Effectiveness of Low-Dose Ketamine and Intravenous Lidocaine Versus Fentanyl for Postoperative Pain for Patients Undergoing Elective Gynecologic Surgery Under General Anesthesia: A Randomized Controlled Trial
Phase: PHASE4
Conditions: Postoperative Pain, Postoperative Nausea and Vomiting
Sponsor: Dilla University

 
 
College of Medicine and Health Science 
Department of Anesthesiology 
The Effectiveness of Low-Dose Ketamine and Intravenous Lidocaine versus Fentanyl for 
Postoperative Pain for Patients Undergoing Elective Gynecologic Surgery under General 
Anesthesia at Dilla University General and Teaching Hospital and Hawassa University 
Comprehensive and Specialized Hospital from April 10, 2023, to June 10, 2023: A Multi-
Centered Randomized Controlled Trial 
The issuance of ethical approval was received with a protocol unique number 
“duirb/037/23-05”  from the College of Medicine and Health Sciences at Dilla 
University following the submission of the study plan to the institutional review board 
 
 
 
 
 
 
 
 
 

 
 
II 
 
I. 
Table of contents 
I. 
Table of contents ..................................................................................................................... II 
II. 
Acronyms and Abbreviations ............................................................................................... IV 
III. 
Executive Summary ....................................................................................................... V 
1. 
Introduction ............................................................................................................................. 1 
1.1. 
Background .................................................................................................................................. 1 
1.1. 
Problem statement ....................................................................................................................... 2 
1.2. 
Significance of the study ............................................................................................................. 4 
2. 
Literature review ..................................................................................................................... 5 
2.1. 
Perspectives on OFA and opoid-based anesthesia ....................................................................... 5 
2.2. 
Opioid-related adverse events between OFA and OBA .............................................................. 5 
2.3. 
Severity of postoperative pain ..................................................................................................... 6 
2.4. 
The effectiveness of drugs used in OFA ..................................................................................... 7 
3. 
Objectives ............................................................................................................................. 10 
3.1. 
General objective ....................................................................................................................... 10 
3.2. 
Specific objectives ..................................................................................................................... 10 
4. 
Methodology and materials................................................................................................... 11 
4.1. 
Study area and period ................................................................................................................ 11 
4.2. 
Study design .............................................................................................................................. 11 
4.3. 
Population .................................................................................................................................. 11 
4.3.1. 
Source population ................................................................................................. 11 
4.3.2. 
Study population ................................................................................................... 12 
4.4. 
Inclusion and exclusion criteria ................................................................................................. 12 
4.4.1. 
Inclusion criteria ................................................................................................... 12 

 
 
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4.4.2. 
Exclusion criteria .................................................................................................. 12 
4.5. 
Sampling procedure and sample size ......................................................................................... 13 
4.6. 
Random sequence generation .................................................................................................... 13 
4.7. 
Allocation concealment and blinding ........................................................................................ 13 
4.8. 
Study variables .......................................................................................................................... 13 
4.8.1. 
Dependent (outcome) variables ............................................................................ 13 
4.8.2. 
Independent variables ........................................................................................... 14 
4.9. 
Operational definitions .............................................................................................................. 14 
4.10. 
Data collection procedures ........................................................................................................ 15 
4.11. 
Data quality assurance ............................................................................................................... 17 
4.12. 
Data Processing and Analysis Procedure .................................................................................. 17 
4.13. 
Ethical Considerations ............................................................................................................... 18 
4.14. 
Dissemination of the Results ..................................................................................................... 18 
4.15. 
Work plan .................................................................................................................................. 19 
References ..................................................................................................................................... 21 
Annexes............................................................................................................................................ i 
4.16. 
Annex One .................................................................................................................................... i 
 

 
 
IV 
 
II. 
Acronyms and Abbreviations   
ACA  
 
Advanced Clinical Anesthesia  
DBP  
 
Diastolic Blood Pressure 
GA 
 
 
General Anesthesia  
ICU   
 
Intensive care Unit 
MAP  
 
Mean Arterial Pressure 
MSC  
 
Masters in Science 
NMDA 
 
N-methyl D-aspartate  
 
NRS   
 
Numerical Rating Scale 
NSAID 
 
Non-steroidal Ant-inflammatory Drug 
OBA   
 
Opoid Based Anesthesia 
OFA   
 
Opoid Free Anesthesia  
PACU  
 
Post-anesthesia Care Unit 
PCM  
 
Paracetamol  
PI  
 
 
Principal Investigator  
POI 
 
 
Post-Operative Ileus  
PONV  
 
Post-Operative Nausea and Vomiting 
SBP 
 
 
Systolic Blood Pressure 
SNNPR 
 
Southern Nations Nationalities and Peoples Region. 

 
 
V 
 
III. 
Executive Summary 
Background: Long-term use of opioids has been linked to various side effects and decreased 
patient satisfaction after anesthesia. A combination of drugs with opoid was used for intraoperative 
analgesia. Multiple drugs, by avoiding opioids, was a new opinion suggested. Opioid-free 
anesthesia with a combination of drugs is a new idea to avoid opoid from postoperative analgesia. 
Objective: To determine the effectiveness of low-dose ketamine and intravenous lidocaine versus 
fentanyl for postoperative pain in patients undergoing elective gynecologic surgery under general 
anesthesia at Dilla University Teaching Hospital and Hawassa University Comprehensive and 
Specialized Hospital from April 10 to October 10, 2023. 
Methodology: A multicenter, randomized, controlled, single-blinded superiority trial will be 
conducted with 70 adult patients undergoing elective gynecologic surgery under general 
anesthesia. Randomization will be done by a computer-generated random allocation sequence in 
equal ratios to the treatment group (T = 35) and the control group (C = 35). The primary dependent 
variable is the pain severity measured by a visual analog scale postoperatively at discharge from 
the post-anesthesia care unit, 6th hour, 12th hour, and 24th hour, and the secondary outcomes are 
postoperative nausea and vomiting, postoperative analgesia request, and intraoperative cardiac 
adverse events. Student’s t-test, analysis of variance, and chi-square test will be used for data 
analysis. A p-value of less than 0.05 was determined as statistically significant. 
Work plan and budgeting: - study will be conducted from April 10, 2023, to October 10, 2023, 
with a cost of 41625 ETB.

1. Introduction  
1.1. 
Background 
Surgical procedures that are performed based on the underlying cause and the specific needs of the 
patient result in nociception, which is mediated by pathways through the nervous system with the 
interplay of various factors involved in the experience of pain. Two-thirds of patients who 
underwent surgery reported moderate to severe postoperative pain. To reduce the effects and 
promote a speedy recovery, surgical pain management techniques were urged to cover both non-
pharmacological and medication-based therapies(1-4).  
According to evidence, fewer than half of people who undergo surgery report satisfactory pain 
alleviation. Inadequate pain control and the use of unmodified techniques harm the quality of life, 
function, and functional recovery of patients who underwent surgery. The perioperative anesthesia 
handling and thorough consideration of medications administered to a surgical patient have been 
applied(3).  
Opioids are commonly used medications to treat perioperative pain for a long period. They have 
been used as anti-nociceptive, decreasing alertness, and reducing the amount of centrally acting 
anesthetics(5). They had also been administered to decrease blood pressure during laryngoscopy 
and intubation and suppress airway reflexes during airway manipulation. However, opoid usage 
has been linked to a variety of adverse effects such as postoperative ileus, constipation, 
postoperative nausea and vomiting (PONV), and  opposite effects  including opioid-induced pain 
modulation and tolerance(6, 7)  
A shift of pain management strategies with the implementation of less invasive surgical techniques 
and the advancement of anesthesia management has been implemented. Drugs that aim at different 
nociceptive receptors have been discovered and applied in perioperative patient care. Multimodal 
analgesia, which combines both opioids and opioid-free analgesics to avoid the negative 
consequences of using opioids alone, has been employed (1, 8). However, the issue of pain 
enhancement and opioid-related adverse events has not been fully resolved and has been reported 
with the technique of multimodal anesthesia (9, 10).  

 
 
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Opioid-free anesthesia (OFA) involving a combination of drugs and techniques was suggested to 
avoid opioids from intraoperative analgesia. It was intended to avoid opoid from the postoperative 
analgesia regimen but was later taken as a viable and optional method for perioperative anesthesia 
management(11, 12). Individual medications such as N-methyl-D-aspartate (NMDA) antagonists, 
sodium channel blockers, anti-inflammatory drugs, and alpha-2 agonists are being administered 
for analgesia. They aimed to reduce the reduction of MAC of volatile anesthetics, avoiding 
negative effects associated with opiates, and providing greater patient satisfaction after surgery 
when used in combination (13-18).  
Intravenous lidocaine in doses less than 2mg/kg is reported to relieve pain by blocking sodium 
channels in both the peripheral and central nervous systems. It was also thought to reduce central 
and deafferentation pain and aid in wound healing. At lower doses up to 1 mg/kg, ketamine can 
provide significant pain relief without negative effects by eliminating opioid tolerance and having 
anti-hyperalgesic effects. A combination of intravenous (IV) lidocaine and low-dose ketamine can 
be used for intraoperative analgesia without adverse effects, even though it has not been routinely 
used for intraoperative anesthesia. 
1.1. 
Problem statement 
The increased utilization of opioids has raised worries and disapproval about the customary 
practice of opioid administration for anesthesia. A study by Chan et al(19) in Canada reported that 
about 73% of patients undergoing major surgery and  66.7% of patients undergoing intermediate 
procedures were using perioperative opoid. It is reported that approximately 11% of patients who 
undergo surgery with opioid anesthesia experience moderate to severe adverse effects related to 
opioids(20). Patients given perioperative opioids were associated with risks including a doubled 
likelihood of inpatient mortality, a 30% rate of readmission within a month, 55% longer hospital 
stays, and tripled hospitalization costs, which highlight the urgent need for effective solutions to 
the problem (20-23). 

 
 
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Both OFA and OBA acknowledge the pain-relieving abilities of opioids but also note that opoid 
can lead to increased pain sensation after surgery and an increased need for analgesics(24, 25). 
According to the nationwide survey in the US(26), the occurrence of pain was 84% postoperatively 
in general surgical patients, and 74% of patients who underwent major surgery reported 
debilitating pain at immediate postoperatively hours. A study in Europe by Buvanendran et al(27) 
reported that greater than 50% of gynecologic surgical patients experience substantial to extreme 
postoperative pain up to discharge from the hospital, which was mainly associated with the 
intraoperative use of opioids.  
A study by R. Park et al(28) in Europe reported the occurrence of severe pain after gynecologic 
surgery was 32% within 24 hours postoperatively, which was mainly associated with poor pain 
management at immediate discharge. A study by Anberbir et al(29) at Addis Ababa reported that 
about 73% of gynecologic surgical patients experience moderate to severe pain more than once 
within 24 hours postoperatively. Preoperative anxiety, urban dwellings, and being uneducated 
were the reported reasons for pain severity. 
Though the literature on OFA technique in procedures such as laparoscopic cholecystectomy, 
gynecologic, and bariatric surgery has shown its advantages(4, 25, 30), certain scholars have 
reported inconclusive and contesting results (31-33). The postoperative opioid-free anesthesia 
(POFA) trial, which was the most comprehensive and current multicenter trial, was stopped due 
to safety concerns after a few patients developed severe bradycardia(24).  
The majority of the research is constrained to certain surgical procedures and is carried out in 
settings with modern facilities; however, a paucity of literature on the subject. Additionally, most 
of the studies done on OFA are carried out in Europe and Asia, and there are the fewest studies in 
Africa (19(4)).  

 
 
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Despite the reported surgeries under OFA techniques were being reported with better profiles, the 
effectiveness of the technique has not been well established. Contrasting research results and lack 
of relevant literature in resource-constrained environments made the implementation of the OFA 
idea challenging and indeterminate. Nevertheless, more research is required to address the issue in 
the resource desiccated settings like our country. The purpose of this trial is to compare the 
effectiveness of low-dose ketamine and intravenous lidocaine for postoperative pain compared 
with fentanyl for patients undergoing gynecologic surgery under general anesthesia. 
1.2. 
Significance of the study 
Even though the OFA concept remained doubtful of its validity and feasibility, reducing opioid-
related harm in surgical patients improves the patient's postoperative recovery. The calamities 
associated with opioid-based anesthesia are obvious and need to be solved. Some works of 
literature on the OFA principle have reported improved postoperative recovery, and others 
reported comparable results and drug-related side effects. Additional studies will narrow these 
gaps within the findings. 
Gynecologic surgery carrying a risk of postoperative nausea and vomiting, as well as moderate to 
severe discomfort, can benefit from avoiding the use of opioid-based anesthesia techniques. This 
can decrease unwanted opoid effects, higher costs, longer hospital stays, higher postoperative pain 
scores, and can increase postoperative patient satisfaction. 
Two recent RCTs conducted in Cameroon and Egypt have shown promising results using the OFA 
protocol without dexmedetomidine, which could lead to the adoption of the OFA technique in 
resource-limited settings. In works of literature on OFA in resourceful settings, drugs like 
ketamine, lidocaine, NSAIDs, and others, can open the eyes of investigators covered in 
dexmedetomidine's fancy, especially for resource-depleted settings. 
This single-blinded prospective randomized controlled trial aimed to determine the effectiveness 
of OFA with low-dose ketamine and intravenous lidocaine vs. general anesthesia with fentanyl for 
postoperative pain in patients undergoing elective gynecologic surgery under general anesthesia. 
Due to the lack of comparable studies on the subject, the outcome of the study can lead to a quick 
pace for patient management and is acceptable in the scientific environment preferred by scientific 
literature. 

 
 
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2. Literature review  
A growing body of knowledge has described the potential adverse effects of opioid analgesics, and 
the latest calamity, the "opioid crisis," needs keen emphasis. To overcome the associated calamity, 
works of literature urged the practice of giving up on opioids and the use of other modalities for 
pain pharmacotherapy(8, 20). OFA is one of the modalities, and the most recent and toothsome 
works of literature are in developed countries, so the idea quickly improved, but the lack of the 
saint drug held back the idea in the developing world(5, 34). 
2.1. 
Perspectives on OFA and opoid-based anesthesia 
Helene Beloeil, in the narrative review, described OFA as a rationale that aimed to avoid the 
intraoperative use of opioid analgesics. He urged that the intraoperative use of opioids is associated 
with an increase in postoperative pain scores by worsening the sensitization of injured tissue during 
surgery. OFA using a combination of modalities and drugs, including NMDA receptor inhibitors, 
anti-inflammatory drugs, Na+ channel blockers, and 2-agonists, was documented at decreasing 
doses of individual drugs by avoiding the side effects associated with specific drugs (35).  
The American Society for Enhanced Recovery and Perioperative Quality's joint consensus 
statement in 2020 proposed the suitability of OFA techniques and praised the findings of existing 
works in the literature, but questioned the availability of significant data on the benefits and harms 
of the strategy. They advocated the feasibility of the OFA technique in terms of reduced recovery 
room time, decreased PONV, reduced analgesic requirements, and a decreased postoperative pain 
scale(36). An article from the American Anesthesiology described OFA as a “fashion” that they 
termed a campaign aimed at eradicating opoid from use as a pain medication (37). 
2.2. 
Opioid-related adverse events between OFA and OBA 
In the systematic review and meta-analysis of five RCTs on the intraoperative use of OFA vs. 
conventional GA on adult patients undergoing non-cardiac surgery, Frauenknecht et al. reported a 
20% reduction in PONV with a CI of 0.77 (0.61–0.9) and a P value of 0.03 in the OFA group. 
They documented the association of delayed recuperation, a higher hospital stay, and increased 
medical costs with patients given opioid anesthesia(25). 

 
 
6 
 
An RCT by Feng et al(38) on 120 adult patients undergoing thoracoscopic lung resection compared 
the incidence of PONV with patients undergoing anesthesia under OFA with ketamine and 
dexmedetomidine and OBA with sufentanil. They reported the occurrence of PONV in the OBA 
group, which was twice as much as the PONV in the OFA group (15% vs. 31.7%), OR = 0.38, at 
95% CI (0.16-0.91), and a p-value of 0.031 at 24 hours postoperatively. 
Massoth et al(32) conducted an RCT comparing the occurrence of PONV in 152 women 
undergoing gynecological surgery by OFA using dexmedetomidine and ketamine with 
conventional GA with sufentanil. They reported no significant difference in the occurrence of 
PONV (71.4% in the opioid-based anesthesia group vs. 70.5% in the OFA group, with a p-value 
of 0.91), vomiting or antiemetic requirements (8.1% vs. 10.5%) with a p-value of 0.57, and the 
occurrence of adverse effects at 24 hours postoperative. 
The large-scale retrospective cohort study on data of 521 patients who underwent laparoscopic 
hysterectomy by Forget et al(39) reported comparable outcomes in the occurrence of nausea (10% 
vs. 7%) and vomiting (2% vs. 1%) with p-values of 0.21 and 0.3, respectively, in the patient groups 
receiving OBA and OFA. The study was conducted on the data of 118 patients who received OFA 
with clonidine and ketamine, and 403 patients given OBA with sufentanyl. 
2.3. 
Severity of postoperative pain 
In a systematic review and meta-analysis of 11 RCTs comparing OFA and standard GA with opoid 
on laparoscopic, gynecological, and abdominal surgeries, Olausson et al. reported significantly 
lower postoperative analgesic consumption in the OFA group (-6.0 mg with a p-value of 0.00001). 
They also documented decreased adverse effects of opioids (0.32, I2 = 56%, and p-value of 
0.00001), while no significant difference in GI symptoms, shivering, and postoperative hypoxemia 
between the two groups (40). 
Unlike Olausson et al.'s, Frauenknecht et al.'s meta-analysis of 5 RCTs on OFA vs. conventional 
GA with opioids found a non-significant difference in postoperative pain scores; a p = 0.38 
difference between the two groups. They noted that the short duration of action of remifentanil, 
which most works of literature they reviewed used, may have affected the outcome of the 
postoperative pain score (25).  

 
 
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A randomized placebo-controlled trial done by Kang et al. on 168 female patients undergoing 
breast surgery in Japan with the OFA group given ketamine 0.5 mg/kg vs. the placebo group has 
documented a lower postoperative pain scale in patients receiving ketamine (69.0% vs. 86.9% with 
P = 0.005 at 3 months) (15) in the patients received OFA. 
An RCT on OFA vs. OBA by Torchier et al(30) on 36 patients without dexmedetomidine for 
gynecologic surgeries, including breast surgery, documented a higher postoperative pain scale 
(reported by the NRS) in patients receiving opioids at 24 hr. and 48 hr. They also reported a 100% 
success rate of intraoperative opioid-free anesthesia with ketamine 0.5 kg/mg followed by 
infusion, and lidocaine 1.5 mg/kg bolus, followed by infusion.  
2.4. 
The effectiveness of drugs used in OFA 
Wang et al., in the review of 12 randomized controlled studies comprising about 900 patients 
undergoing different surgical procedures under GA, compared s-ketamine in bolus doses of 0.075 
to 0.5 mg/kg and infusions from 1.25 to 10 μg/kg/min with placebo. They recorded better pain 
scores at rest up to 24 hours in patients given ketamine and similar pain scores at 48 hours 
postoperatively (p = 0.53) in both ketamine and placebo(41). 
In another meta-analysis of nine randomized controlled trials comparing IV ketamine with placebo 
for adult surgical patients on opioid use, Forget et al also documented a significant decrease in 
postoperative pain scale at 24 hours in patients taking ketamine, with a mean difference of -0.79. 
About a 97 mg and 186 mg decrease in opiate consumption at 24 and 48 hours, respectively, were 
documented in patients taking ketamine (16). 
In the review of recent works of literature on subanesthetic doses of ketamine for intraoperative 
pain and up to 48-hour postoperative administration, Jouguelet et al. reported a reduction of 
postoperative pain score and up to 40% reduction of postoperative analgesic consumption by bolus 
then continuous infusions given of up to 1.2 mg/kg/h or 1.3 mg/kg ketamine doses, respectively. 
On subanesthetic ketamine use, and reported that ketamine, when used in a subanesthetic dose, 
has no documented associated adverse events (42). 
Touchier et al. performed an RCT by using lidocaine with ketamine on 36 gynecologic patients 
without dexmedetomidine and reported better hemodynamic stability in the OFA group (p = 
0.0026) compared to opioid-based anesthesia with remifentanil (30). 

 
 
8 
 
Foo et al., in the statement on the efficacy and safety of lidocaine, described the analgesic, anti-
hyperalgesic, and anti-inflammatory effects of lidocaine from its actions on muscarinic and 
NMDA receptors. They recommended 1–2 mg/kg as an initial bolus followed by a continuous 
infusion of 0.5–3 mg/kg/hr. Avoiding a dose greater than or equal to 3 mg/kg/hr, and avoiding 
lidocaine in patients with hepatic or renal impairment. Lidocaine should not be used on patients 
whose weight is less than 40 kg(12).  
Weibel et al. performed a systematic review and meta-analysis of an RCT with 280 patients who 
used 1–5 mg/kg boluses and infusions of 1–3 mg/kg/h IV lidocaine found a significant reduction 
in pain score up to four hours after surgery, with a mean difference of 0.84, 95% CI 1.10 to 0.59, 
and at 24 hours, with a mean difference of 0.34, 95% CI 0.57 to 0.11. The pain score at 48 hr. was 
similar in both groups, the occurrence of ileus was lower in patients given lidocaine (4.8% vs. 
13.9%), and the time of the first poop was comparable in both groups. The time it took for the first 
flatus and intestinal movement, as well as the time it took for bowel sounds to return, were all 
shorter in the lidocaine group (43). 
OFA has been reported as a better option to general anesthesia with opioids, with a few literary 
masterpieces excluded. According to the findings of works of research, OFA can offer a superior 
perioperative anesthetic substitute, a better quality immediate post-operative recovery, and can 
avoid the usual opioid-related adverse events. Other drugs, as dexmedetomidine, which sprouts 
OFA, and seems to bring bad luck, can be used as fixings for opioid-related issues in settings that 
cannot access this drug. IV lidocaine, low-dose ketamine, dexamethasone, and some more drugs  
 
 
 
 
 
 
 
 

 
 
9 
 
Hypothesis Testing 
Null hypothesis (H0) 
Opoid-free anesthesia with low-dose ketamine and intravenous lidocaine is not more effective than 
general anesthesia with fentanyl for postoperative pain in adult patients undergoing elective 
gynecologic surgery under general anesthesia. 
µ1 ≤ µ2; µ1 is the mean pain severity at the GA with fentanyl group, and µ2 is the mean 
pain severity at the OFA (low dose ketamine and IV lidocaine) group 
Alternative hypothesis (HA) 
Opioid-free anesthesia with low-dose ketamine and intravenous lidocaine is effective for 
postoperative pain compared with general anesthesia with fentanyl for patients undergoing elective 
gynecologic surgery under general anesthesia. 
µ1 > µ2; µ1 is the mean pain severity at the GA with fentanyl group, and µ2 is the mean pain 
severity at the OFA (low dose ketamine and IV lidocaine) group. 
 

 
 
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3. Objectives 
3.1. 
General objective 
To determine the effectiveness of low-dose ketamine and intravenous lidocaine vs. Fentanyl for 
postoperative pain in adult patients who underwent elective gynecologic surgery under general 
anesthesia at Dilla University Teaching Hospital and Hawassa University Comprehensive and 
Specialized Hospital from April 10, 2023, to October 10, 2023 
3.2. 
Specific objectives 
To compare the postoperative pain severity between groups of adult patients who underwent 
elective gynecologic surgery under general anesthesia at Dilla University Teaching Hospital and 
Hawassa University Comprehensive and Specialized Hospital from April 10 to October 10, 2023 
To compare postoperative analgesic requests between groups of adult patients who underwent 
elective gynecologic surgery under general anesthesia at Dilla University General and Teaching 
Hospital and Hawassa University Comprehensive and Specialized Hospital from April 10 to 
October 10, 2023  
To compare the occurrence of PONV between groups of adult patients undergoing elective 
gynecologic surgery under general anesthesia at Dilla University Teaching Hospital and Hawassa 
University Comprehensive and Specialized Hospital from April 10 to October 10, 2023 
To compare the occurrence of intraoperative cardiac adverse events for adult patients undergoing 
elective gynecologic surgery under general anesthesia at Dilla University Teaching Hospital and 
Hawassa University Comprehensive and Specialized Hospital from April 10 to October 10, 2023 

 
 
11 
 
4. Methodology and materials 
4.1. 
Study area and period 
The research will be carried out at Dilla University General and Teaching Hospital in Gedio Zone, 
and Hawassa University Comprehensive and Specialized Hospital in Hawassa, SNNPR Ethiopia, 
from April 10, 2023, to October 10, 2023. 
Dilla University General and Teaching Hospital is located in the administrative center of the Gedeo 
Zone, SNNPR, on the main road, 372 km from Addis Ababa to Nairobi. Dilla University General 
and Teaching Hospital is in the southern part of town, on the main road to Moyale. The hospital 
has about eight specialty departments, such as anesthesiology, surgery, obstetrics and gynecology, 
internal medicine, and pediatrics. 
The general and teaching hospital has one OT with four fully functioning ORs, a post-anesthesia 
care unit (PACU) with four beds, and an intensive care unit (ICU) with eight beds. There are 
elective procedures scheduled five days a week; surgical procedures two days a week, 
gynecological and obstetrics, including elective C/S, two days a week, and orthopedic and trauma 
operations two days a week. The Gedio zone and neighboring areas of SNNPR, Sidama region, 
and Oromia region have millions of residents who use the referral and teaching hospital. 
Hawassa University Comprehensive and Specialized Hospital in Hawassa, situated in 
southwestern part of Hawassa city, the capital of Sidama, is situated 275 kilometers (km) south of 
Addis Ababa. In the Southern Nations, Nationalities, and People Region (SNNPR) and the nearby 
Oromia area, the tertiary Hawassa University Referral Hospital (HURTH) provides medical care 
for almost 12 million people. An operating room, intensive care unit (ICU), 16 wards with 400 
beds, and 11 floors make up this hospital. 
4.2. 
Study design  
A multi-centered, randomized, controlled, single-blinded trial will be conducted at Dilla 
University General and Teaching Hospital and Hawassa University Comprehensive and 
Specialized Hospital. 
4.3. 
Population 
4.3.1. Source population 

 
 
12 
 
All patients undergoing elective gynecologic surgery under general anesthesia at Dilla University 
General and Teaching Hospital and Hawassa University Comprehensive and Specialized Hospital. 
4.3.2. Study population 
Adult patients between the ages of 18 and 65 undergoing elective gynecologic surgery under 
general anesthesia at Dilla University General and Teaching Hospital and Hawassa University 
Comprehensive and Specialized Hospital during the study period. 
4.4. 
Inclusion and exclusion criteria 
4.4.1. Inclusion criteria 
ASA I and II patients between the ages of 18 and 65 undergoing elective gynecologic surgery at 
Hawassa University Comprehensive and Specialized Hospital and Dilla University Teaching 
Hospital under general anesthesia between April 10, 2023, and October 10, 2023, and gave 
informed consent. 
4.4.2. Exclusion criteria 
Patients with allergies to any of the drugs used in the trial 
Patients with chronic pain 
Patients who are diagnosed with CNS diseases, like psychiatric diseases or epilepsy(46) 
Patients who are hypertensive and taking beta-blockers, as well as those who have 
preoperative bradycardia, hypotension, or any type of heart block(47) 
Patients weighing less than 40 kg or obese patients (BMI > 35 kg/m2)(12) 
Patients with a history of smoking 
Patients who are scheduled for postoperative mechanical ventilation 

 
 
13 
 
4.5. 
Sampling procedure and sample size 
The sample size (N) was calculated by the formula for a continuous outcome variable with equal 
sample sizes in both groups, n = 2[(Zά/2 + Z (1-ß)) ² *σ²]/ (d²) by G-power calculator. We assumed: 
significance level (Zα/2) = 0.05, taken 1.96, and power of study Z(1-ß) = 0.80, taken 0.84; σ² is 
the standard deviation taken from a previous study in South Korea(48), which is 1.9. Assuming a 
medium effect size in the OFA group compared to those receiving fentanyl is clinically significant, 
the calculated sample size for each group is 31, resulting in 62 participants in both groups. To 
account for potential contingencies, an additional 10% is added to the final sample size, resulting 
in 70 participants. 
 
4.6. 
Random sequence generation 
The eligible participants presenting for gynecologic surgery at both study areas during the study 
period will be selected. Participants will be allocated to study groups by a computer-generated 
random allocation sequence number created by an independent anesthetist with a 1:1 allocation to 
the treatment group (T) and control group (C) the night before surgery.  
4.7. 
Allocation concealment and blinding 
Participants will be given a sealed envelope with the letter of the study group name in it and will 
be allowed to present it to the OR. Anesthesia providers involved in patient management wii be 
allowed to know the drugs given and groups due to differences in anesthesia techniques, ethical 
issues, and patient diversity. Apart from patient management, the anesthetist will not be involved 
in any other study processes. Only participants assigned to groups will not know which group they 
will be selected for. 
4.8. 
Study variables 
4.8.1. Dependent (outcome) variables 
4.8.1.1. Primary outcome variable  
 The postoperative pain severity 

 
 
14 
 
4.8.1.2. Secondary outcome variables  
 Postoperative analgesic requests between groups 
 The occurrence of postoperative nausea and vomiting (PONV)between the groups 
 The occurrence of intraoperative cardiac adverse events between groups 
4.8.2. Independent variables  
 Age 
 Height 
 Weight 
 ASA physical status 
 BMI 
 Educational background  
 Marital status 
 Anesthetic experience 
 Type of diagnosis and procedure 
 Participants' hemoglobin and hematocrit 
 Preoperative hemodynamic variables  
4.9. 
Operational definitions 
Nausea: The experience associated with the pressure to vomit  
Opoid-free analgesia: A combination of various opioid-sparing techniques with absolute 
avoidance of opioids for pain relief in the pre-and postoperative periods. 
Opoid-free anesthesia: It is a combination of various opioid-sparing techniques with absolute 
avoidance of opioids from induction of anesthesia until the extubation time 
Postoperative nausea and vomiting: Any nausea, retching, or vomiting occurring in the first 24 
hours after surgery 
The Postoperative pain: pain felt up to 24 hours after an operation by the patient's expression 

 
 
15 
 
NRS:  Valid and reliable tool for assessing pain intensity in all populations, regardless of literacy 
level(1, 50). It employs a 0-to-10 rating scale, with zero representing no pain and 10 representing 
the worst possible pain.  
VAS: This is a pain rating scale; the scores are derived from patient-reported valuations of 
symptoms that are recorded at 1 point along a 10 cm line that shows a continuum between the 2 
edges of the scale, which are "no pain" and "worst pain(51) 
Vomiting: Projection of contents of the stomach out through the mouth. 
4.10. Data collection procedures  
After getting ethical clearance from the Dilla University College of Health Sciences and Medicine 
ethical review board, a structured questionnaire will be formed and translated into the respective 
languages by the principal investigator (PI). Two BSC anesthetists involved in patient management 
will be selected at both study areas and trained in the overall process of participant handling and 
data collection.  
During the preoperative period 
Patients undergoing gynecologic operations during the study period will be assessed and told about 
the study process and anesthetic the day before the surgery. The patient will receive maintenance 
fluid, had bilateral peripheral IV lines secured, and was NPO the night before surgery. On the 
morning of the procedure, both a standard informed consent form for the procedure and a separate 
consent form for the study will be checked and available.  
The availability and functionality of the bilateral IV line, and NPO status will be checked, and 
prophylactic drugs will be given. Standard preoperative questionnaires will be used, and data will 
be collected through patient responses and medical records, such as patient monitoring and charts. 
At intraoperative period 

 
 
16 
 
Routine ASA monitoring will be checked and applied for patients in both groups when the patient 
presented to the OR. The functionality and availability of the bilateral IV line and urinary catheter 
will be rechecked. Propofol (3 mg/kg) will be  given to induce anesthesia after the patient had been 
pre-oxygenated for both groups. An intravenous bolus of 0.5 mg/kg of ketamine during the 
induction phase for patients in the treatment group, then a continuous infusion of 0.2 mg/kg/hr. 0f 
ketamine. A bolus of 1.5 mg/kg will be given before induction, and the same dose of lidocaine will 
be administered every 15 to 20 minutes after induction of anesthesia until the start of skin closure.  
Patients in the control group will be induced with fentanyl 2 μg/kg given during induction of 
anesthesia with propofol 3mg/kg. 0.5 μg /kg of fentanyl will be given every 20-30 minutes up to 
the start of skin closure.  
Intubation will be performed after administering 1.5–2 mg/kg IV suxamethonium. Inhalational 
anesthetics as availabilities (Isoflurane 0.75–2% and Halothane 1%_ 2%) were opened after the 
position of the ETT was confirmed, and Dexamethasone 0.15mg/kg IV bolus will be given after 
securing the ETT. 
Anesthesia will be maintained with inhalational agents according to the patient’s tidal volume of 
6–8 ml/kg adjusted to maintain oxygen saturation >95% with 3- 4 ml 100% oxygen flow, and end-
tidal CO2 between 32 and 45 mmHg. Muscle relaxation will be maintained with vecuronium 0.8 
mg/kg. Intraoperative anesthesia depth will be assessed by clinical signs as well as by patient 
monitoring. Estimated intraoperative blood loss will be supplied with ringer lactate or normal 
saline.  
The intraoperative participants’ data will be collected from the anesthesia record chart and patient 
monitoring. Intraoperative hemodynamic variables will be collected every 10 minutes. 
Intraoperative cardiac adverse events such as intraoperative bradycardia (pulse rate less than 50 
bpm), tachycardia (PR greater than 100 bpm), hypertension, and hypotension we diagnosed and 
managed as per institutional protocol. Intraoperative nausea or vomiting in both groups will also 
be managed as an institutional protocol.  

 
 
17 
 
When the surgeon begins skin closure, the inhalational agent will be turned off. A pre-prepared 
reversal agent bolus (neostigmine 0.05 mg/kg with atropine 0.02 mg/kg IV) was administered for 
patients given long-acting muscle relaxants after checking the adequacy of spontaneous 
ventilation, adequate movement of the respiratory bag, oxygen saturation >95percentage and 
ETCO2 between 32 and 45 mmHg after the skin is closed.  
During the postoperative period 
The postoperative pain severity will be assessed by the validated VAS starting from the patient's 
discharge from PACU to 24 hours postoperatively.  Data will be collected at discharge from 
PACU, at 6 hours, 12 hours, and 24 hours postoperatively. Analgesia request at postoperative times 
will be recorded as the patient's request for analgesia according to the VAS score. PONV data will 
be collected from the time of arrival at PACU at 6 hours, 12 hours, and 24 hours postoperatively 
according to the patient's signs and symptoms. 
4.11. Data quality assurance 
The questionnaire will be pretested on 5% of the study population who will not participate in the 
main study in two study areas. Training on the verification and orientation of the study, the data 
collection tools, and the data collection process will be provided to data collectors a week prior to 
the start of data collection 
During data collection, regular supervision and follow-up will be undertaken; the principal 
investigator (PI) will follow the collection process and will collect the filled questionnaire daily. 
The completeness and consistency of the daily data of individual participants will be checked. 
Missing data will be crosschecked and corrected before entered into a computer for analysis. The 
daily collected data was inserted into the locked patient data file on the computer accessed only by 
the PI 
4.12. Data Processing and Analysis Procedure 
After every data collection night, inconsistencies in data collection will be examined and fixed. 
Epi. Info version 7.2 will used for data entry and Statistical Package for the Social Sciences (SPSS) 
version 27will be used for data analysis.  

 
 
18 
 
The normality of data distributions for quantitative variables will be assessed using the 
Kolmogorov-Smirnov test and Levene’s test will be used to check the homogeneity of variance. 
The plot of the Box will be used to check outliers. Histograms and visual inspection of individual 
data will be used to verify the data distribution. 
Independent t-tests and  ANOVA tests will be used to assess continuous data on pain severity at 
different postoperative times, and results will be presented as mean plus standard deviation. The 
categorical data of PONV at different postoperative times will be analyzed by chi-square or Fisher 
exact test and presented as frequencies, percentages, and a bar chart graphically. P-values of less 
than 0.05 will be determined as statistically significant.  
4.13. Ethical Considerations 
Ethical clearance will be obtained from the College of Medicine and Health Sciences of Dilla 
University after the submission of the study protocol to the institutional review board. The support 
letter will be written to Hawassa University Comprehensive and Specialized Hospital. The risks, 
benefits, and objectives will be clearly explained, and written informed consent will be obtained 
from each participant. Throughout the trial period, a data monitoring committee comprised of three 
personnel from the Dilla University anesthesiology department will check on participant concerns, 
process of intervention, and modification of study process as needed.  
After the approval of the IRB at Dilla University College of Health Medicine and Health Sciences, 
the study protocol will be registered on clinicaltrial.gov, and the findings of the study will be 
reported in compliance with the CONSORT statement guidelines for randomized controlled trials. 
Individuals who wish to withdraw from the research will be permitted to depart the premises, and 
any information collected during the administration of anesthesia will be analyzed. 
4.14. Dissemination of the Results 
The results of the result of this study will be presented to the Dilla University College of Medicine 
and Health Sciences Department of Anesthesiology staff. It will also be presented at the annual 
research conference. This research will be submitted to reputable journals for publication. 
 
 

 
 
19 
 
4.15. Work plan 
Time frame or proposal and thesis development 
 
Activities 
 
                                     Time in Months  
Dec./2022  Jan./202
3  
Feb./2023  March/20
23  
Apr./202
3  
May/202
3 
June/
2023 
Research 
title 
defense 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Development 
of 
research proposal 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Acceptance 
of 
research proposal 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Development 
of 
research tools 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Sample selection  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Training of data 
collectors 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Data collection  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Data entry 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 Data analysis  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
First 
 
draft 
submissions 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final thesis defense  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1.1 Time frame for proposal development and thesis 

 
 
20 
 
Budget breakdown for proposal and thesis development 
Budget category 
Unit cost 
Multiplying factor 
Total cost(birr) 
For training 
Supervisor  
400 
1 
400 
Data collectors  
200 
3 
600 
For data collection 
Supervisor  
200 
30*1 
6000 
Data collectors  
200 
30*3 
18000 
Study Drugs 
Lidocaine IV 2% #40 vials   
 
2500 
Fentanyl IV 1mg #35 
ampules’  
 
 
2500 
Stationary  
Writing pad 
30 
20 
600 
Pen  
20 
20 
400 
Pencil 
10 
30 
300 
Coffee/tea 
10 
5*30 
1500 
Eraser 
15 
5 
75 
Printing and binding  
500 
4 
2000 
Sharpener 
35 
10 
350 
Flash disk 
400 
2 
800 
 CD (RW) 
200 
3 
600 
Duplicating Questionnaire 50 
40 
2000 
Total 
 
 
38625 ETB 
10% added 
 
 
41625ETB 
Table1.2. budgeting breakdown for proposal development and thesis development   
 
 
 

 
 
21 
 
References 
1. 
Goudra BG, Duggan M, Chidambaran V, Venkata HPK, Duggan E, Powell M, et al. 
Anesthesiology: A Practical Approach: Springer; 2018. 
2. 
Schwenk ES, Mariano ER. Designing the ideal perioperative pain management plan starts 
with multimodal analgesia. Korean Journal of Anesthesiology. 2018;71(5):345-52. 
3. 
Lamvu G, Feranec J, Blanton E. Perioperative pain management: an update for 
obstetrician-gynecologists. American journal of obstetrics and gynecology. 2018;218(2):193-9. 
4. 
Cividjian A, Petitjeans F, Liu N, Ghignone M, de Kock M, Quintin L. Do we feel pain 
during anesthesia? A critical review on surgery-evoked circulatory changes and pain perception. 
Best Practice & Research Clinical Anaesthesiology. 2017;31(4):445-67. 
5. 
Brown EN, Pavone KJ, Naranjo M. Multimodal general anesthesia: theory and practice. 
Anesthesia & Analgesia. 2018;127(5):1246-58. 
6. 
Frauenknecht J, Kirkham K, Jacot‐Guillarmod A, Albrecht E. Analgesic impact of intra‐
operative opioids vs. opioid‐free anaesthesia: a systematic review and meta‐analysis. Anaesthesia. 
2019;74(5):651-62. 
7. 
Egan TD. Are opioids indispensable for general anaesthesia? British Journal of 
Anaesthesia. 2019;122(6):e127-e35. 
8. 
Kumar K, Singh SI. Neuraxial opioid-induced pruritus: An update. Journal of 
anaesthesiology, clinical pharmacology. 2013;29(3):303-7. 
9. 
Kaye AD, Urman RD, Rappaport Y, Siddaiah H, Cornett EM, Belani K, et al. Multimodal 
analgesia as an essential part of enhanced recovery protocols in the ambulatory settings. Journal 
of anaesthesiology, clinical pharmacology. 2019;35(Suppl 1):S40. 
10. 
White DM, Mair AR, Martinez-Taboada F. Opioid-free anaesthesia in three dogs. Open 
Veterinary Journal. 2017;7(2):104-10. 
11. 
Feldheiser A, Aziz O, Baldini G, Cox B, Fearon K, Feldman L, et al. Enhanced Recovery 
After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia 
practice. Acta Anaesthesiologica Scandinavica. 2016;60(3):289-334. 

 
 
22 
 
12. 
Kharasch ED, Clark JD. Opioid-free Anesthesia: Time to Regain Our Balance. 
Anesthesiology. 2021;134(4):509-14. 
13. 
Boysen PG, Pappas MM, Evans B. An evidence-based opioid-free anesthetic technique to 
manage perioperative and periprocedural pain. Ochsner Journal. 2018;18(2):121-5. 
14. 
Jean-Pierre Estebe M. Corresponding author: Jean-Pierre Estebe. 2017. 
15. 
Kang C, Cho A-R, Kim K-H, Eun-A L, Lee HJ, Jae-Young K, et al. Effects of 
intraoperative low-dose ketamine on persistent postsurgical pain after breast cancer surgery: a 
prospective, randomized, controlled, double-blind study. Pain Physician. 2020;23(1):37. 
16. 
Forget P. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesthesia 
Critical Care & Pain Medicine. 2019;38(2):169-72. 
17. 
Golzari SE, Soleimanpour H, Mahmoodpoor A, Safari S, Ala A. Lidocaine and pain 
management in the emergency department: a review article. Anesth Pain Med. 2014;4(1):e15444. 
18. 
Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674. 
19. 
Choi J, Zamary K, Barreto NB, Tennakoon L, Davis KM, Trickey AW, et al. Intravenous 
lidocaine as a non-opioid adjunct analgesic for traumatic rib fractures. Plos one. 
2020;15(9):e0239896. 
20. 
Opioid free versus opioid based anesthesia in abdominal gynecological surgery: a 
prospective randomized controlled trial [Internet]. 2021. 
21. 
Joshi GP. General anesthetic techniques for enhanced recovery after surgery: Current 
controversies. Best Practice & Research Clinical Anaesthesiology. 2021;35(4):531-41. 
22. 
Shanthanna H, Ladha KS, Kehlet H, Joshi GP. Perioperative Opioid AdministrationA 
Critical 
Review of Opioid-free versus Opioid-sparing Approaches. 
Anesthesiology. 
2021;134(4):645-59. 
23. 
Bedene A, Lijfering WM, Niesters M, van Velzen M, Rosendaal FR, Bouvy ML, et al. 
Opioid Prescription Patterns and Risk Factors Associated With Opioid Use in the Netherlands. 
JAMA Network Open. 2019;2(8):e1910223-e. 

 
 
23 
 
24. 
Beloeil H, Garot M, Lebuffe G, Gerbaud A, Bila J, Cuvillon P, et al. Balanced opioid-free 
anesthesia with dexmedetomidine versus balanced anesthesia with remifentanil for major or 
intermediate noncardiac surgery: the postoperative and opioid-free anesthesia (POFA) randomized 
clinical trial. Anesthesiology. 2021;134(4):541-51. 
25. 
Salomé AH, H.; Fletcher, D.; Martinez, V. Opioid-Free Anesthesia Benefit–Risk Balance: 
A Systematic Review and Meta-Analysis of Randomized Controlled Trials. . 
. J Clin Med. 2021,;10, 2069. 
26. 
Aguerreche C, Cadier G, Beurton A, Imbault J, Leuillet S, Remy A, et al. Feasibility and 
postoperative opioid sparing effect of an opioid-free anaesthesia in adult cardiac surgery: a 
retrospective study. BMC anesthesiology. 2021;21(1):1-11. 
27. 
Baek SY, Kim JW, Kim TW, Han W, Lee DE, Ryu KH, et al. Opioid-free anesthesia with 
a mixture of dexmedetomidine, ketamine, and lidocaine in one syringe for surgery in obese 
patients. Journal of International Medical Research. 2020;48(10):0300060520967830. 
28. 
Basto TP. Effect of opioid-free anaesthesia on perioperative period: A review. 2020. 
29. 
Forget P, De Kock M, Lovqvist L, Lois F. Is intraoperative opioids avoidance A utopia? A 
matched study in laparoscopic hysterectomy. Current Reviews in Clinical and Experimental 
Pharmacology Formerly Current Clinical Pharmacology. 2021;16(1):103-8. 
30. 
Choi H, Song JY, Oh EJ, Chae MS, Yu S, Moon YE. The Effect of Opioid-Free Anesthesia 
on the Quality of Recovery After Gynecological Laparoscopy: A Prospective Randomized 
Controlled Trial. Journal of Pain Research. 2022:2197-209. 
31. 
Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC. Fentanyl or 
dexmedetomidine combined with desflurane for bariatric surgery. Journal of clinical anesthesia. 
2006;18(1):24-8. 
32. 
Ziemann-Gimmel P, Goldfarb A, Koppman J, Marema R. Opioid-free total intravenous 
anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple 
prophylaxis. British journal of anaesthesia. 2014;112(5):906-11. 

 
 
24 
 
33. 
Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, et al. Opioid-free total 
intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic 
cholecystectomy: a prospective, randomized, double-blinded study. Revista brasileira de 
anestesiologia. 2015;65:191-9. 
34. 
Apfel CCT, A.; Souza, K.; Pergolizzi, J.; Hornuss, C. Intravenous acetaminophen reduces 
postoperative nausea and 
vomiting: A systematic review and meta-analysis. . [CrossRef]. Pain. 2013,;154: 677–89. 
35. 
Massoth C, Schwellenbach J, Saadat-Gilani K, Weiss R, Pöpping D, Küllmar M, et al. 
Impact of opioid-free anaesthesia on postoperative nausea, vomiting and pain after gynaecological 
laparoscopy - A randomised controlled trial. Journal of Clinical Anesthesia. 2021;75:110437. 
36. 
Dautaj B, Bulku E, Jaho E, Sturce R, Llazani A, Zhurda T, et al. Effectivness of 
dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium 
sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38(3-4):69-73. 
37. 
García-Navia JT, Tornero López J, Egea-Guerrero JJ, Vilches Arenas A, Vázquez 
Gutiérrez T. Effect of a single dose of lidocaine and ketamine on intraoperative opioids 
requirements in patients undergoing elective gynecological laparotomies under general anesthesia. 
A randomized, placebo controlled pilot study. Farm Hosp. 2016;40(1):44-51. 
38. 
Ibrahim M, Elnabtity AM, Hegab A, Alnujaidi OA, El Sanea O. Combined opioid free and 
loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under 
ERAS protocol: a randomized controlled trial. BMC anesthesiology. 2022;22(1):1-10. 
39. 
Tochie JN, Bengono Bengono RS, Metogo JM, Ndikontar R, Ngouatna S, Ntock FN, et al. 
The efficacy and safety of an adapted opioid-free anesthesia regimen versus conventional general 
anesthesia in gynecological surgery for low-resource settings: a randomized pilot study. BMC 
anesthesiology. 2022;22(1):1-13. 
40. 
Chia PA, Cannesson M, Bui CCM. Opioid free anesthesia: feasible? Current opinion in 
anaesthesiology. 2020;33(4):512-7. 
41. 
Bugada D, Lorini LF, Lavand'homme P. Opioid free anesthesia: evidence for short and 
long-term outcome. Minerva Anestesiol. 2021;87(2):230-7. 

 
 
25 
 
42. 
Salem AM, Hafez MM, Eldin AS, Hagras AM. Opioid-free anesthesia for laparoscopic 
hysterectomy: is it appropriate. J Anesth Inten Care Med. 2019;9(2):555757. 
43. 
Hontoir S, Saxena S, Gatto P, Khalifé M, Ben Aziz A, Paesmans M, et al. Opioid-free 
anesthesia: what about patient comfort? A prospective, randomized, controlled trial. Acta 
Anaesthesiol Belg. 2016;67(4):183-90. 
44. 
Olmos AV, Steen S, Boscardin CK, Chang JM, Manahan G, Little AR, et al. Increasing 
the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department. 
BMJ open quality. 2021;10(3):e001320. 
45. 
Varga BR, Streicher JM, Majumdar S. Strategies towards safer opioid analgesics—A 
review of old and upcoming targets. British Journal of Pharmacology. 2021. 
46. 
Helene B. Opioid-free anesthesia. Best Practice & Research Clinical Anaesthesiology. 
2019;33(3):353-60. 
47. 
McEvoy MD, Raymond BL, Krige A. Opioid-Sparing Perioperative Analgesia Within 
Enhanced Recovery Programs. Anesthesiology Clinics. 2022;40(1):35-58. 
48. 
Forget P, Mulier J, Lavand’homme P, De Baerdemaeker L, Pelosi P, De Boer HD. Opioid-
free anesthesia: Comment. Anesthesiology. 2021;135(4):751-3. 
49. 
Olausson A, Svensson CJ, Andréll P, Jildenstål P, Thörn SE, Wolf A. Total opioid‐free 
general anaesthesia can improve postoperative outcomes after surgery, without evidence of 
adverse effects on patient safety and pain management: A systematic review and meta‐analysis. 
Acta Anaesthesiologica Scandinavica. 2022;66(2):170-85. 
50. 
Mulier JP, Wouters R, Dillemans B, Dekock M. A randomized controlled, double-blind 
trial evaluating the effect of opioid-free versus opioid general anaesthesia on postoperative pain 
and discomfort measured by the QoR-40. Journal of Clinical Anesthesia and Pain Medicine. 
2018;6:2. 
51. 
Lee W-K, Kim M-S, Kang S-W, Kim S, Lee J-R. Type of anaesthesia and patient quality 
of recovery: a randomized trial comparing propofol–remifentanil total iv anaesthesia with 
desflurane anaesthesia. British Journal of Anaesthesia. 2015;114(4):663-8. 

 
 
26 
 
52. 
Massoth C, Schwellenbach J, Saadat-Gilani K, Weiss R, Pöpping D, Küllmar M, et al. 
Impact of opioid-free anaesthesia on postoperative nausea, vomiting and pain after gynaecological 
laparoscopy-A randomised controlled trial. Journal of Clinical Anesthesia. 2021;75:110437. 
53. 
Wang X, Lin C, Lan L, Liu J. Perioperative intravenous S-ketamine for acute postoperative 
pain in adults: a systematic review and meta-analysis. Journal of Clinical Anesthesia. 
2021;68:110071. 
54. 
Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion 
or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature. 
Pain medicine. 2015;16(2):383-403. 
55. 
Foo I, Macfarlane A, Srivastava D, Bhaskar A, Barker H, Knaggs R, et al. The use of 
intravenous lidocaine for postoperative pain and recovery: international consensus statement on 
efficacy and safety. Anaesthesia. 2021;76(2):238-50. 
56. 
Weibel S, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, et al. Efficacy 
and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a 
systematic review with trial sequential analysis †. BJA: British Journal of Anaesthesia. 
2016;116(6):770-83. 
57. 
Myles P, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a 
postoperative quality of recovery score: the QoR-40. British journal of anaesthesia. 2000;84(1):11-
5. 
58. 
Anpuram L. Utility of numerical and visual analog scales for evaluating the post-operative 
pain in rural areas. 2019. 

Annexes  
4.16. Annex One 
Informed consent form English Language version 
This informed consent form is for patients undergoing elective gynecologic surgery under general 
anesthesia at Dilla University Referral and Teaching Hospital and Hawassa University 
Comprehensive and Specialized Hospital inviting them to participate in a study on Low-Dose 
Ketamine and Intravenous Lidocaine vs. Fentanyl for intraoperative pain management. The topic 
of our study is The Effectiveness and Safety of Opioid-Free Anesthesia with Low-Dose Ketamine 
and Intravenous Lidocaine vs. Fentanyl for intraoperative pain Patients Undergoing Elective 
Gynecologic Surgery under General Anesthesia at Dilla University General and Teaching Hospital 
and Hawassa University Comprehensive and Specialized Hospital from April 10, 2023 to June10, 
2023- A Multi-Centered Randomized Controlled Trial 
Purpose of the study 
Surgical pain is the worst and most severe type of pain that requires analgesics to alleviate. Opioids 
have been the cornerstone of intraoperative analgesia for decades. Despite opiate-related side 
effects like shivering, nausea, and vomiting; an increased postoperative pain scale; decreased post-
operative patient satisfaction; and more, some are disfavoring opiate use intraoperatively. Opoid-
free anesthesia is a recent idea aimed at averting opioid-related adverse effects. The purpose of 
this research is to determine the Effectiveness of intraoperative use of Low-Dose Ketamine and 
Intravenous Lidocaine vs. with Fentanyl for Patients Undergoing Elective Gynecologic Surgery 
under General Anesthesia at Dilla University General and Teaching Hospital and Hawassa 
University Comprehensive and Specialized Hospital from April 10, 2023 to June10, 2023. 
Interventions: The study will involve two groups of patients, with the study group undergoing 
surgery under intraoperative opiate-free anesthesia with low-dose ketamine and IV lidocaine and 
the control group receiving standard general anesthesia with opiate (fentanyl 1-3µg/kg).  

 
 
ii 
 
At doses of up to 3-5 mg/kg intramuscularly and 2 mg/kg intravenously, ketamine is a general 
anesthetic that has been used for many years as a non-barbiturate dissociative anesthetic. It was 
linked to sympathetic stimulation and hallucination at doses greater than or equal to 2 mg/kg. 
Ketamine at low doses of up to 1 mg/kg induces analgesia and only mild sedation. The medications 
have been utilized within this dose as a management tool for intraoperative shivering and as 
additional analgesics in multimodal analgesia. When administered intravenously at the 
recommended low dose, it has been reported to have no known side effects. 
Lidocaine is a local anesthetic and anti-arrhythmic drug that has been used intramuscularly to 
block neuromuscular transmission by reversibly inhibiting the generation and propagation of 
action potentials acting on the sodium channel. Intravenous lidocaine is a recent advancement in 
drug preparation that is additive-free. It is documented as having analgesic, anti-inflammatory, and 
decreasing postoperative pain score at IV doses up to 2 mg/kg. Additionally, when used with 
multimodal analgesia, the drug was documented to avoid opioid-related adverse events. 
Lidocaine with additives like adrenaline and sodium carbonate is contraindicated for intravenous 
use. In addition, doses greater than 3 mg/kg are related to adverse effects like tinnitus, vertigo, and 
respiratory compromise, and a much higher dose can result in cardiac arrest. Mostly, IV lidocaine 
is given as a 1.5 mg/kg bolus or infusion, and this dose, when used up to 24 hours, has no reported 
adverse effects.      
Procedure: We call all interested individuals to participate in the study aimed to determine the 
safety and efficacy of opioid-free anesthesia compared with standard general anesthesia with 
opioids in improving the quality of postoperative patient recovery and avoiding opioid-related 
adverse effects such as increased postoperative pain scale, PONV, shivering, and others. You will 
be asked for some information about your situation and health status. With your permission, some 
data will be recorded from your chart, and you will be asked to be monitored for about two days 
after your operation. 

 
 
iii 
 
You will be asked to sign the consent form that explains your willingness to participate in the study 
before the start of the study. You do not have to take part in this research if you do not wish to, 
and refusing to participate will not affect your treatment at this hospital in any way. You will still 
have all the benefits that you would otherwise have at this hospital. You may stop participating in 
the research at any time that you wish without losing any of your rights as a patient here. None of 
your information will be exposed, and all of your data will be coded, including your name. 
Inducement and privateness 
There will be nothing gained by taking part in this study. The information collected from the study 
will be kept confidential and only accessible by the main researcher and the data monitoring 
committee. The data will be coded and locked, with no labeling identifying you or anyone else 
participating in the study, which will only be accessed by the main investigator. The proposal for 
the study will be reviewed and approved by the IRB of the DURTH, and ethical clearance will be 
obtained. 
 
 
 
 
Withdrawal from study 
You will have complete freedom to refuse at any time during the research. You will not be harmed 
or injured in any way by refusing to participate in the research. If you do not want to participate in 
this study, it will not have a positive or negative impact on you during your stay here in our 
hospital.  
You are being asked to take part in a research study. Before you decide to participate in this study, 
it is important that you understand why the research is being done and what it will involve. Please 
read the following information carefully. Please ask the researcher if there is anything that is not 
clear or if you need more information. 
Contacts when anything happened  
You can contact the following personnel from the data monitoring committee anytime you need  

 
 
iv 
 
Voluntary participation  
Your participation in this study is voluntary. It is up to you to decide whether to take part in this 
study. If you decide to take part in this study, you will be asked to sign a consent form. After you 
sign the consent form, you are still free to withdraw at any time and without giving a reason. 
Withdrawing from this study will not affect the relationship you have, if any, with the researcher. 
If you withdraw from the study before data collection is completed, your data will be returned to 
you or destroyed. 
 
 
 

 
 
v 
 
Informed consent 
This consent form is aimed at inviting participants who are going to have an operation to participate in the 
study, which is collecting information for research on the safety and efficacy of opioid-free anesthesia 
compared with conventional anesthesia with opioids at Dilla University Referral and Teaching Hospital, 
Ethiopia 2023. 
 
I am _____________, a member of the research team. We are performing a study on the safety of 
opioid-free anesthesia. I am going to give you information and invite you to be part of this research. 
Before you decide, you can talk to anyone you feel comfortable with about the research. If there are 
any words that, you do not understand. Please ask me to stop as we go through the information, and 
I will take the time to explain. You can ask me any more questions about any part of the research 
study if you wish to. Do you have any questions?  
CONSENT  
I have read and understand the provided information and have had the opportunity to ask questions. 
I understand that my participation is voluntary and that I am free to withdraw at any time, without 
giving a reason and without cost. I understand that I will be given a copy of this consent form. I 
voluntarily agree to take part in this study. 
Participant's signature ______________________________ Date __________  
Investigator's signature _____________________________ Date __________ 
 
 
 
 
 
 

 
 
vi 
 
Informed consent Amharic Language Version 
 
 በመረጃ የተደገፈ የስምምነት ቅጽ 
ይህ በመረጃ የተደገፈ የስምምነት ፎርም በዲላ ዩኒቨርሲቲ አጠቃላይ እና ማስተማሪያ ሆስፒታል እና በሀዋሳ ዩኒቨርሲቲ 
ኮምፕረሄንሲቭ እና ስፔሻላይዝድ ሆስፒታል በአጠቃላይ ሰመመን ውስጥ የማህፀን ቀዶ ጥገና ለሚደረግላቸው 
ታካሚዎች ነው። የጥናታችን ርዕስ “ከopoid ነፃ አጠቃላይ ማደንዘዣ እና የተለመደ አጠቃላይ ማደንዘዣ ከኦፒዮይድ 
ጋር ያለዉን ውጤታማነት እና ደህንነት በምርጫ ላይ የተመሰረተ የማህፀን ቀዶ ጥገና ለሚደረግላቸው ለአዋቂ 
ታካሚዎች፡ በዘፈቀደ፣በቁጥጥር የሚደረግ እና ብዙ ማእከል ያለው ሙከራ፤ በዲላ ዩኒቨርሲቲ አጠቃላይ እና 
ማስተማሪያ ሆስፒታል እና በሀዋሳ ዩኒቨርሲቲ ኮምፕረሄንሲቭ እና ስፔሻላይዝድ ሆስፒታል በኢትዮጵያ፣ በ2015 ዓ.ም  
የዋናው ተመራማሪ ስም፡-  አማኑኤል አሰፋ አኔቴዥያ ት/ት ክፍል የሁለተኛ ድግሪ ተማሪ 
የድርጅቱ ስም፡-  ዲላ ዩኒቨርሲቲ ሪፈራል ሆስፒታል፣ የህክምና እና ጤና ሳይንስ ኮሌጅ የአንስቴዚዮሎጂ ት/ት ክፍል 
ስፖንሰር ያደረገዉ ተቋም፡-  
ዲላ ዩኒቨርሲቲ 
የተመራማሪ ኢሜል አድራሻ  
dawona1@gmal.com 
የተመራማሪ ስልክ ቁጥር  
+251925230585/+251979721905 
በዚህ ምርምር ጥናት ላይ እንድሳተፉ እየተጠየቅን ነው። በዚህ ጥናት ውስጥ ለመሳተፍ ከመወሰንዎ በፊት ጥናቱ 
ለምን እንደሚደረግ እና ምን እንደሚያጠቃልል መረዳትዎ አስፈላጊ ነው። እባክዎ የሚከተለውን መረጃ በጥንቃቄ 
ያንብቡ። ግልጽ ያልሆነ ነገር ካለ ወይም ተጨማሪ መረጃ ከፈለጉ ተመራማሪውን ይጠይቁ። 
 
የጥናቱ ዓላማ: 
የቀዶ ጥገና ህመም የህመም ማስታገሻ መድሃኒቶችን የሚፈልግ በጣም የከፋ እና በጣም ከባድ 
ህመም መሆኑ ይታወቃል። እንደ መንቀጥቀጥ፣ ማቅለሽለሽ እና ማስታወክ ካሉ የተዛመዱ የጎንዮሽ ጉዳቶች 
ቢኖሩምኦፖይዶች ለብዙ አሥርተ ዓመታት በቀዶ ሕክምና ውስጥ የህመም ማስታገሻዎች የማዕዘን ድንጋይ ሆነዉ 
የቆዩ ናቸዉ።  ከቀዶ ጥገና በኋላ የሕመም መጠን መጨመር; ከቀዶ ጥገና በኋላ የታካሚ እርካታ መቀነስ; እና 
በሌሎችም የጎንዮሽ ጉዳቶች አንዳንድ ሀኪሞች በቀዶ ሕክምና ውስጥ ኦፖይድን መጠቀምን አይወዱም። ኦፖይድ-
ነጻ ማደንዘዣ ከላይ የተጠቀሱ ከኦፒዮይድ ጋር የተዛመዱ አሉታዊ ተጽእኖዎችን ለማስወገድ የታለመ የቅርብ ጊዜ 
የሀሳብ ትግበራ ነው። የዚህ ጥናት ዓላማ በዲላ ዩኒቨርሲቲ ሪፈራል እና ማስተማሪያ ሆስፒታል ከመጋቢት 22 2015 
ዓ.ም እስከ ሰኔ 22 2015 ዓ.ም ባለው ጊዜ ውስጥ በአጠቃላይ ማደንዘዣ ውስጥ በምርጫ ቀዶ ጥገና ለሚደረግ 
አዋቂ ታካሚዎች ከኦፒዮይድ-ነጻ ማደንዘዣ እና መደበኛ አጠቃላይ ሰመመን ያለውን ውጤታማነት እና ደህንነት 
ለመወሰን ነው። 

 
 
vii 
 
ጣልቃ-ገብነት፡ 
 ጥናቱ ሁለት ቡድኖችን ያካተተ ሲሆን የጥናት ቡድኑ (ከኦፖይድ ነፃ ማደንዘዣ) በዝቅተኛ መጠን 
በደም ሥር ዉስጥ የሚሰጥ “ketamine ኢና lidocaine” የሚባሉ መዲሃኒቶችን ስወስድ የቁጥጥር ቡድኑ መደበኛ 
አጠቃላይ ሰመመን ከኦፒዮይድ መድኃኒቶችን ይቀበላል።  
እስከ 3-5 mg/kg በጡንቻ ውስጥ እና 2mg/kg በደም ውስጥ የሚሰጥ “ketamine” ለአጠቃላይ ማደንዘዣ 
የሚሰጥ መድሃኒት ሲሆን ለብዙ አመታት እንደ “barbiturate dissociative” ማደንዘዣ ሆኖ ሲያገለግል ቆይቷል። 
ከ 2 mg/kg በላይ ወይም እኩል በሆነ መጠን ከርህራሄ ማነቃቂያ እና ቅዠት ጋር ተያይዟል። እስከ 1 mg/kg 
ባለው ዝቅተኛ መጠን ያለው “ketamine” ደግሞ ህመምን በማስታገስ እና ቀለል ያለ ዕንቅልፍ በማስተኛት 
ይታወቃል። መድሃኒቱ በዚህ መጠን በቀዶ ሕክምና ወቅት   ለሚፈጠር መንቀጥቀጥ እና እንደ መልቲሞዳል የህመም 
ማስታገሻ መድሃኒት ተጨማሪ የህመም ማስታገሻዎች ጥቅም ላይ ውለዋል። በተመከረው ሙከራዎችም ዝቅተኛ 
መጠን በደም ውስጥ በሚሰጥበት ጊዜ ምንም አይነት የጎንዮሽ ጉዳት እንደሌለው ተዘግቧል። 
“Lidocaine” ደግሞ በሴላችን ዉስጥ ባለዉ “sodium channel” በሚባል መረጃ ተቀባይ ላይ በመስራት የነርቭ 
ጡንቻ ስርጭትን ለመግታት በመጀመሪያ በጡንቻ ውስጥ ጥቅም ላይ የዋለ ማደንዘዣ ነው። በደም ውስጥ የሚሰጥ 
lidocaine ከተጨማሪ ነገር ነፃ የሆነ የመድኃኒት ዝግጅት እና የቅርብ ጊዜ ግኝት ነው። የህመም ማስታገሻ እና ፀረ-
ብግነት ውጤቶች እንዳሉት ሆኖ እስከ 1 mg/kg ስንጠቀም ከቀዶ ጥገና በኋላ የህመም ደረጃዉን እንደሚቀንስ 
ተመዝግቧል። በተጨማሪም፣ ከመልቲ ሞዳል የህመም ማስታገሻ ጋር ጥቅም ላይ ሲውል፣ መድሃኒቱ ከኦፕዮይድ ጋር 
የተገናኙ አሉታዊ ክስተቶችን ለማስወገድ እንደሚጠቅም ተመዝግቧል። 
Lidocaine እንደ አድሬናሊን እና ሶዲየም ካርቦኔት ካሉ ከተጭማሪ ነገሮች ጋር ከተዘጋጀ ለደም ሥር ጥቅም 
የተከለከለ ነው። እንዲሁም ከ 3 mg/kg በላይ እንደ ጆሮ ዉስጥ እንደመጮህ፣ ማዞር እና የመተንፈሻ አካላት ችግር 
ካሉ አሉታዊ ውጤቶች ጋር የተገናኙ ናቸው፣ በጣም ከፍ ያለ መጠን የልብ ድካም ሊያስከትል ይችላል። በአብዛኛው, 
በደም ውስጥ የሚሰጥ lidocaine የሚሰጠው እስከ 2 mg/kg በአንዴ ወይም በማስከተል, እና ይህ መጠን እስከ 
24 ሰዓታት ድረስ ጥቅም ላይ ሲውል, ምንም የጎንዮሽ ጉዳት አልተመዘገበበትም። 
የአሰራር ሂደት፡-  ከኦፒዮይድ ነፃ የሆነ ሰመመን ከመደበኛ ኦፖይድ ጋር የሚሰጥ ሰመመን ጋር በማነፃፀር ከቀዶ 
ጥገና በኋላ የማገገሚያ ጥራት የማሻሻል እና ከኦፖይድ ጋር የተዛመዱ የጎንዮሽ ጉዳቶችን ለማስቀረት በሚደረገዉ 
ጥናት ላይ ሁሉም ፍላጎት ያላቸው ግለሰቦች እንዲሳተፉ ጥሪ እናስተላልፋለን ። በተጨማሪም ጥናቱ የህመም ደረጃ 
መጨመር፣ ከቀዶ ጥገና በኋላ የሚከሰት ማቅለሽለሽ እና ማስታወክ፣ መንቀጥቀጥ እና ሌሎች የመሳሰሉ የመድሃኒቱን 
ጉዳቶችን ለማስቀረት ያለመ ነዉ። በእርስዎ ፈቃድ ስለ አጠቃላይ ሁኔታዎ እና የጤና ሁኔታዎ የተወሰነ መረጃ 
ይጠየቃሉ፤ የተቀረዉ ደግሞ ከህክምና መረጃ ገበታዎ ይመዘገባል። ከቀዶ ጥገናዎ በኋላም ለሁለት ቀናት ያህል 
ክትትል ይደረግልዎታል። 

 
 
viii 
 
ተነሳሽነት እና ግላዊነት:- በዚህ ጥናት ውስጥ በመሳተፍ ምንም የሚገኝ ጥቅም አይኖርም። ከጥናቱ የሚሰበሰበው 
መረጃ ሚስጥራዊ ሆኖ በዋና ተመራማሪው እና በመረጃ ተቆጣጣሪው ኮሚቴ ብቻ ተደራሽ ይሆናል። ውሂቡ ኮድ 
ተደርጎ ይቆለፋል፣ እርስዎን እና ሌሎች በጥናቱ ውስጥ የሚሳተፉትን የሚለይ መለያ ይኖራል፤ ይህንም የሚያዉቀዉ 
ዋና መርማሪ ብቻ ነው። ጥናቱ ከመጀመሩ በፊትየጥናቱ ሙሉ የጥናት ሀሳብ በዩኒቨርሲቲዉ ተቋማዊ ግምገማ ቦርድ 
ተገምግሞ እና ጸድቆ የስነምግባር ማረጋገጫ ያገኛል። 
ከጥናት መውጣት:- በማንኛውም ጊዜ ትናቱን አቋርጠዉ የመዉጣትሙሉ ነፃነት ይኖርዎታል። በጥናቱ ውስጥ 
ለመሳተፍ ፈቃደኛ ባለመሆኑዎ እዚህ በሆስፒታል በሚቆዩበት ጊዜ በምንም መልኩ አይጎዱም፤ በዚህ ሆስፒታል ውስጥ 
ሊኖሯቸው የሚችሏቸው ሁሉንም ጥቅሞች ይኖሩዎታል። ጥናቱ ከመጀመሩ በፊት በጥናቱ ለመሳተፍ ፈቃደኛ 
መሆንዎን የሚገልጽ የስምምነት ቅጽ ላይ እንዲፈርሙ ይጠየቃሉ። ካልፈለጉ በዚህ ጥናት ውስጥ መሳተፍ የለብዎትም። 
እዚህ እንደ ታካሚ ምንም አይነት መብትዎን ሳያጡ በፈለጉት ጊዜ በምርምር መሳተፍን ማቆም ይችላሉ። የትኛውም 
መረጃዎ አይጋለጥም እና ሁሉም ውሂብዎ ስምዎን ጨምሮ ኮድ ይደረጋሉ። 
 
 
 
እርዳታ በሚያስፈልግበት ጊዜ የሚገናኙበት 
መረጃ በሚፈልጉበት ጊዜ ከቁጥጥር ኮሚቴ የሚከተሉትን ማግኘት ይችላሉ። 
1) ስለሺ ሃይሉ ረዳት ፕሮፌሰር ኢና የዲላ ዩኒቨርሲቲ የአኔስትዮሎጂ ት/ት ክፍል መምህር 
                ስልክ ቁጥር፡- +251 91 378 5100 
2) መስፍን ጉርሙ የዲላ ዩኒቨርሲቲ የአኔስትዮሎጂ ት/ት ክፍል መምህር 
                  ስልክ ቁጥር፡- +251 92 408 1119 
3) በላይ በቀለ የዲላ ዩኒቨርሲቲ የአኔስትዮሎጂ ት/ት ክፍል መምህር 
      ስልክ፡ +251938511104 
በፈቃደኝነት ተሳትፎ:- በዚህ ጥናት ውስጥ ያለዎት ተሳትፎ በፈቃደኝነት ነው። በዚህ ጥናት ውስጥ ለመሳተፍ ወይም 
ላለመሳተፍ መወሰን የእርስዎ ውሳኔ ነው። በዚህ ጥናት ለመሳተፍ ከወሰኑ፣ የስምምነት ፎርም እንዲፈርሙ ይጠየቃሉ። 
የስምምነት ቅጹን ከፈረሙ በኋላ በማንኛውም ጊዜ ምክንያትዎን በመናገር ከጥናቱ ለመውጣት ነፃ ነዎት። ከዚህ 
ጥናት መውጣት ከተመራማሪው ጋር ወይም ከሆስፒታሉ ጋር ያለዎትን ግንኙነት አይጎዳውም:: መረጃ መሰብሰብ 
ከመጠናቀቁ በፊት ከጥናቱ ከወጡ፣ የእርስዎ ውሂብ ባለዉ መረጃ በጥናቱ ውጤት ውስጥ ይካተታል። 

 
 
ix 
 
በመረጃ የተደገፈ ስምምነት 
ይህ የስምምነት ፎርም ኦፕራሲዮን የሚደርጉ ተሳታፊዎችን በጥናቱ ላይ እንዲሳተፉ ለመጋበዝ ሲሆን ይህም በዲላ 
ዩኒቨርሲቲ ሪፈራል እና ማስተማሪያ ሆስፒታል የተለመደውን የኦፖይድ ሰመመን ከኦፒዮይድ-ነጻ ሰመመን ደህንነት 
እና ውጤታማነት ጋር በማነጻጸር ለምርምር መረጃን በማሰባሰብ ላይ ነው። 
እኔ ____________________________________  የምርምር ቡድን አባል ነኝ። ከኦፒዮይድ-ነጻ ማደንዘዣ 
ደህንነት ላይ ጥናት እያደረግን ነው። መረጃ እንድጸጥ እና የዚህ ጥናት አካል እንድሆኑ እጋብዛለሁ። ከመወሰንዎ 
በፊት, ስለ ጥናቱ ምቾት የሚሰማዎትን ማንኛውንም ጥያቄ ማንኛዉንም ሰው ማነጋገር ይችላሉ. ከፈለጉ ስለ 
የትኛውም የዳግም ፍለጋ ጥናት ክፍል ተጨማሪ ጥያቄዎችን መጠየቅ ይችላሉ። 
ስምምነት 
የቀረበውን መረጃ አንብቤ ወይም ተነቦልኝ ተረድቻለሁ፤ ጥያቄዎችንም ለመጠየቅ እድሉን አግኝቻለሁ። የእኔ ተሳትፎ 
በፈቃደኝነት እንደሆነ ተረድቻለሁ፤ በማንኛውም ጊዜ ምክንያቴን ገልጬ ያለምንም ከልካይ ለመልቀቅ ነፃ መሆኔን 
ተረድቻለሁ። ጥናቱ ከመጀመሩ በፊት የዚህ የስምምነት ቅጽ ቅጂ እንደሚሰጠኝ ተረድቻለሁ። በዚህ ጥናት ለመሳተፍ 
በፈቃዴ ተስማምቻለሁ። 
የተሳታፊ ስም እና ፊርማ _______________________________________________ ቀን ____________ 
የመርማሪው ስም እና ፊርማ ____________________________________________ ቀን ____________