A Comparison Between Dexmedetomidine and Fentanyl as Adjuvants to Thoracic Epidural in Patients Undergoing Thoracotomy Surgery: A Randomized Controlled Trial
Phase: NA
Conditions: Post-operative Pain, Thoracic Epidural, Thoracotomy Surgery
Sponsor: Cairo University

 
A Comparison between 
dexmedetomidine and 
fentanyl as adjuvants to 
thoracic epidural in 
patients undergoing 
thoracotomy surgery: A 
randomized controlled 
trial 
 
 
 
 
 
 
 
 

Investigators 
Candidate Details 
Name: Mohammed gamal Soliman   
Degree: Master in Anesthesia, Surgical ICU & Pain management  
Affiliation: Anesthesia, Surgical ICU & Pain management resident  
Phone No: 01123656410 
Email: Meniawy.zis@gmail.com 
Principle Investigator 
             Name:  D. Hossam Salah El Din El Ashmawi 
Affiliation: Professor of Anesthesia, Surgical ICU & Pain management 
Phone No:  01001707493 
Email:  h.elashmawi@kasralainy.edu.eg 
 
Principle Investigator 
Name: D. Pierre Zarif Tawadros 
Affiliation: Assistant Professor of Anesthesia, Surgical ICU & Pain 
management 
Phone No: 01223647115 
             Email: pierre_zarif@kasralainy.edu.eg   
 
Co-investigator (B): 
Name: D. Mohamed Ahmed Mohamed Ibrahim 
Affiliation: lecturer of Anesthesia, Surgical ICU & Pain management 
            Phone No: 01222226900  
           Email: drmohamed-anaesthesia@hotmail.com 
 

 
Co-investigator (C): 
 Name: D. Rimon soryal adly muhareb 
 Affiliation: Lecturer of Anesthesia, Surgical ICU & Pain management 
Phone No: 01203976471 
Email: Remoon_jesus@live.com 
Introduction: 
Thoracotomy surgeries are associated with painful surgical incisions 
which increase the need for intraoperative and postoperative analgesia. 
Thoracic epidural analgesia (TEA), when combined with general 
anesthesia, provides good intraoperative and postoperative pain relief, 
and also facilitates deep-breathing exercises and early ambulation. (1) 
Opioids, such as fentanyl, have traditionally been used as adjuvants 
for epidural administration in combination with local anesthetics to 
achieve the desired analgesic effect. [2] The addition of opioids provides 
superior analgesia and prolongs the duration, but there is always a 
possibility of an increased incidence of pruritus, urinary retention, 
nausea, vomiting and respiratory depression. [3, 4] 
Recently α2 -agonists have shown promise as an adjuvant to local 
anesthetics in epidural anesthesia. (5−6) Dexmedetomidine, a highly 
selective α2 -adrenoreceptor agonist, has effective analgesic and 
sedative properties (7, 8) and lacks opioid-related side effects. (9) One 
study compared the analgesic efficacy of dexmedetomidine versus 
fentanyl as an adjuvant for thoracic epidural combined with general 
anesthesia in patients undergoing upper abdominal surgery (10).  
Moreover, another study compared the analgesic efficacy of 
dexmedetomidine and fentanyl for epidural analgesia in lower limb 
orthopedic surgeries. (11) These studies show that Dexmedetomidine 
seems to be a better alternative to fentanyl as an epidural adjuvant as it 
provides effective perioperative analgesia, prolonged post-op analgesia, 
lower consumption of rescue analgesia during the postoperative period, 
and much better sedation levels. 
However, the use of dexmedetomidine in thoracic surgery has not been 
well investigated. 

In this study, we aim to compare the analgesic efficacy of bupivacaine 
with dexmedetomidine versus bupivacaine with Fentanyl administered 
in epidural anesthesia in patients undergoing thoracotomy surgery 
under general anesthesia. 
   
Aim of the work: 
This thesis aims to investigate whether the addition of 
dexmedetomidine to epidural bupivacaine provides effective 
intraoperative analgesia comparable to fentanyl. 
 
Objectives: 
To find out if there is a benefit from adding dexmedetomidine to epidural 
bupivacaine as regards: 
 Intra and postoperative opioid consumption 
 Pain score (numerical rating scale) 
 Hemodynamic stability, 
 Patient satisfaction.  
  
 
Hypothesis: 
We hypothesize that adding dexmedetomidine to bupivacaine in 
thoracic epidural would lead to better intraoperative and postoperative 
analgesia compared to fentanyl, with fewer side effects. 
 
Ethical Considerations: 
The study will be conducted after taking approval of research ethical 
committee; Informed consent will be obtained from the patients. 
Documentation of any motor or neurological deficit if present. 
  
  

Methodology 
 
• Study design 
This is a randomized controlled, double-blinded study. 
• Study setting and location 
The study will be conducted at Cairo University Hospital – 
cardiothoracic surgery unit. 
Study population 
Participants will be adult patients, ASA I, II, and III, scheduled for 
thoracic surgeries with posterolateral thoracotomy. 
Eligibility Criteria 
 
Inclusion criteria:  
● Age 18 – 60 years old 
● ASA physical status I-II-III 
● Good mental function.  
● Patient scheduled for thoracic surgery with posterolateral 
thoracotomy.  
● BMI of patient (18 – 30).   
Exclusion criteria:  
● Age less than 18 or more than 60 years old 
● Any contraindications to epidural injection (patient refusal, local 
infection at the site of injection, coagulopathy, patients on 
anticoagulant or antiplatelet drugs, known allergy to local 
anesthetics, significant spine deformity) 
● Inability to provide informed consent or pain score 
 
   Study Procedures  
Randomization  
                      
 Patients will be randomly allocated by a computer-generated table into 
one of the study groups; the randomization sequence will be concealed 
in sealed envelopes. Patients and data collector will be blinded to group 
assignment. 
 

Study Protocol  
 
Following approval from Research Committee of Anesthesia Department 
and the Ethics Committee of the Faculty of Medicine, Cairo University, 
50 patients will be included in the study (25 patients per group). After 
obtaining written informed consents, all patients will be subjected to 
systematic preoperative assessment including history taking, physical 
examination, and review of the results of routine investigations. Upon 
arrival to the preparation room, a 20G IV cannula will be inserted into a 
peripheral vein and midazolam 2-3 mg will be administered unless 
contraindicated. A 20G arterial catheter will be inserted into the radial 
artery of the dependent (non-operative) side, after local infiltration with 
lidocaine 2%. Patients will be transferred to the operating room where 
routine monitoring is applied, including electrocardiography (ECG), 
invasive Blood Pressure (IBP) and pulse oximetry are attached. Baseline 
heart rate, blood pressure, oxygen saturation and respiratory rate will be 
recorded. 
 A thoracic epidural catheter will be inserted at the T6- T7 intervertebral 
space, with the patient in the sitting position with standard aseptic 
precautions using an 18-G Touhy needle via a midline or paramedian 
approach with a loss of resistance method. A test dose of 3 ml of 2% 
lignocaine with adrenaline 5 µ/ml will be administered. 
For thoracic surgery the sensory dermatome blockade needs to cover 
the incision and intercostal drains and may extend from T4 to T8.  
The epidural drug will be administered according to the group allocation 
over a period of 10 minutes as follows: 
 
Group A: 
 
Patients will receive 50 μg dexmedetomidine with 10 ml of 0.125% 
bupivacaine followed by a continuous infusion of (10 ml bupivacaine + 
25 μg dexmedetomidine + 39 ml saline with rate of 5 ml per hour).  
 
Group B: 
 
Patients will receive 50 μg fentanyl in addition to 10 ml 0.125% 
bupivacaine followed by a continuous infusion (10 ml bupivacaine + 100 
μg fentanyl + 38 ml saline with rate of 5 ml per hour). 
 
After documenting the sensory blockade by using a piece of ice or cold 
object, 

If sensory level fail to be achieved, patient will be out of the study.  
 Anesthesia will be induced with Propofol 2–3 mg/kg, together with 
fentanyl 2 mg/kg until loss of verbal response. Muscle relaxation will be 
achieved with atracurium 0.5 mg/kg and the patient’s trachea will be 
intubated using a single or double-lumen tube, as indicated by the 
surgical procedure. Anesthesia will be maintained by isoflurane, and 
muscle relaxation will be maintained with atracurium 0.3 – 0.5 
mg/kg/hr. 
 The lungs will be ventilated with positive pressure ventilation to 
maintain end-tidal carbon dioxide (EtCO2) between 32 and 36 mmHg. 
Patients’ heart rate, blood pressure will be monitored continuously and 
recorded at ten-minute intervals until the end of surgery. Any attack of 
hypotension, defined as a drop of > 20% of baseline blood pressure, will 
be managed by ephedrine 0.2 mg/kg IV, and administering I.V. fluids. On 
the other hand, hypertension, defined as an increase of > 20 % of 
baseline blood pressure, will be managed by increasing the depth of 
anesthesia and administering bolus doses of fentanyl 1 mic/kg (up to 3 
mic/kg maximum dose).   
 Bradycardia (heart rate < 50 beats/min) will be managed by atropine 
0.02 mg/ kg IV  
 
 At the end of surgery residual neuromuscular blockade will be reversed 
and the endotracheal tube will be removed. Patients will be transferred 
to the ICU and will be monitored for 24 hours. Patients’ heart rate, blood 
pressure, oxygen saturation and respiratory rate will be monitored at 
regular intervals and the pain score and sedation level as well. 
 
Epidural infusion will be continued with the same infusion rate. A fixed 
dose of paracetamol (10 – 15 mg/kg) every 8 hours and NASID (0.5 – 
2/kg/ day divided in 2 doses will be administered I.V.  
 Pain will be assessed using the numerical rating scale (NRS) and if the 
pain score is more than 3, 3mg morphine I.V. will be administrated intra 
venous as rescue analgesia (up to .4 mg/kg morphine maximum dose 
every 24 Hours). 
 
Side effect of drugs may appear like 
(Nausea, vomiting that will managed by antiemetic drugs , Shivering will 
be managed by 25 mg Pethidine , Hypotension will manage by ephedrine 
0.2 mg/kg IV, and administering I.V. fluids).  
 

Measured Parameter 
1. Demographic data of the patient (Age, Sex, Weight, Height).  
2. Hemodynamic parameters (heart rate, systolic diastolic, and 
mean arterial blood pressure) will be recorded at baseline 
(before epidural analgesia), ten and twenty minutes after 
epidural activation, immediately after induction, and every 10 
minutes till end of surgery. 
3. Total intraoperative fentanyl consumption 
4. Total postoperative morphine consumption 
5. Postoperative pain score (numerical rating scale (NRS))  
6. Patient satisfaction. 
7. Sedation Score (The Modified Ramsay Sedation Score).    
8. Time to ambulation 
9. Incentive spirometry (It will measure the total amount that you 
were able to exhale, called the forced vital capacity (FVC), as 
well as how much was exhaled in the first second, called the 
forced expiratory volume in 1 second (FEV1). 
10. The incidence of side effects (nausea, vomiting, shivering, 
hypotension, dizziness, dry mouth, and respiratory depression) 
11. Time for the first analgesia  
 
 
VI. 
Study outcomes 
Primary outcome  
Total morphine consumption in the first 24 hours.  
 
 
Secondary outcomes  
 Hemodynamics parameters (systolic and Diastolic blood pressure, 
Mean blood pressure, Heart rate) will be recorded at baseline 
(before epidural analgesia), ten and twenty minutes after epidural 
activation, immediately after induction, and every 10 minutes till 
end of surgery). 

 Total intra operative fentanyl consumption.  
 Pain score (numerical rating scale (NRS)) 
 Sedation score (The Modified Ramsay sedation score).   
 Patient satisfaction after the procedure  
 The incidence of side effects (nausea, vomiting, shivering, 
hypotension, dizziness, dry mouth, and respiratory depression) 
 Time to the first analgesia request.  
 
 
                                                                                                                                     
Statistical Analysis:  
 
1. Sample size:  
Based on a previous study (12) the total morphine consumption 
for rescue analgesia in patients receiving thoracic epidural 
after thoracotomy was 9.6 + 4.3 mg/24 hours. Sample size 
calculation yielded a total number of 44 patients to detect a 
difference of 30% between the two groups with a power of 
80% and an alpha error of 0.05. The number was increased to 
50 patients (25 patients/group) to compensate for possible 
dropouts.  
 
2. Statistical analysis:  
Data will be summarized as mean + SD, median (range), or 
frequency (%) as appropriate. Categorical variables will be 
analyzed using the Chi squared or Fisher’s exact test. Intragroup 
comparisons will be analyzed using ANOVA with repeated 
measures. Comparisons between the two groups will be made 
using the unpaired t-test or the Mann-Whitney U-test as 
appropriate. A p-value <0.05 will be considered statistically 

significant. 
 
References:  
 
1. Wenk M, Schug SA. Perioperative pain management after thoracotomy. Curr Opin 
Anaesthesiol. 2011 Feb;24(1):8-12. doi: 10.1097/ACO.0b013e3283414175. PMID: 
21084984. 
 
2: Benzon, Honorio T. MD; Wong, Hak Y. MD; Belavic, Andrew M. Jr. MD; Goodman, Ira 
MD; Mitchell, Daniel MD; Lefheit, Thomas MD; Locicero, Joseph MD A Randomized 
Double-Blind Comparison of Epidural Fentanyl Infusion Versus Patient-Controlled Analgesia 
with Morphine for Postthoracotomy Pain, Anesthesia & Analgesia: February 1993 - Volume 
76 - Issue 2 - p 316-322  
 
3: Salomäki TE, Laitinen JO, Nuutinen LS. A randomized double-blind comparison of 
epidural versus intravenous fentanyl infusion for analgesia after thoracotomy. 
Anesthesiology. 1991 Nov;75(5):790-5. doi: 10.1097/00000542-199111000-00010. PMID: 
1952204. 
  
 
4: Amr YM, Yousef AA, Alzeftawy AE, Messbah WI, Saber AM. Effect of preincisional 
epidural fentanyl and bupivacaine on postthoracotomy pain and pulmonary function. Ann 
Thorac Surg. 2010 Feb;89(2):381-5. doi: 10.1016/j.athoracsur.2009.10.060. PMID: 
20103303. 
  
5. Soni, Pramila. (2016). Comparative study for better adjuvant with ropivacaine in epidural 
anesthesia. Anesthesia: Essays and Researches. 10. 10.4103/0259-1162.174470. 
 
6. Shaikh SI, Mahesh SB. The efficacy and safety of epidural dexmedetomidine and 
clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries. J 
Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):203-9. doi: 10.4103/0970-9185.182104. 
PMID: 27275050; PMCID: PMC4874075.  
 
7. Sathyanarayana LA, Heggeri VM, Simha PP, Narasimaiah S, Narasimaiah M, Subbarao 
BK. Comparison of Epidural Bupivacaine, Levobupivacaine and Dexmedetomidine in 
Patients Undergoing Vascular Surgery. J Clin Diagn Res. 2016 Jan;10(1):UC13-7. doi: 
10.7860/JCDR/2016/17344.7079. Epub 2016 Jan 1. PMID: 26894153; PMCID: 
PMC4740681.  
 

8. Karhade SS, Acharya SA, Harnagale K. Comparative analysis of epidural bupivacaine 
versus bupivacaine with dexmedetomidine for vaginal hysterectomy. Anesth Essays Res. 
2015 Sep-Dec;9(3):310-3. doi: 10.4103/0259-1162.158007. PMID: 26712965; PMCID: 
PMC4683497.  
 
9.  Zeng X-Z, Lu Z-F, Lv X-Q, Guo Y-P, Cui X-G (2016) Epidural Co-Administration of 
Dexmedetomidine and Levobupivacaine Improves the Gastrointestinal Motility Function after 
Colonic Resection in Comparison to Co-Administration of Morphine and Levobupivacaine. PLoS 
ONE 11(1): e0146215. https://doi.org/10.1371/journal.pone.0146215 
 
10. Neerja Bharti, Shweta N Pokale, Indu Bala & Vikas Gupta (2018) Analgesic 
efficacy of dexmedetomidine versus fentanyl as an adjunct to thoracic epidural in 
patients undergoing upper abdominal surgery: a randomized controlled 
trial, Southern African Journal of Anaesthesia and Analgesia, 24:1, 16-
21, DOI: 10.1080/22201181.2018.1433599 
 
11. Bajwa SJ, Arora V, Kaur J, Singh A, Parmar SS. Comparative evaluation of 
dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries. 
Saudi J Anaesth. 2011 Oct;5(4):365-70. doi: 10.4103/1658-354X.87264. PMID: 22144922; 
PMCID: PMC3227304. 
 
12:  Khalil AE, Abdallah NM, Bashandy GM, Kaddah TA. Ultrasound-Guided Serratus 
Anterior Plane Block Versus Thoracic Epidural Analgesia for Thoracotomy Pain. J 
Cardiothorac Vasc Anesth. 2017 Feb;31(1):152-158. doi: 10.1053/j.jvca.2016.08.023. 
Epub 2016 Aug 21. PMID: 27939192. 
 
 
 
 
 
 
 
 
 
 
 
 
 

 Appendix:  
 
Numerical rating scales (NRS)  
 
 
The-Modified-Ramsay-Sedation-Score  
 
 
 
 
 
 
 
 

Patient satisfaction score:  
 
 
How satisfied are you with the result of your anesthesia? 
 
5 
Very satisfied 
4 
Somewhat satisfied 
3 
Neither satisfied nor dissatisfied 
2 
Somewhat dissatisfied 
1 
Very dissatisfied 
 
We will calculate patient satisfaction scores from answers to previous 
Questions to range between (1) to (5).