Use of neuromuscular blocking medications in critically ill patients

Author:Karen J Tietze, PharmDSection Editor:Polly E Parsons, MDDeputy

Editor:Geraldine Finlay, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer
review process is complete.

Literature review current through: Aug 2017. | This topic last

updated: Feb 16, 2017.

INTRODUCTION — Neuromuscular blocking agents (NMBAs) paralyze

skeletal muscles by blocking the transmission of nerve impulses at the
myoneural junction. NMBAs do not have sedative, amnestic, or analgesic
properties and do not prevent muscles from contracting if directly
stimulated. These drugs may be useful in the intensive care unit (ICU) to
improve patient-ventilator synchrony, enhance gas exchange, and diminish
the risk of barotrauma. They can also be employed to reduce muscle
oxygen consumption, facilitate short procedures, prevent unwanted
movements in patients with increased intracranial pressure, and facilitate
treatment of acute neurologic conditions such as tetanus (table 1) [1-4].

The mechanism of action, clinical use, and potential adverse effects of

NMBAs will be discussed here. Adequate sedation and analgesia, which
are essential prior to initiating therapy with NMBAs, are discussed
separately. (See "Sedative-analgesic medications in critically ill adults:
Selection, initiation, maintenance, and withdrawal" and "Pain control in the
critically ill adult patient".)

NEUROMUSCULAR TRANSMISSION AND BLOCKADE — The

neuromuscular junction consists of the nerve terminal, the synaptic cleft,
and the motor endplate. Acetylcholine (ACh) is released into the synaptic
cleft when nerve impulses reach the nerve terminal and diffuses across the
synaptic cleft to the motor endplate. Attachment of ACh to the nicotinic
(not muscarinic) receptors on skeletal muscle causes a conformational
change in the receptor that increases myocyte cell membrane permeability
to sodium, potassium, chloride, and calcium ions and releases calcium
from the sarcoplasmic reticulum, leading to transmission of an action
potential [5,6]. Depolarization terminates when ACh unbinds from the
receptor. ACh either diffuses back into the nerve terminal or is broken
down by acetylcholinesterase.

Neuromuscular blocking agents (NMBAs) are structurally related to ACh

and act by interfering with the binding of ACh to the motor endplate. They
are divided into depolarizing or nondepolarizing agents based upon their
mechanism of action [2,6-8].

●
Depolarizing NMBAs bind to cholinergic receptors on the motor endplate,
causing initial depolarization on the endplate membrane followed by
blockade of neuromuscular transmission. Because calcium is not
resequestered in the sarcoplasmic reticulum, muscles are refractory to
repeat depolarization until depolarizing NMBAs diffuse from the receptor to
the circulation and are hydrolyzed by plasma pseudocholinesterase [5].

●
Nondepolarizing NMBAs competitively inhibit the ACh receptor on the
motor endplate. Drug binding to the ACh receptor either prevents the
conformational change in the receptor or physically obstructs the ion
channels so that an endplate potential is not generated [5,9].

The ideal NMBA for use in intensive care produces an early, titratable
paralysis, has a moderately rapid offset of action (less than 15 minutes) to
allow for repeated neurologic assessment, no adverse hemodynamic or
other adverse physiologic effects, elimination independent of hepatic or
renal function, inactive metabolites, no propensity to accumulate, stability
over 24 hours to allow for continuous infusion, and modest cost (table 2)
[1].

DEPOLARIZING AGENTS — Succinylcholine is the only depolarizing

agent available in the United States and is utilized almost exclusively to
facilitate intubation or treat laryngospasm (table 2) [1,7]. Although
succinylcholine has a rapid onset (less than one minute) and brief duration
of action (seven to eight minutes), its use is limited because its actions
cannot be reversed by the administration of other medications [10].
Approximately 1 in 3200 patients is homozygous for a defective
pseudocholinesterase and may remain paralyzed for three to eight hours
after a single dose [11].

Significant adverse effects include hypertension, tachycardia, bradycardia,

ventricular arrhythmias, hyperkalemia, and, less commonly, increased
intracranial pressure or malignant hyperthermia. Malignant hyperthermia is
a rare complication, occurring in patients with mutations in the ryanodine
receptor, a homotetrameric calcium channel found in the sarcoplasmic
reticulum of skeletal muscle. The onset of hyperthermia is usually within
the first hour after administration but may be delayed. (See "Severe
nonexertional hyperthermia (classic heat stroke) in adults".)

Serum potassium concentrations increase by 0.5 to 1 meq/L due to an

efflux of potassium from muscle cells; as a result, the drug must be used
cautiously in patients with preexisting hyperkalemia [12]. Succinylcholine is
contraindicated after the acute phase of major thermal injury. Following
thermal injury, extrajunctional acetylcholine receptor expression increases
in proportion to the magnitude of the burn [13]. This results in an
exaggerated release of potassium after administration of succinylcholine;
profound hyperkalemia associated with cardiac arrest may occur [13].
Although the precise onset and duration of risk are not well described, the
risk increases over the first few days following the injury [13,14]. (See
"Causes and evaluation of hyperkalemia in adults".)

NONDEPOLARIZING AGENTS — A number of nondepolarizing

neuromuscular blocking agents are available. The onset of action, half-life,
and route of elimination are variable and drug-specific (table 3 and table 2).
The onset of action of these drugs ranges from 1 to 5 minutes, but all are
slower than succinylcholine. The half-life ranges from five minutes for
mivacurium to 180 minutes for tubocurarine. Older agents such as
tubocurarine are more commonly associated with cardiovascular side
effects and hypotension due to histamine release than are newer
nondepolarizing neuromuscular blocking agents (NMBAs) such as
cisatracurium, pipecuronium, rocuronium, and vecuronium (table
4) [6-8,10].

Nondepolarizing NMBAs are structurally divided into the aminosteroid

compounds (pancuronium, pipecuronium, rocuronium, vecuronium) and
the benzylisoquinolines (atracurium, cisatracurium, mivacurium,
tubocurarine). This classification is important when attempting to reverse
their clinical effects.

The major nondepolarizing NMBAs that are currently available are

discussed in this section.

Atracurium — Atracurium, a mixture of 10 stereoisomers, is a

benzylisoquinoline with an intermediate duration of action. Atracurium is
degraded by both pH- and temperature-dependent Hofmann elimination
(autolysis) and by ester hydrolysis; it therefore does not require a dosage
adjustment in patients with renal or hepatic failure [10,15]. However,
acidosis and severe hypothermia decrease the rate of drug metabolism
and should prompt dose reduction. Specific dosing recommendations are
not available, and the dose should be titrated according to neurologic
response.

The major side effect associated with atracurium is hypotension caused by

histamine release and sympathetic ganglionic blockade. In addition,
laudanosine, an inactive Hofmann elimination metabolite, causes seizures
in dogs at very high doses, but is unlikely to be of clinical significance in
humans [5,16]. As an example, after an infusion of atracurium at a rate of
0.3 to 0.96 mg/kg per hour for 38 days in a 23 year-old woman with
multiple medical problems, no electroencephalography (EEG)
abnormalities were apparent, and the plasma laudanosine level was only
37 percent of concentrations associated with epileptic EEG spiking in
dogs [17].

Cisatracurium — Cisatracurium is an isomer of atracurium with three

times its potency. Like atracurium, cisatracurium is degraded by pH- and
temperature-dependent Hofmann elimination to laudanosine, and acidosis
and severe hypothermia delay its metabolism. However, the greater
potency of cisatracurium allows the administration of smaller doses, which
results in less laudanosine production, less histamine release, and fewer
adverse cardiovascular side effects [18]. Its usefulness in the intensive
care unit (ICU) is limited somewhat by its relatively slow onset of action
(three to six minutes). Critically ill patients with severe sepsis may have a
delayed and reduced response to standard dosing regimens [19].  

Mivacurium — Mivacurium is a short-acting benzylisoquinoline with an

onset of action comparable to that of atracurium but with one-third its
duration of action because of rapid hydrolysis by plasma
pseudocholinesterase. However, patients with renal or hepatic
insufficiency may have depressed pseudocholinesterase activity leading to
delayed elimination [20,21].

Mivacurium is associated with few adverse cardiovascular side effects

following small (0.15 mg/kg) doses, but hypotension, caused by histamine
release, may occur following larger bolus injections [22]. Little information
is available about the use of mivacurium in the ICU, but it is unlikely to
have any advantages over atracurium.

Pancuronium — Pancuronium is a long-acting aminosteroid that is

metabolized to the active compound 3-hydroxypancuronium in the liver
and then eliminated equally in the urine and bile [5,23]. Adverse
cardiovascular effects associated with pancuronium include tachycardia,
hypertension, and increased cardiac output due to vagal blockade.

Pipecuronium — Pipecuronium is an aminosteroid with a longer duration

of action than pancuronium, and is primarily eliminated unchanged by the
kidney. It does not cause histamine release and is associated with minimal
adverse cardiovascular side effects [24]. Pipecuronium is no longer
available in the United States or Canada, but it may be available
elsewhere.

Rocuronium — Rocuronium is similar to but less potent than vecuronium.

It has a rapid onset and short-to-intermediate duration of action [8]. The
drug is eliminated primarily by the liver and is associated with few adverse
cardiovascular side effects.

Tubocurarine — Tubocurarine is a long-acting benzylisoquinoline that is

eliminated by both renal excretion and hepatic metabolism. It causes
dose- and rate-dependent histamine release and is associated with
profound drops in blood pressure following rapid infusions of large doses
[7,25]. Histamine-associated hypotension can be minimized by slow
injection, incremental dose increases, and coadministration of histamine-1
and histamine-2 receptor blockers [25,26]. Tubocurarine is no longer
available in the United States or Canada, but it may be available
elsewhere.

Vecuronium — Vecuronium is an aminosteroid compound with an

intermediate duration of action. It is hepatically metabolized to three active
metabolites, all of which are eliminated by the kidney [5,27,28]. Minimal
adverse cardiovascular side effects have been reported [6].

CLINICAL USE — Neuromuscular blocking agents (NMBAs) are not first

line agents for managing critically-ill patients in the intensive care unit
(ICU). NMBAs are generally reserved for those with severe, refractory, or
life-threatening hypoxemia (eg, acute respiratory distress syndrome
[ARDS]) who are not responsive to other sedatives or analgesics and
patients with overt shivering due to therapeutic hypothermia. These
indications are discussed in detail elsewhere. (See "Acute respiratory
distress syndrome: Supportive care and oxygenation in adults", section on
'Paralysis' and "Post-cardiac arrest management in adults", section on
'Targeted temperature management (TTM) and therapeutic hypothermia
(TH)'.)

The ICU staff must be trained in the administration and monitoring of

NMBAs. Appropriate airway control, mechanical ventilatory support, and
adequate sedation and analgesia are essential prior to the initiation of
NMBA therapy and during NMBA therapy. Appropriate equipment for
monitoring cardiorespiratory function and the capability of assessing the
degree of paralysis must be available [1,3,29]. The Society of Critical Care
Medicine (SCCM) and the Surviving Sepsis Campaign group have
developed clinical practice guidelines to help clinicians manage critically ill
adults requiring sustained neuromuscular blockade (algorithm 1) [30,31].

Selecting an agent — In a national survey of SCCM attending physicians,

vecuronium and pancuronium were the most commonly prescribed agents
for use >24 hours; vecuronium was the most commonly prescribed agent
overall [32]. In contrast, a national survey of Canadian intensivists found
that the most commonly used NMBA agents were pancuronium,
rocuronium, and vecuronium; all three agents were most commonly
administered by intermittent intravenous bolus [33].

A patient's renal and hepatic function, cardiovascular status, and age must
be considered when selecting an NMBA agent (table 2):

●
Normal hepatic and renal function – Pancuronium is the drug of choice for
patients with normal hepatic and renal function who require paralysis for
more than one hour [1].

●
Hepatic and/or renal insufficiency – Atracurium or cisatracurium is
preferred in patients with hepatic and/or renal insufficiency. Both drugs
undergo spontaneous degradation at physiologic pH and temperature (via
Hofmann elimination) and therefore are less dependent on renal or hepatic
function [1,10].

●
Cardiovascular disease – Vecuronium has the least adverse cardiovascular
effects and is the drug of choice for patients with cardiovascular disease
or hemodynamic instability. Pipecuronium and rocuronium are acceptable
alternatives [10].

●
Elderly patients – Drug selection is dictated by age-associated decreases
in renal and hepatic function. Decreased cardiac output prolongs drug
delivery and slows the onset of action of NMBAs [10].

Obesity may also affect dosing requirements, but there is a paucity of

evidence to guide clinicians. This is especially true for critically ill patients
in the ICU, since most data were derived from patients who received a
NMBA during surgery. Existing evidence includes the following:

●
Obesity does not appear to alter the pharmacokinetics or
pharmacodynamics of succinylcholine or rocuronium [34-36]. This
suggests that these agents can be dosed according to actual body weight
rather than predicted body weight [34].

●
In contrast, atracurium and vecuronium have a prolonged duration of
action if they are dosed according to actual body weight [37-39].

Given the variability among NMBAs and the overall paucity of dosing
information from critically ill obese patients, we suggest starting with low
doses and titrating the dose using train-of-four or tetanic stimulation as
described below (see 'Administration' below).

Finally, the degree of NMBA activity can be affected by a number of drugs

or medical conditions, which may make dosing adjustments necessary
(table 5 and table 6) [6,8,40]. Drugs or conditions that inhibit presynaptic
acetylcholine (Ach) release or depress postjunctional sensitivity enhance
the degree and duration of neuromuscular blockade [5,7]. Conversely,
phenytoin and carbamazepine significantly increase the requirement for
nondepolarizing NMBAs by an unknown mechanism.

Glycemic control, physical therapy strategies, and measures that avoid

unintended extubation in patients receiving NMBAs are similar to that in
other critically ill populations and are discussed separately. (See "Glycemic
control and intensive insulin therapy in critical illness" and "Post-intensive
care syndrome (PICS)", section on 'Prevention' and "Complications of the
endotracheal tube following initial placement: Prevention and management
in adult intensive care unit patients", section on 'Prevention of
complications in the ICU' and "Complications of the endotracheal tube
following initial placement: Prevention and management in adult intensive
care unit patients", section on 'Displacement and unplanned extubation'
and "Extubation management", section on 'Unplanned extubation'.)

Administration — NMBAs can be administered by continuous infusion or

intermittent intravenous injection, but should not be prescribed
intramuscularly due to erratic absorption (table 7) [4,8,40]. Generally
speaking, long-acting NMBAs are best given by intermittent injection,
while shorter-acting NMBAs are best given as a continuous intravenous
infusion [40]. Dose and frequency should be titrated to the desired clinical
effect. Ideal or adjusted body weight should be used for dosing obese
patients.

Complete (100 percent) neuromuscular blockade is not necessary for all

patients [8]. As an example, patients with respiratory failure require only 50
to 70 percent neuromuscular blockade [41]. The intended level of paralysis
depends on the clinical situation. When NMBAs are administered, it is
more appropriate to think in terms of controlling motor activity rather than
completely paralyzing the patient. Some patients can be maintained light
enough (eg, 50 percent blockade) that the patient maintains some modest
muscle tone and even motor activity, whereas other patients require nearly
complete paralysis and motor (eg, 80 to 90 percent) blockade [41].

Sensitivity to NMBAs varies and the metabolism of NMBAs cannot always

be predicted in the critically ill (eg, reduced doses may be sufficient in
patients with myasthenia gravis). Monitoring the degree of neuromuscular
blockade with regular clinical assessment (eg, triggering ventilator, degree
of shivering) and peripheral nerve stimulation (PNS) using train-of-four or
tetanic stimulation is recommended [4,30]. Train-of-four is the more
commonly used method and involves electrical stimulation of a peripheral
motor nerve with four sequential stimuli over a two second period and
observation of the responses of a muscle innervated by the stimulated
nerve. Patients treated with NMBAs have progressive reduction in the
magnitude of response to the four stimuli. Although the train-of-four goal
depends on the intended degree of paralysis, the NMBA dose is generally
titrated such that only two visible muscle twitches occur in response to
each train-of-four. Because electrical stimulation can directly trigger
myocyte contraction even in the presence of profound ACh receptor
blockade, nerve stimulation should be performed several centimeters from
the indicator muscle. The ulnar nerve is commonly stimulated at the wrist,
and response of the adductor pollicis is observed (figure 1).

The depth of blockade should be assessed with PNS every 2 to 3 hours

until the NMBA dose is stable, then every 8 to 12 hours [42]. If no or one
twitch is present, the dose should be reduced by 10 percent; if three or
four twitches are present, the dose should be increased by 10 percent.

The use of PNS monitoring in this setting is widely accepted, but data
supporting its use are limited [43,44]. Few prospective, controlled,
randomized studies assessing the utility of PNS have been published, and
conflicting results have been reported:

●
A trial randomly assigned 77 patients in a medical ICU to treatment with
vecuronium guided either by clinical assessment or PNS [45]. The PNS
group used significantly less drug and recovered neuromuscular function
and spontaneous ventilation approximately 55 percent faster than the
control group; patients with renal insufficiency appeared to derive the most
benefit for PNS-guided therapy.

●
In a trial of 36 patients receiving atracurium, the impact of monitoring the
train-of-four was compared to clinical assessment [46]. There was no
difference in the total amount of drug administered or the time to clinical
recovery.

●
A trial randomly assigned 30 patients receiving cisatracurium to be
monitored using the train-of-four or clinical assessment [47]. There was no
difference in the total amount of drug administered or the time to clinical
recovery.

The different outcomes of the three trials may be due, in part, to

differences in the drugs studied [48]. Train-of-four monitoring may
eventually prove more useful for monitoring patients who are receiving
renally or hepatically eliminated drugs, than for monitoring patients who
are receiving drugs that undergo Hofmann elimination. There is insufficient
evidence to warrant a change of current clinical practice.

Daily discontinuation of NMBA for a few hours is recommended to

potentially decrease the incidence of prolonged recovery secondary to
drug and metabolite accumulation and to potentially decrease the
incidence of the postparalytic paralytic quadriparesis, also known as
critical illness myopathy (CIM) and acute quadriplegic myopathy syndrome
(AQMS) [30].

The strongest risk factor for CIM is the use of intravenous glucocorticoids
in critically ill patients, although use of NMBAs is another potential risk
factor for CIM. The pathogenesis of CIM is probably related to steroid-
induced denervation. Major histopathologic findings include myopathy and
myosin loss. Serum CK elevation is seen in approximately one-half of
patients. CIM is usually reversible over weeks to months but it leads to
prolonged ICU stays and increased length of hospital stay overall.
Treatment is directed toward discontinuation or reduction of
glucocorticoids as soon as possible. (See "Neuromuscular weakness
related to critical illness", section on 'Critical illness myopathy'.)

Patients receiving NMBAs require meticulous care because the potential

for complications is great [49]. All paralyzed patients require the following
precautions:

●
Ensure adequate sedation and analgesia prior to paralyzing the patient

●
Supervise patients closely because interruption of the ventilator circuit can
be fatal

●
Since all NMBAs inhibit the cough reflex, suctioning of the endotracheal
tube to remove accumulated secretions should be performed as needed
based on the amount of secretions present

●
Artificial tears should be instilled every two to four hours and eyelids
should be taped shut to prevent corneal drying and ulceration

●
Patients require frequent turning and dry, wrinkle-free bedding in order to
prevent skin breakdown and decubitus ulcers

●
Prophylactic deep venous thrombosis therapy with either low dose
subcutaneous heparin or mechanical compression devices is required

●
The head of the bed should be elevated to reduce the risk of aspiration,
particularly during enteral feeding

●
Pupillary reflexes should be closely monitored to assess neurologic status
(but are unreliable if pancuronium is used because of its antimuscarinic
effects)

Discontinuation — Tapering the dose is not necessary when

neuromuscular blockade is discontinued. Sedation and analgesia
adequate for patient comfort must be maintained as the NMBA is
discontinued.

The action of nondepolarizing NMBAs can be reversed by administration

of an anticholinesterase drug such as neostigmine, 0.035 to 0.07 mg/kg
[7]. Acetylcholine-related side effects such as salivation, bradycardia, and
cardiac standstill are prevented by coadministration of atropine (15 mcg/
kg) or glycopyrrolate (7 mcg/kg) [4].

The action of the steroidal neuromuscular blocking medications

rocuronium and vecuronium can be reversed by administration of
sugammadex sodium [50,51]. Sugammadex is the first of a new class of
medications called selective relaxant binding drugs (SRBA) that has been
approved for use to reverse the effect of NMBAs used during surgery (eg,
2 to 4 mg/kg intravenously; 16 mg/kg if rapid reversal is required after
administration of a single dose of rocuronium) [52]. Its use in the critical
care setting is not well defined. Sugammadex, a cyclic oligosaccharide
carbohydrate, binds 1:1 with the neuromuscular blocking medication in the
blood; the complex is excreted unchanged by the kidneys. There are no
cost-effectiveness data and concerns remain regarding allergic reactions
and bradycardia.

ADVERSE EFFECTS — Anaphylaxis to neuromuscular blocking agents

(NMBAs) is extremely rare, and the drugs have no known effects outside of
muscles and autonomic ganglia. Nevertheless, NMBAs have the potential
for severe adverse effects such as hypotension and prolonged paralysis. In
addition, because NMBAs impair ocular protective mechanisms, patients
are at risk of corneal abrasions, infection, and scarring, thereby prompting
the recommendation for regular eyelid closure and the application of
lubricating eye drops or gel. (See 'Administration' above.)

Cardiovascular effects — Adverse cardiovascular side effects associated

with NMBAs are related to stimulation or blockade of the autonomic
nervous system and vasodilatation due to histamine release. The drugs
with the lowest risk of cardiovascular complications are cisatracurium,
pipecuronium, rocuronium, and vecuronium (table 4).

Prolonged paralysis — Prolonged paralysis following drug

discontinuation results from accumulation of drug or active metabolites, or
an acute myopathy [53]. It is a rare disorder related to prolonged use
(days) of paralytic agents, often in the setting of renal or hepatic
insufficiency. NMBAs that are dependent upon renal clearance –
pancuronium, pipecuronium, and tubocurarine – accumulate in patients
with renal insufficiency if they are not properly dose-adjusted to peripheral
nerve stimulation (PNS) response. Affected patients have flaccid areflexic
tetraplegia. This complication is discussed in greater detail elsewhere.
(See "Neuromuscular weakness related to critical illness", section on
'Prolonged neuromuscular junction blockade'.)

Neuromuscular dysfunction diagnosed in critical illness — A modest

association between the use of neuromuscular blocking drugs and
neuromuscular dysfunction acquired in critical illness, including ICU-
acquired weakness, critical illness polyneuropathy, and critical illness
myopathy, has been reported [54]. The risk of critical illness
polyneuropathy was greater in patients with severe sepsis or septic shock
or more severe illness [54]. These issues are discussed separately. (See
"Neuromuscular weakness related to critical illness".)

SAFETY — Medication errors continue to occur. Examples include

administration of the wrong medication due to look-alike packaging or
sound-alike names, as well as dosing errors due to use of the wrong
concentration of a drug. Given the potential for death if a neuromuscular
blocking agent (NMBA) is administered to a patient without appropriate
ventilatory support, the United States Pharmacopoeia Safe Medication
Use Expert Committee has issued recommendations [55]:

●
NMBA packaging and labeling should clearly differentiated NMBAs from
other medications

●
Special safeguards for storage, labeling, and the use of drugs should be
instituted

●
Health care professionals should be especially vigilant with these drugs

SUMMARY AND RECOMMENDATIONS

●
Neuromuscular blocking agents (NMBAs) paralyze skeletal muscles by
blocking the transmission of nerve impulses at the myoneural junction.
NMBAs do not have sedative, amnestic, or analgesic properties (table 2).
(See 'Introduction' above.)

●
Adequate sedation and analgesia are essential prior to initiating and during
therapy with NMBAs. (See 'Introduction' above.)

●
Depolarizing NMBAs cause initial depolarization of the muscle's
membrane, which renders the muscle refractory to repeat depolarization.
In contrast, nondepolarizing NMBAs competitively inhibit cholinergic
receptors on the muscle's membrane. (See 'Neuromuscular transmission
and blockade' above.)

●
Succinylcholine is the most common depolarizing NMBA. Its onset of
action is rapid (less than one minute) and its duration of effect is brief
(seven to eight minutes). Succinylcholine is generally used to facilitate
intubation or treat laryngospasm. (See 'Depolarizing agents' above.)

●
There are many nondepolarizing NMBAs, each with a different time to
onset and duration of effect. In general, the nondepolarizing NMBAs have
an onset of action of one to five minutes and a half-life ranging from 5 to
300 minutes. (See 'Nondepolarizing agents' above.)

For patients who require paralysis for more than one hour:

●
Pancuronium is appropriate for patients with normal hepatic and renal
function. Cisatracurium or atracurium is appropriate for patients with
hepatic or renal insufficiency. For patients who are hemodynamically
unstable or have cardiovascular disease, vecuronium, pipecuronium,
or rocuronium may be used. (See 'Clinical use' above.)

●
NMBAs are preferably administered by intermittent intravenous injection.
Continuous intravenous infusion is an acceptable alternative. (See
'Administration' above.)

●
The depth of neuromuscular blockade should be monitored by clinical
assessment and by peripheral nerve stimulation (PNS). Assess the PNS
every two to three hours until the NMBA dose is stable, then every 8to 12
hours. Although the depth of paralysis should be tailored to the clinical
situation, in most settings two twitches is an appropriate goal. Reduce the
dose approximately 10 percent if zero or one twitch is present. Increase
the dose by 10 percent if three or four twitches are present. (See
'Administration' above.)

●
When clinically feasible, stop the NMBA daily to reassess the need for
continued paralysis. This may reduce the incidence of prolonged recovery
secondary to drug and metabolite accumulation and may reduce the risk
of post paralytic quadriparesis. (See 'Administration' above.)

●
NMBAs do not need to be tapered (ie, they can be abruptly discontinued).
Nondepolarizing NMBAs can be reversed by an anticholinesterase agent
(eg, neostigmine) and by sugammadex sodium. (See 'Discontinuation'
above.)

●
Numerous adverse effects have been attributed to NMBAs, most
commonly cardiovascular effects and prolonged paralysis. Corneal
abrasions should be avoided by eyelid closure and ocular lubrication. (See
'Adverse effects' above.)

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