“Incidence of Postoperative Residual Neuromuscular

Blockade in the Post Anesthetic care unit: A Prospective

Study in a Tertiary Hospital in Cavite”

Author:
Dr. Ruby Anne D. Batobalonos
Department of Anesthesiology
 

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BACKGROUND AND SIGNIFICANCE OF THE STUDY

When neuromuscular blocking drugs (NMBDs) are administered intraoperatively, residual

neuromuscular block (RNMB) is often observed in the post-anesthesia care unit (PACU). Studies
have established an association between RNMB and increased postoperative morbidity and
mortality, critical respiratory events, and longer PACU stays.

Train-of-four (TOF) nerve stimulation was introduced in the 1970s and is a commonly used
method to access the status of neuromuscular block. It is difficult to exclude residual block using
qualitative monitoring of TOF (tactile or visual), because of the subjectivity involved in these
observations. Quantitative methods should be preferred and acceleromyography monitoring
allows an accurate quantification of small degrees of residual block. The TOF ratio threshold that
represents inadequate neuromuscular recovery, combined with signs and symptoms of muscle
weakness, has changed over the decades. Initially, a TOF ratio >0.7 was considered to represent
adequate neuromuscular recovery. However, current recommendations support a TOF ratio
equal
to or greater than 0.9 to ensure optimal patient safety.

Despite the use of short-acting NMBDs and pharmacological reversal of neuromuscular block, the
incidence of RNMB on arrival to the PACU can be as high as 31%-64%.

An increase in the incidence of critical respiratory events (CRE) at the PACU even in the
presence of small degrees of RNMB has been proved. Many factors related to patients, surgical
procedure and anaesthetic management come into play. Patient risk factors include advanced
age, male sex, chronic obstructive pulmonary disease, diabetes and obesity. Surgery-related
variables include abdominal or orthopaedic surgery, emergency operation and long duration of
surgery.14-16 Finally, the anaesthetic risk factors for CREs in the PACU include the use of
general anaesthesia, opioids and NMBD.

Emergence is the transition from unconsciousness to full wakefulness, and ideally should be
smooth and uneventful. Inadequate emergence is characterized by a disturbance of activity level
in the immediate postoperative period. It can be classified into two subtypes: emergence delirium,
characterized by agitation, restlessness and hyperactivity; and hypoactive emergence,
characterized by a delayed recovery after anaesthesia. Inadequate emergence after anaesthesia
is a frequent complication. Preventable risk factors for emergence delirium are induction of
anaesthesia with etomidate, premedication with benzodiazepines and higher postoperative pain
scores. Hypoactive emergence occurs less frequently than emergence delirium and is associated
with a longer postoperative hospital stay.18 Thus, monitoring the sedation status in the PACU is
important. The Richmond Agitation-Sedation Scale (RASS) has demonstrated excellent interrater

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reliability and criterion, construct, and face validity.

The primary aim of this investigation was to determine the incidence of RNMB in the PACU after
general anaesthesia. The secondary aim was to examine the outcome related to critical
respiratory events (CREs), PACU complications and the length of PACU and hospital stay.

REVIEW OF RELATED LITERATURE

Quantitative Neuromuscular Monitoring: TOF Ratio Less than 0.70 and Less Than 0.90.
Traditionally, residual neuromuscular blockade has been defined using quantitative
neuromuscular monitoring. Although peripheral nerve stimulation was used in the l960s, Ali and
colleagues first described the application of peripheral nerve stimulation for neuromuscular
monitoring using the ulnar nerve–adductor pollicis unit as the site of monitoring in the early
1970s. By comparing the amplitude of the fourth (T4) to the first (T1) evoked mechanical or
electromyographic response (TOF response), the degree of neuromuscular recovery could be
measured. Shortly thereafter, these same investigators performed several studies examining the
association between the degree of residual blockade in the hand (defined using quantified T4/T1
ratio, i.e., TOF ratio) with symptoms of peripheral muscle weakness and spirometry
measurements. At adductor pollicis TOF ratios less than 0.60, signs of muscle weakness,
tracheal tug, and ptosis were observed. When TOF ratios recovered to 0.70, the majority of
patients were able to sustain head lift, eye opening, hand grasp, tongue protrusion, and a vital
capacity exceeding 15 mL/kg. On the basis of these data, a TOF ratio of 0.70 was previously
agreed on to represent acceptable neuromuscular recovery at the end of a general anesthetic
that included administration of nondepolarizing NMBDs. Yet, more recently, clinically significant
muscle weakness and impaired respiratory control have been observed at TOF ratios of up to
0.90. At TOF ratios less than 0.90, awake volunteers exhibit impaired pharyngeal function, airway
obstruction, an increased risk of aspiration of gastric contents, an impaired hypoxic ventilatory
control, and unpleasant symptoms of muscle weakness. In surgical patients, an association
between TOF ratios less than 0.90 and adverse respiratory events and prolonged PACU length of
stay has been observed. At the present time, it is generally agreed that adequate recovery of
neuromuscular function is represented by an adductor pollicis TOF ratio ofat least 0.90 (or even
1.0 when AMG is used.

Clinical Signs and Symptoms

A variety of clinical signs may be present in patients with residual neuromuscular blockade,
including the following: inability to perform a head lift, hand grip, eye opening, or tongue
protrusion; inability to clench a tongue depressor between the incisor teeth; inability to smile,
swallow, speak, cough, track objects with eyes; or inability to perform a deep or vital capacity

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breath. Symptoms of residual blockade that have been reported include subjective difficulty
performing the aforementioned tests, as well as blurry vision, diplopia, facial weakness, facial
numbness, and general weakness. Although the majority of patients with TOF ratios of 0.90 to 1.0
will have recovered satisfactory strength in most muscle groups, signs and symptoms of muscle
weakness may be present in some of these patients.
In contrast, a few patients with significant residual blockade (TOF ratios <0.70) may exhibit no
apparent muscle weakness. The most inclusive and precise definition of residual neuromuscular
blockade should include not only objective and quantifiable monitoring data (a TOF ratio <0.90
demonstrated with AMG, mechanomyography, or electromyography) but also clinical evidence of
impaired neuromuscular recovery (swallowing impairment, inability to speak or perform a head
lift, diplopia, and/or general weakness).

Incidence of Residual Neuromuscular Blockade

Residual neuromuscular Blockade is not a rare event in the PACU. In 1979, Viby-Mogensen
examined the efficacy of neostigmine in reversing d-tubocurarine, gallamine, or pancuronium
blockade.41 On arrival to the PACU, 42% of patients had a TOF ratio less than 0.70, and 24%
were unable to perform a 5-second head lift (the majority of these subjects had TOF ratios <0.70).
The authors concluded that the average dose of neostigmine given (2.5 mg) was insufficient for
reversing neuromuscular blockade. Subsequent studies demonstrated a similarly frequent
incidence of residual blockade in patients receiving long-acting NMBDs; 21% to 50% of patients
in the early postoperative period had TOF ratios less than 0.70. Subsequently, the risk of
postoperative residual blockade was reduced if intermediate-acting NMBDs were used instead of
long-acting drugs. As the use of long-acting NMBDs began to decrease in clinical practices, many
investigators hoped that residual blockade would become an uncommon occurrence in the
PACU. However, incomplete neuromuscular recovery continues to be a common postoperative
event. Large-scale studies (150 to 640 subjects) have demonstrated that approximately 31% to
50% of patients have clinically significant residual neuromuscular blockade with adductor pollicis
TOF ratios less than 0.90 following surgery. In a meta-analysis of data from 24 clinical trials,
Naguib and colleagues calculated the incidence of residual blockade by NMBD type and TOF
ratio.44 The pooled rate of residual blockade, defined as a TOF ratio less than 0.90, was 41%
when studies using intermediate-acting NMBDs were analyzed (Table 35-2). In conclusion, a
frequent incidence of residual neuromuscular blockade still occurs worldwide in the immediate
postoperative period; with current practice and inadequate monitoring, the incidence of this
complication is not decreasing over time. The observed incidence of postoperative residual
blockade varies widely between studies, ranging from 5% to 93%.44 A number of factors may
influence the degree of neuromuscular recovery measured following tracheal extubation,
accounting for the reported variability in the incidence of residual blockade (Box 35-1). The
observed incidence of residual blockade is more frequent if a threshold definition of 0.90 is used

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(versus the previous threshold of 0.70) (see Table 35-2). Similarly, a frequent incidence of
residual paralysis is observed if there is a short time interval between reversal of NMBDs and
quantification of TOF ratios (TOF ratios measured at the time of extubation versus measurement
in the PACU).49 Furthermore, the technology used to quantify neuromuscular recovery may
influence the percentage of patients with TOF ratios less than 0.90 following surgery. For
example, when compared with mechanomyography (MMG), AMG frequently overestimates the
degree of neuromuscular recovery.

Adverse Effects of Residual Blockade

Many investigations have demonstrated that approximately one half of patients will be admitted to
the PACU with TOF ratios less than 0.90, as measured with AMG, MMG, or electromyography
(EMG). The impact of this residual muscle weakness on clinical outcomes has been less well-
documented. Yet even minimal levels of neuromuscular blockade may have clinical
consequences. The following section reviews the effects of residual blockade in both awake
volunteer studies and in postoperative surgical patients.

Adverse Effects of Residual Blockade—Awake Volunteer Studies.

Surgical patients receive a variety of anesthetics in the perioperative period, which complicates
an assessment of the particular effect of residual neuromuscular blockade on clinical outcomes.
Conducting awake volunteer trials allows investigators to more precisely quantify the impact of
NMBDs and various degrees of neuromuscular blockade on physiologic systems in the absence
of anesthetics. In general, these studies have titrated NMBDs to various TOF ratios in awake
subjects, and measured the effects on the respiratory system and on signs and symptoms of
muscle weakness. Early volunteer investigations concluded that respiratory impairment was
minimal at TOF ratios of 0.60 to 0.70. Respiratory frequency, tidal volume, vital capacity, and
peak expiratory flow rates were not altered during the study, although vital capacity and
inspiratory force were both significantly reduced compared with control values at a TOF ratio of
0.60. The authors concluded that these changes were of minor clinical importance. Subsequent
investigations have revealed that pharyngeal and respiratory function is impaired at TOF ratios as
high as 0.90 to 1.0. Return of pharyngeal muscle function is essential for airway control following
tracheal extubation. In series of human studies from the Karolinska Institutet, Sweden, a
functional assessment of the pharynx, upper esophageal muscles, and the integration of
respiration with swallowing was performed during various levels of neuromuscular blockade. At
adductor pollicis TOF ratios less than 0.90, pharyngeal dysfunction was observed in 17% to 28%
of young adult volunteers (Fig. 35-4), increasing more than twofold in patients older than 60 years
and associated with reduced upper esophageal sphincter resting tone and misdirected
swallowing and aspiration (laryngeal penetration) of oral contrast material. Eikermann and

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colleagues conducted several investigations examining the effect of residual paresis on
respiratory muscle function in awake volunteers. Awake subjects were administered a rocuronium
infusion, which was titrated to a TOF ratio 0.50 to 1.0. At a minimal level of residual blockade
(approximately 0.80), the authors observed impaired inspiratory air flow andupper airway
obstruction, a marked decrease in upper airway volumes and upper airway dilator muscle
function, and increased upper airway closing pressure and collapsibility (Fig. 35-5). In addition,
evidence from human studies of respiratory control suggest that residual blockade inhibits
hypoxic ventilatory control while leaving the ventilator control during hypercapnia unaffected. In
human volunteers, the hypoxic ventilatory response was attenuated by 30% after administration
of either atracurium, vecuronium, or pancuronium at an adductor pollicis TOF ratio of 0.70,
returning to normal after spontaneous recovery to a TOF ratio of greater than 0.9052 (Fig. 35-6).
An increase in ventilator drive during hypoxia is primarily mediated by afferent input from
peripheral chemoreceptors in the carotid bodies located bilaterally at the carotid artery bifurcation,
whereas ventilatory regulation during hypercapnia is mediated via CO2 interaction with brainstem
chemoreceptors. In experimental animals, the firing frequencies of carotid body chemoreceptors
is almost abolished by the administration of a nondepolarizing NMBD because of a cholinergic
blockade of nicotinic acetylcholine receptors within the carotid body oxygen signaling pathway.53
Awake volunteer studies have also revealed that unpleasant symptoms of muscle weakness are
present in subjects with small degrees of residual neuromuscular blockade. Conscious subjects
given a small “priming” dose of pancuronium noted blurred vision, difficulty
swallowing and keeping their eyes open, and jaw weakness at a TOF ratio of 0.81.54 Symptoms
of diplopia, dysarthria, and subjective difficulty swallowing were reported by subjects at TOF
ratios of 0.60 and 0.70.34 Reduced clarity of vision was described in all subjects receiving a
mivacurium infusion at a TOF ratio of 0.81.55 Kopman and associates examined 10 volunteers
for symptoms and signs of residual paralysis at various TOF ratios.37 Testing was performed at
baseline (before an infusion of mivacurium), at a TOF ratio of 0.65 to 0.75, at 0.85 to 0.95, and at
full recovery (1.0). All subjects had significant signs and symptoms at a TOF ratio of 0.70 (inability
to maintain incisor teeth apposition, sit without assistance, or drink from a straw, visual
disturbances, facial numbness, difficulty speaking and swallowing, general weakness), and in
seven subjects, visual symptoms persisted for up to 90 minutes after the TOF
ratio had recovered to unity.

Adverse Effects of Residual Blockade —Postoperative Surgical Patients.

Awake volunteers have impairment of respiratory function and a variety of symptoms of muscle
weakness at TOF ratios of 0.50 to 0.90. Similar adverse events have been observed in
postoperative surgical patients with TOF ratios less than 0.90 measured in the PACU. Incomplete
neuromuscular recovery is a risk factor for hypoxemic events, airway obstruction, unpleasant
symptoms of muscle weakness, delayed PACU length of stay, and pulmonary complications

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during the early postoperative period. Clearly, an association exists between neuromuscular
management characteristics and postoperative morbidity and mortality. Beecher and colleagues
collected data from 10 university hospitals between the years 1948 to 1952 to determine
anesthetic-related causes of mortality.56 Risk of death related to anesthesia was six times more
frequent in patients receiving NMBDs (primarily tubocurarine and decamethonium) compared with
those administered no NMBDs (1:370 versus 1:2100). Although the authors conclude that there is
“an important increase in anesthesia death rate when muscle relaxants are added”56 to an
anesthetic, the use or omission of pharmacologic reversal in patients receiving NMBDs was not
reported or analyzed. In another large-scale study, mortality data associated with anesthesia
were collected over a 10-year period (1967-1976) at a single institution in South Africa.57 An
analysis of 240,483 anesthetics revealed that “respiratory inadequacy following myoneural
blockade” was the second-most common cause of death. Again, data relating to the use of
pharmacologic reversal drugs were not provided. A study from the Association of Anaesthetists of
Great Britain and Ireland examined deaths that were judged “totally due to anesthesia” and
reported that postoperative respiratory failure secondary to neuromuscular management was a
primary cause of mortality.58 Rose and associates examined patient, surgical, and anesthetic
factors associated with critical respiratory events in the PACU.59 Of the anesthetic management
factors assessed the most frequent rate of critical respiratory events was observed in patients
receiving large doses of NMBDs (the use of reversal drugs was not analyzed). Two investigations
of anesthetic complications resulting in admissions to the intensive care unit determined that
“failure to reverse after muscle relaxants” and “ventilatory inadequacy after reversal of muscle
relaxants” were the most common causes of admission.60,61 Sprung and colleagues reviewed
the medical records of patients who experienced a cardiac arrest over a 10-year period (223 of
518,284 anesthetics).62 The most important category was the use of NMBDs, involving either
hypoxia caused by inadequate pharmacologic reversal or asystole induced by anticholinesterase
drugs. A large case-control investigation was performed of all patients undergoing anesthesia
over a 3-year period (n = 869,483) in The Netherlands assessing the impact of anesthetic
management characteristics on the risk of coma or death within 24 hours of surgery.63 Reversal
of the effects of NMBDs was associated with a significant reduction (odds ratio, 0.10, 95% CI,
0.03-0.31) in the risk of these complications. Epidemiologic studies thus suggest an association
between incomplete neuromuscular recovery and adverse events in the early postoperative
period. Notably, an important limitation of these outcome studies is that residual paresis was not
quantified at the end of surgery. Therefore, causality (residual blockade results in postoperative
complications) can only be suggested but not proven. In order to address these limitations, more
recent studies have quantified TOF ratios in the PACU and documented a relationship between
residual blockade and adverse outcomes. Several clinical investigations have documented an
association between postoperative residual blockade and adverse respiratory events. In an
observational study by Bissinger and colleagues, patients with TOF ratios less than 0.70 in the
PACU had a more frequent incidence of hypoxemia (60%) compared with patients with TOF

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ratios 0.70 or greater (10%, P < .05).64 Another small study of orthopedic surgical patients
randomized to receive either pancuronium or rocuronium revealed that patients with TOF ratios
less than 0.90 on arrival to the PACU were more likely to develop postoperative hypoxemia (24 of
39 patients) than those with TOF ratios greater than 0.90 (7 of 30 patients, P = .003).65 Murphy
and associates conducted a case-control study examining the incidence and severity of residual
blockade in patients who developed critical respiratory events in the PACU.38 Seventy-
fourpercent of patients in the group with critical respiratory events had TOF ratios less than 0.70,
compared with 0% in the matched control group (matched for age, sex, and surgical procedure).
Because the two cohorts did not differ in any perioperative characteristics with the exception of
neuromuscular recovery, these findings suggest that unrecognized residual paralysis is an
important contributing factor to postoperative adverse respiratory events. Another investigation by
this same group examined the effect of AMG monitoring on postoperative respiratory events.26
Few patients randomized to AMG monitoring had postoperative TOF ratios less than 0.90, and a
less frequent incidence of early hypoxemia and airway obstruction was observed in this group
(compared with patients randomized to standard qualitative monitoring). A study of 114 patients
randomized to neostigmine reversal or placebo (saline) documented a significantly more frequent
incidence of both postoperative residual blockade and hypoxemia in the placebo group.66
Residual blockade in the PACU may also result in pulmonary complications within the first
postoperative week. Berg and colleagues randomized 691 patients to receive pancuronium,
atracurium, or vecuronium.67 TOF ratios were quantified in the PACU, and subjects followed for
6 days for pulmonary complications. In the pancuronium group, significantly more patients with
TOF ratios less than 0.70 developed a pulmonary complication (16.9%) compared with patients
with TOF 0.70 or greater (4.8%). Notably, the study also demonstrated a continuously increased
risk for postoperative pulmonary complications with increased age, a finding of significant clinical
relevance for older adult patients, a growing part of the surgical patient population. Residual
blockade causes unpleasant symptoms of muscle weakness. This symptom of “general
weakness” was the most sensitive “test” for determining whether patients had a TOF ratio of less
than 0.90 in the PACU.17 Orthopedic surgical patients given pancuronium had a more frequent
risk of exhibiting both TOF ratios less than 0.90 and symptoms of blurry vision and general
weakness during the PACU admission, compared with patients randomized to receive
rocuronium.65 Similar findings were observed in a cardiac surgical patient population not
receiving anticholinesterase drugs.68 The subjective experience of residual neuromuscular
blockade after surgery was determined by examining 155 patients for 16 symptoms of muscle
weakness during the PACU admission.27 The presence of symptoms of muscle weakness was
predictive of a TOF ratio less than 0.90 (good sensitivity and specificity). The residual effects of
NMBDs on postoperative muscle strength may impair clinical recovery and prolong PACU
discharge times. In a small study of patients randomized to receive either pancuronium or
rocuronium, the times required to meet and achieve discharge criteria were significantly longer in
the pancuronium group, and patients in the cohort as a whole with postoperative TOF ratios less

8
than 0.90 were more likely to have a prolonged PACU stay compared with those with TOF ratios
greater than 0.90.65 A larger investigation measured TOF ratios in 246 consecutive patients on
arrival to the PACU.39 The PACU length of stay was significantly longer in patients with TOF
ratios less than 0.90 (323 minutes) compared with patients with adequate recovery of
neuromuscular function (243 minutes). Multiple regression analysis revealed that only age and
residual blockade were independently associated with PACU length of stay. In conclusion, a
number of studies conducted over the past 5 decades have documented the effects of small
degrees of residual blockade in human volunteers and surgical patients. Awake volunteer
investigations have demonstrated that subjects with TOF ratios less than 0.90 have reduced
upper airway tone and diameters, upper airway obstruction, pharyngeal dysfunction with impaired
airway integrity, decreased upper esophageal tone, and an increased risk of aspiration, impaired
hypoxic ventilator control, and unpleasant symptoms of muscle weakness. Epidemiologic
outcome investigations have suggested an association between incomplete neuromuscular
recovery and major morbidity and mortality. Prospective clinical trials have revealed that patients
with TOF ratios less than 0.90 in the PACU are at increased risk for hypoxemic events, airway
obstruction, postoperative pulmonary complications, symptoms of muscle weakness, and
prolonged PACU admission times. These data suggest that residual blockade is an important
patient safety issue in the early postoperative period. Therefore, appropriate management of
reversal of neuromuscular blockade is essential to optimize patient outcomes.

Residual neuromuscular blockade can be defined by inadequate neuromuscular recovery as

measured by objective neuromuscular monitoring. It is also referred to as residual paralysis,
residual curarisation, and residual neuromuscular block. More specifically, recent opinion
suggests a definition of inadequate train of four recovery of less than 0.9 (TOF <0.9).

The train of four method of peripheral nerve stimulation was introduced in the 1970s. The use of a
threshold ratio of 0.7 was derived from several studies aiming to establish the concept of
“acceptable recovery”. This ratio was derived from certain clinical signs and subjective
neuromuscular monitoring including the ability of patients to open their eyes widely, cough,
protrude their tongue, attain vital capacity breaths of 15-20 mL/kg, and sustain tetanic stimulation
without fade for 5 seconds.

With advances in monitoring and continued studies, a TOF <0.9 is now considered as residual
neuromuscular blockade. This more stringent ratio was arrived at after several studies
demonstrated an increased risk of aspiration and pharyngeal dysfunction at TOF <0.9, and
impaired inspiratory flow and partial airway obstruction at TOF <0.8.

It should be noted that there is a large variability between patients. Some patients may display
obvious muscle weakness despite a TOF>0.9, whilst complete clinical recovery of muscle

9
strength can be observed in others with a TOF<0.9. Importantly, distressing symptoms in awake
patients may be observed even at subtle levels of neuromuscular block of TOF >0.9 .

The ideal test of neuromuscular recovery would not require an awake, cooperative patient and
would be easily applied, reliable and inexpensive.

Clinical criteria for evaluating adequacy of muscle function include: assessment of a patient’s
ability to maintain adequate head lift, jaw clench, grip strength, and tidal volume. These are
unreliable predictors of neuromuscular recovery. For example, it is possible to maintain a 5
second head lift with TOF <0.5. In addition, many of these tests are not specific for respiratory
function. The table below describes the diagnostic value of 2 common clinical tests

Train-of-four neuromuscular monitoring is commonly conducted with a subjective measurement,

either as a simple train of four count (TOFC) or train of four ratio (TOF). The latter refers to when
there is already a TOFC of 4, and subsequent assessment is made for fade in T4 compared to
T1. Tactile evaluation (movement of patient’s thumb against the observer’s fingers) is more
accurate than visual assessment. However, neither are reliable in detecting fade (37% versus
57% in one study), and the majority of evaluators are unable to detect fade when TOF ratios >
0.4.

Double Burst Stimulation (DBS) is another method of neuromuscular monitoring, but is also
commonly measured in a subjective manner. This improves detection of fade to up to 0.6 – which
is significant, but doesn’t eliminate the incidence and degree of residual neuromuscular blockade.

Objective measurement of neuromuscular monitoring is the only way of accurately assessing

residual neuromuscular blockade. In general, it is conducted via quantitative measurement of the
strength of contraction of a peripheral muscle (eg. adductor pollicis muscle in thumb) in response
to peripheral nerve stimulation (eg. ulnar nerve at wrist) produced by 2 stimulating electrodes.
Each measurement technique measures the force of contraction, either directly or by a factor that
is proportional to force.

It is good practice to always consider giving a reversal agent, unless there is objective
neuromuscular monitoring demonstrating a TOF >0.9 (giving neostigmine to fully recovered

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patients may decrease upper airway muscle activity and tidal volume). Presently,
anticholinesterases are one of the most common techniques for reversing neuromuscular
blockade – neostigmine, pyridostigmine, edrophonium. It should be noted that there is a great
deal of variability in the time to onset and duration of neostigmine reversal. Given given after
TOFC of two, the average time to adequate reversal is 15 minutes, with some patients still
demonstrating residual neuromuscular blockade (TOF<0.9) after 30 minutes.

Residual muscle paralysis represents imminent risk for passive regurgitation and gastric
aspiration by pharyngeal and laryngeal muscles dysfunction, in spite of adequate diaphragm
recovery. More recent studies have shown that neuromuscular blocker residue may also promote
decrease in ventilatory response to hypoxia, cooperating with significant percentage of
postoperative brain hypoxic injuries. This effect is attributed to a "new" neuromuscular blocker
property on carotid chemoreceptors. Equally important are postoperative pulmonary
complications, especially atelectasis and pneumonias.
The incidence of pneumonias is directly related to the type of neuromuscular blocker and varies
20% to 50% for long duration NMBs and approximately 2% to 9% for atracurium and vecuronium
and even higher values in more recent publications. With plasma concentration decrease by
metabolic process or simple redistribution, a "reservoir" remains in the biophase, promoting a
blocking effect until these sites are emptied from the drug. One may then say that NMB recovery
is a function of the affinity constant of the neuromuscular blocker to binding sites during biophase.
Standard method to check motor responses is mechanography. However, these monitors are
difficult to handle needing a relatively long time for their installation, in addition to requiring total
immobility of the studied muscle, thus being currently restricted to research. Accelerometry has
been clinically used to indirectly evaluate muscle strength through an acceleration transducer in
general placed on the thumb. Its efficiency in detecting residual muscle block has been shown in
children and adults. The classic concept to accurately interpret neuromuscular transmission
phenomena implies using current intensity close to the supramaximal, that is, that able to
stimulate all axons of a nerve. However, supramaximal response with stimulations above 30 mA
is painful and uncomfortable for awaken patients. This way, 30 mA, usually submaximal for adult
patients, has been recommended for PACU measurements. Fatigue is often successfully
detected and is never lower than that detected with supramaximal currents . Major advantages of
submaximal stimulation have been currently advocated, especially with accelerometry, because it
would decrease the percentage of baseline deviations, helping the interpretation of fatigue.

RESEARCH OBJECTIVES

General Objective: To assess the incidence of residual neuromuscular blockade in a post

anesthetic care unit in Chong Hua Hospital.
Specific Objectives:

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1. To determine the outcome related to critical respiratory events (CREs), PACU complications
and the length of PACU and hospital stay.
2. To determine incidence of postoperative residual curarization
3. To determine significant difference in postoperative residual curarization in terms of gender,
creatinine concentration, duration of the case, and ASA physical status classification

DEFINITION OF TERMS
Train of four: A peripheral nerve stimulator used to assess neuromuscular transmission when
neuromuscular blocking agents (NMBAs) are given to block musculoskeletal activity. By
assessing the depth of neuromuscular blockade, peripheral nerve stimulation can ensure proper
medication dosing and thus decrease the incidence of side effects.
Suggamadex: A modified γ-cyclodextrin that shows a high affinity for the steroidal NMBDs
rocuronium and vecuronium. Sugammadex is able to form a tight inclusion complex with either of
these steroidal NMBDs, thereby inactivating the effects of rocuronium and vecuronium, resulting
in rapid reversal of neuromuscular blockade.
Rocuronium: A monoquaternary aminosteroid nondepolarizing NMBD with an ED95 of 0.3 mg/kg
that has an onset of action of 1 to 2 minutes and a duration of action of 20 to 35 minutes.
Accelerometry: A devise used to evaluate muscle strength through an acceleration transducer in
general placed on the thumb.
Double Burst Stimulation (DBS): consists of two short lasting, 50-Hz tetanic stimuli or bursts
separated by a 750-ms interval. The response to this pattern of stimulation is two single
separated muscle contractions of which the second is less than the first during nondepolarizing
neuromuscular blockade.
Residual neuromuscular blockade: Inadequate neuromuscular recovery as measured by
objective neuromuscular monitoring. It is also referred to as residual paralysis, residual
curarisation, and residual neuromuscular block
ASA Physical Status Classification System: Risk stratification system based on comorbid
conditions that are a threat to life or that limit activity and thus helps in predicting preoperative
risks.

ASA DEFINITION
1 A normal, healthy patient
2 A patient with mild, systemic disease
3 A patient with severe, systemic disease
4 A patient with severe, systemic disease that is
a constant threat to life
5 A moribund patient who is not expected to
survive without the operation
6 A declared brain-dead patient whose organs
are being removed for donor purposes

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 “E” denotes Emergency surgery

METHODOLOGY
Study Design
This study is a single-center, prospective, observational study.
Study Setting
This study will be conducted in the post anesthetic care unit of Chong Hua Hospital, a 660-bed
capacity tertiary hospital in Cebu City.
Study Population
Inclusion Criteria:
• patients undergoing general anesthesia with neuromuscular blockade
• ASA physical status I and II
• intermediate acting nondepolarizing neuromuscular blocking drug: Rocuronium
• suggamadex as reversal agent
Exclusion Criteria:
• Age <18 years old
• BMI >40kg/m2
• ASA physical status >II
 Allergy to gel electrodes
 Emergency surgical operation
 The need for reoperation during the same hospital admission
• Unable to consent

ETHICAL CONSIDERATIONS

The protocol shall be submitted to the Institutional and Ethics Review Board for review and
approval. The aim of the study, its procedure and importance shall be explained by the principal
investigator to the subjects of the study and an informed consent obtained with the 6 A declared
brain-dead patient whose organs are being removed for donor purposes “E” denotes Emergency
surgery assurance that whatever data gathered shall be confidential and will be exclusively used
for research purposes only. The participants of the study will not be placed in any form of risk.
The participation of the subjects in the study shall be of their own free will and that they can
withdraw from the study anytime and for whatever reason.

DATA GATHERING PROCEDURE

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If the patient met the inclusion criteria, neuromuscular transmission monitoring was immediately
performed, after standard monitoring and oxygen supplementation had been started. In all the
patients, 40-mA TOF stimulation (four pulses of 0.2 ms in duration, at a frequency of 2 Hz) was
performed at the ulnar nerve every 15 s via two surface electrodes. The evoked responses at the
thumb were measured by the TOF-Watch SX acceleromyograph (Organon Teknika, Boxtel, the
Netherlands). The TOF-Watch was used in an uncalibrated mode. Three consecutive TOF
measurements (separated by 15 s) were obtained and the average of the three values was
recorded. If measurements differed by more than 20%, additional TOF measurements were not
obtained and the patient was excluded from the study. Patients were also excluded if three TOF
measurements could not be obtained. On arrival at the PACU, heart rate, blood pressure and skin
temperature (volar surface of the forearm) were recorded.

Patients were categorized into two groups on the basis of TOF data; TOF ratios at least 0.9 and
less than 0.9 were assessed as complete and incomplete neuromuscular recovery following
general anaesthesia, respectively.

For each patient, the following data were recorded after hospital discharge: demographics (age,
sex) and anthropometric (height, weight) data, clinical history, surgical diagnosis, American
Society of Anesthesiologists (ASA) physical status, perioperative data (medication used during
operation, neuromuscular blocker and blockade reversal agents), time between date of enrolment
and date of hospital discharge, comorbidities, adverse events and vital status at discharge.
Postoperative events were grouped into infectious and parasitic; endocrine, nutrition, metabolic
and immunological; blood and blood-forming organs; circulatory system; respiratory system;
digestive system; genitourinary system; skin and subcutaneous system; musculoskeletal system
and connective tissue; and ill-defined conditions. Type of surgery was not recorded.

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APPENDIX A

Table 1. Patient Characteristics

Age

Gender

BMI

ASA classification

Comorbiditities

Type of anesthesia

Introperative fluids

Duration of surgery

Duration of anethesia

Temperature at PACU admission

Length of PACU Stay

Length of hospital Stay

At PACU admission

Systolic BP
Diastolic BP
Heart Rate
SPO2 %

TOF Mean
TOF mean < 90
TOF mean < 80
TOF mean < 70
TOF mean < 60
Critical Respiratory events
Upper airway obstruction
Mild-moderate hypoxia
Severe hypoxia
Respiratory distress
Inability to breathe deeply
Upper airway muscle weakness

15
Table 2. Characteristics of patients with (TOFm <90) and without (TOFm >90) neuromuscular
residual block

TOFm <90 TOFm >90 p

age    

Gender    

BMI    

ASA
I
II
Duration of Surgery

Duration of Anesthesia

Time (min) from last dose of

NMBD to arrival in PACU
Post-operative hypoactive

Temperature at PACU

SPO2 at PACU admission

TOF mean

Length of PACU stay (min)

Length of hospital stay (days)

Table 3 Incidence of critical respiratory events in patients with (TOFm <90) and without (TOFm
>90) neuromuscular residual block in the post-anaesthesia care unit

TOFm <90 TOFm >90 P

Critical respiratory events    

Upper airway obstruction    

Mild moderate hypoxia    

Severe hypoxia

16
 Respiratory distress

Inability to breathe deeply

Upper airway muscle weakness

APPENDIX B

INFORMED CONSENT FORM

This Informed Consent Form is for patients who are admitted at Chong Hua Hospital, subjected to
undergo elective surgery under General Anesthesia and who is invited to participate in research
on the residual curarization in the recovery room. The title of the research project is “Incidence of
postoperative residual neuromuscular blockade in the post anesthetic care unit: an prospective
study”
Dear Sir/Madame:
I am Ruby Anne D. Batobalonos, a second year resident of the Department of Anesthesia of this
institution. I am doing a study on the Incidence of postoperative neuromuscular blockade in the
post anesthetic care unit. I am going to give you information and invite you to be part of this
research. You do not have to decide today whether or not you will participate in the research.
Before you decide, feel free to ask me any questions you may have about the research. There
may be some words that you do not understand. Please ask me to stop as we go through the
information and I will take time to explain. If you have questions later, you can ask them of me,
your attending Anesthesiologist or the staff. Neuromuscular blocking agents are used to provide
skeletal muscle paralysis and facilitate tracheal intubation for surgical procedures. It is the aim of
this study to determine the incidence of postoperative residual neuromuscular blockade in the
post anesthetic care unit. The neuromuscular block was defined as TOF <0.9 and it was
quantified at admission to the PACU using acceleromyography of the adductor pollicis muscle
(TOF-Watch). Two surface electrodes will be attached to the cleansed
skin over the ulnar nerve on the volar side of the wrist. The distal electrode will be
positioned where a proximal bending line crosses the radial side of the flexor carpi
ulnaris muscle. The proximal electrode will be placed 3 cm proximal of the distal
electrode. The piezoelectric transducer will be placed with its largest flat side against the
volar aspect of the distal phalanx of the thumb. The stimulation current was set to 50
mA. The resulting TOF ratios will be obtained (4 pulses of 0.2 ms duration over 2 s at a
frequency of 2 Hz). Three consecutive TOF measurements (separated by 15 s) will be
obtained, and the average of the 3 values recorded. If a value differed from the
others by more than 10%, an additional TOF measurement will be obtained and the closest 3
ratios will be averaged. Neuromuscular block will be re-assessed hourly while patients maintained
TOF<0.9. The initial TOF ratios are measured before any therapeutic in the PACU. Your

17
participation in this research is entirely voluntary. Whether you choose to participate or not, all the
services of the hospital will continue and nothing will change. You may choose to withhold
participation from the study at any time without consequence. The information that will be
collected from this research will be kept confidential. Any information about you will have a
number on it instead of your name. Only the investigator will know what your number is and we
will lock that information up with lock and key.
If you have any questions, you may ask them now or later, even after the study has
started. If you wish to ask questions later, you may contact me thru phone at 09177201606 or via
e-mail at bhi_an@[Link].
This research has been reviewed and approved by the Chong Hua Hospital Institutional Review
Board, which is a committee, whose task it is to make sure that research participants are
protected from harm. If you wish to find out more about the IRB or your rights as a research
participant, you may contact them at 255 8000.
---------------------------------------------------------------------------------------------------------------------------------
I have read the foregoing information, or it has been read to me. I have had the opportunity to ask
questions about it and any questions that I have asked have been answered to my satisfaction. I
consent voluntarily to participate in this research.
Name of Participant (in print) ____________________________
Signature of Participant _____________________________
Date (day/month/year) _____________________________

If Illiterate
I have witnessed the accurate reading of the consent form to the potential participant and the
individual has had the opportunity to ask questions. I confirm that the individual has given consent
freely.
Name of Witness (in print) ______________________ AND Thumb print of
participant
Signature of Witness ______________________
Date (day/month/year) ______________________

I have accurately read out the information sheet to the potential

participant, and to the best of my ability made sure that the participant understands the conduct of
the study. I conform that the participant was given an opportunity to ask questions about the
study and all the questions asked by the participant have been answered to the best of my ability.
I confirm that the individual has not been coerced into giving consent and the consent has been
given freely and voluntarily.
Name of Researcher/person taking the consent ______________________

18
Signature of Researcher/person taking the consent ______________________
Date (day/month/year) ______________________

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