NMB Truelearn

Question 1

Degradation of succinylcholineI and mivacurium done by ….

Answer 1

Butyrylcholinesterase (alternately pseudocholinesterase or plasma cholinesterase) is the enzyme responsible for degradation of succinylcholineI and mivacurium.

Administration of either of these medications to patients with BCHE deficiency therefore results in prolonged neuromuscular blockade and the potential for prolonged apnea

Question 2

What is the most resistance vs most sensitive muscle to NMB? What used to assess for?

Answer 2

After laryngeal muscles and diaphragm, the corrugator supercilii (eyebrow movement) is the most resistant to neuromuscular blockade and most closely resembles the abdominal and laryngeal muscles.

The adductor pollicis is more sensitive to neuromuscular blockade and is the best choice to monitor for extubating conditions. The flexor hallucis (big toe flexion) and orbicularis oculi (eyelid movement) correlate more closely with the adductor pollicis.

Question 3

How TOF can be assessed without acceleromyography?

Answer 3

As already stated, providers cannot reliably assess fade of TOF ratio for extubation. Maximum inspiratory pressure (MIP), vital capacity, tidal volume assessment, and muscle strength assessment can be used to estimate TOF.

These tests correlate with a TOF ratio of < 0.7: MIP > 25 cm H2O, vital capacity > 15 mL/kg, tidal volume assessment, sustained eye-opening, handgrip, and tongue protrusion.

These tests correlated with a TOF ratio between 0.7 and 0.9: MIP > 50 cm H2O, head-lift test, leg-lift test, tongue depressor test, and handgrip (sustained).

There are no clinical tests available to date that can assess for a TOF ratio of ≥ 0.9. Therefore, neuromuscular blockade should be antagonized unless objective measurement of the TOF ratio can be performed, such as with acceleromyography.

Question 4

Which NMB requires the least increase in dose in burn patients?

Answer 4

Mivacurium’s dosing requirements are only slightly increased relative to other NDNMBs as it is metabolized by pseudocholinesterase, the levels of which are decreased in burn patients.

Mivacurium is different from most NDNMBs because it is metabolized by pseudocholinesterase alone. Burn patients have decreased levels of pseudocholinesterase, making them more sensitive to the effects of mivacurium. However, increased ACh receptors still contributes to some resistance to the drug. The net result of these two effects is that the required dose of mivacurium in burn patients is 1-2x the dose used in healthy patients.

Doses of most other NDNMBs must be increased 2-5x in burn patients to achieve the same intubating conditions in the same time period as in healthy patients due to drug resistance.

Question 5

Succinylcholine effect on LES time and intragastric pressure? And dose it increase risk of aspiration?

Answer 5

It increases both

However, unless LES is incompetent, there is no increases risk of aspiration because the increase in LES tone is greater than the increase in intragastic pressure.

If there is a concern for an incompetent LES, the increase intragastric pressure can be offset by pretreatment with a pruning dose of NDNMB

Question 6

Sugammadex dosage?

Answer 6

2 mg/kg: 2 twitches with + TOF

4 mg/kg: 1-2 post-tetanic and -TOF

16 mg/kg: for immediate reversal of 1.2 mg/kg of Roc

The mean time for return to TOF > 0.9 is (1.4-3 min)

For Vecuronium (2.3-3 min)

Question 7

The most common succinylcholine induced arrhythmia is …

Answer 7

Bradycardia

Peds>adults

In Peds, they have high vagal tone which is associated with more Ach receptors in SA node

In adults, it’s observed after second dose given, and its due to heart sensitization to succinylcholine metabolic product (known as succinymonocholine)

This is prevented by premedication of atropine

Question 8

When is a phase 2 block by succinylcholine occurs?

Answer 8

After a single high dose above 4mg/kg or prolonged continuous administration

(Phase 2 is when succinylcholine remains on Ach receptors, keeps the receptors activated and open which allows time for intracellular adaptation).

Question 9

Side effects of glycopyrolate

Answer 9

delays gastric emptying, decreases salivary and gastric secretions, decreases lower esophageal sphincter tone (May increase risk of aspiration), increases heart rate, relaxes bronchial smooth muscle, and causes urinary retention.

Question 10

The most common side effects of the water-soluble propofol prodrug fospropofol are …

Answer 10

paresthesias (typically perianal or genital) and genital pruritus.

Due to its slower onset of action, the incidence of respiratory depression, apnea, and hypotension are lower with fospropofol compared to propofol.

Question 11

Local anesthetic allergy commonly with which class?

Answer 11

Amino-esterses (procaine, chloroprocaine, etc) are more likely to elicit allergic reactions compared to aminoamides (lidocaine, bupivacaine, ropivacaine, etc) because the aminoesters are derivatives of paraaminobenzoic acid (PABA), a known allergen (hapten to be precise).

Although allergic reactions to aminoamides are very rare, patients may occasionally react to preservatives such as methylparaben (structurally related to PABA) and sulfites.

Especially with multiple-dose vials of lidocaine typically contain 0.1% of methylparaben added as preservative, whereas single dose solutions are typically methylparaben free.

Question 12

If allergic reaction to local anesthetic are uncommon, how do you explain the reported allergy by patient’s dentist?

Answer 12

Most untoward reactions to local anesthetics are non-allergic, and most patients who report allergies to local anesthetics are in fact not allergic when tested by skin testing. For example, a patient who recalls pounding in the chest when injected local anesthetic by their dentist is more likely to have had a physiologic (non-allergic) reaction to the epinephrine content of that formulation

Question 13

Immunosuppressant that prolongs NDNMB?

Answer 13

Cyclosporine

Question 14

Lithium effect on NMBs and MAC

Answer 14

It prolongs duration of both DNMB and NDNMB

Li+ decreases ACho release from alpha motor neurons at the NM junction and also it activates K channels and thus inhibits NM transmission presynaptically and muscular contraction postsynaptically.

Li+ also decreases MAC requirement because a it blocks brainstem release of NorEpi, Epi, and dopamine

Question 15

Antibiotics that effects NMBs?

Answer 15

Aminoglycosides
Clindamycin

Inhibits prejunctional Ach release and depressing postjunctional receptor sensitivity to Ach

Question 16

MG affect on DNMB and NDMB

Answer 16

It prolongs NDNMB

Shortness action of DNMB because of the decreased number of receptors avalanche for blockade

Question 17

Psudocholinesterases deficiency is AR that causes prolonged DNMB and only one NDNMB?

Answer 17

Succinylcholine and mivacurium metabolized by psudocholeninesterase

This genetic deficiency happens in 1/5000 Caucasians

Question 18

Side effects of sugammadex?

Answer 18

Anaphylaxis (0.3-1%)

hypersensitivity (nausea, pruritus, urticaria in 7-9%)

Sever bradycardia (1% with 2-4mg/kg) and (5% with 16mg/kg)

Other less common ; tachycardia, hypotension, increases PT/INR and aPTT, unintentional pregnancy

Question 19

Metoclopramide effect on NMB?

Answer 19

It can prolong action of succinylcholine by inhibiting plasma cholinesterase.

Question 20

Anticholinergics and recommenced paired cholinesterase

Answer 20

Atropine (O: 1 min, D: 15-30 min)- endorphonium (O: 1-2 min, D: 1-2 hr)

Glyco (O: 2-3 min, D: 2-4 hr) - Neo (O: 7-11min, D: 4-6 hr)

Pyridostigmine can be used instead of neostigmine (O: 15-20 min, D: 4hr).

Question 21

Muscle relaxation that directly blocks Ca release from SR of skeletal muscle

Answer 21

Dantrolene is unique among muscle relaxants in that its site of action is NOT at the extracellular portion of the nicotinic receptor but INTRACELLULAR on the sarcoplasmic reticulum of the skeletal muscle cells. Dantrolene is not a depolarizing or nondepolarizing neuromuscular blocking drug.

Dantrolene is given initially as an IV bolus (2.5 mg/kg) followed by repeat boluses every 5-10 minutes as needed. Some institutions may choose to place patients on dantrolene infusions or administer dantrolene 1 mg/kg every 6 hours for 24-72 hours in order to prevent recrudescence.

Question 22

Administration of a dose of succinylcholine following previous administration of an anticholinesterase inhibitor (such as neostigmine) will result in …

Answer 22

some degree of succinylcholine prolongation of action (phase I block augmentation). This blockade typically lasts for about 30 minutes.

Question 23

Succinylcholine is associated with multiple side effects including, but not limited to …

Pretreatment with NDNB decreases which side effects? and has no role in in decreasing which side effects?

Answer 23

cardiovascular rhythm changes, hyperkalemia, muscle fasciculations, myalgias, and increases in intracranial pressure (ICP), intragastric pressure, and IOP.

fasciculations and increases in ICP and intragastric pressure may be decreased by NDNB pretreatment.

Cardiac rhythm changes and Increase in IOP will occur despite pretreatment and current recommendations are to avoid succinylcholine in open-eye injuries.

Question 24

Pretreatment with NDNB (dose or dose not) alter the cardiovascular side effects of succinylcholine?

Answer 24

Dose not.

The exact mechanism responsible for bradycardia with nodal or ventricular escape beats and asystole is unknown because succinylcholine has little effect on autonomic cholinergic receptors. Cardiac side effects are more often seen with repeat dosing in children and can be attenuated with the use of glycopyrrolate or atropine. Succinylcholine more commonly causes tachycardia, mediated by catecholamine release. The succinylcholine-associated increases in potassium may be blunted by very high dose NDNB administration, well outside the clinically acceptable range for pretreatment doses.

Question 25

What is the risk of overdosing Neostigmine?

Answer 25

Patients who receive an excessive amount of acetylcholinesterase (AChE) inhibitor are at an increased risk of developing weakness. The recommended maximum dose of neostigmine is 0.07 mg/kg.

It causes weakness by motor axon sodium channel inactivation and presynaptic nicotinic receptor desensitization. Postsynaptic sodium channel inactivation and acetylcholine receptor desensitization also occur.

Question 26

Prolong Non-Depolarizing Blockade:

Answer 26

• Antibiotics (e.g. streptomycin, clindamycin, tetracyclines, aminoglycosides)
• Antiarrhythmics (e.g. calcium channel blockers)
• Dantrolene
• Ketamine
• Local anesthetics (high doses only)
• Lithium
• Magnesium
• Volatile anesthetic agents.
• HypoK.
• Hypothermia.
• HypoCa, HyperMg (Lithium and magnesium potentiate neuromuscular blockade by antagonizing calcium, as do calcium channel blocking medications).

Question 27

Shorten Non-Depolarizing Blockade:

Answer 27

• Anticonvulsants (e.g. phenytoin, carbamazepine)

- Cholinesterase inhibitors (e.g. neostigmine)

Question 28

How Aminoglycosides, Clindamycin, and Tetracyclines potentiate neuromuscular blockade?

Answer 28

Aminoglycosides, polymyxins, lincomycin, and clindamycin primarily inhibit the prejunctional release of acetylcholine and also depress postjunctional nAChR sensitivity to acetylcholine.

Tetracyclines, on the other hand, have postjunctional activity only.

Question 29

HOw dose hypocalceemia and hyperMg potentiate neuromuscular blockade?

Answer 29

Hypocalcemia potentiates neuromuscular blockade because calcium is important for the release of vesicles containing acetylcholine from nerves at the neuromuscular junction. When calcium levels are low, less acetylcholine is released. With less acetylcholine being released there is less competition at the acetylcholine receptor and neuromuscular blockers have a greater effect. Hypermagnesemia acts similarly by blocking calcium from entering alpha motor neurons and preventing the release of some of the acetylcholine containing vesicles.

Question 30

NMB potentiation from greatest to least for volatile anesthetics is …

Answer 30

Desflurane causes greater blockade potentiation than sevoflurane or isoflurane. (desflurane > sevoflurane > isoflurane).

Question 31

Pseudocholinesterase function?

Answer 31

Pseudocholinesterase (PChE), also known as plasma cholinesterase and butyrylcholinesterase (BChE), is a glycoprotein enzyme produced by the liver, circulating in the plasma. It specifically hydrolyzes exogenous choline esters; however, it has no known physiologic function.
Pseudocholinesterase deficiency is typically an inherited enzyme abnormality that results in abnormally slow metabolic degradation of exogenous choline ester drugs such as succinylcholine, mivacurium, ester local anesthetics, cocaine, and heroin.

Question 32

Pseudocholinesterase deficiency prolong the effect of which commonly medications used?

Answer 32

Succinylcholine, mivacurium, ester local anesthetics (2-chloroprocaine, tetracaine, procaine), cocaine, and heroin are metabolized via hydrolysis by pseudocholinesterase, also known as plasma cholinesterase and butyrylcholinesterase. A deficiency or defect in this enzyme would result in decreased metabolism and prolonged effects of the substance.

Remifentanil and esmolol are metabolized by nonspecific blood and tissue esterases and would not be affected by a pseudocholinesterase deficiency.

Question 33

Cisatracurium undergoes nonenzymatic Hofmann elimination in plasma. The reaction speed is increased with higher …

Answer 33

The Hofmann elimination reaction is a pH- and temperature-dependent reaction that proceeds more readily when pH and temperature are increased.

The reaction speed is increased as pH and/or temperature is increased. Therefore, the effects of cisatracurium will last longer in patients who are acidotic and/or cold and the drug will need to be re-dosed less frequently.

Question 34

The recommended precurarization dosage for a nondepolarizing agent is …

Answer 34

10% of the ED95, given about 3-5 minutes prior to succinylcholine. Using 10% of the intubating dose (20% of the ED95) is associated with an unacceptably high rate of side effects, including dyspnea in an awake patient.

    Doses ->  ED95  	    Precurarization   Intubating   Rocuronium	 0.3 mg/kg   0.03 mg/kg      2-4 x ED95

Question 35

Precurarization risks?

Answer 35

overdosage of the nondepolarizing agent may cause weakness, patient distress, difficulty breathing, gastroesophageal regurgitation, and even pulmonary aspiration. Furthermore, precurarization reduces the neuromuscular blocking potency of succinylcholine and it also delays the onset of action. The intubating dosage of succinylcholine should be increased from 1 mg/kg to 1.5 mg/kg when precurarization is used due to this antagonism from the nondepolarizing agent.

Question 36

Treatment of choice for delirium associated with scopolamine/ atropine-induced delirium is …

Answer 36

Physostigmine

Question 37

The typical DOC to prevent amnesia in hemodynamically unstable patients?

Answer 37

Scopolamine.

This is typically done for hemodynamically unstable patients, such as during massive hemorrhage or trauma. Scopolamine IV may also be given preoperatively to reduce the risk of awareness in selected populations. The sedative effects may be desirable for premedication but can interfere with awakening following short procedures. Because of its pronounced ocular effects, scopolamine is best avoided in patients with closed-angle glaucoma. Additionally, the surgical team should be aware that mydriasis and CNS depression may interfere with neurologic assessment after surgery (e.g. trauma patients).

Question 38

What is the meaning of ED95 dose in reference to neuromuscular blockers?

Answer 38

The ED95 of a neuromuscular blocking drug is the effective dose required to achieve 95% block of a single twitch in 50% of individuals.

In general pharmacology, ED95 refers to the effective dose needed to get the desired effect for 95% of the population. Unfortunately, this term has a different meaning specifically for neuromuscular blocking agents. For these agents, ED95 refers to the median dose required to achieve a 95% reduction in the maximal twitch response from baseline, in 50% of the population. A more appropriate term would be ED5095, however the terminology ED95 has stuck for this context.

Question 39

The ED95 for rocuronium is … and what is the effective relaxation dose of rocuronium during intubation?

Answer 39

0.3 mg/kg, which means that half of patients will achieve at least a 95% blockade of a single twitch if they receive this weight-based dose. For effective relaxation during intubation, one to two times the ED95 is typically needed. This is why most practitioners use, for example, at least 0.6 mg/kg of rocuronium for intubation. The rapid sequence intubation dose of rocuronium is therefore four times ED95 (1.2 mg/kg).

Question 40

Contraindication for Sugammadex?

Answer 40

• known hypersensitivity to sugammadex or its components (γ-cyclodextrin).
• pediatric patients
• severe renal failure
• reversal of neuromuscular blocking drugs (NBDs) other than rocuronium and vecuronium,
• for reversal following rocuronium or vecuronium administration in intensive care units.

Question 41

Can Sugammadex be administered with Zofran?

Answer 41

Sugammadex is physically incompatible with ondansetron, ranitidine, and verapamil and should not be co-administered with these medications. If sugammadex and one of the above drugs are to be administered in the same line, the line should be adequately flushed with saline between administration of the two drugs.

Question 42

Do you increase or decrease intubating vs maintenance dose of rocuronium in liver cirrhosis patients?

Answer 42

Intubating doses of neuromuscular blocking drugs are increased in cirrhosis because of the increase in volume of distribution. (Neuromuscular blocking agents are highly water-soluble due to quaternary amine structures and thus an increase in body water, such as with cirrhosis, CHF, or renal failure, results in decreased plasma concentration of neuromuscular blockers requiring an increase in intubating dose.)

Maintenance doses of hepatically metabolized and/or cleared drugs should be reduced and neuromuscular function carefully monitored as duration of action is prolonged.