Comparison of Flexor Hallicus Brevis and Adductor Pollicis as Sites for Neuromuscular Monitoring With Electromyography (Thumb vs Great Toe) After Sugammadex Administration
Phase: NA
Conditions: Residual Neuromuscular Blockade
Sponsor: Mayo Clinic

 
 
Comparison of Flexor Hallicus Brevis and 
Adductor Pollicis as Sites for Neuromuscular 
Monitoring With Electromyography (Thumb vs 
Great Toe) After Sugammadex Administration 
 
 
NCT04312256  
 
 
1/15/2021 

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J. Ross Renew, MD 
 
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Comparison of Flexor Hallucis Brevis and 
Adductor Pollicis Muscles (Thumb vs. Great Toe) 
as Sites for Neuromuscular Monitoring with 
Electromyography after Sugammadex 
Antagonism 
 
 
Regulatory Sponsor 
Principal Investigator: 
J. Ross Renew, MD 
Funding Sponsor: 
 
Protocol Number:  
Departmental Resources 
 
IRB # 19-011705 
Study Product: 
TetraGraph 
 
 
 
 
Initial version: [10Jan2020] Version (1.0)  
Revision: [02Dec2020] Version (2.0) 
 
    [14Dec2020] Version (2.1) 
                 [15Jan2021] Version (3.0) 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
 
PROTOCOL APPROVAL  FORM ................................................................................................... 4 
1
 
LIST OF ABBREVIATIONS ............................................................................................................ 5 
2
 
STUDY SUMMARY ........................................................................................................................ 6 
3
 
INTRODUCTION ........................................................................................................................... 7 
4
4.1 
ABSTRACT .................................................................................................................................... 7 
4.2 
BACKGROUND ............................................................................................................................... 7 
4.3 
RISKS AND BENEFITS ...................................................................................................................... 9 
 
STUDY OBJECTIVES................................................................................................................... 10 
5
 
STUDY DESIGN ........................................................................................................................... 10 
6
6.1 
GENERAL DESCRIPTION ................................................................................................................ 10 
6.2 
NUMBER OF SUBJECTS .................................................................................................................. 10 
6.3 
DURATION OF PARTICIPATION ........................................................................................................ 10 
6.4 
PRIMARY STUDY ENDPOINTS ......................................................................................................... 11 
6.5 
SECONDARY STUDY ENDPOINTS ..................................................................................................... 11 
6.6 
IDENTIFICATION OF SOURCE DATA ................................................................................................. 11 
 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL.................................................... 12 
7
7.1 
INCLUSION CRITERIA .................................................................................................................... 12 
7.2 
EXCLUSION CRITERIA ................................................................................................................... 12 
7.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING .................................................................... 12 
7.4 
EARLY WITHDRAWAL OF SUBJECTS ................................................................................................ 12 
7.4.1 
When and How to Withdraw Subjects ..................................................................................... 12 
7.4.2 
Data Collection and Follow-up for Withdrawn Subjects ........................................................... 13 
 
STUDY DEVICE ........................................................................................................................... 13 
8
8.1 
DESCRIPTION .............................................................................................................................. 13 
8.2 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ............................................................. 13 
8.3 
MASKING/BLINDING OF STUDY ...................................................................................................... 13 
 
STUDY PROCEDURES ................................................................................................................. 14 
9
9.1 
VISIT 1 (SCREENING AND ENROLLMENT UP TO THE DAY OF SURGERY) .................................................. 14 
9.2 
VISIT 2 (RANDOMIZATION AND TREATMENT – DAY OF SURGERY) ........................................................ 14 
9.3 
SCHEDULE OF EVENTS .................................................................................................................. 15 
 
STATISTICAL PLAN.................................................................................................................... 15 
10
10.1 
SAMPLE SIZE DETERMINATION .................................................................................................. 15 
10.2 
STATISTICAL METHODS ............................................................................................................ 15 
10.3 
SUBJECT POPULATION(S) FOR ANALYSIS ..................................................................................... 16 
 
SAFETY AND ADVERSE EVENTS ............................................................................................... 16 
11
11.1 
DEFINITIONS ........................................................................................................................... 16 
11.1.1 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) .............................. 16 
11.1.2 
Adverse Event ................................................................................................................. 16 
11.1.3 
Serious Adverse Event ..................................................................................................... 16 

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11.1.4 
Adverse Event Reporting Period........................................................................................ 17 
11.1.5 
Preexisting Condition ...................................................................................................... 17 
11.1.6 
Post-study Adverse Event ................................................................................................. 17 
11.1.7 
Hospitalization, Prolonged Hospitalization or Surgery ......................................................... 17 
11.2 
RECORDING OF ADVERSE EVENTS .............................................................................................. 18 
11.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS .................................... 18 
11.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB ....................................................... 18 
11.4 
MEDICAL MONITORING ............................................................................................................ 20 
 
DATA HANDLING AND RECORD KEEPING .............................................................................. 20 
12
12.1 
CONFIDENTIALITY ................................................................................................................... 20 
12.2 
SOURCE DOCUMENTS ............................................................................................................... 20 
12.3 
CASE REPORT FORMS ............................................................................................................... 20 
12.4 
DATA MANAGEMENT ............................................................................................................... 20 
12.5 
DATA PROCESSING ................................................................................................................... 21 
12.6 
DATA SECURITY AND CONFIDENTIALITY ..................................................................................... 21 
12.7 
DATA QUALITY ASSURANCE ..................................................................................................... 21 
12.8 
DATA CLARIFICATION PROCESS ................................................................................................. 21 
12.9 
RECORDS RETENTION ............................................................................................................... 21 
 
STUDY MONITORING, AUDITING, AND INSPECTING ............................................................. 22 
13
13.1 
STUDY MONITORING PLAN ........................................................................................................ 22 
13.2 
AUDITING AND INSPECTING ....................................................................................................... 22 
 
ETHICAL CONSIDERATIONS ..................................................................................................... 22 
14
 
STUDY FINANCES ....................................................................................................................... 22 
15
15.1 
FUNDING SOURCE .................................................................................................................... 22 
15.2 
CONFLICT OF INTEREST............................................................................................................. 23 
15.3 
SUBJECT STIPENDS OR PAYMENTS .............................................................................................. 23 
 
PUBLICATION PLAN .................................................................................................................. 23 
16
 
REFERENCES .............................................................................................................................. 23 
17
 
LIST OF IN-TEXT TABLES .......................................................................................................... 25 
18
18.1 
SCHEDULE OF EVENTS .............................................................................................................. 25 
18.2 
INTRAOPERATIVE DATA ............................................................................................................ 25 
18.3 
MONITORING DATA .................................................................................................................. 26 
 
LIST OF IN-TEXT FIGURES ........................................................................................................ 28 
19
19.1 
TETRAGRAPH .......................................................................................................................... 28 
 
 
 
 
 
 
 
 

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 Protocol Approval  Form 
1
 
 
Protocol Number:   19-011705  
 
 
Study Name: Comparison of Flexor Hallucis Brevis and 
Adductor Pollicis Muscles (Thumb vs Great Toe) as Sites for 
Neuromuscular Monitoring with Electromyography after 
Sugammadex Antagonism 
 
 
 
 
This protocol has been reviewed and approved by the following: 
 
 
 
 
_________________                              __01/15/2021__ 
J. Ross Renew, MD 
                     
 
 
 
Date 
Principal Investigator 
 
 
 
 

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List of Abbreviations 
2
 
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 
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 
3
Title 
Comparison of Flexor Hallucis Brevis and Adductor Pollicis Muscles 
(Thumb vs Great Toe) as Sites for Neuromuscular Monitoring with 
Electromyography after Sugammadex Antagonism 
Running Title 
Thumb vs Great Toe Recovery 
Phase 
N/A 
Methodology 
Randomized, Open-Label 
 
Overall Study 
Duration 
12 months 
Subject Participation 
Duration 
2 to 5 hours  
Single or Multi-Site  
Single site 
Objectives 
The primary aim of this study is to assess the onset of neuromuscular 
blockade and recovery profiles of aminosteroidal NMBAs after 
sugammadex at the flexor hallucis brevis and adductor pollicis muscles 
Number of Subjects 
130 
Diagnosis and Main 
Inclusion Criteria 
Patients undergoing elective surgery and requiring administration of 
aminosteroidal NMBAs (rocuronium, vecuronium) intraoperatively 
Study Device 
TetraGraph 
 
Duration of 
Administration 
Single stimulation of flexor hallucis brevis and adductor pollicis 
muscles repeated at specific intervals as outlined in the Study 
Procedures (Section 9.2) 
 
 
 

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 Introduction 
4
 
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 occurrence 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 use of these devices.  For instance, there is a paucity of quantitative 
neuromuscular monitors commercially available.  Also, two modalities of quantitative 
monitoring, kinemyography and acceleromyography, rely on movement of the muscles of 
interest, a characteristic frequently compromised during patient positioning for surgical 
procedures in which the patient’s arms are secured under surgical drapes (laparoscopic, bariatric, 
robotic, spine, and neurosurgical procedures) or in uncooperative awake patients in the PACU or 
intensive care unit (ICU).  The aim of this investigation is to determine the different muscle 
sensitivities to NMBA and reversal agents by comparing responses at two different monitoring 
sites as measured with a new quantitative monitor.  The TetraGraph (Senzime AB, Uppsala, 
Sweden) is a standalone electromyography (EMG)-based quantitative monitor that recently 
received Conformité Européene (CE) and US Food and Drug Administration (FDA) approvals.  
EMG measures electrical activity within the muscle following peripheral nerve stimulation, and 
is unaffected by involuntary patient motion or by restricted muscle movements from surgical 
positioning.  We plan to compare measurements obtained with two Tetragraph devices, one 
monitoring the adductor pollicis (thumb) muscle and the other monitoring the flexor hallucis 
brevis (great toe) muscle, during onset, maintenance, and recovery of neuromuscular blockade. 
This will include monitoring every 20 sec for onset of blockade (defined as Train-of-four count, 
TOFC =0) following rocuronium administration, during maintenance of neuromuscular block as 
required by surgical conditions, and following reversal administration until adequate recovery is 
documented (train-of-four ratio, TOFR > 0.9). 
 
4.2 
Background 
 
Postoperative residual weakness from neuromuscular blockade continues to be a common 
problem in the post-anesthesia care unit (PACU). Despite the routine use of reversal agents, a 
significant number of patients continue to arrive in the PACU with objective evidence of residual 
neuromuscular blockade (Naguib, Kopman, and Ensor 2007; Cammu et al. 2006; Fortier et al. 
2015; Renew and Brull 2019).  While not every patient with residual weakness develops a 
postoperative complication, many can develop avoidable critical respiratory events (Murphy et 
al. 2008; Berg et al. 1997).  Furthermore, special populations such as the elderly, are at particular 

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risk for developing complications related to postoperative residual weakness (Murphy et al. 
2015).  The use of quantitative monitoring has been demonstrated to reliably reduce the 
incidence of postoperative residual weakness and the ensuing complications (Todd, Hindman, 
and King 2014; Todd and Hindman 2015; Murphy et al. 2011).  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 (Naguib et 
al. 2018).   
Quantitative neuromuscular monitoring devices objectively measure muscle responses 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 (T4/T1).  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 (Sundman et al. 
2000; Eriksson et al. 1997).  Although evidence strongly suggests objective monitors should be 
used perioperatively whenever NMBAs are administered, these devices can be expensive and 
require additional training.  Many clinicians default to using the antiquated qualitative 
(subjective) neuromuscular stimulating units such as a peripheral nerve stimulator (PNS) 
(Grayling and Sweeney 2007; Naguib et al. 2010). The major limitation of PNSs is that they 
cannot measure the muscle responses (TOFR), and therefore cannot assure complete recovery of 
muscle strength prior to tracheal extubation and spontaneous respiration. 
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 
busy OR environment or 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.”  MMG responses are precise and reproducible, 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).  

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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 (and uncooperative) patients who may involuntarily move their thumb 
during measurements, making interpretation of responses impossible.  Kinemyography (KMG) is 
based on similar principles to AMG, and also 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.”(Naguib et al. 2018) 
TetraGraph (Senzime AB, Uppsala, Sweden) is a standalone EMG-based device that recently 
received Conformité Européene (CE) and US Food and Drug Administration (FDA) approvals.    
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 (Octotober 2017, October 2012), European Society of Anaesthesiology (June 
2018, June 2015).  Furthermore, we have 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.   
Utilizing recommendations from the Good Clinical Research Practice (GCRP) Guidelines for 
monitoring of neuromuscular function (Fuchs-Buder et al. 2007), we will investigate the 
performance of the TetraGraph at two muscle groups: adductor pollicis and flexor hallucis 
brevis.  Specifically, the time points of interest will include the onset of blockade (Train-of-four 
count =0), maintenance of neuromuscular block as clinically indicated by surgical needs, and 
recovery from rocuronium blockade with sugammadex, and every 20 seconds following reversal 
administration until tracheal extubation (as determined by the SOC practice). 
 
4.3 
Risks and Benefits 
• The benefits of using neuromuscular blockade monitoring devices:  
Early detection of optimal time for tracheal intubation; optimal management of 
intraoperative depth of neuromuscular block to facilitate surgical procedures; 

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determination of appropriate time and dose of sugammadex reversal; and detection of 
residual neuromuscular blockade 
• 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 
5
 
Primary Objective 
To compare the time to onset of blockade, level of blockade prior to reversal, and the rate of 
recovery between flexor hallucis brevis and adductor pollicis muscles following sugammadex 
administration.  
 
Secondary Objective 
Determine the incidence of postoperative residual weakness at the time of extubation at a center 
that predominately utilizes quantitative monitoring (defined as TOFR <0.90) and sugammadex. 
 
 Study Design 
6
 
6.1 
General Description 
 
This pilot unblinded, single center, prospective, randomized, observational study will involve 
130 patients undergoing surgical procedure that requires administration of neuromuscular 
blocking agents intraoperatively.  
 
6.2 
Number of Subjects 
 
One hundred twenty 
6.3 
Duration of Participation 
 
2-5 hours, depending on duration of surgery 
 
 
 

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 Subject Selection Enrollment and Withdrawal 
7
7.1 
Inclusion Criteria 
 
• Age > or = 18 years old 
• Patients willing to participate and provide an informed consent 
• Patients undergoing an elective surgical procedure that requires use of non-depolarizing 
NMBA agents administered intraoperatively. 
• Patients with planned administration of sugammadex as a neuromuscular blocking 
reversal agent. 
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 10 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 
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) 

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• 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
8.1 
Description 
 
TetraGraph 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. 
 
8.2 
Method for Assigning Subjects to Treatment Groups 
 
This is an open-label pilot investigation and all study participants are assigned to both standard 
of care and investigational device use in the operating room. The randomization involves the use 
of dominant vs non-dominant arm. The placement of the lead on the great toe will correspond 
with the randomization assignment (if patient’s dominant hand is right, and then the right great 
toe will be used). 
 
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 investigation. Masking and blinding procedures are not applicable.   
 

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 Study Procedures 
9
 
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 per standard of care 
• Anesthetic management will include rocuronium, sevoflurane, and sugammadex at the 
discretion of the attending anesthesiologist as per standard of care practice. 
• Prior to induction of anesthesia, Tetragraph electrodes will be placed over the ulnar nerve 
and the thumb to measure the response of adductor pollicis, and over the posterior tibial 
nerve and the great toe to measure the response of the flexor hallucis brevis.  
• Following induction of anesthesia but prior to NMBA administration, baseline values will 
be recorded at both muscle groups after instrument calibration.  
• Near the conclusion of the operation but prior to reversal of NMBA, another set of 
measurements will be taken at both muscle groups. 
• Intraoperatively, measurements will be taken every minute until the sugammadex 
administration, as per usual clinical routine.  
• After sugammadex administration, measurements will be taken every 20 seconds until the 
patient’s trachea is extubated.   
• Anesthesia providers will be guided on the intraoperative management of neuromuscular 
block based on the responses recorded from the adductor pollicis muscle, as per usual 
clinical routine. 
• Each neurostimulation with the TetraGraph will be conducted simultaneously by a single 
study team member.  
• Following measurements obtained with both devices at these specified time intervals and 
assuming TOF ratio is >0.9, the devices will be disconnected and the patient will proceed 
along the standard recovery pathway. 
 
 
 
 
 
 
 

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9.3 
Schedule of Events 
 
 
Schedule of Events 
Study Activity 
Visit  1 
Visit 2 
Tetragraph 
 
X 
Informed consent 
X 
 
Review of Medical 
Record 
X 
 
Adverse event 
evaluation 
 
X 
 
 Statistical Plan 
10
10.1 Sample Size Determination 
 
Based on paired t test, 97 patients will provide 90% power to detect a difference of 0.5 min or 
larger between hands and feet at 0.05 significance level. A common standard deviation of 1.5 
min for hands and feet is assumed based on previous work comparing flexor hallucis brevis and 
adductor pollicis muscles. However, we will enroll 130 patients to take into account patient loss 
or missing data. We want to determine a shorter time difference between hand and foot in order 
to make it applicable in all clinical settings, including rapid sequence induction and intubation.  
10.2 Statistical Methods 
 
Descriptive Statistics 
 
Analysis of agreement between the muscle groups will be compared between the two monitoring 
sites using the Wilcoxon signed rank test. 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.  
 
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; 

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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=100 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
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:  
• 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 

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• 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). 
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. 
 

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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 
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) 

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• 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. 
 
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. 
 

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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
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 
• 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 

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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 
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 
100 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: 

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• As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy” 
   
 
 Study Monitoring, Auditing, and Inspecting 
13
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. 
 Ethical Considerations 
14
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
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. 

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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 
16
 
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 
with the posting of the results within 12 months of final data collection for the primary outcome 
measure.  
 
 References 
17
 
 
Berg, H., J. Roed, J. Viby-Mogensen, C. R. Mortensen, J. Engbaek, L. T. Skovgaard, and J. J. Krintel. 
1997. '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, 41: 1095-103. 
Cammu, G., J. De Witte, J. De Veylder, G. Byttebier, D. Vandeput, L. Foubert, G. Vandenbroucke, and T. 
Deloof. 2006. 'Postoperative residual paralysis in outpatients versus inpatients', Anesth Analg, 
102: 426-9. 
Elyassi, A. R., and H. H. Rowshan. 2009. 'Perioperative management of the glucose-6-phosphate 
dehydrogenase deficient patient: a review of literature', Anesth Prog, 56: 86-91. 
Eriksson, L. I., E. Sundman, R. Olsson, L. Nilsson, H. Witt, O. Ekberg, and R. Kuylenstierna. 1997. 
'Functional assessment of the pharynx at rest and during swallowing in partially paralyzed 
humans: simultaneous videomanometry and mechanomyography of awake human volunteers', 
Anesthesiology, 87: 1035-43. 
Evora, P. R., L. Alves Junior, C. A. Ferreira, A. C. Menardi, S. Bassetto, A. J. Rodrigues, A. Scorzoni 
Filho, and W. V. Vicente. 2015. 'Twenty years of vasoplegic syndrome treatment in heart surgery. 
Methylene blue revised', Rev Bras Cir Cardiovasc, 30: 84-92. 
Faber, P., A. Ronald, and B. W. Millar. 2005. 'Methylthioninium chloride: pharmacology and clinical 
applications with special emphasis on nitric oxide mediated vasodilatory shock during 
cardiopulmonary bypass', Anaesthesia, 60: 575-87. 

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Fortier, L. P., D. McKeen, K. Turner, E. de Medicis, B. Warriner, P. M. Jones, A. Chaput, J. F. Pouliot, and 
A. Galarneau. 2015. 'The RECITE Study: A Canadian Prospective, Multicenter Study of the 
Incidence and Severity of Residual Neuromuscular Blockade', Anesth Analg, 121: 366-72. 
Fuchs-Buder, T., C. Claudius, L. T. Skovgaard, L. I. Eriksson, R. K. Mirakhur, J. Viby-Mogensen, and 
Meeting th International Neuromuscular. 2007. 'Good clinical research practice in 
pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision', Acta 
Anaesthesiol Scand, 51: 789-808. 
Grayling, M., and B. P. Sweeney. 2007. 'Recovery from neuromuscular blockade: a survey of practice', 
Anaesthesia, 62: 806-9. 
Kaisers, U., J. M. Langrehr, M. Haack, A. Mohnhaupt, P. Neuhaus, and R. Rossaint. 1995. 'Hepatic 
venous catheterization in patients undergoing positive end-expiratory pressure ventilation after 
OLT: technique and clinical impact', Clin Transplant, 9: 301-6. 
McCartney, S. L., L. Duce, and K. Ghadimi. 2018. 'Intraoperative vasoplegia: methylene blue to the 
rescue!', Curr Opin Anaesthesiol, 31: 43-49. 
Murphy, G. S., J. W. Szokol, M. J. Avram, S. B. Greenberg, J. H. Marymont, J. S. Vender, J. Gray, E. 
Landry, and D. K. Gupta. 2011. 'Intraoperative acceleromyography monitoring reduces symptoms 
of muscle weakness and improves quality of recovery in the early postoperative period', 
Anesthesiology, 115: 946-54. 
Murphy, G. S., J. W. Szokol, M. J. Avram, S. B. Greenberg, T. D. Shear, J. S. Vender, K. N. Parikh, S. S. 
Patel, and A. Patel. 2015. 'Residual Neuromuscular Block in the Elderly: Incidence and Clinical 
Implications', Anesthesiology, 123: 1322-36. 
Murphy, G. S., J. W. Szokol, J. H. Marymont, S. B. Greenberg, M. J. Avram, and J. S. Vender. 2008. 
'Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit', 
Anesth Analg, 107: 130-7. 
Naguib, M., S. J. Brull, A. F. Kopman, J. M. Hunter, B. Fulesdi, H. R. Arkes, A. Elstein, M. M. Todd, and 
K. B. Johnson. 2018. 'Consensus Statement on Perioperative Use of Neuromuscular Monitoring', 
Anesth Analg, 127: 71-80. 
Naguib, M., A. F. Kopman, and J. E. Ensor. 2007. 'Neuromuscular monitoring and postoperative residual 
curarisation: a meta-analysis', Br J Anaesth, 98: 302-16. 
Naguib, M., A. F. Kopman, C. A. Lien, J. M. Hunter, A. Lopez, and S. J. Brull. 2010. 'A survey of current 
management of neuromuscular block in the United States and Europe', Anesth Analg, 111: 110-
9. 
Renew, J. R., and S. J. Brull. 2019. 'The RECITE-US study: Stacking the odds in a chronic patient safety 
threat', J Clin Anesth, 56: 132-33. 
Sundman, E., H. Witt, R. Olsson, O. Ekberg, R. Kuylenstierna, and L. I. Eriksson. 2000. 'The incidence 
and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: 
pharyngeal videoradiography and simultaneous manometry after atracurium', Anesthesiology, 92: 
977-84. 
Todd, M. M., and B. J. Hindman. 2015. 'The Implementation of Quantitative Electromyographic 
Neuromuscular Monitoring in an Academic Anesthesia Department: Follow-Up Observations', 
Anesth Analg, 121: 836-8. 
Todd, M. M., B. J. Hindman, and B. J. King. 2014. 'The implementation of quantitative electromyographic 
neuromuscular monitoring in an academic anesthesia department', Anesth Analg, 119: 323-31. 
Woehlck, H. J., B. T. Boettcher, K. K. Lauer, D. C. Cronin, J. C. Hong, M. A. Zimmerman, J. Kim, and M. 
Selim. 2016. 'Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration 
of Blood Pressure Without Vasospasm', A A Case Rep, 7: 247-50. 
 
 
 

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 List of In-Text Tables 
18
18.1 Schedule of Events 
 
 
Schedule of Events 
Study Activity 
Visit  1 
Visit 2 
Tetragraph 
 
X 
Informed consent 
X 
 
Review of Medical 
Record 
X 
 
Adverse event 
evaluation 
 
X 
 
18.2 Intraoperative Data 
 
Study ID: 
 
Examiner 
Initials: 
 
Date (dd / mm / 
yyyy): 
 
 
Muscle relaxant name: 
 
Muscle relaxant total dose (mg): 
 
Time of last muscle relaxant dose (mm : hh): 
                           :                        am  /  pm 
 
Reversal agent name: 
 
Reversal agent dose (mg): 
 

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Time of reversal agent administration (mm : hh): 
                       :                   am  /  pm 
 
Time of extubation: 
                               :                               am  /  pm 
 
TOF ratio / TOF count at the time of reversal (if available): 
Monitor used 
during reversal: 
PNS  /  TetraGraph / IntelliVue NMT  /  ToFscan  /  None 
Site of monitoring 
during reversal: 
Hand  /  Face  /  Leg 
 
TOF ratio / TOF count at the time of extubation (if available): 
Monitor used at 
extubation: 
PNS  /  IntelliVue NMT  /  ToFscan  /  None 
Site of monitoring: 
Hand  /  Face  /  Leg 
 
18.3 Monitoring data 
 
Study ID  
 
Date of Surgery (dd / mm / yyyy): 
 
Initials: 
 
Dominant side: L  /  R 
Age (yrs): 
 
Wrist circumference (right): 
Wrist circumference (left): 
Ankle circumference (right): 
Ankle circumference (left): 
Weight (kg): 
 
Height (cm): 
 
BMI: 
 
 

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TetraGraph (TG)  
 
 
Arm tested:   dominant / non-dominant 
 
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TOFR #3 (if 
needed) 
Calibrated baseline 
TOFR and supramax 
current 
 
 
 
Time to TOFC=0 
 
 
 
pre-SGX 
 
 
 
+20 sec 
 
 
 
+40 sec 
 
 
 
+60 sec 
 
 
 
+120 sec 
 
 
 
+140 sec 
 
 
 
+180 sec 
 
 
 
+200 sec 
 
 
 
+220 sec 
 
 
 
+240 sec 
 
 
 

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+260 sec 
 
 
 
TOFC or TOFR +280 sec  
 
 
TOFC or TOFR +300 sec  
 
 
TOFC or TOFR at 
extubation  
 
 
 
Time to recovery 
following SGX (TOFR 
≥0.9) (two consecutive 
measurements) 
 
 
 
 
 List of In-Text Figures 
19
19.1 TetraGraph