4  equal groups  
 

Group C(Control Group) n=(37): patient will take 1 mL of 0.9% saline 
intranasal 30 min before induction . 
Dexmedetomidine group (D group) n= (37): patient will take 2.0 μg/kg 
intranasal dexmedetomidine, with 0.9% saline added to make a final 
volume of 1 mL. 
Ketamine group (K group) n=(37) : patient will take 2mg/kg intranasal 
ketamine with concentration 50 mg/ ml, with 0.9% saline added to make a 
final volume of 1 mL. 
Midazolam group (M group) n= (37): patient will take 0.1 mg/kg  
intranasal midazolam with 0.9% saline added to make a final volume of 1 
mL. 
The prepared drug solution will be administered cautiously in both nostrils 
using a needleless 1-mL syringe, drop by drop, each nostril will have 0.5 ml 
and the children will be positioned on the parent’s lap in a recumbent 
position during administration.  
After 30 minutes in the operating room (OR), a peripheral iv cannula(22-
24gauge) will be inserted and secured. Devices for monitoring heart rate 
(HR), noninvasive mean arterial pressure (MAP), respiratory rate(RR) and 
peripheral oxygen saturation(SpO2) will be applied to the patients . 

General anesthesia will be induced by iv injection of 1 ug/kg of fentanyl 
sulfate and inhalation of 8% sevoflurane in air/oxygen, atracurium 0.5mg/kg 
is given, then oral endotracheal intubation is done with a tube in 
appropriate size to child age, tube fixed to the middle of the chin.  
Immediately after endotracheal intubation, all the patient will receive 10 
mg/kg acetaminophen suppository to avoid or at least minimize 
postoperative pain. Anesthesia was maintained with 1.5-2%sevoflurane in 
air /oxygen (50%:50%) and mechanical ventilation will be aided by IV 
administration of 0.4mg/kg atracurium basilate keeping a tidal volume of at 
least 6ml/kg, respiratory rate/minute between  15 to 25, an etCO2 below 40 
mmHg together  with a trigger flow of 2.0 . 
Intra-operatively, all patients will receive ringer lactate solution IV. At the 
end of surgery, inhalational anesthesia will be discontinued and on the start 
attempts of spontaneous respiration, a mixture of 4ug/kg of neostigmine 
and 2ug/kg of atropine will be given IV for reversal of muscle relaxant 
effect, then pharyngeal suction. after that, the patient will be shifted  from or 
to Post Anesthesia Care Unite(PACU) for continuous monitoring till full 
recovery from general anesthesia then  shifting the patients to the ward. 
In this study the following parameters and scales will be recorded in each 
group: 

 
 
 
 
Measurements 
1. Assessment of the vital signs mean blood pressure, heart rate, 
respiratory rate, and oxygen saturation preoperative baseline before 
administration of the intranasal drug (0 min)in the holding area, 10 min 
preoperative after giving the intranasal drug, at time of induction 30 min 
after giving the intranasal drug(0 min), 10 min intraoperative after induction 
of anesthesia, 30 min intraoperative after induction of anesthesia ,at the 
end of surgery and postoperative in recovery (0 min), 10 min postoperative 
in the recovery, 30 min postoperative in the recovery 
2. The incidence and severity of post-extubation laryngospasm: 
Incidence of post -extubation laryngospasm during 30 minutes duration 
after extubation will be assessed using scale in table(1): 
 
 
 
 
 

 
 
Table (1): The incidence and severity of post-extubation laryngospasm 
]17 [. 
      
Lack of laryngospasm 
0 
Partial of cords, stridor during inspiration with decreased tidal 
volume and a stable pulse o oximeter oxygen saturation(SpO2 
>95%) 
1 
Total occlusion of cords(i.e respiratory silence which can be 
characterized by inspiratory efforts of accessory muscles and 
paradoxical thoracic movements, and SpO2 >85% 
2 
Cyanosis associated with desaturation (SpO2 <85%)  
3 
       
Treatment of post-extubation laryngospasm will be standardized as the 
following: at first removal of the offending stimulus, jaw thrust, and manual 
ventilation with 100% oxygen by bag and mask is performed ]18 [. When the 
first measure fail, application of a firm pressure at a laryngospasm point, 
which lies behind the ear lobe, between the mastoid process and the ramus 
of the mandible is preformed ]19[. When the above mentioned two 

measures fail, 0.5mg/kg of succinylcholine is  injected iv and manual 
ventilation with 100% oxygen by bag and mask with manual face mask 
ventilation  is performed till return back of spontaneous breathing. When 
the above mentioned three measures fail, laryngospasm is considered 
sustained and treated like severe laryngospasm from the start by airway 
,breathing and circulation resuscitation will be started by paralyzing dose of 
vocal cord by iv injection of 0.5mg/kg of succinylcholine, endotracheal 
intubation and manual ventilation with 100%oxygen till return back of 
spontaneous breathing ]20 [. 
3-Assessment of the sedation level done by Ramsay sedation score 
will be recoded at different time intervals: preoperative baseline before 
administration of intranasal medication, then 10 min, just before  induction 
and 10 min, 20 min postoperative.  "Ramsay Sedation Score" is described 
in 1974 it divides the pts level of sedation into 6 Categories ranging from 
severe agitation to deep coma as shown in table (2)  
 
 
 
 
 

 
Table(2): Ramsay sedation score ]21 [. 
Level 
1 
Patient awake, anxious and agitated or restless ,or both 
Level 
2 
 
Patients awake, cooperative, oriented, and tranquil.  
Level 
3 
 
Patients awake, responds to commands only 
Level 
4 
 
Patient asleep, brisk response to light glabellar tap or loud auditory 
stimulus. 
 
Level 
5 
 
Patient asleep, sluggish response to light glabellar tap or loud 
auditory stimulus 
 
Level 
6 
Patient asleep, no response to light glabellar tap or loud auditory 
stimulus. 
 

4-Assessment of distress associated with potentially painful event 
using Groningen distress scale at time of canulation. (GDS) was 
developed to grade distress associated with a potentially painful event. It 
can be used to monitor a phobic patient's experience towards a triggering 
stimulus. The original scale was developed at the University of Groningen 
in The Netherland as shown in table (3) 
 
 
Table(3): Groningen distress scale ,]22[ . 
1 calm 
2 Mild distress 
 
3 Serious distress, in control 
 
 
4 
 
 
Sever distress , out of control 
 
5 panic 

    
 5-  All children observed postoperative till discharge criteria will met 
and monitored for presence of sedation, nausea/vomiting, and/or any 
other complications. Prior to discharge, each patient should be assessed 
and examined by an anesthesia provider to ensure patient safety before 
transfer to the intensive care unit, inpatient floor, or home with 
parents/guardians. With more pediatric cases being scheduled on an both 
an inpatient and outpatient basis, careful and efficient assessment of 
discharge readiness is important. The Modified Aldrete Score assesses 
patient activity, respiration, blood pressure, consciousness, and color.  A 
score >9 is required for discharge from the post anesthesia care unit . 
Table (3): Modified Aldrete Score ]23[. 
Criteria 
Characteristics 
Points 
Activity 
Able to move 4 extremities 
Able to move 2 extremities 
Unable to move extremities 
2 
1 
0 
Respiration 
Able to breathe deeply and cough freely 
Dyspnea or limited breathing 
Apneic 
2 
1 
0 

Circulation 
BP +/- 20% of pre-anesthetic level 
BP +/- 20-49% of pre-anesthetic level 
BP +/- 50% of pre-anesthetic level 
2 
1 
0 
Consciousness Fully awake 
Arousable on calling 
Not responding 
2 
1 
0 
Oxygen 
saturation 
Able to maintain O2 saturation >92% on room air 
Needs oxygen to maintain O2 saturation >90% 
 
 
 
 
Data collection: 
Patient characteristics: 
From each patient the following data will be collected 
upon admission: 
• Name 
• Age 
• Body mass index 
• Date of operation 

• Medical and past history 
• Duration of operation 
• incidence and severity of post extubation laryngospasm in the first 30 
minutes. 
• sedation level preoperative as a baseline before administration of 
intranasal midazolam, dexmedetomidine or ketamine then 10 min after 
administration of the previous intranasal medications, then just before 
induction of anesthesia after  (30min) and after extubation and recovery 10 
minutes and 30 minutes postoperative using Ramsey sedation scale. 
• Assessment of distress associated with potentially painful event using 
Groningen distress scale at time of canulation 
• Vital signs: measuring preoperative baseline of assessment of the vital 
signs: mean blood pressure, heart rate, respiratory rate, and oxygen 
saturation before administration of the intranasal drug (0 min) in the holding 
area, 10 min preoperative after giving the intranasal drug,  at time of 
induction 30 min after giving the intranasal drug(0 min). 
• then 10 min intraoperative after induction of anesthesia, 30 min 
intraoperative after induction of anesthesia ,at the end of surgery  for 
assessment of mean blood pressure, heart rate ,respiratory rate and 
oxygen saturation  

•  postoperative in recovery (0 min), 10 min postoperative in the recovery, 30 
min postoperative in the recovery for assessment of the vital signs mean 
blood pressure, heart rate, respiratory rate, and oxygen saturation 
• the incidences of the various associated complication as bradycardia 
(guidelines for bradycardia based on 24-hour Holter monitoring are as 
follows:2-6byears:,60bpm during sleep or awake.6-11 years:,45bpm during 
sleep or awake.  
Low mean arterial pressure is under 60mm Hg, bradypnea from 3 to 6 
years:22to34 breaths per minute and age from 6 to 12 years :18to 30 
breaths per minute. 
 Hypoxemia : when arterial oxygen pressure(PaO2) below 75mmHg  . 
Hypoxia: when saturation below 90%. 
 
 
 
 
  
 
 
 
 
 

 
 
 
 
 
References 
 
 
1. 
Shen F, Zhang Q, Xu Y, Wang X, Xia J, Chen C, et al. Effect of 
intranasal dexmedetomidine or midazolam for premedication on the 
occurrence of respiratory adverse events in children undergoing 
tonsillectomy and adenoidectomy: a randomized clinical trial. JAMA 
network open. 2022;5(8):e2225473-e. 
2. 
Tariq S, Syed M, Martin T, Zhang X, Schmitz M. Rates of 
perioperative respiratory adverse events among Caucasian and African 
American children undergoing general anesthesia. Anesthesia & Analgesia. 
2018;127(1):181-7. 
3. 
McCann ME, Kain ZN. The management of preoperative anxiety in 
children: an update. Anesthesia & Analgesia. 2001;93(1):98-105. 
4. 
Yuki K, Daaboul DG. Postoperative maladaptive behavioral changes 
in children. Middle East J Anesthesiol. 2011;21(2):183-9. 
5. 
Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of 
emergence agitation in the pediatric postanesthesia care unit. Anesthesia & 
Analgesia. 2003;96(6):1625-30. 

6. 
Fortier MA, Del Rosario AM, Rosenbaum A, Kain ZN. Beyond pain: 
predictors of postoperative maladaptive behavior change in children. 
Pediatric Anesthesia. 2010;20(5):445-53. 
7. 
Jun JH, Kim KN, Kim JY, Song SM. The effects of intranasal 
dexmedetomidine premedication in children: a systematic review and meta-
analysis. Canadian Journal of Anesthesia/Journal canadien d'anesthésie. 
2017;64(9):947-61. 
8. 
Prescilla RP. Clinical Pharmacology of Sedatives, Reversal Agents, 
and Adjuncts.  Pediatric Sedation Outside of the Operating Room: 
Springer; 2021. p. 171-97. 
9. 
Diwan G, Bharti AK, Rastogi K, Gupta PK. Comparison of intranasal 
dexmedetomidine and midazolam as premedication in pediatric surgical 
patients: A prospective, randomized double-blind study. Anesthesia, 
Essays and Researches. 2020;14(3):384. 
10. 
Naaz S, Ozair E. Dexmedetomidine in current anaesthesia practice-a 
review. Journal of clinical and diagnostic research: JCDR. 
2014;8(10):GE01. 
11. 
Raj TY, Quan R. Recent Advances in Ketamine Research: An 
Update. Open Journal of Anesthesiology. 2020;10(3):89-100. 

12. 
Boddu SH, Kumari S. A short review on the intranasal delivery of 
diazepam for treating acute repetitive seizures. Pharmaceutics. 
2020;12(12):1167. 
13. 
Sonvico F, Clementino A, Buttini F, Colombo G, Pescina S, 
Stanisçuaski Guterres S, et al. Surface-modified nanocarriers for nose-to-
brain delivery: from bioadhesion to targeting. Pharmaceutics. 
2018;10(1):34. 
14. 
Lu C, Zhang L-M, Zhang Y, Ying Y, Li L, Xu L, et al. Intranasal 
dexmedetomidine as a sedative premedication for patients undergoing 
suspension laryngoscopy: a randomized double-blind study. PloS one. 
2016;11(5):e0154192. 
15. 
Akitt TL, Christie S, Jackson E, Paling K. Child Life: Developmental 
Considerations in the Emergency Department. Essentials of Pediatric 
Emergency Medicine. 2018:6. 
16. 
Cristoforo T, Gonzalez D, Bender M, Uy G, Papa L, Ben Khallouq BA, 
et al. A Pilot Study Testing Intranasal Ketamine for the Treatment of 
Procedural Anxiety in Children Undergoing Laceration Repair. Journal of 
Child & Adolescent Trauma. 2022;15(2):479-86. 

17. 
Leicht P, Wisborg T, Jørgensen BC. Does intravenous lidocaine 
prevent laryngospasm after extubation in children? Anesthesia & 
Analgesia. 1985;64(12):1193-6. 
18. 
Gennuso SA, Hart BM, Komoto H, Parker-Actlis T. Catastrophic 
complications in pediatric anesthesiology.  Catastrophic Perioperative 
Complications and Management: Springer; 2019. 261-74. 
19. 
Larson PC. Laryngospasm-the best treatment. The Journal of the 
American Society of Anesthesiologists. 1998;89(5):1293-4. 
20. 
de Souza Hobaika AB, Lorentz MN. Laryngospasm. Brazilian Journal 
of Anesthesiology. 2009;59(4):487-95. 
21. 
Ramsay M, Savege T, Simpson B, Goodwin R. Controlled sedation 
with alphaxalone-alphadolone. Br med J. 1974;2(5920):656-9. 
22. 
Humphrey GB, Boon CM, van Linden van den Heuvell GC, van de 
Wiel HB. The occurrence of high levels of acute behavioral distress in 
children and adolescents undergoing routine venipunctures. Pediatrics. 
1992;90(1):87-91. 
23. 
Aldrete J. The post-operative recovery score revisited. J Clin Anesth. 
1995;7(1):89-91. 
 Preoperative anxiety and respiratory complications are among the most frequent challenges 
faced by children undergoing adenotonsillectomy. Respiratory complications during the 
perioperative period, ranging from minor issues such as oxygen desaturation, airway obstruction, 

coughing, and wheezing to severe events like laryngospasm and bronchospasm, are particularly 
concerning in pediatric anesthesia. These complications can extend hospitalization, increase 
medical expenses, and result in both physical and psychological impacts on children and their 
families. 
Preoperative anxiety in children, marked by feelings of tension, apprehension, and worry, often 
manifests in various behavioral changes. It can also lead to postoperative maladaptive behaviors 
such as enuresis, feeding issues, apathy, and sleep disturbances. Studies indicate that up to 60% 
of children undergoing surgery may experience adverse behavioral changes two weeks 
postoperatively, with factors like age and parental anxiety in the preoperative setting acting as 
predictors. 
To address these challenges, premedication plays a crucial role by easing the separation from 
parents and reducing stress, thereby enabling smoother induction of anesthesia. Intranasal 
administration of medications, such as dexmedetomidine, ketamine, and midazolam, has 
emerged as a promising approach. This method is non-invasive, offers high bioavailability due to 
bypassing first-pass hepatic metabolism, and is well-suited for pediatric patients. 
Dexmedetomidine, a highly selective alpha-2 adrenergic agonist, is known for its sedative, 
anxiolytic, and analgesic effects without causing respiratory depression. It induces a natural 
sleep-like state by stimulating inhibitory pathways in the brainstem. Ketamine, on the other hand, 
produces dissociative anesthesia by interacting with N-methyl-D-aspartate (NMDA) receptors, 
reducing pain sensitization and minimizing opioid requirements. Midazolam, a benzodiazepine 
with rapid onset and short duration, acts on receptors in the olfactory nerves, producing sedation 
and an amnesic effect. 
Despite their individual advantages, the comparative effectiveness of intranasal 
dexmedetomidine, ketamine, and midazolam in minimizing respiratory complications and 
anxiety in pediatric adenotonsillectomy remains unclear. This study aims to evaluate and 
determine the most efficient intranasal premedication for reducing these perioperative challenges 
in children.