General about NMBA & Succ

Question 1

Benefits of NMBA

Answer 1

Improve surgical conditions, allow for CV/Neuro/transplants, facilitate ETT.

Question 2

Risks of NMBA

Answer 2

No analgesis or anesthetic properties

Question 3

Describe the nicotinic acetylcholine receptor

Answer 3

5 subunit complex with 2 alpha, 1 beta, 1 delta & 1 gamma subunit

Question 4

What happens when ACh binds and where does it bind on the nACHR

Answer 4

It binds to the alpha subunits, creates a conformational change & the channel opwns

Question 5

ED50 of NMBA

Answer 5

50% depression of twitch tension in the nACHR

Question 6

What does succinylcholine do the nACHR

Answer 6

binds to the nACHR, causes the conformational change, but does not allow any further action potential to be generated by desensitizing the nACHR, inactivating the VGNaC & NMJ, & increases K permeability in the surrounding membrane

Question 7

Prejunctional nicotinic receptors & ACh

Answer 7

Have a positive feedback role in making ACh available to the nACHR when needed, involved in mobilization (not release of) ACh

Question 8

Prejunctional muscarinic receptors & ACh

Answer 8

Involved in facilitation and inhibition of the release of ACh through modulation of Ca influx

Question 9

How do nondepolarizers affect prejunctional nicotinic & muscarinic receptors

Answer 9

Blockade of nicotinic will affect availability of ACh when needed fast (TOF) - may explain fade, do not appear to block muscarinic

Question 10

Where do NMBAs block fastest, deepest, and wear off fastest from?

Answer 10

Blocks centrally located (larynx, diaphragm) fastest, blocks peripheral deeper, wears off quickest from central. (If twitch shows paralyzed at adductor pollicis, likely not going to respond to intubation.

Question 11

What are all NMBAs related to?

Answer 11

Acetylcholine - they are all quaternary ammonium compounds

Question 12

How do NMBAs attach to the nACHR and what does that mean for the rest of the body?

Answer 12

They have positive charges that mimic the quaternary nitrogen atom of ACh.. this means they can also affect other nACHR sites (autonomic ganglia, SNS, PNS, prejunctional nicotinic/muscarinic receptors)

Question 13

Depolarizing relaxant(s)

Answer 13

Succinylcholine

Question 14

How does succ work?

Answer 14

2 ACh molecules connected by ester bond, mimics action of ACh by binding to the alpha subunits (at both nicotinic & muscarinic receptors) & holds the channel open which does not allow any further depolarizations

Question 15

ED95 of Succ

Answer 15

0.3 mg/kg-0.63 mg/kg

Question 16

Typical dose of succ

Answer 16

1 mg/kg (“Newer: 0.5-0.6 mg/kg)

Question 17

How quickly does succ act & recover?

Answer 17

45- 60 seconds, get recovery in 8-15 minutes with 1 mg/kg dose

Question 18

How is succ metabolized?

Answer 18

Butrylcholinesterase - to succinylmonocholine (also a weaker NMBA, metabolized slowly to succinic acid & choline)& choline… only about 10% of the succ dose reaches the NMJ.

Question 19

How is the action of succ terminated?

Answer 19

Diffusion away from the NMJ back into circuation

Question 20

What effects the level of metabolism of succ?

Answer 20

Liver disease, age, malnutrition, pregnancy, burns, oral contraceptives, MAOIs, ecothiphate, cytotoxic drugs, neoplasms, anticholinesterases, tetrahydroaminacrine, hexafluorenium, metoclopramide –> less Butrylcholinesterase activity (longest lasting from these things has been 23 minutes)

Question 21

Dibucaine test

Answer 21

Drug inhibits action of normal Butrylcholinesterase by about 80%, it does not measure the concentration of the enzyme or the efficiency of the enzyme – Determines QUALITY not quantity (the greater the percentage indicates normal pseudocholinesterase)

Question 22

What the dibucaine numbers mean

Answer 22

How much dibucaine inhibits Butrylcholinesterase activity… 70-80 - succ lasts the normal amount of time, 50-60 (heterozygous atypical BCE)- succ lasts about 50-100% longer = 15-30 minutes, 20-30 (homozygous atypical BCE) - succ can last 4-24 hours)

Question 23

What does it mean if the dibucaine number is low?

Answer 23

The BCE is atypical and will not metabolize succ well

Question 24

Succ CV Side Effects & explanations

Answer 24

• -Effects nicotinic receptors on sympathetic & parasympathetic ganglia & muscarinic receptors in sinus node
• Bradycardia (stimulation of cardiac muscarinic receptors in sinus node) particularly bad in patients with a lot of vagal tone (peds) or 2nd dose about 5 minutes after 1st, can give atropine
• Negative inotropic
• High dose = tachycardia
• Dysrhythmias- junctional (nodal) due to stimulation of muscarinic receptors in sinus node, AV pacemaker takes over momentarily
• Circulating catecholamines increase 4fold & potassium increase may lead to ventricular dysrhythmias (along with other compounding effects - hypoxia, hypercapnia, ETT, surgery)

Question 25

Succ & hyperkalemia

Answer 25

Causes a 0.5 mEq/L increase from the potassium movement out of the cells- **even more is release in patients with hypovolemia, metabolic acidosis, intra-abdominal infections >1 week, increase in extrajunctional receptors (hemiplegia, paraplegia, muscular dystrophies, Guillain-Barre, burns)

Question 26

Treatment for severe rapid onset hyperkalemia

Answer 26

Hyperventilate, 1-2 mg CaCl, 50 mL D50W IV + 10 units Insulin (or kids 1 mL/kg D50W + 0.15 U/kg insulin), BiCarb 1 mEq/kg

Question 27

Succ & IOP

Answer 27

Open anterior chamber eye injury- succ is contraindicated. Increases IOP within 1 min, peaks 2-4 min, subsides in 6 min. If patient becomes light and starts moving during eye surgery - do NOT give succ (may result in extrusion of eye contents = blindness)

Question 28

Succ & Intra-gastric Pressure

Answer 28

Increases potentially above 28 cm H2O (will vomit)- may increase aspiration risk especially in pregnancy, ascites, bowel obstruction, hiatal hernia. Does not happen in children & infants

Question 29

Succ & ICP

Answer 29

Increases, no clinical significance

Question 30

What side effects can predosing nondepolarizing NMBAs before succ help?

Answer 30

IOP, ICP,

Question 31

Succ & myalgia

Answer 31

More frequent in minor surgery, women & ambulatory patients, unsure of what it is related to

Question 32

Succ & masseter spasm

Answer 32

Due to exaggerated contraction of the NMJ in the jaw (not related to MH)

Question 33

Succ & MH

Answer 33

Potentially the worst agent to trigger MH

Question 34

Dantrolene administration

Answer 34

Initial dose 2 mg/kg, repeat 2 mg/kg up to 10 mg/kg if required to stop MH

Question 35

How do you know when dantrolene has worked?

Answer 35

Clinical response - decrease in temp, end-tidal CO2

Question 36

When can MH occur?

Answer 36

Anytime! No prior family history needed, multiple unremarkable anesthetics (even succ), during maintenance or postop)

Question 37

Succ & phase II block

Answer 37

Acts like non-depolarizing blockade a NMJ, TOF will show a fade pattern, if TOF is < 0.4 and it has been 20-30 minutes since admin, reversal may be attempted but extubation not attempted until TOF is 0.9

Question 38

Succ & neostigmine

Answer 38

If neostigmine has been given to reverse nondepolarizing agent, and you give succ, it will last 30-60 minutes from baseline

Question 39

What conditions are resistant to succ?

Answer 39

Myasthenia gravis (fewer receptors to work with)