Effect of Propofol and Dexmedetomidine-Based Total Intravenous Anesthesia Versus Sevoflurane-Based Inhalational Anesthesia on the Level of Inflammatory Markers in Patients Undergoing Inguinal Hernia Repair.
Phase: NA
Conditions: Anesthesia
Sponsor: Ain Shams University

 
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Title of the study: Effect of Propofol and 
Dexmedetomidine-Based Total Intravenous Anesthesia 
Versus Sevoflurane-Based Inhalational Anesthesia on 
the Level of Inflammatory Markers in Patients 
Undergoing Inguinal Hernia Repair. 
 
 
 
NCT: Pending 
 
Document Type : Protocol Of A Thesis For Partial 
Fulfilment 
Of Medical Doctorate Degree In Anesthesiology, 
Intensive Care And Pain Management 
 
Date: 30 September 2025 
 
Sponsor: Ain Shams University 
 
Study ID: FMASU MD256/2025 
 
 
 
 
 
 
 
 
 
 
 

 
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PROTOCOL OF A THESIS FOR PARTIAL FULFILMENT 
OF MEDICAL DOCTORATE DEGREE IN ANESTHESIOLOGY, 
INTENSIVE CARE AND PAIN MANAGEMENT 
 
Effect of Propofol and 
Dexmedetomidine-Based Total Intravenous Anesthesia Versus 
Sevoflurane-Based Inhalational Anesthesia on the Level of 
Inflammatory Markers in Patients Undergoing Inguinal Hernia Repair. 
 
 
Postgraduate Student: Doha Atef Elgamal 
Degrees:  MBBCh, MSc, Ain Shams University.  
  
DIRECTOR: Professor Dr. Ayman Mokhtar Kamaly  
Academic Position: Professor of Anesthesia, Intensive Care and Pain 
Management, Faculty of Medicine, Ain Shams University.  
  
Co-DIRECTOR:  Professor Dr. Waleed Abdalla Ibrahim  
Academic Position: Professor of Anesthesia, Intensive Care and Pain 
Management, Faculty of Medicine, Ain Shams University.  
  
Co-DIRECTOR:  Assistant Professor Dr. Ashraf Ahmed Abd Elhamid 
Abou Slemah 
Academic Position: Assistant Professor of Anesthesia, Intensive Care 
and Pain Management, Faculty of Medicine, Ain Shams University.  
  
Co-DIRECTOR:  Dr. Marwa Mustafa Salem  
Academic Position: Lecturer of Anesthesia, Intensive Care and Pain 
Management, Faculty of Medicine, Ain Shams University.  
 
Co-DIRECTOR: Dr. Hanaa Moustafa Elsaied Mohamed 
Academic Position: Lecturer of Clinical Pathology and Immunology, Faculty of 
Medicine, Ain Shams University. 
  
 

 
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        What is already known on this subject? What does this study add? 
  Several studies showed that the anesthetic technique can affect several postoperative outcomes including the level of 
inflammatory markers such as Interleukins (ILs), C-reactive protein (CRP), ferritin, and neutrophil-to-lymphocyte ratio 
(NLR). This study will compare the effect of propofol and dexmedetomidine-based total intravenous anesthesia (TIVA) 
versus (vs) sevoflurane-based inhalational anesthesia (IA) on postoperative levels of inflammatory markers in patients 
undergoing inguinal hernia repair. 
   
   
1. INTRODUCTION 
  A hernia is a condition in which part of the abdominal cavity contents bulges out through a weak part in the abdominal 
wall. Common types of hernias include inguinal, incisional, femoral, ventral, hiatal, umbilical, and epigastric. However, 
inguinal hernias are the most common type. Surgical intervention is usually needed to avoid complications which can 
range from mild discomfort or pain to intestinal strangulation. (Liu et al., 2025; Costantini et al., 2025) 
Surgical injury is followed by an initial systemic inflammatory response which is necessary for tissue repair. However, 
its effects on the body depends on the balance between pro-inflammatory and anti-inflammatory cytokine production. 
(Ostović et al., 2025)  
Disturbances in this balance can lead to a number of complications, such as delayed wound healing, an increased risk of 
infection, and multiple organs failure. (Yediyıldız et al., 2025)  
The stress response to surgery involves dynamic interactions between several different components of both the innate 
and adaptive immune systems throughout the inflammatory process. Cytokines are soluble proteins which are secreted 
from several immune cells, such as lymphocytes, macrophages, and natural killer (NK) cells. They modulate the 
immune response and act as important mediators in the inflammatory process. (Liu et al., 2021)  
IL-6 is considered the most representative cytokine in the inflammatory response to tissue injury. It stimulates neutrophil 
production in the bone marrow, helps in the differentiation of T helper cells, which, in turn, produce other cytokines 
(Silva et al., 2024), and activates antigen-presenting cells, such as natural killer (NK) cells, which induce apoptosis in 
damaged cells. IL-6 also stimulates production of serum proteins known as acute phase reactants, such as CRP, 
ferritin, fibrinogen, and D-dimer. (Cusack and Buggy, 2020; Richardson, 2025) 
Activation of the adaptive immune system requires interaction between T-lymphocytes and antigen-presenting cells. The 
immune response induced by surgery causes a relative increase in T-helper 2 (Th2) lymphocytes compared with T-
helper 1 (Th1) lymphocytes. The imbalance in Th1:Th2 causes impaired adaptive immunity, leading to postoperative 
complications. (Cusack and Buggy, 2020) 
The NLR is a ratio derived from a complete blood count and serves as an important hematological parameter reflecting 
systemic inflammation and immune response. It has gained attention as a potential biomarker for several conditions, 
including inflammation. (Zhang et al., 2024) 
Several studies have shown that anesthetic management can influence the inflammatory response by modulating 
immune cell function. Thus, the choice of anesthetic technique affects the balance between pro- and anti-inflammatory 
responses, potentially altering postoperative outcomes. (Silva et al., 2024) 
It has been standard practice worldwide to maintain general anesthesia with inhalational anesthetics due to their rapid 
onset, easy titration, and predictable recovery profiles. However, the use of TIVA has gained popularity over the last 
few decades. This can be attributed to its lower environmental impact compared with inhalational anesthetics which 
contribute considerably to greenhouse gas emissions. (Daccache et al., 2025) 
Propofol is an intravenous (IV) anesthetic agent of rapid onset, short duration of action, and low incidence of side 
effects, all of which make propofol an ideal anesthetic agent (Kotani et al., 2023). Research has shown that propofol has 
an antioxidant effect as it induces the expression of oxidative stress biomarkers. It has been proven to help modulate the 
systemic inflammatory response by inhibiting the production of pro-inflammatory cytokines. (Jin et al., 2023) 
Moreover, it has been reported to enhance infiltration of NK cells, T cells, and Th cells into tissues without affecting 
total T cell counts or leukocyte apoptosis.(Yediyıldız et al., 2025) 

 
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Dexmedetomidine is a selective alpha-2 (α2)-adrenergic receptor agonist which has gained wide use in anesthesia and 
critical care due to its ability to induce sedation, analgesia, and anxiolytic effect without causing respiratory depression 
(Liu et al., 2024;  Kocaoğlu et al., 2025). Moreover, it has been reported to have protective and healing effects, as well 
as antioxidant, anti-inflammatory and anti-apoptotic effects on various tissues and organs. (Kocaoğlu et al., 2025). 
On the other hand, inhalational anesthetic agents have been proven to have pro-inflammatory effects. For instance, 
sevoflurane has been associated with apoptosis in T and B lymphocytes, altered Th1/Th2 ratios, reduced lymphocyte 
and NK cell counts, and elevated neutrophil levels. (Yediyıldız et al., 2025) 
 
2. AIM  
This study aims to compare the postoperative levels and trends of change of inflammatory markers, namely IL-6, CRP, 
ferritin, and NLR in patients undergoing inguinal hernia repair using propofol and dexmedetomidine-based total 
intravenous anesthesia (TIVA) vs sevoflurane-based inhalational anesthesia (IA). 
 
3. METHODOLOGY: 
Type of Study: Prospective, randomized, double-blind, comparative clinical study. 
Study Setting: Ain Shams University hospitals, Cairo, Egypt.  
Study Period: 6-12 months. 
Study Population: Adult patients scheduled for elective inguinal hernia repair. 
Inclusion Criteria: 
1. Adult patients between 18 and 50 years of age undergoing elective inguinal hernia repair. 
2. American Society of Anesthesiologists physical status classification (ASA) I and II.  
Exclusion Criteria: 
1. Patient’s refusal. 
2. ASA > II 
3. Complicated hernia. 
4. Previous hernia repair with mesh.  
5. History of allergy to any of the study drugs.  
6. History of any heart disease affecting cardiac function or rhythm or receiving medications that decrease the heart 
rate (HR). 
7. Baseline HR≤60 beat/min. 
8. Baseline mean arterial pressure (MAP)≤70 mmHg. 
9. Psychiatric illness.  
10. Patients with chronic kidney or liver disease. (Creatinine clearance<50 mL/min or serum albumin level<2g/dL.) 
11. Patients with immunological disorders or receiving immunosuppressive treatment or anti-inflammatory drugs. 
12. Patients with neoplasms, chronic inflammatory states, or active infections. 
13. Patients with any type of anemia or those who received iron therapy or blood transfusion within 4 weeks. 
Sampling Method:  Random sampling  
Sample Size: Using the PASS 15 program from sample size calculation, reviewing results from the previous study 
(Yediyıldız et al., 2025) showed that postoperative IL-6 levels were significantly lower in the TIVA group than in the 
sevoflurane group 20,1±23,5 versus 54,8±45,4, based on these findings a sample size of at least 20 patients per group 
achieve 80% power to reject the null hypothesis of equal means when the population mean difference is μ1-μ2 = 54.8-
20.1 = 34.7 with standard deviations of 45.0 for group 1 and 23.5 for group 2, and with a significance level (alpha) of 
0.050 using a two-sided two-sample unequal-variance t-test. 

 
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Ethical Considerations: The study protocol will receive ethical approval from the Research Ethical Committee, 
Faculty of Medicine Ain Shams University. Informed consent will be obtained from all participants before starting study. 
Randomization and blinding: Group allocation will be contained in sequentially numbered, sealed opaque 
envelopes, which will be opened by the primary investigator. The collector of blood samples and the data analyzer will be 
blinded about the study group. 
Study Procedures:  
All patients will be assessed preoperatively by careful history taking and airway examination. Complete blood count 
(CBC), coagulation profile, liver and kidney function tests for all patients and electrocardiogram (ECG) for patients older 
than 40 years of age will be reviewed from patients medical records. A written informed consent will be signed by all 
patients before the surgery. All patients will be admitted after completing fasting hours for both solid food and clear 
fluids. Upon arrival to the operating room (OR), IV access of the size 20 gauge (G) will be inserted. Venous blood 
samples for baseline levels of IL-6, ferritin, and CRP and CBC (for baseline NLR) will be collected (sample 0). All 
patients will be monitored with a five-lead ECG, non-invasive blood pressure (NIBP) measurement and finger pulse 
oximetry. Baseline vital data (MAP, HR, and oxygen saturation (SO2)) will be recorded. HR and SO2 will be monitored 
continuously and BP will be measured every 5 minutes (min) till the end of the surgery.  
All patients will be premedicated with 0.03 mg/kg IV midazolam. Preoxygenation will be performed using 100% oxygen 
at a fresh gas flow (FGF) of 10 L/min via face mask for 3 minutes, followed by induction of general anesthesia. 
• Group A (TIVA group): will receive 1 μg/kg IV dexmedetomidine over 10 min, 1 μg/kg IV fentanyl, 2 mg/kg IV 
propofol, and 0.5 mg/kg IV atracurium. Maintenance of anesthesia will be achieved by 0.5 μg/kg/h 
dexmedetomidine IV infusion and 6-12 mg/kg/h propofol IV infusion titrated according to bispectral index value 
(BIS) with target BIS 40–60. 
• Group B (Sevoflurane group): will receive 1 μg/kg IV fentanyl, 8% sevoflurane via face mask and 0.5 mg/kg IV 
atracurium. Maintenance of anesthesia will be achieved with 2%-4% sevoflurane titrated according to BIS with 
target BIS 40–60. 
After induction, intubation will be done for all patients using suitable size endotracheal tube (ETT). Both groups will be 
mechanically ventilated using volume control mode with tidal volume 7-10 ml/kg/min, positive end-expiratory pressure 
(PEEP) 5 cmH2O and oxygen-air mixture with fraction of inspired oxygen (FiO2) 50% and FGF of 3 L/min, and 
respiratory rate adjusted with target end-tidal carbon dioxide (ET CO2) 30-40 mmHg. 0.1 mg/kg IV atracurium will be 
given as needed to maintain muscle relaxation. 0.5 mcg/kg fentanyl will be given if HR or MAP increase ≥20% from 
their basal value. HR and MAP ≤20% of the basal value will be treated with needed doses of atropine and ephedrine, 
respectively. All patients will be extubated in the operating room and transferred to postanesthesia care unit (PACU). 
Sample Collection and Laboratory Analysis: 
Venous blood samples will be collected from each patient at three time points: preoperative (baseline, sample 0), 6 hours 
postoperative (sample 1), and 24 hours postoperative (sample 2). At each time point, 5 mL of venous blood will be 
aseptically withdrawn into a sterile plain tube. The blood will be allowed to clot at room temperature, followed by 
centrifugation at 2000–3000 rpm for 20 minutes. The resulting serum will be carefully separated and stored at −80°C for 
subsequent analysis.  
Serum interleukin-6 (IL-6) levels will be measured using the enzyme-linked immunosorbent assay (ELISA) method. 
Ferritin and C-reactive protein (CRP) concentrations will be analyzed using a COBAS automated analyzer.  
Additionally, a 2 mL blood sample will be collected in an EDTA tube for complete blood count (CBC) analysis, which 
will be performed using the Sysmex Coulter hematology analyzer.  
All laboratory analysis will be conducted at the main laboratories of Ain Shams University Hospital. 
Primary outcome: 
IL-6 level 24 h postoperatively compared to baseline value. 
Secondary outcomes:  
1. Trend of change of IL-6 level within the postoperative 24 h. 
2. Trends of change and levels of CRP, NLR, and ferritin 24 h postoperatively. 
3. Time to discharge. 

 
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4. Incidence of PONV. 
Both time to discharge and incidence of PONV will be reviewed from patients medical records. 
❖ The main researcher of the study will be the principal investigator responsible for the preparation and conduct of 
the study under supervision of the director and co-directors. Each member of the team will ensure that the study is 
conducted according to the protocol approved in their meetings that will be arranged on regular basis. Results of 
the study and any complications that might occur during the study will be recorded and reported by the principal 
investigator and revised by the director and co-directors. 
Statistical Analysis   
The collected data will be revised, coded and introduced to a PC using statistical package for social science (SPSS 23). 
Data will be presented as mean and standard deviation (+/-SD) for quantitative parametric data, median and range for 
quantitative non-parametric data and as numbers and percentage for qualitative data. Suitable analysis will be done 
according to the type of data obtained. P< 0.05 will be considered significant. 
 
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