Comparison of Dexmedetomidine and Dexamethasone for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Controlled Trial
Phase: PHASE3
Conditions: Postoperative Nausea and Vomiting
Sponsor: Patel Hospital, Pakistan

15-Feb-26 
COVER LETTER 
To 
Protocol Registration and Results System (PRS) Team 
ClinicalTrials.gov 
U.S. National Library of Medicine 
Subject: Clinical Trial Registration Submission 
Dear Sir/Madam, 
I am submitting our study titled “Comparison of Dexmedetomidine and Dexamethasone for the 
Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic 
Cholecystectomy: A Randomized Controlled Trial” for registration on ClinicalTrials.gov. 
This is a prospective, double-blind, randomized controlled trial to be conducted at Patel Hospital, 
Karachi, Pakistan. The study aims to compare the effectiveness of intravenous dexmedetomidine and 
dexamethasone in preventing postoperative nausea and vomiting in adult patients undergoing elective 
laparoscopic cholecystectomy.  
The protocol follows Good Clinical Practice guidelines. Ethical approval will be obtained from the 
Ethical Review Committee of Patel Hospital and CPSP. Written informed consent will be obtained from 
all participants. 
We kindly request registration of this trial and assignment of a ClinicalTrials.gov Identifier. Please let us 
know if further information is required. 
Sincerely, 
Dr. Marium Rafiq 
Principal Investigator 
Patel Hospital, Karachi, Pakistan 
 
 

15-Feb-26 
TITLE: 
COMPARISON OF DEXMEDETOMIDINE AND DEXAMETHASONE FOR THE 
PREVENTION 
OF 
POSTOPERATIVE 
NAUSEA 
AND 
VOMITING 
IN 
PATIENTS UNDERGOING LAPAROSCOPIC CHOLECYSTECTOMY;  
A RANDOMIZED CONTROLLED TRIAL 
INTRODUCTION: 
Currently, laparoscopic cholecystectomy (LC) is the gold standard for treating gallstones. It provides 
faster recovery, less pain postoperatively, shorter hospital stays, and a lower morbidity rate and suffering 
following surgery [1]. However, postoperative nausea and vomiting (PONV) is one of the most 
distressing symptoms that are commonly observed after laparoscopic cholecystectomy under general 
anesthesia [2]. PONV incidence ranges from 12-38% and sometimes as high as 70% in patients who 
underwent laparoscopic cholecystectomy but did not receive prophylactic antiemetic therapy. Most 
PONV cases are reported during the first 24 hours after laparoscopic cholecystectomy [3,4].  The most 
predictive factors for a higher risk of postoperative nausea and vomiting include age (less than 50 years), 
female gender, history of motion sickness and/or PONV, the use of opioids, exposure to volatile 
anesthetics, long duration surgeries, prolonged anesthesia, carbon dioxide retention, and the type of 
surgical procedure. Surgical techniques that manipulate the stomach and GI tract by creating 
pneumoperitoneum or the Trendelenburg position cause raise in intraabdominal pressure leading to an 
increased risk of postoperative nausea and vomiting (PONV) such as laparoscopic surgeries [5]. 
For the prevention and treatment of PONV, a number of pharmacological agents have been used. 
Dexmedetomidine is a potent and highly selective α2-adrenoceptor agonist, exhibits sedative, hypnotic, 
analgesic, sympatholytic and antiemetic properties [6,7]. Dexamethasone is an economical 
corticosteroid drug with excellent anti-inflammatory and antiemetic properties with negligible side 
effects [8,9]. Different studies reported the antiemetic effects of dexmedetomidine and dexamethasone 
for prevention of PONV after laparoscopic cholecystectomy. A study by Singh M, et al. reported the 
significantly low PONV score in the dexmedetomidine group as compared to dexamethasone group 
(2.9±1.6 Vs. 4.0±1.6) [3]. A study by Khadka B, et al. reported the 23.25% and 27.9% PONV in the 
dexmedetomidine and dexamethasone group respectively [10]. Another study by Bakri MH, reported the 
21.0% and 28.0% PONV in the dexmedetomidine and dexamethasone group respectively [11]. 
Despite continuing advancement in anesthetic and surgical techniques, both the incidence and severity 
of postoperative nausea and vomiting is continuously increasing after laparoscopic procedures [12]. 

Therefore, different drugs have been used and compared for better outcomes. However, no gold standard 
has been established yet. Recently, the effect of dexmedetomidine on PONV has been the focus of 
clinical researchers. Nevertheless, controversy about the effectiveness of dexmedetomidine as compared 
to dexamethasone for PONV is still ongoing, for different results reported in associated literature. No 
such research work has been done in Pakistan. Therefore, to fill this gap, this study has been 
designed to determine the relative effectiveness of dexmedetomidine and dexamethasone in preventing 
postoperative nausea and vomiting following laparoscopic cholecystectomy in our population. 
OBJECTIVES: 
❑ To compare the postoperative nausea and vomiting score between patients receiving 
dexmedetomidine and dexamethasone after laparoscopic cholecystectomy. 
 
OPERATIONAL DEFINITION: 
▪ Nausea is a subjective unpleasant sensation with awareness of urge to vomit. 
▪ Vomiting is a spasmodic contraction of abdominal wall & diaphragm muscles with forceful 
expulsion of gastric contents. 
 
▪ 
POSTOPERATIVE NAUSEA AND VOMITING (PONV): 
            It will be assessed by using Postoperative nausea and vomiting (PONV) scaling score: 
 
PONV score 
Patient response 
0 
Without PONV 
1 
Nausea without vomiting 
2 
Nausea with vomiting (<3 times/day) 
3 
Vomiting ≥ 3 times/day 
 
ASSOCIATED FACTORS: will be assess in terms of following:  
▪ Diabetes Mellitus: documented history of diabetes and on treatment 
▪ Hypertension: documented history of hypertension and on treatment 
▪ Smoking status:  
✓ Smoker: individual having smoked 100 or more cigarettes in life and smoked in last 
month too will be taken as smoker 

✓ Ex-smoker: individual having smoked 100 or more cigarettes in life and not smoked in 
last month will be taken as Ex-smoker 
HYPOTHESIS: 
▪ There is difference in postoperative nausea and vomiting scores between patients receiving 
dexmedetomidine and dexamethasone after laparoscopic cholecystectomy. 
MATERIAL AND METHODS: 
STUDY DESIGN: Double blind randomized controlled trial  
STUDY SETTING: The study will be conducted in the operating room, post anesthesia care unit 
(PACU) and in the wards at Patel Hospital, Karachi. 
DURATION OF STUDY: Minimum six months after approval of synopsis by the Ethical Review 
Committee, Patel Hospital and College of Physicians and Surgeons Pakistan (CPSP). 
SAMPLE SIZE: The sample size calculation was done using the Open EPI software for “Sample size 
For Comparing Two Means” by using findings of Singh M, et al. who reported the significantly low 
PONV score in the dexmedetomidine group as compared to dexamethasone group (2.9±1.6 Vs. 4.0±1.6) 
[3], by taking confidential interval 95% and power 80%, the sample size stands to be n=68 (34 in each 
group). 
▪ Group A (Dexmedetomidine Group): 34 patients 
▪ Group B (Dexamethasone Group): 34 patients 
SAMPLING TECHNIQUE: Non-Probability Consecutive Sampling. 
SAMPLE SELECTION: 
➢ INCLUSION CRITERIA: 
❑ Both male and female patients will be included 
❑ Patient between the age of 18 to 60 years. 
❑ Patient undergoing elective Laparoscopic Cholecystectomy. 
❑ Patients with American Society of Anesthesiologists (ASA) physical status I and II. 
 
 

 
➢ EXCLUSION CRITERIA: 
❑ Patient not willing to participate in study.  
❑ Patients with a history of allergy to dexmedetomidine and dexamethasone.  
❑ Patients having motion sickness and history of PONV in past anesthesia experience.    
❑ Patients receiving antiemetic drugs during the last 48 hours before laparoscopic cholecystectomy.  
❑ Patients with body mass index ≥ 30 kg/m2  
❑ Patients with emergency laparoscopic cholecystectomy.  
❑ Laparoscopic cholecystectomy lasts for more than one hour.  
❑ Laparoscopic cholecystectomy converting to open cholecystectomy. 
DATA COLLECTION PROCEDURE:  
This study will be performed after the permission of Research evaluation unit (REU) of College of 
Physicians and Surgeons Pakistan (CPSP) and written informed consent for the study will be obtained 
from the patient one day before the procedure. Trial registration number will be obtained after the 
approval of synopsis.  
Patients admitted at Patel Hospital, Karachi for elective Laparoscopic cholecystectomy and who fulfill 
the inclusion criteria will be included in the study. Before inclusion the purpose, procedure, risks and 
benefits of the study will be explained. Confidentiality will be ensured. Demographic details of each 
patient including name, gender, age, smoking status, history of comorbid conditions like diabetes 
mellitus and hypertension (confirmed on medical records) will be obtained. Weight will be measured on 
a digital scale in kg without shoes and in hospital gown. Height of each patient will be measured by 
using stadiometer, in meters without shoes and cap. BMI of each patient will be calculated by using 
BMI formula (BMI=weight in kg/height in meter2).  
Patients will be allocated into two groups by computer generated randomization table with two-armed 
blocks of four. 
The group allocation will be concealed in sealed opaque envelopes that will only be opened by the 
respective anesthesia resident who will be preparing and administering the drug just before the 
procedure.  
Group A patients will receive an intravenous (IV) single dose of 1 μg/kg of dexmedetomidine, and 
Group B patients will receive an IV single dose of 8 mg dexamethasone after induction of anesthesia. 
During the procedure, patients and the data collector will be blinded to group allocation. The study drugs 

will be prepared and administered to the patients by the anesthesia resident. The anesthetist providing 
the respective study drugs will not take part in collecting data postoperatively nor in the data analysis.  
Anesthesia management will be the same for both groups using standard protocols. LC will be 
performed according to standard protocol.  
On arrival in operation theatre, standard monitoring will be applied to the patient including pulse 
oximeter, noninvasive blood pressure, and capnograph. After denitrogenation with 100% oxygen for 3 
minutes, anesthesia will be induced with IV nalbuphine 0.1mg/kg and propofol 2mg/kg, followed by IV 
atracurium 0.5 mg/kg to facilitate endotracheal intubation. Patients will be ventilated with a tidal volume 
(VT) of 6–8 ml/kg, respiratory rate (RR) of 10–12 breaths/min, and inspiratory to expiratory ratio of 1:2. 
Ventilatory parameters (VT, RR) will be adjusted to maintain ETCO2 tension between 35-45 mm of Hg. 
Anesthesia will be maintained with a fraction of inspired oxygen (FIO2) of 0.6 using a mixture of 
oxygen and air with volume-controlled ventilation and isoflurane (MAC of 1.0). Atracurium will be 
given intermittently to maintain neuromuscular blockade. During anesthesia, all patients will receive 1 g 
IV paracetamol and IV lactated Ringer’s solution at a rate of 10 ml/kg. They will be maintained at 2 
ml/kg/h during recovery until they are able to tolerate oral fluids. 
All patients will be positioned in a standard reverse Trendelenburg position (rT) during surgery with 
head up 30⁰ and left lateral tilt 15⁰. Pneumoperitoneum will be established with carbon dioxide, and the 
intra-abdominal pressure will be maintained around 12 mmHg.   
Upon completion of surgery, neostigmine and glycopyrrolate (2.5/0.5mg) will be given slowly IV to 
restart spontaneous breathing, which will be followed by tracheal extubation. Patients will be sent to the 
recovery room and later to their respective wards. 
Postoperatively, the score of PONV will be evaluated using the PONV scaling score by the anesthesia 
resident blinded to both the intervention and control group at the following intervals: on arrival in the 
PACU (T0), at 4 h (T1), at 12 h (T2) and finally at 24 h (T3) postoperatively. 
The rescue antiemetic drug (ondansetron 8mg) IV will be received by the patients reporting a high 
PONV score (2-3). All results will be collected and filled in proforma accordingly by the anesthesia 
resident. 

DATA ANALYSIS PROCEDURE: 
After collection of data the analyses will be conducted by using Statistical Package for Social Science 
(SPSS) software, Version 25. 
To check the normality of quantitative data Shapiro Wilk test will be applied. Mean and standard 
deviation (SD) or median and interquartile range (IQR) as appropriate will be calculated for quantitative 
variables like age (years), weight (kg), height (m) and BMI (kg/m2).  
For qualitative variables like gender, ASA status, history of diabetes and hypertension frequency and 
percentages will be computed.  For comparison of PONV score between groups independent T-test or 
Mann Whitney U test will be applied. Effect modifiers like age, gender, ASA status, History of 
hypertension, diabetes and BMI will be stratified to observe the effect of these on outcome. Post 
stratification independent T-test or Mann Whitney U test will be applied and p-value ≤0.05 will be 
considered significant. 
 
 
 

REFERENCES: 
1. Amreek FN, Hussain SZ, Mnagi MH, Rizwan A. Retrospective analysis of complications 
associated with laparoscopic cholecystectomy for symptomatic gallstones. Cureus. 2019 Jul 
16;11(7):e5152. 
2. Reddy GS, Manjusruthi B, Jyothsna G. Postoperative nausea and vomiting prophylaxis: a 
comparative study of ramosetron and palonosetron in patients Undergoing Laparoscopic 
Cholecystectomy - A Prospective Randomized Trial. Anesth Essays Res. 2019 Jan-
Mar;13(1):68-72. 
3. Singh M, Tiwari AB, Taank P, Singh S, Kaur A, Sood M, et al. Comparative study on effects of 
dexmedetomidine and dexamethasone on the incidence of postoperative nausea and vomiting in 
patients undergoing laparoscopic surgery. J Acute Dis. 2022 Apr 1;11(2):59-64. 
4. Sinha V, Vivekanand D, Singh S. Prevalence and risk factors of post-operative nausea and 
vomiting in a tertiary-care hospital: a cross-sectional observational study. Med J Armed Forces 
India. 2022 Sep;78(Suppl 1):S158-62. 
5. Stoops S, Kovac A. New insights into the pathophysiology and risk factors for PONV. Best 
Practice & Research Clinical Anaesthesiology. 2020 Dec 1;34(4):667-79.   
6. Jin S, Liang DD, Chen C, Zhang M, Wang J. Dexmedetomidine prevent postoperative nausea 
and vomiting on patients during general anesthesia: a PRISMA-compliant meta-analysis of 
randomized controlled trials. Medicine. 2017 Jan;96(1):e5770. 
7. Masoori TA, Gupta K, Agarwal S, Bansal M, Zuberi A, Samad A. Clinical efficacy of 
dexmedetomidine in two different doses to attenuate the hemodynamic changes during 
laparoscopic cholecystectomy. Int J Res Med Sci. 2018 Mar;6:959-65. 
8. Jamil K, Qaisar R. The effect of dexamethasone on postoperative pain in patients after 
laparoscopic cholecystectomy. Cureus. 2022 Nov 30;14(11):e32067. 
9. Gul G, Bilgic T, Aydin MA. Evaluation of the effects of preoperative dexamethasone 
administration on postoperative patient comfort in laparoscopic cholecystectomy. Cureus. 2020 
May 5;12(5):7968. 
10. Khadka B, Sharma NR. A Prospective comparative study of dexmedetomidine and 
dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic 
cholecystectomy. J Soc anesthesiol Nepal. 2021 Jul 5;8(1):e307. 
11. Bakri MH, Ismail EA, Ibrahim A. Comparison of dexmedetomidine and dexamethasone for 
prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Korean J 
Anesthesiol. 2015 Jun;68(3):254-60. 
12. Bajaj V, Singh S, Sharma R, Taank P, Dwivedi D. Effect of palonosetron monotherapy versus 
palonosetron with dexamethasone combination therapy for prevention of post operative nausea 
vomiting in children undergoing strabismus surgery. Int J Biomed Res. 2019 Feb 
14;10(2):e5080.   
 
 

PROFORMA 
MR No: _____________                              
GROUP: 
     ☐ Group A (Dexmedetomidine Group)           
     ☐ Group B (Dexamethasone Group) 
PATIENT DETAILS: 
▪ Name: ____________________ 
▪ Gender:      ☐   Male     ☐ Female 
▪ Age (Years): ________ 
▪ Height (m): _________ 
▪ Weight (kg): ________ 
▪ BMI (kg/m2): _______ 
▪ Smoking:         
 
☐ Yes    ☐ No 
▪ ASA Status:     
 
☐ I   ☐ II 
▪ H/O diabetes Mellitus:  ☐ Yes    ☐ No  
▪ H/O Hypertension:  
☐ Yes    ☐ No  
▪ Postoperative nausea and vomiting (PONV) scaling score:      
PONV score 
Patient response 
0 
Without PONV 
1 
Nausea without vomiting 
2 
Nausea with vomiting (<3 times/day) 
3 
Vomiting ≥ 3 times/day 
 

 
• on arrival in the PACU (T0) PONV score: ________ 
• at 4 h (T1) postoperatively PONV score: _________ 
• at 12 h (T2) postoperatively PONV score: ________ 
• at 24 h (T3) postoperatively PONV score: ________