Electromyographic and Acceleromyographic Monitoring in Restricted Arm Movement Surgical Setting. A Prospective, Randomized Trial.
Phase: NA
Conditions: Residual Neuromuscular Blockade
Sponsor: Mayo Clinic

Electromyographic and 
acceleromyographic monitoring 
in restricted arm movement 
surgical setting. A prospective, 
randomized trial. 
 
NCT04352140 
 
 
10MAY2021 

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Electromyographic and acceleromyographic 
monitoring in restricted arm movement surgical 
setting. A prospective, randomized trial. 
  
 
 
 
Regulatory Sponsor 
Principal Investigator: 
J. Ross Renew, MD 
Funding Sponsor: 
 
Protocol Number:  
Departmental Resources 
 
IRB # 20-000629 
Study Product: 
TetraGraph 
 
TOFScan 
 
 
 
 
Initial version: [21Jan2020] Version (1.0)  
Revision: [19Oct2020] Version (2.0) 
Revision: [23Feb2021] Version (3.0) 
Revision: [10May2021] Version (4.0) 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
 
PROTOCOL APPROVAL FORM ...................................................................................5 
 
LIST OF ABBREVIATIONS ...........................................................................................6 
 
STUDY SUMMARY .........................................................................................................7 
 
INTRODUCTION .............................................................................................................8 
4.1 
ABSTRACT ....................................................................................................................8 
4.2 
BACKGROUND ..............................................................................................................9 
4.3 
RISKS AND BENEFITS .................................................................................................. 11 
 
STUDY OBJECTIVES ................................................................................................... 11 
 
STUDY DESIGN ............................................................................................................. 12 
6.1 
GENERAL DESCRIPTION .............................................................................................. 12 
6.2 
NUMBER OF SUBJECTS ................................................................................................ 12 
6.3 
DURATION OF PARTICIPATION ..................................................................................... 12 
6.4 
PRIMARY STUDY ENDPOINTS ...................................................................................... 12 
6.5 
SECONDARY STUDY ENDPOINTS.................................................................................. 13 
6.6 
IDENTIFICATION OF SOURCE DATA .............................................................................. 13 
 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL .............................. 13 
7.1 
INCLUSION CRITERIA .................................................................................................. 13 
7.2 
EXCLUSION CRITERIA ................................................................................................. 13 
7.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING ............................................. 13 
7.4 
EARLY WITHDRAWAL OF SUBJECTS ............................................................................ 14 
7.4.1 When and How to Withdraw Subjects ..................................................................... 14 
7.4.2 Data Collection and Follow-up for Withdrawn Subjects......................................... 14 
 
STUDY DEVICE ............................................................................................................. 14 
8.1 
DESCRIPTION .............................................................................................................. 14 
8.2 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ...................................... 15 
8.3 
MASKING/BLINDING OF STUDY ................................................................................... 15 
 
STUDY PROCEDURES ................................................................................................. 15 
9.1 
VISIT 1 (SCREENING AND ENROLLMENT UP TO THE DAY OF SURGERY) .......................... 15 
9.2 
VISIT 2 (RANDOMIZATION AND TREATMENT – DAY OF SURGERY) ................................. 15 
9.3 
SCHEDULE OF EVENTS ................................................................................................ 16 
 STATISTICAL PLAN .................................................................................................... 16 
10.1 
SAMPLE SIZE DETERMINATION ................................................................................... 16 
10.2 
STATISTICAL METHODS .............................................................................................. 17 
10.2.1 
Descriptive Statistics .......................................................................................... 17 
10.2.2 
Handling of Missing Data .................................................................................. 17 
10.3 
SUBJECT POPULATION(S) FOR ANALYSIS ..................................................................... 17 

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 SAFETY AND ADVERSE EVENTS .............................................................................. 17 
11.1 
DEFINITIONS............................................................................................................... 17 
11.1.1 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) ......... 17 
11.1.2 
Adverse Event .................................................................................................... 18 
11.1.3 
Serious Adverse Event ........................................................................................ 18 
11.1.4 
Adverse Event Reporting Period......................................................................... 18 
11.1.5 
Preexisting Condition......................................................................................... 19 
11.1.6 
Post-study Adverse Event ................................................................................... 19 
11.1.7 
Hospitalization, Prolonged Hospitalization or Surgery ...................................... 19 
11.2 
RECORDING OF ADVERSE EVENTS ............................................................................... 19 
11.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ............... 19 
11.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB .................................... 20 
11.4 
MEDICAL MONITORING .............................................................................................. 21 
 DATA HANDLING AND RECORD KEEPING ........................................................... 21 
12.1 
CONFIDENTIALITY ...................................................................................................... 21 
12.2 
SOURCE DOCUMENTS ................................................................................................. 22 
12.3 
CASE REPORT FORMS ................................................................................................. 22 
12.4 
DATA MANAGEMENT .................................................................................................. 22 
12.5 
DATA PROCESSING ..................................................................................................... 22 
12.6 
DATA SECURITY AND CONFIDENTIALITY ..................................................................... 22 
12.7 
DATA QUALITY ASSURANCE ....................................................................................... 23 
12.8 
DATA CLARIFICATION PROCESS .................................................................................. 23 
12.9 
RECORDS RETENTION ................................................................................................. 23 
 STUDY MONITORING, AUDITING, AND INSPECTING......................................... 23 
13.1 
STUDY MONITORING PLAN ......................................................................................... 23 
13.2 
AUDITING AND INSPECTING ........................................................................................ 23 
 ETHICAL CONSIDERATIONS .................................................................................... 24 
 STUDY FINANCES ........................................................................................................ 24 
15.1 
FUNDING SOURCE ....................................................................................................... 24 
15.2 
CONFLICT OF INTEREST ............................................................................................... 24 
15.3 
SUBJECT STIPENDS OR PAYMENTS ............................................................................... 24 
 PUBLICATION PLAN ................................................................................................... 24 
 REFERENCES ................................................................................................................ 25 
 LIST OF IN-TEXT TABLES .......................................................................................... 28 
18.1 
SCHEDULE OF EVENTS ................................................................................................ 28 
18.2 
INTRAOPERATIVE DATA .............................................................................................. 28 
18.3 
TETRAGRAPH SUS ...................................................................................................... 32 
18.4 
TOFSCAN SUS .......................................................................................................... 33 
 LIST OF IN-TEXT FIGURES ........................................................................................ 34 
19.1 
TETRAGRAPH ............................................................................................................. 34 

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19.2 
TOFSCAN .................................................................................................................. 34 
 
 

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 Protocol Approval Form 
 
 
Protocol Number:   20-000629 
 
 
Study Name: Electromyographic and acceleromyographic 
monitoring in restricted arm movement surgical setting. A 
prospective, randomized trial. 
 
 
 
 
 
 
This protocol has been reviewed and approved by the following: 
 
 
 
 
_________________                         May, 2021 
J. Ross Renew, MD 
                     
 
 
 
Date 
Principal Investigator 
 
 
 
 

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List of Abbreviations 
 
AE 
Adverse Event/Adverse Experience 
AMG 
Acceleromyography 
CE 
Conformite Europeene 
CFR 
Code of Federal Regulations 
cMAPs 
Compound Muscle Action Potentials 
CRF 
Case Report Form 
CTSA 
Center for Translational Science Activities 
DSMB 
Data and Safety Monitoring Board 
EHR 
Electronic Health Record 
EMG 
Electromyography 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICU 
Intensive Care Unit 
IRB 
Institutional Review Board 
KMG 
Kinemyography 
MMG 
Mechanomyography 
NMBA 
Neuromuscular Blocking Agent 
Non-UPIRTSO 
Non-Unanticipated Problems Involving Risk to Subjects or 
Others 
PACU 
Post Anesthesia Care Unit 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PTC 
Post-tetanic count 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SGX 
Sugammadex 
SOP 
Standard Operating Procedure 
TOF 
Train-of-four 
TOFC 
Train-of-four count 
TOFR 
Train-of-four ratio 
UPIRTSO 
Unanticipated Problems Involving Risk to Subjects or Others 
VNRS 
Verbal Numeric Rating Scale 
 
 
 
 

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 Study Summary 
Title 
Electromyographic and acceleromyographic monitoring in restricted 
arm movement surgical setting. A prospective, randomized trial. 
Running Title 
Subjective vs. Objective 
Phase 
N/A 
Methodology 
Randomized, Open-Label 
 
Overall Study 
Duration 
12 months 
Subject Participation 
Duration 
2 – 5 hours 
Single or Multi-Site  
Multi site 
Objectives 
The primary aim of this study is to compare the ease of use and 
repeatability of AMG vs. EMG neuromuscular responses in surgical 
settings in which the patients’ arm movement is restricted (placed 
under surgical drapes) in laparoscopic or robotic procedures. 
Number of Subjects 
105 
Diagnosis and Main 
Inclusion Criteria 
Patients undergoing elective robotic or laparoscopic surgery and 
requiring administration of neuromuscular blocking agents 
intraoperatively 
Study Device 
TetraGraph and TOFScan 
 
Duration of 
Administration 
Single stimulation of ulnar nerve repeated at specific intervals as 
outlined in the Study Procedures (Section 9.2) 
 
 
 

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 Introduction 
 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the applicable United States government regulations and Mayo Clinic research 
policies and procedures.  
4.1 
Abstract 
 
Residual neuromuscular blockade is a common complication in the post-anesthesia care unit 
(PACU) when neuromuscular blocking agents (NMBAs) have been used in the operating room.   
The only method of reliably detecting residual neuromuscular blockade is through the use of 
quantitative neuromuscular monitors.  Unfortunately, several barriers exist that have prevented 
the widespread application of these devices, and many practitioners are still using qualitative 
(subjective) methods (i.e., use a peripheral nerve stimulator) as an assessment of neuromuscular 
blockade despite the lack of accuracy of subjective methods and the well-described morbidity 
and mortality associated with residual blockade.  
 
The aim of this study is to determine the usability of two different monitors, the 
acceleromyography (AMG)-based TOFScan (which relies on muscle movement for 
measurement of function) and the electromyography (EMG)-based TetraGraph (which relies on 
measurement of electrical activity) in surgical settings in which access to the arms and hand 
muscle movements are restricted. 
  
The TetraGraph (Senzime AB, Uppsala, Sweden) is a standalone EMG-based quantitative 
monitor that received Conformité Européene (CE) and FDA approvals.  EMG measures 
electrical activity within the muscle following peripheral nerve stimulation and is unaffected by 
involuntary patient motion or restricted muscle movements from surgical positioning. The 
IntelliVue (Philips, Amsterdam, The Netherlands) is a modular AMG-based monitor that is being 
used routinely at Mayo Clinic for all surgical procedures in which NMBAs are administered. 
TOFScan (Draeger Medical Inc., Telford, PA) is another standalone AMG-based quantitative 
monitor available for routine clinical use in the United States. We plan to compare measurements 
obtained with Tetragraph and TOFScan monitors during surgical procedures in which the 
patients’ arms are tucked under surgical drapes and access is limited. The comparison will be 
based on a validated usability scale, the System Usability Scale (SUS) Plus (Table 18.3 and 
Table 18.4) that was designed to rate the usability of medical devices.  
 
The original System Usability Scale (SUS) was developed by John Brooke in 1986 
(https://www.usabilitest.com/system-usability-scale), and it allows investigators to evaluate a 
wide variety of products and services, including hardware, software, mobile devices and 
websites. It is a simple, ten-item Likert scale with five response options for respondents; the 
responses vary from “Strongly agree” to “Strongly disagree.”  The scale provides a quick and 
reliable tool for measuring the usability of the product in question.  
 

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The usability of the two monitors will be determined throughout various stages of neuromuscular 
blockade, including onset of blockade following neuromuscular relaxant administration, 
maintenance, and reversal of blockade with sugammadex or neostigmine until adequate recovery 
(train-of-four ratio >0.9) is confirmed. At the end of each surgical case, the healthcare provider 
will be asked to rate the usability of the TetraGraph and the usability of the TOFScan monitors 
based on the ten items on the SUS scale. 
 
4.2 
Background 
 
Neuromuscular blocking agents (NMBAs) are a class of medications routinely used during 
anesthesia to facilitate endotracheal intubation (1) and improve conditions for optimal surgery 
(2). However, these medications are also associated with respiratory complications in the early 
postoperative period due to residual neuromuscular blockade (RNMB) (3-5). Even when 
neuromuscular blockade is reversed in the operating room, postoperative residual weakness 
continues to be a common problem in the post-anesthesia care unit (PACU), and a significant 
number of patients continue to arrive in the PACU with objective evidence of residual 
neuromuscular blockade (6, 7).  While not every patient with residual weakness develops a 
postoperative complication, many can develop avoidable critical respiratory events (8, 9).  
Furthermore, special populations such as the elderly are at particular risk for developing 
complications related to postoperative residual weakness (10).  The use of quantitative 
monitoring has been demonstrated to reliably reduce the incidence of postoperative residual 
weakness and the ensuing complications (11-13).   
Quantitative neuromuscular monitoring devices objectively measure residual weakness and 
display the results numerically.  This is traditionally accomplished by performing a train-of-four 
(TOF) stimulation at the ulnar nerve and measuring the response of the adductor pollicis muscle.  
The degree of muscle weakness is determined by calculating the TOF ratio, which consists of the 
ratio of the fourth muscle contraction to the first.  Adequate recovery that excludes clinically 
significant weakness from neuromuscular blockade is defined as a TOF ratio ≥ 0.9, a 
measurement that can be determined reliably only with a quantitative monitor (14, 15).  With an 
abundance of literature supporting the use of objective neuromuscular monitors, a panel of 
experts recently recommended the universal adoption of such devices whenever NMBA are 
utilized (16)  however, quantitative monitors can be expensive and require additional training.  
There are several types of quantitative neuromuscular monitors.  These devices can be 
incorporated into the anesthesia workstation, allowing data to be seamlessly integrated into the 
electronic medical record.  Unfortunately, this setup can preclude using these monitors in the 
PACU as portability is sacrificed.  In contrast, other monitors exist as standalone, portable (hand-
held) units.   
Aside from portability, objective monitors can further be categorized based on the modality 
utilized to measure responses. Mechanomyography (MMG) measures the force of contraction of 
the adductor pollicis (thumb) muscle following ulnar nerve stimulation and has served as the 
traditional “gold-standard”.  Mechanomyographic responses are precise and reproducible, 

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however the setup is cumbersome and the lack of commercially available devices has relegated 
MMG to strictly research purposes. Acceleromyography (AMG) measures acceleration of a 
muscle group (typically the thumb) in response to stimulation (typically the ulnar nerve). This 
technique is similar to MMG, but instead of measuring the force of muscle contraction, an 
accelerometer fixed to the thumb measures the acceleration of the thumb in response to ulnar 
nerve stimulation.  Based on Newton’s Second law that states force is proportional to 
acceleration, the measured acceleration is correlated with the force of contraction in the clinical 
setting.  There are currently two standalone AMG-based monitors available for clinical use: the 
STIMPOD (Xavant Technologies, Pretoria, South Africa) and the ToFscan (Draeger Medical 
Inc., Telford, PA).  These devices represent improvements in AMG technology over its 
predecessor, the TOF-Watch (Schering-Plough Corp., Kenilworth, NJ, USA) as they utilize three 
dimensional transducers that can better quantify the complex motion of the thumb.  Despite these 
advances, the use of AMG can be limited due to patient positioning that precludes free motion of 
the thumb, as well instances of awakening patients moving their thumb during measurements.  
Kinemyography (KMG) is based on similar principles to AMG, and relies on the thumb being 
able to move freely.  Upon neurostimulation, KMG utilizes a piezoelectric motion sensor that is 
bent between the thumb and index fingers following muscle contraction.  The degree of this 
bending is quantified and used to determine a TOF ratio.  While Datex-Ohmeda (Helsinki, 
Finland) manufactures a KMG device that can be incorporated into the anesthesia work station, 
there are no currently available standalone KMG devices.  Electromyography (EMG) devices 
measure electrical activity, termed compound muscle action potentials (cMAPs) following nerve 
stimulation (typically at the adductor pollicis muscle after ulnar nerve stimulation).  As EMG 
measures cMAPs and does not require freely moving thumbs for accurate measurements, many 
experts have referred to this monitoring modality as the “new gold standard”. TetraGraph 
(Senzime AB, Uppsala, Sweden) is a standalone EMG-based device that is FDA-approved.  We 
have previously investigated this device and presented our findings at several annual meetings 
such as International Anesthesia Research Society (May 2018, May 2017, May 2013), the 
Society for Technology in Anesthesia (January 2018), and the American Society of 
Anesthesiologists (October 2017, October 2012), European Society of Anaesthesiology (June 
2018, June 2015) (17). Furthermore, we have recently submitted abstracts to the PostGraduate 
Assembly in Anesthesiology in December 2018 as well as a manuscript describing a multi-
center, volunteer study investigating TetraGraph versus AMG-based monitors.  Our work thus 
far has found this device to be easy to apply, reliable, and able to provide comparable 
measurements to other quantitative monitors.   
Many clinicians default to the antiquated practice of subjective monitoring (18, 19), which refers 
to visual or tactile evaluation of the train-of-four (TOF) in response to neurostimulation provided 
by peripheral nerve stimulation. However, subjective evaluation may provide inaccurate 
information and assessment of full recovery compared to objective evaluation (20, 21). A 
consensus statement by the international panel of experts in neuromuscular blockade issued in 
2018 state that subjective evaluation is not predictive of adequate neuromuscular recovery, and is 
not sensitive to the presence of residual weakness. They state that their use should be abandoned 

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in favor of objective monitoring, because after the TOFR recovers to >0.40, anesthesia providers 
can no longer detect the presence of fade by subjective evaluation and they may assume a 
complete recovery from neuromuscular blockade, despite the presence of minimal levels of 
NMB(16). It is worth highlighting that after tracheal extubation, even minimal degrees of 
residual block is associated with impaired function of respiratory and pharyngeal muscles, upper 
airway obstruction (22),hypoxemia (23), and awareness during anesthesia (24)  
 
Utilizing recommendations from the Good Clinical Practice (GCP) Guidelines for monitoring of 
neuromuscular function (25), we will compare acceleromyographic and electromyographic 
responses to train-of-four stimulation of the ulnar nerve in surgical settings where the arm 
movement is restricted by the surgical drapes (such as laparoscopic and robotic surgery). The 
time points of interest will include the onset of blockade following neuromuscular relaxant 
administration, maintenance of block, and reversal of blockade with sugammadex or neostigmine 
until adequate recovery (train-of-four ratio >0.9). The reliability of the two monitors will be 
evaluated post hoc by comparing the repeatability of responses, and the usability of the two 
monitors will be evaluated by the healthcare providers using the System Usability Scale (SUS) 
Plus scale, a simple, 10-item Likert scale with 5 response options for the evaluators 
(https://www.usabilitest.com/system-usability-scale). 
 
4.3 
Risks and Benefits 
• The benefits of using neuromuscular blockade monitoring devices:  
Early detection of optimal time for tracheal extubation; optimal management of 
intraoperative depth of neuromuscular block to facilitate surgical procedures; 
determination of appropriate time and dose of sugammadex reversal; and detection of 
residual neuromuscular blockade. This is currently the standard of care practice at Mayo 
Clinic. 
• The risks of using neuromuscular blockade monitoring devices: 
Slight discomfort when electrical stimulation is administered in awake volunteers; 
however, our patients will be anesthetized, rendering this risk as extremely minor. 
 Study Objectives 
 
Primary Objective 
Compare the objective EMG-derived data using TetraGraph (TOFR, TOFC, PTC) with those 
obtained from the AMG-based TOFScan monitor and assess the reliability and usability of the 
two objective monitors. 
 
Secondary Objective 
Determine the incidence of failure to calibrate and monitor neuromuscular responses using the 
two monitors.  

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The primary endpoint of the study will be to determine the usability of the two monitors using 
the SUS Plus scale.  
6.5 
Secondary Study Endpoints 
 
The secondary endpoint is to determine the reliability of the two monitors, by comparing the 
frequency of each monitor’s failure to calibrate and measure evoked responses.  
6.6 
Identification of Source Data 
 
The study data points will be recorded on the developed Case Report Forms (CRFs) by the study 
team members. In addition to the data collected intraoperatively, several intraoperative 
characteristics will also be extracted from the medical record (Table 18.2).  These will include 
type and total dose of NMBA used, time and dose of last NMBA administration, time and dose 
of specific reversal agent administration, time of tracheal extubation, and TOF ratio at the time 
of extubation (if available). 
 
 Subject Selection Enrollment and Withdrawal 
7.1 
Inclusion Criteria 
 
• Age > or = 18 years old 
• Patients willing to participate and provide an informed consent 
• Patients undergoing an elective laparoscopic or robotic surgical procedure that requires 
use of NMBA agents administered intraoperatively. 
7.2 
Exclusion Criteria 
 
• Patients with disorders, such as stroke, carpal tunnel syndrome, broken wrist with nerve 
damage, Dupuytren contracture, or any similar wrist injury.  
• Patients with systemic neuromuscular diseases such as myasthenia gravis 
• Patients with significant organ dysfunction that can significantly affect pharmacokinetics 
of neuromuscular blocking and reversal agents, i.e., severe renal impairment or end-stage 
liver disease. 
• Patients having surgery that would involve prepping the arm or leg into the sterile field 
 
7.3 
Subject Recruitment, Enrollment and Screening 
 
On a daily basis, there are over 20 elective surgical cases performed at Mayo Clinic in Florida 
and thus no difficulties in accrual are anticipated based on historical volumes. We will target at 
least 3 participants per week to complete this study. The initial accrual period will last at least 3 
months followed by interim analysis and additional time for accrual will be determined to meet 
the target. Patients will be provided with a Research Participant Consent and Privacy 

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Authorization Form describing the study devices, protocol, inclusion and exclusion criteria, as 
well as risks and benefits of participation.  
7.4 
Early Withdrawal of Subjects 
7.4.1 When and How to Withdraw Subjects 
 
Patients are free to withdraw at any time and for whatever reason. If patient withdraws consent 
prior to arrival to operating room, the study data will not be collected. If patient withdraws 
consent after study data was already completed, the participant will need to provide instructions 
to the study team to remove his/her data from the data set. Pre-specified reasons for 
discontinuing include, but are not limited to, the following:  
• Patient Request: Patient decided that he/she did not want to continue (for any reason) 
• Adverse Event: Patient experienced a related or unrelated event that would interfere with 
the study objectives/evaluation  
• Inclusion/Exclusion Discrepancy/Violation: Patient should not have been enrolled 
• Other: Any other reason 
 
7.4.2 Data Collection and Follow-up for Withdrawn Subjects 
 
If a Participant withdraws from the study, no additional attempts will be made to contact the 
Participant. 
 Study Device  
8.1 
Description 
 
TetraGraph (Figure 19.1) device is a FDA approved neuromuscular transmission monitor 
capable of measuring the depth of neuromuscular block in anesthetized patients who received 
neuromuscular blocking agents. TetraGraph uses EMG to measure the muscle action potentials 
that are generated in response to electrical neurostimulation via skin (ECG) electrodes.  
TetraGraph data is recorded on the monitor’s built-in SD card, and all intraoperative data will be 
recorded and later downloaded for purposes of analysis. The recorded data do not contain PHI, 
only the date/time of recording, and any additional intraoperative interventions, such as the time 
of NMBA dose administration, time of antidote administration, time of extubation, etc.  These 
events are flagged in the monitor’s integrated SD card recordings. 
 
TetraGraph uses EMG to measure the muscle action potentials that are generated in response to 
percutaneous electrical neurostimulation, and is not subject to the limitations imposed by the 
AMG-based monitors: the measurement of the electrical compound muscle action potentials 
(cMAPs) can be made even when the thumb movement is restricted. 
 

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The TOFScan (Figure 19.2) is a neuromuscular transmission monitor that is based on AMG 
technology, and is used routinely in clinical care at Mayo Clinic. It can measure and record the 
evoked responses (acceleration) of the hand muscle adductor pollicis (thumb) and calculate the 
degree of neuromuscular block (the TOF ratio). 
 
8.2 
Method for Assigning Subjects to Treatment Groups 
 
This is an open-label investigation and all study participants are assigned to both TetraGraph and 
TOFScan devices. The randomization involves the use of dominant vs non-dominant arm for the 
placement of TetraGraph device. 
 
The randomization will be performed utilizing REDCap and assigned anesthesia clinical care 
team will be informed of patients’ assigned to guide them with the selection of the assigned 
treatment option. 
 
8.3 
Masking/Blinding of Study  
 
This is an open-label pilot investigation. Masking and blinding procedures are not applicable. 
 Study Procedures 
 
9.1 
Visit 1 (Screening and Enrollment up to the day of surgery) 
 
• Review of medical record 
• Informed Consent - Patients will be identified during their preoperative appointment and 
introduced to a study; they will be provided with a copy of the consent document and 
information about the study. The consenting will take place after additional discussion on 
the day of surgery.  
 
9.2 
Visit 2 (Randomization and Treatment – day of surgery) 
 
• Elective surgical procedure as in which intraoperative access to the arms is restricted 
because of surgical draping.  
• Anesthetic management will be standardized to utilize rocuronium, sevoflurane, and 
sugammadex or neostigmine at the discretion of the attending anesthesiologist 
• Prior to induction of anesthesia, the Tetragraph electrodes will be placed over the ulnar 
nerve and the thumb to measure the response of adductor pollis nerve. Randomization 
will be performed utilizing REDCap and involves the use of dominant vs non-dominant 
arm.  

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• Following induction of anesthesia but prior to NMBA administration, baseline values will 
be recorded from both monitors after calibration.  
• Anesthesia providers will have access to the TetraGraph and TOFScan values during the 
entire procedure, and will make clinical decisions as per usual clinical routine at Mayo 
Clinic.  
• After NMBA administration, sets of measurements will be taken with the two monitors at 
regular intervals (every 12 sec, 20 sec, 1 min, 15 min, etc.) as required per usual clinical 
routine and determined by the anesthesia attending. 
• Near the conclusion of the operation but prior to the reversal of neuromuscular block, 
another set of measurements will be taken, with the two monitors, as per usual clinical 
routine, in order to determine the appropriate reversal drug dosage.  
• After sugammadex or neostigmine administration, measurements will be taken every 20 
seconds until return of neuromuscular function is documented.   
• Following documentation of adequate neuromuscular function (TOF ratio is >0.9,) the 
devices will be removed and the patient will proceed along the standard recovery 
pathway. 
 
9.3 
Schedule of Events 
 
 
Schedule of Events 
Study Activity 
Visit  1 
Visit 2 
Tetragraph 
 
X 
TOFScan 
 
X 
Informed consent 
X 
 
Review of 
Medical Record 
X 
 
Adverse event 
evaluation
 
X 
 
 Statistical Plan 
10.1 Sample Size Determination 
 
Based on paired t-test, 23 enrolled patients will give 90% power to detect a difference in TOF 
ratios with a significance level of 0.05 (JMP Pro Software version 13.0.0 
 [August 23, 2018]; SAS Institute Inc., Cary, NC). We utilized a standard deviation of 0.07 that 
was determined during our multi-center volunteer study comparing another AMG device and 
TetraGraph. However, each participating center  will enroll 35 patients to take into account 

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patient loss or missing data. The total number of patients for this study from all 3 centers will be 
aimed at 105 participants.  
   
10.2 Statistical Methods 
 
10.2.1 Descriptive Statistics 
 
Analysis of agreement between the two monitors will be assessed using Bland-Altman. The 
limits of agreement are defined as bias ± 2 SD, where SD denotes the standard deviations of the 
differences.  Limits of agreement are interpreted as the reference range within which 95% of the 
differences will lie.  The bias and the limits of agreements surrounding the bias (± 2 SD) will be 
calculated with 95% confidence intervals.  Statistical significance will be defined as a p-value 
<0.05.  Comparison of the usability of the two monitors will be made using the System Usability 
Scale (SUS) Plus. The SUS is particularly relevant to user experience when comparing two 
monitors that are based on different technologies (AMG and EMG). It will allow us to make a 
comparison of the two monitors in a surgical setting in which access to the monitoring muscle 
site (the thumb and hand) is limited. Because SUS is technology-neutral, we will be able to 
continue to use it in usability testing as technology evolves over the years, allowing us to 
continually evaluate and select the optimal monitoring technology available.  
10.2.2 Handling of Missing Data 
 
This is a prospective pilot study and therefore we do not anticipate any missing data.  In the 
event of any unexpected missing data, no attempt to impute this missing data will be made; 
missing data will simply be treated as missing in the statistical analysis, and replacement 
participants will be enrolled to achieve the target accrual of n=35 participants. 
10.3 Subject Population(s) for Analysis 
 
Each participant who goes through the surgery and completes monitoring of residual 
neuromuscular blockade will be included in the primary analysis regardless of study withdrawal 
for any reason. In the event of any study withdrawals, in secondary analysis we will examine the 
sensitivity of our results to the exclusion of patients who withdrew. 
 Safety and Adverse Events 
11.1 Definitions 
11.1.1 Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  

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• Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; (6) 
breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
• Unanticipated: (i.e. unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, or not part of an underlying 
disease. A problem or event is "unanticipated" when it was unforeseeable at the time of its 
occurrence. A problem or event is "unanticipated" when it occurs at an increased 
frequency or at an increased severity than expected, AND 
• Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
11.1.2 Adverse Event 
An untoward or undesirable experience associated with the use of a medical product (i.e. drug, 
device, biologic) in a patient or research subject. 
11.1.3 Serious Adverse Event 
Adverse events are classified as serious or non-serious.  Serious problems/events can be well 
defined and include; 
• death 
• life threatening adverse experience 
• hospitalization 
• inpatient, new, or prolonged; disability/incapacity 
• persistent or significant disability or incapacity 
• birth defect/anomaly 
 
and/or per protocol may be problems/events that in the opinion of the sponsor-investigator 
may have adversely affected the rights, safety, or welfare of the subjects or others, or 
substantially compromised the research data. 
 
All adverse events that do not meet any of the criteria for serious, should be regarded as non-
serious adverse events.  
 
11.1.4 Adverse Event Reporting Period 
 
For this study, the follow-up period is defined as up to 10 minutes after arrival to PACU or TOF 
ratio is > 0.9 (whichever occurs first). 
 

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11.1.5 Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
should be recorded as an adverse event if the frequency, intensity, or the character of the 
condition worsens during the study period. 
11.1.6 Post-study Adverse Event 
All unresolved adverse events should be followed by the sponsor-investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the sponsor-investigator should instruct each subject to report, to the sponsor-
investigator, any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.  
 
11.1.7 Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise in 
this protocol.  Any condition responsible for surgery should be documented as an adverse event 
if the condition meets the criteria for an adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
adverse event in the following circumstances:  
• 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. 
 
11.2 Recording of Adverse Events 
At each contact with the subject, the study team must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event section of the electronic case report form (CRF). All clearly related signs, symptoms, and 
abnormal diagnostic, laboratory or procedure results should recorded in the source document. 
 
All adverse events 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 ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious adverse event that occurs during the Adverse Event Reporting 
Period and is considered to be at least possibly related to the study treatment or study 
participation should be recorded and reported immediately. 
11.3 Reporting of Serious Adverse Events and Unanticipated Problems 
 
When an adverse event has been identified, the study team will take appropriated action 
necessary to protect the study participant and then complete the Study Adverse Event Worksheet 

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and log.  The sponsor-investigator will evaluate the event and determine the necessary follow-up 
and reporting required. 
 
11.3.1 Sponsor-Investigator reporting: notifying the Mayo IRB  
 
The sponsor-investigator will report to the Mayo IRB any UPIRTSOs and Non-UPIRTSOs 
according to the Mayo IRB Policy and Procedures. Each participating site will report SAEs to 
their respective IRB or Ethics Committee with copy of submission and review provided to the 
leading site. Should there be any SAEs at any of the participating sites; the study team at that site 
will notify the primary site (Mayo Clinic in Florida) within 24 hours of learning of the event.  
 
Any serious adverse event (SAE) which the Principal Investigator has determined to be a 
UPIRTSO will be reported to the Mayo IRB as soon as possible but no later than 5 working days 
after the investigator first learns of the problem/event. 
 
The following information will be collected on the adverse event worksheet (and entered in the 
research database):  
• Study ID 
• Disease  
• The date the adverse event occurred 
• Description of the adverse event 
• Relationship of the adverse event to the research device* 
• Determination if the adverse event was expected  
• The severity of the adverse event (severity scale described below**) 
• If any intervention was necessary 
• Resolution (was the incident resolved spontaneously, or after discontinuing treatment) 
• Date of Resolution 
 
The sponsor-investigator will review all adverse event reports to determine if specific reports 
need to be made to the IRB.  The sponsor-investigator will sign and date the adverse event report 
when it is reviewed.  For this protocol, only directly related SAEs/UPIRTSOs will be reported to 
the IRB. 
 
 
* Relationship Index 
 
The relationship of an AE to the Investigational Device is a clinical decision by the sponsor-
investigator (PI) based on all available information at the time of the completion of the eCRF and 
is graded as follows: 
 
1. Not related: a reaction for which sufficient information exists to indicate that the etiology is 
unrelated to the use and proper application of study device. 
 

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2. Unlikely: a clinical event, including laboratory test abnormality, with a temporal relationship 
to use of the study device which makes a causal relationship improbable and in which use of 
other devices, chemicals, or underlying disease provide plausible explanations. 
 
3. Possible: a clinical event, including laboratory test abnormality, with a reasonable time 
sequence to use of the study device but which could also be explained by concurrent disease or 
use of other devices or chemicals. 
 
4. Probable: a clinical event including laboratory test abnormality, with a reasonable time 
sequence to use of the study device, unlikely to be attributed to concurrent disease or use of other 
devices or chemicals. 
 
5. Definite: a reaction that follows a reasonable temporal sequence from the use of the study 
device. 
 
** Severity Scale 
 
The maximum intensity of an AE during a day should be graded according to the definitions 
below and recorded in details as indicated on the CRF. If the intensity of an AE changes over a 
number of days, then separate entries should be made having distinct onset dates.  
 
1. Mild: AEs are usually transient, requiring no special treatment, and do not interfere with 
patient’s daily activities. 
 
2. Moderate: AEs typically introduce a low level of inconvenience or concern to the patient and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic measures. 
 
3. Severe: AEs interrupt a patient's usual daily activity and traditionally require systemic drug 
therapy or other treatment. 
 
11.4 Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan (see section 10  “Study Monitoring, Auditing, and Inspecting”).  Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
 
 Data Handling and Record Keeping 
12.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 

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• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (long term survival status that 
the subject is alive) at the end of their scheduled study period. 
12.2 Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.  Examples of these original documents and data records 
include: hospital records and any forms completed specifically for this study.  
12.3 Case Report Forms 
 
All data necessary for this study will be obtained from EHR or at the time devices are being used 
and recorded on the electronic Case Report Forms (CRFs) created in REDCap. All missing data 
will be explained.  
 
12.4 Data Management 
 
Study data to be collected and managed using EHR and study-generated source documents and 
transcribed into electronic CRFs in REDCap, electronic data capture software, hosted by CTSA 
at Mayo Clinic.  REDCap (Research Electronic Data Capture) is a secure, web-based application 
designed to support data capture for research studies, providing 1) an intuitive interface for 
validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) 
automated export procedures for seamless data downloads to common statistical packages; and 
4) procedures for importing data from external sources. 
 
12.5 Data Processing 
 
All study date will be stored and analyzed at Mayo Clinic in Florida using the REDCap 
electronic data capture tool.  
 
12.6 Data Security and Confidentiality 
 
All source documents including clinical findings, observations or other activities will be stored in 
a REDCap database that will be designed by an Investigator.  Access to the REDCap database 

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will be limited to the Principal Investigator, Investigators, Study Team members, and 
Statistician. 
12.7 Data Quality Assurance 
 
Once the study is completed the Principal Investigator will randomly select 3 participants and 
compare the data documented in the EHR with what is entered into the REDCap database.  If 
there is any discrepancy, the Principal Investigator and/or Investigators will cross-reference all 
35 patients to ensure accuracy.  
12.8 Data Clarification Process 
 
For any data query the Principal Investigator and Investigators will meet to clarify the data 
queried and make corrections based on consensus.  
12.9 Records Retention 
 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents. Principal 
Investigator will maintain regulatory and essential study documents to ensure compliance with 
local and federal policies/guidelines.  
 
The sponsor-investigator will retain the specified records and reports: 
• As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy” 
   
 
 Study Monitoring, Auditing, and Inspecting 
13.1 Study Monitoring Plan 
 
The investigator will allocate adequate time for such monitoring activities.  The Investigator will 
also ensure that the compliance or quality assurance reviewer is given access to all the study-
related documents. 
 
13.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, and government regulatory agencies, of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).   
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 

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 Ethical Considerations 
This study is to be conducted according to United States and International government 
regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the Approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject and the individual obtaining the informed consent. 
 
 Study Finances 
15.1 Funding Source 
 
This investigator initiated study is not funded. Study coordinator’s time is supported by the 
Department of Anesthesiology and funding for statistical analysis will be provided from the 
Principal Investigator’s research fund. 
15.2 Conflict of Interest 
 
Any study team member who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) must 
have the conflict reviewed by a properly constituted Conflict of Interest Committee with a 
Committee-sanctioned conflict management plan that has been reviewed and approved by the 
study sponsor-investigator prior to participation in this study. 
 
No financial conflicts of interested are anticipated or have been identified for this study. 
15.3 Subject Stipends or Payments 
 
No payment is given to study participants. 
 
 Publication Plan 
 
The primary responsibility for publication of the study results is with the Primary Investigator. 
After the complication of study and prior to publication, the study results will be shared with all 
Investigators. The study will be registered at ClinicalTrials.gov prior to subject recruitment along 

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with the posting of the results within 12 months of final data collection for the primary outcome 
measure.  
 
 References 
 
 
1. Lieutaud T, Billard V, Khalaf H, Debaene B. Muscle relaxation and increasing doses of 
propofol improve intubating conditions. Canadian journal of anaesthesia = Journal 
canadien d'anesthesie. 2003;50(2):121-6. 
2. Blobner M, Frick CG, Stäuble RB, Feussner H, Schaller SJ, Unterbuchner C, et al. 
Neuromuscular blockade improves surgical conditions (NISCO). Surgical Endoscopy. 
2015;29(3):627-36. 
3. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: 
definitions, incidence, and adverse physiologic effects of residual neuromuscular block. 
Anesth Analg. 2010;111(1):120-8. 
4. Hayes AH, Mirakhur RK, Breslin DS, Reid JE, McCourt KC. Postoperative residual 
block after intermediate-acting neuromuscular blocking drugs. Anaesthesia. 
2001;56(4):312-8. 
5. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single 
intubating dose of nondepolarizing muscle relaxant with an intermediate duration of 
action. Anesthesiology. 2003;98(5):1042-8. 
6. Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual 
curarisation: a meta-analysis. Br J Anaesth. 2007;98(3):302-16. 
7. Cammu G, De Witte J, De Veylder J, Byttebier G, Vandeput D, Foubert L, et al. 
Postoperative residual paralysis in outpatients versus inpatients. Anesth Analg. 
2006;102(2):426-9. 
8. Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual 
neuromuscular blockade and critical respiratory events in the postanesthesia care unit. 
Anesth Analg. 2008;107(1):130-7. 
9. Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, et al. 
Residual neuromuscular block is a risk factor for postoperative pulmonary complications. 
A prospective, randomised, and blinded study of postoperative pulmonary complications 
after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 
1997;41(9):1095-103. 
10. Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Vender JS, et al. Residual 
Neuromuscular Block in the Elderly: Incidence and Clinical Implications. 
Anesthesiology. 2015;123(6):1322-36. 
11. Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic 
neuromuscular monitoring in an academic anesthesia department. Anesth Analg. 
2014;119(2):323-31. 
12. Todd MM, Hindman BJ. The Implementation of Quantitative Electromyographic 
Neuromuscular Monitoring in an Academic Anesthesia Department: Follow-Up 
Observations. Anesth Analg. 2015;121(3):836-8. 
13. Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Vender JS, et al. 
Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness 

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and improves quality of recovery in the early postoperative period. Anesthesiology. 
2011;115(5):946-54. 
14. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence 
and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed 
humans: pharyngeal videoradiography and simultaneous manometry after atracurium. 
Anesthesiology. 2000;92(4):977-84. 
15. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, et al. Functional 
assessment of the pharynx at rest and during swallowing in partially paralyzed humans: 
simultaneous videomanometry and mechanomyography of awake human volunteers. 
Anesthesiology. 1997;87(5):1035-43. 
16. Naguib M, Brull SJ, Kopman AF, Hunter JM, Fulesdi B, Arkes HR, et al. Consensus 
Statement on Perioperative Use of Neuromuscular Monitoring. Anesth Analg. 
2018;127(1):71-80. 
17. Nemes R, Nagy G, Murphy GS, Logvinov, II, Fulesdi B, Renew JR. Awake Volunteer 
Pain Scores During Neuromuscular Monitoring. Anesth Analg. 2019. 
18. Grayling M, Sweeney BP. Recovery from neuromuscular blockade: a survey of practice. 
Anaesthesia. 2007;62(8):806-9. 
19. Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, Brull SJ. A survey of current 
management of neuromuscular block in the United States and Europe. Anesth Analg. 
2010;111(1):110-9. 
20. Brull SJ, Silverman DG. Real time versus slow-motion train-of-four monitoring: a theory 
to explain the inaccuracy of visual assessment. Anesth Analg. 1995;80(3):548-51. 
21. Brull SJ, Silverman DG. Visual and tactile assessment of neuromuscular fade. Anesth 
Analg. 1993;77(2):352-5. 
22. Herbstreit F, Peters J, Eikermann M. Impaired upper airway integrity by residual 
neuromuscular blockade: increased airway collapsibility and blunted genioglossus muscle 
activity in response to negative pharyngeal pressure. Anesthesiology. 2009;110(6):1253-
60. 
23. Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. A new 
property of muscle relaxants? Acta anaesthesiologica Scandinavica. 1996;40(5):520-3. 
24. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a 
prospective case study. Lancet (London, England). 2000;355(9205):707-11. 
25. Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen 
J, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular 
blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand. 2007;51(7):789-
808. 
26. Woehlck HJ, Boettcher BT, Lauer KK, Cronin DC, Hong JC, Zimmerman MA, et al. 
Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration of 
Blood Pressure Without Vasospasm. A A Case Rep. 2016;7(12):247-50. 
27. Faber P, Ronald A, Millar BW. Methylthioninium chloride: pharmacology and clinical 
applications with special emphasis on nitric oxide mediated vasodilatory shock during 
cardiopulmonary bypass. Anaesthesia. 2005;60(6):575-87. 
28. McCartney SL, Duce L, Ghadimi K. Intraoperative vasoplegia: methylene blue to the 
rescue! Curr Opin Anaesthesiol. 2018;31(1):43-9. 

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29. Evora PR, Alves Junior L, Ferreira CA, Menardi AC, Bassetto S, Rodrigues AJ, et al. 
Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised. 
Rev Bras Cir Cardiovasc. 2015;30(1):84-92. 
30. Kaisers U, Langrehr JM, Haack M, Mohnhaupt A, Neuhaus P, Rossaint R. Hepatic 
venous catheterization in patients undergoing positive end-expiratory pressure ventilation 
after OLT: technique and clinical impact. Clin Transplant. 1995;9(4):301-6. 
31. Elyassi AR, Rowshan HH. Perioperative management of the glucose-6-phosphate 
dehydrogenase deficient patient: a review of literature. Anesth Prog. 2009;56(3):86-91. 
 
 
 

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 List of In-Text Tables 
18.1 Schedule of Events 
 
 
Schedule of Events 
Study Activity 
Visit  1 
Visit 2 
Tetragraph 
 
X 
TOFScan 
 
X 
Informed consent 
X 
 
Review of 
Medical Record 
X 
 
Adverse event 
evaluation
 
X 
 
18.2 Intraoperative Data 
 
Study ID:  
Date of Surgery  
(dd / mm / yyyy): 
Examiner’s Initials: 
Wrist circumference (right): Wrist circumference (left): 
Dominant side: L / R 
Ankle circumference (right): Ankle circumference (left): 
Age (yrs): 
Weight (kg): 
Height (cm):  
BMI: 
Muscle relaxant name: 
 
Muscle relaxant total dose (mg): 
 
Time of first muscle relaxant dose (mm : hh):                            :                        am  /  pm 

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Reversal agent name: 
 
Reversal agent dose (mg): 
 
Time of reversal agent administration (mm : hh): 
                       :                   am  /  pm 
 
Time of extubation: 
                               :                               am  /  pm 
 
 
TetraGraph (TG) / TOFScan 
 
 
 
Time 
TetraGraph 
(TG) 
 
Arm L / R 
TOFScan 
Arm L / R 
TOFR # 3 (if 
needed) 
Calibrated baseline 
TOFR and supramax 
current 
 
 
TOFC=0 (post initial 
dose of NMBA) 
 
 
Time Interval (first 
recheck) 
 
 
Time Interval (second 
recheck) 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 

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Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 
Time Interval 
 
 

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Time Interval 
 
 
pre-SGX 
 
 
+60sec after SGX 
 
 
+120 sec after SGX 
 
 
+180 sec after SGX 
 
 
+260 sec after SGX 
 
 
Extubation  
 
 
Time to recovery 
following SGX 
(TOFR ≥0.9)  
 
 
T0 (on arrival to 
PACU) 
 
 
T5 (5 min after PACU 
arrival) 
 
 
T10 (10 min after 
PACU arrival) 
 
 
 
 
 

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18.3 Tetragraph SUS 
 
Question 
 
Rating 
 
I think that I would like to use TetraGraph 
frequently. 
 
1 
2 
3 
4 
5 
 
Strongly Disagree ○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I found TetraGraph unnecessarily complex. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I thought TetraGraph was easy to use. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I think that I would need the support of a 
technical person to be able to use TetraGraph. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I found the various functions in TetraGraph 
were well integrated. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I thought there was too much inconsistency in 
TetraGraph. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I would imagine that most people would learn 
to use TetraGraph very quickly. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I found TetraGraph very cumbersome to use. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I felt very confident using TetraGraph. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
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Strongly Agree 
I needed to learn a lot of things before I could 
get going with TetraGraph. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
○ 
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○ 
Strongly Agree 

AMG vs EMG limb restricted 
 
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18.4 TOFScan SUS 
 
Question 
 
Rating 
 
I think that I would like to use TOFScan 
frequently. 
 
1 
2 
3 
4 
5 
 
Strongly Disagree ○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I found TOFScan unnecessarily complex. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
○ 
○ 
○ 
Strongly Agree 
I thought TOFScan was easy to use. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I think that I would need the support of a 
technical person to be able to use TOFScan. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
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○ 
○ 
Strongly Agree 
I found the various functions in TOFScan were 
well integrated. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
○ 
○ 
○ 
Strongly Agree 
I thought there was too much inconsistency in 
TOFScan. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
○ 
○ 
○ 
Strongly Agree 
I would imagine that most people would learn 
to use TOFScan very quickly. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
○ 
○ 
○ 
○ 
○ 
Strongly Agree 
I found TOFScan very cumbersome to use. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
○ 
○ 
○ 
Strongly Agree 
I felt very confident using TOFScan. 
 
1 
2 
3 
4 
5 
 
 
Strongly Disagree 
 
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○ 
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○ 
Strongly Agree 
I needed to learn a lot of things before I could 
get going with TOFScan. 
 
1 
2 
3 
4 
5 
 
 

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CONFIDENTIAL 
Strongly Disagree 
 
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○ 
Strongly Agree 
 
 List of In-Text Figures 
19.1 TetraGraph 
 
 
 
 
19.2 TOFScan 
 
  
 
 

AMG vs EMG limb restricted 
 
Version 4.0 
 
 
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Page 35 of 35 
J. Ross Renew, MD 
 
CONFIDENTIAL