To compare the effect of Dexmedetomidine and Ketamine nebulization as premedication to reduce the Preoperative anxiety and Post operative agitation in Pediatric patients undergoing Tonsillectomy surgery: A Randomized controlled trial

INTRODUCTION Preoperative anxiety is common in pediatric patients especially in the age

group of. 3-10 yearuy .Preoperative anxiety can be more harmful, children are more

likely to experience increased autonomic nervous activity compared to adults, leading

to prolonged anesthesia induction time, anesthesia duration, and recovery time. This

1S Complicated further by the psychological characteristics of3 to 10 years old children

are generally more variable, impulsive, and react unintentionally (2). They are aware of

the existence of their parents and are more likely to experience fear and separation

anxiety. In this proposed study, it is intended to address the gap in existing research

by specifically exploring the use of dexmedetomidine and ketamine nebulization for

pediatric patients in Tonsillectomy surgery. The study will assess various parameters,

including hemodynamic changes, sedation levels, parental separation anxiety, mask

acceptance and post operative agitation.

OBJECTIVE AND SCOPE OF THE STUDY

Previously several drugs such as dexmedetomidine, midazolam,

ketamine etc. have been used through different routes (intravenous, intramuscular,

intranasal spray, nebulization) to alleviate the preoperative anxiety (), reduce parental

separation anxiety etc. (6] So, we hypothesize that these drugs in nebulization can be a

useful premedication to alleviate preoperative anxiety and easy parental separation in

paediatric patients, while producing minimal adverse events.

Our plan in this study primarily is to compare the effect of nebulization with

dexmedetomidine or ketamine as premedication to alleviate preoperative anxiety and

-reduce parental separation anxiety for paediatric-patients undergoing Tonsillectomy

surgery and then Secondarily to compare the post operative Emergence Agitation in

this group.

PRELIMINARY WORKALREADY DONE AND COMPLETED:

has

been

done’ and

study protocol

made.

Literature search was

STATEWHETHER ANY WORK PERTAINING TO THE PROPOSED

WORK HAS BEEN IN THE DEPARTMENT EARLIER: no preliminary wok

has been done in the department.

LACUNAE IN KNOWLEDGE OF THE SUBJECT:

The use of dexmedetomidine or ketamine for nebulization as premedication is

been done in previous studies like ketamine, at a dosage of 6 mgkg-l given orally,

reduced the incidence of emergence agitation by 34% in children under anesthesia

with desflurane for adenotonsillectomyuy,but there is no such study done using

Dexmedetomidine or Ketamine nebulization premedication for pediatric patient to

reduce the postoperative emergence agitation as well as preoperative anxiety in

tonsillectomy surgeries. Further, there is no previous literature stating about the

post operative events and mask acceptance for children pre operatively due to these

drugs in pediatric tonsillectomy Surgery.

Inclusion Criteria:

1. Age range 3 to 10 years.

2. ASA I or II physical status

3.Parentguardian’s written consent.

Exclusion criteria:

1. Refusal to take part in the study.

2. Heart rate below 70/min or above 140/min.

3. Mean Arterial pressure less than 70mm of hg.

4. Patient with Upper Respiratory Tract Infection.

5. Surgery duration longer than 2 hours.

6. History of allergic reaction to the drugs mentioned in study.

METHODOLOGY:

The patients fulfilling all the inclusion criteria will be enrolled and will be

divided using Randomized computer generated number which will be sealed in an

opaque envelope technique into two equal groups.

Two study group cach of 36 will be received premedication by nebulization as

follow:

Group K (n=36) will receive nebulized solution ketamine 2 mg kg .

Group D (n-36) will receive nebulized solution dexmedetomidine 2 ug kg.

An independent investigator not involved in the study will open the envelopes 1

hourr before the induction of anesthesia and will prepare the study drug solution as

per the random group. Study drugs will be diluted in 3 ml of 0.9% saline and will

be administered by standard hospital pediatric nebulizer mask via a mouthpiece

with a continuous flow of 100% oxygen at 6 L min for 10-15 min until the

solution is empty. The patient will be kept calm by keeping in lap of mother if

possible or in the bed if cooperative to receive the nebulization. The attending

anesthesiologist, data collection personnel and the patient will be blinded to the

study. Each patient had to complete the three phases of the study: preoperative

phase (30 min after end of administration of nebulizer study drug), intra operative

phase, and the early postoperative phase (1 h after operation).

ASSESSMENT PARAMETERS

Preoperative assessments

The heart rate(HR), non-invasive blood pressure such as systolic blood

pressure(SBP), diastolic blood pressure(DBP), mean arterial blood pressure(MAP),

respiratory rate (RR) and oxygen saturation(SpO2) will be assessed at (0 min i.e.

baseline) and at 5, 10, 20 and 30 min after the end of study drug administration. The

sedation level will be assessed at the same time points mentioned using a five-point

sedation scale score.

At the end of the preoperative phase, parental separation will be assessed by a four

point parental separation anxiety score (PSAS).

1| Agitated; clinging to parent/erying

2 Alert; anxious not clinging to parent, may whimper but not cry

3 Calm; sitting or lying comfortably with eyes open

4| Drowsy; eyes closed but responding to verbal or tactile stimulation

5| Asleep; does not respond to minor stimulation

1Easy separation

2 Whimpers

Cries and not easily reassured but not clinging to parents

4 Crying and clinging to parents

1Excellent; unafraid, cooperative, accepts mask readily

2 Good; slight fear of mask, easily reassured

3 Fair: not calmed with reassurance

4 Poor; terrified; crying or combative

Intraoperative assessments

After arrival in the operating room (0R) all standard monitors such as 12 lead

electrocardiogram (ECG), non-invasive blood pressurc monitor, pulse oximetry will

be attached. An intravenous cannulation of appropriate sizc will be placed and ringer

lactate will be started. Then an appropriate size anesthesia mask will be applied for

Dreoxygenation. The patient’s acceptance of the mask will be assessed using a four

point mask acceptance score (MAS). The ancsthesia will be started by giving Inj

Midazolam 0.15 mg/Kg, Inj Fentanyl I meg/Kg followed by induction with Inj

Propofol2 mg/kg and muscle relaxant Inj.cistaracurium 0.15 mg/Kg. After adequate

depth of anesthesia and muscle relaxation, appropriate size Endotracheal Tube fixed

at Midline to secure the ventilation will be confirmed by EtCo2 monitor. The intra

operative anaesthesia will be maintained by inhalation isoflurane, nitrous oxide and

Oxygen with intermittent doses of Inj cisatracurium and Inj fentanyl.

Mask Acceptance Score (MAS)

The hemodynamic vitals as mentioned in preoperative phase will be recorded intra

operatively at (0 min i.e., baseline) and at every five minutes till the end of surgery.

Early postoperative assessment

The recovery will be assessed using the three-point emergence agitation (EA) score:

The post operative sedation level will be assessed previously using a five

point sedation scale score immediately after extubation and the time required

in min to achieve the score of3.

The haemodynamic vitals will be recorded after admission to the Post

Anaesthesia Care Unit (PACU)at (0 min i.e., baseline) and at 15, 30, 45, and

60 min thereafter.6

Emergence agitation score (EAS)

1 Calm

2 Restless but calms to verbal instructions

3 Combative and disoriented

SCORE CATEGORY

DESCRIPTION

7

Dangerous agitation

Pulling off tracheal tube, trying to remove catheters,

climbing over bedrail, striking the staff

6

Very agitated

Requiring restrain and frequent verbal reminding of

limits.

Agitated

Anxious or mildly agitated, attempting to sit up and

calms down on instructions

4

Calm, cooperated

Calms and follows commands

3

Sedated

Difficult to arouse but awakens to verbal stimuli or

gentle shaking but drifts off again; follows simple

commands.

2

Very sedated

Arouse to physical stimuli but does not communicate or

follow commands; may move spontaneously.

Unarousable

Minimal or no response to noxious stimuli; does not

communicate or follow commands.

Riker Sedation-Agitation Scale (SAS)

Guidelines for SAS Assessment(]

1. Agitated patients are scored by their most severe degree of agitation as

described

2. If patient is awake or awakens easily to voice (awaken means responds

with voice or head shaking to a question or follows commands), that’s a SAS

4 (same as calm and appropriate - might even be napping)

3. If more stimuli such as shaking is required but patient eventually does

awaken, that’s SAS 3

4. If patient arouses to stronger physical stimuli (may be noxious) but never

awakens to.the point of responding yes/no or following commands, that’s a

SAS 2.

5. Little or no response to noxious physical stimuli represents a SAS1. This

helps separate sedated patients into those you can eventually wake up (SAS

3. those yoç can’t awaken but can arouse (SAS 2), and those you can"t arouse

(SAS 1)

STATISTICAL EVALUATION

The obtained data shall be recorded &result shall be statistically analyzed

by appropriate statistical method. A p value of 0.05 will be considered as

significant &<0.01 will be considered as highly significant

The sample size formula of two independent proportions as given below has been

used by taking 10% level of significance and 90% power.

4 = (Z1-/z + Z,-)P(-P) +pa(1-P)

Where Z1-a/2=1.96 at 10% level of significance

Z1-b = 1.282 at 90% power

P1 = proportion improved in dexmedetomidine group 0.47

Q1-1-p1

Qz-1-p2

The sample size thus calculated is n=32 further assuming 10% loss to follow up the

required sample size for present study will be 36 in each group.

REFERENCES: -

1. Kain Z. N, Caldwell- Andrews A..A. Maranets 1. et al. Preoperative anxiety and

emergence delirium and post operative maladaptive behaviors.

AnesthAnalg. 2004; 99:1648-1654

2. Zanaty O.M. Metainy E.L. SA. A comparative evaluation of nebulized

dexmedetomidine, nebulized ketamine, and their combination as premedication

for outpatient paediatric dental surgery AnesthAnalg 2015;121:167-171

3. Abdel- Ghaffar HS. Kamal SM, EI sherif FA, et al. comparision of nebulized

dexmedetomidine, ketamine or midazolam for premedication in preschool

children undergoing bone marrow biopsy, Br J Anaeshth. 2018; 121(2):445-452

4. Hosey MT, Asbury AJ, Bowman AW, Millar K, Martin K, Musiello T, Welbury

R. The effect of transmucosal 0.2 mg/kg midazolam premedication on dental

anxiety, anaesthetic induction and psychological morbidity in children

undergoing general anaesthesia for tooth extraction. Br Dent J. 2009;207:E2

5. Kain ZN, Caldwell-Andrews AA, Maranets I, McClain B, Gaal D, Mayes LC,

Feng R, Zhang H. Preoperative anxiety and emergence delirium and postoperative

maladaptive behaviors. AnesthAnalg. 2004;99:1648-54

6. Irola T, Vilo S, Manner T, Aantaa R, Lahtinen M, Scheinin M, Olkkola KT.

Bioavailability of dexmedetomidine after intranasal administration. Eur J Clin

Pharmacol. 2011;67:825-31

7. Yang X, Hu Z, Peng F, Chen G, Zhou Y, Yang Q, Yang X, Wang M. Effects of

Dexmedetomidine on Emergence Agitation and Recovery Quality Among Children

Undergoing Surgery Under General Anesthesia: A Meta-Analysis of Randomized

Controlled Trials. Front Pediatr. 2020 Nov 13;8:580226. doi:

10.3389/fped.2020.580226. PMID: 33304867; PMCID: PMC7694572.

8. Mortensen M, McMullin C. Discharge score for surgical outpatients. Am J

Nurs.1986;86:1347--9

9. Qiao, H., Xie, Z. & Jia, J. Pediatric premedication: a double-blind randomízed

tria! of dexmedetomidine or ketamine alone versus a combination of

dexmedetomidine and ketamine. BMC Anesthesiol 17, 158 (2017)

t0.K. Jonkman, A. Duma, M. Velzen, A. Dahan; Ketamine inhalation, BJA: British

Journal of Anaesthesia, Volume 118, Issue 2, February 2017, Pages 268-269

11.Kararnmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Oral ketamine premedication can prevent

emergence agitation in children after desflurane anaesthesia. PaediatrAnaesth. 2004

Jun;14(6):477-82. doi: 10.1111/j.1460-9592.2004.01224.x. PMID: 151532 10.

0 COMPARE THE EFFECT OF DEXMEDETOMIDINE AND KETAMINE NEBULIZATION

AS PREMEDICATION TO REDUCE THE PREOPERATIVE ANXIETY AND POST OPERATIVE

AGITATION IN PEDIATRIC PATIENTs UNDERGOING TONSILLECTOMY SURGER Y: A

RANDOMIZED CONTROLLED TRIAL"

Signature of HOD:

Signature of Guide:

Signature of Candidate:

Signature of D.R.C members:

CONSENT FORM

Introdoction:

You are requested to participate in a study "A comparative evaluation of nebulization with

dexmedetomidine and ketamine as premedication for paediatrie patients undergoing tonsillectomy

surgery. Your participation in this study is voluntary. You may refuse to participate or withdraw

from the study at any time without this affecting in anyway the medical treatment that you are

receiving. Please read this consent form thoroughly and ask the consultant any questions you may

have about the study before signing.

Explanation of procedures:

If you agree to participate in this study, we will either nebulizer the patient by ketamine 2

mg kg (Group K), or dexmedetomidine 2 ug kg (Group D). We will observe the effect of the

drug used in premedication to alleviate preoperative anxiety and improve cooperation during mask

application in pediatric patients, while producing minimal adverse events. Data from the study will

be used for research purpose and for your treatment. You will be made the data available relevant

to your medical care only and not all the results. You will bear no expenses for your participation

in this study.

Potential benefits:

Your participation will help us to know effects of ketamine 2 mg kg and

dexmedetomidine 2 ug kgfor premedication in paediatric population undergoing tonsillectomy

procedure. The result of this study will be beneficial for the paediatric patients undergoing such

procedure.

Assurance of confidentiality:

The infomation concerning your participation in this study will be kept confidential to the

full extent permitted by law and will be used only for scientific purpose. None, except the members

of the research team will have access to the test results. Your name will not be used in any report

or released in any way.

Parent/Guardian’s Consent:

I have read the explanation about this study and have been given the opportunity to

discuss it and to ask questions. I hereby consent to take part in the study.

Signature of Parent/Guardian

Date.. ...

Signature of witness

Date.

aRE.....

ee....

Aypendix

PROFORMA

DEMOGRAPHIC DATA

NAME

AGE/GENDER

M.R.D. NUMBER

WEIGHT

ASA PHYSICAL STATUS

DATE OF SURGERY

GROUP

Hemodynamic Parameters; Preoperative:

Parameters

TO(min) T5(min)

T10(min) T20(min) T30(min)

Systolic

BP(SBP)

Diastolic

BP(DBP)

Mean BP(MAP)

Heart Rate(HR)

Respiratory

Rate(RR)

Oxygen

Saturation(Spo2)

TO(min)- At the time of starting nebulisation

TS(min)- Smin After the nebulisation

T10(min)-1Omin After the nebulisation

T20(min)-20min After the nebulisation

T30(min)-3Omin After the nebulisation

1-Agitated; clinging to parent/crying

2=Alert; anxious not clinging to parent, may

whimper but not cry

3= Calm; sitting or lying comfortably with

eyes open

4= Drowsy; eyes closed but responding to

verbal or tactile stimulation

5=Asleep; does not respond to minor

stimulation

Five-point sedation score:

Parental separation anxiety score: PSAS

1= Easy separation

2= Whimpers

3= Cries and not easily reassured but not

clinging to parents

4= Crying and clinging to parents

Intraoperative assessments:

Mask acceptance score: MAS

1= Excellent;, unafraid, cooperative, accepts

mask readily

2= Good; slight fear of mask, easily

reassured

3= Fair: not calmed with reassurance

4- Poor; terrified; crying or combative

Hemodynamic Parameters:

Parameters TO(min) TS(min) T10(min) T15(min) T20(min) T25 (min) T30(min)

Systolic

BP (SBP)

Diastolic

BP (DBP)

Mean BP

(MAP)

Heart Rate

(HR)

Respiratory Rate (RR)

Oxygen

Saturation

(Spo2)

TO= At the time of starting of general anaesthesia

T5= Smin after the induction of general anaesthesia

T10= 10 min after the induction of general anaesthesia

T15= 15 min after the induction of general anaesthesia

T20= 20 min after the induction of general anaesthesia

T25=25 min after the induction of general anaesthesia

T30=30 min after the induction of general anaesthesia

Early Post operative assessment:

Post operative sedation score: POSS

l=Agitated; clinging to parcnt/crying

2=Alert; anxious not clinging to parent, may

whimper but not cry

3=Calm; sitting or lying comfortably with

eyes open

4= Drowsy; eyes closed but responding to

verbal or tactile stimulation

5=Asleep; does not respond to minor

stimulation

Time required to achieve POSS of 3 (in minutes):

Hemodynamic Parameters:

Parameters TO(min)

T15(min) T30(min)

T45(min) T60(min)

Systolic

BP(SBP)

Diastolic BP

(DBP)

Mean BP

(MAP)

Heart Rate

(HR)

Respiratory

Rate (RRO

Oxygen Saturation

(SPo2)

T0- At the time of admission to the Post Anesthesia Care Unit

T15- 15 min after the.admission to the Post Anesthesia Care Unit

T30- 30 min after the admission to the Post Anesthesia Care Unit

T45- 45 min after the admission to the Post Anesthesia Care Unit

T60- 60 min after the admission to the Post Anesthesia Care Unit