Comparison of Dexmedetomidine Versus Ketofol For Moderate Sedation In Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Controlled Trial
Phase: PHASE4
Conditions: Sedation
Sponsor: Sindh Institute of Urology and Transplantation

Dated: 12th February 2023 
 
COMPARISON OF DEXMEDETOMIDINE VERSUS KETOFOL FOR 
MODERATE SEDATION IN ENDOSCOPIC RETROGRADE 
CHOLANGIOPANCREATOGRAPHY (ERCP): A RANDOMIZED 
CONTROLLED TRIAL 
 
 
 
 
This document is the property of Sindh Institute of Urology & Transplantation (SIUT) and contains 
confidential information. Any unauthorized use, reproduction, or distribution of this document is 
strictly prohibited.  
 
The protocol is approved by the ethical review committee of SIUT (CRP #: 234). 
 
 
 
 

COMPARISON OF DEXMEDETOMIDINE VERSUS KETOFOL FOR 
MODERATE SEDATION IN ENDOSCOPIC RETROGRADE 
CHOLANGIOPANCREATOGRAPHY (ERCP): A RANDOMIZED 
CONTROLLED TRIAL 
Introduction  
The utilization of endoscopic retrograde cholangiopancreatography (ERCP) for both diagnosis and 
treatment of pancreaticobiliary diseases has witnessed a significant surge in recent times.1,2 
Conscious sedation is routinely administered during ERCP procedures to enhance patient comfort 
and facilitate gastroenterologist interventions.3,4 However, it is essential to acknowledge that 
sedation in ERCP carries the potential for adverse intraoperative events.5,6 Various 
pharmacological agents, including midazolam, propofol, ketamine, and dexmedetomidine, are 
available, offering rapid induction and smooth recovery.3-8  
Dexmedetomidine, a relatively recent addition to the pharmacological arsenal, has gained 
prominence as an alternative sedative in conscious sedation. It acts as a potent and highly selective 
α-2 adrenergic receptor agonist, demonstrating sympatholytic, sedative, amnestic, and analgesic 
properties.9 Dexmedetomidine stands out for its unique ability to provide conscious sedation and 
analgesia without inducing respiratory depression. However, it is crucial to note the potential side 
effects, such as bradycardia and hypotension.10  
Ketamine, characterized as an N-methyl D-aspartate receptor antagonist, offers sedative, 
analgesic, and amnestic effects without causing respiratory depression. On the other hand, 
propofol, a sedative-hypnotic agent, boasts a rapid onset and fast recovery time.6  
The ERCP procedure, vital for diagnosing and managing biliary and pancreatic disorders, has 
become increasingly prevalent. Recognized as a complex, protracted, and uncomfortable 
procedure, ERCP necessitates adequate sedation and analgesia to mitigate agitation and 
discomfort, which have been identified as potential factors contributing to ERCP failure. Despite 
the escalating demand for ERCP, there remains a dearth of local and international studies 
comparing the efficacy of these two pharmacological agents in patients undergoing ERCP, leading 
to clinical equipoise. Sedation in gastrointestinal endoscopy not only alleviates patient discomfort 
but also enhances operator performance. This study aims to address this gap by providing current, 
locally relevant statistics, offering insights into the comparative effectiveness of dexmedetomidine 
and ketamine-propofol combination during ERCP procedures. The outcomes of this study could 
contribute to the refinement of management protocols, optimizing the balance between patient 
comfort and procedural success.  
 
 

Methodology  
Study design: 
Randomized controlled trial. 
Study setting: 
Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan. 
Study duration: 
December 2021 to June 2022 
Sample selection 
Inclusion criteria 
• Aged 20-60 years  
• Any gender  
• Scheduled for elective ERCP  
• American Society of Anesthesiologists (ASA) classification I or II 
Exclusion criteria 
• Allergic to dexmedetomidine, Ketofol, or related medications 
• BMI over 36 kg/m2 (morbidly obese) 
• History of stroke, renal impairment, chronic obstructive pulmonary disease, asthma, 
chronic liver disease, hypothyroidism, and congestive cardiac failure 
• Pregnant, or breastfeeding women  
• Patients who reported chronic use of sedative medications or substance abuse 
• Known contraindications to ERCP  
• Already enrolled in another clinical trial study 
Sample size 
The sample size for the study will be 62, i.e., 31 in each group. The sample size will be 
calculated by using the Open Epi software where alpha will be taken as 5%, power of the test 1-
beta 90, mean time to good recovery as 11.4±0.5 versus 12.5±1.8 [10]. 
Data collection procedure 
A brief history of demographic data will be taken from each patient. Preoperative assessment 
included history, general physical examination, systemic examination, and routine laboratory 
investigations.   
Patients will be randomly divided into two groups using computer randomization. All patients will 
be taken to the procedure room and venous access will be secured on a non-dominant hand by 20G 
IV cannula, intravenous (I/V) fluid (ringer lactate or normal saline) will be started by 8 ml/kg/h, 

and oxygen support will be provided by nasal cannula at 4 liters per minute. Standard monitors 
will be attached for heart rate (HR), noninvasive blood pressure (systolic and diastolic), mean 
arterial blood pressure (MAP), and peripheral oxygen saturation SpO2. Injection midazolam 0.05 
mg/kg will be also given I/V to every patient in both groups to decrease the anxiety of patients.   
Patients received either Dexmedetomidine or Ketofol for sedation. All syringes and infusion sets 
will be covered by silver paper and these infusions will be labeled as infusion 1 or 2. In patients 
who receive Dexmedetomidine, a 2ml ampule of 100 ug/ml will be diluted in 18 ml of normal 
saline, making a total volume of 20 ml. Patients received dexmedetomidine as a bolus over 10 
minutes in a dose of 1ug/kg followed by an infusion at the rate of 0.5ug/kg/hr and it will be labeled 
as “infusion 1”. In the Ketofol group, 2 ml ketamine (50mg/ml) and 10 ml of propofol 1% 
(10mg/ml) will be diluted in 8ml of normal saline. This mixture will be 20 ml each, making 5mg/ml 
of ketamine and propofol. Patients will receive 1mg/kg over 10 minutes followed by 50ug/kg/min 
of infusion, labeled as “infusion 2”. 
During infusion, vitals were recorded at 0,1,3,5, and 10-minute intervals from the start, and the 
Ramsay Sedation scale score (RSS) was recorded every 1 minute. Both infusions were started as 
per the randomization of groups. The mean difference in time to achieve adequate sedation and 
time to good recovery were noted as outcomes in each group. In addition, complications during 
the procedure and recovery were also noted. Adequate sedation was defined as the time from 
initiation of infusion to achieve an RSS score of 4. While Modified Aldrete’s score (MAS) was 
used to assess the recovery. Time from discontinuation of the infusion to achieve an MAS score of 
9 was labeled as a good recovery. 
Statistical analysis 
Statistical Package for Social Sciences (SPSS) version 26 will be used for the purpose of statistical 
analysis. Mean ±Standard Deviation (SD) will be computed for quantitative variables such as age, 
time to achieve RSS, and time to achieve MAS. Frequency and percentages will be calculated for 
gender, ASA status, diabetes, hypertension, smoking, cough during procedure, gagging during 
procedure, apnea during procedure, apnea during recovery, and post-operative nausea and 
vomiting. Comparison will be done to see the association of baseline characteristics, complications 
during procedure, and complications during recovery on the outcome. Chi-Square test will be 
applied. Moreover, the mean difference of time to achieve RSS and time to achieve MAS will be 
explored using independent t-test. The p-value of ≤0.05 will be considered as significant.  
 
   
 
 

References  
 
1. Vozzo CF, Sanaka MR. Endoscopic Management of Pancreaticobiliary Disease. Surg 
Clin North Am 2020; 100(6):1151-68. doi: 10.1016/j.suc.2020.08.006.   
2. Irisawa A, Miyoshi H, Itoi T, Ryozawa S, Kida M, Inui K. Recent innovations in 
therapeutic endoscopy for pancreatobiliary diseases. Dig Endosc 2020; 32(3):309-15. 
doi: 10.1111/den.13473.   
3. Henriksson AM, Thakrar SV. Anaesthesia and sedation for endoscopic retrograde 
cholangiopancreatography. 
BJA 
Educ 
2022; 
22(10):372-5. 
doi: 
10.1016/j.bjae.2022.04.002.   
4. Guo P, Wu H, Liu L, Zhao Q, Jin Z. Efficacy of an Oxycodone-Propofol Combination 
versus a Fentanyl-Propofol Combination in Conscious Sedation during Therapeutic 
Endoscopic Retrograde Cholangiopancreatography in Elderly Patients. Gerontology 
2021; 67(1):9-16. doi: 10.1159/000511173.   
5. Inal FY, Daskaya H, Yilmaz Y, Kocoglu H. Evaluation of bispectral index monitoring 
efficacy in endoscopic patients who underwent retrograde cholangiopancreatography 
and received sedoanalgesia. Wideochir Inne Tech Maloinwazyjne 2020; 15(2):358-
65.   
6. Behrens A., Kreuzmayr A., Manner H. Acute sedation-associated complications in GI 
endoscopy (ProSed 2 Study): results from the prospective multicentre electronic 
registry of sedation-associated complications. Gut 2019; 68:445–52.  
7. Tokmak S, Cetin MF, Torun S. Efficacy and safety of endoscopic retrograde 
cholangiopancreatography in the very elderly by using a combination of intravenous 
midazolam, ketamine and pethidine. Geriatr Gerontol Int 2021; 21(10):887-92. doi: 
10.1111/ggi.14252.   
8. Choi EJ, Kim CH, Yoon JY, Kim EJ. Ketamine-propofol (ketofol) in procedural 
sedation: a narrative review. J Dent Anesth Pain Med 2023; 23(3):123-133. doi: 
10.17245/jdapm.2023.23.3.123.   
9. Liu X, Li Y, Kang L, Wang Q. Recent Advances in the Clinical Value and Potential of 
Dexmedetomidine. J Inflamm Res. 2021; 14:7507-7527. doi: 10.2147/JIR.S346089.   
10. Morse JD, Cortinez LI, Anderson BJ. A Universal Pharmacokinetic Model for 
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10.3390/jcm9113480.   
 
 

CONSENT FORM  
  
Research Title: Comparison of Dexmedetomidine versus Ketofol for Moderate Sedation in 
Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Controlled Trial 
  
Principle Investigator: Dr. Syed Muhammad Abbas 
  
Institute: Sindh Institute of Urology & Transplantation (SIUT)  
  
1. Introduction: You are being requested to voluntarily participate in a research project described 
below. Please read the consent form that describes nature of the study. If you have any queries, 
please feel free to contact the study researcher or the study staff.   
  
2. Purpose of the study: This study is being conducted to compare the efficacy of 
dexmedetomidine versus ketofol for moderate sedation in patients undergoing ERCP.  
  
3. Confidentiality: All information collected during this study will be kept confidential. Your 
personal information will not be disclosed to anyone outside the research team, and your data will 
be anonymized to protect your privacy. 
  
4. Risks & benefits: There are potential risks and benefits associated with both Dexmedetomidine 
and Ketofol. Participants may experience side effects such as drowsiness, low blood pressure, or 
respiratory depression. However, these effects will be closely monitored by the medical team. The 
benefits include effective sedation for a successful ERCP procedure. 
  
Contact Information: 
 
If you have any questions or concerns about the study, you can contact Dr. Syed Muhammad Abbas 
at +92 333 1318838.  
  
You are welcome to contact the investigator if you have any questions.  
  
Authorization Statement  
Date: ____________  
  
I have read the conditions about the study. I know that being in this study is voluntary.  
I am willing to give the blood samples for laboratory investigation for the research.  
  
Participant Name: ________________ Age: ____________ Participant Signature:_______________  
Contact #: _____________________