Neuromuscular Blocking Agents

Summary

Neuromuscular blocking agents (NMBAs) are used to facilitate endotracheal intubation and provide
skeletal muscle relaxation during surgery or mechanical ventilation.

NMBAs do not provide sedation, analgesia, or amnesia; administer only after unconsciousness has
been induced and maintain adequate amnesia and analgesia throughout paralysis.

NMBA selection depends on clinical application and patient factors; consider the onset and duration
of action, adverse effects, and metabolism/excretion of each agent.

Pharmacology
Neuromuscular blocking agents (NMBAs) cause skeletal muscle relaxation by blocking acetylcholine,
and therefore, the transmission of nerve impulses at the neuromuscular junction. Depolarizing NMBAs
bind to and activate cholinergic receptor sites, making the muscle fiber refractory to the action of
acetylcholine. Nondepolarizing NMBAs competitively antagonize cholinergic receptors. Nondepolarizing
NMBAs are divided into 2 broad structural classes: aminosteroidal and benzylisoquinolinium agents.
Differences in chemical structure reflect little but variance in drug elimination pathways.[52452][52486]
[65358][65369][65389]

Neuromuscular Blocking Agent General Pharmacology[65358][65369]

Metabolism/
Drug Mechanism Class
Elimination

plasma esterase/
Atracurium Nondepolarizing Benzylisoquinolinium
Hofmann elimination

plasma esterase/
Cisatracurium Nondepolarizing Benzylisoquinolinium
Hofmann elimination*

Mivacurium Nondepolarizing Benzylisoquinolinium plasma cholinesterase

Pancuronium Nondepolarizing Aminosteroidal renal > hepatic

Rocuronium Nondepolarizing Aminosteroidal renal < hepatic

Succinylcholine Depolarizing Acetylcholine-like plasma cholinesterase

Vecuronium Nondepolarizing Aminosteroidal renal <= hepatic

*Less than 20% of elimination occurs via renal and hepatic pathways combined

Onset and Duration of Action of Neuromuscular Blocking Agents[52452][52486][65358][65369][65389]

Drug Onset (minutes) Duration (minutes)

Succinylcholine 0.5 to 1.5 5 to 10

Short-acting
Mivacurium 2 to 3 10 to 20

Atracurium 3 to 5 20 to 35

Cisatracurium 2 to 5 20 to 60
Intermediate-acting
Rocuronium 1 to 2 20 to 35

Vecuronium 3 to 5 20 to 45

Long-acting Pancuronium 2 to 5 60 to 100

Pharmacodynamics of Neuromuscular Blocking Agents[42613][52452][65345] [65358][65369]

Ganglionic/Vagal
Histamine
Drug Muscarinic Receptor Effect Prolonged Blockade
Release Blockade

Atracurium low to minimal none minimal to none rare

Cisatracurium minimal to none none none rare

Mivacurium low to minimal none none rare

Pancuronium minimal to none moderate blockade yes yes

Rocuronium minimal to none minimal blockade at high doses no

Succinylcholine minimal stimulation none with reduced plasma cholinesterase activity

Vecuronium none none at high doses yes

Therapeutic Use
Therapeutic Use Table
Export to CSV (Excel)

Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium

Indications
Besylate Besylate Chloride Bromide Bromide Chloride Bromide

Renal
Impairment
Yes Yes Yes Yes
Dosing
Adjustment

Hepatic
Impairment
Yes Yes Yes
Dosing
Adjustment

endotracheal
Yes Yes Yes Yes Yes Yes Yes
intubation

neuromuscular
blockade
during Yes Yes Yes Yes Yes Yes
mechanical
ventilation

neuromuscular
blockade Yes Yes Yes Yes Yes Yes Yes
during surgery

rapid-
sequence Yes † Yes Yes Yes †
intubation

Yes – Labeled
Yes † – Off-label, Recommended
NR – Off-label, Not Recommended

Neuromuscular blocking agent (NMBA) selection depends on clinical application and patient
factors; consider the onset and duration of action, adverse effects, and metabolism/elimination of
each agent.

Succinylcholine is the NMBA of choice for rapid-sequence intubation (RSI) due to its rapid onset
and short duration; it can also be given intramuscularly in patients without venous access. Several
adverse effects (i.e., hyperkalemia, malignant hyperthermia, increased intraocular and intracranial
pressures) limit its use.[44868][52452][65345]

Aminosteroidal NMBAs depend on organ function for metabolism and excretion; they tend not to
cause histamine release, making them preferred NMBAs in patients with asthma.

Rocuronium and vecuronium are considered preferred NMBAs in patients with cardiac conditions or
hemodynamic instability due to their cardiovascular stability. Rocuronium is an attractive alternative
for RSI due to its relatively short onset.[44868][52441][52452][65345]

Pancuronium may cause significant tachycardia and hypertension. Due to its long duration,
intermittent doses can be considered as an alternative to continuous infusions of shorter-acting
 NMBAs in patients requiring sustained paralysis.[52443]

Benzylisoquinolinium NMBAs undergo organ-independent degradation; they lack vagolytic activity

but are more likely to cause histamine release.[52452]

Atracurium and cisatracurium are attractive for continuous infusion use in critically ill patients, as
their metabolism is largely unrelated to hepatic or renal function.[65358]

A short course (48 hours or less) of NMBA by continuous infusion is recommended for patients with
early acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 less than 150 mmHg.[61770]
[62859]

Comparative Efficacy

Succinylcholine is considered the neuromuscular blocking agent (NMBA) of choice for rapid-
sequence intubation (RSI) due to its rapid onset and shorter duration; however, adverse effects limit
its use. Rocuronium is an attractive alternative.[44868][52452][65345]

Both agents offer similar safety and efficacy for RSI when used in various patient populations.
[65441][65442][65443] When dosed at 0.9 to 1.2 mg/kg, rocuronium's onset of action is similar to
succinylcholine with a longer duration.[65442]

Neuromuscular Blocking Agent Comparative Efficacy Trials for Rapid-Sequence Intubation (RSI)

Citation Design/Regimen Results Conclusion

Marsch SC, et Randomized, controlled, single-blind trial comparing Incidence of Incidence and severity of oxygen
al. Crit Care succinylcholine 1 mg/kg IV (n = 208) vs. rocuronium oxygen desaturations, quality of intubation
2011;15:R199. 0.6 mg/kg IV (n = 208) for rapid-sequence intubation desaturation, conditions, and incidence of failed intubation
[65441] in critically ill adults. Patients were premedicated with defined as a attempts did not differ between
fentanyl 1 mcg/kg IV, and etomidate 0.2 mg/kg IV or decrease in succinylcholine and rocuronium in critically ill
propofol 1 mg/kg IV were used for induction. oxygen adults. The mean intubation sequence was
saturation of 14 seconds shorter after succinylcholine
5% or more: compared to rocuronium. Hemodynamic
effects of intubation were similar in both
Succinylcholine: groups.
37%

Rocuronium:
34%

(p = 0.67)

Incidence of
severe oxygen
desaturation,
resulting in a
saturation
value of 80%
or less:

Succinylcholine:
10%
 Rocuronium:
10%

(p = 1)

Duration of
intubation
sequence:

Succinylcholine:

81 +/- 38
seconds

Rocuronium:

95 +/- 48
seconds

(p = 0.002)

Incidence of
failed first
intubation
attempt:

Succinylcholine:
16%

Rocuronium:
18%

(p = 0.4)

Intubation
conditions
(maximal
score = 9):

Succinylcholine:

8.3 +/- 0.8

Rocuronium:

8.2 +/- 0.9

(p = 0.7)

Magorian T, et Randomized, controlled trial comparing rocuronium Mean onset of Onset of action for rocuronium 0.9 and 1.2
al. 0.6, 0.9, or 1.2 mg/kg IV, vecuronium 0.1 mg/kg IV, or action: mg/kg was similar to succinylcholine.
Anesthesiology succinylcholine 1 mg/kg IV (total n = 50) for rapid- Rocuronium's duration of action was
1993;79:913- sequence induction of anesthesia in adult patients Rocuronium 0.6 prolonged compared to succinylcholine at
who were ASA physical status 1 thru 3. Patients were mg/kg: these doses; duration of action with
918. [65442]
premedicated with midazolam 0.02 to 0.05 mg/kg IV, rocuronium 1.2 mg/kg was significantly
and incremental doses of thiopental 1 to 2 mg/kg IV 89 seconds longer compared to all other agents/doses.
were given before neuromuscular blockade. Recovery index was significantly shorter for
Rocuronium 0.9
mg/kg: succinylcholine but similar for all other
agents/doses.
75 seconds

Rocuronium 1.2
mg/kg:

55 seconds

Vecuronium 0.1
mg/kg:
144 seconds

Succinylcholine
1 mg/kg: 50
seconds

Mean duration
of action:

Rocuronium 0.6
mg/kg: 37
minutes

Rocuronium 0.9
mg/kg: 53
minutes

Rocuronium 1.2
mg/kg: 73
minutes

Vecuronium 0.1
mg/kg: 41
minutes

Succinylcholine
1 mg/kg: 9
minutes

Mean recovery
index:

Rocuronium 0.6
mg/kg: 14
minutes

Rocuronium 0.9
mg/kg: 22
minutes

Rocuronium 1.2
mg/kg: 24
minutes

Vecuronium 0.1
mg/kg: 20
minutes

Succinylcholine
1 mg/kg: 2
minutes
April MD, et al. International, multicenter, observational series Incidence of First-pass intubation success, glottic view,
Ann Emerg comparing succinylcholine (n = 2,275; mean dose: first-pass and incidence of adverse effects did not
Med 1.8 mg/kg IV) and rocuronium (n = 1,800; mean intubation differ between succinylcholine and
2018;72:645- dose: 1.2 mg/kg IV) for rapid-sequence intubation in success: rocuronium during emergency department
653. [65443] the emergency department in patients older than 14 intubation.
years. Sedation agents included etomidate, Succinylcholine
ketamine, and propofol. 87%

Rocuronium
87.5%

(risk difference
0.5%; 95% CI
-1.6% to 2.6%)

Cormack-
Lehane grade
1 or 2 view:

Succinylcholine:
88.5%

Rocuronium:
89%

Incidence of
adverse
events:

Succinylcholine:
14.7%

Rocuronium:
14.8%

Adverse Reactions / Side Effects

Top 20 Adverse Reactions / Side Effects Table
Export to CSV (Excel)

Adverse
Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium
Reaction /
Besylate Besylate Chloride Bromide Bromide Chloride Bromide
Side Effect

acute
quadriplegic
Reported Reported Reported Reported Reported Reported Reported
myopathy
syndrome

bronchospasm Reported 0.2 - 1.5% <1% Reported <1% Reported Reported

erythema 0.5 - 0.6% Reported <1% Reported Reported Reported Reported

flushing 1 - 29.2% 0.2% 16 - 25% Reported Reported Reported Reported

hypotension 0.6% 0.2% 0.3 - 4% Reported 0.1 - 2% Reported Reported

pruritus Reported Reported Reported Reported <1% Reported Reported

rash Reported 0.1% <1% Reported <1% Reported Reported

 Adverse
Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium
Reaction /
Besylate Besylate Chloride Bromide Bromide Chloride Bromide
Side Effect

sinus
Reported Reported <1% Reported <1.4% Reported Reported
tachycardia

urticaria Reported Reported <1% Reported Reported Reported Reported

wheezing 0.2 - 0.3% Reported <1% Reported <1% Reported Reported

bradycardia Reported 0.4% <1% Reported

hypertension Reported 0.1 - 2% Reported

injection site
Reported <1% <1%
reaction

dizziness <1%

edema <1%

hiccups <1%

muscle
<1%
cramps

nausea <1%

phlebitis <1%

vomiting <1%

Anaphylactoid reactions
Although rare, severe anaphylactic or anaphylactoid reactions to neuromuscular blocking agents
(NMBAs) have been reported; some cases have been fatal. Immediate availability of appropriate
emergency treatment for anaphylaxis is advised because of the potential life-threatening severity of a
reaction.[42039] [48672] NMBAs are the most common cause of IgE-mediated anaphylaxis in anesthesia,
with succinylcholine and rocuronium being the most frequent culprits.[65358] Cross-reactivity between
NMBAs, both depolarizing and nondepolarizing, has been reported.[42039] [48672]

Histamine-related reactions
Neuromuscular blocking agents (NMBAs) with histamine-releasing properties (e.g., atracurium,
mivacurium, succinylcholine) are more likely to cause bronchospasm, flushing, hypotension, and/or
tachycardia. Histamine release may be related to dose or administration rate.[42613] [52452] [65358]
[65389]

Cardiovascular reactions
Pancuronium, atracurium, and succinylcholine have the greatest potential among neuromuscular
blocking agents (NMBA) to cause adverse cardiovascular effects. Pancuronium causes tachycardia and
increased blood pressure as a result of vagal blockade and norepinephrine release from adrenergic
nerve endings. Atracurium causes significant histamine release which may result in hypotension and
tachycardia. Succinylcholine can cause vagal-mediated bradycardia, hypotension, and cardiac
arrhythmias; tachycardia and hypertension may occur due to sympathetic stimulation.[52452] [54407]
Pretreatment with atropine may prevent bradycardia associated with anticholinesterases.[42039] [65330]
[65345]

Seizures
Seizures have been reported in intensive care unit patients after long-term infusion of atracurium to
support mechanical ventilation. These patients usually had predisposing causes, such as head trauma,
cerebral edema, hypoxic encephalopathy, viral encephalitis, or uremia. Laudanosine, a major
biologically active metabolite of atracurium and cisatracurium without neuromuscular blocking activity,
produces cerebral excitatory effects (i.e., generalized muscle twitching and seizures) at higher doses
when administered to several species of animals; however, the relationship between CNS excitation and
laudanosine concentrations in humans has not been established.[42614] [48671]

Tachyphylaxis
Patients who receive neuromuscular blocking agents for a prolonged period may develop tachyphylaxis.
Prolonged blockade leads to proliferation of acetylcholine receptors at the neuromuscular junction
resulting in increased drug requirements. Switch patients who develop tachyphylaxis to 1 agent and still
require paralysis to another agent. Continuous monitoring of neuromuscular transmission with a
peripheral nerve stimulator is strongly recommended during continuous infusion or repeated dosing.
[52441][52503]

Acute quadriplegic myopathy syndrome

Acute quadriplegic myopathy syndrome (AQMS) has been associated with prolonged neuromuscular
blocking agent (NMBA) exposure and presents as acute paresis, myonecrosis with increased creatine
phosphokinase (CPK), and abnormal electromyography (EMG). Flaccid paralysis, decreased deep
tendon reflexes, and respiratory insufficiency are present after drug discontinuation. Prolonged
rehabilitation as well as chronic ventilatory support are often needed in patients with AQMS. Recovery
may take weeks to months. To reduce the risk of prolonged recovery and AQMS, periodic screening of
CPK during ongoing neuromuscular blockage may be helpful. Though periodic interruption of therapy is
often not feasible and there is no direct evidence showing that it reduces the incidence of AQMS, daily
'drug holidays' may be considered for patients who will tolerate an interruption in therapy.[52503] [52486]

Immobility complications
Prolonged paralysis is associated with pooling and stasis of blood in the veins, which increases the risk
of thrombosis. Skin breakdown, slowed gastrointestinal motility, peripheral muscle weakness, muscle
atrophy are other complications of immobility.[65358] Prophylactic interventions, including frequent
repositioning, physical therapy, and sequential compression devices are warranted in intensive care
patients receiving prolonged neuromuscular blockade.[52482] [52503]

Corneal ulcers
Paralysis results in impaired eyelid closure and loss of corneal reflex, placing the cornea at risk for
drying, scarring, ulceration, and infection.[65358] Prophylactic eye care is essential; use artificial tears or
ophthalmic ointment at regular intervals in critically ill patients receiving prolonged neuromuscular
blockade.[52482][52503]
Malignant hyperthermia
Malignant hyperthermia, an inherited disorder of muscle metabolism, often presents as prolonged
masseter spasm (jaw rigidity), which may progress to generalized rigidity, rhabdomyolysis, increased
oxygen demand, lactic acidosis, increased heart rate, profound fever, disseminated intravascular
coagulation (DIC), and cardiac arrhythmia. Malignant hyperthermia can be precipitated by
succinylcholine; consider patients receiving nondepolarizing neuromuscular blocking agents (NMBAs)
also to be at risk. If malignant hyperthermia is suspected, discontinue anesthesia immediately,
implement supportive care, and administer dantrolene.[52486][54418][54419]

Hyperkalemia
Succinylcholine-induced depolarization may cause sufficient potassium efflux to produce hyperkalemia.
[65369] In predisposed patients, a sudden, large increase in serum potassium may cause cardiac
dysrhythmias and cardiac arrest.[52452] There have been rare reports of acute rhabdomyolysis with
hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death after the administration of
succinylcholine to apparently healthy pediatric patients who were subsequently found to have
undiagnosed skeletal muscle myopathy, most frequently Duchenne's muscular dystrophy. This
syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes after the
administration of succinylcholine in healthy appearing pediatric patients (usually, but not exclusively,
males, and most frequently 8 years or younger). There have also been reports in adolescents.
Therefore, when a healthy appearing infant or child develops cardiac arrest soon after administration of
succinylcholine, not felt to be due to inadequate ventilation, oxygenation, or anesthetic overdose,
institute immediate treatment for hyperkalemia, including intravenous calcium, bicarbonate, glucose with
insulin, and hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures
are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts have resulted
in successful resuscitation in some reported cases.[42039]

Increased intracranial pressure

Succinylcholine may cause transient increased intracranial pressure immediately after administration
and during the fasciculation phase. Slight increases in pressure may persist after the onset of paralysis.
Induction of adequate anesthesia before succinylcholine administration may minimize the drug's effect
on intracranial pressure.[42039] [52486]

Drug Interactions

Antibiotics
Systemic administration of certain antibiotics, such as aminoglycosides, clindamycin, vancomycin,
tetracyclines, bacitracin, polymyxins, colistin, and sodium colistimethate, may enhance or prolong the
neuromuscular blocking action of neuromuscular blocking agents (NMBAs). If these or other newly
introduced antibiotics are used in conjunction with NMBAs, consider unexpected prolongation of
neuromuscular block a possibility. The use of peripheral nerve stimulator is strongly recommended to
evaluate the level of neuromuscular blockade, to assess the need for additional doses of the NMBA,
and to determine whether adjustments need to be made to the dose with subsequent administration.
[42031] [42614] [48672]

Anticonvulsants
Concomitant use of a nondepolarizing neuromuscular blocking agent (NMBA) in patients receiving
anticonvulsants, such as carbamazepine or phenytoin, may increase resistance to the neuromuscular
blockade action of nondepolarizing NMBAs, resulting in shorter durations of neuromuscular blockade
and higher infusion rate requirements. The use of peripheral nerve stimulator is strongly recommended
to evaluate the level of neuromuscular blockade, to assess the need for additional doses of NMBA, and
to determine whether adjustments need to be made to the dose with subsequent administration. While
the mechanism for development of resistance is not known, receptor up-regulation may be a
contributing factor.[42031] [42614]

Corticosteroids
An acute myopathy has been observed with the use of high doses of corticosteroids in patients
receiving concomitant long-term therapy with neuromuscular blockers. Limit the period of use of
neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs
outweigh the risks for acute myopathy. Clinical improvement or recovery after stopping therapy may
require weeks to years.[41961] [42031] [54278] [61750]

Inhalational anesthetics
Use of volatile inhalational anesthetics with neuromuscular blocking agents (NMBAs) will enhance
neuromuscular blockade. Potentiation is most prominent with use of enflurane and isoflurane. Reduction
of the initial dose or infusion rate of the NMBA may need to be considered.[41961] [42031] [42613] [42614]
[48671] [48672]

Local anesthetics
Local anesthetics have been shown to increase the duration of neuromuscular block and decrease
infusion requirements of neuromuscular blocking agents (NMBAs). The use of peripheral nerve
stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the
need for additional doses of NMBA, and to determine whether adjustments need to be made to the dose
with subsequent administration.[42031][42039][42614]

Magnesium salts
Magnesium may enhance or prolong the neuromuscular blocking action of neuromuscular blocking
agents. The use of peripheral nerve stimulator is strongly recommended to evaluate the level of
neuromuscular blockade, to assess the need for additional doses of NMBA, and to determine whether
adjustments need to be made to the dose with subsequent administration.[42031][42039][42614][48672]

Drugs that reduce plasma cholinesterase activity

Consider the possibility of prolonged neuromuscular block after administration of mivacurium or
succinylcholine in patients with reduced plasma cholinesterase activity. Plasma cholinesterase activity
may be diminished by chronic administration of oral contraceptives, corticosteroid therapy, certain
monoamine oxidase inhibitors, or by drugs that irreversibly inhibit plasma cholinesterase, such as
organophosphate insecticides and certain antineoplastic drugs.[42039] [42613]

Safety Issues
Safety Issues Table
Export to CSV (Excel)

Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium

Safety Issue
Besylate Besylate Chloride Bromide Bromide Chloride Bromide

REMS

MedGuide

benzyl alcohol
X
hypersensitivity

bromide
X X X
hypersensitivity

burns X

children BBW

hyperkalemia BBW

infants BBW

malignant
X
hyperthermia

myopathy X

neonates X BBW

neuromuscular
blocking agent X
hypersensitivity

premature
X
neonates

requires an
experienced BBW BBW
clinician

rhabdomyolysis BBW

trauma X

X – Contraindicated

X-BBW – Contraindicated and Black Box Warning

BBW – Black Box Warning, Not Contraindicated
Yes – REMS or MedGuide is available

Requires specialized care setting

Neuromuscular blocking agent administration requires an experienced clinician who is familiar with its
actions and the possible complications that may occur after its use as well as requires a specialized
care setting where facilities for intubation, artificial respiration, oxygen therapy, and reversal agents are
immediately available.[42031] [42614] [48672]

Awareness
Neuromuscular blocking agents (NMBAs) do not provide sedation or analgesia and, in general, should
be administered only after unconsciousness has been induced. Maintain adequate amnesia and
analgesia throughout paralysis to avoid patient distress. Use of a peripheral nerve stimulator will permit
the most advantageous use of NMBAs, minimize the possibility of overdosage or underdosage, and
assist in the evaluation of recovery. Monitor visual and tactile stimulation on muscle movement as well
as heart rate, blood pressure, and mechanical ventilator status during administration.[52441]

Burns
Succinylcholine is contraindicated in patients after the acute phase of major burn injury due to the risk of
hyperkalemia. In addition, patients with burns have a decreased sensitivity to nondepolarizing agents'
ability to produce neuromuscular blockade. Resistance to blockade usually develops in patients with
burns more than 10% total body surface area approximately 1 week after thermal injury. Increased
doses may be required in burn patients; alteration in drug effect may be seen for up to 1 year.[52478]
[52482]

Electrolyte and acid-base imbalance

Electrolyte imbalance can alter a patient's sensitivity to neuromuscular blocking agents (NMBAs).
Hypercalcemia can decrease sensitivity to NMBAs, while most other electrolyte disturbances increase
sensitivity (e.g., hypokalemia, hypocalcemia, hypermagnesemia). Use NMBAs cautiously in patients
with conditions that may lead to electrolyte imbalances, such as adrenal insufficiency. Severe acid/base
imbalance may alter a patient's sensitivity to NMBAs: metabolic alkalosis, metabolic acidosis, and
respiratory acidosis may enhance neuromuscular blockade and/or prolong recovery time, while
respiratory alkalosis reduces the potency of the drug.[42031] [48672] [52846] Use succinylcholine with
caution in patients with electrolyte abnormalities because of the potential for developing severe
hyperkalemia.[42039] [52486] Do not use succinylcholine in any patient with a serum potassium of more
than 5.5 mEq/L.[54427]

Neuromuscular disease
Use neuromuscular blocking agents with caution in patients with neuromuscular disease (e.g.,
myasthenia gravis, myasthenic syndrome [Eaton Lambert syndrome]); prolonged or exaggerated
neuromuscular blockade may occur after neuromuscular blocking agent use.[48672] [52486] [53645]
Because myasthenia gravis involves destruction of acetylcholine receptors instead of receptor
upregulation, as seen in other neuromuscular diseases, these patients tend to be less sensitive to the
effects of succinylcholine compared to nondepolarizing agents (e.g., rocuronium, vecuronium).[53645]
[54397] Additionally, patients with weak muscle tone are at an increased risk for airway and ventilation
complications. Monitor patients carefully until recovery is fully complete.[48672]

Obesity
Obese patients are at an increased risk for airway and ventilation complications. [48672] Use ideal body
weight or adjusted body weight for dosing in obese and morbidly obese adult patients (body mass index
30 kg/m2 or more).[62859] Guidelines for sustained neuromuscular blockade in critically ill children
recommend calculating the dose according to IBW.[52443]

Pseudocholinesterase deficiency
Consider the possibility of prolonged neuromuscular block after administration of mivacurium or
succinylcholine in patients with reduced plasma cholinesterase activity (pseudocholinesterase
deficiency). Plasma cholinesterase activity may be diminished in the presence of genetic abnormalities
of plasma cholinesterase (e.g., patients heterozygous or homozygous for atypical plasma
cholinesterase gene), liver or kidney disease, malignant tumors, infection, burns, anemia,
decompensated heart disease, peptic ulcer disease, or myxedema. Plasma cholinesterase activity may
also be diminished by chronic administration of oral contraceptives, corticosteroid therapy, or certain
monoamine oxidase inhibitors and by cholinesterase inhibitor toxicity due to irreversible inhibitors of
plasma cholinesterase (e.g., organophosphate insecticides, echothiophate, and certain antineoplastic
drugs). Use mivacurium with caution, if at all, in patients known or suspected of being homozygous for
the atypical plasma cholinesterase gene; initial doses more than 0.03 mg/kg are not recommended in
homozygous patients. Mivacurium infusions are not recommended in homozygous patients. Mivacurium
has been used safely in patients heterozygous for the atypical plasma cholinesterase gene and in
genotypically normal patients with reduced plasma cholinesterase activity. After an initial dose of
mivacurium 0.15 mg/kg, the clinically effective duration of block in heterozygous patients may be
approximately 10 minutes longer than in patients with normal genotype and normal plasma
cholinesterase activity. Lower infusion rates of mivacurium are recommended in these patients.[42039]
[42613]

Pediatric patients
Based on physiologic differences, neonates and infants tend to be more sensitive to paralysis with
neuromuscular blocking agents, while children tend to require larger doses than those of infants or
adults.[52501] [52452] Acute rhabdomyolysis, hyperkalemia, cardiac dysrhythmia, and fatal cardiac arrest
has been associated with succinylcholine use in pediatric patients with undiagnosed myopathies.
Because it is difficult to assess which patients are at risk, limit the use of succinylcholine in pediatric
patients for emergency intubation or when immediate securing of the airway is necessary (e.g.,
laryngospasm, difficult airway, full stomach) or for intramuscular use when a suitable vein is
inaccessible.[42039]

Hepatic impairment
Hepatic impairment may enhance or prolong neuromuscular blockade associated with aminosteroidal
neuromuscular blocking agents due to prolonged half-life and reduced clearance.[42031] [48672] [65345]
Although organ-independent elimination is the primary pathway for cisatracurium elimination, the liver
plays a minor role in metabolite elimination. Metabolite (e.g., laudanosine) half-life is prolonged and
concentrations may be higher after long-term cisatracurium administration in patients with hepatic
dysfunction.[42614]

Renal impairment
Substantial variability can be seen in the duration of neuromuscular blockade associated with
aminosteroidal neuromuscular blocking agents in patients with renal impairment.[42031] [48672] [65345]
Although organ-independent elimination is the primary pathway for cisatracurium elimination, the
kidneys play a minor role in metabolite elimination. Metabolite (e.g., laudanosine) half-life is prolonged
and concentrations may be higher after long-term cisatracurium administration in patients with renal
dysfunction.[42614]

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