NMB

Question 1

If 4th twitch is absent on TOF, that indicates …

What about if the 3rd twitch is absent …

Answer 1

TOF with absence of the fourth twitch represents a 75% blockade of Ach-R, so therefore “Approximately 25% of the Ach-R are unblocked”.

Absence of the third twitch represents blockade of 80% of Ach-R and second twitch 90%.

Question 2

Fade on TOF vs tetanus ?

Answer 2

Fade on TOF can be due to two situations: First, use of nondepolarizing muscle relaxants, and Second: phase II block following succinylcholine. Phase II block is where prolonged depolarization of the perijunctional muscle endplate results in conformational changes to the Ach-R, such that it resembles the block of a nondepolarizer.

Tetanus is a related concept to TOF and is best used to gauge recovery from muscle relaxation, not so much redosing.

In the situation of 4th twitch absence, one would expect fade on tetanus, regardless of the Hz used.

Question 3

Which muscles recover first from NMB? What is the muscle that is most sensitive and best indicator for recovery from blockade?

Answer 3

The muscles of the diaphragm, larynx, and rectus abdominus are more resistant to the effects of nondepolarizing muscle relaxants and recover sooner as compared to peripheral muscles on the extremities.

It just so happens that monitoring eyebrow twitch parallels the characteristics of these important muscle groups for breathing and airway patency. To confuse the situation, however, is the fact that the eyebrow twitch is actually the function of the “corrugator supercilii” which will be more resistant to fade following cisatricurum administration and have faster recovery. What about the oculi orbicularis? Well technically, the oculi orbicular does slightly differ from the adductor polices in the same fashion (loses twitches slower and recovers faster), but far less so than the corrugator supercilii and diaphragm, larynx, and rectus abdomens.

Because adductor pollicis is more sensitive to muscle relaxation, its recovery is theoretically a better indicator that all of the muscles of the patient have recovered from blockade.

Question 4

What conditions makes succinylcholine prolonged it’s action?

Answer 4

First, cholinesterase inhibitors can also inhibit (to variable degrees) pseudocholinesterase, so neostigmine, physostigmine, etc, can cause a prolongation. Of the cholinesterase inhibitors, however, the most “famous” is ecothiophate.

An assortment of other drugs can inhibit psedocholinesterase as well, and memorizing them is pretty low yield, but common ones are: esmolol, pancuronium, cyclophosphamide, and phenelzine.

Another cause of prolongation of succinylcholine is reduction in the amount of pseudocholinesterase per liter of blood, either by decreased production or dilution (pregnancy and cirrhosis).

Question 5

Time of blockade difference between heterozygous and homozygous psudocholensterse deficiency after succinylcholine? And Dibucaine number for both would be…?

Answer 5

The heterozygote (one normal, one variant gene) results in about a 30 minute block. Two abnormal genes result in a 4-8 hour block.

Dibucaine, an inhibitor of normal pseudocholinesterase, will inhibit its activity by 80%. In heterozygotes the inhibition is 40-60% and in homozygotes it is 20% .

Question 6

Would esmolol metabolism be affected in patients with psudocholensterse deficiency?

Answer 6

Esmolol is metabolized by an esterase located in the red blood cell, which is distinctly different than the pseudocholinesterase responsible for succinylcholine metabolism, therefore the metabolism of esmolol will be normal (normal esmolol half life is 10-20 minutes).

Question 7

MH testing?

Answer 7

halothane-caffeine contracture test is a screening test for malignant hyperthermia, which can be induced by succinylcholine

Question 8

Is succinylcholine contraindicated in heterozygous psudocholensterse deficiency patients?

Answer 8

Succinylcholine is not absolutely contraindicated since the block only lasts 30 minutes (answer C), but the only remaining advantage over other muscle relaxants (which can be reversed) is quick onset (30 seconds versus 1 minute at high dose rocuronium). Pretreatment with other muscle relaxants has no bearing on the dibucaine number (answer D), as the dibucaine number is purely a function of the drugs effects on the enzyme (in vitro).

Question 9

The highest risk of hyperkalaemic cardiac arrest following succinylcholine

Answer 9

Normally, following an intubating dose of succinylcholine, serum potassium will rise by 0.5 mEq/L (due to wide spread coordinated depolarization). The presence of exrajunctional Ach-Rs means that the number of receptors and muscle cells affected increases, and life-threating hyperkalaemic cardiac arrest can occur. The odds are increased with the amount of tissue affected and the chronicity of the injury (greatest period of risk is probably 7-10 days following denervation).

A typical rule-of-thumb is to absolutely avoid succinylcholine 24 hours after the injury until at least a year.

Question 10

The strength of association between muscle fasciculations and untoward effects of succinylcholine are controversial. The association between fasciculations and both … and … increases are the strongest.

Answer 10

ICP and abdominal pressure increases are the strongest.

The association of fasciculations and myalgia is strong, but far from 100%

Question 11

Defasciculating doses of nondepolarizing muscle relaxants tend to decrease …. and it won’t prevent …

Answer 11

1. increases in ICP
2. decrease myalgia incidence and perioperative NSAIDS decrease post-operative pain from myalgia.
3. Although abdominal pressure increases secondary to muscle fasciculations, succinylcholine is also associated with an increase in lower esophageal sphincter tone, offsetting the theoretical increased risk of pulmonary aspiration.

Intraocular pressure increases with succinylcholine and is independent of fasciculations and, in fact, transection of intraocular muscles do not prevent pressure increases much less defasciculating doses of nondepolarizing muscle relaxants

Question 12

3 NMB causes release of histamine

Answer 12

Benzylisoquinolone muscle relaxants (ending with –curium except cisatrcurium) tend to release histamine and steroidal muscle relaxants (ending with –curonium) tend to be vagolytic.

Of benzylisoquinolone muscle relaxants, atracurium and mivacurium (answer D) are most likely to result in mast cell degranulation with resultant histamine release leading to flushing, vasodilatation, and of course, bronchospasm.

Slow injection rates and pretreatment with H1 & H2 blockers are recommended.

Succinylcholine also causes histamine release with variable frequency, although in the great majority of cases no adverse effects other than a transient rash are present.

Cisatracurium does not appear to result in histamine release even at very high doses.

Steroidal coumponds tend to be vagolytic, with the prototype being pancuronium, which predictably results in dose dependent tachycardia and hypertension primarily through vagolytic mechanisms, but also sympathetic stimulation as well. Rocuronium and vecuronium have mild (if any) vagolytic properties at high doses.

Question 13

What is priming dose for NMB

Answer 13

Priming dose is a concept where about 1/10th the intubation dose of a nondepolarizer is given about 3-5 minutes prior to intubation so that when the actual intubation dose is given, onset will be greatly accelerated.

Question 14

Potentiates NMBs?

Answer 14

Volatile anesthetics (less so nitrous oxide)
magnesium supplementation (as in obstetrics)
hypocalcaemia
hypokalaemia
acidosis
hypothermia are classics.
neonates are more sensitive than adults to muscle relaxants.

Question 15

Conditions increases sensitivity to non-depolarizers …

Answer 15

Extremes of age
MS
most peripheral neuropathies
most neuromuscular junction disorders
most myopathies
muscular dystrophies
some channelopathies

as a general rule anything that makes one weak all the time will most ilk have sensitivity whereas periodic (episodic) weakness is less profound (some sensitivity in MS probably no sensitivity in hyper- or hypo-kalaemic periodic paralysis).

Question 16

A patient with myasthenic syndrome would have …. to NDNM and … to DNMB

Answer 16

Increased sensitivity to both nondepolarizing muscle relaxants and succinylcholine

Remember myasthenic syndrome is another name for Eaton-Lambert Syndrome (ELS). With ELS there is an up-regulation of acetylcholine receptors at the neuromuscular junction due to decreased acetylcholine release. Because there are more receptors, depolarization is easier (requires a smaller dose) with succinylcholine. As for nondepolarizers, although there are more receptors that need to be bound, nondepolarizers work through competitive inhibition and with less acetylcholine present, a lower dose of nondepolarizing muscle relaxant is needed.

Question 17

Patient with CP would have … to succinylcholine and …. to NDNMB

Answer 17

Resistance to nondepolarizing muscle relaxants and normal response with succinylcholine

CP does not have an increased risk of hyperkalaemia with succinylcholine, even in the setting of contractures, as there is no proliferation of extrajunctional nicotinic acetylcholine receptors. Some CP patient can be mildly sensitive to succinylcholine, however. Some sources report that these patients are resistant to nondepolarizers whereas others do not. It is probably due to a combination of 1) CP being symptom complex made up from many etiologies (some etiologies may have resistance where other may not), 2) coexisting medications used to treat CP, and 3) a very minor effect.

Question 18

A patient with extensive burns 2 weeks ago would have …. to NDNMB and … with succinylcholine

Answer 18

Resistance to nondepolarizing muscle relaxants and hyperkalaemia with succinylcholine

extensive deep burns result in proliferation of extrajunctional acetylcholine receptors which is the set-up for hyperkalaemia following succinylcholine. Using the general rule of increased receptors (binding sites) for nondepolarizers to competitively occupy conferring resistance (requiring an increased dose), provides a way to remember how muscle relaxants respond in the setting of burns.

Question 19

A patient with systemic lupus erythematosus (SLE) would have … to NDNMB and … to succinylcholine

Answer 19

Sensitivity to nondepolarizers, sensitivity to succinylcholine

Autoimmune disorders, in general, are reported to have hypersensitivity to all muscle relaxants. This is likely only true for those disorders associated with rheumatologically derived weakness, with muscle relaxants simply just exacerbating this.

Question 20

cisatracurium Degredation by … can be decreased with …

Answer 20

Degredation by Hofmann elimination can be decreased with hypothermia

it is metabolized by organ-independent Hoffman elimination in the plasma, and that process is slowed in hypothermia.

Question 21

laudanoside is a product of … & …

Answer 21

Second, one of the breakdown products of cisatracurium is a compound called laudanosine, which is metabolized by the liver and excreted by the kidneys. At extremely high levels, it can result in CNS excitation (increased MAC requirements) and seizures, but has no intrinsic ability for neuromuscular blockade.

Atracurium (cis-atracurium is a stereoisomer of atracurium) also produces laudanoside, and since it is less potent, a greater dose (number of molecules needed) of atracurium is needed than cisatracurium. This results in increased levels of laudanosine with atracurium as compared to cisatracurium.

Question 22

A patient with a dibucaine number of 20% has a prolonged neuromuscular blockade for four hours. Which of the following muscle relaxants were most likely used:

Answer 22

Mivacurium or succinylcholine

Both Mivacurium and succinylcholine are metabolized by pseudocholinesterase, and in the setting of homozygous atypical pseudocholinesterase, both can result in a blockade for hours. Of the nondepolarizing muscle relaxants in clinical use, pancuronium has the longest duration of action, but would not be expected to produce a 4 hour long blockade (even in renal failure).

Question 23

A patient in the ICU is difficult to ventilate with mechanical ventilation and a vecuronium gtt is initiated. Which of the following muscle relaxants would be a better choice for this purpose:

Answer 23

Cisatracurium gtt

Prolonged vecuronium gtt has led to cases of prolonged polyneuropathy with weakness lasting months, and is therefore contraindicated for this purpose. This was especially true in the setting of steroid use (which was more common in the past). Cisatricurium has been shown to be a much safer alternative with far less risk of polyneuropathy. It is important to note that even long cases in the OR with steroids do not lead to polyneuropathies using vecuronium or other steroidal based compounds (pancuronium & rocuronium).

Question 24

Which is better choice choosing Rocuronium or vacronium in lifer failure patients?

Answer 24

Rocuronium is devoid of metabolites

Therefore, in the setting of a dysfunctional liver with poor bile excretion, rocuronium is not metabolized and not excreted, prolonging its blockade.

Question 25

Which of the following Pancuronium, Rocuronium, or Vacuronium has the most metabolism in liver and Renault excretion, what about the most has bile excretion?

Answer 25

pancuronium having the most metabolism (by the liver, of course) and the greatest amount of renal excertion (40%) and the least amount of bile excretion (10%). Rocuronium, on the other side of the spectrum undergoes (essentially) no metabolism and is cleared by the liver via the bile (~10% excreted unchanged in the urine). Vecuronium is in the middle with minimal metabolism (and therefore metabolites), 25% renal excretion and 75% bile excretion.

Question 26

Which of NDNMB can lead to pulmonary embolism?

Answer 26

Both rocuronium and vecuronium can precipitate with thiopental leading to pulmonary emboli .

Question 27

Which is more potent: Rocuronium or vecuronium.

Answer 27

A greater dose of rocuronium is needed for an equipotent effect as compared to vecuronium, and is therefore less potent than vecuronium.

Question 28

Extubation Criterion

Answer 28

1) tidal volume should be over 5 cc/ kg, 2) vital capacity over 10 cc/ kg, 3) NIF more negative than -20 cc H20, 4) PaCO2 < 50, 5) RR < 30, 6) sustained tetanus at least 5 seconds, head lift of at least 5 seconds. 7) RSBI is a calculation of RR/ tidal volume and should be less than 105.

Question 29

What’s one way to measure ventilation strength?

Answer 29

RSBI Remember a low RSBI (RR/TV in liters) means that they are taking large breaths slowly. This means not only must they be ventilating well, have ok lung compliance, but they must also be strong - therefore making it an indirect measure of strength).

Question 30

How would hypoglycemia can lead to delayed emergence?

Answer 30

Long standing hypoglycaemia can result in cerebral ischaemia in a similar fashion to hypoxia. Delayed emergence in the setting of diabetes deserves a finger-stick on the boards (especially oral boards). And by process of elimination, it should be ruled out.

Question 31

Neostigmine excepted effects ? It stimulates... receptors indirectly by inhibiting anticholinesterases and increase ...

Answer 31

``` Muscurinic stimulation results in myosis, salivary secretion, bradycardia, bronchospasm, insulin secretion, bowel motility, bladder sphincter relaxation. ``` Both quaternary (neostigmine) and tertiary (physostigmine) cholinesterase inhibitors appear to result in myosis, while only the tertiary drugs pass the blood brain barrier to the extent to lead to diffuse cerebral excitation.

Question 32

Which is the only anticholenergic drug would not cause mydriasis?

Answer 32

Anticholinergic drugs (prototype atropine) have the opposite effect as anticholinesterases, and are used to offset their effects. All of the answer choices are predictable effects of anticholinergics, including bronchodilitation, tachycardia, decreased GI motility, urinary retention, decreased salivation, confusion and mydriasis. Atropine is a tertiary amine, which means it easily crosses the blood brain barrier; therefore,you will see central effects such as mydriasis, disorientation, and delirium (depending on dose, of course). Glycopyrrolate has a quaternary structure which means it mostly does not cross the blood brain barrier, therefore CNS and pupillary effects are not seen.

Question 33

Central anticholenrgic syndrome reversed with ?

Answer 33

physostigmine. Therefore it would be a good choice if you used so much atropine (due to a glycopyrrolate shortage...which has happened!) that you developed central anticholinergic syndrome. Scopolamine has significant CNS effects, causing sedation, amnesia, and sometimes delirium. Its anticholinergic effects on other organ systems are generally far less pronounced than with atropine, with the exception of its potency as an antisalagogue. Physostigmine has a tertiary amine structure, making it able to cross the blood brain barrier (unlike neostigmine and edrophonium), to “reverse” the effects of scopolamine

Question 34

Central cholenergic syndrome caused by atropine vs scopolamine sx?

Answer 34

Remember in practice there are two terry amines we use: atropine and scopolamine. They both cross the blood brain barrier. At high doses they can cause CNS effects: Atropine: restlessness, hallucinations, delirium Scopolamine: sedation, amnesia, euphoria

Question 35

Recurization?

Answer 35

Recurization of rocuronium is an elusive concept, that I very much doubt will be on the boards as it is poorly defined. There is no accepted standard treatment for recurization (not due to subsequent administration). Some authors think that in some individuals that the rocuronium excreted in the bile can be reabsorbed and therefore auto-transfused for a subsequent dose (remember, rocuronium is not metabolized, so it is still potentially active). Only at very high doses of rocuronium could one imagine the duration of action outlasting that of neostigmine

Question 36

Neostigmine duration of action

Answer 36

Neostigmine’s onset is about 5 minutes, its effects peak at 10 minutes, and its duration is at least an hour. Neostigmine can cross the placenta, whereas glycopyrolate cannot. Therefore, in pregnant patients atropine can be used (even though its onset is quicker and duration of action shorter; whereas glycopyrolate has a more similar profile to neostigmine). Neostigmine can be used as an adjuvant for spinal anesthesia, prolonging sensory blockade, but is associated with many side-effects. Furthermore, intrathecal administration (usually less than 100 mcg) will not reverse muscle relaxation.

Question 37

A patient with hyperkalemic periodic paralysis presents for laparoscopic colon resection. Which of the following muscle relaxants should be avoided:

Answer 37

Succinylcholine Of the choices, succinylcholine is the best choice for two reasons. First succinylcholine predictably increases potassium levels which theoretically could exacerbate the syndrome (typically patients will have K > 5.5 mEq/L during symptoms). Second, both hyper- and hypo-kalaemic periodic paralysis is associated with malignant hyperthermia*, although the association is relatively weak. Non depolarizing muscle relaxants have a normal response as does regional anesthesia. *Neither Miller, Brash, or Co-existing diseases advises to avoid volatile anesthetics only sux.

Question 38

Participating factors for familial hyperkalaemic vs familial hypokalaemic periodic paralysis

Answer 38

For both: hypothermia and rest after exercise. For the hypokalaemic form, decreased levels of potassium lead to periodic paralysis* and administration of insulin, respiratory or metabolic alkalosis, etc (anything that decreases potassium) will precipitate or worsen an attack. For the hyperkalaemic form, increased levels of potassium leads to paralysis*, which includes succinylcholine, fasting, respiratory or metabolic acidosis, and, of course, potassium administration (food or drug). In this patient, we see a history of fasting, and a respiratory acidosis, both of which are more specific for the hyperkalaemic form. Hypothermia is consistent with both forms of familial periodic paralysis. * - Important note: paralysis can occur with NORMAL levels of serum potassium as well, and the disease process is not only rare but very complex. For the purpose of the boards, think in these simplistic terms with the exception regarding the treatments as discussed below. In reality these conditions received their names (hyperkalaemic- and hypokalaemic- familial periodic paralysis based on provocation tests (insulin vs potassium load), not the actual disease processes – a fact that seems to have been forgotten!

Question 39

Treatment of familial hyperkalemic periodic paralysis

Answer 39

Hyperkalemic: 1) Calcium, in itself would do little to reverse the hyperkalaemia, but it does help decrease the activity of sodium channels that is at the root of this pathophysiology (remember in the setting of hyperkalaemia, membranes are more excitable and calcium reduces this hyperexcitablitiy). It is worth saying that truly understanding the mechanism of the disease is very complex and not as simple as what I’m making it out to be – I want to help you find a way to get your head around this disease. 2) Other treatments include treatments directed towards reducing potassium (insulin, glucose (because of organic insulin release), and diuretics (including acetazolamide which causes a metabolic acidosis!).

Question 40

Treatment of familial hypokalemic periodic paralysis

Answer 40

1) K+ replacement, 2) acetazolamide, 3) reversing causes of hypokalaemia (hypothermia, alkalosis, etc). The causative mutations in this disease are voltage-gated calcium channels (not sodium channels).

Question 41

Which muscles are most affected in familial hyper/hypo kalemic periodic paralysis? And which are most preserved ?

Answer 41

With both diseases, trunk and extremity muscles are mostly affected and diaphragm and cranial muscles are mostly preserved.

Question 42

What would be the expected response to NMB and twitch monitor in patients with familial hypo/hyper kalemic periodic paralysis?

Answer 42

Response to muscle relaxants would be expected to be normal and a standard reversal with neostigmine should work as expected. Twitch monitoring as far as I can tell should be reliable and normal as well.