The Effects of Dexmedetomidine Dose on Motor Evoked Potentials During Spine Surgery: A Randomized, Single-blind Trial
Phase: PHASE4
Conditions: Spinal Fusion
Sponsor: Hospital for Special Surgery, New York

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VIEW000072 
Study Identification Information
This is the first step in your Human Research Application.  You will automatically be guided
to the appropriate forms needed to complete your submission.
 
1.0
Title: (please do not use initials)
The effect of dexmedetomidine dose on motor evoked potentials during spine
surgery: A randomized, single-blind trial
 
* Short Title for EPIC:
Dexmedetomidine and MEPs during spine surgery (If Not Applicable, please enter
N/A)
 
2.0
Description:
This parallel group, two-arm, randomized superiority trial will compare the effect of
two different doses of dexmedetomidine on motor evoked potentials during spine
surgery.
 
3.0
* Principal Investigator:
Ronald Emerson, MD
 
4.0
Study Contact:
 
 
5.0
Co-Investigators:
First Name
Last Name
Organization
Matthew
Cunningham, MD, PhD
Spine
Kara
Fields
Research
Han Jo
Kim, M.D.
Spine
Frank
Schwab, M.D.
Spine
Michael
Urban, MD PhD
Anesthesiology
 If a name does
not appear in
Co-Investigators
directory, please
contact
zhouy@hss.edu
to have an eCAP
account created.
6.0
Other Study Staff/Collaborators:
FirstName
LastName
Organization
Email
Role
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7.0
* Type of Application:
Clinical Research Proposal
Expedited Retrospective Chart Review
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New Registry
Existing Approved Registry
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Designs.
8.0
Select appropriate funding sources for this study: 
Name
Internally Funded Support
 
Other Funding Sources: 
Note: If the funding source of the study is 'Industry Funded
Support', Clinical Research Administration (CRA) will be
notified.
If your study requires CRA review, please upload applicable documents,
including sponsor protocol, drug brochure, etc :
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ID: 2017-1304
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CRP Information
 
 
1.0
The proposal should be submitted to the appropriate Clinical
Review Panel (CRP) for scientific review. If you are unsure of
which Clinical Review Panel to select, please contact
Barbara Bosco at 212.606.1914 
* 
Name
Neurology
 
 
 
 
 
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ID: 2017-1304
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Regulatory Status of Drugs and Devices
 
1.0
The regulatory status of the drugs or devices in this research
proposal is:
Name
Approved for use by the FDA and being used according to “label” (for approved
indication)
 
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FDA Approved Drugs/Devices
 
1.0
Add all FDA Approved Drugs administered in this study:
Drug Name
Manufacturer
Drug Name (if other)
Manufacturer (if other)
Other
 
Dexmedetomidine
Pfizer
 
 
Propofol
Pfizer
 
 
2.0
Add all FDA Approved Devices administered in this study:
 
Device Name Manufacturer Device Name (if other)
Manufacturer (if other)
View  
 
Cadwell Cascade
Cadwell, Inc.
View  
 
NICOM
Cheetah Medical
 
ID: 2017-1304
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Pharmacy Involvement / Impact to EPIC
1.0
Is this an inpatient study?
  
Yes 
No
 
2.0
* Will this study have Investigational Drug Service involvement?
(Pharmacy will be purchasing/dispensing any medications being
used and/or study requires placebo and patient randomization) 
  
Yes 
No
 
3.0
If the answer to either question is yes, please explain briefly below
AND contact Mylinh Duong at 646.797.8410 (duongm@hss.edu) or
Nicole Oliva at 646.797.8324 (OlivaN@hss.edu).
This is an inpatient study to be performed during surgery.  Anesthetic drugs to be
 

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used are routinely used during surgery and will not require pharmacy involvement.
 
 
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ID: 2017-1304
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Study Locations
 
1.0
Select the Research Facilities where this study will be
conducted:
Facility
HSS
 
1.1 If Other, please specify:
 
2.0
* Is this a multi-Center study?
No
 
 
 
ID: 2017-1304
This section will be reviewed by the appropriate Clinical Review Panel. Each
of the headings in this section must be addressed.
Help 
Specific Aims or Research Questions
 
1.0
What is the condition or intervention to be studied?
We will study motor evoked potentials under two anesthetic conditions, one using
propofol and lower dose of dexmedetomidine, another using a lower dose of
propofol with a higher dose of dexmedetomine during multilevel posterior spinal
fusions.
Please click
Here for
example.
2.0
What is/are the research question(s)/specific aim(s)? Pose
very specific questions that can be addressed within the
proposed design of the study. Prioritize them in order of
 

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importance.
 
Aim 1 (definitive): To compare the percentage of spine cases with monitorable
motor evoked potentials (MEPs) for the purpose of monitoring spinal cord integrity
under two anesthetic conditions, one using a higher dose of propofol and a lower
dose of dexmedetomidine, and the other using a lower dose of propofol and a
higher dose of dexmedetomidine.
Aim 2 (exploratory): To estimate the difference in percentage of spine cases with
monitorable MEPs for the purpose of monitoring nerve root integrity between two
anesthetic conditions.
Aim 3 (exploratory): To estimate the association between MEP metrics (peak to
peak amplitude, waveform integral, waveform line-length, trial variability of peak to
peak amplitude, trial variability of waveform integral, and trial variability of
waveform line-length) and cardiac output. 
3.0
What is/are the hypothesis(es)?
There will be a difference in the percentage of spine cases with monitorable MEPs
for the purpose of monitoring spinal cord integrity under two anesthetic conditions.
 
 
4.0
Identify and define the primary outcome and when the
outcome will be measured. If measuring change in post-
operative function is the most important, that will be your
primary outcome.
Monitorable MEPs for the purpose of monitoring spinal cord integrity (yes vs. no).
 This outcome measure will be assessed during the initial two hours of surgery
following induction of anesthesia and establishment of stable anesthesia.  MEP
recordings will be obtained in sets of 3-4 trials, approximately every 15-20 minutes,
as permitted by the surgeon.
Monitorable will be defined as having MEPs present in 3 muscles in each lower
extremity, with mean peak-to-peak amplitude of at least 50 uV, with mean-
normalized interquartile variability of 0.9 or less. 
 
5.0
Identify and define the secondary outcome(s) and when they
will be measured (list additional goals one at a time with their
corresponding outcomes).
1) Monitorable MEPs for the purpose of monitoring nerve root integrity present at
all assessments (yes vs. no). For this purpose, MEPs will be separately assessed
in quadriceps, tibialis anterior, extensor hallucis longus, medial gastrocnemius and
abductor hallucis in each lower extremity. Monitorable will be defined as having
MEPs with mean peak-to-peak amplitude of at least 50 uV, with mean-normalized
interquartile variability of 0.9, separately for each muscle. This outcome measure
will be made during the first two hours of surgery following induction of anesthesia
 

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and establishment of stable anesthesia.
2) MEPs (peak to peak amplitude, waveform integral, waveform line-length, trial
variability of peak to peak amplitude, trial variability of waveform integral, and trial
variability of waveform line-length) measured in quadriceps, tibialis anterior,
extensor hallucis longus, gastrocnemius, and abductor hallucis. These measures
will be calculated from data recorded throughout the case, following establishment
of stable anesthesia through the conclusion of surgery.
3) Cardiac output, measured continually during surgery.
 
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ID: 2017-1304
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BACKGROUND - Be sure to answer each question individually
 
1.0
Explain why these research questions are being asked:
Many general anesthetic agents can affect MEPs in ways that can make
them difficult to monitor and can confound their interpretation.
 Dexmedetomidine in increasingly being used as a component of total
intravenous anesthesia during surgery requiring MEP monitoring. It is
therefore important to determine the effect of dexmedetomidine of MEPs. 
Optimal fluid management is challenging during complex spine surgery
accompanied by large amounts of blood loss, for reasons detailed in 2.0.  This
study aims to determine if there a correlation between MEP waveform measures
and cardiac output, that could potentially could be useful as a guide to fluid
management. 
Peak-to-peak amplitude is the most commonly clinically employed measure of
MEPs.  For reasons discussed in 2.0, the integral of the rectified waveform or
waveform line-length may be superior measures.  
 
 
 
 
2.0
What is the background of the topic that you believe is
important for the reviewer to know in considering this
protocol, including prior studies by this research team. 
Describe strengths and deficiencies of prior studies; explain
how this study fits in.  Include references.
Motor evoked potentials (MEP), monitored during spine surgery as measures
of spinal cord integrity, are known to be attenuated in a dose related fashion
by nitrous oxide and volatile anesthetic agents.   Propofol has been shown to
better preserve MEPs. For this reason, propofol is commonly used, along
 

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with an opioid and often ketamine, for cases requiring MEP monitoring.  The
addition of dexmedetomidine to total intravenous anesthesia  during spine
surgery has recently been shown to reduce the required propofol dose as
well as improve the quality of recovery, possibly related to decrease the
release of cytokines.  Reduction of propofol dose is desirable, both because
of rare metabolic risks as well as the known effect of delayed emergence [1-
8].  
A challenge for the anesthesiologists during complex spine surgery is to
maintain end organ perfusion despite large blood losses in an attempt to
prevent devastating complications such as spinal cord ischemia, ischemic
optic neuropathy (ION), renal failure, myocardial ischemia and stroke. The
best approach to achieve euvolemia and prevent end-organ ischemia and
metabolic acidosis is still a dilemma. Despite the ubiquitous use of central
venous pressure (CVP) monitoring during large blood loss procedures, there
is a poor direct correlation between CVP and blood volume, as well as the
ability of changes in CVP to predict the hemodynamic response to a fluid
challenge. Volume resuscitation with a pulmonary artery catheter (PAC) has
been shown to be beneficial during adult reconstructive spinal surgery.
However, multiple published reports have questioned the value of PAC
monitoring. Arterial and central venous blood gas analysis may provide
information regarding tissue oxygenation requirements and perfusion. Urine
output alone correlates poorly with adequate tissue perfusion, since oliguria
may be a consequence of excess antidiuretic hormone release rather than
hypovolemia and therefore, attempts to increase urine output intraoperatively
may result in excessive fluid administration. Devices which measure arterial
pulse pressure variation and provide non-invasive cardiac output
measurements have been shown to be efficacious in providing goal directed
fluid therapy during complex spine procedures. The Cheetah NICOM uses
thoracic bioreactance, a measure based on phase modulation of an
oscillating current traversing the thoracic cavity, to noninvasively measure
cardiac output and fluid responsiveness. Cardiac output measured by the
NICOM device has been shown to correlate with measurements made by
thermodilution and pulse contour analysis, and has been found to be
efficacious in fluid management during large blood loss procedures [9-12]. 
Motor evoked potentials are dependent on adequate perfusion in watershed
regions along anterior spinal artery, as well as within the gray matter of the
lumbar enlargement. As such, they are highly sensitive to hemodynamic
effects [13].  Anecdotal observations suggest that MEP changes, particularly
changes observed in MEPs from higher stimulation threshold muscles, may
be early indictors of inadequate perfusion. This study aims to better
characterize this relationship, and determine whether MEP changes precede
changes in measured cardiac output, potentially serving as guides to
fluid management. 
The motor evoked potential signal is a complex polyphasic waveform
comprising the sum of signals generated by individual motor units within the
listening spheres of the recording electrodes; approximately 5% of motor
units in a large muscle are sampled in the typical clinical recording.   Ideally,
a MEP metric would be linearly proportional to the number of motor units
activated.  Although most commonly employed clinically, it is unlikely that
peak-to-peak amplitude is ideal, because the signals from individual motor
units are asynchronous with varying phase relationships, and are influenced

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unevenly by proximity the recording electrodes.  The extreme case,
occasionally encountered, is a large, brief, biphasic signal, with large peak-
to-peak amplitude, probably generated by a single motor unit very close a
recording electrode [13].  Although also imperfect, it is likely that the integral
of the rectified waveform, or line-length of the waveform, may well be better
measures. The strength of correlation of each of these measures to
cardiac output may inform selection of the most robust measure.   
MEP signals commonly exhibit considerably trial-to-trial variability.  This
variability does not reflect “measurement error”, but rather reflects
spontaneous fluctuation of motor-pool excitability resulting in changing motor
unit contributions to the MEP signal.  Trial-to-trial variability is influence by
numerous factors, including anesthesia and hemodynamics.   If shown to
correlate with cardia output, MEP  (peak-to-peak amplitude, integral, line-
length) variability, may also provide additional, useful, metrics. 
 
1.    Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: A novel
sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13–21.
2.    Liolios A, Guerit JM, Scholtes JL et al. Propofol infusion syndrome associated
with short-terms large dose infusions during surgical anesthesia in an adult. Anesth
Analg 2005;100:1804-6.
3.    Grottke O, Dietrich PJ, Wiegles S et al. Intraoperative wake-up test and
postoperative emergence in patients undergoing spinal surgery: A comparison of
intravenous and inhaled anesthetic technique using short acting anesthetics. 
Anesth Analg 2004;99:1521-1527.
4.    Dutta S, Karol MD, Cohen T, et al. Effect of dexmedetomidine on propofol
requirements in healthy subjects. J Pharm Sci. 2001; 90:172-81.
5.    Mahmoud M, Sadhasivam S, Sestokas AK,et al. Loss of transcranial electric 
motor  evoked  potentials  during  pediatric  spine  surgery  with  dexmedetomidine.
Anesthesiology. 2007;106:393-6
6.    Bala E, Sessler DI, Nair DR et al.   Motor and somatosensory evoked
potentially are well maintained in patients given dexmedetomidine during spine
surgery.  Anesthsiology 2008; 109:417-425.
7.    Tobias JD, Gobel TJ, Bates G, et al. Effects of dexmedetomidine on
intraoperative motor and somatosensory evoked potential monitoring during spinal
surgery in adolescents.  Ped Athesth 2008; 18: 1082-1088.
8.    Li Y, Meng L, Peng Y, et al. Effects of dexmedetomidine on motor- and
somatosensory-evoked potentials is patients with thoracic spinal cord tumor: a
randomized controlled trial. BMC Anesthesiol 2016:16;51.
9.    Kossari N, Hufnagel G, Squara.  Bioreactance: A new tool for cardiac output
and thoracic fluid content monitoring during hemodialysis.  Hemodialysis
International. 2009;13:512-517.
10.  Marik P et al. The use of bioreactance and carotid Doppler to determine
volume responsiveness and blood flow redistribution following passive leg raising in
hemodynamically unstable patients. Chest 2013; 143:364-370.

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11.  Waldron N et al. A prospective comparison of a noninvasive cardiac output
monitor versus esophageal Doppler monitor for goal directed fluid therapy in
colorectal surgery patients. Anesth Analg 2014; 118:966-75.
12.  Dunham, CM et al. Emergency department noninvasive (NICOM) cardiac
outputs are associated with trauma activation, patient injury severity and host
conditions and mortality. J Trauma Acute Care Surg. 2012; 73:479-85.
13.  MacDonald DB, Skinner S, Shills J and Yingling C. Motor evoked potential
monitoring - a position statement of the American Society for Neurophysiological
Monitoring. Clinical Neurophsiology 2013;124:2291-2316.
3.0
Identify specific gaps in current knowledge that this study is
intended to fill.
Both propofol and dexmeditomidine produce dose-related attenuation of MEPs. 
There is limited data concerning the combined effect of the two agents.  Taken
together, the limited available literature suggests that combined with propofol at 70
ug/kg/min, dexmeditomidine 0.5 ug/ml/hr does not produce significant attenuation
of MEPs, although attenuation of MEPs may occur when it is combined with higher
propofol doses.  Significant attenuation of MEPs is more frequent at higher doses
of dexmedtomidine in combination with propofol, although previous studies have
been conducted using propofol doses higher than are proposed in this study.
It is not known whether MEP changes may be useful as guides for fluid
management during complex spine procedures.
The optimal metric for quantitative characterization of MEPs in not known.  
 
 
 
4.0
How will answering these questions change clinical practice,
change concepts about the topic or confirm the work of other
investigators?
This study will inform the best practice of intraoperative monitoring by establishing
acceptable doses of dexmeditomidine, in combination with propofol, for use in
conjunction with MEP monitoring.   This study will also provide insight into the
relationship between MEPs and cardiac output, and provide insight into whether
MEP changes may potentially be useful into the management of fluid status during
spine surgery.   This study will also provide insight into improved MEP metrics, that,
perhaps in the future, could be incorporated into clinical recording systems. 
 
5.0
Is this a pilot study that could lead to a more definitive
protocol or different study?   
Yes 
No
 
5.1 If you answered No, please explain below: 
 

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6.0
Please upload reference or additional document here (if
needed).
Name
Description
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ID: 2017-1304
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Study Design
 
1.0
Observational:
Name
Description
There are no items to display
 
2.0
Experimental:
Name
Description
Randomized
Controlled
Clinical Trial
This is the “gold standard” for clinical research. These prospective
studies have at least two groups. Patients meeting strict
inclusion/exclusion criteria are enrolled and randomly assigned to
receive either an experimental intervention or to receive what is
considered to be an acceptable alternative – usually the current
standard of care or a placebo (e.g., study of hylauronic acid injection
versus cortisone for arthritis).
 
2.1 If Other, please specify: 
 
2.2 If Randomized Controlled Clinical Trial is selected, please
choose one of the following:
Name
Other
 
If other, please list name or indicate N/A below:
Randomized trial of different doses of standard FDA approved anesthetics.
 
ID: 2017-1304
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Recruitment
 
1.0
Check all that apply to describe your study population:
 

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Population
Patients
Vulnerable Populations
There are no items to display
1.1 If Other, please specify: 
 
2.0
Inclusion Criteria: list characteristics that potential subjects and
controls need to have. Use a bullet format, if applicable.
Subjects will be within the age range of 18 – 70 years.
Subjects will be patients undergoing multi-level posterior spine fusions
requiring MEP monitoring
 
 
 
3.0
Exclusion Criteria: list characteristics that would cause you to
exclude potential subjects and controls.
Justify any age, ethnicity, language, or gender-based
exclusion criteria. Use a bullet format, if applicable.
Allergy to any of the anesthetic medications included in the protocol
Non-English speaking
Younger than 18 and older than 70 years of age
Any other surgery other than multi-level posterior spine fusions
 
 
 
4.0
Age Range:
18-70 years
 
5.0
Describe how you will identify and recruit potential subjects
for participation in the study.
 
Potential patients will be recruited as a consecutive series of patients
undergoing multi-level posterior spine fusions requiring MEP monitoring. 
Recruitment will begin following approval of the study, and will be conducted
by the principal investigator or an IRB approved co-investigator.
 
 

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6.0
* Please select enrollment type from following drop down list: 
Over Course of Study
 
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ID: 2017-1304
 
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Target Enrollment
 
1.0
* What is the maximum number of subject you plan to enroll in
this study at HSS?(Please enter a number)
68
 
2.0
If this is a multi-center study, indicate the projected total
subject accrual across all sites.
 
 
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ID: 2017-1304
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Patients  
 
1.0
Please check the box(es) below that best reflect how patients
will be identifed and recruited for participation. 
 
How subjects will be identified
Potential subjects will be identified after a review of medical records of
patients under the care of one or more of the study investigators
Medical records and/or other Institution sources (databases,registries,billing
records,pathology reports,admission logs) will be reviewed to identify potential
participants. May involve access of records by individuals not involved in the
patient's care.
Potential subjects will be identified by their treating physicians and referred to
the researchers. Patients' private and identifiable information will not be shared
prior to receiving permission from the patient to do so.
Potential subjects will be identified from a registry of individuals interested in
research opportunities.
Subjects will roll-over from another research study.
Potential subjects will self-refer in response to advertisements.
 
 
 
ID: 2017-1304
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Interventions and Observations
 
1.0
 

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Be specific and describe the Interventions or
Observations that will be part of this research project. Include
a detailed description of the treatment arms, if applicable.
Patient will undergo endotracheal intubation and general anesthesia will be
induced using propofol, fentanyl, midazolam, and vecuronium.
All patients will be monitored with standard ASA monitors.  An indwelling
arterial catheter will be placed, and electrode for the NICOM monitor will be
applied. During the procedure, an arterial blood sample will be assessed for
blood gas analysis, pH, blood glucose, Hb and lactate.
Once positioned prone, maintenance anesthetic will include 02/Air, diazepam
2 mg/hour up to a maximum total of 10 mg, and an infusion of fentanyl 1
mcg/ kg/hr and ketamine 2 mcg/kg/hr, a loading dose of 1 mcg/kg of
dexmedetomidine administered over, plus one of two anesthetic Treatments.
Treatment 1: Propofol 50 mcg/kg/min + dexmedetomidine 0.5 mcg/kg/hr
Treatment 2: Propofol 25 mcg/kg/min + dexmedetomidine 1.0 mcg/kg/hr.
If MEPs are clinically determined to be unmonitorable for patients receiving
treatment 2, they will be converted to treatment 1.  If MEPs continue to be
unmonitorable, anesthetic management will be at the discretion of the
attending anesthesiologist.   If MEPs are unmonitorable for patient receiving
treatment 1, anesthetic management will be at the discretion of the attending
anesthesiologist.
Cardiac output will be measured continuously during the procedure. A
decrease in cardiac output by 20% or an increase in lactate >2mEq/l will
prompt the administration of fluid and/or blood is the Hb is less than 8mg/dl.;
to restore the values to baseline. Any deterioration of MEPs will prompt the
assessment of metabolic acidosis, cardiac output and Hb level.
Patients may also receive boluses vaso-active medications to control HR and
BP.
Motor evoked potentials will be performed in the standard manner. Simulating
electrodes will be placed 2 cm anterior to C1 and C3, and C2 and C4
locations of the International 10-20 system.  C1 and C3, and C2 and C4
electrodes will be joined using a Y connector, to produce one right and one
left cranial electrode.  Recording electrodes will be placed in right and left
tibialis anterior, abductor hallucis, extensor hallucis longus, medial
gastrocnemius, vastus lateralis and rectus femoris muscles. Stimuli will be
two sequential trains of 2 then 5 pulses, each pulse 50 microsecond
durations, with an inter-pulse intervals of 2 milliseconds and an inter-train
interval of 10 and 20 milliseconds.  Stimulation voltage will be adjusted to
obtain responses in all muscles if possible.  MEPs will be performed at
standard intervals, typically once every 20 minutes, as permitted by the
surgeon.
Additionally, following establishment of stable anesthesia, the stimulation
voltage threshold for each muscle will be determined by beginning at 125
volts and increasing at 25 volt increments until a response is obtained in
each muscle, and recording the voltage at which the MEP was first recorded

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in each muscle.
 
2.0
Will you be collecting human fluid or tissue?   
Yes 
No
 
If yes, what will you be collecting?   
  Fluid      
  Tissue
(Intraoperative and/or outpatient collection)
 
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ID: 2017-1304
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Data Collection
 
1.0
Indicate what data will be collected.
MEP voltage threshold values for each muscle will be recorded manually.
Timestamped MEP waveform data are recorded and stored automatically by
the Cadwell clinical intraoperative monitoring machine.
Timestamped cardiac output data are stored automatically by  the NICOM
device.
Anesthesia data and blood pressure are stored automatically in EPIC.
Arterial PO2, PCO2, pH, lactate, glucose, and hemoglobin will be sampled
and recorded at clinically determined intervals.
 
 
 
2.0
Who will collect the data:
Ronald
 
Emerson, MD
 
Michael
 
Urban, MD PhD
 
 
3.0
When the data will be collected? Include timing of visits(either
SOC or specifically for the study). 
During each surgery
 
4.0
From what source:
Medical Records
No Private Office Charts     Please specify which private office:
No Registries     Please specify which registry: 
 

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 Other   Please specify:  NICOM and Cadwell Cascade machines
 
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General Methods and Procedures
 
1.0
* Are controls included in the study? No
 
1.1 If yes, describe how they will be matched with the study subjects; state
whether the controls will have identical data recorded, or describe any
differences compared to the intervention subjects. 
 
2.0
* Are all tests Standard of care? No
If not, identify which tests are not standard of care. What source of funds
will be used to pay for them (text box below):
Use of the NICOM monitor is not standard of care at HSS, but HSS does own a
NICOM monitor.  There will be charge to the patient for its use.
 
3.0
* Will surveys/questionnaires be used?  No
 
4.0
* Does the study involve randomization?  Yes
 
5.0
* Does your study included Placebo or No-Treatment Arm? No
 
6.0
* Does your study included Washout of Previous Medication?
No
 
7.0
Data collection sheet should be created for the study and
uploaded: 
Name
Version
There are no items to display
 
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ID: 2017-1304
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Randomization
1.0
Please state who will do the Randomization:
The randomization schedule will be generated by a member of the Healthcare
Research Institute not otherwise involved in the trial.
 
2.0
Please state when the Randomization will be done:
 

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The randomization schedule will be generated prior to the start of study enrollment.
After consent is obtained, the anesthesiologist will be given a sealed opaque
envelope corresponding to the patients study ID number and randomized to one of
the two treatment groups. The envelope will be opened in the operating room, not
in the presence of other investigators.
3.0
Please state how the Randomization will be performed:
A Healthcare Research Institute member not otherwise involved in the trial will
prepare the randomization schedule using SAS software.  Group assignment will
be indicated on cards within numbered sealed opaque envelopes.  The envelopes
will be prepared by a staff member not otherwise involved in the trial. 
 
4.0
Please state who will insure that the Randomization is carried
out and if anyone will be blinded to the Randomization group:
All investigators except for the anesthesiologist will be blind to the randomization
group.
 
 
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ID: 2017-1304
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Sample Size and Data Analysis
If you are uncertain about how to calculate your sample size and determine appropriate
data analysis, please contact the Epidemiology and Biostatistics Core at biostats@hss.edu
for assistance in completing this section.
 
1.0
Is this is a case series based only on the patients available
using descriptive statistics in lieu of a sample size
calculation?
* No
 
 
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ID: 2017-1304
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Sample Size and Data Analysis 
Support estimates with evidence from the literature of prior studies and perform an
appropriate sample size calculation.
 

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For hypothesis testing (e.g., the calculation of p-values using statistical tests), you need to
estimate your available sample size and calculate the effect size that will be detectable
using your proposed statistical analysis plan. This also applies to a case series where you
plan hypothesis testing.
 
1.0
If you have consulted with a statistician, please indicate their
name:
Kara Fields
 
2.0
Proposed sample size analysis, include the following:
Student's t-test, ANOVA, chi-square, regression, etc;
Alpha level;
Beta or power level;
Primary outcome variable estimate (mean +/-s.d. for
continuous outcome, frequency/percentage for
categorical variable);
Number of groups being compared (use 1 for paired
analysis within the same subjects);
Effect size or change expected between groups;
Resulting number per group
1. Proposed analysis (e.g., student’s t-test, ANOVA, chi-square,
regression, etc.):  Fisher’s exact test
2. Alpha level:   0.05 (two-sided)
3. Beta or power level:  80% power
4. Primary outcome variable estimate (mean +/- s.d. for continuous
outcome, frequency/percentage for categorical variable): 
Percentage of patients with monitorable MEPs for the purpose of monitoring
spinal cord integrity in 0.5 ug/kg/hr dexmedetomidine group = 100% *.
 Percentage of patients with monitorable MEPs for the purpose of
monitoring spinal cord integrity in 1.0 ug/kg/hr dexmedetomidine group =
75%.
5. Number of groups being compared (use 1 for paired analysis within
the same subjects):  2
6. Effect size or change expected between groups:  25 percentage point
difference
7. Resulting number per group: 31
Total sample size required:  62 + 10% to account for missing/unusable data = 68
* Li Y, Meng L, Peng Y.  Effects of Dexmedetomidine on motor-
and somatosensory-evoked potentials in patients with thoracic spinal cord
tumor: a randomized controlled trial.  BMC Anesthesia. 2016;16:51. DOI
10.1186/s12871-016-0217-y
 
3.0
Data Analysis: describe how the primary outcome will be
 

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analyzed and what types of statistical calculations will be
used. Do the same for each secondary outcome. Reiterate
briefly the main analysis to be done, which groups, which
variables, possible confounders. Address how possible
confounders will be identified and handled in analysis: 
The percentage of patients with monitorable MEPs for the purpose of monitoring
spinal cord integrity present at all assessments (yes vs. no), the primary outcome,
will be compared between groups using Fisher’s exact test.
The percentage of patients in each group with monitorable MEPs for the purpose of
monitoring nerve root integrity present at all assessments (yes vs. no) will be
presented as risk difference and relative risk with 95% confidence intervals.
The correlation between MEP metrics (peak to peak amplitude, waveform integral,
waveform line-length, trial variability of peak to peak amplitude, trial variability of
waveform integral, and trial variability of waveform line-length) and CO over time
will be assessed via mixed modeling. Correlation coefficients will be presented as
point estimates along with 95% bootstrap confidence intervals.
Balance on demographics and baseline characteristics will be assessed by
calculating standardized differences (difference in means or proportions divided by
the pooled standard deviation) between groups. Balance will be assessed using
two thresholds: (1) 1.96 x (2/34)1/2 = 0.475 and (2) 0.2 (Austin 2009).
 
References
1. Austin PC. Balance diagnostics for comparing the distribution of baseline
covariates between treatment groups in propensity-score matched samples.
Stat Med 2009; 28: 3083-107.
 
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Consent Information
 
1.0
Describe how, when, and where the consent process will be
initiated:
Informed consent will be obtained in the holding area, prior to surgery, by the
principal investigator or an IRB approved co-investigator 
 
2.0
Who will obtain informed consent from subjects for this
research?
First Name
Middle Name
Last Name
Title
Ronald
 
Emerson, MD
 
 

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Michael
 
Urban, MD PhD
 
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ID: 2017-1304
 
You have completed the Clinical Research Proposal for this study. Click FINISH button
to save and exit the proposal.
When you are ready to submit your proposal for pre-review, hit the SUBMIT STUDY link
on your study homepage. The appropriate Clinical Review Panel (CRP) will receive and
review your proposal.
Should you have any questions, please contact Barbara Bosco at 212.606.1914.