Download Deep Neuromuscular Blockade - American Association of Nurse

Supplement to
June 2011
Volume 79 „ Number 3
ISSN 0094-6354
Established in 1933, the AANA Journal is the official publication of the American Association of Nurse Anesthetists.
December 2013
CNE
Learning Objectives
At the conclusion of this activity,
participants should be able to:
• Summarize the importance of achieving
deep neuromuscular blockade during
surgical procedures.
• Describe the benefits and limitations of
currently available reversal agents.
• Evaluate strategies such as the use
of novel reversal agents that allow for
deep neuromuscular blockade and their
potential impact on surgical practice.
• Assess multidisciplinary approaches to
managing surgical patients who require
deep neuromuscular blockade.
Deep Neuromuscular
Blockade: Exploration
and Perspectives on
Multidisciplinary Care
4
The Role of Deep Neuromuscular
Blockade in Surgical Procedures
8
Reversal of Neuromuscular
Blocking Agents: Current Practice
12
New and Advanced Options in
Neuromuscular Blockade Management
This activity is provided by
This continuing educational activity is supported by an educational grant from
VINDICO
medical education
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Supplement to
June 2011
Volume 79 „ Number 3
ISSN 0094-6354
Established in 1933, the AANA Journal is the official publication of the American Association of Nurse Anesthetists.
Course Chair:
Mark D. Welliver, CRNA, DNP, ARNP
Associate Professor of Professional Practice
School of Nurse Anesthesia
Harris College of Nursing and Health Sciences
Texas Christian University
Fort Worth, TX
Accreditation and
Credit Designation:
Matt L. Kirkland, MD, FACS
No relevant financial relationships to disclose.
Vindico Medical Education, LLC is accredited as a provider
of continuing nursing education by the American Nurses
Credentialing Center’s Commission on Accreditation.
John J. Nagelhout, CRNA, PhD, FAAN
No relevant financial relationships to disclose.
Faculty:
Matt L. Kirkland, MD, FACS
Clinical Assistant Professor of Surgery
Director, Bariatric Surgery at Pennsylvania
Hospital
Philadelphia, PA
This program has been prior approved by the American
Association of Nurse Anesthetists for 1 CE Credit; AANA
Code Number 1028889; Expiration Date: 11/30/2014.
John J. Nagelhout, CRNA, PhD, FAAN
Director of the Kaiser Permanente School of
Anesthesia
California State University Fullerton
Pasadena, CA
Vindico Medical Education
Ronald Codario, MD, FACP, FNLA, CCMEP
Medical Director
Vindico Medical Education will provide 1.0 contact hours
for nurses.
This enduring material is approved for 1 year from the date
of original release, December 1, 2013 to November 30,
2014.
How To Participate in this Activity
and Obtain CME Credit:
To participate in this CNE activity, you must read the
objectives and articles, and complete the CNE posttest and
evaluation. Provide only one (1) correct answer for each
question. A satisfactory score is defined as answering 8
out of 10 of the posttest questions correctly. Upon receipt
of the completed materials, if a satisfactory score on the
posttest is achieved, Vindico Medical Education will issue
a certificate of completion within 4 to 6 weeks. Retesting is
not permitted for those who did not achieve a satisfactory
score in their first attempt.
Chris Rosenberg
Director of Medical Education
Medical Writer:
Sharon Powell
Medical Editor
Reviewer:
Kimi Dolan
David Barker
Theresa McIntire
Publication Design
This monograph is based on a roundtable discussion
held Sept. 29, 2013 in Philadelphia.
Education activities are distinguished as separate
from endorsement of commercial products. When
commercial products are displayed, participants will
be advised that accredited status as a provider refers
only to its continuing education activities and does
not imply ANCC Commission on Accreditation
endorsement of any commercial products.
Michael F. Kinslow, CRNA, MS
Barbara A. Niedz, PhD, RN, CPHQ
Disclosures:
CNE providers are required to disclose to the activity
audience the relevant financial relationships of the
planners, teachers, and authors involved in the development
of CNE content. An individual has a relevant financial
relationship if he or she has a financial relationship in any
amount occurring in the last 12 months with a commercial
interest whose products or services are discussed in the
CNE activity content over which the individual has control.
Relationship information appears on this page.
The authors disclose that they do have significant financial
interests in any products or class of products discussed
directly or indirectly in this activity, including research
support.
Planning Committee and
Faculty members report the
following relationship(s):
Mark D. Welliver, CRNA, DNP, ARNP
Speakers Bureau: Merck & Co., Inc.
Consultant: Merck & Co., Inc.
Created and published by Vindico Medical Education, 6900 Grove Road, Building
100, Thorofare, NJ 08086-9447. Telephone: 856-994-9400; Fax: 856-384-6680.
Printed in the USA. Copyright © 2013. Vindico Medical Education. All rights
reserved. No part of this publication may be reproduced without written permission
from the publisher. The material presented at or in any of Vindico Medical Education
continuing medical education activities does not necessarily reflect the views and
2
Valerie Zimmerman, PhD
No relevant financial relationships to disclose.
Reviewer:
Michael F. Kinslow, CRNA, MS
No relevant financial relationships to disclose.
Lead Nurse Planner:
Barbara A. Niedz, PhD, RN, CPHQ
No relevant financial relationships to disclose.
Vindico Medical Education staff report the following
relationship(s):
No relevant financial relationships to disclose.
Signed disclosures are on file at Vindico Medical Education,
Office of Medical Affairs and Compliance.
Target Audience:
The intended audience for the activities is nurse anesthetists
and other healthcare professionals involved in the treatment
of patients undergoing surgery.
Overview:
Valerie Zimmerman, PhD
Lead Nurse Planner:
Kristin Riday
Program Manager
Medical Writer:
Neuromuscular blockade, induced by neuromuscular
blocking agents (NMBAs), although a powerful anesthetic
tool has the potential for significant adverse outcomes.
In addition, termination of the effects of neuromuscular
blocking agents has remained limited. Complete control
of neuromuscular blockade with immediate reversibility
would allow anesthesiologists and nurse anesthetists to offer
surgeons optimal conditions that are not always achieved at
present. The cholinesterase inhibitor drugs, first used to
reverse curare, currently remain the standard for reversing
all NMBAs. A new class of drugs, selective relaxant
binding agents (SRBAs), has the potential to overcome the
limitations and side effects of cholinesterase inhibitors. The
assurance of full, rapid reversal of neuromuscular blockade
will allow improved conditions for surgery and, possibly,
improved patient recovery and reduced postoperative
morbidity. This monograph will examine the science
focusing on the issues relevant to neuromuscular blockade
in the operating room, as well as its safe reversal.
Unlabeled and Investigational Usage:
The audience is advised that this continuing medical
education activity may contain references to unlabeled uses
of FDA-approved products or to products not approved by
the FDA for use in the United States. The faculty members
have been made aware of their obligation to disclose
such usage. All activity participants will be informed if
any speakers/authors intend to discuss either non-FDA
approved or investigational use of products/devices.
opinions of Vindico Medical Education. Neither Vindico Medical Education nor the
faculty endorse or recommend any techniques, commercial products, or manufacturers.
The faculty/authors may discuss the use of materials and/or products that have
not yet been approved by the US Food and Drug Administration. All readers and
continuing education participants should verify all information before treating patients
or utilizing any product.
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Introduction
CONTENTS
3
Introduction
4
The Role of Deep Neuromuscular
Blockade in Surgical Procedures
Matt L. Kirkland, MD, FACS
8
Reversal of Neuromuscular
Blocking Agents:
Current Practice
John J. Nagelhout, CRNA, PhD, FAAN
12
New and Advanced Options in
Neuromuscular Blockade
Management
Mark D. Welliver, CRNA, DNP, ARNP
18
CNE Posttest
19
CNE Instructions and
CNE Registration Form
The plant toxin curare was introduced in the early 1940s as
tubocurarine, a neuromuscular blocking agent, in addition to the
armamentarium of anesthesia practice to provide muscle relaxation
during surgery. This advance in anesthesiology was followed by the
recommendation that small doses of an anticholinesterase should
be administered at the end of surgery as a relaxant reversal. After
50 years, anticholinesterases still provide the main pharmacologic
approach to reversing neuromuscular blockade; however, consistent
and complete reversal is frequently not universally achieved. In addition, techniques to monitor the effects of neuromuscular blocking
agents and their reversal, available since the 1970s, are limited in
capability and not widely used.
Inconsistent monitoring of neuromuscular blockade and the continued incidence of residual paralysis continue to be all too common.
The types and stimulation modes of neuromuscular monitors, the
clinical correlation of extrapolated data, and the inherent limitations
of these monitors may not be fully understood by anesthesia providers
or surgeons. These issues coupled with the limitations of neuromuscular blockade reversal agents highlight an area for continued study.
Additionally, the benefits of novel approaches being introduced are
important new educational opportunities for surgical team members.
To help anesthesia providers and surgeons increase their knowledge,
which may help change attitudes and modify practices, Vindico
Medical Education sponsored a panel discussion of experts representing key members of the surgical team. The objective was to
share their experience and expertise, highlighting the ideal surgical conditions associated with a neuromuscular blockade from a
surgeon’s perspective, describing methods to assess the depth of the
neuromuscular blockade, reviewing available methods for reversing
the blockade, and explaining the significance of residual paralysis.
New approaches to reversal, which can allow more rapid reversal at
all blockade levels, were reviewed. Finally, no surgical environment
can be ideal without effective collaboration and communication
among the surgical team. Examples of the adverse consequences of
deficient communication and ways to remove constraints to effective
interaction were provided.
Readers can expect to become more knowledgeable about neuromuscular blocking agents and their reversal, and characteristics associated
with the depth of neuromuscular blockade that affect agent use,
monitoring, and recovery. In addition, readers should be motivated to
advocate for mutual understanding and improved teamwork, which
may encompass standardization of terms, clarification of responsibilities and procedures, and assurance that management plans are
understood among the team members.
Mark D. Welliver, CRNA, DNP, ARNP
Course Chair
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The Role of Deep Neuromuscular
Blockade in Surgical Procedures
Matt L. Kirkland, MD, FACS
eneral anesthesia is the uppermost level on a
sedation continuum.1 According to the American Society of Anesthesiologists’ definition, the
patient under general anesthesia is unarousable,
even with painful stimuli, often requires airway intervention, spontaneous ventilation is frequently inadequate, and
cardiovascular function may be impaired.1
A “triad of anesthesia” typically includes hypnosis (amnesia), lack of pain (analgesia), and immobility (paralysis).2
To achieve general anesthesia, modern techniques usually
include drugs specific for each component; that is, instead
of a single drug, a hypnotic drug, an analgesic drug, and a
muscle relaxant are used. Common hypnotic drugs are the
inhalation anesthetics such as desflurane, isoflurane, and
sevoflurane; injectable agents include propofol, etomidate,
midazolam, and ketamine. Analgesia is often achieved with
an opioid narcotic such as fentanyl, remifentanil, nalbuphine,
or tramadol.
Muscle relaxation induced by a neuromuscular blocking
agent (NMBA) has become the standard means to achieve
required levels of blockade. Their use is important during intubation; however, they are not always needed for or beyond
this application.3 Shorter acting opioid narcotics, particularly when used with propofol, can be used in circumstances
when analgesia and anesthesia are desired, but deep blockade is not required, such as in controlling muscle movement
of the diaphragm.
G
Neuromuscular Blocking Agents
Neuromuscular blocking agents were first used to facilitate tracheal intubation by paralyzing the vocal cords with a
concomitant reduction in laryngeal trauma.3,4 After being introduced for this application and surgical relaxation in 1942,
their use has been expanded, when appropriate, to assist with
efforts to achieve ideal surgical conditions. Relaxation can
provide an important contribution to optimizing the surgical
field by inhibiting spontaneous ventilation, relaxing skeletal
muscle, and inhibiting spontaneous movement.
Mechanism of the neuromuscular blockade
An uninhibited nerve impulse begins as an electrical current through the nerve.4 It is chemically transmitted across
the synapse in the form of acetylcholine, which binds to a
4
nicotinic receptor on the muscle for a few milliseconds. This
binding generates another chemical-electrical impulse, which
results in muscle contraction. Muscle relaxation occurs when
the acetylcholine is enzymatically cleaved by the acetylcholinesterase that is present in the basal lamina of the muscle.
Neuromuscular blocking agents inhibit the transmission of the impulse across the synapse by inhibiting the
action of acetylcholine on the receptor. There are 2 classes of drugs with different mechanisms of action that can
produce this inhibition: depolarizing and non-depolarizing agents. Depolarizing agents are represented by succinylcholine, which structurally is composed of 2 joined
acetylcholine molecules. When succinylcholine occupies
the receptor, depolarization occurs, which contributes to
the biphasic action of these agents, launching a complex
interaction of activation and inhibition.5 Succinylcholine
is not hydrolyzed by local acetylcholinesterase, and its
prolonged occupation of the receptor allows depolarization that lasts longer than a few milliseconds, preventing the spread of the action potential and inhibiting the
contraction. Succinylcholine has a rapid onset of action
(1 to 2 minutes), with an ultrashort (<10 minutes) duration of action. It undergoes rapid inactivation by plasma
cholinesterases.
Non-depolarizing neuromuscular blocking agents
are competitive antagonists of acetylcholine. They initiate clinically significant inhibition of muscle contraction when approximately 70% of receptors are occupied
by the blocking agent.4 There are 2 structural classes of
non-depolarizing agents: benzylisoquinoliniums and
aminosteroids. They are classified as having short, intermediate, or long durations of action.4
Ideal Surgical Conditions
From a surgeon’s perspective, there are 2 basic questions
related to neuromuscular blockade: (1) What are the components of an ideal surgical condition, particularly during
laparoscopic procedures; and (2) What are the challenges to
achieving the ideal condition?
Surgeon’s needs
Several criteria that can be affected by the level of neuromuscular blockade are associated with achieving an ideal
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surgical condition. Many of these conditions are interrelated. A larger operative space is always important to
the surgeon, particularly when working laparoscopically.
In addition to other benefits, a larger operative space can
help fulfill the need for better visualization, which is associated with fewer intraoperative technical errors and
contributes to fewer postoperative complications. The
surgeon needs access to tight spaces, which is more critical
in the setting of laparoscopic and robotic surgery. Classic tight spaces are in the pelvis for gynecologic and urologic procedures, and in the upper abdomen around the
esophageal hiatus, especially during laparoscopic esophagectomy. Immobilization is always important, and can be
essential for some procedures. Involuntary movement can
have disastrous consequences in tight spaces, particularly
when working in a relatively fixed platform. If the patient
moves, the instruments on the fixed platform can become
dislodged and injuries can result. Finally, lower insufflation
pressures are desirable to reduce hypercarbia. Authors of a
meta-analysis that included 15 randomized controlled trials comparing low with standard pressure during laparoscopic cystectomy concluded that low pressure is effective
in reducing postoperative pain in these patients.6 Using
a deep neuromuscular block in this and other abdominal
laparoscopies may increase the working space at lower carbon dioxide insufflation pressures and provide improved
patient outcomes.7
Ideal conditions
• Larger operative space
• Better visualization
• Access to tight spaces
• Immobilization
• Lower insufflation pressures (laparoscopy)
Challenges
One conflict surgeons encounter is the different definitions of relaxation that are used by surgeons and anesthesia providers. To allow a safe operation with good visualization, the triad of anesthesia, that is, hypnosis, analgesia,
and relaxation must be provided. In many situations, the
use of NMBAs is not adjunctive; rather, it is an essential
component of achieving ideal surgical conditions. However, particularly at the end of a case when a surgeon asks
for more relaxation, what may actually be needed is a better level of analgesia and hypnosis, which can be achieved
with a narcotic and propofol or a similar agent, rather
than more muscle relaxant. If unnecessary relaxant is given, recovery delays with residual paralysis may result. It is
important for surgeons to differentiate between the need
for analgesia and/or anesthesia and relaxation.
The requirements to achieve these ideal conditions
are not completely understood by many surgeons. There
are times when deeper degrees of muscle relaxation are
necessary, but that does not apply throughout the duration of the procedure. Different situations may require
greater and lesser degrees of neuromuscular blockade.
For example, intra-abdominal laparoscopies for hernia
repair, cholecystectomy, and sling procedures for urinary
incontinence require a shorter duration and less deep
levels of relaxation compared with laparoscopic transhiatal esophagectomy, and possibly robotic prostatectomy.
Most surgical procedures, however, are in between; that
is, they may need a short period of deep relaxation that
is reversed relatively quickly, or an intermediate level of
relaxation required throughout the procedure, as with
laparoscopic cholecystectomy and laparoscopic nephroureterectomy. When excising the bladder orifice, which
is adjacent to the obturator nerve, urologists may inadvertently stimulate the nerve, resulting in abduction of
the leg. Problems may arise with positioning and injuries
resulting from the leg falling out of position. In addition,
intra-abdominal and pelvic injuries may result if relaxation level is not adequate.
The impact of the agents used is often not understood,
nor is the concept of reversal, particularly the potential
impact of an incompletely reversed neuromuscular blockade. Even with standard practices for managing patients
who are given neuromuscular blocking agents, many studies have shown that actual practices diverge considerably
from these ideals.
Measuring the Depth of Paralysis
Monitoring the depth of paralysis when using neuromuscular blocking agents is considered an essential part
of standard practice.8,9 Traditionally, this was done with
clinical criteria alone; however, several studies have shown
this to be unreliable for detecting clinically significant residual block.10,11
Train-of-four
Train-of-four (TOF) stimulation, introduced in 1970
by Ali and colleagues, measures response to a sequence of
4 electrical impulses given over 2 seconds and, when
used continuously, repeated every 10 or 20 seconds.12,13
Each impulse causes the muscle to twitch, and the
number and height of the 4 twitches are recorded.
The ratio between the fourth and first twitch (T4/
T1) has become a criterion for adequate recovery from
the NMBA. Prior to administering the agent, the
4 twitches should be the same height, producing a TOF
ratio of 1.0. Under influence of a non-depolarizing
NMBA, the twitch height fades, and the ratio decreases,
followed by a decrease in the number of twitches.14 A
TOF ratio of 0.9 is considered adequate recovery. The
twitch response becomes less as the depth of the block
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increases, and twitches are abolished when 100% blockade is reached. Moderate neuromuscular block is often
defined as a TOF that has 1 or 2 twitches.15 Although
normal volunteers, known to have no neuromuscular
blocking agent occupying their acetylcholine receptors,
will have 4 twitches, a postoperative patient recovering
from an NMBA who has 4 twitches may have up to 75%
of his receptors occupied by the agent.
TOF is more useful in monitoring non-depolarizing
than depolarizing neuromuscular block. During onset
and recovery following use of a depolarizing block, the 4
twitch heights are equally affected, unless larger doses are
given, which may produce a phase 2 block.13
Subjective or qualitative neuromuscular monitoring
uses visual or tactile assessments of response to peripheral
nerve stimulation.16 Fade cannot be accurately detected
using subjective monitoring when TOF ratios are between
0.6 and 1.0.
Several devices are available that provide quantitative
neuromuscular monitoring. Acceleromyography devices
are small, portable, and considered by some as the most
versatile devices for the clinical setting.17
Post-tetanic count
When a deeper blockage is reached, post-tetanic
count (PTC) replaces TOF as a measure of the depth
of the block.18 A motor nerve is stimulated 50 times/
second, followed 3 seconds later by 1 stimulus/second.
The number of twitches that occur during this interval
are the PTC. Twitch recovery to PTC occurs before recovery of TOF twitches, which commonly return with a
PTC of 9 for atracurium or vecuronium, although TOF
twitches often do not return until the PTC is at least
10.13,16,17 During intense block, there is no response to
the tetanic or post-tetanic stimulation. A PTC of 1 or
2 represents profound (or “deep”) block.14
Understanding the ways to achieve ideal surgical
conditions related to neuromuscular blockade and the
importance of quantitative neuromuscular monitoring
is critical for surgeons as well as anesthesia providers.
It is imperative for intraoperative safety to understand
the anesthesia drugs being given and their effects. The
surgeon must be able to accomplish the procedure efficiently; likewise, efficient recovery and turnover times
must be achieved. Patients should arrive in the postanesthesia care unit (PACU) extubated, and should not
need reintubation, which depends on monitoring and
managing the level of paralysis appropriately. It is important for the postoperative patient to be able to generate adequate negative inspiratory force in a milieu of
pain, narcotics, and hypercarbia. All of these considerations translate into patient safety.
6
Q&A
What are some specific examples of levels
of neuromuscular block needed and their
rationale?
Matt L. Kirkland, MD, FACS: I believe there is a distinct difference between the level of paralysis that is needed for pelvic surgery
compared with that needed for subdiaphragmatic surgery or transdiaphragmatic surgery. Working in the pelvis, the level of relaxation
and paralysis needed is less than what is needed in areas that are
closer to the diaphragm. The patient can have a few twitches, and
pelvic surgery can still be safely accomplished. Conversely, during
a liver resection or laparoscopic splenectomy, direct stimulation of
the diaphragm can occur from touching it or by cautery conducting
to it, or it may be produced by stimulating the phrenic nerve.
A transhiatal procedure provides an example of a situation that often
requires deep relaxation. There is a fixed platform holding the hiatus
open as the surgeon dissects along the esophagus. In these settings,
if there is not a very deep degree of muscle relaxation or if the patient
moves spontaneously or makes any attempt at spontaneous ventilation, this movement can result in catastrophic injury if an instrument
becomes dislodged and makes a random unintended perforation.
Also, because of its blood supply, the diaphragm recovers comparatively early from muscle relaxation. There may be diaphragmatic
excursions and movement while the extremities are immobile.
Conversely, a laparoscopic cholecystectomy can typically be done
with minimal relaxation. Patients commonly do not receive muscle
relaxants after their intubating dose.
Mark D. Welliver, CRNA, DNP, ARNP: The question of using
muscle relaxants (neuromuscular blocking agents) for surgical
needs is pertinent. As Dr. Kirkland states, sometimes the surgeon
needs immobility, not necessarily neuromuscular block-induced
paralysis. If the surgeon is experiencing less than ideal conditions
due to patient movement or diaphragmatic excursion deepening
the anesthetic may be all that is necessary. Increasing the volatile
anesthetic, propofol infusion, or administering an opioid is all that
may be required. Neuromuscular blocking agents used for immobility that may be achieved via other mechanisms may not always
be the best choice, especially considering the limitation of current
reversal modalities. On the other hand, surgeries that are impeded
by muscular tone, tension, or resistance are more likely to benefit
from muscular paralysis induced by NMBAs. It is important to
differentiate paresis from paralysis when discussing the third component of general anesthesia immobility. Is complete cessation of
motor function necessary? Can surgical procedures and outcomes
be improved in cases where deeper levels of neuromuscular block
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are used? I am aware that pneumoperitoneum may cause some
localized tissue perfusion alterations, acidosis, and hypoxia.19 Some
research has also found mesothelial lining structural changes,
immune suppression, as well as specific cell function alterations
that include changes to ATP production, increased metastatic cell
production, and cell apoptosis.20,21 This has caused some to ask
if lower pneumoperitoneum pressures would be better. These are
interesting findings. Equally interesting are studies exploring the
use of lower pneumoperitoneum pressures achieved with deeper
levels of neuromuscular blockade and what, if any, is the effect on
surgical visualization.22
John J. Nagelhout, CRNA, PhD, FAAN: Laparoscopic procedures that require moderate to deep relaxation yet end very quickly
can be challenging. The surgeon needs relaxation up to the end of
the procedure. Profoundly blocked patients must be emerged as
quickly as possible; time is of the essence because the anesthesia
provider cannot wean down the anesthetic as is done with many
procedures. This is a critical objective for patients who are maintained in deep relaxation up to the end of the procedure.
9.
10.
11.
12.
13.
14.
15.
REFERENCES
1. ASA. Continuum of Depth of Sedation. 2009. http://www.
asahq.org/For-Members/Standards-Guidelines-and-Statements.aspx. Accessed October 3, 2013.
2. Urban BW, Bleckwenn M. Concepts and correlations relevant to general anesthesia. Brit J Anaesth. 2002;89:3-16.
3. Woods AW, Allam S. Tracheal intubation without the use of
neuromuscular blocking agents. Brit J Anaesth. 2005;94:150158.
4. Wilson J, Collins AS, Rowan BO. Residual neuromuscular
blockade in critical care. Critical Care Nurse. 2012;32:e1-e9.
5. Martyn J DM. Succinycholine. New insights into mechanisms
of action of an old drug. Anesthesiology. 2006;104:633-634.
6. Gurusamy KS, Samraj K, Davidson BR. Low pressure versus
standard pressure pneumoperitoneum in laparoscopic cholecystectomy Cochrane Database of Systematic Reviews 2009,
Issue 2. Art. No.: CD006930. DOI: 10.1002/14651858.
CD006930.pub2. 2009.
7. Lindekaer AL, Halvor Springborg H, Istre O. Deep neuromuscular blockade leads to a larger intraabdominal volume
during laparoscopy. J Vis Exp. 2013;76:doi: 10.3791/50045.
8. Miller RD, Ward TA. Monitoring and pharmacologic reversal of a nondepolarizing neuromuscular blockade should be
routine. Anesth Analg. 2010;111:3-5.
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Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St Louis,
MO: Elsevier Mosby; 2014.
Hayes AH, Mirakhur RK, Breslin DS, et al. Postoperative
residual block after intermediate-acting neuromuscular
blocking drugs. Anaesthesia. 2001;56:312-318.
Debeane B, Plaud B, Dilly MP, et al. Residual paralysis in
the PACU after a single intubating dose of nondepolarizing
muscle relaxant with an intermediate duration of action.
Anesthesiology. 2003;98:1042-1048.
Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in humans. Brit J Anaesth.
1970;42:967-978.
McGrath CD, Hunter JM. Monitoring of neuromuscular
block. CEACCP. 2006;6:7-12.
Boon M, Martini CH, Aarts LPHJ, et al. Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients
undergoing laparoscopic renal or prostatic surgery (BLISS
trial): study protocol for a randomized controlled trial. Trials. 2013;14:63-73.
Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesth Analg. 2010;111:129-140
Hemmerling T, Lee N. Brief review: neuromuscular
monitoring: an update for the clinician. Can J Anaesth.
2007;54:58-72.
Viby-Mogensen J, Howardy-Hansen P, Chraemmer-Jorgensen B, et al. Post-tetanic count (PTC): a new method
of evaluating an intense nondepolarizing neuromuscular
blockade. Anaesthesiology. 1981;55:458-461.
Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anesthesia. Expert Opin Pharmacother. 2008;9:1375-1386.
Brokelman WJ, Lensvelt M, Borel Rinkes IH, et al. Peritoneal changes due to laparoscopic surgery. Surg Endosc.
2011;25(1):1-9.
Neuhaus SJ, Watson DI. Pneumoperitoneum and peritoneal surface changes: a review. Surg Endosc. 2004;18(9):
1316-22. .
Wildbrett P, Oh A, Naundorf D, et al. Impact of laparoscopic gases on peritoneal microenvironment and essential
parameters of cell function. Surg Endosc. 2003;17(1):78-82.
Lindekaer AL, Halvor Springborg H, Istre O. Deep
neuromuscular blockade leads to a larger intraabdominal volume during laparoscopy. J Vis Exp.
2013;(76):doi:10.3791/50045.
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Reversal of Neuromuscular Blocking
Agents: Current Practice
John J. Nagelhout, CRNA, PhD, FAAN
outine reversal of non-depolarizing neuromuscular blocking agents (NMBAs) is more common in the United States than in Europe.1 In a
survey comparing practice in both areas, 34% of
U.S. clinicians vs. 18% of European respondents said they
always administer an anticholinesterase at the end of a surgery where a non-depolarizing relaxant was given.2 When a
reversal drug was not given, a factor in the decision not to
reverse was measurement of the train-of-four (TOF) ratio
using a quantitative TOF monitor in 12% (United States)
vs. 46% (European) of respondents.
The need for a better agent for relaxant reversal motivates
continuing research in this area. An ideal agent would have a rapid onset, would reliably and predictably re-establish muscle function in all patients in all degrees of relaxation including complete
block, and would exhibit high effectiveness in the presence of
inhalation anesthetics, which can impede reversal when patients
are still significantly anesthetized. In addition, as with all drugs,
the ideal reversal agent would have minimal adverse effects.
The current practice to reverse non-depolarizing relaxants
is to use a anticholinesterase drug, primarily neostigmine.
Although some direct neostigmine effects have been noted,
these agents primarily have an indirect mechanism of action
that is less than ideal. Unlike the direct receptor reversal,
such as the mechanism by which naloxone reverses opiates
and flumazenil reverses benzodiazepine, these drugs do not
achieve their effect by direct competition with the muscle receptor. Rather, they work indirectly by inhibiting the enzyme
cholinesterase, thus allowing acetylcholine to accumulate and
compete with the relaxant at the nicotinic receptor on the
muscle, re-establishing normal function.
There are several disadvantages with these agents. The
indirect reversal mechanism increases the time required to
produce the reversal. In an average healthy person, it commonly requires 10 to 15 minutes for adequate reversal, and
longer in a person with less than average health.3 Onset of
reversal can frequently be delayed in a person with a low temperature, which commonly occurs during surgery. Reversal is
unreliable, unless clinically significant spontaneous recovery
has already occurred. Residual blockade, with its associated
complications, remains a clinical problem. When monitoring patients, keeping them slightly less than 100% paralyzed
is targeted; that is, with 1 or 2 twitches using the TOF test.
R
8
This provides an adequate amount of relaxation for most
procedures. If the patient is weaned off the NMBA and allowed to begin recovery toward the end of the procedure,
neostigmine will work more effectively if it is given when
there are 3 to 4 twitches on a TOF test.4 If the end of the
procedure is reached and the patient has 0 or 1 twitch, an appropriate reversal with neostigmine cannot be guaranteed, as
these agents cannot reverse profound block.5
In addition, the increased systemic acetylcholine must be
countered by co-administration of an anticholinergic drug
such as atropine or glycopyrrolate to minimize adverse effects
associated with the accumulation of acetylcholine at muscarinic cholinergic parasympathetic sites. The anticholinesterases may have other adverse effects resulting from parasympathomimetic actions secondary to the induced buildup
of systemic acetylcholine. These may include bradycardia,
arrhythmias, increased gastric motility, airway secretions,
miosis, and bronchoconstriction. Although controversial, the
increased gastric motility may be associated with increased
postoperative nausea and vomiting. Bronchoconstriction is
especially common in patients with asthma and people who
are prone to respiratory problems.
The concurrent administration of an anticholinergic
drug to minimize the adverse effects of the anticholinesterase is also associated with adverse effects, including
tachycardia, arrhythmias, cardiac conduction changes, dry
mouth, blurred vision, and urinary retention. Atropine can
cause some initial stimulation, followed by sedation in the
post-anesthesia care unit (PACU).
There is some evidence that neostigmine may produce
muscle weakness when administered as a safety measure
after spontaneous recovery from non-depolarizing block
has occurred.4
Neostigmine Dosing
Requirements for adequate reversal using
anticholinesterase drugs
The recommendation is to have a minimum of 2 twitches
from a TOF, which indicates an approximate 80% blockade, when neostigmine is administered. However, success
is enhanced when the antagonist is given early (>15 to
20 minutes before tracheal extubation) and if there is a
shallower block (when there are 4 TOF twitches).5
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Response is also related to the dose of neostigmine.
There is an upper limit to the amount of acetylcholinesterase inhibition that is possible at the neuromuscular junction.5 When this ceiling is reached, if a patient is not adequately reversed, additional dosing of neostigmine will not
produce additional reversal.
The rate of recovery depends on the relaxant used as well.
Neostigmine does not affect the elimination of the relaxant;
therefore, long-acting relaxants take longer to reverse than intermediate-acting drugs. Liver or renal disease that may affect the
metabolism or elimination of the relaxant can also affect recovery.
In addition, the concentration of the inhalation anesthetic present when reversal is initiated can affect the reversal. Greater levels of inhalation anesthetics can make reversal
more difficult by increasing the time to recovery or impeding
the ability to reverse.
Patient characteristics also affect the ability to achieve
adequate reversal. It is more difficult to reverse hypothermic patients. Age, metabolic imbalances such as hypokalemia, and some concurrent medications may also adversely
impact reversal.
In summary, if a person does not adequately reverse, possible explanations should be considered. The reversal may
have been started when the patient was in too deep a block;
for example, with 0 or 1 twitch on a TOF. There may be an inadequate interval since initiation of the reversal; for example,
reversal may take up to 30 minutes in patients who are hypothermic, have poor circulation, or have several comorbidities
such as vascular disease and diabetes. A 100% blockade is too
intense to be antagonized. In these cases, reversal should be
delayed until some spontaneous recovery has occurred. Attention to the dose of neostigmine, drug interactions, and the
possibility of an unrecognized process ongoing in the patient
may explain deficiency in recovery.
Some considerations when reversal of the non-depolarizing relaxant is incomplete are shown in Table 1.
The maximum recommended total dose of neostigmine
is 0.07 mg/kg, or 5 mg, whichever is less.6 If the maximum
dose has been given and reversal has not been achieved, the
patient should be kept in the PACU and remain sedated
so they do not awaken while paralyzed. Adequate ventilation should be provided until the relaxant effects dissipate
and full recovery is established, which may require from a
few minutes to several hours.
All of these scenarios exemplify the importance of providing quantitative neuromuscular monitoring as part of
the routine management of patients receiving a neuromuscular blockade agent. This becomes especially important in
relation to the possibility of residual paralysis.
Postoperative Residual Neuromuscular Block
Residual neuromuscular block can be defined as the presence of postoperative signs and symptoms of muscle weakness after administration of a neuromuscular blocking drug.7
This was initially related to a TOF ratio ⬍0.7. Several studies, particularly those by Eriksson and Kopman, showed that
normal vital muscle function, including that of the muscles
of the pharynx, requires a TOF ratio of at least 0.9.8 Using
objective monitoring to determine return of TOF ratio to
0.9, however, does not obviate the need for careful clinical assessment for adverse effects related to blocking agents. Some
patients exhibit muscle weakness at a TOF ratio >0.9, and
others may show complete recovery of muscle strength at a
TOF ratio ⬍0.9.7 Spontaneous recovery cannot always be
assumed.9 Studies have shown evidence of residual paralysis
after a single dose of an NMBA in up to 37% of patients
>2 hours after dosing, and in one study 33% of patients had
a TOF ⬍0.75, 3 hours after a single dose of vecuronium.
Although reversal of the blockade may reduce the incidence
of postoperative paralysis, complete recovery in the PACU
should not be assumed simply based on the use of an anticholinesterase reversal agent.
Table 1. Considerations When Return of Muscle Function Is Incomplete
• As with any reversal agent, the ability to counteract a
nondepolarizing blocking agent depends on the amount
of spontaneous recovery before the administration of a
reversal drug.
• Has enough time been allowed for the anticholinesterase to
antagonize the block (at least 15 to 30 minutes)?
• Has an adequate dose of antagonist been given?
• Are the other anesthetics and adjunctive agents
contributing to patient weakness?
• Has metabolism or excretion of the relaxant been reduced
by a possibly unrecognized process?
• Is the neuromuscular blockade too intense to be
antagonized?
• Have acid-base and electrolyte status, temperature, age,
drug interactions, and other factors that may prolong
relaxant action been contemplated?
• Even if recovery appears clinically adequate, a small dose
of neostigmine may be prudent if the time since relaxant
administration is ⬍4 hours.
• The safest approach when any question about successful
reversal remains is to provide proper sedation and
controlled ventilation until adequate recovery is ensured.
TOF = train-of-four
Source: Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St Louis, MO: Elsevier Mosby; 2014.
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Table 2. Factors Influencing Residual
Neuromuscular Blockade
Objective TOF measurements (TOF ratio < 0.9)
Clinical signs or symptoms of muscle weakness
Type and dose of NMBD administered intraoperatively:
Intermediate-acting NMBD
Long-acting NMBD
Use of neuromuscular monitoring intraoperatively:
Qualitative monitoring (TOF and DBS studied)
Quantitative monitoring (acceleromyography studied)
No neuromuscular monitoring (clinical signs)
Degree of neuromuscular blockade maintained
intraoperatively:
TOF count of 1-2
TOF count of 2-3
Type of anesthesia used intraoperatively:
Inhalation drugs
TIVA
Type and dose of anticholinesterase reversal drug:
Neostigmine
Edrophonium
Duration of anesthesia
Time interval between anticholinesterase administration and
objective
TOF measurements
Patient factors: metabolic derangements in the PACU
(acidosis, hypercarbia, hypoxia, hypothermia)
Drug therapy in PACU: opioids, antibiotics
TOF = train-of-four; PACU = postanesthesia care unit, NMDB = neuromuscular blocking drug; DBS = double-burst stimulation; TIVA = intravenous anesthesia.
Source: Murphy GS, Brull SJ. Anesth Analg. 2010;111(1):120-128; Nagelhout JJ, Plaus KL.
Nurse Anesthesia. 5th ed. St Louis, MO: Elsevier Mosby; 2014.
The incidence of a TOF ratio ⬍0.9 in PACU patients
is estimated to range from approximately 30% to almost
60%.4,7,10-12 Clinically evident events have been reported in
a small proportion, ⬍1% to 3%, of patients with residual
block.7 However, there is an association between neuromuscular blocking agent use / residual block, and increased perioperative morbidity and mortality. Serious complications can
result, including respiratory complications, with acute events
such as hypoxia and airway obstruction reported in up to
20% of patients.4 A case control study compared 42 cases of
critical respiratory events (CRE) in the PACU with controls
matched for age, gender, and surgical procedure, but who did
10
not develop a CRE.13 Mean TOF ratio was 0.62 in the cases,
compared with 0.98 in controls (P⬍.0001). This reflected
that no control patients had a TOF ratio ⬍0.7, compared
with 74% of cases with adverse events (P⬍.0001). The authors concluded that residual paralysis contributes to the development of respiratory adverse events in the PACU.
These complications, even when not serious, may impose a
delay on tracheal extubation or require reintubation to ensure
the patient has adequate oxygenation. Muscles in the hypoglossal area, which help protect the airway against aspiration,
are among the last to recover; therefore, patients who experience vomiting postoperatively may have an increased risk of
aspiration. Several unpleasant symptoms, including muscle
weakness, that are associated with residual blockage can be
disconcerting when a patient is also recovering from sedation.
When patients are transported between the operating room
and the PACU, they often are not being ventilated directly
and their oxygen content decreases, which may contribute to
adverse events occurring during transport. Patients with residual blockage may also have a longer PACU stay.7
Clinical factors influencing the incidence of postoperative
residual blockade are listed in Table 2.
Clinical Tests of Residual Muscle Weakness
Several clinical tests are commonly used to assess restoration of muscle functioning, including:
1. General weakness
2-4. Inability to smile, swallow, or speak
5-6. Inability to lift the head or leg for 5 seconds
7. Inability to sustain a hand grip for 5 seconds
8. Inability to resist removal of tongue depressor
from between the teeth
The 5-second head lift has been the most frequently used
clinical criterion used to assess muscle function. Studies
have shown, however, that a successful head lift was associated with a TOF ratio of ⩽0.5 in a majority of patients.9
The sensitivity, specificity, positive predictive value, and
negative predictive value of a failure to complete a 5-second
head lift for detecting residual paralysis (TOF ⬍0.9) were
19%, 88%, 51%, and 64%, respectively, in another study.11 In
that study, when the results of these 8 clinical assessments
were summed, the combined sensitivity and specificity for
a scenario where all tests were negative were 46% and 67%.
Key Points
The reversal agent neostigmine is widely used; however, it has several disadvantages. When possible, intermediate-acting relaxants with a 30-minute to 60-minute
effect are preferred.
Although neuromuscular monitoring should be more
available, particularly quantitative monitoring, it is essential
that practitioners receive adequate training on its use and
include it in the standard management of patients receiving
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neuromuscular blocking agents. However, it is also important to work towards better use of neuromuscular blocking
agents, and development of new blocking and/or reversal
agents. Finally, a better understanding between surgeons
and anesthesiologists regarding the specific limitations and
needs of each other’s disciplines should be pursued.
Q&A
Where does neuromuscular monitoring fit
in with managing neuromuscular block and
preventing residual paralysis?
Mark D. Welliver, CRNA, DNP, ARNP: Despite all the
reports highlighting the importance of objective neuromuscular
function monitoring, recent studies show a very low rate of neuromuscular function monitoring, both qualitative and quantitative.
Although objective quantitative monitoring (accelerometry) is
preferable, subjective qualitative (peripheral nerve stimulator)
monitoring is primarily used in clinical practice.9 Qualitative monitoring uses a peripheral nerve stimulator and visual or tactile assessment of the twitch response. Numerous studies have shown
limitations in detecting TOF fade using this subjective evaluation.
Only 50% of 32,002 surgical procedures between 2006 and 2010
in a single hospital where intermediate-acting non-depolarizing
blocking agents were administered included neuromuscular
monitoring, defined as subjective assessment of response to
peripheral nerve stimulation.14
Several survey studies have shown the lack of knowledge and
use of appropriate practices related to postoperative residual
paralysis among anesthesia providers. One survey reported 17%
use of objective monitoring, with 52% of anesthesiologists relying
on clinical judgment instead of TOF data as their criterion for
safe extubation.15 Another survey reported that 9% of American
anesthesiologists who had both quantitative TOF monitors and
conventional nerve stimulators available used neither, and 63%
used the conventional nerve stimulator.2 When anesthesiologists
were asked in another survey about the incidence of postoperative
residual paralysis, it was underestimated by 91%.16 Additionally,
27% and 75% believed, incorrectly, that clinical tests and tactile/
visual evaluation of a TOF stimulation can be used to exclude
residual paralysis.
REFERENCES
1. Kopman AF Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia.
2009;64:22-30.
2. Naguib M, Kopman AF, Lien CA, et al. A survey of current
management of neuromuscular block in the United States
and Europe. Anesth Analg. 2010;111:110-119.
3. Srivastava A, Hunter JM. Reversal of neuromuscular block.
Brit J Anaesth. 2009;103:115-129.
4. Donati F. Residual paralysis: a real problem or did we invent
a new disease? Can J Anaesth. 2013;60:714-729.
5. Brull SJ, Kopman AF, Naguib M. Management principles
to reduce the risk of residual neuromuscular blockade. Current Anesthesiology Reports. 2013;3:130-138.
6. Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St Louis,
MO: Elsevier Mosby; 2014.
7. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse
physiologic effects of residual neuromuscular block. Anesth
Analg. 2010;111:120-128.
8. Viby-Mogensen J. Postoperative residual curarization and
evidence-based anaesthesia. Brit J Anaesth. 2000;84:301303.
9. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesth Analg. 2010;111:129-140.
10. Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis. Brit J Anaesth. 2007;98:302-316.
11. Cammu G, De Witte J, De Veylder J, et al. Postoperative
residual paralysis in outpatients versus inpatients. Anesth
Analg. 2006;102:426-429.
12. Maybauer DM, Geldner G, Blobner M, et al. Incidence and
duration of residual paralysis at the end of surgery after
multiple administrations of cisatracurium and rocuronium.
Anaesthesia. 2007;62:12-17.
13. Murphy GS, Szokol JW, Marymont JH, Greenberg SB,
Avram MJ, Vender JS. Residual neuromuscular blockade
and critical respiratory events in the postanesthesia care
unit.Anesth Analg. 2008;107(1):130-137.
14. Grosse-Sundrup M, Henneman JP, Sandberg WS, et al. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study.
Brit Med J. 2012;345:e6329.
15. Phillips S, Stewart PQ, Bilgin AB. A survey of the management of neuromuscular blockade monitoring in Australia
and New Zealand. Anaesth Intensive Care. 2013;41:374379.
16. Sorgenfrei IF, Viby-Mogensen J, Swiatek FA. Does evidence lead to a change in clinical practice? Danish anaesthetists’ and nurse anesthetists’ clinical practice and knowledge of postoperative residual curarization. Ugeskr Laeger.
2005;167:3878-3882.
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New and Advanced Options in
Neuromuscular Blockade Management
Mark D. Welliver, CRNA, DNP, ARNP
anagement of patients given neuromuscular blocking agents (NMBAs) is often less than ideal and
available management options should be improved.
Cholinesterase inhibitors are the only drugs available in the United States to pharmacologically reverse neuromuscular blockade. Cholinesterase inhibitors reverse NMBAs
indirectly by increasing acetylcholine to compete for binding
to the nicotinic acetylcholine receptor. One of the main limitations of cholinesterase inhibitors is their inability to reliably
produce a train-of-four (TOF) ratio >0.9 within 30 minutes
of administration, regardless of the TOF count when the agent
was given.1 Additionally, developing neuromuscular blocking
drugs that quickly and reliably degrade or can be directly reversed would be an improvement. These improvements would
have several benefits, including the potential of avoiding postoperative residual neuromuscular paralysis.
Currently, there are several methods by which the effects of
NMBAs can be ended. Physiologically, some agents are metabolized through common pharmacokinetic pathways that
result in their elimination, while some are excreted unchanged.2
Inactivation can also occur by ester hydrolysis or spontaneous
degradation (Hofmann elimination), as occurs with atracurium and cisatracurium. The investigational ultra-short-acting
isoquinoline NMBAs gantacurium, CW011, and CW002
were shown to be non-enzymatically terminated by cysteine
adduction of the chloride atom on their esther linkage. Exogenous L-cysteine was found to reverse these agents within 2 to
3 minutes after intravenous administration in monkeys.3 This
cysteine adduction represents another potential mechanism
for reversing neuromuscular blocking agents but first requires
clinical study of these new agents.
Direct encapsulation is another novel approach to reversing NMBAs. The selective relaxant binding agent, sugammadex, is the first-in-class using this approach. Since its
first approval in the European Union in 2008, sugammadex
has been approved in more than 50 countries worldwide for
the reversal of neuromuscular blockade; however, it has yet
to gain approval from the U.S. FDA.4,5
M
Sugammadex
Sugammadex is a cyclodextrin, which is a family of compounds composed of cyclic dextrose units that have been
used since 1953 as solubilizing agents. Sugammadex is a
12
modified γ-cyclodextrin, comprising 8 sugar molecules that
form a rigid ring with a central lipophilic cavity.6
Sugammadex was initially discovered when a compound
was needed to increase the solubility of rocuronium in a
specific media, and cyclodextrins were explored for that
purpose.4 When essentially permanent binding of the rocuronium molecule was observed, this novel mechanism to
reverse neuromuscular block was further investigated, and
sugammadex was selected for clinical development. The steroid nucleus of the aminosteroid NMBA molecule fits and
binds into the central sugammadex cavity, creating a 1:1 irreversible bond.7,8
Sugammadex was also subsequently shown to be effective in reversing the effects of vecuronium-induced neuromuscular block.9-11 Limited data suggest it has lesser
efficacy against pancuronium.12 Because of its specificity
for aminosteroidal NMBAs, sugammadex is not effective
against benzylisoquinolinium NMBAs.
Following intravenous administration of sugammadex,
rocuronium or vecuronium molecules in the plasma are rapidly encapsulated.13 This creates a concentration gradient of
no free unbound NMBA molecules in the plasma compartment to the extravascular compartment, where the NMBAs
are exerting their effect on acetylcholine receptors. This favors
movement of the NMBAs back into the plasma. Once in the
plasma, the NMBA molecules are also rapidly encapsulated
by the available free sugammadex molecules. Sugammadex
has been shown in a dose-dependent fashion to reverse any
depth of neuromuscular blockade to a TOF ratio 肁0.9 within 3 minutes.
Clinical trials
The phase I to III clinical trial experience with sugammadex, investigating its potential to reverse rocuronium,
vecuronium, and to a lesser extent pancuronium, is quite
extensive.14 Several studies explored the ability of sugammadex to reverse profound neuromuscular block and reported
a dose-dependent time to recovery. For example, a phase
III randomized controlled trial of sugammadex 4.0 mg/kg
compared with neostigmine 70 μg/kg plus glycopyrrolate
14 μg/kg in patients with profound neuromuscular block
(post-tetanic count [PTC] 1-2) found that sugammadex
was 17- and 15-fold faster at reversing rocuronium- and
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vecuronium-induced block compared with neostigmine.15
In a trial of immediate reversal, sugammadex (16 mg/kg) was
administered 3 minutes after profound neuromuscular block
was induced with rocuronium and reversal was significantly
found effective and faster compared with patients who underwent spontaneous recovery from succinylcholine.16
A systematic review and meta-analysis included 18 randomized controlled trials, which included studies of sugammadex for reversal of rocuronium-induced neuromuscular
blockade at reappearance of 2 TOF twitches (2 mg/kg),
1 to 2 post-tetanic counts (4 mg/kg), and 3 to 5 minutes after
rocuronium (16 mg/kg).14 The authors concluded that sugammadex can reverse rocuronium-induced neuromuscular
blockade more rapidly than neostigmine, regardless of the
depth of the block.
Several additional studies are ongoing or have been completed that explore the potential role of sugammadex in special patient groups, the incidence of residual blockade using
sugammadex, and comparative outcomes using low or standard insufflation pressure in laparoscopic cholecystectomy.
Observation study comparing recovery from deep
and shallow neuromuscular block: neostigmine
and sugammadex
Recently, a large multicenter, prospective, observational
study was undertaken in Italy, which enrolled 359 adult patients receiving sevoflurane, desflurane, or propofol maintenance anesthesia for abdominal surgery that required either
shallow or deep intramuscular block with rocuronium.17
Only centers familiar with objective TOF monitoring (TOFWatch or TOF-Watch SX) participated. Treatment decisions and doses were at the discretion of the investigators
according to their standard practice. Patients were given the
reversal agent at T2 reappearance (“shallow/moderate block”)
or at a post-tetanic count of 1 or 2 (“deep block”). The primary
outcome was time from the start of neostigmine (n=150) or
sugammadex (n=207) administration to recovery of a TOF
ratio ⩾0.9. Reversal was significantly faster after sugammadex compared with neostigmine in patients with either a
shallow (2.2 vs. 6.9 min; P⬍.0001) or deep (2.7 vs. 16.2 min;
P⬍.0001) block. No adverse events were reported in either
group in the first 24 hours postoperative.
Randomized controlled trial comparing recovery in
laparoscopy patients
A recent randomized controlled trial in 10 sites in 4
countries explored the comparative recovery times in patients undergoing laparoscopic cholecystectomy or appendectomy, who were randomized to receive sugammadex 4.0
mg/kg (n=66) when they were in deep neuromuscular block
(PTC 1-2), or neostigmine 50 μg/kg plus atropine 10 μg/
kg (n=65) when they had reached shallow/moderate block
(T2 reappearance).17 The primary efficacy variable was time
from the start of reversal agent administration until recovery of the TOF ratio to 0.9. Data were expressed as geometric means and 95% confidence intervals (CI). Patients were
also assessed for residual block and recurrence of blockade.
Quantitative post-induction neuromuscular monitoring was
performed continuously at the adductor pollicis muscle.
Time from starting the reversal agent until a TOF ratio
of ⩾0.9 was reached was significantly less in the sugammadex group (2.4; 95% CI; 2.1, 2.7) compared with the
neostigmine group (8.4 min; 95% CI; 7.2, 9.8). Therefore, recovery when sugammadex was given during deep
neuromuscular block was 3.4 times more rapid compared
with waiting until patients had a moderate neuromuscular
block before administering neostigmine. Put in the perspective of a similar baseline between treatment groups,
times from the last dose of rocuronium until recovery were
13.3 (95% CI; 11.6, 15.3) minutes in the sugammadex group
and 35.2 (95% CI; 30.8, 40.2) minutes in the neostigmine
group (P⬍.0001). Times in the operating room and PACU
were similar between groups, while time from study drug
administration to tracheal extubation and operating room
discharge ready were significantly less in the sugammadex
group (P⬍.0001 for both comparisons). There was no residual blockade or recurrence of neuromuscular blockade in
either group, based on neuromuscular monitoring. Adverse
events were similar between groups, with the exception that
5 cases of clinically significant bradycardia occurred in the
neostigmine group.18
Applications for Sugammadex
Blocking after reversal with sugammadex
Occasions arise in which neuromuscular block must
be re-established after reversal. The half-life of sugammadex is approximately 2.5 h,19 with >90% excreted within
24 hours, mostly as unchanged sugammadex. It is feasible, therefore, that active sugammadex may be circulating
that could interfere with an attempt to re-paralyze when
needed after a short interval. A study with Rhesus monkeys explored the ability to restore a neuromuscular block
using rocuronium after reversal with sugammadex.20 This
study evaluated the time course of action of sugammadex
and aided the authors in developing a model to predict the
degree of rocuronium-induced block that may be expected
after prior reversal with sugammadex. Data from a model
developed using equilibrium constants for the 2 drugs
suggested that re-establishing a blockage was possible by
raising the amount of rocuronium present based on estimations of remaining drug.21 Accordingly, a second reversal with sugammadex should be possible by using doses
between 8 and 20 mg/kg compared with the normal dose
of 2 to 4 mg/kg. Although these theoretical discussions
are interesting, the associated costs and increased potential for inadequate dosing of either drug precludes this as
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a viable clinical practice. The use of benzylisoquinolinium
NMBAs cisatracurium or atracurium is unaffected by
sugammadex and will establish neuromuscular blockade.
Reversal of benzylisoquinolinium NMBAs must be done
using cholinesterase inhibitors. Re-paralysis after sugammadex can be achieved with standard doses of rocuronium
only after sugammadex has been cleared from the body.
Can’t intubate / Can’t ventilate
Situations where difficult intubations present a Can’t Intubate / Can’t Ventilate (CICV) scenario are extremely rare;
however, when they occur these emergency situations require
rapid and decisive management. Because of its rapid reversal
of rocuronium, sugammadex was suggested as a possible rescue drug to be used in CICV situations. Several case reports
of the use of sugammadex in CICV patients have produced
mixed opinions.
A patient with pharyngeal stenosis who was scheduled
for dilatation under anesthesia had a non-traumatized airway; however, limited cervical spine movement suggested
intubation would be difficult.22 Mask ventilation failed and
laryngoscopy was not attempted. The patient was given
400 mg sugammadex to allow recovery from rocuronium,
and had a return of spontaneous breathing. In another
case report, a morbidly obese (BMI = 38.5 kg/m2) patient
who could not be intubated was given sugammadex and
achieved effective spontaneous ventilation within 45 seconds after treatment.23
Another recent case report described a patient with upper
airway pathology who deteriorated into CICV after 3 failed
intubation attempts.24 Sugammadex successfully reversed
the neuromuscular block; however, airway patency was not
restored, and after emergency oxygenation was provided, a
tracheostomy was performed. The authors recommended
that if sugammadex is to be considered as part of a rescue
management plan, it should be given prior to repeated airway manipulations. In another case with airway pathology,
sugammadex reversed the rocuronium blockade but did not
resolve the CICV situation.25
In summary, there was considerable variation among
these cases and the specific management plans that were
followed in response. Case reports alone and their inconsistent outcomes are not enough to draw conclusions on
the possible benefit of sugammadex in CICV cases. Despite full reversal of rocuronium-induced neuromuscular
blockade by sugammadex, continued sedation, respiratory depression, and airway collapse caused by other induction drugs may predominate. Assessing airway anatomy,
anticipating difficult intubations, making optimal preparations, and having backup plans for airway management
should be continued standard practice without reliance
of immediate neuromuscular block reversal as a fail-safe
mechanism.
14
Sugammadex and Hypersensitivity Reactions
In an early volunteer study, sugammadex infusion was
stopped at 8.4 mg/kg in a patient with no known history
of allergy during a first exposure to sugammadex. During
sugammadex infusion, the patient developed several signs
and symptoms of a hypersensitivity reaction. The reaction
was self-limiting, and no treatment was required.26 Elevated
tryptase levels, suggestive of an allergic reaction and followup skin tests showed the subject likely had a hypersensitivity
reaction to sugammadex. Six incidences overall in the clinical trials (19.4.105, 19.4.106 and 19.4.109) of sugammadex
have been disclosed that indicate possible hypersensitivity reactions.27 In response to this occurrence, other subjects who
were exposed to sugammadex with signs of possible hypersensitivity were tested. A subsequent study was performed,
exploring the potential for hypersensitivity symptoms following both initial and repeat exposure to sugammadex.27 The
results of this hypersensitivity study are pending.
Since its approval in 2008, more than 5 million vials of
sugammadex have been sold. During this interval, some case
reports of hypersensitivity reactions in clinical practice have
emerged. For example, 3 patients in Japan had symptoms of
an allergic reaction with varying degrees of severity within
4 minutes after receiving 100 mg sugammadex immediately
before extubation.28 Two of the patients agreed to skin tests,
which were positive for sugammadex. Signs and symptoms
of hypersensitivity in the 2 tested patients included cutaneous reactions in 1 patient, and hypotension (systolic arterial
pressure ⬍50 mm Hg), tachycardia (>110 beats/min), generalized erythema, and increased peak airway pressure from
24 mm Hg to a maximum of 33 mm Hg in the other. The
third patient developed a wheeze on auscultation, a decrease
in oxygen saturation from 99% to 91%, and heart rate increase
to >110 beats/min. The authors qualified these reactions as
“possibly” induced by sugammadex; however, they cautioned
that practitioners should be alert for the potential development of allergic and non-allergic adverse reactions following sugammadex administration. Another case in Japan was
reported and although a hypersensitivity reaction was suspected and successfully treated with epinephrine and corticosteroid administration, no follow-up testing was conducted
to confirm a specific reaction to sugammadex.29 Although
a hypersensitivity reaction was suspected and successfully
treated with epinephrine and corticosteroid administration,
no follow-up testing was conducted to confirm a specific reaction to sugammadex. 29
Other single case experiences of possible drug allergy related to sugammadex have been reported. A patient in France
had intense erythema without edema, with a systolic blood
pressure drop to ⬍45 mm Hg, tachycardia (150 beats/min),
and oxygen saturation of 40% without bronchospasm.30 A
subsequent skin test was positive for sugammadex and negative for all the other drugs used on the patient. A 17-year-old
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Spanish patient developed a severe reaction 1 minute after
administration of 3.2 mg/kg sugammadex.31 The patient
had intense erythema over the anterior thorax, severe lip and
palpebral edema, and bilateral wheeze, with blood pressure
78/32 mm Hg, and tachycardia (100 to 110 beats/min).
Subsequent skin testing produced a reaction to sugammadex,
with no reaction to any of the other drugs tested. The authors
of these case reports postulated that sensitization may have
occurred through ingestion of cyclodextrins in food.
In summary, the potential for hypersensitivity to sugammadex requires further investigation. Operational concerns
about the hypersensitivity study were provided to the manufacturer of sugammadex by the FDA in September 2013,
and are being addressed.32
Education, Guidelines, and Teamwork in the
Management of Surgical Patients
The report from the large, prospective, observational
study comparing neuromuscular block reversal using either
neostigmine or sugammadex provided valuable effectiveness
data on the ability of sugammadex to reverse the effects of
rocuronium in the real world.33 Perhaps equally as important is the insight that study provided into the variability of
behavior among clinical anesthetists. The authors reported
that there was considerable variation in the doses of reversal
agents used, despite clear dosage information in the prescribing information for both drugs. Doses used were lower than
suggested for both shallow /moderate and deep block reversal for 79% of sugammadex and 55% of neostigmine group
patients. In addition, the study required the use of objective
TOF monitoring. Despite this monitoring, 4.5% of patients
were tracheally extubated when their TOF ratio was ⬍0.9.
Finally, 29% of patients did not have TOF ratio data for the
study-defined 10-minute and 20-minute time points, precluding determination of postoperative residual block.
The lack of consistency in practice clearly indicates
that evidence-based guidelines defining best practices for
monitoring and managing perioperative administration of
NMBAs are needed.34,35 This need is supported by experts
in the field.36-38 Standards can guide but are not intended to
replace institutional policies, and they can have a motivating influence on developing policies and procedures that are
more consistent with available evidence. Practice standard
Ve by the American Association of Nurse Anesthetists calls
for monitoring neuromuscular responses to assess depth of
blockade and degree of recovery.39
Additional practice guidelines for postanesthetic care updated by the ASA in 2013 also recommend assessment of
neuromuscular function during emergence and recovery for
patients who received non-depolarizing NMBAs.40 In addition, the guidelines recommend that specific antagonists
for reversal of “residual” neuromuscular blockage should be
administered when indicated.
Clarification of context and consistency of terms are needed. For example, published assertions are that there is no evidence that neuromuscular monitoring decreases the incidence
of residual paralysis.41 These authors have acknowledged that
the use of peripheral nerve stimulators to maintain a level of
neuromuscular block at TOF count of 1 may be too deep to
effectively reverse using cholinesterase inhibitors. Intraoperative monitoring should guide managing the appropriate level
of block considering the reversal drug at the conclusion of
surgery. Shallow to moderate neuromuscular block, defined
as the return of the second twitch on TOF count, may be better to consider when reversing with cholinesterase inhibitors.
Deeper levels of neuromuscular block, including profound
(PTC 1-2), should be reserved only for cases where necessary
and adequate time for significant spontaneous recovery can be
allowed. The use of post-tetanic facilitation to assess for low
level residual paralysis may be of benefit after reversal. Additionally, clinical assessments, including head lift and tongue
depressor (bite test), offer better indication of recovery than
TOF count alone. The use of accelerometry and TOF ratios
may improve the management of neuromuscular blockade
as it provides more reliable and objective data than that derived from peripheral nerve stimulators. TOF ratio differs
from TOF count as it refers to height of the fourth twitch
compared to the first. Train-of-four ratio is more difficult to
assess by visual or tactile assessment and is usually reserved
to accelerometry measurements. More guided and consistent
management of neuromuscular blockade is needed.
The potentially catastrophic effect of a lack of implementation guidelines was demonstrated in a European simulation study that included 18 anesthetic 2-person teams
(staff physician anaesthetist and nurse anaesthetist or nurse
anaesthetist and anaesthetic trainee).42 The teams were instructed to use sugammadex to antagonize the effects of
rapid sequence induction with a high dose of rocuronium
for a case that had deteriorated into a “can’t intubate/can’t
ventilate” situation. Sugammadex was kept in a central storage room rather than on a crash cart or other immediately
available source. The elapsed time to administer sugammadex was 6.7 minutes and was not different between the
2 staff groupings. Assuming 2.2 minutes for sugammadex
to achieve its effect, a total of 8.9 minutes would have passed
before the patient reached a TOF ratio of 0.9. This delayed
administration could have been fatal if a real patient were
involved. In addition to the time to go to the storage room
and return, other factors that contributed to delays were
searching for sugammadex by brand name rather than generic name, and taking time to read the package insert. In
addition, dosing errors were made by 88% of the teams. Ten
(56%) teams gave less, and 4 (22%) gave a dose that was
higher than the recommended dose for that patient. One
team discovered they were preparing rocuronium instead
of sugammadex, having removed the wrong drug from the
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storage room. The authors attributed the errors to a lack of
familiarity and limited education, and recommended that
a strict protocol should guide the introduction and use of
infrequently used medicines, accommodating factors that
contribute to human error.
The Importance of Communication and
Coordination Between the Surgeon,
Anesthesiologist, and Nurse Anesthetist
Poor communication is implicated in nearly 80% of adverse events in health care.43 The barriers to effective communication in the chaotic OR setting was identified as the
third-most important practice issue by AANA member
nurse anesthetists.44 European counterparts, in a qualitative survey study of factors that positively and negatively
affect the work environment of nurse anesthetists in Norway, found collaboration through teamwork was reported
as a crucial factor for favorable work conditions.45
Effective communication and coordination are essential
among the surgical team to ensure improved outcomes and
fewer complications in patients requiring neuromuscular
blockade. A wide range of outcome criteria contribute to a
successful operation, and their measurement can allow assessment of the effectiveness of the management plan.
A 1-week online survey conducted in 2012 explored
the opinions of surgical and anesthesia providers regarding communication and collaboration.46 A total of 507 respondents representing all demographic areas in the United
States included 202 anesthesiologists, 50 registered nurse
anesthetists, and 255 surgeons. Ninety-three percent of
anesthesiologists and 86% of nurse anesthetists reported
that communication with surgeons has an impact on their
ability to manage the anesthesia plan. Likewise, 88% of
surgeons believed that communication with the anesthesia
team impacts their ability to manage the surgical procedure.
Most of the respondents believed that several strategies
and tools could be somewhat or very effective at improving collaboration and communication in the OR, including assuring understanding of the surgical and anesthesia
plan by the anesthesia providers and surgeons, reaching an
agreement on the overall anesthesia plan before the surgery
begins, and having a checklist of guidelines to streamline
communication at all stages of an operation. The lesser interest in a checklist is in contrast to the reported success of
a World Health Organization Surgical Safety Checklist.47
Pilot test data showed major postoperative complications
decreased by one-third after introduction of the checklist,
and inpatient deaths by more than 40%.
Team communication and collaboration are important
not only for assurance of safe and effective care, but also for
the establishment of a positive work environment. Patient
safety depends on clear understanding and communication
of each team member’s role, responsibilities, and require-
16
ments. Team members who collaborate can ensure planned
improvements are given appropriate opportunities for success.
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unlearned. Part II: methods to reduce the risk of residual weakness. Anesth Analg. 2010;111:129-140.
2. Tripathi S. Neuromuscular blocking drugs in the critically ill.
CEACCP. 2006;6:119-123.
3. Savarese JJ, McGilvra JD, Sunaga H, et al. Rapid chemical antagonism of neuromuscular blockade by l-cysteine adduction
to and inactivation of the olefinic (double-bonded) isoquinolinium diester compounds gantacurium (AV430A), CW 002,
and CW 011.. Anaesthesiology. 2010;113:58-73.
4. Caldwell JE. Sugammadex: Past, Present, and Future. Adv
Anesth. 2011;29:19-37.
5. Merck. Merck receives complete response letter for investigational medicine sugammadex sodium injection. September 23,
2013; http://www.mercknewsroom.com. Accessed October 3,
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6. Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anesthesia. Expert Opin Pharmacother.
2008;9:1375-1386.
7. Bom A, Bradley M, Cameron K, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Engl. 2002;41:266–270.
8. Zhang M-Q. 2003. Drug-specific cyclodextrins: The future of rapid neuromuscular block reversal? Drugs Future.
2003;28:347–354.
9. Lemmens HJ, El-Orbany MI, Berry J, et al. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC Anesthesiology. 2010;10:15.
10. Khuenl-Brady KS, Wattwil M, Vanacker BF, et al. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter,
randomized, controlled trial. Anesth Analg. 2010;110(1):64-73.
11. Duvaldestin P, Kuizenga K, Saldien V, et al. A randomized,
dose-response study of sugammadex given for the reversal
of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg.
2010;110(1):74-82.
12. Decoopman M, Kamu G, Suy K, et al. Reversal of pancuronium induced block by the selective relaxant binding agent sugammadex. Eur J Anaesthesiol. 2007;24(Suppl 39):110–111.
13. Epemolu O, Bom A, Hope F, et al. Reversal of neuromuscular
blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal
agent Org 25969. Anesthesiology. 2003;99(3):632-637.
14. Abrishami A, Ho J, Wong J, et al. Sugammadex, a selective
reversal medication for preventing postoperative residual neuromuscular blockade. Cochrane Database Syst Rev. 2009;(4):
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CD007362. doi: 10.1002/14651858.CD007362.pub2.
15. Flockton EA, Mastronardi P, Hunter JM, et al. Reversal of
rocuronium-induced neuromuscular block with sugammadex
is faster than reversal of cisatracurium-induced block with neostigmine. Br J Anaesth. 2008;100(5):622-630.
16. Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular block by sugammadex administered three minutes
after rocuronium: a comparison with spontaneous recovery
from succinylcholine. Anesthesiology. 2009;110(5):1020-1025.
17. Della Rocca G, Pompei L, Pagan DE Paganis C, et al. Reversal
of rocuronium induced neuromuscular block with sugammadex or neostigmine: a large observational study. Acta Anaesthesiologica Scandinavica. 2013;57(9):1138-1145.
18. Geldner G, Niskanen M, Laurila P, et al. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing
laparoscopic surgery. Anaesthesia. 2012;67(9):991-998.
19. Bridion [Package insert]. Dublin, Ireland: Organon; 2013.
20. de Boer H, an Egmond J, van de Pol F, et al. Time course of
action of sugammadex (Org 25969) on rocuronium-induced
block in the Rhesus monkey, using a simple model of equilibration of complex formation. Br J Anaesth. 2006; 97(5):681-686.
21. de Boer HD DJ, van Egmond J, Booij LHDJ. Non-steroidal
neuromuscular blocking agents to re-establish paralysis after
reversal of rocuronium-induced neuromuscular block with sugammadex. Can J Anaesth. 2007;55:124-125.
22. Desforges JCW, McDonnell NJ. Sugammadex in the management of failed intubation in a morbidly obese patient. Anaesth
Intensive Care. 2011;39:763-764.
23. Curtis R, Lomax S, Patel B. Use of sugammadex in a ‘can’t intubate, can’t ventilate’ situation. Brit J Anaesth. 2012;108:612-614.
24. Kyle BC, Gaylard D, Riley RH. A persistent ‘can’t intubate, can’t
oxygenate’ crisis despite rocuronium reversal with sugammadex. Anaesth Intensive Care. 2012;40:344-346.
25. Bisschops MM, Holleman C, Huitink JM. Can sugammadex
save a patient in a simulated ‘cannot intubate, cannot ventilate’
situation? Anaesthesia. 2010;65:936-941.
26. Peeters P, Passier P, Smeets J, et al. Single intravenous high-dose
sugammadex (up to 96 mg/kg) is generally safe and well tolerated in healthy volunteers. Eur. J. Anaesthesiol. 2008;25(Suppl
44).
27. Schering-Plough. Sugammadex NDA 22-225. http://
www.fda.gov/ohrms/dockets/ac/08/slides/2008-4346s101-Schering-Plough-corebackup.pdf slide 141-146. March
2008. Accessed Sept 28, 2013.
28. Godai K, Hasegawa-Moriyama M, Kuniyoshi T, et al. Three
cases of suspected sugammadex-induced hypersensitivity reactions. Brit J Anaesth. 2012;109:216-218.
29. Asahi Y, Omichi S, Adachi S, et al. Hypersensitivity reaction
probably induced by sugammadex. Acta Anaesthesiologica Taiwanica. 2012;50:183-184.
30. Soria A MC, Haouar H, Chemam S, et al. Severe reaction
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following sugammadex injection: hypersensitivity? J Investig
Allergol Clin Immunol. 2012;22:382.
Menendez-Ozcoidi L, Ortiz-Gomez JR, Olaguibel-Ribero
JM, et al. Allergy to low dose sugammadex. Anaesthesia.
2011;66:217-219.
Merck. http://www.mercknewsroom.com. Accessed October
3, 2013.
Lemmens Hj, El-Orbany MI, Berry J, et al. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC
Anesthesiol. 2010;10:15.
Murphy GS, Brull SJ. Residual neuromuscular block: lessons
unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg.
2010;111(1):120-128
Murphy GS, Szokol JW, Avram MJ, et al. Postoperative residual neuromuscular blockade is associated with impaired
clinical recovery. Anesth Analg. 2013;117(1):133-141.
Kopman AF. Managing neuromuscular block: where are the
guidelines? Anesth Analg. 2010;111:9-10.
Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, Brull
SJ. A survey of current management of neuromuscular block in
the United States and Europe. Anesth Analg. 2010;111:110-119.
Viby-Mogensen J, Claudius C. Evidence-based management
of neuromuscular block. Anaesth Analgesia. 2010;111:1-2.
AANA. Standards for Nurse Anesthesia Practice. http://
www.aana.com/resources2/professionalpractice/Documents/PPM%20Standards%20for%20Nurse%20Anesthesia%20Practice.pdf ) Accessed Sept 29, 2013.
Apfelbaum JL, Silverstein JH, Chung FF, et al. Practice guidelines for postanesthetic care: an updated report by the American Society of Anesthesiologists Task Force on Postanesthetic Care. Anesthesiology. 2013;118:291-307.
Naguib M, et al. Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis. Br. J. Anaesth.
2007; 98(3):302-316.
Bisschops MM, Holleman C, Huitink JM. Can sugammadex
save a patient in a simulated ‘cannot intubate, cannot ventilate’
situation? Anaesthesia. 2010;65:936-941.
WHO. http://www.who.int/patientsafety/safesurgery/pilot_
sites/en/index.html. Accessed October 8, 2013.
Wilson W. AANA Annual Business Meeting Report of the
Executive Director. August 11, 2013. AANA Annual Meeting, Las Vegas NV.
Averlid G. AANA Journal. 2012;80:S74-S80.
OR Xchange. A program by Merck. About the Survey.
Available at: http://www.or-xchange.com/java/orxchange/
survey/ Accessed Oct 2, 2013WHO. http://www.who.int/
patientsafety/safesurgery/pilot_sites/en/index.html. Accessed October 8, 2013.
WHO. http://www.who.int/patientsafety/safesurgery/pilot_
sites/en/index.html. Accessed October 8, 2013.
Supplement to AANA Journal • December 2013
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1.1
CNE Posttest
1.
Which of the following groups of agents include a hypnotic,
an analgesic, and a neuromuscular blocking agent, in that
order?
A. Desflurane, etomidate, tramadol
B. Isoflurane, propofol, fentanyl
C. Propofol, tramadol, cisatracurium
D. Nalbuphine, fentanyl, vecuronium
7.
Qualitative neuromuscular function monitoring
A. Produces valid and reliable assessment of TOF ratios.
B. Is commonly done using acceleromyography.
C. Is the only monitoring method available outside the
research setting.
D. Requires visual or tactile assessments of response to
peripheral nerve stimulation.
2.
A train-of-four ratio of 0.20
A. Means there were 2 twitches in response to the
4 electrical impulses.
B. Is equivalent to 80% of receptors blocked.
C. Designates the appropriate time to reverse the
blockade with neostigmine.
D. Indicates that the height of the first twitch was
5 times that of the fourth twitch.
8.
Which of the following is true about sugammadex?
A. It acts through irreversible encapsulation of all
neuromuscular blocking agents.
B. It is a modified cyclodextrin, with a central
hydrophilic cavity.
C. It is effective at reversing the neuromuscular block
induced by all neuromuscular blocking agents.
D. It has been approved for reversing neuromuscular
blockade in more than 50 countries since 2008.
3.
Which requires a greater level of neuromuscular block:
pelvic or subdiaphragmatic surgery?
A. Pelvic
B. Subdiaphragmatic
C. They both require the same blockade level.
D. They are the same if the subdiaphragmatic surgery
is a liver resection.
9.
In the randomized controlled trial comparing sugammadex
(deep block) with neostigmine (moderate block) in
laparoscopic cholecystectomy or appendectomy patients
A. Time from reversal agent administration to recovery of
a TOF ratio 肁0.9 was similar in both groups; however,
time from last rocuronium dose until adequate recovery
was significantly less in the sugammadex group.
B. Times in the operating room and PACU were significantly
greater in the neostigmine group compared with the
sugammadex group.
C. Both time from reversal agent administration to recovery
of a TOF ratio 肁0.9 and time from last rocuronium dose
until adequate recovery were significantly less in the
sugammadex group.
D. Five cases of clinically significant bradycardia occurred
in the sugammadex group.
4.
Neostigmine treatment
A. Induces neuromuscular blockade reversal less rapidly in
febrile patients.
B. Requires co-administration of an anticholinergic drug.
C. Reliably reverses deep neuromuscular block.
D. Is not associated with residual paralysis if given when 4
TOF twitches are present.
5.
Which of the following non-depolarizing neuromuscular
blocking agents is not an aminosteroid?
A. Atracurium
B. Rocuronium
C. Vecuronium
D. Pancuronium
6.
Which of the following is a long-acting non-depolarizing
neuromuscular blocking agent?
A. Pancuronium
B. Atracurium
C. Cisatracurium
D. Rocuronium
18
10. Which of the following is true about sugammadex and
hypersensitivity?
A. It has been observed only at doses 肁16 mg/kg.
B. No postmarketing cases have yet been reported.
C. There have been no reported cases of anaphylaxis.
D. Sensitization to sugammadex may have been produced
by cyclodextrins in food.
Supplement to AANA Journal • December 2013
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Deep Neuromuscular Blockade:
Exploration and Perspectives on
Multidisciplinary Care
6. I plan to make the following changes to my practice:
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Supplement to AANA Journal
December 2013
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POSTTEST
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Y N 2 1
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______________________________________________________________________
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Deep Neuromuscular Blockade:
Exploration and Perspectives on
Multidisciplinary Care
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