SYNOPSIS (RESEARCH PROPOSAL) ON THE THESIS FOR

M.D. ANAESTHESIOLOGY
Session: 2022-2025

PROPOSED TITLE OF THE THESIS

“A Comparative Study to Assess Response of Intravenous
Paracetamol and Dexmedetomidine on Perioperative Hemodynamics
and Postoperative Pain in Patients Undergoing Elective General
Surgery”

DR. Arunanshu Pal

1st YEAR POST GRADUATE TRAINEE
DEPARTMENT OF ANAESTHESIOLOGY
NILRATAN SIRCAR MEDICAL COLLEGE AND HOSPITAL
KOLKATA - 700014

GUIDE
DR. SAIKAT MAJUMDAR
ASSOCIATE PROFESSOR
DEPARTMENT OF ANAESTHESIOLOGY
NILRATAN SIRCAR MEDICAL COLLEGE AND HOSPITAL
KOLKATA - 700014

THE WEST BENGAL UNIVERSITY OFHEALTH SCIENCES

 To,
The Chairman
Scientific Advisory Committee
NRS Medical College and Hospital
(Through proper channel)

SUB: Clearance of research proposal (synopsis) on the thesis entitled “A

Comparative Study to Assess Response of Intravenous Paracetamol and
Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain in
Patients Undergoing Elective General Surgery”
Respected Sir,
With due respect, I, Dr. Arunanshu Pal, 1st year MD PGT(session 2022-25),
Department of Anesthesiology, NRS Medical College & Hospital, would like to
inform you that I wish to submit the research proposal (synopsis) on the topic “A
Comparative Study to Assess Response of Intravenous Paracetamol and
Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain in
Patients Undergoing Elective General Surgery” My guide is Dr. Saikat Majumdar,
Associate Professor, Department of Anesthesiology, NRS Medical College &
Hospital. My place of work is Anesthesiology department of NRS Medical College &
Hospital.
I am hereby submitting my research proposal(synopsis) on the above-mentioned
thesis for the kind clearance by the Institutional Ethics Committee.

Thanking you,
Yours faithfully,

Signature of candidate

Forwarded

Signature of guide

With official seal and date

Signature of Head of the Department

To,
The Principal
NRS Medical College and Hospital
(Through proper channel)

SUB: Clearance of research proposal (synopsis) on the thesis entitled “A Comparative Study to
Assess Response of Intravenous Paracetamol and Dexmedetomidine on Perioperative
Hemodynamics and Postoperative Pain in Patients Undergoing Elective General Surgery”

Respected Sir,

With due respect, I, Dr. Arunanshu Pal, 1st year MD PGT(session 2022-25),
Department of Anaesthesiology, NRS Medical College & Hospital, would like to inform you
that I wish to submit the research proposal (synopsis) on the topic “A Comparative Study to
Assess Response of Intravenous Paracetamol and Dexmedetomidine on Perioperative
Hemodynamics and Postoperative Pain in Patients Undergoing Elective General Surgery”
My guide is Dr. Saikat Majumdar, Associate Professor, Department of Anesthesiology, NRS
Medical College & Hospital. My place of work is the General Anaesthesiology Department of
NRS Medical College & Hospital.

I am hereby submitting my research proposal (synopsis) on the above-mentioned thesis for the
kind clearance of the Institutional Ethics Committee.

Thanking you,
Yours faithfully,

Signature of candidate
Dr. Arunanshu Pal
1ST YEAR POST GRADUATE TRAINEE
DEPARTMENT OF ANAESTHESIOLOGY
NRS MEDICAL COLLEGE AND HOSPITAL
To,
The Chairperson,
Institutional Ethics Committee,
Nilratan Sircar Medical College, Kolkata

Sub: Application for approval of research proposal for thesis of M.D. Anaesthesiology
course (Session 2022-2025)
Respected Sir,
I, Dr. Arunanshu Pal, 1st year post-graduate trainee in Anaesthesiology
course (Session 2022-2025) has selected the thesis topic “A Comparative Study to Assess
Response of Intravenous Paracetamol and Dexmedetomidine on Perioperative
Hemodynamics and Postoperative Pain in Patients Undergoing Elective General
Surgery”
I am hereby submitting my synopsis and patient consent form.
I shall be grateful to you if you kindly approve my thesis topic in this regard.

Date:
Place: Kolkata

Thanking you

Yours sincerely,

Dr. Arunanshu Pal.

1 Year Post-Graduate Trainee,
ST

M.D Anaesthesiology
Department of Anaesthesiology
N.R.S Medical College and Hospital
Kolkata.

Forwarded

Signature of guide

With official seal and date

Signature of Head of the Department
 INVESTIGATOR’S UNDERTAKING

I Arunanshu Pal, M.D. Anaesthesiology 1st year post graduate trainee, for the
session 2021-24, hereby declare that I am doing the study titled “A
Comparative Study to Assess Response of Intravenous Paracetamol and
Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain
in Patients Undergoing Elective General Surgery” under the guidance of
Associate Prof. Dr. Saikat Mazumdar, Department of Anaesthesiology, Nilratan
Sircar Medical College and Hospital, Kolkata, solely for the purpose of my
thesis as part of fulfillment of my M.D. course. I shall be liable to bring to the
notice of Ethics Committee the developments regarding this study, including
any adverse outcome. The treatment protocol will be in parity with present
standards maintained in this hospital. The treatment and investigations will be
done in the hospital’s own setup and any special cost of treatment will be borne
by me, putting no extra financial burden on the patient.

Dr. Arunanshu Pal

M.D. Anaesthesiology PGT
Session: 2022-2025
Nilratan Sircar Medical College and Hospital
 SYNOPSIS PROPOSAL
TITLE OF THE THESIS
“A Comparative Study to Assess Response of Intravenous Paracetamol
and Dexmedetomidine on Perioperative Hemodynamics and
Postoperative Pain in Patients Undergoing Elective General Surgery”

PRIMARY
INVESTIGATOR
DR. Arunanshu Pal
1st YEAR POST GRADUATE TRAINEE
DEPARTMENT OF ANAESTHESIOLOGY
NILRATAN SIRCAR MEDICAL COLLEGE AND HOSPITAL
KOLKATA - 700014

GUIDE
DR. SAIKAT MAJUMDAR
ASSOCIATE PROFESSOR
DEPARTMENT OF ANAESTHESIOLOGY
NILRATAN SIRCAR MEDICAL COLLEGE AND HOSPITAL
KOLKATA - 700014
 A) Summary OF PROPOSAL

A. NAME OF THE CANDIDATE: -

Dr. Arunanshu Pal 1st year PGT, Department of Anesthesiology, Nilratan Sircar

Medical College and Hospital

B. PLACE OF PROPOSED RESEARCH WORK: -

Department of Anaesthesiology, Nilratan Sircar Medical College and Hospital, Kolkata

C. BROAD AREA: -Clinical

D. SPECIFIC AREA: - General Anaesthesiology

E. NAME OF GUIDE: -

Dr. Saikat Majumdar, Associate Professor, Department of Anaesthesiology, Nilratan

Sircar Medical College and Hospital

F. PROPOSED TOPIC OF RESEARCH: -

“A Comparative Study to Assess Response of Intravenous Paracetamol and

Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain in Patients

Undergoing Elective General Surgery”

G. OBJECTIVES: -

Prospective descriptive study to assess the perioperative hemodynamics and postoperative

analgesic response of Intravenous Dexmedetomidine and Paracetamol in patients undergoing

elective general surgery.

H. BACKGROUNDS: -

Unrelieved post-operative pain may bring about physical suffering as well as a couple of

physiological and mental effects, which may adversely affect the peri-operative outcome and

make contributions to growth during the period of stay in the health center.
Dexmedetomidine is an incredibly selective α2 adrenoceptor agonist that provides sedation,

analgesia, and sympatholytic without causing respiratory depression. Paracetamol is an

extensively used and popular analgesic and antipyretic. So, we have planned this study to see

the effect of Dexmedetomidine and Paracetamol on perioperative hemodynamics status,

postoperative pain relief and adverse effects, in patients undergoing surgical procedures

under general anesthesia.

I. METHODOLOGY: -

This is a prospective descriptive study to assess the perioperative hemodynamics and

postoperative analgesia response of the Intravenous Dexmedetomidine and Paracetamol.

Data will be collected from the patients undergoing elective general surgery of age 18 to 60

and belonging to ASA class I and II receiving these drugs. Then later will be divided in two

groups.

 Group P (n = 104) who will receive IV 1g Paracetamol infusion over 10min pre-

operatively 10 mint pre-induction period.

 Group D (n = 104) will receive IV Dexmedetomidine 1 μg/kg bolus over 10 min per-

operatively and 0.3 μg/kg/hr thereafter till the end of the surgery.

Standardized GA will be given to all patients. Induction will be done by Fentanyl 2.5 μg/kg

IV, and injection of Etomidate 0.3 mg3/kg IV. Anesthesia will be maintained by N2O,

O2(1:1) and Isoflurane 0.5-0.1%, controlled ventilation will be adjusted to normocarbia.

Heart rate (HR), systolic blood pressure (SBP) diastolic blood pressure (DBP), and mean

arterial pressure (MAP), will be recorded. Preoperative hemodynamic variables,

postoperative pain scores, and the needs for rescue analgesics will be recorded and compared.

J. EXPECTED OUTCOME: -

It is expected paracetamol will produce better analgesia with less sedation compare to

dexmedetomidine. VAS score at 4hours will be better with paracetamol than

dexmedetomidine.

B) OUTLINE OF PROPOSED RESEARCH TOPIC

1) Proposed Topic of Research:

“A Comparative Study to Assess Response of Intravenous Paracetamol and

Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain in

Patients Undergoing Elective General Surgery”

2) OBJECTIVES OF THE RESEARCH: -

General objectives:

To assess the perioperative hemodynamics and postoperative analgesic response of

Intravenous Dexmedetomidine and Paracetamol in patients undergoing elective general

surgery

Specific objectives:

 To measure perioperative hemodynamic response among patients receiving

Intravenous Dexmedetomidine and Intravenous Paracetamol

 To identify postoperative analgesic response in both groups of patients

 To assess VAS score between two groups

 To find out the adverse effects, if any of each drug

 To estimate postoperative liver enzyme changes after administration of each drug

3) RESEARCH HYPOTHESIS: -

Null Hypothesis: - There will be no difference in efficacy between IV

dexmedetomidine and IV Paracetamol in perioperative hemodynamics status and post

operative pain relief as per VAS scale.

Alternate Hypothesis: - There may be considerate amount of difference in

perioperative hemodynamic parameters and post operative analgesia between two study

groups one receiving Intravenous paracetamol while other receiving Intravenous

Dexmedetomidine.

4) Background of Research

A) Rationale of the study: -

Most of the previous studies calculated the long-term effects of I.V

dexmedetomidine as a maintenance dose of 24 hours causing higher incidences of

requirement of HDU monitoring which is not a feasible option in a case of general

surgery. In our study we are giving the drugs, that is, injection Dexmedetomidine

and injection paracetamol in their respective groups till the end of surgery to

review and compare hemodynamic and analgesic activity against one another.

B) Introduction: -

Adequate and satisfactory pain control is one of the major concerns in anesthetic practice.

Along with pain control, good sedation, and smooth recovery without complications results

in better patient satisfaction, shorter hospital stays, and reduced healthcare cost. Acute pain

inside the preoperative setting will increase the sympathetic response of the body with a

subsequent rise in oxygen consumption of the body, the chance of deep vein thrombosis due
to immobility, and consequent pulmonary embolism. Similarly, there may be sizable effects

on the gut and urinary tract motility, which may lead, in turn to postoperative illus, nausea,

vomiting, and urinary retention. Increased opioid usage for good control of postoperative

pain results in unwanted complications such as respiratory depression, nausea and vomiting,

increased sedation, and slow gastrointestinal functioning.

The nonopioid drugs can be used as an adjuvant to opioids or as sole agents, for an effective

reduction in the need for further opioid doses. Dexmedetomidine is a highly selective

alpha-2 receptor agonist, which is eight times more specific compared to clonidine.

Dexmedetomidine binds to the G-protein coupled with the alpha-2 receptors and generates

the required clinical outcomes. Sedation occurs due to action on the locus coeruleus. The

pain score was significantly lower with good patient satisfaction in terms of hemodynamic

changes, amount of opioid use, complications, and sedation scale. Paracetamol is a

preeminent analgesic, known for its safety and better tolerance. Acetaminophen or

paracetamol has a central analgesic effect that is mediated through activation of descending

serotonergic pathways. Debate exists about its primary site of action, which may be

inhibition of prostaglandin synthesis. The mechanism of action has been debated. In animal

models, it has been seen to inhibit COX-3. At the spinal cord level, it has been shown to

antagonize neurotransmission by N-methyl-d-aspartate (NMDA), substance P, and nitric

oxide pathways. Intravenous (iv) paracetamol provides a rapid and predictable therapeutic

concentration in plasma. In 2010, Food and Drug Administration approved paracetamol iv

infusion as a first-line drug for the management of mild to moderate pain and as an adjuvant

for moderate to severe pain. It can be used as an adjuvant that works synergistically with

anesthetics to help enhance the duration and quality of analgesia in regional techniques.

[1,2]
So, we have planned this study to see the effect of Dexmedetomidine and Paracetamol on

postoperative pain relief, adverse effects, and hemodynamics in patients undergoing elective

surgical procedures under general anesthesia.

C) Review of Literature: -

 Swaika S et al. (2013) have conducted a study “A comparative study of the

efficacy of intravenous Paracetamol and Dexmedetomidine on peri-operative

hemodynamics and post-operative analgesia for patients undergoing

laparoscopic cholecystectomy.” A total of 80 participants of ASA grade I were

randomly allocated in 2 groups.: Group P (n = 40) received IV 1 g Paracetamol

infusion over 10 min pre-operatively and 6 hourly thereafter and Group D (n = 40)

received IV Dexmedetomidine 1 μg/kg bolus over 10 min pre-operatively and 0.2-

0.4 μg/kg/h thereafter for 24 hour. They have found Profiles of intra-operative

hemodynamic changes were similar in both groups in respect to heart rate (HR),

diastolic blood pressure, mean arterial pressure except in the systolic blood pressure

where Dexmedetomidine significantly reduced it in compare to Paracetamol. Post-

operatively 4th h and 24th hour changes in mean HR between two groups was a

statistically significant. Visual analog scale scores were significantly lower in the

Group P compared with Group D at 8th, 16th, and 24th hour. Sedation score were

statistically higher in the Group D compared with the Group P at post-operative 4th,

8th, 16th, and 24th hour. [1]

 Fakhri T et al. (2023) have conducted a study “Comparative Study of

Intravenous Paracetamol and Dexmedetomidine on Perioperative

 Hemodynamics and Postoperative Pain Relief for Laparoscopic

Cholecystectomy.” A total of 50 participants of ASA grade I and II were randomly

allocated in 2 groups. Group P (n= 25) received IV 1g Paracetamol infusion over 10

min preoperatively and 6 hourly thereafter and group D (n = 25) received IV

Dexmedetomidine 1 μg/kg bolus over 10 min pre-operatively and 0.2-0.4 μg/kg/hr

thereafter for 24 hrs. They found that intra-operative hemodynamic changes had

been similar in each group regarding heart rate (HR), diastolic blood pressure

(DBP), and mean arterial pressure (MAP) except within the systolic blood pressure

(SBP) where Dexmedetomidine significantly decreased it compared to Paracetamol.

(Visual analog scale scores have been significantly lower inside group P than in

group D. Sedation scores have been statistically better inside group D compared

with group P.) Paracetamol is superior to Dexmedetomidine for analgesia in short

surgical procedures and should form a part of multi-modal analgesia. The use of

paracetamol provides multimodal analgesia with minimum sedation in short surgical

procedures and dexmedetomidine provides analgesia and cooperative sedation. [2]

 Kamali A et al. (2018) have conducted a study “A comparative study on the

prophylactic effects of paracetamol and dexmedetomidine for controlling

hemodynamics during surgery and postoperative pain in patients with

laparoscopic cholecystectomy.” A total of 132 participants of either sex of ASA

grade I&II in the age group of 18 to 70 years were randomly allocated in 2 groups.

Group A (n=66) received IV dexmedetomidine 1mg/kg stat and then 0.5mg/kg per

hour for up to 6hours after surgery. Group B (n=66) first received 1g paracetamol

intraoperative before surgery, and 500mg paracetamol was also prescribed every

6hours until 24hours. They observed Pain score in the paracetamol group was

significantly lower than that in the dexmedetomidine group; nevertheless, there were
 no group differences in the mean scores of pain during these hours. The median

opioid use in 24hours after operation in the paracetamol group was lower when

compared with that in the dexmedetomidine group, and the mean duration of

analgesia in the paracetamol group was higher when comparing with

dexmedetomidine group. Furthermore, in both groups, mean arterial pressure and

preoperative PR interval were similar at various times. The findings demonstrated

that both regimens of drugs can control the hemodynamic status of patients during

laparoscopic cholecystectomy, which provides effective postoperative analgesia for

pain management. [3]

 Sharma R et al. (2017) have studied “Postoperative Analgesia with Intravenous

Paracetamol and Dexmedetomidine in Laparoscopic Cholecystectomy

Surgeries: A Prospective Randomized Comparative Study.” A total of 100

participants of either sex of ASA grade I&II in the age group of 18 to 60 years were

randomly allocated in 2 groups. Group I (n=50) received 1 g intravenous PCM, in

100 ml solution before incision. Group 2 (n=50) received i.v. dexmedetomidine 1

µg/kg as bolus over 10 min followed by infusion of 0.5 µg/kg/h until the removal of

gallbladder. They observed postoperative analgesic requirement significantly

decreased with a lower score on VAS, better patient satisfaction scores, and Ramsay

Sedation Score ranges from 3 to 5 (62%) in Group I. The incidence of nausea and

vomiting, hypotension, and bradycardia was comparable in both the groups except

shivering, which was found significantly less in Group II. Incorporation of

dexmedetomidine as a part of multimodal analgesia provides better hemodynamic

profile, analgesic, sedative, and amnesic properties along with negligible serious

adverse effects. [4]

 Manjula Sarkar et al. (2016) have studied “Comparative Study of Intravenous

 Dexmedetomidine versus Paracetamol for Postoperative Pain Relief in

Laparoscopic Surgery.” A total of 60 participants of either sex of ASA grade I&II

in the age group of 18 to 65 years were randomly allocated in 2 groups. Group D

(n=30) received IV Dexmedetomidine 1μg/kg over 10 min followed by 0.2-0.7 μg

/kg/hr for next 4 hours and Group P (n=30) received IV Paracetamol 15 mg/kg prior

to extubation. In group D, 12 patients required rescue analgesia as compared to 4

Patients in group P. VAS scores were similar in both groups with group P showing

trend towards low score. Median time at which the first dose of rescue analgesia was

administered in group P was longer. Incidence of bradycardia and hypotension was

higher in group D. Paracetamol is a superior to Dexmedetomidine for analgesia in

short surgical procedures and should form a part of multimodal analgesia. [5]

 Goswami S et al. (2023) have conducted a study “A COMPARATIVE STUDY

OF THE EFFICACY OF INTRAVENOUS PARACETAMOL AND

DEXMEDETOMIDINE ON PERI OPERATIVE HEMODYNAMICS AND

POST OPERATIVE ANALGESIA FOR PATIENTS UNDERGOING

LAPAROSCOPIC SURGERY.” A total of 60 participants of either sex of ASA

grade I&II in the age group of 18 to 66 years were randomly allocated in 2 groups.:

Group P (n = 30) received IV 1-gram Paracetamol diluted in 100 ml 0.9 percent

Normal Saline IV over 10 minutes before induction Group D (n = 30) received IV

Dexmedetomidine Bolus 1 mcg/kg diluted in 100 ml 0.9 percent Normal Saline IV

over 10 minutes before induction. Perioperative Hemodynamic parameters, post

operative analgesia were compared. Increase in heart rate, blood pressure was found

to be more in Group P compared to Group D. Patients in both groups had moderated

pain postoperatively and requires rescue analgesia after extubation. They observed

the use of Dexmedetomidine is very effective in managing Perioperative

 Hemodynamic instability when compared to paracetamol. [6]

 Kumar S et al. (2022) have conducted a study “A clinical study of post-operative

analgesia with intravenous paracetamol versus dexmedetomidine in patients

undergoing laparoscopic cholecystectomy.” A total of 60 participants of either sex

of ASA grade I&II in the age group of 18 to 50 years were randomly allocated in 2

groups. Group D (n=30) received intravenous dexmedetomidine 1µg/kg as bolus

over 10 min followed by dexmedetomidine infusion at 0.25ml/kg/h. Group P (n=30)

received 1g intravenous paracetamol in 100ml solution of normal saline over 10 min

followed by infusion of 0.25ml/kg/h of normal saline. They observed time for first

rescue analgesia, and total doses of analgesia in 24 h in group D was 225.33±29.12

and 2.73±0.64 and in group P was 143.33±28.96 and 4.23±0.77 respectively with p

value 0.001 which was statistically significant. Dexmedetomidine loading dose

1µg/kg and maintenance dose 0.5µg/kg is a good anesthetic adjuvant for general

anesthesia to reduce post-operative requirement of analgesia in laparoscopic

surgeries. [7]

D) Gap in the existing research: -

All the researches done previously monitored the effects of IV dexmedetomidine through

24hours as maintenance dose. All those studies have found that such dose over a prolonged

period showed a higher incidence of bradycardia and hypotension requiring a HDU set up.

This costly set up is not possible for every patient in elective general surgery with minimal

surgical risks. Therefore, in this study we are reducing the duration of the drugs just to the

end of surgery so that a better comparison can be made between hemodynamic and

analgesic components of IV dexmedetomidine and IV Paracetamol.

 E) Relevance and expected outcome of proposed study

It is expected paracetamol will produce better analgesia with less sedation compare to

dexmedetomidine. VAS score at 4hours will be better with paracetamol than

dexmedetomidine.

5) METHODOLOGY

A. Study Design: - The study is prospective descriptive study.

B. Study Setting: - General Surgery operation theater in Nilratan Sircar Medical

College and Hospital.

C. Place of study: - Nilratan Sircar Medical College and Hospital.

D. Period of study: - One and a half year after receiving permission from Ethical

committee of Nilratan Sircar Medical College and Hospital.

E. Study population: - Patients posted for elective general surgeries of age group 18-

60 years of both male and female gender of ASA grade I and II

F. Sample size: -Sample size is calculated using formula

2 2 2
n=(zα + zβ) (2 S p )/ d
 Zα= the critical value of the standard normal distribution at alpha level. 1.96 (two

tailed) at 95% confidence interval.

Zβ= the critical value of the standard normal distribution at beta level. 0.842 at 80%

power of the study.

S p =Pooled Standard deviation.

d =Permissible error.

From the literature [Anesthesia, Essays and Researches. 2013 Sep; 7(3):331.], the

VAS score at 4 hours in the postoperative period is noted as 2.43 ± 1.31 versus

1.94± 1.14 for paracetamol and dexmedetomidine group. Thus, form the above

literature 1.5 can be considered as pooled population variance. It is assumed that

therapy will lead to a difference of about 0.5 VAS score difference at 4 hours of

postoperative period. Hence the effect size (d) of 0.5 is assumed here. A two tailed

assumption was done. The sample size calculation was done using the following

formula and method as described in the literature [10, 11]. Setting the power of

study at 80% and allowing alpha error of 5%, the sample size for each group is

calculated as 98 is double to get 188 assuming 1:1 group allocation. Considering a

10% drop out, the sample size is finally adjusted to 208. Hence, 104 patients will be

assigned in each group.

G. Selection Criteria: -

 Inclusion Criteria

a. Age groups of 18-60 years of male and female having ASA grade I and II having

elective general surgery with signed informed consent form

b. Patients with normal Liver function test

c. Patients with normal coagulation profile

  Exclusion Criteria: -

a. Patient refused to give consent

b. Hypersensitivity to test drugs used in study

c. Patients with cardiovascular disorder, broncho-pulmonary disorder, renal,

neurologic, gastrointestinal, and hepatic dysfunction

d. Patients with long-time period use of medicinal drugs which includes beta-

blocker and different anti-hypertensives, antipsychotics, analgesics, alcohol,

sedative, TCA, etc

e. Patients with psychiatric illness

H. Study Variables

1. Preoperative variables

a) Age (in years)

b) Sex

c) Height (in meters)

d) Weight (in kg)

e) ASA

f) Heart Rate (beats/min)

g) Respiratory rate (/min)

h) Systolic Blood pressure (SBP), Diastolic Blood pressure (DBP), Mean arterial

pressure (MAP)

i) Oxygen Saturation (SPO2)

j) ECG

k) Chest auscultation

l) Auscultation of heart sounds

 m) Mallampati score

2. Intraoperative parameters and recovery parameters

a) Heart Rate (beats/min)

b) Respiratory rate (/min)

c) Systolic Blood pressure (SBP), Diastolic Blood pressure (DBP), Mean arterial

pressure (MAP)

d) Oxygen Saturation (SPO2)

e) End tidal CO2 (ETCO2)

f) Capnography

g) Ramsay Sedation Score

3. Post Operative variables

a) Heart Rate (beats/min)

b) Respiratory Rate (/min)

c) Systolic Blood pressure (SBP), Diastolic Blood pressure (DBP), Mean arterial

pressure (MAP)

d) Oxygen Saturation (SPO2)

e) Chest auscultation

f) Auscultation of heart sounds

g) VAS Score

I. Study Tools

 Written informed consent

 Proforma for data collection

 Patient Information Sheet

J. Data Collection and Interpretation

The study will be conducted in Nil Ratan Sirkar Medical College and Hospital,

Department of Anesthesiology and Critical Care.

After approval from institutional Ethics committee and obtaining written consent, data

will be collected from those patients undergoing elective general surgery of age 18 to 60

and belonging to ASA class I and II receiving these specific drugs. Then later will be

divided in two groups

Patients with body weight >80kg, cardiovascular disorder, broncho-pulmonary disorder,

renal, neurologic, gastrointestinal, and hepatic dysfunction, records of allergy, long-time

period use of medicinal drugs which includes beta-blocker and different anti-

hypertensives, antipsychotics, analgesics, alcohol, sedative, TCA, etc., Patients with

psychiatric illness, patient refusal will be excluded from this study.

Patients will be randomly assigned to one of the following groups:

 Group P (n = 104) will receive IV 1g Paracetamol infusion over 10min pre-

operatively

 Group D (n = 104) will receive IV Dexmedetomidine 1 μg/kg bolus over 10 min per-

operatively and 0.3 μg/kg/hr thereafter till the end of the surgery.

Within the pre-operative holding area, the patients found out and familiarized about 10

points visible analog scale (VAS)to assess their baseline pain with 0 = none to 10 =

maximum.
Without delay earlier than entering the operating room patients will be pre-medicated

with Midazolam 0.3mg/kg, Ondansetron 0.15mg/kg, and Glycopyrrolate 4 mcg/kg IV.

Intra-operative monitoring devices like pulse-oximetry, noninvasive blood pressure,

ECG, and capnography will be attached with patients accordingly.

After acquiring bottom-line measurement of the heart rate (HR), systolic blood pressure

(SBP) diastolic blood pressure (DBP), and mean arterial pressure (MAP), infusion of

Paracetamol 1g will be given over 10 min for group P and infusion Dexmedetomidine

will be given 1μg/kg (diluting in normal saline making a 50 ml solution) over 10 min and

0.3 μg/kg/hr thereafter for the end of the surgery.

After pre-oxygenation with 100% O2, Anesthetic induction will be done with injection of

Fentanyl 2.5 μg/kg IV, and injection of Etomidate 0.3 mg/kg IV followed by using an

injection Atracurium to facilitate tracheal intubation.

Anesthesia will be maintained with nitrous oxide (N2O) 50% and oxygen (O2) 50% the

mixture in combination with 0.5-1% Isoflurane, and injection Atracurium dose 0.5mg/kg

IV.

The end-tidal carbon dioxide will be maintained inside 35-40 mmHg. The HR, SBP,

DBP, and MAP were recorded intra-operatively at every 5 min interval from starting to

end of the surgery.

Hypotension (defined as MAP value <25% of the baseline value on 2 consecutive

readings within 2-3 min) not responding to a reduction in inspired Isoflurane

concentration and 200 ml fluid bolus will be treated with injection Mephenteramine 5 mg.

The infusion of study medication will be discontinued if the hypotension persisted >2 min

after those interventions. Upon return of the MAP ± 25% of the baseline values, we will

take a look at remedy infusion became resumed at 50% of the initial infusion rate.

Hypertension (defined as MAP value >25% of the baseline values on two consecutive

readings within 2-3 min) and or tachycardia (described as HR value >25% of the baseline

value on 2 consecutive readings within 2-3 min) inspired concentration of Isoflurane and

study medication will be increased.

Bradycardia (defined as HR <45/min) persisting for >2 min become treated with an

injection of Atropine.

(Postoperative pain and sedation score were recorded at 1st, 2nd, 4th, 6th hrs )

During the operation, patients will obtain similar quantities of IV crystalloid solutions. IM

Diclofenac 75mg will be given to both patients after 30 minutes of starting surgery.

The residual neuromuscular block will be reversed with Neostigmine 40 μg/kg and

Glycopyrrolate 5 μg/kg IV after the end of the operation.

Post-operatively injection Tramadol will be given as a rescue analgesic at a dose of 100

mg IV when VAS > 5.

6. Statistical Analysis Plan

After collection of all data those will be put into spreadsheet and check for

completeness. After the completion of spreadsheet statistical analysis will be done

using suitable statistical test (if any) and result will be presented using appropriate

charts and graphs etc.

7. ETHICAL CLEARANCE

 Ethical approval

The protocol will be submitted to the Institutional Ethics Committee (IEC) of Nil Ratan

Sircar Medical College and Hospital, Kolkata for approval.

 Informed consent

The purpose and method of the study will be explained to the participants and/ or his/her

guardian and an informed consent will be obtained.

 Confidentiality and Anonymity will be maintained. The participant and their

respective guardian/ legally authorized representative (LAR) will be assured of

confidentiality and anonymity of the data collected.

8. WORK PLAN

Whole 1.5 years study period will be divided into following stages-

a) Preparatory phase – 4 months,

b) Data collection phase – 8 months

c) Data compilation & analysis phase – 4 months,

d) Report writing & submission – 2 months

Gantt chart:
 Duration

Activities July, Aug, Sep, Oct, Nov, Dec, Jan, Feb, Mar, Apr, May, June, July, Aug, Sep, Oct, Nov, Dec,

2023 2023 2023 2023 2023 2023 2024 2024 2024 2024 2024 2024 2024 2024 2024 2024 2024 2024

Preparatory Phase

Data Collection

Data entry &

Analysis

Report Writing &

Submission

References

1. Swaika S, Parta N, Chattopadhyay S, Bisui B, Banarjee SS, Chattarjee S. A

comparative study of the efficacy of intravenous Paracetamol and Dexmedetomidine

on peri-operative hemodynamics and post-operative analgesia for patients undergoing

laparoscopic cholecystectomy. Anesthesia, Essays and Researches. 2013

Sep;7(3):331.

2. Taqui Fakhri DV, Kumari N, Singh R. Comparative Study of Intravenous

Paracetamol and Dexmedetomidine on Perioperative Hemodynamics and

Postoperative Pain Relief for Laparoscopic Cholecystectomy. Journal of

Pharmaceutical Negative Results. 2023 Jan 1;14(2):599-605.

3. Kamali A, Ashrafi TH, Rakei S, Noori G, Norouzi A. A comparative study on the

 prophylactic effects of paracetamol and dexmedetomidine for controlling

hemodynamics during surgery and postoperative pain in patients with laparoscopic

cholecystectomy. Medicine. 2018 Dec;97(51).

4. Sharma R, Gupta R, Choudhary R, Bajwa SJ. Postoperative analgesia with

intravenous paracetamol and dexmedetomidine in laparoscopic cholecystectomy

surgeries: a prospective randomized comparative study. International Journal of

Applied and Basic Medical Research. 2017 Oct;7(4):218.

5. Sarkar M, Desai P, Pawaskar S, Sarkar S. Comparative Study of Intravenous

Dexmedetomidine versus Paracetamol for Postoperative Pain Relief in Laparoscopic

Surgery. Indian Journal of Clinical Anaesthesia. 2016;3(1):44-7.

6. Goswami S J, Goel K, Patel D et al. A comparative study of the efficacy of the

efficacy of intravenous paracetamol and dexmedetomidine on perioperative

hemodynamics and post operative analgesia for patients undergoing laparoscopic

surgery. Indian Journal of Applied Research. 2023 Feb;13(2):4-7

7. Kumar S. A clinical study of post-operative analgesia with intravenous paracetamol

versus dexmedetomidine in patients undergoing laparoscopic cholecystectomy.

European Journal of Molecular & Clinical Medicine. 2022;9(2):1431-35

8. Srinithi A, Prasad TK, Krishnan R, Kumar SA. A comparison of intravenous

paracetamol and intravenous paracetamol with dexmedetomidine for postoperative

 analgesia management in gynecological surgeries–A prospective randomized double-

blinded study. Journal of Medical Society. 2022 Sep 1;36(3):118.

9. Bielka K, Kuchyn I, Babych V, Martycshenko K, Inozemtsev O. Dexmedetomidine

infusion as an analgesic adjuvant during laparoscopic сholecystectomy: a randomized

controlled study. BMC anesthesiology. 2018 Dec;18(1):1-6.

10. De Cassai A, Sella N, Geraldini F, Zarantonello F, Pettenuzzo T, Pasin L, Iuzzolino

M, Rossini N, Pesenti E, Zecchino G, Munari M. Preoperative dexmedetomidine and

intraoperative bradycardia in laparoscopic cholecystectomy: a meta-analysis with trial

sequential analysis. Korean Journal of Anesthesiology. 2022 Jan 12;75(3):245-54.

11. Chilkoti GT, Karthik G, Rautela R. Evaluation of postoperative analgesic efficacy and

perioperative hemodynamic changes with low dose intravenous dexmedetomidine

infusion in patients undergoing laparoscopic cholecystectomy–A randomised, double-

blinded, placebo-controlled trial. Journal of Anaesthesiology, Clinical Pharmacology.

2020 Jan;36(1):72.

12. Aouad MT, Zeeni C, Al Nawwar R, Siddik-Sayyid SM, Barakat HB, Elias S, Karam

VG. Dexmedetomidine for improved quality of emergence from general anesthesia: a

dose-finding study. Anesthesia & Analgesia. 2019 Dec 1;129(6):1504-11.

13. Aweke Z, Seyoum F, Shitemaw T, Doba DN. Comparison of preemptive paracetamol,

paracetamol-diclofenac & paracetamol-tramadol combination on postoperative pain

after elective abdominal surgery under general anesthesia, Ethiopia: a randomized

 control trial study, 2018. BMC anesthesiology. 2020 Dec;20(1):1-9.

14. Stagg K. Intravenous versus oral paracetamol for postoperative analgesia: a

systematic review. Journal of Perioperative Practice. 2021 Oct;31(10):373-8.

15. Kharbuja K, Sharma M, Sharma NR. Comparative evaluation of effectiveness of

intravenous paracetamol and intravenous diclofenac as post-operative analgesia in

laparoscopic cholecystectomy. Journal of Lumbini Medical College. 2018 Nov

3;6(2):73-8

16. Babar A, Sifatullah A, Haq IU, Khan MJ, Farid K, Islam R. Role of Intervenous

Paracetamol as Preemptive Analgesic for Laparoscopic Cholecystectomy. Pakistan

Journal of Medical & Health Sciences. 2023 Mar 10;17(01):681-.

APPENDIX 1

PARTICIPANTS INFORMATION SHEET

● Only a small amount (few milliliters) of blood sample will be collected from
the subjects participating in this study.
● There is no potential risk for the participation in this study.
● The participation is voluntary.
● There is no association of any influence in the treatment procedures whether
the subject participates in this or not.
● The subject may withdraw his participation from the study at any time
without giving any reason, without his / her medical care or legal rights being
affected.
● Any investigation relating to this study will be free of cost for the trail period
only.
● There will be no drug trial in this study.
● The study will not immediately affect the treatment of the subject but may
find out some correlation among some pre-operative parameters and the disease
which may in future serve in better understanding and treatment of the diseases
for the benefit of medical science and society.
Signature of the witness _________________________

Date ________________________________________

Appendix 2

INFORMED CONSENT FORM

NAME OF THE STUDY: “A Comparative Study to Assess Response of Intravenous
Paracetamol and Dexmedetomidine on Perioperative Hemodynamics and Postoperative
Pain in Patients Undergoing Elective General Surgery”

I, ____________________, S/D/o, ____________________, Age, ____________________,

residing at _________________________________________________________________,
do hereby declare that I am voluntarily giving my consent to participate in the above
mentioned study.
I have been explained in my own language, in vivid details, to my full satisfaction about the
procedure involved in the study along with my right to refuse to participate in the study at
any time during the course of the study. However, my refusal is not going to affect my right
to receive the treatment of the illness from the admitting department. I confirm that I have
been made aware of the potential risks involved, which are manageable. I am aware that I
will not receiving any financial benefits in exchange of my participation in the study.
I do hereby declare that I will provide medical history of the disease, undergo clinical
examination, allow any procedure to be performed, and come for follow up if / when
required. I consent to the collection, analysis and publication of my data generated during the
study, provided my identity is kept confidential at all times.
I have been also informed to contact Dr. Arunanshu Pal, Department of Anaesthesiology,
Nil Ratan Sircar Medical College and Hospital, Kolkata (Ph. no.- 7908206132), in case
of any emergency arising during the course of the study.
Name of the participant / guardian (in case of minor) ________________________________

Signature of the participant / guardian (in case of minor) _____________________________

OR

Left thumb impression of the participant:

Date: Place: Kolkata

Name of the witness __________________________________________________________

रोगीसहमतिफॉर्म

अध्ययनकानाम: “A Comparative Study to Assess Response of Intravenous Paracetamol and

Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain in Patients
Undergoing Elective General Surgery”

नाम(श्री/ श्रीमती/कु मार/ कु मारी) _________________________, आयु __________________, पता

_______________________________________________________________________,
मैं घोषणा कर रहा हूँ कि मैं स्वेच्छा से उपर्युक्त अध्ययन में भाग लेने के लिए अपनी सहमति दे रहा हूँ। मुझे अध्ययन में शामिल प्रक्रिया के बारे में
मेरा पूरा संतुष्टि के लिए अपनी भाषा में, विशद विवरण में समझाया गया है। मुझे अध्ययन के पाठ्यक्रम के दौरान किसी भी समय अध्ययन में भाग
लेने के लिए मना करने का अधिकार है। लेकिन मेरे इनकार के कारण बीमारी के उपचार प्राप्त करने के अपने अधिकार को प्रभावित नहीं किया
जाएगा।

मैं पुष्टि करता हुन के मुझे अध्ययन से जुड़े सभी प्रक्रिया और संभभीत खतरों के बारे में संपूर्ण तरीके से अपनी भाषा में विश्लेषण दिया गया है।
और यह आश्वाशन दिया गया है के मुझे किसी भी तरीके से हानि होगा या पौछाया जायेगा।अध्ययन में भाग लेने के लिए मुझे कोई भी आर्थिक
सहायता नहीं मिलेगा।

मैं अपनी बीमारी की पूरी जानकारी दूंगा, कोई भी शारीरिक परीक्षा और अध्ययन से सम्बंधित कोई भी कार्य अपने ऊपर करने की अनुमति देता
हूँ। मैं अध्ययन से जुड़े सबही जानकारी का संग्रह, विश्लेषण या किसी भी प्रकार के पत्रिका में प्रकाशनकी अनुमति देता हूँ यह शर्त पर के मेरा
परिचय गुप्त रखा जायेगा।

अध्ययन के पाठ्यक्रम के दौरान कोई भी समस्या होने से मुझे अधिकार हैं के मैं Dr. Arunanshu Pal, Department of
Anaesthesiology, Nil Ratan Sircar Medical College and Hospital, Kolkata (Ph. no.-
7908206132), से संपर्क करूँ ।

प्रतिभागी/ अभिभावक का नाम ___________________________________________________

प्रतिभागी / अभिभावक का हस्ताक्षर ________________________________________________

या

बॉय अंघूटे का चिन्ह

दिनांक: जगह: कोल्कता

गवाह का नाम ________________________________________________________________

गवाह का हस्ताक्षर _____________________________________________________________

या

बॉय अंघूटे का चिन्ह

दिनांक: जगह: कोल्कता

अन्यवेशक का नाम____________________________________________________________

अन्यवेशक का हस्ताक्षर _________________________________________________________

दिनांक: जगह: कोल्कता

রুগীসম্মতিফর্ম

অধ্যায়ন এর নাম: “A Comparative Study to Assess Response of Intravenous

Paracetamol and Dexmedetomidine on Perioperative Hemodynamics and
Postoperative Pain in Patients Undergoing Elective General Surgery

নাম(শ্রী / শ্রীমতি / কু মার/কু মারী) _________________________, বয়স _______________,ঠিকানা

____________________________________________________________________,
আমি সজ্ঞানে এই অধ্যায়ন এ অংশগ্রহণ করার সম্মতি জানাইছি। আমাকে অধ্যায়ন সম্পর্কি ত সব তথ্য
সম্পূর্ণ ভাবে নিজের ভাষাতে আমার সন্তুষ্টি করিয়ে বোঝানো হয়েছে। আমার যে কোনো মুহূর্তে এই অধ্যায়ন
থেকে অংশ গ্রহণ প্রত্যাহার করার অধিকার আছে। আমার অসম্মতির জন্যে আমার রোগ এর চিকিৎসায়
কোনো ত্রুটি হবে না। অধ্যায়ন সম্বন্ধিত সব পার্শ্ব প্রতিক্রিয়া আর ঝুঁকি আমায় জানানো হয়েছে এবং আমায়
আশ্বস্থ করা হয়েছে যে এর ফলে আমার কোনো ক্ষতি হবে না। এই অধ্যায়ন এ অংশগ্রহণ এর বিনিময় আমায়
কোনো প্রকারের আর্থিক সাহায্য দেয়া হবে না।

আমি প্রতিশ্রুতি দিচ্ছি যে আমি পূর্ণ সহযোগিতা করবো, নিজের রোগ সম্বন্ধিত সব তথ্য জানাবো এবং
প্রয়োজনে ফল্লওয়াপ এ আসবো। কোনো প্রকারের স্বাস্থ পরীক্ষা বা চিকিৎসা পদ্ধতি করার অনুমতি আমার
রয়েছে। অধ্যায়ন এর তথ্য সংগ্রহে, বিশ্লেষণ, বা প্রকাশন এ আমার সম্মতি আছে এই শর্তে যে আমার পরিচয়
গোপন রাখা হবে।

অধ্যায়ন চলাকালীন যে কোনো প্রকার সমস্যা হলে আমার অধিকার থাকবে যে আমি Dr. Arunanshu Pal,
Department of Anaesthesiology, Nil Ratan Sircar Medical College and Hospital, Kolkata
(Ph. no.- 7908206132), কে যোগাযোগ করবো।
অংশগ্রাহীর নাম / অভিভাবক এর নাম ___________________________________________

অংশগ্রহের সই / অভিভাবকের সই ______________________________________________

বা

বাম আঙ্গুল এর ছাপ

তারিখ: স্থান : কলকাতা

সাক্ষী এর নাম _______________________________________________________________

সাক্ষী এর সই _______________________________________________________________

বা

বাম আঙ্গুল এর ছাপ

তারিখ: স্থান : কলকাতা

অন্বেষীর নাম _______________________________________________________________

অন্বেষীর সই ________________________________________________________________

তারিখ: স্থান : কলকাতা

Appendix 3

CASE RECORD FORM

CASE NO:

Pre-Anaesthetic Checkup: -

1. Name
2. Age
3. Sex
4. Religion
5. Occupation
6. Address
7. Unit
8. Registration no
9. Date of admission
10. Chief complaint
11. Mode of injury
12. Time of injury
13. Place of injury
14. Past history
15. Drug history
16. History of allergy

General Survey
 1. Pallor
2. Cyanosis
3. Jaundice
4. Edema
5. Clubbing
6. Weight
7. Pulse
8. Blood pressure
9. Respiratory rate
10. SpO2 at room air
11. Temperature
12.ASA status

Local Examination

Mouth opening Mallampati grading

Neck Movement Any injury or infection at local site

Systemic Examination

Cardiovascular system
Respiratory system
Neurological system

Routine Investigations

1. Haemoglobin
2. TC, DC
3. Platelet count
4. Fasting blood sugar, post prandial blood sugar
5. Serum creatinine
6. Serum urea
7. Sodium
8. Potassium
9. Chest X-ray
10.ECG

Operating Room
Preoperative vitals:
1) Blood pressure
2) SpO2
3) Heart rate
4) VAS scale score

Premedication

Preoxygenation

Induction

Maintenance
Intra Operative Vitals

Heart
Parameters rate
SBP DBP MAP SPO2 RR

Baseline
Before
Induction
1 minute after
intubation

3 minutes after
intubation

5 minutes after
intubation
10 minutes
after
intubation
30 minutes
after
intubation
45 minutes
after
intubation
60 minutes
after
intubation
90 minutes
after
intubation
120 minutes
after
intubation

Reversal

Post operative Vitals

Hours 1st hour 2nd hour 4th hour 6th hour

Pulse
SBP
DBP
MAP
SpO2
RR
VAS
score

VAS Score

15-minute 1 hour post 2 hours post 4 hours post 6 hours

post operative operative operative post
extubation operative

Rescue analgesia

Time Drug Given

Adverse effects

Hyperventilation
Hematoma at injection site
Bradycardia

CURRICULUM VITAE

Name of the investigator: - Dr. Arunanshu Pal

Education qualification: - M.B.B.S. (WBUHS)

Date of birth: - 08/10/1993

Address: -
Town – English Bazar
PO – Mokdumpur
PS – Mokdumpur
Dist – Malda
PIN –732103

Contact no: - 7908206132

Present designation: - Post Graduate Trainee (Anaesthesiology)

Present training institute: -Nilratan Sircar Medical College and Hospital

138, A.J.C. Bose Road, Kolkata – 700014

Brief Academic History: - Completed MBBS from Malda Medical College &
Hospital, Malda in 2018, joined as M.D. PGT (Anaesthesiology) at Nilratan Sircar
Medical College and Hospital in 2022.
 STATEMENT OF EXPENDITURE AND FINANCIAL
DISCLOSURE

This is to inform that research proposal for the study purpose entitled “A Comparative
Study to Assess Response of Intravenous Paracetamol and
Dexmedetomidine on Perioperative Hemodynamics and Postoperative Pain
in Patients Undergoing Elective General Surgery ” will not need any financial
support from any foundations, pharmaceutical or any other private companies except hospital
supply of medicines. Expenses of materials which are not supplied by the hospital will be
borne by the undersigned.
 Dr Arunanshu Pal
Principal Investigator of the research proposal
M.D. Anaesthesiology PGT
Nilratan Sircar Medical College and Hospital
Session 2022-25

UNDERTAKING BY P.G. RESIDENTS

1. I have reviewed the clinical protocol and agree that it contains all the necessary
information to conduct the study. I will not begin the study until all necessary ethics
committee and regulatory approvals have been obtained.
2. I agree to conduct the study in accordance with the current protocol. I will not
implement my deviation form or changes of the protocol without prior review and
documented approval from the ethics committee of the amendment, except where
necessary to eliminate an immediate hazard to the trial subjects or when the change
involved are only logistical or administrative in nature.
3. I agree to personally conduct and supervise the clinical study at my site.
4. I agree to inform all subjects that drugs are being used for investigational purposes
and I will ensure that the requirements relating to obtaining informed consent and ethics
committee review and approval specified in GCP guidelines are met.
5. I agree to report to the institutional ethics committee all adverse experiences that
occupies the course of the study in accordance with the regulatory and GCP
guidelines.
6. I have read and understood the information in the investigator’s brochure, including
the potential risks and side effects of the drug.
7. I agree to ensure that all associates, colleagues and employees assisting in the
conduct of the study are suitably qualified and experienced and they have been
informed about their obligations in meeting their commitments in the study.
8. I agree to maintain adequate and accurate records and to make those records
available for audit by the ethics committee.
9. I agree to promptly report to the ethics committee all changes in the activities and
all unanticipated problems involving risks to human subjects or other.
10. I agree to inform all unexpected serious adverse events to the ethics committee
withing seven days.
11. I will maintain confidentiality of the identification of all participating study patients
and assure security and confidentiality of study data.
12. I agree to comply with all other requirements, guidelines and statutory obligations as
applicable to clinical investigators participating in clinical study.
Sign of the Investigator