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Sugammadex: Implications for Future Clinical Practice
Kari Bentley CRNA MSN
Sothida Berry CRNA MSN
Heather Rawlings CRNA MSN
Major Peter Strube CRNA MSNA APNP ARNP
Rosalind Franklin University
1
Objectives
Describe the mechanism of action of sugammadex.
Discuss the effectiveness of various dosages of sugammadex for reversing rocuronium and vecuronium induced neuromuscular blockade.
Describe the efficacy of sugammadex following maintenance of anesthesia with inhalation and intravenous anesthesia.
Discuss the potential for residual blockade following administration of sugammadex
Describe the various clinical scenarios in which sugammadex may provide favorable surgical or intubating conditions.
List the potential advantages and disadvantages for the future use of sugammadex.
Discuss the use of sugammadex in specific patient populations such as elderly, renal failure, and pediatric patients.
2
Abstract
Sugammadex, a new selective muscle relaxant-binding drug, is used to rapidly
reverse muscle relaxation, regardless of the depth of neuromuscular blockade. The ability
of sugammadex to reverse both shallow or moderate vecuronium and rocuronium
induced neuromuscular blockade may greatly impact the future clinical practice of
anesthesia. Dose finding studies have demonstrated the effectiveness of sugammadex at
reversing deep neuromuscular blockade. Sugammadex is effective when used in
conjunction with either inhalational or intravenous anesthesia. Studies have been
conducted to demonstrate its use in different clinical scenarios and patient populations.
Scenarios such as a potential difficult airway, short duration procedures, and scenarios
where succinylcholine is contraindicated have been examined. Use of sugammadex in
morbidly obese patients, obstetrics, pediatrics, and geriatrics has proven to be safe and
effective. This review highlights the current research surrounding the use of sugammadex
and its potential implications for the future practice of anesthesia.
Keywords: sugammadex, neuromuscular block, reversal, rocuronium, neostigmine
3
Neuromuscular-blocking agents (NMBAs) are frequently used in patients
undergoing surgical procedures to facilitate endotracheal intubation, provide patient
immobility, and enhance surgical exposure. Commonly used agents in clinical practice
are rocuronium and vecuronium, both aminosteroid non-depolarizing NMBAs and
succinylcholine, a depolarizing NMBA. Since succinylcholine is metabolized quickly by
the enzyme pseudocholinesterase, a reversal medication is not necessary to reverse
muscle paralysis. Recovery from aminosteroid non-depolarizing NMBAs can take place
spontaneously through hepatic and renal metabolism and elimination, but this process is
slow and may result in residual muscle paralysis.
Reversal of NMBAs is currently accomplished using acetylcholinesterase
inhibitors, most commonly neostigmine, to decrease the risk of residual postoperative
muscle weakness. The suppression of the breakdown of acetylcholine, allows it to
accumulate and displace neuromuscular blockade (NMB) molecules from binding sites
on the nicotinic receptors.1 Acetylcholinesterase inhibitors have a significant side effect
profile due to undesired stimulation of muscarinic receptors, which can cause
cardiovascular, gastrointestinal, and respiratory adverse events.1 Co-administration of
muscarinic antagonists is necessary to counteract these adverse effects. Anticholinergic
agents cause additional side effects, such as tachycardia, sedation, confusion, and blurry
vision.2 A major disadvantage of acetylcholinesterase inhibitors is the inability to
adequately displace enough neuromuscular blocking molecules to reverse a profound
depth of neuromuscular block.1 A reversal agent with improved clinical utility and safety
is desirable to eliminate the routine use of acetylcholinesterase inhibitors.
An alternative to indirect reversal of NMBAs with acetylcholinesterase
4
inhibitors is sugammadex, a selective relaxant-binding agent, which directly encapsulates
aminosteroid non-depolarizing NMBAs.1 Sugammadex, a modified gamma cyclodextrin,
is capable of rapid reversal of muscle relaxation, regardless of the depth of
neuromuscular blockade.1 Sugammadex forms a tight complex with unbound steroidal
NMBAs.1 The interaction of the two agents decreases the amount of NMBA in the
plasma, which leads to a shift of NMBA from the tissue into the plasma and reduces the
level of free NMBA at the neuromuscular junction.3 Studies in surgical patients have
revealed that sugammadex provides well-tolerated and dose-dependent rapid reversal of
shallow and profound rocuronium-induced neuromuscular block.4 Sugammadex is also
capable of encapsulating vecuronium molecules, but to a lesser extent.2 Sugammadex is
regarded as an ideal reversal agent that will likely change the future practice of
anesthesia.5
Impact on Clinical Practice
Sugammadex has been evaluated at various doses in many clinical scenarios,
primarily related to the timing of administration in relation to when the NMBA was given
and the depth of the neuromuscular block. Level of blockade is most commonly
monitored using a peripheral nerve stimulator to assess the train-of-four (TOF) ratio.
TOF consists of 4 electrical impulses delivered at 2 Hz over a 1.5 second interval. The
ratio is determined by comparing the height of the fourth twitch (T4) to the height of the
first twitch (T1). When T4 is no longer present, 70-75% of the nicotinic acetylcholine
receptors have been occupied by NMBA. If twitches are absent, a tetanus stimulus is
applied and a post-tetanic count (PTC) is assessed to determine the depth of blockade.
Shallow or moderate block relates to the reappearance of the second twitch (T2) or
5
approximately 30 min after the administration of rocuronium or vecuronium.6 Deep block
is associated with absence of TOF twitches with a PTC of 1-2 or an average of 10-15 min
after administration of rocuronium or vecuronium.6
Dose-finding studies have demonstrated the effectiveness of sugammadex at
rapidly reversing aminosteroid-induced neuromuscular blockade, including profound
blockade.1, 3-5 Sugammadex will have important clinical implications in surgical patients
requiring maintenance of deep neuromuscular block throughout the entire surgical
procedure. This will also be a beneficial drug in cases where surgery ends earlier than
expected and a dose of an aminosteroid neuromuscular blocking agent was recently
administered. The incidence of residual paralysis and associated post-operative
complications is reduced with administration of sugammadex compared to
acetylcholinesterase inhibitors.17 Sugammadex is also advantageous in patients requiring
rapid sequence induction, in procedures that require a very short duration of muscle
paralysis, and in situations where succinylcholine is contraindicated.
Reversal of Shallow / Moderate Block
Schaller et al.7 researched shallow residual rocuronium-induced blockade (TOF
ratio 0.4-0.7) since this is a common depth of blockade encountered in the clinical
setting. This study used sugammadex at doses of 0.0625, 0.125, 0.25, 0.5 or 1 mg/kg and
was compared with the use of neostigmine at doses of 5, 8, 15, 25, or 40 mcg/kg to
reverse a shallow block once TOF ratio reached 0.5 -0.9.7 Results from this study found
that sugammadex 0.22 mg/kg is able to reverse a TOF ratio > 0.5 in an average of 2 min,
while neostigmine 34 mcg/kg reverses the same level of blockade within 5 min.7
A study by Suy et al.8 investigated the dose response relationship of sugammadex
6
as a single dose reversal agent for a rocuronium or vecuronium-induced block after the
reappearance of T2. Results of the study concluded that when compared to those in the
placebo group, a decrease in the mean time to recovery was found for all TOF ratios with
both rocuronium and vecuronium.8 Patients who received rocuronium were found to have
a mean recovery time of 31.8 min with placebo, 3.7 min with 0.5 mg/kg sugammadex,
and 1.1 min with 4 mg/kg sugammadex.8 Vecuronium-induced patients had a recovery
time of 48.8 min with placebo, 2.5 min with 1 mg/kg sugammadex, and 1.4 min with 8
mg/kg sugammadex.8
Khuenl-Brady et al.2 compared the use of neostigmine versus sugammadex in the
reversal of 0.1 mg/kg vecuronium. The results indicated that time to recovery of TOF
ratio to 0.9 averaged 2-3 min after administration of 2 mg/kg sugammadex compared to
17-18 min after 50 mcg/kg neostigmine.2
Research by Duvaldestin et al.9 evaluated the use of sugammadex in reversing
rocuronium and vecuronium-induced NMB under sevoflurane anesthesia. One group
received vecuronium 0.1 mg/kg and mean time to recovery to TOF ratio of 0.9 was 68.4
min when sugammadex was administered at 0.5 mg/kg, 9.1 min (2 mg/kg), 3.3 min (4
mg/kg), and 1.7 min (8 mg/kg).9 Another group received 0.6 mg/kg rocuronium and
mean time to recovery of TOF ratio of 0.9 was 79.8 min when sugammadex was
administered at 0.5 mg/kg, 3.2 min (2 mg/kg), 1.7 min (4 mg/kg), and 1.1 min (8
mg/kg).9
Flockton et al.10 compared reversal of 0.6 mg/kg rocuronium with 2 mg/kg
sugammadex to reversal of 0.15 mg/kg cisatracurium with 50 mcg/kg neostigmine. The
efficacy variable measured in this study was the time to TOF ratio of 0.9 after reversal
7
agent administration at reappearance of T2.10 The time to recovery of TOF ratio to 0.9
was almost five times faster with sugammadex, 1.4 min with sugammadex versus 17.6
min with neostigmine.10
Research by Sorgenfrei et al.11 studied the use of sugammadex, administered at
reappearance of T2, to reverse a NMB induced by 0.6 mg/kg rocuronium in a group of
patients anesthetized with fentanyl and propofol. Patients in the placebo group recovered
from NMB at 21 min, while those in the sugammadex group with doses greater than or
equal to 2 mg/kg recovered in 3 min.11
Reversal of Deep / Profound Block
When the level of NMBA is profound, the increase in acetylcholine concentration
following administration of acetylcholinesterase inhibitors is inadequate to displace
enough NMBA molecules to reverse NMB.1 Studies have been conducted to examine the
effects of sugammadex used in reversal of deep NMB produced by aminosteroid non-
depolarizing NMBAs. Some studies investigated a single dose of sugammadex, while
others trialed various doses to determine optimal dosing to achieve a T4/T1 ratio of
0.9.1,3,5,12-14 Recovery from deep neuromuscular blockade, defined as 1-2 PTCs, is
considerably faster with sugammadex versus neostigmine.1,3,5,12-14
Jones et al.1 conducted a study using sugammadex at a dose of 4 mg/kg to reverse
a deep rocuronium-induced block, which resulted in a recovery time that was 17 times
faster than neostigmine at a dose of 70 mcg/kg. Sugammadex or neostigmine was
administered at reappearance of 1-2 PTCs.1 Recovery to TOF ratio of 0.9 occurred within
3 min in 70% of sugammadex patients and all except one recovered within 5 min.1 In the
neostigmine group, 73% of the patients achieved a TOF ratio of 0.9 in 30-60 min and
8
23% of the patients required more than 60 min to reach this recovery parameter.1
Research by Pavoni et al.5 found that 16 mg/kg sugammadex administered 3 min
after 1.2 mg/kg rocuronium resulted in a mean recovery time to TOF ratio of 0.9 in 114
+/- 75 sec. A second group in this study received 4 mg/kg sugammadex 15 min after 0.6
mg/kg rocuronium was given, which resulted in a mean time to TOF ratio of 0.9 in 186
+/- 105 sec.5
Puhringer et al.3 studied sugammadex at doses of 2, 4, 8, 12, or 16 mg/kg
administered at either 3 or 15 min following 1.0-1.2 mg/kg rocuronium. This research
concluded that the encapsulation of rocuronium by sugammadex allows for significantly
faster, in a dose-dependent manner, reversal of high dose rocuronium.3 There were no
occurrences of residual neuromuscular blockade in any of the dosing groups.3 There were
no differences in recovery time at the two different time points of administration, with the
exception of the 2 mg/kg and 4 mg/kg doses.3 A plateau effect existed in the time to
recovery at doses of 8 mg/kg or greater.3 Sugammadex 16 mg/kg given at 3 or 15 min
after rocuronium was significantly faster in reversing high-dose rocuronium (1.6 and 0.9
min vs. placebo at 111 and 91 min).3
Boer et al.14 revealed a dose-dependent relationship for reversal of rocuronium-
induced neuromuscular blockade following administration of sugammadex at 2, 4, 8, 12,
and 16 mg/kg. Sugammadex was administered 5 min after a dose of 1.2 mg/kg
rocuronium. Patients who recovered spontaneously required an average of 122 min,
while those who received sugammadex recovered in less than 2 min.14
Additional clinical studies have supported the dose-dependence of sugammadex
to speed of recovery.12-13 A study by Sparr et al.12 consisting of 98 subjects found that
9
time to TOF ratio of 0.9 was less than 3 min following 6 mg/kg sugammadex. When
sugammadex was given at 2 mg/kg, recovery to TOF ratio of 0.9 was 15 min.12 Research
by Groudine et al.13 supported that reversal with sugammadex at higher doses resulted in
faster recovery times. Sugammadex administered at a dose of 4- 8mg/kg to reverse a
profound neuromuscular blockade resulted in a mean recovery time of 1.7 min compared
with 44.2 min in the group that received 0.5 mg/kg sugammadex.13
Use with Inhalation Anesthesia vs. Intravenous Anesthesia
Volatile anesthetics potentiate the duration of action of NMBAs. Vanacker et
al.15 studied the effects of sugammadex administration following maintenance anesthesia
with either propofol or sevoflurane. The study found that sevoflurane does not reduce the
efficacy of sugammadex in reversing rocuronium-induced NMB.15 Time from
administration of 0.6 mg/kg rocuronium to reappearance of T2 was 33 min in the
propofol group and 51.8 min in the sevoflurane group.15 The mean time from
administration of 2 mg/kg sugammadex to TOF ratio of 0.9 was 1.8 min in both the
propofol and sevoflurane groups.15 The results confirm that sevoflurane enhances NMB,
but it does not reduce the efficacy of sugammadex in reversing NMB.15
Rex et al.16 concluded that a single dose of sugammadex after continuous
rocuronium infusion is equally effective in maintenance anesthesia with sevoflurane or
propofol. The study of 52 subjects found the type of maintenance anesthesia had a
significant effect on plasma rocuronium concentration measured prior to administration
of sugammadex.16 The propofol group had 33% lower rocuronium plasma concentration
than the sevoflurane group.16 Both groups received a continuous infusion of rocuronium
at 7 mcg/kg/min, which was adjusted to maintain a depth of zero twitches with no more
10
than 10 PTC.16 Following rocuronium infusion discontinuation, subjects received a dose
of 4 mg/kg sugammadex at T1 of 3-10%.16 Mean recovery time from administration of
sugammadex to a TOF ratio of 0.9 was 1.4 min in the sevoflurane group and 1.3 min in
the propofol group.16
Residual Blockade
Peripheral nerve stimulation (PNS) is the most widely used monitor to assess the
depth of neuromuscular blockade and to determine adequacy of NMBA reversal.17 A
TOF ratio of 0.9 or greater is the desired parameter to achieve prior to tracheal
extubation. Despite utilizing the TOF as an assessment tool to determine the level of
block, many patients will be extubated prior to full return of pharyngeal and respiratory
muscle function.17 The consequences of residual neuromuscular blockade in the early
postoperative period include hypoventilation, hypoxia, airway obstruction, pulmonary
complications, aspiration, and increased mortality.1,17
The use of subjective visual assessment for determination of twitch response may
lead to overestimation of the level of neuromuscular recovery. Illman et al.17 conducted
research to determine if sugammadex is able to reduce the potentially unsafe period of
neuromuscular recovery. The time gap between loss of visual fade by using a PNS until
TOF ratio > 0.9 using objective monitoring equipment is considered to be a potential
period of unsafe recovery.17 This trial demonstrated that reversal of a moderate
rocuronium-induced block with sugammadex reduces the potentially unsafe recovery
period to less than 20 sec as compared to neostigmine, which averaged 10 min.17 The use
of sugammadex to antagonize NMBA will decrease the incidence of critical respiratory
events associated with residual blockade.17
11
Clinical Scenarios & Patient Populations
Procedures of short duration requiring muscle relaxation
Kadoi et al.18 researched three different doses of sugammadex to determine
optimal dosing to produce equal recovery time from rocuronium-induced muscle
relaxation compared with spontaneous recovery from succinylcholine in patients
undergoing electroconvulsive therapy (ECT). Neuromuscular recovery of T1 to 90% and
time to first spontaneous breath with sugammadex at a dose of 16 mg/kg was
significantly shorter than with 1 mg/kg succinylcholine.18 Sugammadex 4 mg/kg resulted
in a longer time to recovery of T1 to 10% and 90% and longer time to first spontaneous
breath compared to succinylcholine.18 Comparable recovery times were seen with
succinylcholine and sugammadex at a dose of 8 mg/kg.18 Sugammadex used to reverse
rocuronium is an efficacious alternative to succinylcholine in short duration procedures
requiring muscle relaxation.
Contraindications to Succinylcholine
Succinylcholine is associated with many adverse effects and contraindications,
including history of neuroleptic malignant syndrome, severe osteoporosis, amyotrophic
lateral sclerosis, pseudocholinesterase deficiency, and malignant hyperthermia.19 Clinical
scenarios in which succinylcholine is contraindicated poses challenges for anesthesia
providers. An alternate agent that will quickly induce muscle relaxation and expedite fast
recovery time is necessary in many clinical situations.
Sugammadex used to reverse a deep rocuronium-induced block has been
compared with spontaneous neuromuscular recovery time following succinylcholine.
Lee et al.26 studied reversal of profound high-dose rocuronium (1.2 mg/kg) with 16 mg/kg
12
sugammadex and found significantly faster recovery compared to spontaneous recovery
from 1 mg/kg succinylcholine.4 Efficacy parameter, T1 to 90%, was achieved in 6.2 min
in the sugammadex-rocuronium group compared with 10.9 min in the succinylcholine
group.4
Difficult Airway
Succinylcholine has been the preferred medication utilized in patients with a
potential difficult airway. Recent studies indicate that succinylcholine may no longer be
the drug of choice due to the limited time available for successful intubation.20 If the
airway is not secured within the timeframe of maximum effect of succinylcholine,
intubating conditions can be suboptimal and lead to prolonged time of hypoxia.
Sugammadex can potentially reverse neuromuscular blockade faster than spontaneous
recovery from succinylcholine.21
Mcternan et al.22 describes an advantage for the use of sugammadex in a difficult
airway caused by a large infraglottic polyp. Unlike many scenarios where neuromuscular
blockers are avoided in a potentially difficult airway, the effectiveness of sugammadex in
reversing rocuronium may be useful in cases where complete muscle relaxation is
required to surgically operate on a threatened airway. Mcternan et al.22 reports a surgical
case in which 60-80% of the airway circumference was occupied by a large pedunculated
polyp located underneath the right vocal cord. Jet ventilation was utilized to facilitate
laser ablation of the tumor. Sugammadex 4 mg/kg was used to reverse the patient with a
TOF of 0 and a PTC of 5.22 Return of TOF >0.9 was achieved in 1 min 45 sec and
extubation proceeded without complications.22 The ability of sugammadex to fully
antagonize the actions of rocuronium in a deep neuromuscular blockade scenario is
13
advantageous for operations involving the airway.
Morbidly Obese
Reversal from neuromuscular blockers and the ability to protect the upper airway
reflexes is one critical goal following general anesthesia with the use of NMBAs.
Avoiding residual paralysis decreases the risk of aspiration and other respiratory
complications. Similar to other drugs used to induce general anesthesia such as
rocuronium, pharmacokinetic studies indicate that weakly lipophilic drugs are dosed on
ideal body weight rather than actual body weight.23 The dosing of sugammadex has
commonly been calculated based on total body weight.23 Van Lanker et al.23 suggests the
ideal formula that should be used when calculating an appropriate sugammadex dose for
a morbidly obese patient to be 2 mg/kg IBW + 40%.
Desforges and McDonnell 24 describe a case scenario in which sugammadex was
administered to reverse rocuronium in a failed intubation attempt in a morbidly obese
patient weighing 110 kg. After multiple unsuccessful attempts for securing an airway, the
researchers attempted ventilation through a laryngeal mask airway (LMA).24 The oxygen
saturation continued to drop and attempts at ventilation were unsuccessful, so the
researchers administered 700 mg of sugammadex approximately 5 min after the
administration of rocuronium.24 Within 45 sec, the patient made strong respiratory effort
through the LMA.24 This case report demonstrates a successful outcome of using
sugammadex in an unanticipated difficult airway emergency in a morbidly obese patient.
Gaszynski et al.25 investigated the outcome of sugammadex versus neostigmine
for reversal of NMB in severely morbidly obese patients scheduled for bariatric surgery.
Sugammadex at a dose of 2 mg/kg resulted in a mean recovery time to TOF ratio of 0.9
14
that was 3.5 times shorter than neostigmine at a dose of 0.05 mg/kg.25
Obstetrics
The obstetric population is well known for having a potential difficult airway. The
use of NMBAs has been a topic of controversy in this patient population, as advantages
and disadvantages must be weighed when using muscle relaxation for a cesarean section.
General anesthesia in the obstetric population involves rapid sequence induction (RSI)
with succinylcholine. Succinylcholine has a significant side-effect profile, however no
NMB exists that has as favorable onset and offset characteristics needed to perform
tracheal intubation in this patient population. Rocuronium is typically avoided as its
duration of action is much longer than the time required to perform a cesarean section.
Recent data showing the effectiveness of sugammadex has piqued interest of providers to
the possibility of using rocuronium in the obstetric population as opposed to
succinylcholine. A large dose of rocuronium (1.2 mg/kg) has been shown to have a mean
onset time of 55 sec in comparison to 50 sec when succinylcholine is used.26
A study by Williamson et al.26 examined the use of sugammadex to reverse a
profound rocuronium-induced NMB at the end of obstetric procedures. A group of 18
patients received 4 mg/kg sugammadex to reverse 1.2 mg/kg rocuronium, which resulted
in a mean time to TOF ratio > 0.9 in 62 sec.26 Results also revealed a more rapid return of
neuromuscular function than the spontaneous offset of succinylcholine.26
Pediatrics
The use of sugammadex in the pediatric population has proven to be safe and
effective in clinical trials.27 Pharmacologic treatment differs in the pediatric population in
comparison to the adult population in clinical effect, duration, metabolism and excretion.
15
The clinical duration of rocuronium is prolonged in infants when compared to children.27
Rocuronium potency is greater in infants and less in children compared to adults. Plaud
et al.27 examined the safety and efficacy of sugammadex in 8 infants (28 days-23 mo.), 24
children (2-11 yr.), 31 adolescents (12-17 yr.) and 28 adults (18-65 yr.). The study found
the mean time from administration of rocuronium to the appearance of T2 was 29 min in
the infant group, 21.8 min in the children group, 26 min in the adolescent group, and 32.9
min in the adult group.27 Time to a TOF ratio of 0.9 decreased with increased doses of
sugammadex in all age groups.27 Recovery times to TOF ratio of 0.9 after sugammadex
administration were 0.6-3.7 min (infants), 0.6-3.7 min (children), 1.1-4.6 min
(adolescents) and 1.2-4.2 min (adults) in a dose-dependent manner.27 At a dose of 2
mg/kg sugammadex, recovery of TOF to 0.9 in all age groups occurred with a median
time of 1.1-1.2 min.27 No formal dose-response relation was achieved in the infant group
because of the small number of subjects in each dose group.27 Results indicated that
sugammadex dosing based on body weight had similar plasma sugammadex levels
independent of age group.27 No clinical differences were seen in regards to dose and age
groups with the incidence of adverse effects.27
Elderly
Postoperative morbidity and mortality in the elderly population is higher than in
the adult population. Several factors that contribute to this are physiologic changes in
cardiovascular, respiratory and renal function. Pharmacokinetics and pharmacodynamics
of drugs can vary in clinical effect, duration, metabolism and elimination among the
elderly population. Volume of distribution, albumin levels, and organ function in the
elderly also contribute to unpredictable responses to medications. Renal function declines
16
rapidly after the fourth decade of life and the onset, duration, metabolism and elimination
time of drugs are prolonged.28
McDonagh et al.28 studied the efficacy, safety, and pharmacokinetics of
sugammadex in moderate rocuronium-induced neuromuscular blockade in adults (18-64
yr.), elderly (65-74 yr.), and old-elderly (75 yr. or older) patients. The mean time from
administration of sugammadex (2 mg/kg) to recovery of TOF ratio to 0.9 increased
slightly in the elderly and the old-elderly groups.28 The mean time to recovery was 2.3
min in the adult group, 2.6 min in the elderly group and 3.6 min in the old-elderly
group.28 All patients recovered within 10 min, although fewer patients in the elderly or
old-elderly group recovered to a TOF ratio of 0.9 within 10 min compared to the adult
group (75.5% vs. 85.4%, respectively).28 The study concluded that recovery to a TOF
ratio of 0.9 was 0.7 min faster in the adult group compared with subjects 65 yr. and
older.28 Sugammadex clearance had an inverse relationship with increasing age and was
decreased by half compared with the adult subject.28 Sugammadex half-life was doubled
in the elderly compared with the typical adult subject (4.6 vs. 2.4 hr., respectively).28 The
study found that sugammadex at a dose of 2 mg/kg was safe and effective at reversing
rocuronium-induced NMB in both adult and elderly patients.28
A study comparing reversibility of rocuronium-induced neuromuscular block with
sugammadex in younger (20-50 yr.) and older (≥70 yr.) patients demonstrated adequate
neuromuscular recovery in both groups.29 A dose of 4 mg/kg sugammadex was
administered at a PTC of 1-2 and the time required to achieve a TOF ratio of 0.9 was
measured.29 Results revealed a significant increase in the amount of time required to
achieve a TOF of 0.9 in the older population, 3.6 min in the older group versus 1.3 min in
17
the younger group.29 This study confirmed the safety of sugammadex in the elderly
population.
Renal Failure
Mean time to recovery from rocuronium-induced neuromuscular blockade is
significantly prolonged in patients with end-stage renal failure. Staals et al.30 studied the
safety and efficacy of sugammadex in reversal of rocuronium-induced neuromuscular
blockade in patients with normal kidney function compared to patients with severe
kidney impairment.30 The study compared the effects of 2 mg/kg sugammadex in 15
patients with renal impairment (creatinine clearance <30 ml/.min.) and 15 patients with
normal renal function (creatinine clearance >80 ml/min.).30 Time from administration of
rocuronium to reappearance of T2 was 53.8 min in the renal-impaired group compared to
40.6 min in the normal kidney function group.30 Time from sugammadex administration
to TOF ratio 0.9 was 2 min in the renal insufficiency group compared to 1.65 min in the
control group.30 No recurrence of NMB was seen in any subjects in either group.30
Hematology and urine studies were similar between the two groups when comparing
differences that existed at baseline.30 The study concluded that sugammadex at a dose of
2 mg/kg can safely and effectively reverse rocuronium-induced NMB in patients with
renal compromise.30
Conclusion
Reversal of neuromuscular blockade with acetylcholinesterase inhibitors is
associated with significant adverse side effects, inability to reverse profound
neuromuscular blockade, and potential for residual blockade. A reversal agent with
improved clinical utility and safety is desirable to eliminate the routine use of
18
acetylcholinesterase inhibitors. Dose-finding studies have demonstrated the effectiveness
of sugammadex to provide rapid reversal of any depth of neuromuscular block. An
important clinical implication of sugammadex is the reduced incidence of residual
paralysis and associated post-operative complications in comparison to
acetylcholinesterase inhibitors. Sugammadex is also advantageous in patients requiring
rapid sequence induction, in procedures that require a very short duration of muscle
paralysis, and in situations where succinylcholine is contraindicated.
Discussion
Research to date has shown that sugammadex is a safe and effective agent for
reversal of NMB induced by rocuronium or vecuronium. The future of the drug in the
United States will remain to be seen, pending Food and Drug Administration (FDA)
approval.31 In 2008, the FDA did not approve the original new drug application (NDA)
for sugammadex and requested more information regarding hypersensitivity reactions
and coagulation events.31 Merck submitted the requested data with the NDA
resubmission.31 In January 2013, the FDA concluded the NDA on sugammadex is now
complete for review, which is a significant breakthrough in Merck’s efforts to bring
sugammadex to the U.S.31 Merck expects the review of the NDA to be completed by the
FDA by mid-2013.31
Use of sugammadex could ultimately negate the use of succinylcholine in clinical
practice and permit the use of non-depolarizers for rapid sequence intubation.
Sugammadex provides fast reversal of profound NMB and reduces the incidence of post-
operative respiratory complications associated with residual weakness. FDA approval for
use of sugammadex in the U.S. could greatly impact future anesthesia practice.
19
References
1. Jones RK, Caldwell, JE, Brull, SJ, Soto RG. Reversal of profound rocuronium-induced
blockade with sugammadex: a randomized comparison with neostigmine.
Anesthesiology. 2008;109:816-824. doi: 10.1097/ALN.0b013e31818a3fee.
2. Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H,
Alvarez-Gomez JA. Sugammadex provides faster reversal of vecuronium-induced
neuromuscular blockade compared with neostigmine: a multicenter, randomized,
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Questions
1. Traditional neuromuscular reversal agents work by______ and may lead to significant side effects due to the blocking of _______receptors which may result in bradycardia.
a. pseudocholinesterase; muscarinicb. pseudocholinesterase; nicotinicc. inhibiting acetylcholinesterase; muscarinicd. inhibiting acetylcholinesterase; nicotinic
Answer: c
2. Sugammadex is a modified gamma cyclodextrin, which directly encapsulates amino- steroid non-depolarizing neuromuscular agents.
a. true b. false
Answer: true
3. Studies have shown that sugammadex can effectively reverse:a. shallow or deep neuromuscular block from non-depolarizing
neuromuscular agentsb. only when one or more twitches are present from non-depolarizing
neuromuscular agentsc. deep block from depolarizing neuromuscular agentsd. only when one or more twitches are present from depolarizing
neuromuscular agents
Answer: a
4. Studies have found there is no dose response relationship with sugammadex and time to adequate neuromuscular recovery.
a. trueb. false
Answer: false
5. Sugammadex is notably less effective following maintenance anesthesia with a volatile agent compared to maintenance anesthesia with propofol.
a. trueb. false
Answer: false
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6. Potential implications for sugammadex use following rocuronium include:a. potential difficult airwayb. short proceduresc. morbidly obesed. all of the abovee. none of the above
Answer: d
7. Sugammadex must be co-administered with:a. anticholinesterase b. muscarinic antagonistc. both A & Bd. none of the above
Answer: d
8. Research has found that rocuronium duration of action in patients with significant renal dysfunction is:
a. slightly increasedb. slightly decreasedc. no change
Answer: a
9. Studies have found that time to full neuromuscular recovery following sugammadex administration in patients with renal failure is not significantly different that patients with normal creatinine function.
a. trueb. false
Answer: true
10. The FDA denied approval of sugammadex during initial drug approval due to:a. morbidity and mortality during initial drug studiesb. increased incidence of perioperative myocardial ischemia/infarctionc. unknown potential hypersensitive reactions and coagulation events
Answer: c
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11. Metabolism and elimination of aminosteroid non-depolarizing agents occur via:a. hepatic and renal routesb. plasma esterasec. 1st pass effectd. diffusion
Answer: a
12. Neostigmine works by suppressing breakdown of acetylcholine and allowing it to accumulate and displace neuromuscular blocking molecules from binding sites on the nicotinic receptors.
a. trueb. false
Answer: true
13. Anticholinergic agents side effects include:a. tachycardiab. bradycardiac. sedationd. blurry visione. a, c, & df. b, c, & d
Answer: e
14. Sugammadex can adequately reverse:a. rocuroniumb. atracurium c. succinylcholine d. all of the above
Answer: a
15. Sugammadex has proven to effectively reverse neuromuscular blocking drugs that are eliminated via Hoffman elimination.
a. trueb. false
Answer: false
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16. Studies have shown that sugammadex is not effective in reversal of shallow neuromuscular blockade
a. trueb. false
Answer: false
17. Succinylcholine is metabolized by:a. acetylcholinesteraseb. pseudocholinesterasec. Hoffman eliminationd. rapid diffusion
Answer: b
18. When T4 is no longer present how many nicotinic receptors are occupied by neuromuscular blocking agent:
a. 0-25%b. 25-50% c. 50-75%d. 70-75%e. 75-100%
Answer: d
19. When assessing level of blockade with a train of four ratio, the ratio is determined by:a. comparing the height of T4 to T1b. comparing the height of T1 to T4c. comparing the height of T4 to T3d. comparing the height of T3 to T4
Answer: a
20. Sugammadex studies indicate a higher incidence of recurization with sugammadex compared to neostigmine
a. trueb. false
Answer: false
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