Stoelting Study 7B Nmdb

Front 1

54. What is a concern regarding patients receiving long-term nondepolarizing neuromuscular blocking drugs in the intensive care unit?

Back 1

54. Most patients receiving neuromuscular blockilg drugs for a prolonged period of time in the intensive care unit recover full muscle strength within a few hours of discontinuation of the drug. There have been reports of a subset of patients who, after receiving neuromuscular blocking drugs for several days or weeks, have had persistent skeletal muscle weakness after the discontinuation of the neuromuscular blocking drug. In some cases the skeletal muscle weakness has persisted for months. Weaning the patient from mechanical ventilation of the lungs is therefore delayed.

Front 2

56. How common are aIlergic reactions to nondepolarizing neuromuscular blocking drugs?

Back 2

56. Allergic reactions to neuromuscular blocking drugs are rare. When an allergy d?es exist, the antigenic group is believed to be the quaternary ammonium nitrogen molecule. Because the quaternary ammonium nitrogen molecule is common to all the neuromuscular blocking drugs, including succinylcholine, there is likely to be a cross-sensitivity among all the neuromuscular blocking drugs when an allergy is present. (98)

Front 3

58. How is the clearance of pancuronium affected by renal or liver disease?

Back 3

58. The principal route of clearance of pancuronium, like the other long-acting nondepolarizing neuromuscular blocking drugs, is by glomerular filtration. The clearance of all these long-acting nondepolarizing neuromuscular blocking drugs is g:-eatly affected by renal disease, such that the plasma clearance of pancuronium in patients with renal failure is decreased by 30% to 50%. Patients with renal disease are therefore likely to exhibit prolonged neuromuscular blockade with the administration of conventional doses of pancuronium. Pancuronium is also metabolized by the liver to a limited degree. A metabolite of pancuronium, 3-desacetylpancuronium, possesses limited muscle relaxant properties. Patients with biliary obstruction or cirrhosis of the liver may also manifest decreased plasma clearance and prolonged elimination half·times of pancuronium, although not to as great an extent as that seen with renal disease.

Front 4

59. What are the cardiovascular effects associated with the administration of pancuromum? What is the mechanism by which these effects occur?

Back 4

59. The administration of Jancuronium results in a modest increase in heart rate and arterial blood pressure by 10% to 15%. This effect of pancuronium is primarily due to muscarinic receptor blockade at the sinus node of the heart exerted directly by pancuronium. This selective vagal blockade of the heart is similar to the mechanism by which atropine increases heart rate. The increase in heart rate associated with the administration of pancuronium is dose-related and additive, such that subsequent doses of pancuronium will result in similar, additional increases in heart rate as previous doses. This increase in heart rate cannot be blunted or avoided through the slower injection of the drug. A minimal contributor to the increases in heart rate and blood pressure associated with the administration of pancuronium is activation of the sympathetic nervous system. Patients with altered atrioventricular conduction of cardiac impulses, such as patients with atrial fibrillation, appear to be the most likely to have marked increases in heart rate associated with the administration of pancuronium.

Front 5

61. What are some advantages and disadvantages of intermediate-acting nondepolarizing neuromuscular blocking drugs when compared with long-acting nondepolarizing neuromuscular blocking drugs?

Back 5

61. There are two advantages of the intermediate-acting nondepolarizing neuroing neuromuscular blocking drugs. First, intermediate-acting nondepolarizing ing neuromuscular blocking drugs. First, intermediate-acting nondepolarizing neuromuscular blocking drugs have minimal cumulative effects when administered as a continuous intravenous infusion. This is as a result of their rapid, efficient clearance from the plasma. Second, these drugs possess a relative lack of cardiovascular effects. One disadvantage of the intermediate-acting nondepolarizing neuromuscular blocking drugs when compared with the longacting nondepolarizing neuromuscular blocking drugs is their relatively higher cost.

Front 6

62. How is vecuronium excreted from the body? How does renal failure affect the clearance of vecuronium?

Back 6

62. Vecuronium is metabolized by de acetylation in the liver to 3-, 17-, and 3,17Iroxy metabolites. Only the 3-hydroxy metabolite has any significant neuromuscular blocking properties. Up to 60% of the injected dose of vecuromum, whether metabolized or unchanged, is excreted in the bile. Vecuronium is also partially cleared by the kidneys. Patients with renal failure may have impaired excretion of the unchanged form of vecuronium as well as the active 3-hydroxy metabolite of vecuronium. This may result in cumulative effects of vecuronium with the administration of large or repeated doses of vecuronium in renal failure patients. There are reports of prolonged neuromuscular blockade in renal failure patients in the intensive care unit being administered continuous infusions of vecuronium.

Front 7

63. How does the time of onset of rocuronium compare with the time of onset of succinylcholine?

Back 7

63. Rocuronium has an onset time of 1 to 2 minutes at its ED95 dose, which makes it unique among the intenneoote-acting nondepolarizing neuromuscular blocking drugs. In the event that a more rap:d onset time is desired, rocuronium may be administered at a dose of three to four times its ED95 dose. This increased dose results in an onset time similar to that of succinylcholine. Because of the relative decreased potency of rocuronium when compared with the other intermediate-acting nondepolarizing neuromuscular blocking drugs, the duration of action of rocuronium at this increased dose remains intermediate. (

Front 8

64. How is rocuronium excreted from the body? How does renal failure affect the clearance of rocuronium?

Back 8

64. Rocuronium is mostly cleared from the plasma tlrough the bile largely unchanged. About 30% of rocuronium administered is excreted renally. Large or repeated doses of rocuronium in patients with renal failure may theoretically produce prolonged effects of the drug, although this has not been seen clinically

Front 9

65. How are cisatracurium and atracurium structurally related?

Back 9

65. Cisatracurium is an isolated form of a stereoisomer of atracurium.

Front 10

66. How are atracurium and cisatracurium cleared from the plasma? How does renal failure affect the clearance of these drugs?

Back 10

66. The clearance of atracurium and cisatracurium from the plasma is completely independent of the kidneys. Two thirds of administered atracurium or cisatracurium undergoes ester hydrolysis, whereas the remaining third undergoes nonenzymatic spontaneous degradation by Hofmann elimination. Hofmann elimination is dependent on the pH and temperature of the plasma. The metabolism of these drugs is also independent of plasma cholinesterase since nonspecific plasma esterases are responsible for the ester hydrolysis. Both of the routes of metabolism for these drugs are independent of the kidneys or liver, making the duration of action of atracurium or cisatracurium unaltered in patients with hepatic or renal failure.

Front 11

70. Name a short-acting nondepolarizing neuromuscular blocking drug. What is its approximate time of onset and duration of action?

Back 11

70. A short-acting nondepolarizing neuromuscular blocking drug is mivacurium. Its approximate time of onset is 3 to 5 minutes. Its approximate duration of action is 10 to 20 minutes, or 30% to 40% shorter than intermediate-acting neuromuscular blocking drugs. (

Front 12

71. How is mivacurium cleared from the plasma? How is the duration of action of rnivacurium altered in patients who have deficiencies in plasma cholinesterase :yme, liver disease, or renal disease?

Back 12

71. Mivacurium is dependent on the enzyme plasma cholinesterase for its clearance. Patients who have either atypical plasma cholinesterase or a decreased concentration of plasma cholinesterase will have a prolonged duration of the administration of an intubating dose of mivacurium i

Front 13

72. Does the administration of neostigmine reverse the neuromuscular blockade produced by mivacurium?

Back 13

72. Neostigmine is an anticholinesterase that inhibits the activity of both plasma cholinesterase and true cholinesterase. The reversal of the neuromuscular blockade produced by mivacurium may be accomplished with the administration of neostigmine. The benefits of increasing the concentration of acetylcholine available to compete for binding sites on the nicotinic cholinergic receptor in the neuromuscular junction outweigh the inhibition of the activity of plasma cholinesterase in this circumilance, and the actions of mivacurium may be reversed

Front 14

73. What are some of the cardiovascular effects of mivacurium?

Back 14

73. The administration of mivacurium rapidly and at doses of three times ED95 may result in histamine release and associated transient decreases in systemic blood pressure.

Front 15

77. What is the most common method for monitoring the effects of neuromuscular blocking drugs dunng general anesthesia?

Back 15

77. The most common method for monitoring the effects of neuromuscular blocking drugs during general anesthesia is through the use of a peripheral nerve stimulator. the peripheral nerve stimulator works by stimulating a motor nerve to conduct an impulse. A mechanically evoked muscle response is then evaluated by the clinician. The mechanical motor response of the muscle reflects the number of muscle fibers that are blocked and provides an indication to the clinician of the degree of neuromuscular blockade.

Front 16

78. What are two ways in which a peripheral nerve stimulator may be useful during the administration of neuromuscular blocking drugs during general anesthesia

Back 16

78. A peripheral nerve stimulator may be useful during the administration of neuromuscular blocking drugs during gi!neral anesthesia in at least two ways. First, a peripheral nerve stimulator allows the clinician to titrate the neuromuscular blocking drug to optimize skeletal muscle relaxation for SUfgery without unnecessarily overdosing the patient. Second, a periphe~a1 nerve stimulator may be used as an objective means with which to judge the recovery from neuromuscular blockade at the conclusion of surgery either before or after the antagonism of a nondepolarizing neuromuscular blocking drug with an anticholinesterase drug. (1

Front 17

79. Which nerve and muscle are most commonly used to evaluate the neuromuscular blockade produced by neuromuscular blocking drugs

Back 17

79. The ulnar nerve and adductor pollicis muscle are the nerve and muscle most commonly used for the evaluation of the neuromuscular blockade produced by neuromuscular blocking drugs through the use of a peripheral nerve stimulator. The adductor pollicis muscle is solely innervated by the ulnar nerve. This means that the only source for motm stimulation of the adductor pollicis muscle is through the mechanical stmulation of the ulnar nerve. Different muscle groups differ in their sensitivities to neuromuscular blocking drugs. The adductor pollicis muscle is more sensitive to the effects of neuromuscular blcckers than are the diaphragm or upper airway muscles.

Front 18

80. Which nerves may be used for the evaluation of the neuromuscular blockade produced by neuromuscular blocking drugs through the use of a peripheral nerve I stimulator when the arm is not available to the anesthesiologist?

Back 18

80. When the arm is not available to the anesthesiologist, the facial nerve and orbicularis oculi muscle are often used for the evaluation of the neuromuscular blockade produced by neuromuscular blocking drugs through the use of a peripheral nerve stimulator. Other nerves that may be used include the lledian, posterior tibial, and cornman peroneal nerves.

Front 19

81. How do the neuromuscular blocking drugs vary with regard to their time of onset at the adductor pollicis muscle, orbicularis oculi muscle, laryngeal muscles, and diaphragm?

Back 19

81. In general, the administration of nondepolarizing neuromuscular blocking drugs produces laryngeal muscle relaxation and conditions favorable for intubation of the trachea more rapidly than relaxation of the adductor pollicis muscle as measured by ulnar nerve stimulation. Facial nerve stimulation and measurement of neuromuscular blockade of the orbicularis oculi muscle more closely correlate laryngeal muscle relaxation and vocal cord paralysis than ulnar nerve stimulation

Front 20

83. How may the duration of neuromuscular blockade be defined using a single muscle twitch lS the mechanically evoked response?

Back 20

83. The duration of neuromuscular blockade may be defined as the time difference between the time of drug administration and the time a mechanically evoked single twitch recovers to a certain percentage of is control height.

Front 21

84. How may the depth of neuromuscular blockade be defined using a single muscle twitch as the mechanically evoked response?

Back 21

84. The depth of neuromuscular blockade may be defined as the percent inhibition of a mechanically evoked single twitch from its control height. (l02)

Front 22

85. What percent of depression of a mechanically evoked single twitch response from its control height correlates with adequate neuromuscular blockade for intubation of the trachea or for the performance of intra-abdominal surgery? What approximate percent of nicotinic cholinergic receptors must be occupied by a nondepolarizing neuromuscular blocking drug to achieve this effect?

Back 22

86. The train-of-four (TOP) stimulus delivered by a peripheral nerve stimulator is four electrical stimuli at 2 Hz each delivered every 0.5 second. The TOP stimulus is useful for the evaluation of the degree of neuromuscular blockade based on the premise that each successive electrical stimulus will further deplete stores of acetylcholine in the nerve terminal. In the presence of neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs, there will be a resultant decrease in the mechanically evoked muscle response with each stimulus. The amount of decrease in the mechanical muscle response correlates with the degree of neuromuscular blockade. Only four twitches are used in the rOF stimulus because any further stimulation of the nerve after the fourth does not result in any further depletion of acetylcholine stores at the nerve terminal.

Front 23

86. What is the train-of-four stimulus delivered by a peripheral nerve stimdator? What is its clinical use?

Back 23

86. The train-of-four (TOF) stimulus delivered by a peripheral nerve stimulator is four electrical stimuli at 2 Hz each delivered every 0.5 second. The TOF stimulus is useful for the evaluation of the degree of neuromuscular blockade based on the premise tha each successive electrical stimulus will further deplete stores of acetylcholine in the nerve terminal. In the presence of neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs, there will be a resultant decrease in the mechanically evoked muscle response with each stimulus. The amount of decrease in the mechanical muscle response correlates with the degree of neuromuscular blockade.

Front 24

87. What is the train-of-four ratio? What is its clinical use'?

Back 24

87. The train-of-four (TOF) ratio is a calculation of the height of the fourth evoked twitch response divided by the height of the first evoked twitch response of a TOF stimulus. For example, if the height of the fourth twitch is one half the height of the first twitch, the TOF ratio would be 0.5. The TOF ratio reflects how much fade has occurred, which correlates with the e~a~:~::~;~s~:~~r;;~;~~~ ~:s~~~~~~~~,~~e~~:~:~?~t~~~;c~~2 be 1.0 before the administration of neuromuscular blocking drugs. this corresponds to a height of the fourth mechanically evoked twitch response being equal to the height of the first evoked twitch response.

Front 25

88. What train-of·four ratio correlates with the complete return to control height of a single twitch response?

Back 25

88. A train-of-four (lOF) ratio of 0.7 or greater correlates with the complete [0 control height of a single twitch response. That is, when the height of the fourth mechanically evoked twitch response is 70% of the height of the first evoked twitch response in a TOF stimulus, a smgle twitch response will have returned to its control height.

Front 26

89. What is the train-of-four ratio during phase I neuromuscular blockade resulting from the administration of a depolarizing neuromuscular blocking drug such as succinylcholine?

Back 26

89. After the administration of succinylcholine for neuromuscular blockade, phase I neuromuscular blockade is reflected in the train-of-four (TOF) as a TOF ratio near 1.0. This means that the decrease in height of the first twitch is the same as the decrease in height of the fourth twitch, and there is no fade in the mechanically evoked muscle response.

Front 27

90. What is the train-of-four ratio during phase II neuromuscular blockade resulting from the administration of a depolarizing neuromuscular blocking drug such a succinycholine?

Back 27

90. After the administration of succinylcholine for neuromuscular blockade, phase II neuromuscular blockade may be reflected in the train-of-four (TOF) response as a TOF ratio less than OJ. The TOF response thus shows some fade of the fourth twitch when compared with the first twitch of the TOF stimulus when phase IT neuromuscular blockade is present.

Front 28

91. How accurate is the estimation of the train-of-four ratio by clinicians evaluating the response visually and manually? What percent of the first twitch control height must be present before the fourth twitch be detectable?

Back 28

91. Estimation of the train-of-four (TOF) response by clinicians evaluating the response visually and manually is not very accurate. Although clinicians ha've difficultJ assessing the TOF ratio, the assessment of the absolute number of twitches evoked by the TOF stimulus is much more reliable. When the first twitch is approximately 35% of the control twitch height, the fourth twitch is able to be detected. this corresponds to a TOF ratio of about 0.35. (103;

Front 29

92. What is the double burst suppression stimulus delivered by a peripheral nerve stimulator? What is its clinical use?

Back 29

The double burst suppression stimulus delivered by a peripheral nerve stimutwo bursts of three 50 Hz electrical stimuli separated by 750 milliseconds between each, but it is perceived by the clinician as two separate twitches. The use of the double burst suppression stimulus appears to make the estimation of the fade response easier for clinicians. It is thought that the estimation of the ratio between the two twitches is easier for clinicians because the middle two twitches of the train-of-four (TOF) response are eliminated. A TOF ratio of 0.3 or less is most accurately detected by clinicians when using the double burst suppression stimulus. Accuracy of the estimation of a TOF ratio grealer than 0.7 is still poor,

Front 30

93. What is tetany? How might it be mechanically produced by a peripheral nerve stimulator?

Back 30

93. Tetany is a continuous skeletal muscle contraction that occurs secondary to continuous stimulation of the post junctional receptors. Tetany can be mechanically produced through the use of a peripheral nerve stimulator. The delivery of a continuous electrical stimulus of about 50 Hz for 5 seconds is frequently used in clinical aneithesia practice to induce tetany for the evaluation of neuromuscular blockade. I

Front 31

95. What must the train·of·four ratio be to have a sustained response to a tetanic stimulus?

Back 31

95. A sustained response to a tetanic stimulus correlates to a train-of-four ratio greater than 0.7

Front 32

96. What is post-tetanic stimulation? What is its clinical use?

Back 32

96. Post-tetanic stimulation refers to the evaluation of a train·of-four (TOF) response after a tetanic stimulus has been delivered. The mechanical muscle response to a TOF stimulus after the delivery of a tetanic stimulus is useful during intense neuromuscular blockade when there is no evoked mechanical response to either a single twitch or a TOF stimulus. The clinical use of posttetanic stimulation is derived from the transient enhancement of the mechanical muscle response obtained when a TOF stimulus is delivered immediately after a tetanic stimulus. This enhancement is due to an increase in the available stores of acetylcholine in the nerve terminals after a tetanic stimulus and is tenned pest-tetanic facilitation.

Front 33

97. What is the mechanism by which the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs is antagonized?

Back 33

97. The an~gonism of the neuromuscular blockade produced by nondepolarizing tion of anticholinesterases. The anticholinesterases most often used for this tion of anticholinesterases. The anticholinesterases most often used for this purpose are neostigmine and edrophonium. These drugs exert their effect by inhibiting me activity of acetylcholinesterase, the enzyme that hydrolyzes acetylcholine in the neuromuscular junction. As a result of the inhibition of the hydrolysis of acetylcholine, acetylcholine accumulates in the neuromuscular junction. With more acetylcholine available at the neuromuscular junction the competition between acetylcholine and the nondepolarizing neuromuscular blocking drug is altered sud that it is more likely that acetylcholine will bind to the post junctional receptor. In addition to increasing the amount of acetylcholine available in the neuromuscular junction to compete for sites on the nicotinic cholinergic receptors, acetylcholine also accumulates at the muscarinic cholinergic receptor tes furou~ the same mechanisn

Front 34

98. How are the cardiac muscarinic effects of anticholinesterases attenuated?

Back 34

98. Anticholinesterases increase the concentration of acetylcholine available at the muscarinic cholinergic receptors as well as the nicotinic cholinergic receptors. This may result in profound bradycardia through the stimulation of muscarinic cholinergic receptors in the heart. To attenuate the cardiac muscarinie effects of anticholinesterases, a peripheral-acting anticholinergic such as atropine or glycopyrrolate is administered intravenously before or simultaneous with the intravenous administration of the anticholinesterase

Front 35

99. Which class of anticholinesterase is used for the antagonism of the neuromuscular blockade produced by neuromuscular blocking drugs?

Back 35

99. Anticholinesterases that have a quaternary ammonium structure are used for the antagonism of the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs. In contrast to the tertiary amine-structured anticholinesterases, the quaternary ammonium structure makes these agents less lipid soluble and prevents them from easily crossing lipid membranes. This restricts their ability to gain access to the central nervous system by crossing the blood-bnin barrier, thereby minimizing their central nervous system effects.

Front 36

100. Name two factors that influence the choice of anticholinesterase drug to be administered to antagonize the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs.

Back 36

100. Two factors that influence the choice of anticholinesterase drug to be administered to antagonize neuromuscular blockade include the approximate duration of action of the nondepolarizing neuromuscular blocking drug that had been administered and the intensity of the neuromuscular blockade that exists at the conclusion of surgery

Front 37

101. When might neostigmine or edrophonium be an appropriate choice of anticholinesterase drug to be administered to antagonize neuromuscular blockade? What anticholinergic drug is often paired with each?

Back 37

[01. Neostigmine and edrophonium are the quaternary ammonium-structured anticholinesterases that are most frequently administered for the antagonism le effects of nondepolarizing muscle relaxants. Neostigmine should be dministered for the antagonism of the effects of nondepolarizing neuromuscular blocking drugs when the neuromuscular blockade is intense and/or when the neuromuscular blocking drug that had been administered is long acting. This is primarily due to the prolonged duration of effect of neostigmine when compared with the duration of effect of edrophonium. Glycopyrrolate is often paired with neostigmine as the anticholinergic of choice because its delayed cardiac anticholinergic effects more closely parallel the time of onset of the muscarinic effects produced by neostigmine. Conversely, edrophonium has a shorter time of onset and shorter duration of action than neostigmine

Front 38

102. When is the antagonism of the neuromuscular blockade produced by neuromuscular blocking drugs not recommended?

Back 38

102. Antagonism of the neuromuscular blockade produced through the ldministration of anticholinesterases is not recommended when a mechanical muscle twitch response to an electrical stimulus is unable to be evoked. The degree neuromuscular blockade in Ihese patien~ i! believed to be so intense that Its antagonism by an anticholinesterase is not possible. Instead, these patients should be maintained 00 mechanical ventilation of the lungs until a twitch response can be evoked.

Front 39

103. What are some tests that can be done to evaluate the adequacy of the recovery from the effects of neuromuscular blockade?

Back 39

· Clinical tests that may also be used to evaluate the adequacy of the reversal of neuromuscular blockade he patient's ability to open the eyes, cough, stick out the tongue, and sustain a head lift for 5 to 10 seconds; grip strength; vital capacity; and maximal inspiratory force. Of these clinical tests, a sustained head lift is considered to be the most sensitive test to evaluate the adequacy of the recovery from neuromuscular blockade.

Front 40

104. Which type of neuromuscular blocking drug is most commonly associated with postoperative weakness

Back 40

104. Long·acting neuromuscular blocking drugs such as pancuronium are most commonly associated with postoperative weakness.

Front 41

105. How might the residual effects of neuromuscular blockers be manifest clinically in the awake patient?

Back 41

105. Residual effects of neuromuscular blockers may manifest clinically in awake patients as diplopia, decreased hand grip strength, difficulty swallowing, and difficulty speaking. Patients may also have difficulty sustaining their minute ltilation without assistance.

Front 42

106. What are some pharmacologic or physiologic factors that may interfere with the antagonism of the neuromuscular blockade pro:luced by neuromuscular blocking drugs?

Back 42

106. There are several pharmacologic and physiologic factors that may interfere with the antagonism of the neuromuscular blockade produced by neuromuscublocking drugs. Physiologic factors include abnormalities in the patient's temperature, acid-base status, electrolytes, or metabolism pathways_ These with the metabolism and clearance of the neuromuscular blocking drug. In particular, renal or liver disease may result in markedly prolonged elimination times and plOlonged clinical effects of certain nondepolUscular blocking drugs. Pharmacologic factors include the concurrent administration of aminoglycoside antibiotics, local anesthetics, volatile anesthetics, magnesium, dantrolene, and cardiac antidysrhythmic agents. Another cause of an apparent inability to antagonize the effects of nerromuscuiar blocking drugs is not allowing sufficient time to pass for an anticholinesterase to begin exerting its effect. Finally, the lack of a mechanically evoked muscular response to a train-of-four stimulus is an indication that the antagooi!ll of ~ neuroIDUicular blockade is not possible