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NON-DEPOLARISING AGENTS e.g.

atracurium, mivacurium, pancuronium,


rocuronium, vecuronium

These agents are competitive anatagonists at ACh receptors - 75% must be


blocked before there is no longer muscle contraction
Highly ionised at body pH with two quaternary ammonium groups
Poorly lipid soluble and poorly protein bound
Rapid redistribution from blood --> ECF
Used for prolonged paralysis when rapid intubation is not required
Reversible by increasing ACh with anticholinisterases

DEPOLARISING AGENTS e.g. suxamethonium

Stimulation of ACh receptor causes depolarisation. Mimics action of ACh at ACh


receptors without rapid hydrolysis by acetylcholinesterase
Peristance of the ligand prevents repolarisation and is therefore refractory to
further stimulation
Reversal of the block can occur by diffusion of the drug away from the junction
or from competitive agonist ACh (Increased by anticholinesterases)
Rapid onset of muscle fasciculation before blockade
May --> muscle pains
Suxamethonium used for paralysis of rapid onset and short duration e.g. to
allow tracheal intubation

Dr. Ni Putu Wardani Residen Anestesiologi Reanimasi Om Awighnam Astu Namo Siddham
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Table. Depolarizing and Nondepolarizing Muscle Relaxants.


Depolarizing

Nondepolarizing

Short-acting

Short-acting

Succinylcholine

Mivacurium
Intermediate-acting
Atracurium
Cisatracurium
Vecuronium
Rocuronium
Long-acting
Doxacurium
Pancuronium
Pipecuronium

Table. A Summary of the Pharmacology of Nondepolarizing Muscle


Relaxants
Relaxant

Metaboli Primary
sm
Excretion

Onse Duratio Histamine


t2
n3
Release4

Vagal
Blockade5

Atracurium B

+++

Insignificant

++

++

Cisatracuri
um

+++

Insignificant

++

++

Mivacurium B

+++

Insignificant

++

Doxacuriu
m

Insignifica Renal
nt

+++

Pancuroniu S
m

Renal

++

+++

++

Pipecuroniu S
m

Renal

++

+++

Vecuronium S

Biliary

++

++

Rocuronium S

Insignifica Biliary
nt

+++ ++

1.
2.
3.
4.
5.

Chemical
Structure1

B, benzylisoquinolone; S, steroidal.
Onset: +, slow; ++, moderately rapid; +++, rapid.
3
Duration: +, short; ++, intermediate; +++, long.
4
Histamine release: 0, no effect; +, slight effect; ++, moderate effect; +++, marked effect.
5
Vagal blockade: 0, no effect; +, slight effect; ++, moderate effect.
2

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Table. Clinical Characteristics of Nondepolarizing Muscle Relaxants.


Drug

ED95 for
Adductor
Pollicis
During N2/O2
Anesthesia
(mg/kg)

Intubatio Onset of
n Dose
Action for
(mg/kg)
Intubating
Dose (min)

Duration
of
Intubating
Dose (min)

Maintenance
Dosing by
Boluses
(mg/kg)

Maintenance
Dosing by
Infusion
(g/kg/min)

Succinylcholi 0.5
ne

1.0

0.5

510

0.15

215 mg/min

Rocuronium

0.3

0.8

1.5

3575

0.15

912

Mivacurium

0.08

0.2

2.53.0

1520

0.05

415

Atracurium

0.2

0.5

2.53.0

3045

0.1

512

Cisatracuriu
m

0.05

0.2

2.03.0

4075

0.02

12

Vecuronium

0.05

0.12

2.03.0

4590

0.01

12

Pancuronium 0.07

0.12

2.03.0

60120

0.01

Pipecuroniu
m

0.05

0.1

2.03.0

80120

0.01

Doxacurium

0.025

0.07

4.05.0

90150

0.05

Characteristics of Neuromuscular Blockade


Depolarizing (Phase I) Block
Muscle fasciculation preceding the onset of neuromuscular blockade
Absence of posttetanic potentiation
Lack of fade to frequent stimulation (e.g., tetanus, train of four, or double burst)
Block antagonized by nondepolarizing drugs
Block potentiated by acetylcholinesterase inhibitors
Nondepolarizing and Phase II Block
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Absence of muscle fasciculation


Presence of posttetanic potentiation
Fade with frequent stimulation
Possible synergism between various groups of nondepolarizing relaxants
Phase II block and nondepolarizing block potentiate each other
Block may be reversed by acetylcholinesterase inhibitors
Criteria of Adequate Recovery

Criteria used depend on whether the patient is awake or somnolent.


Patient Is Awake

Opens eyes widely to command and denies diplopia


Sustains tongue protrusion
Swallows effectively
Sustains a head lift for 5 seconds
Sustains a firm hand grip
Has an effective cough
Has a vital capacity of at least 15 mL/kg
Can generate an inspiratory force of at least 30 cm H2O

Patient Is
Somnolent

Can generate an inspiratory force of at least 30 cm H2O


Responds to nerve stimulator appropriately, including
sustained tetanic response to 50 Hz for 5 seconds
TOF or DBS stimulus yields ratio >0.7 or no discernible
fade of fully abducted thumb

* DBS, double-burst stimulation; TOF, train of four.

ANESTHESIA SECRET
1. Describe the anatomy of the neuromuscular junction (NMJ)
A motor nerve branches near its terminus to contact many muscle cells, losing myelin
to branch further and come into closer contact with the junctional area of the muscle
surface. Within the most distal aspect of the motor neuron, vesicles containing the
neurotransmitter acetylcholine (ACh) can be found. The terminal neuron and muscle
surface are loosely approximated with protein filaments, and this intervening space is
known as the junctional cleft. Also contained within the cleft is extracellular fluid and
acetylcholinesterase, the enzyme responsible for metabolizing ACh. The postjunctional
motor membrane is highly specialized and invaginated and the shoulders of these
folds are rich in ACh receptor

2. What is the structure of the ACh receptor?


The ACh receptor is contained within the motor cell membrane and consists of five
glycoprotein subunits: two alpha and one each of beta, delta, and epsilon. These are
arranged in a cylindrical fashion; the center of the cylinder is an ion channel. ACh
binds to the alpha subunits.
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3. In regards to neuromuscular transmission, list all locations for


ACh Receptors
ACh receptors are found in several areas:
1. About 5 million ACh receptors per NMJ are located on the postjunctional motor
membrane.
2. Prejunctional receptors are present and influence the release of ACh. The
prejunctional and postjunctional receptors have different affinities for ACh.
3. Extrajunctional receptors are located throughout the skeletal muscle in
relatively low numbers owing to suppression of their synthesis by normal neural
activity. In cases of traumatized skeletal muscle or denervation injuries, these
receptors proliferate.

4. Review the steps involved in normal neuromuscular


transmission
1. A nerve action potential is transmitted and the nerve terminal is depolarized.
2. ACh is released from storage vesicles at the nerve terminal. Enough ACh is
released to bind 500,000 receptors.
3. ACh molecules bind to the alpha subunits of the ACh receptor on the
postjunctional membrane, generating a conformational change and opening
receptor channels. Receptors do not open unless both alpha receptors are
occupied by ACh (a basis for the competitive antagonism of nondepolarizing
relaxants).
4. Sodium and calcium flows through the open receptor channel generating an
end-plate potential.
5. When between 5% and 20% of the receptor channels are open and a threshold
potential is reached, a muscle action potential (MAP) is generated.
6. Propagation of the MAP along the muscle membrane leads to muscle
contraction.
7. The rapid hydrolysis of acetylcholine by acetylcholinesterase (true
cholinesterase) within the synaptic cleft and return of normal ionic gradients
return the neuromuscular junction to a nondepolarized, resting state, and the
ACh receptors are closed.
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5. What are the benefits and risks of using muscle relaxants?


By interfering with normal neuromuscular transmission, these drugs paralyze skeletal
muscle and can be used to facilitate endotracheal intubation, assist with mechanical
ventilation, and optimize surgical conditions. Occasionally, they may be used to
reduce the metabolic demands of breathing and to facilitate the treatment of raised
intracranial pressure. Because they paralyze all respiratory muscles, they are
dangerous drugs to use in the unintubated patient unless the caregiver is trained in
airway management.

6. How are muscle relaxants classified?

Depolarizing relaxants: Succinylcholine (SCH) is two molecules of ACh bound


together, is an agonist at the NMJ, and is the only depolarizing relaxant available
clinically. As such, SCH binds to the alpha subunits of the ACh receptor. After
binding, SCH can open the ion channel and depolarize the end plate. Though
SCH, like ACh, binds only briefly to the receptor, it is not hydrolyzed in the
synaptic cleft by acetylcholinesterase. In fact, SCH molecules may unbind and
rebind receptors repeatedly. SCH must diffuse away and be broken down in the
plasma by enzymes called plasma- or pseudocholinesterase, and time for
clearance from the body is an accurate measure of its duration of effect.

Nondepolarizing relaxants: These drugs are competitive antagonists to ACh


at the postsynaptic membrane. They need only bind to one of the two alpha
subunits to prevent opening of the ionic pore.

7. What are the indications for using SCH?


SCH provides the most rapid onset and termination of effect of any NMB currently
available. Its onset is 60-90 seconds and duration of effect only 5-10 minutes. When
the patient has a full stomach and is at risk for pulmonary aspiration of gastric
contents, rapid paralysis and airway control are priorities, and SCH is often the drug
indicated. (Rocuronium when given in large doses also has a succinylcholine-like onset
of action, though a prolonged duration of effect would contraindicate its use in
patients likely to be difficult to ventilate or intubate.) Patients at risk for full stomachs
include those with diabetes mellitus, hiatal hernia, obesity, pregnancy, severe pain,
bowel obstructions, and trauma.
8. If SCH works so rapidly and predictably, why not use it all the time?
Succinylcholine has numerous side effects:

SCH stimulates both nicotinic and muscarinic cholinergic receptors. Stimulation


of muscarinic receptors within the sinus node results in numerous

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bradyarrhythmias, including sinus bradycardia, junctional rhythms, ventricular


escape and asystole.

SCH is a trigger for malignant hyperthermia.

Prolonged exposure of the receptors to SCH results in persistent open receptor


channel and ionic fluxes through the ion pore, known as phase II or
desensitization blockade. Normal depolarization/repolarization is not possible
until SCH is metabolized.

In patients ambulatory soon after surgery, random generalized muscle


contractions (fasciculations) have been associated with painful myalgias.
Whether pretreating with a subparalyzing dose of a nondepolarizing relaxant
prior to SCH is effective in reducing myalgias continues to be a matter of
debate.

SCH increases intracranial pressure (ICP). The etiology is not completely


understood but it is known that a subparalyzing dose of a nondepolarizing
relaxant prior to SCH administration reduces the increase in ICP, so perhaps
fasciculations are the cause of the increase in ICP.

In the presence of immature extrajunctional receptors, administration of SCH


may result in severe hyperkalemia and malignant ventricular arrhythmias.
Extrajunctional receptors are normally suppressed by activity. Any condition that
decreases motor-nerve activity results in a proliferation of these receptors.
Examples include spinal cord and other denervation injuries, upper and lower
motor neuron disease, closed head injuries, burns, neuromuscular diseases, and
even prolonged immobility.

SCH increases intraocular pressure (IOP). There is a theoretical risk for the use
of SCH in patients with open eye injury, that being extrusion of extraocular
contents. However, the increases in IOP are modest and from a clinical
perspective, extrusion of ocular contents has not been observed. Certainly if a
nondepolarizing agent is administered instead of SCH, and the patient is
intubated prior to optimal intubating conditions, coughing on the endotracheal
tube (called "bucking") increases IOP significantly and puts the patient at risk for
extruding ocular contents.

9. Differentiate between qualitative and quantitative deficiencies


in pseudocholinesterase
Pseudocholinesterase is produced in the liver and circulates in the plasma.
Quantitative deficiencies of pseudocholinesterase are observed in liver disease,
pregnancy, malignancies, malnutrition, collagen vascular disease, and
hypothyroidism; they slightly prolong the duration of blockade with SCH.
There may also be qualitative deficiencies in pseudocholinesterase; that is, the
activity of the enzyme is impaired. These are genetic diseases and as such can be
present in heterozygotic or homozygotic forms. The most common form is called
dibucaine-resistant cholinesterase deficiency and refers to the laboratory test that
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characterizes it. When added to the serum under study, dibucaine inhibits normal
plasma cholinesterase by 80%, while the atypical plasma cholinesterase is inhibited
by only 20%. Hence, a patient with normal pseudocholinesterase is assigned a
dibucaine number of 80. If a patient has a dibucaine number of 40-60, then that
patient is heterozygous for this atypical pseudocholinesterase and will have a
moderately prolonged and usually clinically insignificant block with SCH. If a patient
has a dibucaine number of 20, the patient is homozygous for atypical plasma
cholinesterase and will have an extremely prolonged block with SCH.

10. Review the properties of nondepolarizing muscle relaxants


Nondepolarizing relaxants are competitive antagonists at the NMJ and are classified by
their duration of action (short-, intermediate-, and long-acting).

Table . PROPERTIES OF NONDEPOLARIZING MUSCLE RELAXANTS


Relaxant

Short-acting
Mivacurium
Rocuronium
Intermediate-acting
Rocuronium
Vecuronium
Atracurium
Cisatracurium
Long-acting
Pancuronium
Pipecuronium
Doxacurium

ED95*
(mg/kg
)

Intubating Dose
(mg/kg)

Onset after Intubating


Dose (minutes)

Duration
(minutes)

0.08
0.3

0.2
0.6

1-1.5
2-3

15-20
30

0.3
0.05
0.23
0.05

1.2
0.15-0.2
0.75
0.2

1.0
1.5
1-1.5
2

60
60
45-60
60-90

0.07
0.05
0.025

0.08-0.12
0.07-0.85
0.05-0.08

4-5
3-5
3-5

90
80-90
90-120

*ED95 = dose expected to reduce single twitch height by 95%.

Duration measured as return of twitch to 25% of control.

Rocuronium, when administered in a dose of 1.2 mg/kg, has an onset similar


to succinylcholine, though the duration is significantly longer.

11. Review the metabolism of nondepolarizing NMBs

Aminosteroid relaxants (e.g., pancuronium, vecuronium, pipecuronium, and


rocuronium) are diacetylated in the liver, and their action may be prolonged in
the presence of hepatic dysfunction. Vecuronium and rocuronium also have
significant biliary excretion, and their action may be prolonged with extrahepatic
biliary obstruction.

Relaxants with significant renal excretion include tubocurarine,


metocurine, doxacurium, pancuronium, and pipecuronium.

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Atracurium is unique in that it undergoes spontaneous breakdown at


physiologic temperatures and pH (Hoffmann elimination) as well as ester
hydrolysis, and thus it is ideal for use in patients with compromised hepatic or
renal function.

Mivacurium, like SCH, is metabolized by pseudocholinesterase.

12. Describe common side effects of nondepolarizing NMBs


Histamine release is most significant with d-tubocurarine but is also noted with
mivacurium, atracurium, and doxacurium. The amount of histamine released is
frequently dose related. Cisatracurium does not seem to cause significant histamine
release. Tachycardia is usually a side effect of pancuronium due to ganglionic
stimulation and vagolysis.
13. Review medications that potentiate the actions of muscle
relaxants

Volatile anesthetics potentiate relaxants for a number of reasons, including


central nervous system (CNS) depression, increasing blood flow (and relaxant
molecules) to muscle, and desensitization of the postjunctional membrane.

Local anesthetics affect the prejunctional, postjunctional, and motor


membranes, depressing normal functions at all these sites.

Calcium channel and -adrenergic blockers impair ion transport but the clinical
significance at the NMJ is probably not important.

Antibiotics, and most notably aminoglycosides, appear to have negative


prejunctional and postjunctional effects. Penicillin and cephalosporins do not
affect relaxant activity.

Magnesium inhibits the release as well as the depolarizing effect of ACh and
decreases muscle fiber excitability. Lithium also potentiates neuromuscular
blockade.

Long-term use of steroids results in a myopathy and also has some affect on the
NMJ, particularly when muscle relaxants have been used for a prolonged period.

Dantrolene depresses skeletal muscle directly and impairs excitationcontraction.

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14. What clinical conditions potentiate the actions of


neuromuscular blockers?
Respiratory acidosis, metabolic alkalosis, hypothermia, hypokalemia, hypercalcemia,
and hypermagnesemia potentiate blockade. Hepatic or renal dysfunction also
increases the duration of action of relaxants.

15. Discuss important characteristics of a nerve stimulator


A nerve stimulator should be capable of delivering single-twitch stimulation at 0.1 Hz
(1 stimulus every 10 seconds), train of four (TOF) at 2 Hz (2 per second), and tetanic
stimulation at 50 Hz (50 per second). The black electrode of the stimulator is
negatively charged and the red electrode is positively charged. The black electrode
depolarizes the membrane while the red electrode hyperpolarizes the membrane.
Although stimulation is possible however the electrodes are placed, maximal twitch
height occurs when the negative electrode is placed in closest proximity to the nerve.

16. List the different patterns of stimulation

Single stimulus

TOF stimulation

Tetanic stimulation

Posttetanic facilitation and posttetanic count

Double-burst stimulation

17. Which is the simplest mode of stimulation?


Single stimulus is the simplest mode of stimulation. It consists of the delivery of single
impulses separated by at least 10 seconds but is of limited clinical utility.
18. Which mode is most commonly used to assess degree of
blockade? How is it done?
TOF stimulation is the most common modality used to assess degree of blockade. Four
stimuli are delivered at a frequency of 2 Hz (2 per second), and the ratio of the
amplitude of the fourth to the first response in a train (T4:T1 ratio) estimates the
degree of block. The four twitches of the TOF disappear in reverse order as the degree
of blockade deepens. The fourth twitch of the TOF disappears when 75-80% of the
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receptors are occupied, the third twitch disappears at 85% occupancy, the second
twitch disappears at 85-90% occupancy, and the first twitch disappears at 90-95%
occupancy. However, there is accumulating evidence that visual or tactile evaluation
of the TOF response is inadequate for evaluating neuromuscular function because it
has been demonstrated repeatedly that even with experienced practitioners,
subjective TOF estimations correlate poorly with true TOF fade. There has recently
been a call for more objective measures of return of motor function, such as
accelomyography, strain-gauge monitoring, and electromyography.

19. What is tetanic stimulation?


Tetanic stimulation consists of repetitive, high-frequency stimulation at frequencies of
50 Hz or greater. Loss of contraction during tetanic stimulation, known as tetanic fade,
is a sensitive indicator of residual neuromuscular blockade. Tetanus stimulates the
release of ACh from the prejunctional membrane, decreasing the validity of further
nerve stimulation for upward of 30 minutes, leading to overestimating the return of
neuromuscular function. A tetanic stimulus is painful.
KEY POINTS: MUSCLE RELAXANTS
1. Metabolism of relaxants is more important that
pharmacological reversal for termination of relaxant effect.
2. Train-of four assessment is highly subjective and has been
repeatedly demonstrated to underestimate residual
neuromuscular blockade.
3. It may be a best practice to administer reversal agents to all
patients receiving nondepolarizing relaxants.
4. Leave clinically weak patients intubated and support
respirations until the patient can demonstrate return of
strength.

20. Explain posttetanic facilitation and posttetanic count


This mode of stimulation is useful during periods of intense neuromuscular blockade
(when there is no response to TOF stimulation) and extends our range of monitoring.
It provides an indication as to when recovery of a single twitch is anticipated and,
hence, when reversal of neuromuscular blockade is possible. An application of a 50-Hz
stimulus for 5 seconds is followed in 3 seconds by repetitive single twitches at 1 Hz.
The number of twitches observed is inversely related to the degree of blockade.

21. What is double-burst (DB) stimulation?

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DB stimulation appears to be more sensitive than TOF stimulation for detecting small
degrees of residual neuromuscular blockade. DB involves the application of an initial
burst of three 0.2-millisecond impulses at 50 Hz followed by an identical stimulation in
750 milliseconds. The magnitude of the responses to double burst is approximately
three times greater than that of TOF stimulation, thus making it easier to assess
degree of fade present.

22. Which nerves can be chosen for stimulation?


Any easily accessible nerve may be used, but the most common nerve stimulated is
the ulnar nerve. Contraction of the adductor pollicis muscle of the thumb is observed.
The ophthalmic branch of the facial nerve may also be stimulated, monitoring the
contraction of the orbicularis oculi muscle. Stimulating the peroneal nerve near the
fibular head results in dorsiflexion of the ankle. Stimulating the posterior tibial nerve
and ankle results in plantar flexion of the big toe.

23. What are the characteristic responses to the various patterns


of stimulation produced by nondepolarizing agents?

Repetitive stimulation (TOF or tetanus) is associated with fade in the muscle


response.

Following a tetanic stimulus, response to subsequent stimulations is increased


(posttetanic facilitation). This may be due to increased ACh release or increased
sensitivity at the end plate).

24. Summarize the characteristic responses to the various


patterns of stimulation produced by depolarizing relaxants
(succinylcholine)
The single-twitch, TOF, and tetanus amplitudes are uniformly decreased at any level
of blockade. There is lack of fade in response to TOF and tetanus and lack of
posttetanic facilitation. A desensitization or phase II blockade may develop with
prolonged exposure to SCH. Phase II blockade has the same twitch characteristics as
nondepolarizing blockade
25. For surgical purposes, based on nerve stimulation, what is
adequate muscular relaxation?
Adequate relaxation is generally present when one to two twitches of the TOF
response are present, correlating with 80% depression of single-twitch height.
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However, volatile anesthetics, other medications, and the patient's underlying health
also affect strength and, under these conditions, lighter levels of blockade may be
satisfactory.
26. Discuss the appropriate time to reverse neuromuscular
blockade, based on nerve stimulation
The best method of terminating the relaxant effect is to dose sparingly and allow the
relaxant to be metabolized. Recall that only one of the alpha subunits of the
postjunctional receptor need be occupied by a relaxant molecule to inhibit function,
whereas two molecules of ACh are necessary to stimulate the receptor, so, even
though the nondepolarizing relaxants are competitive antagonists, the receptor
dynamics favor the relaxants. With these caveats, neuromuscular blockade can be
reversed when there is at least one twitch with TOF stimulation. However, this still
reflects a very deep level of blockade and the clinician should monitor the patient
closely for clinical signs of inadequate return of strength. The greater the TOF when
reversed, the better. It is also important to remember that recent tetanic stimuli will
result in overestimating the TOF.
27. Review the drugs and doses commonly used to antagonize
nondepolarizing blockade
Acetylcholinesterase inhibitors prevent the breakdown of acetylcholinesterase,
increasing the amount of ACh available at the NMJ. Neostigmine 25-70 g/kg and
edrophonium 0.5-1 mg/kg are commonly used for this purpose perioperatively.
Edrophonium also stimulates the prejunctional membrane, increasing release of ACh.
These medications contain positively charged quaternary ammonium groups, are
water soluble, and are renally excreted.
28. Review important side effects of acetylcholinesterase
administration
Increasing the available acetylcholine at the NMJ (a nicotinic receptor) will also
stimulate muscarinic cholinergic receptors. Of particular concern is the effect on
cardiac conduction. Unopposed muscarinic effects will impair sinus-node conduction,
resulting in sinus bradycardia, junctional rhythms, and in the extreme, asystole. To
prevent this, anticholinergics are administered in concert with the
acetylcholinesterase. Glycopyrrolate 7-15 g/kg is coadministered with neostigmine
and atropine 7-10 g/kg with edrophonium so that the onset of anticholinergic activity
is appropriately timed with the onset of acetylcholinesterase inhibition.
29. Should all patients who receive nondepolarizing relaxants be
reversed?
There is mounting evidence that residual neuromuscular blockade and clinical
weakness occur with disturbing frequency, even when the patient has received only
one dose of an intermediate-duration nondepolarizing relaxant. These residual effects
have been noted even 2 hours after a single dose. Part of the problem appears to be
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subjective misinterpretations of full return of TOF, as discussed earlier. It appears that


routine reversal of all patients might be a prudent practice.
30. Review the clinical signs associated with return of adequate
strength

Table. TESTS OF RETURN OF NEUROMUSCULAR FUNCTION


Percentage of
Test
Results
Receptors Occupied
Tidal volume
>5 mL/kg
80
Single twitch
Return to baseline
75-80
Train of four
No fade
70-75
Sustained tetanus (50 Hz, 5 No fade
70
seconds)
Vital capacity
>20 mL/kg
70
Double-burst stimulation
No fade
60-70
Sustained tetanus (100 Hz, No fade
50
5 seconds)
Inspiratory force
>-40 cm H2O
50
Head lift
Sustained 5 seconds
50
Hand grip
Return to baseline
50
Sustained bite
Sustained clinching of a
50
tongue depressor

31. A patient appears weak after pharmacologic reversal of


neuromuscular blockade. What factors should be considered?
Has enough time elapsed to observe peak reversal effect? Was blockade so intense
that reversal is not possible? Is your twitch monitor functioning and are leads well
placed? Are body temperature, acid-base status, and electrolyte status normal? Is the
patient receiving medications that potentiate neuromuscular blockade? What is the
patient's renal and hepatic function? Importantly, if the patient is weak, do not
extubate. Time usually cures all that ails.

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