Incidence of Postoperative Residual Curarization, a Prospective Observational Study
Conditions: Neuromuscular Blockade, Residual
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study title: Neuromuscular monitoring and incidence of postoperative residual curarization: a prospective 
observational study (PORC trial) 
Date of approval of the study protocol (ID 5991) by the Independent Ethics Committee: 23 November 
2023  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Neuromuscular monitoring and incidence of postoperative residual curarization: a prospective 
observational study (PORC trial) 
 
Abstract  
Neuromuscular blocking agents are commonly used in clinical anesthetic practice to facilitate tracheal 
intubation and allow muscle relaxation during surgical interventions. 
An incomplete postoperative recovery of neuromuscular function (postoperative residual curarization – 
PORC) continues to represent a common problem in post-anesthesia care units (PACU), potentially 
exposing the patient to adverse respiratory events. 
Anesthesiologist's subjective qualitative assessment of the patient's recovery of muscle strength before 
extubation based solely on clinical signs is not predictive of adequate neuromuscular recovery and an 
expert consensus statement in 2018 suggested that a quantitative and objective assessment of 
neuromuscular function using the train-of-four ratio (TOFR) acceleromyographic method at the level of the 
adductor muscle of the thumb represents the best way to minimize this risk after administration of a non-
depolarizing neuromuscular blocker. 
This monitoring system, introduced by Ali in the early 1970s, is based on the application of Newton's 
second law of motion (force=mass x acceleration). Since the mass of the thumb is constant, its acceleration 
is directly proportional to the force applied. 
The acceleration measurement is performed by a piezoelectric sensor fixed at the thumb level which, when 
moving in response to 4 supramaximal 2 mA stimuli at 0.5 second intervals (2 Hz frequency) delivered by 2 
surface electrodes positioned at the level of the distal portion of the forearm along the course of the ulnar 
nerve, produces an electrical signal in the sensor, proportional to the acceleration of the thumb. 
This signal is digitized, processed and then the muscular response to the fourth stimulus is compared with 
that to that to the first stimulus, and displayed in real time on a monitor as a numerical value in a range of 
0-100. Recovery of neuromuscular function is considered acceptable when a TOFR ≥ 0.9 is achieved. 
In case of TOFR ≤ 0.9, reversal of the neuromuscular block is normally performed with drugs belonging to 
the class of acetylcholinesterase inhibitors or with sugammadex, a selective antagonist of rocuronium and 
vecuronium which acts by encapsulating the neuromuscular blocking molecule making it ineffective. 
Recurrence of neuromuscular blockade may, however, occur primarily due to mechanisms of redistribution 
of the muscle relaxant or if insufficient doses of the reversal drug are administered.  
Primary outcome of this prospective observational study is the evaluation of the incidence of residual 
curarization upon arrival in the PACU, defined as a TOFR≤0.9, assessed by acceleromyographic method in 
interventions in which non-depolarizing neuromuscular blockers with intermediate duration of action were 
administered at the time of tracheal intubation, and/or for maintaining a condition of myoresolution during 
surgery. 
Secondary outcomes 
- number of possible respiratory adverse events during the stay in the PACU and during the hospital stay. 
- Estimation of a logistic regression model to define risk factors for residual curarization. Age of the patient, 
type of administered anesthesia (inhalational or intravenous), duration of anesthesia, repeated doses of 
neuromuscular blockers, the reversal of the neuromuscular blockade and the type of neuromuscular 
blocker used during the procedure will be considered as possible risk factors.  

Respiratory adverse events will be defined as episodes of desaturation (SpO2 <92%) requiring oxygen 
supplementation or the finding of atelectasis, pneumonia or pleural effusion of non-cardiac origin found on 
thoracic imaging tests possibly performed during the hospital stay. 
 
Background 
Neuromuscular blocking agents are commonly used in clinical anesthetic practice to facilitate tracheal 
intubation and allow muscle relaxation during surgical interventions. 
Anesthesiologist's subjective qualitative assessment of the patient's recovery of muscle strength before 
extubation is not predictive of adequate neuromuscular recovery even if many surveys conducted at an 
international level [1,2,3] demonstrate how this modality of evaluation is often used above all due to the 
not always widespread availability of tools for quantitative monitoring of neuromuscular blockade3. 
An incomplete recovery of neuromuscular function at the end of surgery (Postoperative residual 
curarization – PORC) exposes the patient to potential adverse respiratory events and a Consensus 
Statement [4] of experts in 2018 suggested a quantitative and objective evaluation of neuromuscular 
function using the train acceleromyographic method -of-four ratio (TOFR) at the level of the adductor 
muscle of the thumb represents the best way to minimize this risk after administration of non-depolarizing 
neuromuscular agents. 
This monitoring system, introduced by Ali in the early 1970s, present in every operating room of this 
hospital and routinely used in clinical anesthetic practice, is based on the application of Newton's second 
law of motion (force=mass x acceleration) . 
Since the mass of the thumb is constant, its acceleration is directly proportional to the force applied. 
The acceleration measurement is performed by a piezoelectric sensor fixed to the thumb which, when 
moving in response to the delivery of 4 2 mA stimuli at 0.5 second intervals (2 Hz frequency) by 2 surface 
electrodes positioned at the distal portion of the forearm, along the course of the ulnar nerve, produces an 
electrical signal in the sensor, proportional to the acceleration of the thumb [5]. 
This signal is digitized, processed, and the muscular response to the fourth stimulus is compared with that 
to the first stimulus, and displayed in real time on a monitor as a numerical value in a range of 0-100. 
Recovery of neuromuscular function is considered acceptable when a TOFR ≥ 0.9 is achieved [5,7,8]. 
In case of TOFR ≤ 0.9, reversal of the neuromuscular block is normally performed with drugs belonging to 
the class of acetylcholinesterase inhibitors (e.g. neostigmine 0.03-0.05 mg/kg, associated with an 
antimuscarinic agent such as atropine to counteract the cholinergic effects) or by sugammadex (2 or 4 
mg/Kg), a selective antagonist of rocuronium and vecuronium which acts by encapsulating the 
neuromuscular blocking molecule making it ineffective. 
Recurrence of neuromuscular blockade may, however, occur primarily due to mechanisms of redistribution 
of the muscle relaxant or if insufficient doses of the reversal drug are administered.  
Study outcomes 
Primary outcome 
- evaluation of the incidence of postoperative residual curarization upon arrival in the PACU, defined as a 
TOFR≤0.9, by acceleromyographic method in interventions in which non-depolarizing neuromuscular 
blockers with intermediate duration of action were administered at the time of tracheal intubation and/or 
for maintaining a condition of myoresolution during surgery. 

Secondary outcomes 
- Number of any adverse respiratory events that occurred during the stay in the PACU and during the 
hospital stay.  Respiratory adverse events will be defines as episodes of desaturation (SpO2<92%) requiring 
oxygen supplementation or the finding of atelectasis, pneumonia or pleural effusion of non-cardiac origin 
found on thoracic imaging tests possibly performed during the hospital stay; 
- Estimation of a logistic regression model to define risk factors for residual curarization Will be considered 
as possible risk factors those reported in the literature : the patient's age, the duration of anesthesia, the 
type of anesthesia administered (inhalation or totally intravenous), the number of administrations and the 
total dose of neuromuscular blocker, reversal or not of the neuromuscular blockade, the antagonist drug 
and the type of neuromuscular blocker used during surgery [7]. 
Study endpoints 
Primary endpoint 
- incidence of postoperative residual curarization 
Secondary endopoints 
- number of possible respiratory adverse events during the stay in the PACU and during the hospital stay 
- estimation of a logistic regression model to define the risk factors associated with residual curarization 
Methods 
Since this is an observational study, the anesthetic conduct will not be standardized - dose of 
neuromuscular blocker administered during surgery, possible administration of pharmacological 
antagonist, neuromuscular monitoring and the decision regarding the moment in which to proceed with 
extubation of the patient will be left to discretion of the treating anesthetist consistently with their clinical 
routine. 
Upon arrival of the spontaneously breathing patient in the Post-Anesthesia Care Unit, a researcher will note 
from the anesthesia record the type of surgical intervention performed and the type of non-depolarizing 
neuromuscular blocker agent administered. The TOFR will then evaluated to detect any residual 
neuromuscular block using the acceleromyographic method at the level of the adductor thumb. 
In analogy with other studies [9,10], 2 TOFR measurements will be performed 30 seconds apart. If the 
difference between the two measurements is ≤ 0.1, the average value will be considered for the purposes 
of the analysis. In case of a difference > 0.1, a third measurement will be taken and the average of the two 
closest results will be considered. 
If a residual block is detected sugammadex will be administered (2 mg/kg in the case of at least 2 
contraction responses to TOF stimulation or 4 mg/kg in the case of no contraction response) to restore 
normal neuromuscular function , assessed by subsequent TOFR measurement. 
Furthermore, data relating to the patient's age, sex, BMI, comorbidities and the TOFR value before 
induction of anesthesia and that reported at the time of extubation will be recorded, reporting them on a 
specific form, if reported in the medical record. 
The time of induction of general anesthesia and the end of surgery will also be noted; the type of 
neuromuscular blocker administered, the time of its administration and related dosage, as well as any drug 
(acetylcholinesterase inhibitor or sugammadex) with relative dosage, used as reversal agents.  

Any adverse respiratory events that occurred during the stay in the PACU will also be reported before 
discharge to the ward and during the stay in the ward. 
By respiratory adverse events we mean episodes of desaturation (SpO2<92%) requiring oxygen 
supplementation or the finding of atelectasis, pneumonia or pleural effusion of non-cardiac origin found on 
thoracic imaging tests possibly performed during the hospital stay. 
The collected data will then be transcribed on a personal computer to a Microsoft ExcelTM spreadsheet for 
analysis. 
Only the people identified as Data Managers in the aforementioned protocol will have access to the final 
database of the study. The personal computer used for the analyzes is the property of the Promoter and 
intended exclusively for research purposes conducted within the structure. 
Study design and duration 
Prospective, observational, single-center study, lasting 12 months from the time of approval by the Ethics 
Committee; involves the total enrollment of 90 patients. 
Study population 
Inclusion criteria 
Adult patients aged ≥ 18 years, American Society of Anesthesiologists (ASA) physical status I-III, who have 
expressed written consent to participate in the study and who will undergo surgery under general 
anesthesia with the use of non-depolarizing neuromuscular blocking agents at intermediate duration of 
action, for the purposes of tracheal intubation and/or for maintaining a condition of myoresolution during 
surgery. 
Exclusion criteria 
Patients undergoing emergency surgery, who do not require the administration of non-depolarizing 
neuromuscular blockers, patients with neuromuscular pathologies, or who require postoperative 
monitoring in the Intensive Care Unit. 
Sample size calculation 
From the data obtained from a meta-analysis published in 2020 [11] conducted on 53 studies and a total of 
12664 patients, 22 studies were selected (n=4268), with population, objectives and methodology similar to 
those under study. In these studies, regardless of whether or not an intraoperative monitoring system of 
neuromuscular function was adopted, the incidence of postoperative residual curarization (defined as a 
TOFR ≤ 0.9%) after the use of intermediate-acting neuromuscular blockers was detected in PACU with 
acceleromyographic method, it was 28%. 
Assuming an equal incidence of 28% we estimated that the study requires a sample size of 78 patients to 
estimate the expected proportion with an absolute precision of 10% and a confidence level of 95% 
(https://www.calculator.net/sample-size-calculator.html?type=1&cl=95&ci=10&pp=28&ps=&x=Calculate). 
Assuming a drop-out of 15%, the sample was increased to 90 patients. 
Statistics 
The sample will be described in its demographic, clinical and laboratory characteristics through descriptive 
statistics techniques. Continuous quantitative variables with normal distribution will be reported as mean 
and standard deviation; the variables distributed differently will be summarized with median and 
interquartile range. The normality of the distribution of the variables will be verified graphically using 

histograms and with the Shapiro-Wilk test. Categorical variables and missing data will be presented as 
absolute value and percentage, n (%). 
A logistic regression model will be estimated to define the risk factors associated with residual curarization. 
Those reported in the literature will be considered as possible risk factors: the patient's age, the duration of 
anesthesia, the type of anesthesia administered (inhalation or totally intravenous), the number of 
administrations and the total dose of neuromuscular blocker, the antagonization or not of the 
neuromuscular blockade, the antagonist drug and the type of neuromuscular blocker used during the 
operation. 
All tests used will be 2-sided with an α significance level of 0.05. 
All analyzes will be performed with the statistical software R version 4.1.2 (R Foundation for Statistical 
Computing, Austria). 
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