Clinical trial NCT03643796
Conditions: Anterior Cervical Discectomy and Fusion (ACDF)
Sponsor: University of Arkansas
Start date: 2018-07-15; Completion date: 2022-07-05
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will help the investigators learn more about the best way to give anesthesia for these kinds of surgery. The investigators will be using 2 different groups of medications that is commonly used in ACDF surgery, one group has a Narcotic, and the other group does not. The investigators wish to test whether a narcotic free anesthetic will result in an overall safer surgery, better patient recovery, and satisfaction. The investigators think also that eliminating the Narcotic from the Anesthetic regimen will allow patients to recover faster after surgery , and consume less pain medicines in the postoperative period.

Detailed description:

Arms: arm 1: Remifentanil infusion of 0.05 to 0.2 mcg/kg/minute started just prior to induction and stopped at emergence from anesthesia. arm 2: dexmedetomidine bolus of 0.5 mcg/kg over 10 minutes starting 5 minutes prior to induction followed by an infusion of 0.2-0.7 mcg/kg/hour that will be stopped with the start of closing the surgical wound.

Ketamine infusion of 2 mcg/kg/minute will be started at induction. It will be stopped at the beginning of the emergence from anesthesia, roughly 45 minutes from extubation.
Interventions: intervention 1: Remifentanil intervention 2: Ketamine intervention 3: Dexmedetomidine
Intervention descriptions: intervention 1: Remifentanil infusion of 0.05 to 0.2 mcg/kg/minute started just prior to induction and stopped at emergence from anesthesia. intervention 2: Ketamine infusion of 2 mcg/kg/minute will be started at induction. It will be stopped at the beginning of the emergence from anesthesia, roughly 45 minutes from extubation. intervention 3: dexmedetomidine bolus of 0.5 mcg/kg over 10 minutes starting 5 minutes prior to induction followed by an infusion of 0.2-0.7 mcg/kg/hour that will be stopped with the start of closing the surgical wound.

Protocol documents:
Prot_SAP_000.pdf: 
Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 1 
University of Arkansas for Medical Sciences (UAMS) Clinical Protocol 
 
Study Title 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the 
incidence of unacceptable movements under general 
Anesthesia during  ACDF (Anterior Cervical Discectomy and 
Fusion) surgery: A Randomized Controlled Trial 
 
Principal Investigator: 
Mohamed Abdeldayem, MD, PhD 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone:  (224) 427-9747 
Email:  maabdeldayem@UAMS.EDU 
 
 
Sub-Investigator (s): 
Trevor Wright, DO 
 
University of Arkansas for Medical Sciences 
 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone:  (501) 603-1656   
Email:  tbwright@uams.edu 
 
 
Benjamin Keating, MD 
 
University of Arkansas for Medical Sciences 
 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone:  (501) 686-7565   
Email:  BGKeating@uams.edu 
 
Caesar Augustus Guevara, CRS 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot # 515 
Little Rock, AR 72205 
Telephone:  (501) 766-4392   
Email:  CAGuevara@uams.edu 
 
 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 2 
 
Study location: 
University of Arkansas for Medical Sciences  
4301 W. Markham Street 
Little Rock, AR  72205 
 
 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 3 
Table of Contents 
Table of Contents ............................................................................................................... 3 
Background and Rationale ................................................................................................. 4 
Hypothesis .......................................................................................................................... 4 
Primary Outcome ................................................................................................................ 5 
Secondary Outcomes ......................................................................................................... 5 
Study Design and Procedures ........................................................................................... 6 
Remifentanil (R) Group ................................................................................................... 6 
Ketamine and Dexmedetomidine (KT) Group ................................................................ 6 
Study Population ................................................................................................................ 8 
Inclusion Criteria ............................................................................................................. 8 
Exclusion Criteria ............................................................................................................ 8 
Adverse Events................................................................................................................... 9 
Definitions ....................................................................................................................... 9 
Adverse Event Reporting Period .................................................................................. 10 
Pre-existing Condition................................................................................................... 10 
General Physical Examination Findings ...................................................................... 10 
Post-study Adverse Event ............................................................................................ 10 
Abnormal Laboratory Values ........................................................................................ 10 
Hospitalization, Prolonged Hospitalization or Surgery................................................. 11 
Recording of Adverse Events ....................................................................................... 11 
Reporting Procedures for Adverse and Serious Adverse Events ............................... 12 
Data Safety and Monitoring Plan.................................................................................. 12 
Medical Monitor ............................................................................................................. 12 
Risks and Benefits ............................................................................................................ 12 
Data Handling and Recordkeeping .................................................................................. 13 
Data Analysis .................................................................................................................... 14 
Ethical Considerations ...................................................................................................... 14 
Dissemination of Data ...................................................................................................... 15 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 4 
References........................................................................................................................ 15 
Appendices ....................................................................................................................... 15 
 
Background and Rationale 
Anterior Cervical Discectomy and fusion (ACDF) is one of the most common spine 
surgeries, with patients typically presenting with neck pain and possibly some 
neurological deficits in their upper or lower limbs.  Given the critical location of the 
surgery on the neck and being very close to the cervical spinal cord, neurophysiological 
monitoring is routinely used to insure safety and help guide the surgeon.  The use of 
remifentanil-based total intravenous anesthesia (TIVA) to facilitate neurophysiological 
monitoring for neurosurgery has become a common/standard of care. 
Neurophysiological monitoring such as transcranial motor-evoked potentials (TC-MEPs) 
and somatosensory evoked potentials (SSEPs) are routinely done under an anesthetic 
regimen that includes propofol infusion, 0.5 minimum Alveolar Concentration (MAC)I or 
less of sevoflurane and remifentanil infusion without muscle relaxation. 
Remifentanil is an excellent medication that possesses an ultrashort half-life, reliable 
hemodynamic stability, decreased inappropriate patient movement profile under general 
anesthesia and a favorable effect on the quality of neuromonitoring.1  
Some detractors of remifentanil has been its association with postoperative 
hyperalgesia and increased postoperative narcotic consumption which may lead to an 
increase incidence of postoperative side effects related to narcotic analgesics. 
Recent attention to the overall use of narcotics and their social and medical impact has 
increased interest in narcotic-sparing anesthesia regimens. 
Ketamine Low dose infusion, Lidocaine infusion, and Dexmedetomidine infusion are all 
drugs that have been used successfully as narcotic sparing drugs, and proved to 
decrease stress response of surgery, improve patient recovery, decrease narcotic 
consumption and decrease postoperative length of stay, thus overall decreasing 
hospital costs, and improving patient outcome. The use of these drugs has been 
investigated in multiple studies as single drug infusion or in a multimodal approach3,4  .  
Hypothesis 
We hypothesize a multimodal approach to intraoperative analgesia, without remifentanil, 
based on dexmedetomidine and ketamine infusion, provides a safe, and a, 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 5 
hemodynamically stable anesthesia, with the added benefits of decreased postoperative 
narcotic consumption. 
Primary outcome: 
 
1. The incidence of unacceptable movement(UM) that is induced by nociception, or 
head manipulation and positioning by the surgical or anesthesiology Team or 
during a Motor evoked potential stimulation and defined as (gross visible 
movement reported by the Anesthesia or surgical team, bucking, chewing, or 
reaching to the endotracheal tube).  
The total number of occurrences for each case, and the total number of patients 
experiencing any UM for each of the study arms will be measured. 
 
Secondary outcomes: 
       
1. Heart rate and blood pressure will be recorded from Arterial line. The 
hemodynamic stability is defined as any increase in the heart rate by more 
than 20% of the base line. Base line recording will be calculated as the average 
of the readings taken in the preop- holding area and the reading  that is recorded 
before induction of Anesthesia. Number and length of occurrences will be 
measured.  Heart rate and blood pressure will be assessed per standard of care 
and the study data will be taken from the medical record. 
 
2. Time to Extubation will be calculated from the time where the attending 
Anesthesiologist start emergence from Anesthesia till time of Extubation. 
Extubation Criteria will be eye opening, or toe wiggling or hand squeeze in 
response to verbal command. 
 
3. Pain Scores will be assessed  per standard of care and the study data will be taken 
from the medical record. Narcotic consumption in PACU, 24 hours will be 
calculated and transferred to morphine equivalents. Modified Aldrete score will be 
used as a criteria for readiness of the patient for PACU discharge. 
 
4. Psychometric assessment of recovery from general anesthesia will be assessed 
using Quality of Recovery score, QoR-15. Assessment will be done twice first time 
in the preoperative holding area, and second on the following morning after 
surgery. Answers of the questions are given scores from 1 to 10 on a Likert scale. 
The score ranges from 0 to 150 and the questionnaire is designed to assess the 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 6 
emotional state, physical comfort, psychological support, physical independence, 
and pain.  
Study Design and Procedures 
We intend to approach patients scheduled for ACDF surgery, as all of these cases will 
require neurophysiological monitoring and a subsequent anesthetic technique based on 
total intravenous anesthesia with no paralysis.  Additionally, a majority of these patient 
group will not have a chronic pain diagnosis which will mandate the use of high doses of 
intraoperative narcotics. 
Study personnel will approach prospective subjects either during their pre-surgery clinic 
visit (preferably) or the day of surgery, before any pre-operative medications have been 
administered. 
This study will be randomized, controlled trial consisting of two treatment groups: 
Remifentanil (R) Group 
Remifentanil is a short-acting synthetic opioid analgesic drug structurally related to 
fentanyl and other piperidine-based analgetics 
The remifentanil (R) group will have a remifentanil infusion of 0.05 to 0.2 mcg/kg/min 
started just prior to induction and stopped at emergence from anesthesia.  Remifentanil 
is a highly hydrophilic narcotic with high potency and short-context sensitive half-life.  
The remifentanil dose will be adjusted depending on the patient age, weight, blood 
pressure, and sex as determined by the attending anesthesiologist based on their 
clinical Judgment. 
Ketamine and Dexmedetomidine (KT) Group 
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that induces 
dissociative amnesia and analgesia.  Dexmedetomidine is alpha2-adrenergic agonist 
anesthetic with sedative properties. 
The ketamine and dexmedetomidine (KT) Group will receive a dexmedetomidine bolus 
of 0.5 mcg/kg over 10 minutes starting 5 minutes prior to induction followed by an 
infusion of 0.2- 0.7 mcg/kg/hr that will be stopped with the start of closing the surgical 
wound.  The ketamine infusion shall be started at induction and will be 2 mcg/kg/min, it 
shall be stopped at the beginning of emergence from anesthesia, roughly 45 minutes 
prior to extubation.  The dexmedetomidine and ketamine bolus and infusion will be 
titrated at the clinical judgment of the attending anesthesiologist based on the age, 
weight, and heart rate of the patient in the same manner he/she would manage those 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 7 
medications any other clinical situation.  The doses used for the study is the normal 
clinical range that is used within standard clinical practice and the attending 
anesthesiologist will be manipulating the doses of the drugs within the ranges stated in 
this protocol  
Each treatment group will receive a balanced general anesthesia based on the 
discretion of the attending anesthesiologist.  A propofol infusion titrated to a bispectral 
index (BIS) of 40-60 combined with 0.5 Monitored MAC of sevoflurane will be used to 
maintain anesthesia. 
The attending Anesthesiologist from the UAMS Anesthesiology department will receive 
a closed envelope 15 minutes before the procedure with the case code and assigned 
group. The randomization will be computer based.  Using MS Excel software, study 
subject numbers will be entered to spread sheet, numbered from 1 through 80, and the 
software will be used to randomly assign each number to one of the 2 groups. The 
Envelopes will be prepared and handed to the attending anesthesiologist by the study 
personnel. 
Any attending anesthesiologist would be asked to do the case, but the consent process 
will be always done by the research personnel.  The study drugs will be then checked 
out from the operating room pharmacy and prepared for infusion in the regular manner 
as within the usual clinical situation. All the prepared drugs will be prepared out of site of 
the blind assessor. The assessor (surgeon, surgical resident, or study personnel) will be 
blinded to the regimen used and will be asked to monitor for the incidence of 
inappropriate movements. 
We will define inappropriate movements as any movement that is visible by the surgical 
team. Patient movements under general Anesthesia might occur, and commonly seen 
by the surgical team during surgical stimulation especially in non-paralyzed Patients, 
and usually communication between surgical team and Anesthesia personnel will occur. 
Anesthesia response is usually deepening the Anesthetic level or giving muscle 
relaxants. In the case of ACDF surgery Muscle relaxants cannot be used as part of the 
neuromonitoring prerequisites. We are monitoring the incidence of inappropriate 
movements, and hemodynamic stability as signs of adequate levels of depth of 
anesthesia and pain management under general anesthetic regimen in the 2 groups. 
The attending anesthesiologist, and resident or Certified Nurse Anesthetist (CRNA) will 
be aware of the study group.  The primary surgeon or surgical resident will be 
functioning as a blinded observer counting the incidence of inappropriate movements.  
The postoperative evaluators who will be a study staffer (another attending 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 8 
anesthesiologist, or resident physician) will be blinded of the study group and will be 
asked to conduct the Quality of Recovery (QoR) questionnaire.  All other data collected 
will be part of the patient chart and will be collected by the study personnel. 
The following subject demographics will be collected from the patient record: 
1. 
Age 
2. 
Sex 
3. 
Weight 
 
All patients having ACDF surgery will stay in the hospital as inpatients for at least 24 
hours post-operatively as a standard of care.  With timing of our QoR questionnaire we 
will be able to follow up all of our patients and at the same time do not affect their 
standard postoperative care plan. The QoR questionnaire is completed for research 
purposes only and is not part of the standard of care.  The questionnaire will be 
administered by study personnel. 
Study Population 
We will include 18-80 year old men and women presenting for an (ACDF) surgery of 1-2 
levels.  These patients will be required to fall into the Anesthesiology Society of America 
(ASA) classification 1, 2, or 3 and must consent to their participation.  Should the 
patients have a history of seizure disorder or refuse to participate they will be excluded 
from the study. 
Inclusion Criteria 
• Men and women 18- to 80-years old 
• ASA 1, 2, 3 
• 1 or 2 levels ACDF 
Exclusion Criteria 
• ASA 4 
• Seizure disorders 
• Chronic narcotic use  
• Opiate abuse 
• Major cardiac comorbidity, or significantly elevated blood pressure 
• Known hypersensitivity to fentanyl analogs, ketamine, or propofol injectable 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 9 
emulsions. 
• Known allergy to eggs, egg products, soybeans, or soy products 
Adverse Events 
Definitions 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence that develops or worsens in 
severity during the course of the study, whether or not it has a causal relationship to the 
study treatment. Concurrent illnesses or injuries should be regarded as AEs. Abnormal 
results of diagnostic procedures are considered AEs if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
Serious Adverse Event 
Adverse events are classified as serious or non-serious. A serious adverse event 
(SAE) is any AE that is: 
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance.  They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  For example, 
drug overdose or abuse, a seizure that did not result in in-patient hospitalization or 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 10 
intensive treatment of bronchospasm in an emergency department would typically be 
considered serious. 
All adverse events that do not meet any of the criteria for serious should be regarded as 
non-serious adverse events. 
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as 
the period from the initiation of any study procedures to the end of the study treatment 
follow-up.  For this study, the study treatment follow-up is defined as within 1 day 
following the last administration of study treatment. 
Pre-existing Condition 
A pre-existing condition is one that is present at the start of the study.  A pre-existing 
condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period (e.g. if behavior worsens). 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a pre-existing 
condition.  At the end of the study, any new clinically significant findings/abnormalities 
that meet the definition of an adverse event must also be recorded and documented as 
an AE. 
Post-study Adverse Event 
All unresolved AEs should be followed by the investigator until the events are resolved, 
until the events are otherwise stable or the subject is lost to follow-up.  At the last 
scheduled visit, the investigator should instruct each subject to report any subsequent 
event(s) that the subject, or the subject’s personal physician, believes might reasonably 
be related to participation in this study. 
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an AE if any one of the 
following conditions is met: 
• The laboratory abnormality is not otherwise refuted by a repeat test to confirm 
the abnormality 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 11 
• The abnormality suggests a disease and/or organ toxicity 
• The abnormality is of a degree that requires active management; e.g. change of 
dose, discontinuation of the investigational product, more frequent follow-up 
assessments, further diagnostic investigation, etc. 
Hospitalization, Prolonged Hospitalization or Surgery 
Any AE that results in hospitalization or prolonged hospitalization should be 
documented and reported as a SAE unless specifically instructed otherwise in this 
protocol. Any condition responsible for surgery should be documented as an AE if the 
condition meets the criteria for an AE. 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are 
reported as an AE in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a pre-existing condition.  Surgery should not be reported as an 
outcome of an AE if the purpose of the surgery was elective or diagnostic and the 
outcome was uneventful. 
• Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of 
the study, unless it is a worsening or increase in frequency of hospital 
admissions as judged by the clinical investigator. 
Recording of Adverse Events  
At each contact with the subject, the investigator must seek information on adverse 
events by specific questioning and Monitoring in the intraoperative and postoperative 
period and, as appropriate, by examination. Information on all AEs should be recorded 
immediately in the Anesthesia Record.  All clearly related signs, symptoms, and 
abnormal diagnostic procedures results should be recorded also on the Anesthesia 
Record  
All AEs occurring during the study period must be recorded.  The clinical course of each 
event should be followed until resolution, stabilization, or until it has been determined 
that the study treatment or participation is not the cause.  Serious adverse events that 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 12 
are still ongoing at the end of the study period must be followed up to determine the 
final outcome. 
Reporting Procedures for Adverse and Serious Adverse Events 
All adverse and SAEs will be reported in accordance with FDA and local IRB 
requirements. 
All SAEs that meet the IRB’s Unanticipated Problem Involving Risks to Subjects or 
Others (UPIRTSO) requirements must be submitted to the IRB within 10 working days.  
All other SAEs will be submitted to the IRB at continuing review.  Copies of each report 
and documentation of IRB notification and receipt will be kept in the Clinical 
Investigator’s binder. 
Data Safety and Monitoring Plan 
All safety data will be reviewed by the Medical Monitor after each patient and after the 
completion of each cohort.  A Data Safety and Monitoring Board will not be appointed. 
Medical Monitor 
A Medical Monitor (MM) will be selected.  The MM will be a licensed physician who is 
familiar with cardiovascular disease, neurological assessment, and adverse 
neurological outcome.  For this study, the medical monitor will be the Principal 
Investigator.  The MM will review the data collected after each patient.  As part of the 
review, the MM will review all AEs and assure that any SAEs have been reported 
appropriately.  
Risks and Benefits 
We do not anticipate any increase in risk using the multimodal KD anesthetic regimen 
as compared to the R regimen and others.  Narcotic-sparing anesthesia has been 
documented in multiple studies with a favorable clinical outcomes.2,3,4  The attending 
anesthesiologist will always have the ability and prerogative to withdraw the subject 
from the study, stop the study medication and / or administer narcotics if he feels by his 
clinical judgment this is better for the patient. 
Common risks associated with the use of remifentanil include but are not limited to: 
bradycardia, hypotension, pruritus, nausea, vomiting, and apnea. Contraindications to 
its use would include hypersensitivity to it or its components, intrathecal or epidural 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 13 
administration. 
Common risks associated with the use of ketamine include but are not limited to: 
prolonged emergence, confusion, delirium, hallucinations, irrational behavior. 
Contraindications to the use of ketamine would include but not be limited to 
hypersensitivity to it or its components, conditions in which an increase of blood 
pressure would be hazardous, increased intracranial or intraocular pressure (relative).  
Common risks associated with the use of dexmedetomidine include but are not limited 
to: bradycardia, hypotension, hypertension, agitation, constipation, respiratory 
depression.  Contraindications to the use of dexmedetomidine would include but not be 
limited to hypersensitivity to it or its components. 
Should a participant experience any adverse reaction to the medications in the study, 
the medication will be stopped, patient will be treated appropriately as the case with any 
other patient who is outside the study .   
Both of study arm infusions has been used in clinical Practice safely, but if any 
persistent repeating event is occurring with one group, we will stop the whole study.  
As with all clinical research, there exists the risk to the study participants’ privacy 
violated in the form of a loss of confidentiality.  Measures to protect the confidentiality of 
study participants will be implemented as described in the Data Handling and 
Recordkeeping section below. 
There will be no direct benefits to the study participants; however, knowledge gained 
from the study could potentially benefit patients in the future. 
Data Handling and Recordkeeping 
The Principal Investigator will carefully monitor study procedures to protect the safety of 
research subjects, the quality of the data and the integrity of the study.  All study subject 
material will be assigned a unique identifying code or number.  The key to the code (the 
instrument associating the data with subject identity) will be kept in a locked file in the 
principal investigator’s office, if hardcopy, or on a password-protected UAMS server, 
both located behind locked doors in a restricted access area of the UAMS campus.  
Only Mohamed Abdeldayem, M.D. PhD.  Principal Investigator of this protocol will have 
access to the code and information that identifies the subject in this study. 
Once all of the study data have been validated, it will be de-identified by destroying the 
key associating the assigned study number and the subject identity.  The resulting de-
identified data will be retained, and then, ultimately destroyed per UAMS Policy. 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 14 
Data Analysis 
We are expecting to recruit 80 patients to our study, and including 60 to 70 patients in 
the data analysis. Sample Size is based on being able to detect non-inferiority on both 
inappropriate movements, and postoperative narcotic consumption. The samples size 
estimation is based on our experience from similar studies. We defined hemodynamic 
instability as a 20% increase in the heart rate from base line. The Quality of Recovery 
questionnaire will be scored for every patient. Our primary outcome is the incidence of 
intraoperative inappropriate movements, and postoperative narcotic consumption. 
Means(M) and Standard Deviations(STD) will be calculated for each group. We will test 
the non-inferiority of Dexmetetomidine/Ketamine group to Remifentanil group on 
narcotic consumption & inappropriate movement incidence using a 1-tailed Wilcoxon 
rank sum test. Independent t test will be used to compare quality of recovery scores, 
between 2 groups. Non-inferiority on the hemodynamic stability will be assessed using a 
1-tailed t test from a repeated measures ANOVA model. Treatment effect will be 
calculated using difference in means between groups with interim-adjusted 95% 
confidence intervals (CIs). 
Ethical Considerations 
This study will be conducted in accordance with all applicable government regulations 
and University of Arkansas for Medical Sciences research policies and 
procedures.  This protocol and any amendments will be submitted and approved by the 
UAMS Institutional Review Board (IRB) to conduct the study. 
The formal consent of each subject, using the IRB-approved consent form, will be 
obtained before that subject is submitted to any study procedure.  All subjects for this 
study will be provided a consent form describing this study and providing sufficient 
information in language suitable for subjects to make an informed decision about their 
participation in this study.  The person obtaining consent will thoroughly explain each 
element of the document and outline the risks and benefits, alternate treatment(s), and 
requirements of the study. 
The consent process will take place in a quiet and private room, and subjects may take 
as much time as needed to make a decision about their participation.  Participation 
privacy will be maintained and questions regarding participation will be answered.  No 
coercion or undue influence will be used in the consent process.  This consent form 
must be signed by the subject and the individual obtaining the consent.  A copy of the 
signed consent will be given to the participant, and the informed consent process will be 
documented in each subject’s research record. The consent will be done by the 


Study Title: 
Narcotic Free TIVA (Total Intravenous Anesthesia) and the incidence 
of unacceptable movements under general Anesthesia  during  ACDF (Anterior 
Cervical Discectomy and Fusion) surgery: A Randomized Controlled Trial 
PI: 
Mohamed Abdeldayem MD, PhD 
Institution: 
UAMS 
 
Version #: 7 
 
IRB# 207374 
Date: 
04/24/2019 
Page 15 
Principal investigator, attending anesthesiologist or one of the trained study personnel. 
The consent will be done before the patient has received any preoperative sedation or 
medications. 
Dissemination of Data 
Results of this study may be used for presentations, posters, or publications. The 
publications will not contain any identifiable information that could be linked to a 
participant. 
 
References 
1. Beers R, Camporesi E. Remifentanil update: clinical science and utility. CNS 
Drugs.  2004;18:1085–1104. 
2. Shobana Rajan, MD, Matthew T. Hutcherson, BS, Daniel I. Sessler, MD, Andrea 
Kurz, MD, Dongsheng Yang, MS,  Michael Ghobrial,  MD, Jinbo Liu, MD,  and 
Rafi Avitsian, MD: The Effects of Dexmedetomidine and Remifentanil on 
Hemodynamic Stability and Analgesic Requirement After Craniotomy: A 
Randomized Controlled Trial. JNS. 2016:28. 
3. Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z.: 
Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and 
lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, 
double-blinded study. Braz J Anesthesiol. 2015 May-Jun;65(3):191-9. 
4. Ziemann-Gimmel P, Goldfarb AA, Koppman J, Marema RT.: Opioid-free total 
intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric 
surgery beyond triple prophylaxis. Br J Anaesth. 2014 May;112(5):906-11 
 
Appendices 
1. QoR15 questionnaire V2 04.24.2019